Single and multiple dose pharmacokinetics and safety of ZSP1273, an RNA polymerase PB2 protein inhibitor of the influenza A virus: a phase 1 double-blind study in healthy subjects

摘要

Background: Influenza is an acute respiratory illness. Treating with antiviral drugs can decrease the duration of illness and serious complications . ZSP1273 is a small-molecule anti-influenza drug targeting the RNA polymerase PB2 subunit of the influenza virus. The aim of this clinical trial was to evaluate the safety and pharmacokinetics (PKs) of ZSP1273 in healthy subjects. Research design and methods: This was a double-blind, placebo-controlled phase 1 study consisting of three parts. 100 volunteers were enrolled and randomized to receive either single or multiple doses of ZSP1273 or placebo. Results: A total of 31 (31.0%) subjects experienced at least one mild or moderate adverse event. The linear regression relationship between dose and plasma Cmax, AUC0-t, and AUC0-∞ showed an increasing trend and rapid absorption of ZSP1273. A high-fat diet had little effect on the PKs. The plasma concentration of ZSP1273 reached steady state on day 5 without drug accumulation. Conclusions: ZSP1273 was safe in healthy volunteers. Based on the preclinical resuilts, safety profile and PK characteristics of ZSP1273, the dose of ZSP1273 (≥200 mg) may be used for future clinical trials in influenza patients. Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT03679143).