Pharmacokinetics and Safety of Deuremidevir Hydrobromide (JT001) in Subjects with Mild and Moderate Renal Impairment: An Open‐Label, Parallel‐Group Phase I Study

Abstract

JT001 (deuremidevir hydrobromide, VV116) is an oral antiviral prodrug that is rapidly converted in vivo to its active metabolite, 116‐N1. Since 116‐N1 is mainly cleared by the kidneys, renal impairment may increase its systemic exposure. This study evaluated the pharmacokinetics of 116‐N1 following a single 0.3‐g oral dose of JT001 in participants with mild or moderate renal impairment and matched healthy controls. Absorption was generally similar across groups, with comparable time to peak concentration. However, declining renal function increased exposure to 116‐N1 and slowed its elimination. Terminal half‐life increased from 5.31 to 8.13 and 11.2 h in mild and moderate impairment. Apparent oral clearance decreased from 34.3 L/h in healthy participants to 21.4 and 13.8 L/h in patients with mild and moderate renal impairment, respectively. Twenty‐four participants (eight per renal function group) were enrolled. Geometric mean AUC _0–t increased by 63% in participants with mild renal impairment (geometric mean ratio [GMR] 163.31%, 90% CI 135.99%–196.12%) and by 157% in those with moderate renal impairment (GMR 257.42%, 90% CI 214.35%–309.13%), whereas C _max remained comparable between groups. JT001 was generally well tolerated, with no serious or grade ≥3 treatment‐related adverse events. To further assess clinical relevance of these findings, the renal impairment data were incorporated into an updated population pharmacokinetic model. Simulations suggested that the approved regimen was suitable for patients with mild renal impairment, whereas a reduced regimen of 300 mg twice daily on Day 1 followed by 200 mg twice daily on Days 2–5 was recommended for patients with moderate renal impairment.