Bioavailability of a novel anti-influenza agent, onradivir granules, in healthy Chinese adults: a first-in-human study

Abstract

Background Onradivir (ZSP1273) is a novel inhibitor of the RNA polymerase PB2 subunit of influenza A virus, developed for the treatment of acute uncomplicated influenza A. The onradivir tablet, launched in 2023, is intended for adult patients and is not suitable for children. This project aims to evaluate the pharmacokinetic profile of the onradivir granule formulation, providing evidence to support its use in the target pediatric population as well as in adult patients. Methods This study adopted a open, four-period, repeated crossover design. Thirty-two healthy adult males received 200 mg doses of either the onradivir granules or onradivir tablets under fasting conditions. To quantify the plasma concentration of onradivir using an LC-MS/MS method and evaluate its pharmacokinetic parameters. Results During the trial, no SAEs or SUSARs occurred in any participants. The coefficient of variation for Cmax of the onradivir tablets was 74.91%, indicating high variability and necessitating the use of the RSABE method for evaluating Cmax equivalence between the two formulations. Within-subject standard deviation of the reference formulation (SWR) value of Cmax was 0.667, exceeding the cutoff of 0.294. Cmax met both acceptance criteria: its 95% upper confidence bound, at −0.1769, was <0, and the point estimate of the least-squares geometric mean ratio is 81.58%, fell within the 80.00%–125.00% range, meeting the RSABE equivalence determination criteria; The coefficients of variation for AUC0-t and AUC0−∞ of the onradivir tablets were 18.11% and 15.47%, respectively; therefore, the ABE method was employed to assess the equivalence of AUC0-t and AUC0−∞ . The geometric mean ratios and 90% confidence intervals for AUC0-t and AUC0−∞ were 98.13% and 97.52%, with their corresponding 90% confidence intervals of 93.91%–102.54% and 93.22%–102.03%, respectively, all falling within the 80.00%–125.00% range, meeting the ABE equivalence determination criteria. Conclusion The two formulations demonstrated comparable bioavailability and met the criteria for bioequivalence. Clinical Trial Registration https://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier CTR20242821.