First-in-Human, Single- and Multiple-Ascending-Dose Studies in Healthy Subjects to Assess Pharmacokinetics, Pharmacodynamics, and Safety/Tolerability of Iberdomide, a Novel Cereblon E3 Ligase Modulator.

ABSTRACT: Pharmacokinetics, pharmacodynamics, and safety/tolerability of iberdomide (CC-220), a highly potent oral cereblon E3 ligase modulator (CELMoD), were evaluated in escalating single-dose (0.03, 0.1, 0.3, 1, 2, 4, 6 mg) and multiple-dose (0.3 mg once daily for 14 days, 1 mg once daily for 28 days, 0.3 mg once daily for 28 days, or 1 mg once daily for 7 days with a 7-day washout, then once daily for 7 more days) studies in healthy subjects (n = 99). Iberdomide exposure increased in a dose-proportional manner. Terminal half-life was 9-13 hours after a single dose. Iberdomide decreased peripheral CD19+ B lymphocytes (E_max , 92.4%; EC₅₀ , 0.718 ng/mL), with modest reductions in CD3+ T lymphocytes (E_max , 34.8%; EC₅₀ , 0.932 ng/mL). Lipopolysaccharide-st

SUBMITTER: Ye Y 

PROVIDER: S-EPMC8246954 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature