| I |
Define doses and dosing frequency that applicable for a particular study with reference to pharmacokinetic data. Most likely a controlled laboratory experiments than population-based clinical trials. |
Narrow scale of healthy volunteers (generally ~ 20 subjects) |
- Mircrodose trials at total dose ≤ 100 μg.
- Microdose trials at cumulative dose ≤ 500 μg.
- Single Dose Studies at Sub – therapeutic Doses or into the Anticipated Therapeutic Range.
- Dosing up to 14 days into the therapeutic range but not intended to evaluate clinical MTD.
- Dosing up to 14 days and not to exceed duration of dosing in non- rodent; into therapeutic range but not intended to evaluate clinical MTD.
|
- Estimation of Initial safety and tolerability.To determine tolerability of dose range for later stage and to determine the nature of adverse reactions.
- Pharmacokinetic.ADME study with priority to determine clearance of product and possibility accumulation of parent drug and metabolites as well as potential drug-drug interaction.
- Assessment of pharmacodynamic.Studies of drug blood levels to response (PK/PD studies).
- Early measurement of drug activity.Preliminary study of drug benefit.
|
|
II
|
Investigates the occurrence of possible clinical benefits and existence of side effects. The trial sometimes is set up to screen for few drugs with genuine potential. |
Small scale of homogenous patients that usually conducted at one site (generally ~ 100-200 subjects but it is advised that sample size is calculated for specific studies) |
Dose-escalation design
Parallel dose-response design |
To evaluate for efficacy and safety profile for drug’s therapeutic indication, potential study endpoints, therapeutic regimens and potential target populations |
|
III
|
A well randomized controlled clinical trial research program for a new drug evaluation to conclusively demonstrate the efficacy of the investigational drugs in a population by means of compilation of all clinical trials results in this phase into one package evidence to be presented to the regulatory authority for approval. |
Large scale of patients presenting diseases symptoms that usually conducted at multiple study sites (generally > 200 subjects but it is advised that sample size is calculated for specific studies) |
Dose-response relationship in:
- wider population (multiple site)
- different stages of disease
- combination with other drugs
|
To confirm preliminary evidence accumulated in Phase II. |
IV
STUDY ENDPOINTS
|
A trial of products that already have marketing authorization. Studies may be undertaken to expand the indications listed on a marketing authorization either for a different diseases or to gain more safety data for newly registered product. |
Post-marketed product |
Additional:
- Drug-drug interaction studies
- Dose-response
- Safety studies
|
To support use under the approved indication. |
