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Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease
Paula T Trzepacz1, Jeffrey Cummings, Thomas Konechnik
1Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA. ptt@lilly.com
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.
Insights
Mibampator did not significantly improve agitation and aggression in Alzheimer's disease (AD) patients, although it showed benefits on the Frontal Systems Behavior Inventory (FrSBe). Further research is needed to understand these findings.
Area of Science:
- Neuroscience
- Pharmacology
- Geriatrics
Background:
- Alzheimer's disease (AD) is associated with significant agitation and aggression (A/A).
- Mibampator, an AMPA receptor potentiator, was investigated as a potential treatment for A/A in AD patients.
Purpose of the Study:
- To evaluate the efficacy and safety of mibampator in treating agitation and aggression in patients with probable Alzheimer's disease.
Main Methods:
- A 12-week, double-blind, placebo-controlled trial involving 132 outpatients with probable AD and A/A.
- Primary outcome assessed using the Neuropsychiatric Inventory (NPI-4-A/A).
- Secondary outcomes included the Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia, Frontal Systems Behavior Inventory (FrSBe), and Alzheimer's Disease Assessment Scale-Cognitive.
Main Results:
- No significant group differences were observed for the primary outcome (NPI-4-A/A).
- Mibampator showed a significant improvement compared to placebo on the FrSBe (p = 0.007).
- Adverse events were similar between groups; one death occurred in the placebo group.
Conclusions:
- The trial did not meet its primary endpoint for reducing agitation and aggression in AD.
- Potential explanations for the lack of significant findings include issues related to caregivers, drug target engagement, or trial design.
- Further investigation is warranted to clarify the role of mibampator in AD management.
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