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Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease

Published online by Cambridge University Press:  21 December 2012

Paula T. Trzepacz ,
Jeffrey Cummings ,
Thomas Konechnik ,
Tammy D. Forrester ,
Curtis Chang ,
Ellen B. Dennehy ,
Brian A. Willis ,
Catherine Shuler ,
Linda B. Tabas  and
Constantine Lyketsos
Paula T. Trzepacz*
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
Jeffrey Cummings
Affiliation:
Cleveland Clinic, Lou Ruvo Center, Las Vegas, Nevada, USA
Thomas Konechnik
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
Tammy D. Forrester
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
Curtis Chang
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
Ellen B. Dennehy
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
Brian A. Willis
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
Catherine Shuler
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
Linda B. Tabas
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
Constantine Lyketsos
Affiliation:
Department of Psychiatry, Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
*
Correspondence should be addressed to: Paula T. Trzepacz, MD, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. Phone: +317-997-7148; Fax: +317-276-7100. Email: [email protected].
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Abstract

Background: Mibampator, an amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor potentiator, was evaluated for treatment of agitation and aggression (A/A) in Alzheimer's disease (AD).

Methods: Outpatients (n = 132) with probable AD and A/A randomized to 12 weeks of double-blind treatment with 3-mg po mibampator or placebo were assessed using the 4-domain A/A subscale of the Neuropsychiatric Inventory (NPI-4-A/A) derived from the Neuropsychiatric Inventory. Secondary measures included the Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia, Frontal Systems Behavior Inventory (FrSBe), and Alzheimer's Disease Assessment Scale-Cognitive. Efficacy was analyzed using mixed-effects model repeated measures from baseline to endpoint. Adverse events (AEs), labs, vital signs, and electrocardiograms were monitored.

Results: Baseline characteristics were comparable between groups. Both groups improved on the NPI-4-A/A, but without group differences. Among secondaries, mibampator was significantly better (p = 0.007) than placebo only on the FrSBe. AEs were similar between groups. One death occurred in the placebo group.

Conclusion: Possible explanations for no significant group differences include caregiver, drug target engagement, and design issues.

This trial is registered on ClinicalTrials.gov; ID: NCT00843518.

Keywords

AMPAAlzheimer's diseasemibampatoragitationaggressionneuropsychiatric symptomsglutamateNeuropsychiatric Inventory
Type
Research Article
Information
International Psychogeriatrics , Volume 25 , Issue 5 , May 2013 , pp. 707 - 719
Copyright
Copyright © International Psychogeriatric Association 2012

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