E8: GENERAL CONSIDERATIONS FOR CLINICAL STUDIES

Question 1

3.1 Considerations for the Development Plan

3.1.1 Non-Clinical Studies

Important considerations for determining the nature of non-clinical studies and their timing with respect to clinical trials include:

Answer 1

a) duration and total exposure proposed in individual patients

b) characteristics of the drug (e.g. long half life, biotechnology products)

c) disease or condition targeted for treatment

d) use in special populations (e.g. women of childbearing potential)

e) route of administration

The need for non-clinical information including toxicology, pharmacology and
pharmacokinetics to support clinical trials is addressed in the ICH M3 and S6
documents.

Question 2

3.1 Considerations for the Development Plan

3.1.1.1 Safety Studies

Answer 2

For the first studies in humans, the dose that is administered should be determined
by careful examination of the prerequisite non-clinical pharmacokinetic,
pharmacological and toxicological evaluations (see ICH M3). Early non-clinical
studies should provide sufficient information to support selection of the initial human
dose and safe duration of exposure, and to provide information about physiological
and toxicological effects of a new drug.

Question 3

3.1 Considerations for the Development Plan

3.1.1.2 Pharmacological and Pharmacokinetic Studies

Answer 3

The basis and direction of the clinical exploration and development rests on the nonclinical
pharmacokinetic and pharmacology profile, which includes information such
as:
a) Pharmacological basis of principal effects (mechanism of action).
b) Dose-response or concentration-response relationships and duration of action
c) Study of the potential clinical routes of administration
d) Systemic general pharmacology, including pharmacological effects on major organ
systems and physiological responses
e) Studies of absorption, distribution, metabolism and excretion