Guidelines for conducting bridging studies in Alzheimer disease

Abstract

This report provides guidelines for conducting bridging studies in patients with Alzheimer disease (AD). Bridging studies are late phase I safety/tolerance studies that determine the maximum tolerated dose (MTD) in patients before phase II efficacy studies are initiated, facilitating the transition from phase I to phase II development. Determining the MTD in patients maximizes the potential to detect efficacy by permitting the use of the highest tolerated doses in phase II while providing a good understanding of potential adverse events. Bridging studies should be double-blind, placebo-controlled, inpatient studies conducted in acute-care facilities by clinical personnel who are equipped to handle unexpected contingencies under the oversight of a competent, multidisciplinary review board. Patients should be in good physical health (excluding AD), and a comprehensive informed consent procedure must be instituted. We recommend initially using a fixed-dose panel design with a dose schedule based on the MTD in normal volunteers and later establishing the dose titration MTD.