ABSTRACT:
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 (
n
= 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–
t
), 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–
t
, 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–
t
, 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 TRIALS:
This study is registered with ClinicalTrials.gov as
NCT05814926
.