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 (Cmax, AUC0-t, AUC0-∞, t1/2) 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 (Tmax) but a reduced elimination half-life (t1/2) 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 Cmax, 54.19% for AUC0-t, and 56.83% for AUC0-∞ 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.