A phase I study to evaluate the effect of hepatic impairment on the pharmacokinetics and safety of suraxavir marboxil: a novel oral antiviral for influenza

Suraxavir marboxil (GP681, abbreviated as suraxavir) is a novel, orally active small-molecule polymerase acidic (PA) inhibitor for the treatment of influenza. Its active metabolite, GP1707D07, specifically inhibits PA endonuclease activity. Suraxavir has been approved for use in adolescents (≥12 years) and adults with uncomplicated influenza A and B. This non-randomized, open-label, parallel-group phase I clinical trial evaluated the effects of hepatic impairment on the pharmacokinetics (PK) and safety of suraxavir. Subjects with mild or moderate hepatic impairment and matched healthy controls (<i>n</i> = 8 per group) received a single oral dose of 40 mg suraxavir. PK parameters, including maximum plasma concentration (C_max), area under the plasma concentration-time curve from time 0 to last time point of measurable concentration (AUC_0-<i>t</i>), and area under the plasma concentration-time curve from time 0 to infinity (AUC_0-∞), were compared. Compared with subjects with normal hepatic function, the least-squares geometric mean ratios (90% CI) of GP1707D07 in subjects with mild hepatic impairment were 101.50% (72.63%-141.83%) for C_max, 86.98% (69.80%-108.38%) for AUC_0-<i>t</i>, and 87.06% (70.57%-107.40%) for AUC_0-∞. In subjects with moderate impairment, the corresponding ratios were 203.63% (147.50%-281.13%) for C_max, 155.23% (129.11%-186.64%) for AUC_0-<i>t</i>, and 157.26% (131.39%-188.22%) for AUC_0-∞. Mild impairment had minimal effect on GP1707D07 exposure, while moderate impairment increased C_max and AUC by ~1-fold and 0.5-fold, respectively, without resulting in clinically significant changes. A single 40-mg dose of suraxavir was safe and well tolerated in subjects with mild or moderate hepatic impairment. No dose adjustment is required for these populations.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05814926.