Related Experiment Video
Updated: Jun 30, 2025
Enhancing Efficiency and Radiolabeling Yields of Carbon-11 Radioligands for Clinical Research Using the Loop Method
Published on: December 20, 2024
A Phase I, Open-Label, Mass Balance Study of [14C]-Iberdomide in Healthy Subjects
Yiming Cheng1, Xiaomin Wang1, Liangang Liu2
1Clinical Pharmacology, Pharmacometrics, Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, NJ, USA.
Insights
Iberdomide, a novel cereblon modulator, undergoes biotransformation in humans, with excretion primarily through urine and feces as both unchanged drug and metabolites. This study characterized its metabolic pathways and excretion profile.
Area of Science:
- Pharmacology
- Drug Metabolism and Pharmacokinetics
- Clinical Pharmacology
Background:
- Iberdomide is a novel cereblon modulator (CELMoD®) agent under clinical development for hematological malignancies.
- A human mass balance study was conducted to characterize the biotransformation and excretion pathways of iberdomide (NCT03294603).
Purpose of the Study:
- To characterize the biotransformation and excretion pathways of iberdomide in healthy human subjects.
- To assess the mass balance and pharmacokinetic profile of a single oral dose of radiolabeled iberdomide.
Main Methods:
- Six healthy subjects received a single oral dose of 1 mg of radiolabeled [14C]-iberdomide.
- Blood, urine, and fecal samples were collected for analysis of radioactivity, pharmacokinetics, and clinical laboratory assessments.
Main Results:
- A single oral dose of iberdomide was well tolerated.
- Total recovery of radioactivity was 88.5%, with 45.9% in urine and 42.6% in feces.
- Iberdomide and its major metabolite M12 accounted for approximately 59% and 14% of circulating radioactivity, respectively. Approximately 27% was excreted as unchanged iberdomide and 62% as metabolites.
Conclusions:
- Human biotransformation of iberdomide involves oxidation and hydrolysis pathways.
- Iberdomide is the predominant circulating component, with M12 as the main metabolite.
- Excretion of iberdomide-derived radioactivity occurs in similar amounts in urine and feces.
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.
Related Concept Videos
01:21Drugs for Treatment of Constipation-Predominant IBS
01:26Imaging Studies III: Gastrointestinal Motility Studies and Virtual Colonoscopy
Radionuclide Testing
Radionuclide testing is a sophisticated medical technique for assessing gastrointestinal motility. It focuses on gastric emptying and colonic transit time. Radioactive markers track the movement of food through the digestive system, providing insights into gastrointestinal disorders.
In gastric emptying studies, a meal's liquid and...