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

ABSTRACT

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 C_max, AUC_0-t, and AUC_0-∞ 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).

KEYWORDS:

• Influenza
• ZSP1273
• healthy volunteers
• pharmacokinetics
• safety

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Author contributions

Yue Hu, Haijun Li, Min Wu, Yanhua Ding, and Zhenxiang Yu were involved in the conception, design, and analyses of the data; Yue Hu, Hong Zhang, Yun Peng, and Xiaojiao Li performed the clinical trials and interpretation of the data; Yue Hu, Zhenxiang Yu, and Yanhua Ding participated in the drafting of the paper; All authors contributed to revising the paper critically for intellectual content and approving the final approval of the version to be published; All authors agree to be accountable for all aspects of the work.

Additional information

Funding

This work was financially supported by the capital construction funds within the provincial budget in 2020 (innovation capacity construction, project: 2020C038-1).