To conduct the single-center, single-dose, open-label mass balance clinical trial using radioactive radiolabeling technology，the human [14C]-AME study monitors the absorption, metabolism, and excretion process after administration of [14C] test article formulation. The main research scope includes:
1) Determining the radiolabeled test article’s mass balance results and human main excretion route,
2) Analyzing the ratio of whole blood to plasma and the pharmacokinetics of total radioactivity in plasma,
3) Identifying the major metabolites in urine, feces, and plasma.
The human [14C]-AME study could evaluate the overall pharmacokinetic characteristics of the test article, including absorption, excretion route (mass balance), and metabolite identification. The study can also provide the basis for clinical PK and DDI experimental design and guidance for drug instruction. The WuXi AppTec's DMPK platform cooperates with the Clinical Center to conduct the human [14C]-AME clinical study.
The human [14C] -AME study is usually carried out after the phase I clinical escalation experiment. The safe and reliable human radioactive dose is estimated based on the results of single-dose or multiple-dose escalation experiments and the QWBA experiment. Subjects are given a dose of [14C] test article, and urine, feces, plasma are collected. Total radioactivity (TRA) in urine and feces is measured to obtain the mass balance results. In addition, metabolite profiling is performed on selected plasma, urine, and feces samples. Possible metabolic pathways and major metabolites of the test article are provided, and the toxicity or activity of the major metabolites should be tested. The comprehensive results can guide further clinical study design to ensure test articles can be used safely and effectively in patients.