Pharmacokinetics, safety, and tolerability of onradivir in participants with severe renal impairment and matched healthy control participants.

Abstract

Onradivir is an influenza A virus RNA polymerase basic protein 2 inhibitor that is currently under development for the treatment of influenza A. Renal impairment can influence drug absorption, metabolism, and transport, potentially altering the pharmacokinetics (PK) of onradivir. This study aimed to provide guidance on clinical dosing for patients with renal impairment by evaluating the impact of renal impairment on the PK, safety, and tolerability of onradivir in a nonrandomized, parallel, single-dose study. Participants with severe renal impairment (estimated glomerular filtration rate 15-29 mL/min) along with healthy participants (n = eight per group) received a single oral dose of 600 mg onradivir. All participants exhibited good safety and tolerability after oral administration of onradivir, with treatment-emergent adverse events being limited to mild or moderate severity. Compared to participants with normal renal function, the maximum plasma concentration (C_max) of onradivir in those with severe renal impairment was similar; however, the area under the plasma concentration time curve from zero to the last quantifiable concentration (AUC_0-t) and the AUC from zero to infinity (AUC_0-inf) were slightly lower. The geometric mean ratios and 90% confidence intervals for C_max, AUC_0-t, and AUC_0-inf were 101.35% (63.85%-160.86%), 76.31% (52.47%-110.97%), and 76.56% (51.02%-114.90%), respectively. Severe renal impairment did not have a clinically meaningful effect on the PK, tolerability, or safety of onradivir. Therefore, no dose adjustment is necessary for patients with mild-to-severe renal impairment who are taking onradivir.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT06248567.