Phase I clinical trials have traditionally been focused on populations of normal healthy volunteers with the goal of determining the safety, tolerability, and pharmacokinetic profile of new investigational agents. As CNS drug development shifts its focus to the development of novel molecular entities, this approach will undergo an evolution. In this first part of a two-part series, the authors describe the traditional Phase I approach as well as challenges facing CNS drug development. The second half of the series will propose modifications to the traditional phase I design, including the incorporation of different populations, bio-marker surrogates, and adaptive designs.
*Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine-Wichita, and KU-Wichita Clinical Trials Unit
†Janssen Pharmceutical Companies of Johnson & Johnson, Titusville, NJ
Dr. Preskorn maintains a website at www.preskorn.com where readers can access previous columns and other publications.
Material in this column is adapted with permission from the chapter, “Phase I Trials: From Traditional to Newer Approaches,” by Matthew Macaluso, DO, Michael Krams, MD, PhD, and Sheldon H. Preskorn, MD, in Kalali A, ed. Essential CNS Drug Development. Cambridge University Press, in press.
Disclosure statement: Dr Macaluso has conducted clinical trial research as principal investigator funded by Abbott, Envivo, Evotec, Lilly, Naurex, Pfizer/Wyeth, Takeda, and Targacept. Within the last 12 months, Dr Preskorn, as chief science officer of the KU-Wichita Clinical Trials Unit and, in many cases, as principal investigator, has received grants/research support from or has served as a consultant for, on the advisory board, or on the speakers bureau for the following entities: Abbott, Allergan, Biovail, Boehringer Ingelheim, Bristol-Myers-Squibb, Eisai, Eli Lilly, Evotec, Ipsen, Johnson & Johnson, Labopharma, Link Medicine, Merck, NovaDel Pharma, Orexigen, Prexa, Psylin, Pfizer, Sunovion, Takeda, and Targacept.