Tolerability and pharmacokinetics of leritrelvir in Chinese participants with severe renal impairment and healthy matched control subjects

Aims The study's aim is to evaluate the pharmacokinetics (PK) and safety of leritrelvir, a novel 3‐chymotrypsin‐like cysteine protease (3CLpro) inhibitor, in patients with severe renal impairment (RI; n = 7) compared to healthy controls ( n = 8). Methods This nonrandomized, open‐label, parallel‐group, single‐dose trial included primary PK endpoints ( C max , AUC 0‐t , AUC 0‐∞ , t 1/2 ) and safety endpoints (AEs, vital signs, laboratory tests). Log‐transformed PK parameters were analysed by ANOVA to calculate GMRs (90% confidence intervals [CIs]) for group comparisons, with statistical significance assessed for exposure differences. Results PK analysis revealed similar median time‐to‐peak concentration ( T max ) but a reduced elimination half‐life (t 1/2 ) in the RI group (4.20 h vs . 5.09 h). The geometric mean ratios (90% CI) of systemic exposure parameters indicated increases of 30.34% for C max , 54.19% for AUC 0‐t , and 56.83% for AUC 0‐∞ in the RI group compared to controls. Conclusions Modest PK alterations in severe renal impairment are clinically insignificant given leritrelvir's wide therapeutic index. The drug is well‐tolerated (mild‐to‐moderate, short‐duration AEs), and no dose adjustment is needed for patients with renal impairment.