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Comparison of Phase-0/Microdosing with Traditional Phase-1 Approaches

Phase-0 including microdosing approaches have many similar features to traditional Phase-1 program. However, Phase-0 approaches are usually shorter, smaller, quicker, and therefore cheaper to run.

The following table is adopted from: Burt T, Yoshida K, Lappin G, Vuong L, John C, et al. 2016. Microdosing and other Phase-0 Clinical Trials: Facilitating Translation in Drug Development. Clinical and Translational Science 9:74-88.

Comparison of Phase-0/Microdosing with Traditional Phase-1 Approaches.
  Phase-0/Microdosing (eIND) Traditional Phase-1 (IND)
Therapeutic intent None Possible
Study of systemic tolerability None Yes
Proof of Mechanism Possible (e.g., PET receptor binding and displacement) Possible
Preclinical Package Limited, variable; depends on extent of exposure to the test article and experimental goals Full requirements
-       in-vitro models Full requirement Full requirements
-       toxicology Limited, variable Full requirements
-       genotoxicology None or limited Full requirements
GMP Flexible, depending on available preclinical information and route of administration (e.g., sterility ensured for IV route) Full requirements
Regulatory Review 30-day 30-day
Usual Duration of Program 4-12 months 12-24 months
Cost of Program $ 0.5-0.75 M $ 1.5-2.5 M
Studies
-       size (typical) 4-10 participants 6-30 participants
-       duration (per participant) 1-14 days* 6-60 days*
-       number of study sites Single Single/Multiple
-       maximal dose <MTD MTD
-       exposure Limited (see Table 1) Multiple doses allowed
-       population Healthy volunteers or patients
Vulnerable populations
Mostly healthy volunteers (unless toxicity risk is high, e.g., in oncology trials)
* - on average, could be longer with longer half-life drugs; MTD – maximum tolerated dose