Pharmacokinetics and Safety of VV116 in Subjects With Mild or Moderate Hepatic Impairment Compared With Healthy...

VV116 (Mindvy, JT001) is a deuterated oral derivative of remdesivir hydrobromide developed for the treatment of COVID-19. Because hepatic dysfunction may influence drug exposure, this Phase 1, open-label, parallel-group study characterized the pharmacokinetics and safety of VV116 in adults with mild or moderate hepatic impairment (classified by the Child-Pugh method) compared with matched healthy controls. Each participant received a single oral 0.3-g dose of VV116 under fasting conditions, and serial plasma samples were collected through 72 h to quantify VV116 and its active metabolite, 116-N1, by validated LC-MS/MS. Overall exposure (AUC) in mild and moderate impairment was comparable to controls (AUC_0-t GMRs 94.10% [90% CI 71.59%-123.68%] and 97.72% [74.34%-128.44%]), with similar median T_max and t_1/2; C_max was lower in both impairment cohorts. Treatment-emergent adverse events occurred in 12.5% (mild), 37.5% (moderate), and 12.5% (control) groups; all were mild or moderate, transient, and resolved without treatment. The higher incidence in the moderate group was not considered clinically meaningful, as events were isolated and not related to VV116 exposure. No serious adverse events, deaths, or discontinuations occurred. Overall, hepatic impairment had no clinically relevant effect on VV116 pharmacokinetics, and dose adjustment appears unnecessary for patients with mild or moderate hepatic impairment.