ABSTRACT
As indicated in 21 CFR 312.21, the primary objectives of phase I clinical investigation are to (i) determine the metabolism and pharmacological activities of the drug, the side effects associated with increasing dose and early evidence in effectiveness and (ii) obtain sufficient information regarding the drug’s pharmacokinetics and pharmacological effects to permit the design of well controlled and scientifically valid phase II clinical studies. Thus, phase I clinical investigation includes studies of drug metabolism, bioavailibility, dose ranging and multiple dose. The primary objectives of phase II studies are not only to initially evaluate the effectiveness of a drug based on clinical endpoints for a particular indication or indications in patients with disease or condition under study but also to determine the dosing ranges and doses for phase III studies and common short-term side effects and risks associated with the drug. In practice, the focus of phase I dose response studies is safety, while phase II dose response studies emphasize the efficacy.
