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

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.

• Authors: Paula T Trzepacz, Jeffrey Cummings, Thomas Konechnik, Tammy D Forrester, Curtis Chang, Ellen B Dennehy, Brian A Willis, Catherine Shuler, Linda B Tabas, Constantine Lyketsos
• Journal: International psychogeriatrics (Int Psychogeriatr) Vol. 25 Issue 5 Pg. 707-19 (May 2013) ISSN: 1741-203X [Electronic] England
• PMID: 23257314 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biphenyl Compounds
• N-((2-(4'-(2-(methylsulfonyl)amino)ethyl)(1,1'-biphenyl)-4-yl)propyl)-2-propanesulfonamide
• Sulfonamides

Topics

• Aged
• Aged, 80 and over
• Aggression (drug effects, psychology)
• Alzheimer Disease (complications, drug therapy, psychology)
• Biphenyl Compounds (pharmacology, therapeutic use)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Neuropsychological Tests
• Outpatients
• Psychomotor Agitation (drug therapy, etiology, psychology)
• Sulfonamides (pharmacology, therapeutic use)
• Surveys and Questionnaires
• Treatment Outcome