Efficacy and Safety Study of ELND005 as a Treatment for Agitation and Aggression in Alzheimer's Disease

Study Overview
=================
Brief Summary
-----------------
The primary purpose of this study is to determine whether ELND005 is effective in treating symptoms of agitation and aggression in patients with Alzheimer's disease

Official Title
-----------------
A Prospective, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Efficacy and Safety Study of Oral ELND005 for Treatment of Agitation and Aggression in Patients With Moderate to Severe Alzheimer's Disease

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: ELND005
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of Probable AD according to the National Institute on Aging- Alzheimer's Association (NIA-AA) guidelines (McKhann et al 2011). MMSE score of 5 to 24 (inclusive) at the Screening Visit. Has clinically significant agitation/aggression defined as Neuropsychiatric Inventory (NPI)-agitation/aggression subscore of ≥4. No response or suboptimal response to standard nonpharmacological interventions. Exclusion Criteria: The agitation/aggression is attributable to concomitant medications, environmental conditions, or active medical or psychiatric condition. Current diagnosis of major depressive disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM IV TR). Has persistent and distressing psychotic symptoms (delusion and/or hallucinations) that require psychiatric hospitalization.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 95 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ELND005<br>ELND005 film coated tablets, BID for 12 weeks | Drug: ELND005<br> <br> * Other names: Scyllo-inositol;|
| Placebo Comparator: Placebo<br>Matched placebo BID for 12 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in NPI-C Combined Agitation and Aggression Subscores (NPI-C A+A). | The NPI-C (de Medeiros et al 2010) is a validated and reliable behavioral measure that assesses psychopathology in dementia subjects. It evaluates 14 neuropsychiatric disturbances common in dementia.Higher scores on the NPI-C are associated with a greater clinical severity of symptoms. The NPI-C Agitation and Aggression score ranges from 0-63. The analysis of the NPI-C A+A score was performed on the mITT population. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Modified-ADCS-CGIC Agitation Scores | The Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) is a widely used scale for the global assessment of change in AD trials.It is a 7-point Likert scale that ranges from marked improvement scored as 1 to marked worsening scored as 7, with no change scored as 4. The range is from 1 to 7. Higher scores indicate worsening agitation. | Week 12 | 
| Change From Baseline in NPI Total Scores | The NPI (Cummings et al 1994) is a behavioral measure that assesses psychopathology in dementia subjects. It evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, nighttime behavior disturbances, and appetite and eating abnormalities. Higher scores on the NPI are associated with greater frequency and severity of symptoms. The scale range is 0-144. | Week 12 | 
| Change From Baseline in MMSE Scores | The Mini-Mental State Exam (MMSE) (Folstein et al 1975) is a brief cognitive test assessing general cognitive function that has been employed in numerous clinical trials of products approved for the treatment of AD. The score can range from 0 to 30, with lower scores indicating greater impairment in function. | Week 12 | 
| Change From Baseline in ADCS-ADL Scores | The Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) (Galasko et al 1997) is a functional assessment that measures instrumental and basic activities of daily living. The total score for the 23-item ADCS-ADL ranges from 0 to 78 points, with lower scores indicating greater impairment in function. | Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Agitation, Aggression, patients