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

Paula T. Trzepacz, Jeffrey Cummings, Thomas Konechnik, Tammy D. Forrester, Curtis Chang, Ellen B. Dennehy, Brian A. Willis, Catherine Shuler, Linda B. Tabas, Constantine G Lyketsos

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)707-719
Number of pages13
JournalInternational Psychogeriatrics
Volume25
Issue number5
DOIs
StatePublished - May 2013

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N-((2-(4'-(2-(methylsulfonyl)amino)ethyl)(1,1'-biphenyl)-4-yl)propyl)-2-propanesulfonamide
Aggression
Alzheimer Disease
Randomized Controlled Trials
Equipment and Supplies
Placebos
Isoxazoles
Vital Signs
Caregivers
Dementia
Electrocardiography
Outpatients
Depression

Keywords

  • aggression
  • agitation
  • Alzheimer's disease
  • AMPA
  • glutamate
  • mibampator
  • Neuropsychiatric Inventory
  • neuropsychiatric symptoms

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Gerontology
  • Clinical Psychology

Cite this

Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease. / Trzepacz, Paula T.; Cummings, Jeffrey; Konechnik, Thomas; Forrester, Tammy D.; Chang, Curtis; Dennehy, Ellen B.; Willis, Brian A.; Shuler, Catherine; Tabas, Linda B.; Lyketsos, Constantine G.

In: International Psychogeriatrics, Vol. 25, No. 5, 05.2013, p. 707-719.

Research output: Contribution to journalArticle

Trzepacz, PT, Cummings, J, Konechnik, T, Forrester, TD, Chang, C, Dennehy, EB, Willis, BA, Shuler, C, Tabas, LB & Lyketsos, CG 2013, 'Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease', International Psychogeriatrics, vol. 25, no. 5, pp. 707-719. https://doi.org/10.1017/S1041610212002141
Trzepacz, Paula T. ; Cummings, Jeffrey ; Konechnik, Thomas ; Forrester, Tammy D. ; Chang, Curtis ; Dennehy, Ellen B. ; Willis, Brian A. ; Shuler, Catherine ; Tabas, Linda B. ; Lyketsos, Constantine G. / Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease. In: International Psychogeriatrics. 2013 ; Vol. 25, No. 5. pp. 707-719.
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