Phase I clinical studies represent the first step of testing a new drug on humans. Usually the subjects are healthy volunteers. These studies are often referred to as clinical pharmacology studies, as they are designed in such a way as to determine the tolerability, safety, existence of therapeutic action, pharmacokinetic and pharmacodynamic characteristics, and sometimes initial efficacy parameters in studies in humans.
Therapeutic parameters under investigation include the following: parameters of absorption, distribution, metabolism, excretion, as well as the advantageous route of administration and safe dosage level. Usually Phase I studies last from 6 months to one year.
The purpose of Phase I:
to determine tolerability of the study drug and potential therapeutic effect
Usually Phase I clinical studies involve more than 100 healthy volunteers being closely monitored. The exception is studies of oncologic drugs in humans. From the standpoint of medical ethics, with regard to the potential toxicity of oncologic drugs, it is preferable to test them in cancer patients and not in healthy volunteers. The main parameters that are studied in Phase I clinical studies, are the following:
- Safety, tolerability of single and multiple dosing of the drug
- Interindividual and individual variability
- Effect on basic physiological parameters
- Bioavailability after administration of single dose and relation to food intake
- The constants of elimination rate, absorption and excretion of the drug and its metabolites
- Peak serum concentrations of the drug and its metabolites
- Time to reach maximum concentration
- Metabolism and drug interactions
- Half-life of the drug
- Pharmacokinetic and pharmacodynamic parameters of the drug
- Binding to blood proteins
- Comparison of the activity and above mentioned parameters between dosage forms and doses
- Area under the curve “concentration-time” (AUC)