Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development
Clinical and Translational Science February 26, 2016 T Burt, K Yoshida, G Lappin et al. 91 citations
Phase 0 clinical trials, including microdosing, limit drug exposure in first-in-human studies to reduce risks, costs, and time in drug development. These exploratory trials, governed by ICH M3 guidelines, involve subtherapeutic doses—for small molecules, no greater than 100 μg or 1/100th of the NOAEL—and require sensitive analytical tools like LC-MS/MS. Evidence supports extrapolating pharmacokinetic and pharmacodynamic data from microdose to therapeutic doses, though validity depends on drug properties and modeling. Applications include studying metabolism, receptor binding, and local drug effects. Ethical advantages include reduced human and animal exposure. The term 'in humano' is proposed for such limited human testing. An increasing number of applications demonstrate the versatility of these approaches.