A Phase I, Open-Label, Mass Balance Study of [14C]-Iberdomide in Healthy Subjects.
Eur J Drug Metab Pharmacokinet
; 49(3): 355-365, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38521893
ABSTRACT
BACKGROUND:
Iberdomide is a novel potent cereblon modulator (CELMoD®) agent, which is currently under clinical development for hematological malignancies. A human mass balance study was conducted to characterize the biotransformation and excretion pathways of iberdomide.METHOD:
After a single dose of radiolabelled [14C]-iberdomide (1 mg) in six healthy subjects. Blood, urine, and fecal samples were collected for pharmacokinetics, mass balance, and clinical laboratory assessments.RESULTS:
Results showed that a single oral dose of 1 mg iberdomide was generally well tolerated in healthy subjects. The recovery of [14C]-iberdomide-derived radioactivity in humans was 45.9% in urine and 42.6% in feces. Based on exposure (area under the concentration-time curve [AUC0-24]), iberdomide and M12 (metabolites) accounted for approximately 59% and 14% of circulating total radioactivity (TRA) exposure, respectively. Of the 88.5% TRA excreted, approximately 27% was excreted as unchanged iberdomide and 62% as metabolites, with similar amounts of excreted metabolites in the urine (16%) and feces (11%).CONCLUSION:
Biotransformation of iberdomide in humans included multiple oxidations of the morpholino moiety as well as glutarimide ring hydrolysis of parent and oxidized metabolites and a combination of these pathways. Iberdomide was the predominant component in human plasma, with metabolite M12 being the most prominent circulating metabolite. In excreta, similar iberdomide-derived radioactivity was found in urine and feces. TRIAL REGISTRATION NUMBER NCT03294603.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carbon Radioisotopes
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Feces
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Healthy Volunteers
Limits:
Adult
/
Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Eur J Drug Metab Pharmacokinet
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Francia