Hu Yue, Li Haijun, Wang Kun, Wu Dandan, Zhang Hong, Ding Yanhua, Wu Junyan, Ye Suiwen, Peng Yun, Liu Li
Phase I Clinical Research Center, First Hospital of Jilin University, Changchun, China.
Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, China.
Antimicrob Agents Chemother. 2025 Mar 5;69(3):e0145024. doi: 10.1128/aac.01450-24. Epub 2025 Jan 31.
Coronavirus disease 2019, which leads to pneumonia, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RAY1216 is a 3C-like protease inhibitor that targets SARS-CoV-2. The aim of our study was to assess the pharmacokinetics (PK) and safety of RAY1216 in healthy volunteers. This was a randomized, placebo-controlled, double-blind study consisting of four components: a single ascending dose study, a drug-drug interaction study, a multiple ascending dose study, and a food-effect study. All participants were randomly assigned to receive either a single dose or multiple doses of RAY1216 or placebo. A total of 88 healthy adult participants (male-to-female ratio of 1:1) aged 18-50 years were enrolled. A total of 37 participants (42%) experienced at least one adverse event (AE). All AEs were mild or moderate and were resolved without additional treatment. The most commonly reported adverse drug reactions were hypertriglyceridemia, hyperuricemia, and elevated serum creatinine levels. RAY1216 was well-absorbed after administration with exposure increasing in a dose-dependent manner. Food appeared to increase exposure and delay the absorption of RAY1216. Ritonavir significantly inhibited drug metabolism, and increased drug exposure increased the associated safety risks. RAY1216 was found to be well tolerated and safe in healthy participants. On the basis of preclinical results, PK characteristics, and the safety profile of RAY1216, a dosage of 400 mg three times daily was selected, thereby establishing a foundation for future research and for the clinical application of RAY1216.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05829551.
2019冠状病毒病可导致肺炎，它由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起。RAY1216是一种靶向SARS-CoV-2的3C样蛋白酶抑制剂。我们研究的目的是评估RAY1216在健康志愿者中的药代动力学（PK）和安全性。这是一项随机、安慰剂对照、双盲研究，包括四个部分：单次递增剂量研究、药物相互作用研究、多次递增剂量研究和食物效应研究。所有参与者被随机分配接受单次剂量或多次剂量的RAY1216或安慰剂。共招募了88名年龄在18至50岁之间的健康成年参与者（男女比例为1:1）。共有37名参与者（42%）经历了至少一次不良事件（AE）。所有不良事件均为轻度或中度，无需额外治疗即可缓解。最常报告的药物不良反应是高甘油三酯血症、高尿酸血症和血清肌酐水平升高。RAY1216给药后吸收良好，暴露量呈剂量依赖性增加。食物似乎会增加RAY1216的暴露量并延迟其吸收。利托那韦显著抑制药物代谢，增加的药物暴露会增加相关的安全风险。结果发现，RAY1216在健康参与者中耐受性良好且安全。基于临床前结果、PK特征和RAY1216的安全性概况，选择了每日三次400毫克的剂量，从而为RAY1216的未来研究和临床应用奠定了基础。临床试验本研究已在ClinicalTrials.gov注册，注册号为NCT05829551。
