1. Chrispy on June 4, 2007 9:34 PM writes...

Perhaps Phase 0 would also apply to microdosing, where a subclinical dose of radiolabelled compound is given in order to assess its bioavailability and metabolism.

http://en.wikipedia.org/wiki/Microdosing

My understanding is that the kinetics remain first order down to low doses -- like 1/100 -- anyone know if this is true?

2. Petros on June 5, 2007 1:57 AM writes...

The term Phse 0 is not new, although the context applied in this case is very different from that used previously.

Some years ago Pharmagene (noow Asterand) coined teh term to describe the studying of novel drugs on human tissue i.e. a preclinical study. While Roche's website used to use the phase 0 term to indicate those compounds which were in preclinical development (This category are now no longer listed).

3. Kay on June 5, 2007 7:37 AM writes...

The fact that Abbott allowed NCI to fiddle with 888 indicates that the compound had no path to the clinic (we assume that Abbott is not so poor that it is forced to work with NCI). In this case, this is all upside for Abbott.

Because our current in vitro and animal-based approaches are so effective, there is no reason to take this level of risk.

4. Keith Robison on June 5, 2007 8:14 AM writes...

Phase 0 has also been used to describe the validation of a pathway biomarker in a disease without any drug exposure.

5. Morten on June 5, 2007 1:27 PM writes...

"The NCI is already conducting a second phase 0 trial, using an imaging technique rather than biomarkers, and is planning a third."
I would think that PET-imaging to look at BBB permeability would be the most useful application of phase 0 trials. I think IMAnet in Uppsala killed some drug already on the market because they showed that there was only BBB permeability in some humans (and apparently not enough).
Might be good for cancer as well if you expect the drug to target cancer cells.

6. Groby Lington on June 5, 2007 2:25 PM writes...

This may not be so much to determine if the target is being hit but rather to provide an early dose validation of the biomarker for its subsequent use in Phase I and 2 studies where one can correlate dose level with toxicities and efficacy.

7. Oren Grad on June 5, 2007 8:53 PM writes...

NCI's detailed explanation of what they mean by Phase 0 is here.

8. Groby Lington on June 6, 2007 12:31 PM writes...

This excerpt from the useful NCI link (thanks Oren) seemed relevant here:

There are several different types of phase 0 trials, ranging from those that examine new drugs to those that test new imaging agents. Some examples include:

* Testing to see if a new drug that was developed in the lab can bind to, and inhibit, its target in humans
* Provide PD and PK data prior to definitive testing in more people
* Refine what type of biomarker is most effective using tumor tissue
* Determine which of two agents is the most promising
* Using a variety of novel imaging technologies, determine the extent of drug that is distributed in the body and whether it effectively acts upon its target

9. Nilesh Jadhav on October 3, 2007 9:11 AM writes...

Phasse zero study not only examine safety and effectveness ,insted they gather data on the targetting, action and metabolism of adrug in the body.

10. Dr. Swapnil bhowaet on November 9, 2009 11:56 AM writes...

Exploratory IND studies are clinical trials conducted early in phase I (hence, the term phase 0) that involve limited human exposure and have no therapeutic or diagnostic intent.2 The purpose of the phase 0 study is to assist in the go versus no-go decision-making process of a drug’s fate earlier in the development process, using
relevant human models instead of relying on sometimes inconsistent animal data, thus helping to confirm end points such as mechanism of action, pharmacology, bioavailability, pharmacodynamics, and metabolic
microdose assessments. These studies of novel agents expose a small number of patients (perhaps 10 or fewer) to a limited duration (eg, 7 days or less) and dose (in the range of one 100th of the dose required to yield a pharmacologic effect of the test substance with a maximum dose of _ 100 _g). They are conducted before the traditional phase I dose-escalation safety and tolerance studies. By not having the traditional phase I objectives of toxicity and dose finding, phase 0 studies can be conducted early in the development process and are actually considered more of a discovery, rather than development, tool. There must be several considerations before initiating a phase 0 trial, given that not all novel agents will be appropriate for pre–phase I analysis. To
evaluate target effect, a biomarker must be known and an assay to measure it must be developed and validated before study initiation.6 It is imperative that proper sample handling be acknowledged, and if a
surrogate is being used, that it gives meaningful results relative to the tissue/organ target of attack. The ethics of doing phase 0 trials must also be considered carefully. These trials have no therapeutic intent and often will require significant invasive procedures. They have a finite treatment duration and, theoretically, are not in the range of efficacious dosing. Fewer toxicology data are necessary, so there is some concern that this limited
toxicology will be insufficient and not well defined in every drug scenario to maximize patient safety. The patient must be made aware of the investigational nature of these studies, the lack of therapeutic intent, and the limited toxicology and safety testing.