Guidelines for conducting bridging studies in Alzheimer disease

This report provides guidelines for conducting bridging studies in patients with Alzheimer disease (AD). Bridging studies are late phase I safety/tole rance studies that determine the maximum tolerated dose (MTD) in patients b efore phase LI efficacy studies are initiated, facilitating the transition from phase I to phase II development. Determining the MTD in patients maxim izes the potential to detect efficacy by permitting the use of the highest tolerated doses in phase II while providing a good understanding of potenti al adverse events. Bridging studies should be double-blind, placebo-control led, inpatient studies conducted in acute-care facilities by clinical perso nnel who are equipped to handle unexpected contingencies under the oversigh t of a competent, multidisciplinary review board. Patients should be in goo d physical health (excluding AD), and a comprehensive informed consent proc edure must be instituted. We recommend initially using a fixed-dose panel d esign with a dose schedule based on the MTD in normal volunteers and later establishing the dose titration MTD.