A population pharmacokinetic analysis to evaluate the impact of renal impairment on the pharmacokinetics of iberdomide

Abstract

Iberdomide, a novel potent cereblon E3 ligase modulator, is under investigation for multiple myeloma. This study assessed how renal impairment (RI) affects iberdomide pharmacokinetics (PK). Twenty-six subjects with varying renal function, including those with severe renal impairment and those requiring intermittent hemodialysis (IHD), received a single oral 1 mg dose of iberdomide. Plasma, urine, and dialysate samples were analyzed to evaluate the PK of iberdomide and its major active metabolite, M12. Data were subsequently pooled with PK data from four other clinical trials involving 354 patients to develop a parent – metabolite population PK model using nonlinear mixed-effects modeling to assess the impact of various degrees of RI on drug exposure. The population PK model effectively described the PK of iberdomide and M12, showing that normal, mild, and moderate RI had no significant impact on iberdomide PK exposure, whereas severe RI reduced total clearance and increased PK exposure of iberdomide and M12. Subjects with kidney failure on IHD had comparable total clearance and PK exposure to those with normal renal function. These findings systematically examined the effects of various degrees of RI on iberdomide PK and provide a basis for informing iberdomide dosing in patients with varying degrees of renal impairment.