Arzneimittelforschung

Abstract

Phase I clinical trials are of particular importance in drug research. In this phase, a new chemical entity is applied for the first time to humans, normally to young healthy volunteers. The primary aims are safety and tolerability, the pharmacokinetic, and as far as possible the pharmacodynamic behaviour of the new substance in the human body. The effects of age, gender, race, drug interactions, food intake and organ damage are examined in studies of later phase I. This article deals mainly with "first into human" studies during early phase I. We describe the processes before, as well as the technical, medical and regulatory requirements during, the conduct of a "first into human" trial. Furthermore, the choice of galenic formulation, route of application, and study population, and the risks at trial participation are addressed. In addition to different dose escalating schemes, which serve for the identification of the maximum tolerated dose, and other common study designs for "first into human" trials, this article reviews the literature on the determination of the first dose.