Grants and Contracts Operations Branch (GCOB)

In January 2006, the Food and Drug Administration (FDA) published "Guidance for Industry, Investigators, and Reviewers: Exploratory IND Studies" ( http://www.fda.gov/cder/guidance/7086fn.pdf). The first-in-human, exploratory IND studies conducted early in Phase 1 are intended to assess feasibility for further development of the drug or candidate products. For example, the most promising lead product can be selected from a group of structurally related candidates on the basis of pharmacokinetic or pharmacodynamic properties observed during these studies. This guidance discusses pharmacology, toxicology, and clinical studies, as well as chemistry, manufacturing, and controls information that should be considered when planning exploratory IND studies. Examples of possible trials include:

• Clinical pharmacokinetics, metabolism, or imaging studies with single, sub-pharmacologic microdoses of candidate products administered to a limited nubmer of patients or healthy volunteers;
• Clinical studies for extrapolating efficacy-related mechanisms of action from preclinical systems to patients, e.f., binding properties of candidates or inhibition of a target enzyme by candidates; and
• Clinical trials to study pharmacologic effects of candidate products with repeated administration of a pharmacologic dose for up to seven days, or escalated dose studies to investigate pharmacodynamic endpoint(s), not to determine the limits of tolerability.

Contact your Program Director for further discussion or appropriate referral ( http://dtp.nci.nih.gov/branches/gcob/gcob_staff.pdf).