Microdosing in Phase O: A Q&A with J. Scott Tarrant, Xceleron

Microdosing, sometimes referred to as a human Phase 0 study, is the administration of subpharmacologic doses of experimental drugs to human volunteers, up to a maximum of 100 μg. For purposes of this discussion, I will only address studies conducted using accelerator mass spectrometry (AMS), but studies have also been conducted using positron emission tomography and, in some cases, liquid chromatography–tandem mass spectrometry (LC–MS/MS). The intent of the microdose study is to get a very early read on the PK of novel molecules to make critical decisions about which molecules to advance. This evaluation can be accomplished in as little as six months with minimal preclinical toxicology and GLP [good laboratory practices] material under an exploratory investigational new drug application (eIND) in the United States or under an abbreviated common technical document (CTD) in Europe (1, 2). A microdose study allows drug developers to rank the order of several drug candidates coming out of discovery and select those that are most appropriate based upon human PK data. In the traditional development cycle, this evaluation can take up to 18 months for one molecule at a cost of $3–5 million. In a Phase 0 study, however, one can test as many as five molecules in one clinical study and gain all of the relevant PK data in six months. Microdosing is about making decisions on early drug-candidates in the context of all the other tools at a company's disposal by using humans as the model instead of animals while at the same time de-risking the likelihood of clinical failure later.