Trial methodology for clinical trials in stroke depends upon the specific purposes of the particular trial. Phase II clinical investigation is intended to include early controlled clinical trials designed to demonstrate safety, to gather information on the pharmacokinetic profile of the investigational drug and to establish first proof of efficacy. Phase III clinical trials are expanded controlled trails. They are performed after efficacy has been established, at least to a certain degree, and are intended to gather additional evidence on efficacy, plus further evidence of safety and tolerance.