PI-007 - PHARMACOKINETICS OF REMDESIVIR AND ITS METABOLITES IN PARTICIPANTS WITH MODERATE AND SEVERE HEPATIC IMPAIRMENT.

S. Regan, T. Chang, M. Abdelghany, J. Llewellyn, A. Baysa, S. Davies, D. Xiao, G. Shen, S. Girish, H. Winter, R. Humeniuk; Gilead Sciences, Foster City, CA, USA.

Background: Remdesivir (RDV) is an RNA polymerase inhibitor approved for treatment of COVID-19 [200 mg loading dose, 100 mg qd thereafter] in adult and pediatric patients, primarily metabolized by the high-capacity carboxylesterase 1 pathway (80% of metabolism), and by cathepsin A and CYP3A (10% each). The extensive hepatic contribution to RDV elimination and the prevalence of liver comorbidities in COVID-19 patients warranted a study in participants with hepatic impairment (HI).

Methods: This is a phase I, open-label study of RDV consisting of moderate and severe HI participants and healthy matched controls (HMC) based on age (±10 years), sex, and BMI (±20%). Participants received a single 100 mg IV dose of RDV and remained in the clinic for 8 days. The primary endpoint was pharmacokinetic (PK) parameters of RDV and metabolites.

Results: Preliminary PK and safety data from 10 moderate and 6 severe HI participants and their HMC are available. The average PK fold-change for all analytes and matrices assessed in the study are presented in Table 1. No serious treatment-related adverse events and no clinically significant changes in participant lab values were reported.

Conclusion: The 1.52 RDV AUCinf fold increase is within expected ranges and justifies no dose adjustment in COVID-19 patients with impaired hepatic function.

Average AUC and Cmax Fold-change estimates of RDV and Metabolites in Plasma and PBMC in Hepatic Impairment Participants Compared to Healthy Matched Participants