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

  • Paula T. Trzepacz (a1), Jeffrey Cummings (a2), Thomas Konechnik (a1), Tammy D. Forrester (a1), Curtis Chang (a1), Ellen B. Dennehy (a1), Brian A. Willis (a1), Catherine Shuler (a1), Linda B. Tabas (a1) and Constantine Lyketsos (a3)...

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.

Copyright

Corresponding author

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: ptt@lilly.com.

References

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