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Front Pharmacol. 2018 Jun 20;9:643. doi: 10.3389/fphar.2018.00643. eCollection 2018.

Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers.

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Phase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
State Key Laboratory of Natural Medicines and Center of Drug Discovery, College of Pharmacy, China Pharmaceutical University, Nanjing, China.
First Hospital and Institute of Immunology, First Hospital, Jilin University, Jilin, China.
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Jiangsu Vcare PharmaTech Co. Ltd., Nanjing, China.
Hua Medicine Ltd., Shanghai, China.
Department of Hepatology, First Hospital, Jilin University, Jilin, China.
Department of Hand Surgery, First Hospital, Jilin University, Jilin, China.


Background: Vicagrel is a novel anti-platelet drug and hydrolyzed to the same intermediate as clopidogrel via esterase, instead of CYP2C19. Here we report the first clinical trial on the tolerability, pharmacokinetics and pharmacodynamics of different doses of vicagrel, and comparison with clopidogrel in healthy Chinese volunteers. Methods: This study was conducted in two parts. Study I was a dose-escalating (5-15 mg) study. For each dose, 15 participants were randomized into three groups (total n = 45); nine participants were given vicagrel, three were given clopidogrel, and three were given a placebo. Study II was conducted to assess interactions between vicagrel and aspirin in 15 healthy participants. The plasma concentrations of the metabolites of vicagrel and clopidogrel were determined using a LC-MS/MS method. Platelet aggregation was assessed using the VerifyNow-P2Y12 assay. Results: Vicagrel (5-15 mg per day) dosing for 10 days or addition of aspirin was well tolerated in healthy volunteers. The exposure of the active metabolite increased proportionally across the dose range and was higher (~10-fold) than clopidogrel. The levels of IPA dosing 75 mg clopidogrel were between the responses of 5 mg and 10 mg vicagrel. After a single loading dose of vicagrel (30 mg) and a once-daily maintenance dose (7.5 mg) for 8 days, the maximum inhibition of platelet aggregation was similar to that seen with the combined use of vicagrel and aspirin (100 mg/day). Conclusion: Oral vicagrel demonstrated a favorable safety profile and excellent anti-platelet activity, which could be a promising P2Y12 antagonist as anti-platelet drug and can be further developed in phase II/III studies, and marketing for the unmet medical needs of cardiovascular diseases. The study was registered at (ChiCTR-IIR-16009260).


clopidogrel; pharmacodynamics; pharmacokinetics; safety; vicagrel

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