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Abstract
Objective: To investigate the efficacy and safety of the positive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid modulator LY451395 in patients with mild to moderate Alzheimer disease (AD) (Mini-Mental State Examination scores 14 to 26).
Methods: One hundred eighty-one patients were randomized to treatment in an 11-week, double-blind, placebo-controlled trial. Patients received either LY451395 0.2 mg BID for 28 days and 1.0 mg BID thereafter (n = 90) or placebo (n = 91). The primary outcome measurement was the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) with several secondary outcome measurements: Clinician's Interview-Based Impression of Change, Trail Making Part A, Stylus Tapping Test, Single Digit Modality Test, and Neuropsychiatric Inventory (NPI).
Results: Baseline demographics were similar between the two groups. Patients did not show any mean change from baseline in the ADAS-Cog after treatment with LY451395 for 4 weeks (p = 0.60) or 8 weeks (p = 0.83). The only secondary outcome measurement that showed changes from baseline compared with placebo was the NPI Total Score: p = 0.06 (marginal significance) after 4 weeks of treatment and p = 0.03 after 8 weeks of treatment. Ninety-two percent of LY451395-treated patients and 95% of placebo-treated patients completed the trial. Adverse events were experienced by 83% of LY451395-treated patients and 86% of placebo-treated patients, the majority of which were rated mild in severity.
Conclusion: Patients treated with LY451395 did not show a statistically significant separation from patients taking placebo on the Alzheimer's Disease Assessment Scale-Cognitive Subscale, the primary outcome measure.
Footnotes
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Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the March 27 issue to find the title link for this article.
Commentary, see page 971
Disclosure: Sponsored by Eli Lilly and Company. Drs. Chappell, Gonzales, Williams, Witte, and Mohs are employees and stockholders in Eli Lilly and Company. Dr. Sperling was an investigator in this study. All authors have had full access to the data.
Received May 4, 2006. Accepted in final form January 27, 2007.
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