E8: General Consideration for Clinical Trials

Question 1

3.1.3.5

Development of an application unrelated to original approved use

Answer 1

After initial approval, drug development may continue with studies of new or modified indications, new dosage regimens, new routes of administration or additional patient populations. If a new dose, formulation or combination is studied, additional human pharmacology studies may be indicated, necessitating a new development plan.

The need for some studies may be obviated by the availability of data from the original development plan or from therapeutic use.

Question 2

3.1.4

Special Considerations

Answer 2

A number of special circumstances and populations require consideration on their own when they are part of the development plan.

Question 3

3.1.4.1

Studies of Drug Metabolites

Answer 3

Major active metabolite(s) should be identified and deserve detailed pharmacokinetic
study. Timing of the metabolic assessment studies within the development plan
depends on the characteristics of the individual drug.

Question 4

3.1.4.2 Drug-Drug Interactions

Answer 4

If a potential for drug-drug interaction is suggested by metabolic profile, by the results of non-clinical studies or by information on similar drugs, studies on drug interaction during clinical development are highly recommended. For drugs that are frequently co-administered it is usually important that drug-drug interaction studies be performed in non-clinical and, if appropriate in human studies. This is particularly true for drugs that are known to alter the absorption or metabolism of other drugs (see ICH E7), or whose metabolism or excretion can be altered by effects by other drugs.