Regular Research ArticlesMemantine Treatment in Mild to Moderate Alzheimer Disease: A 24-Week Randomized, Controlled Trial
Section snippets
Participants
This study (MEM-MD-10) was approved by the Institutional Review Boards of all participating sites. Each participant and his or her caregiver or legally authorized representative read and assented to participation guidelines and provided written informed consent before participating in any study procedures. The trial was conducted between October 8, 2001, and June 16, 2003. Four hundred three participants were recruited from 42 U.S. sites. All met clinical diagnostic criteria for probable AD
Participants
Participant disposition is summarized in Figure 1. Of the 403 participants who entered the study, 202 were assigned placebo and 201 were assigned memantine. No participants discontinued during the placebo lead-in period for lack of compliance. A total of 394 participants (198 in the placebo group, 196 in the memantine group) received at least one dose of double-blind study medication and had at least one postbaseline efficacy assessment, forming the ITT population used in the efficacy analysis.
DISCUSSION
Overall, this double-blind, placebo-controlled phase III study of mild to moderate AD supports the efficacy of memantine for 24 weeks. A measure of cognitive function, the ADAS-cog, demonstrated efficacy with both the protocol-specified LOCF imputation as well as an MMRM approach. A measure of clinical significance, the CIBIC-Plus, also supported the efficacy of memantine. Finally, memantine was shown to have an advantage over placebo on the NPI, an important measure of behavioral
CONCLUSION
This study supports the safety and efficacy of memantine, an NMDA receptor antagonist, for treatment of patients with mild to moderate AD.
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This research was funded by Forest Laboratories, Inc., New York, NY.
Some of the data in this article have been previously presented. Some of the data in this article have been previously presented. The first presentations of patient demographics, baseline characteristics, LOCF data by week for the ADAS-cog, CIBIC-Plus and NPI, LOCF data at week 24 for the ADCS-ADL23, emergence of behavioral symptoms by NPI domain, and most frequent AEs, have occurred at the following meetings: American Association for Geriatric Psychiatry, February 21–24, 2004, Baltimore, MD; American College for Neuropsychopharmacology, December 12–16, 2004, San Juan, Puerto Rico; American Association for Geriatric Psychiatry, March 3–6, 2005, San Diego, CA; American Academy of Neurology, April 9–16, 2005; American Neurological Association, September 25–28, 2005; and International College of Geriatric Psychoneuropharmacology, November 2–5, 2005, Pittsburgh, PA.
The trial was conducted at multiple sites and led by Forest Laboratories, Inc. The effort to produce this research report was conducted at the Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine and VA Northwest Network Mental Illness Research, Education, and Clinical Center, Seattle, WA, and at Forest Research Institute, Jersey City, NJ.
Dr. Peskind has participated in speakers' bureau and received grant support and honoraria from Forest Laboratories, Inc. She has participated in a speakers' bureau and consulting for Janssen, speakers' bureau and consulting as well as unrestricted educational grant receipt from Novartis, speakers' bureau and honoraria from Pfizer, speakers' bureau, consulting, and stock ownership (<$1,000) from Bristol-Myers Squibb, and stock ownership (<$1,000) from Elan. Dr. Potkin has received grant/funding from AstraZeneca, Bristol-Myers Squibb, Forest Laboratories, Fujisawa-Astellas, Janssen Pharmaceutical, Mitsubishi, Novartis, Organon, Otsuka, ONO, Pfizer, Sanofi-Synthelabo, Solvay, and Wyeth. He has been involved in consultancy/advisory board/honoraria from Acadia Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Janssen Pharmaceutical, Forest Laboratories, Mitsubishi Pharma Corp., Novartis, Organon, Otsuka, Pfizer, Praecis, Roche, and Solvay Pharmaceuticals and has participated in a speakers' bureau for AstraZeneca, Bristol-Myers Squibb, Novartis, Pfizer, and Otsuka. Dr. Pomara has received grants or been a consultant for Forest Laboratories, Inc., Merck & Co., Inc., Pharmacia & Upjohn, Eli Lilly, Novartis Pharmaceuticals Corp., Astra-Zeneca Pharmaceuticals Group, Janssen Research Foundation, Hoechst-Roussel Pharmaceutical Inc., G.D. Searle & Company, Roussel Uclaf, Pfizer, Inc., and Neurochem and has participated in speakers' bureau for Forest Laboratories. Dr. Ott has received grant funding from Forest Laboratories, Inc., Sanofi-Synthelabo, and Fujisawa-Astellas. He has been a consultant for Forest Laboratories, Inc., Pfizer, Ortho-McNeil, Jannsen, and Sanofi-Synthelabo. He has participated in a speakers' bureau for Forest Laboratories, Inc., Pfizer, OrthoMcNeil, Jannsen, and Novartis. Drs. Graham, Olin, and McDonald are employees of Forest Laboratories, Inc.
Forest Laboratories, Inc. provided all financial and material support for the research, consulted with the authors and the members of the Memantine MEM-MD-10 Study Group on the study design, monitored the conduct of the study as well as the collection of the data, provided statistical analysis of the data, and assisted the authors in the preparation, review, and approval of the manuscript. Specifically, we acknowledge from Forest Laboratories, Inc., Joanne M. Bell, Ph.D. (formerly at Forest Laboratories, Inc.), E. Malca Resnick, Ph.D., and Eugene Schneider, M.D., who provided editorial and technical support for the manuscript, and Xinwei Daniel Jia, Ph.D., and Yang Xie, Ph.D. (formerly at Forest Laboratories, Inc.), who provided statistical support for the analysis of the data. From Prescott Medical Communications Group, we acknowledge Merrilee Johnstone, Ph.D., Annalise Nawrocki, B.A., and Kristen Andersen, Ph.D., for editorial support.
The Memantine MEM-MD-10 Study Group consists of the following members: Piero Antuono, M.D.; William Au, M.D.; Nancy Barbas, M.D.; Barry Baumel, M.D.; Lesley Blake, M.D.; John Blass, M.D.; Greg E. Cooper, M.D., Ph.D.; Michael DePriest, M.D.; David Drachman, M.D.; Eugene A. Duboff, M.D.; Steven L. Dubovsky, M.D.; Larry Eisner, M.D.; Jay Mark Ellis, D.O.; James M. Ferguson, M.D.; Concetta Forchetti, M.D.; James Galvin, M.D.; Neill Graff-Radford, M.D.; Lindy E. Harrell, Ph.D.; Jonathan Harris, M.D.; William P. Jennings, M.D.; Ronald Landbloom, M.D.; Thomas Littlejohn III, M.D.; Peter Londborg, M.D.; William McIntosh, D.O.; John C. Morris, M.D.; Brian R. Ott, M.D.; John Overman, M.D.; Elaine R. Peskind, M.D.; Nunzio Pomara, M.D.; Steven G. Potkin, M.D.; Joseph Quinn, M.D.; Elizabeth Reeve, M.D.; Murray Rosenthal, D.O.; Joel Ross, M.D.; Donald Royall, M.D.; Carl Salzman, M.D.; Michael Sauter, M.D.; Beth Safirstein, M.D.; Douglas Scharre, M.D.; David Seiden, M.D.; Stuart Stark, M.D.; Stephen Thein, M.D.; Michael M. Tuchman, M.D.; and Kerry Wilks, M.D.