Multiple Dose Studies

Abstract

The development of a New Chemical Entity (NCE) in man is highly regulated (ICH-E8 1997), and normally starts with a single ascending dose study in healthy young male volunteers. As virtually all drugs are administered repeatedly, it is important that the safety and pharmacokinetics are also investigated following multiple dosing. A single ascending dose study is therefore normally followed by a multiple ascending dose study in healthy volunteers. In this, the investigator aims to establish the safety, maximum tolerated dose at steady state, and pharmacokinetics of the NCE before proceeding into patients. This may be one of the few opportunities for assessing the pharmacokinetics of the compound in detail following multiple dosing, albeit not usually in patients. The route and, ideally, the dose regime should be those proposed for the final product at registration. The choice of subjects is often young healthy male volunteers, but regulatory authorities encourage the use of females at an early stage in development. Healthy volunteers may also include the elderly and individuals of different races if appropriate for the development program.