Safety,tolerability,and pharmacokinetics of VV116,an oral nucleoside analog against SARS-CoV-2,in Chinese healthy subjects  

作　　者：Hong-jie Qian Yu Wang Meng-qi Zhang Yuan-chao Xie Qing-qing Wu Li-yu Liang Ye Cao Hua-qing Duan Guang-hui Tian Juan Ma Zhuo-bing Zhang Ning Li Jing-ying Jia Jing Zhang Haji Akber Aisa Jing-shan Shen Chen Yu Hua-liang Jiang Wen-hong Zhang Zhen Wang Gang-yi Liu 

机构地区：[1]Central Laboratory,Shanghai Xuhui Central Hospital/Xuhui Hospital,Fudan University,Shanghai 200031,China [2]Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs,Shanghai 200031,China [3]CAS Key Laboratory of Receptor Research,Drug Discovery and Design Center,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [4]Lingang Laboratory,Shanghai 201602,China [5]Clinical Department,Vigonvita Life Sciences Co.,Ltd,Suzhou 215123,China [6]Research and Development Department,Shanghai Junshi Biosciences Co.,Ltd,Shanghai 200126,China [7]Phase 1 Clinical Research Center,Huashan Hospital,Fudan University,Shanghai 200040,China [8]State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization,Xinjiang Technical Institute of Physics and Chemistry,Chinese Academy of Sciences,Urumqi 830011,China [9]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [10]Department of Infectious Diseases,Huashan Hospital,Fudan University,Shanghai 200040,China

出　　处：《Acta Pharmacologica Sinica》2022年第12期3130-3138,共9页中国药理学报（英文版）

基　　金：he studies were sponsored by Vigonvita Life Science Co.,Ltd and Shanghai JunTop Biosciences Co.,Ltd.This work was partially supported by the National Key Research and Development Program of China(No.2021YFC0865000);the Lingang Laboratory(No.LG202103-04-04);the 2020 ANSO Collaborative Research Project(No.ANSO-CR-SP-2020-03);Shanghai Science and Technology Committee(No.21S11903100).

摘　　要：VV116(JT001)is an oral drug candidate of nucleoside analog against SARS-CoV-2.The purpose of the three phase I studies was to evaluate the safety,tolerability,and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects,as well as the effect of food on the pharmacokinetics and safety of VV116.Three studies were launched sequentially:Study 1(single ascending-dose study,SAD),Study 2(multiple ascending-dose study,MAD),and Study 3(food-effect study,FE).A total of 86 healthy subjects were enrolled in the studies.VV116 tablets or placebo were administered per protocol requirements.Blood samples were collected at the scheduled time points for pharmacokinetic analysis.116-N1,the metabolite of VV116,was detected in plasma and calculated for the PK parameters.In SAD,AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25–800 mg.T_(1/2)was within 4.80–6.95 h.In MAD,the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116.In FE,the standard meal had no effect on Cmax and AUC of VV116.No serious adverse event occurred in the studies,and no subject withdrew from the studies due to adverse events.Thus,VV116 exhibited satisfactory safety and tolerability in healthy subjects,which supports the continued investigation of VV116 in patients with COVID-19.

关 键 词：VV116 nucleoside analog SARS-CoV-2 SAFETY PHARMACOKINETICS healthy subjects 

分 类 号：R96[医药卫生—药理学]