A Phase 0 study (also known as an exploratory IND study or microdosing study) is a very early clinical study in humans that can be conducted before conventional Phase I studies.
The aim is to obtain initial information on pharmacokinetics, distribution, or target binding with minimal risk—often using very low doses and without therapeutic intent.
What distinguishes Phase 0 from Phase I?
While Phase I studies primarily investigate safety, tolerability, and dose finding, Phase 0 focuses on early, exploratory data to support decision-making within the development program.
Typical differences:
- Very low dose (often a microdose, e.g., 1/100 of the expected pharmacologically active dose)
- Small number of participants and short study duration
- No intention to achieve a therapeutic effect
- Strongly analytics-driven (e.g., sensitive bioanalysis, PET tracer approaches)
What are Phase 0 studies used for?
Phase 0 studies can help make an early decision on whether a drug candidate should be further developed. They are used, among other things, to:
- collect initial human PK data and assess animal-to-human extrapolation
- investigate target engagement or tissue distribution
- prioritize candidates within a compound class
Regulatory framework and limitations
From a regulatory perspective, Phase 0 studies are possible, but they still require a robust study protocol, ethics approval, and appropriate quality standards for the investigational product approach. The data are generally not sufficient to infer safety for higher doses.
Positioning in project management
From an economic perspective, Phase 0 can make development more efficient because early “go/no-go” decisions are based on human data. At the same time, it creates additional effort and is only meaningful if the results are truly decision-relevant.
FAQ
Is a Phase 0 study mandatory?
No. It is optional and is only conducted if it provides clear additional insight.
Who participates in Phase 0 studies?
Mostly healthy volunteers; in some cases, patients may also be included if this is scientifically or ethically appropriate.
Why is a microdose often used?
A microdose reduces risk, while still allowing measurement of PK parameters or distribution if sufficiently sensitive analytical methods are available.