Single-dose tolerability and pharmacokinetics of leritrelvir in Chinese patients with hepatic impairment and healthy matched controls

Abstract

This study evaluated the safety and pharmacokinetics (PK) of a single dose of leritrelvir, a novel inhibitor of 3-chymotrypsin-like cysteine protease (3CLpro), in patients with hepatic impairment versus healthy participants with normal hepatic function. Eight participants with mild (Child-Pugh A) hepatic impairment, eight with moderate (Child-Pugh B) hepatic impairment, and eight healthy matched control participants were enrolled in this open-label, parallel clinical trial. After administration of leritrelvir of 400 mg, PK parameters were calculated and compared across groups. In total, 24 participants were enrolled and completed the study. Leritrelvir was generally well tolerated, with no serious adverse events or deaths reported during the study. Compared to the group with normal hepatic function, the geometric least-squares mean ratios (90% confidence intervals) for C_max, AUC_0-t, and AUC_0-∞ of leritrelvir in participants with mild hepatic impairment were 96.9% (69.3%, 135%), 92.2% (69.6%, 122%), and 92.1% (69.7%, 122%), respectively. For moderate hepatic impairment, the corresponding ratios were 91.6% (61.7%, 136%), 113% (80.0%, 160%), and 113% (80.0%, 159%). Leritrelvir exposures were comparable among the three groups. Overall, there was no clinically relevant difference in leritrelvir exposure in participants with hepatic impairment compared to normal controls. No dose adjustment is required for leritrelvir in patients with mild or moderate hepatic impairment.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT06161259.

Keywords: COVID-19; hepatic impairment; leritrelvir; pharmacokinetics; safety.

Fig 1

Mean plasma leritrelvir concentrations after administration in participants with normal hepatic function and participants with mild or moderate hepatic impairment (A) semi-log scale and (B) linear scale.

Fig 2

Box plot of leritrelvir C_max (A) and AUC_inf (B) in participants with normal hepatic function and participants with mild or moderate hepatic impairment. AUC_inf, area under the plasma concentration–time curve from time zero extrapolated to infinity; C_max, maximum observed plasma concentration.

Fig 3

Scatterplots of leritrelvir C_max (A) and AUC_inf (B) versus severity of hepatic impairment (mild [score 5–6] and moderate [score 7–9]). AUC_inf, area under the plasma concentration–time curve from time zero extrapolated to infinity; C_max, maximum observed plasma concentration.