Study Evaluating TheSafety And Efficacy Of PF-05212377 Or Placebo In Subjects With Alzheimer's Disease With Existing Neuropsychiatric Symptoms On Donepezil

Study Overview
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Brief Summary
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This study will evaluate safety and efficacy of PF-05212377 in subjects with mild-to-moderate Alzheimer's Disease with existing neuropsychiatric symptoms on a stable dose of Donepezil. The 4-week run-in will minimize placebo effect. The 12-week treatment period is considered the minimum length necessary to reliably evaluate the effect PF-05212377 on cognition and and neuropsychiatric symptoms in this population. The 2-week washout will allow to monitor re-emergence of neuropsychiatric and cognitive symptoms.

Official Title
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A Randomized, 18-week, Placebo-controlled, Double-blind, Parallel Group Study Of The Safety And Efficacy Of Pf-05212377 (Sam-760) In Subjects With Mild-to-moderate Alzheimer's Disease With Existing Neuropsychiatric Symptoms On A Stable Daily Dose Of Donepezil

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: PF-05212377 (SAM-760)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of probable AD with supportive brain imaging documentation Have existing neuropsychiatric symptoms as defined by a score equal or greater than 10 on the NPI at screening, arising from item scores equal or greater than 2 (frequency X severity) on at least 2 domains. Has been on donepezil (stable dose of 5 mg or 10 mg) for at least four months, with no intent to change such for the duration of the study. Exclusion Criteria: Demonstrate extreme agitation, physical aggression or violence to themselves, their caregiver, or others, and/or an inability to complete the ADAS-cog assessment at Screening. Have major structural brain disease other than Alzheimer's Disease Other severe acute or chronical medical or psychiatric condition or laboratory abnormality

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 30 mg QD of PF-05212377<br> | Drug: PF-05212377 (SAM-760)<br>* 30 mg QD of PF-05212377 (SAM-760)<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in ADAS-cog13 Total Score at Week 16 | ADAS-cog13 (13-item ADAS cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. | Baseline and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score at Week 16 (Visit 5) | The NPI evaluates both frequency and severity of 12 neuropsychiatric disturbances including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, as well as appetite/eating. The NPI total score (for 12 behavioral domains) is calculated as the product of frequency and severity for each domain, and ranges from 0 to 144. An increase in score indicates a worsening of symptoms. | Baseline and Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized, Double Blind, Safety and Efficacy