AMPA potentiator treatment of cognitive deficits in Alzheimer disease.

Abstract

OBJECTIVE:

To investigate the efficacy and safety of the positive alpha-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.

• Authors: A S Chappell, C Gonzales, J Williams, M M Witte, R C Mohs, R Sperling
• Journal: Neurology (Neurology) Vol. 68 Issue 13 Pg. 1008-12 (Mar 27 2007) ISSN: 1526-632X [Electronic] United States
• PMID: 17389305 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biphenyl Compounds
• Excitatory Amino Acid Agonists
• N-((2-(4'-(2-(methylsulfonyl)amino)ethyl)(1,1'-biphenyl)-4-yl)propyl)-2-propanesulfonamide
• Placebos
• Receptors, AMPA
• Sulfonamides
• Glutamic Acid

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (drug therapy, metabolism, physiopathology)
• Biphenyl Compounds (administration & dosage, adverse effects)
• Brain (drug effects, metabolism, physiopathology)
• Cognition Disorders (drug therapy, etiology, physiopathology)
• Double-Blind Method
• Excitatory Amino Acid Agonists (administration & dosage, adverse effects)
• Female
• Glutamic Acid (metabolism)
• Humans
• Male
• Middle Aged
• Neuropsychological Tests
• Placebos
• Receptors, AMPA (agonists, metabolism)
• Sulfonamides (administration & dosage, adverse effects)
• Synaptic Transmission (drug effects, physiology)
• Treatment Outcome