A human AME (hAME) phase I study administers a radiolabeled compound to evaluate the total fate of drug-related material (represented by the radiolabel). The study assesses tghe pharmacokinetics, mass balance, routes of excretion and metabolic pathways of the parent drug to ensure that the metabolite profile is comparable to what was seen in preclinical ADME studies and to identify any disproportionate or unique human metabolites.
Human AME studies aim to characterize any circulating metabolites greater than 10% of the AUC (area under the curve) of drug-related material and more than 80% of the recovered radioactivity from excreta.
- Safety Testing of Drug Metabolites
- ICH M3 (R2)
- EMA DDI
Human AME Study Timing
Conduct hAME studies earlier, especially if there are any possible toxic metabolites or metabolites that may be unique to humans compared to animals, and/or if you need to establish early information regarding major metabolites and excretion patterns in order to plan future study designs.
hAME studies are not typically conducted after Phase II of a clinical trial.
hAME Team & Process
The hAME team consists of nuclear pharmacists, radiation safety committee members, medical doctors, and DMPK scientists working with sponsors and clients to develop customized study designs that follow requirements from global regulatory authorities [e.g., FDA (including MIST, ICH) and EMA].
The ability to quickly analyze samples is key to a hAME study. In the United States, our shared campus in Wisconsin between the phase 1 clinical unit and the DMPK radioanalysis laboratory allows delivery of real-time radioanalysis results to manage subject-to-subject variability and facilitate timely subject release.
In the UK, DMPK labs and clinical sites have hospital collaborations to successfully complete patient human AME studies in addition to normal healthy volunteers.
- In vitro ADME characterization
- In vitro plasma protein binding / blood partitioning
- Radiosynthetic & metabolic synthesis
- Metabolite identification (to support MIST)
Human AME Study Outputs
- Tabulated proportions of metabolites
- High res MS/MS spectra
- Analysis of spectra
- Proposed biotransformation pathway