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11 - Phase 1 Trials in Alzheimer’s Disease Drug Development

from Section 3 - Alzheimer’s Disease Clinical Trials

Published online by Cambridge University Press:  03 March 2022

By
Manfred Windisch
Edited by
Jeffrey Cummings ,
Jefferson Kinney  and
Howard Fillit
Jeffrey Cummings
Affiliation:
University of Nevada, Las Vegas
Jefferson Kinney
Affiliation:
University of Nevada, Las Vegas
Howard Fillit
Affiliation:
Alzheimer’s Drug Discovery Foundation
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Summary

Phase 1 clinical trials are the entrance to the further clinical development of new compounds. The chapter describes the regulatory background and highlights most important issues about selection of the maximum recommended starting dose, dose escalation steps, and definition of maximum tolerated dose, or maximum applied dose in a study considering actual guidelines. There is an overview about selection of subject populations and frequently used trial designs. The principles of single-ascending-dose and multiple-ascending-dose tolerance studies are described with a few examples of studies in Alzheimer’s disease (AD). The safety assessment is important in clinical practice, as AD drugs will be used over many years, so excellent tolerability is a must! In Phase 1, a careful assessment of pharmacokinetic (PK) properties of a new compound forms the basis for dose selection in Phase 2 and 3 studies and supports the decision on the treatment regimen. The importance of inclusion of different biomarkers in these studies to allow assessment of pharmacodynamic and PK relationship and to potentially identify first signals in human studies indicating therapeutic usefulness in the indication.

Keywords

Alzheimer’s diseasepharmacokineticspharmacodynamicsbiomarkersabsorptionmetabolismexcretionsafetytolerabilitydrug-drug interaction
Type
Chapter
Information
Alzheimer's Disease Drug Development
Research and Development Ecosystem
 , pp. 135 - 149
Publisher: Cambridge University Press
Print publication year: 2022

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