Phase-0 Microdosing Network - Accelerating Clinical Development

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

Phase-0 microdosing operations have many similar features to traditional Phase-1 programs. However, Phase-0 approaches are usually shorter, smaller, quicker, and therefore cheaper to run. Phase-0 Microdosing operations are primarily defined by the sub-therapeutic exposures to the test drug. This means the exposure is safer than traditional approaches, but also that research participants cannot expect therapeutic benefit. This has ethical, methodological, and technological implications.

Table 1. The table is adapted 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 Operations with Traditional Phase-1 Approaches.
  Phase-0/Microdosing (eIND, ICH M3 guideline) 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  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

 

 

 

 

 

 

 

 

test

test

test

test

test

Phase-0 Microdosing operations

Phase-0 Microdosing operations versus Phase-1