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A Double-blind, Placebo-Controlled Study

Piero G. Antuono, MD; Mentane Study Group; Piero G. Antuono, MD; Jean Ravanelli-Meyer, RN, CCRC; Jan Beyer, RN; Walter A. Brown, MD; James Cordoza, MSN; Deborah Guilmette; Steven R. Cohen, MD, PhD; Charles J. Hirsch, MD; Karen G. Cohen, LPN; Jose E. DeLaGandara, MD; Angela Pedraza, MD; Susan Bley, LPN; Dawna L. Dean, MS; Suzanne Manor, MT; Richard F. Holub, MD; Sharon Bright Holub, MPA; Nancy Siciliano, RN; James H. Little, MD; M. Lynn Crismon, PharmD, FCCP; Guadalupe Garcia, PharmD; Richard Margolin, MD; Caryn Crenshaw, RN; Pam Brooks, RN; Ralph W. Richter, MD; Jan Schweiger, RN; Andrew Donnely; Robert A. Riesenberg, MD; Sharon M. Irwin; Robyn L. Cristol; Murray H. Rosenthal, DO; Robert Daigneault, MD; Andrew J. Ferber, RN, MSN; Walter F. Speakman, MD; Jack R. Tomlinson, MD; Penny McDonald, RN; Richard L. Strub, MD; James A. Wilkens, MD; Bruce J. Lepler, MD; Frank P. Zemlan, PhD; Michael A. Keys, MD; Sharon L. Nelson, RNC

Arch Intern Med. 1995;155(16):1766-1772.

Abstract
Background
Alzheimer's disease is characterized by cognitive and behavioral disturbances that are mediated in part by cholinergic brain deficits.

Objective
To evaluate the long-term effectiveness and safety of an investigational cholinesterase inhibitor, that is, velnacrine maleate, in treating patients with clinically probable Alzheimer's disease (according to the criteria of the National Institute of Neurological Disorders and Stroke [Washington, DC]-Alzheimer Disease and Related Disorders Association [Chicago, Ill]).

Methods
This was a double-blind, placebo-controlled study. After a single-blind washout period, patients were randomized to receive placebo (n=152), velnacrine maleate, 150 mg/d (n=149), or velnacrine maleate, 225 mg/d (n=148) for 24 weeks. Primary end points were cognitive behavior and memory components of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale. Secondary end points were caregiver-rated scales.

Results
The scores for the cognitive behavior and memory components of the Alzheimer's Disease Assessment Scale deteriorated in the placebo-treated group (P<.05) but not in the velnacrine-treated groups. Between-group comparisons favored velnacrine maleate, 225 mg over 150 mg (P<.05). Findings were similar for the Clinical Global Impression of Change scale and three of the four caregiver-rated scales. Treatment-related adverse clinical events occurred in 36%, 28%, and 30% of patients in the groups that received placebo, velnacrine maleate (150 mg), and velnacrine maleate (225 mg), respectively. The most common adverse clinical event was diarrhea, which rarely interrupted therapy. Treatment was stopped because of reversible abnormal liver function test results (five or more times the upper limits of normal) in 3%, 30%, and 24% of the patients who received placebo, velnacrine maleate (150 mg), and velnacrine maleate (225 mg), respectively.

Conclusions
Velnacrine produces modest but significant benefits in patients with Alzheimer's disease. Velnacrine maleate (225 mg) is more effective than 150 mg of velnacrine. Both dosages have acceptable safety profiles.

(Arch Intern Med. 1995;155:1766-1772)

Author Affiliations
Medical College of Wisconsin, Milwaukee; Clinical Programs Limited, Providence, RI; Suncoast Medical Clinic, St Petersburg, Fla; North Broward Medical Center, Pompano Beach, Fla; Neurological Associates of Albany (NY), PC; Austin (Tex) Diagnostic Clinic, Center for Clinical Research; Vanderbilt University Medical Center, Nashville, Tenn; Clinical Pharmaceutical Trials Inc, Tulsa, Okla; Biobehavioral Research Center, Decatur, Ga; Behavioral Medicine Resources Inc, San Diego, Calif; Alzheimer's Diagnostic Clinic, Wichita Falls, Tex; Alton Ochsner Medical Foundation, New Orleans, La; Psychiatric Professional Services Inc, University of Cincinnati (Ohio) College of Medicine

From the Neurology Department, Medical College of Wisconsin, Milwaukee. Members of the Mentane Study Group are listed at the end of this article.

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