To Evaluate Effects of AZD1446, Placebo and Donepezil in Patients With Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether treatment with single and multiple oral doses of AZD1446 for 1 week will have effect on Quantified Electroencephalography and Event-Related Potentials in patients with Alzheimers Disease. The total treatment period is 9 weeks, divided into 5 equally long sub-periods of 7 days and 4 wash-out periods of 7 days each.

Official Title
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A Phase II, Multi-center, Randomized, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Pharmacodynamic Effect of Single and Multiple Oral Doses of AZD1446/ Placebo and a Single Dose of Donepezil on Quantified Electroencephalography and Event-Related Potentials in Patients With AD

Conditions
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Alzheimer´s Disease

Intervention / Treatment
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* Drug: AZD1446
* Drug: Donepezil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of probable Alzheimer´s Disease Hachinski Ischaemic score < 4 MSE score 18 to 24 Exclusion Criteria: History of any clinically significant disease or dementia other than Alzheimer´s Disease Current major depressive disorder or other major psychiatric disorders

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>2,5 mg once daily | Drug: AZD1446<br>* Capsule, oral single and multiple dose<br>|
| Active Comparator: 2<br>single dose of 5 mg | Drug: Donepezil<br>* Capsule, oral and single dose<br>|
| Placebo Comparator: 3<br> | Drug: Placebo<br>* Capsule, oral and single dose<br>|
| Experimental: 4<br>60 mg once daily | Drug: AZD1446<br>* Capsule, oral single and multiple dose<br>|
| Experimental: 5<br>60 mg three times daily | Drug: AZD1446<br>* Capsule, oral single and multiple dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of single and multiple dosing of AZD1446 and a single dose of donepezil on Quantified electroencephalography (qEEG) and Event-related potentials (ERP) in patients with mild-to-moderate AD. |  | collected from the time of informed consent is signed, throughout the study. The total study period is 9 weeks, divided into 5 equally long treatment periods of 7 days and 4 wash-out periods of 7 days each. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the relationship between plasma concentration of AZD1446/donepezil and qEEG and ERP. |  | Information on these will be collected from the time of randomization, throughout the study. | 
| To evaluate the correlation between changes in qEEG/ERP and changes in cognition, if applicable |  | Information on these will be collected from the time of informed consent is signed, throughout the study. | 
| Safety as measured by Adverse Events, Vital Signs, ECGs, Clinical Chemistry, Haematology, Urinalysis and Physical Examination. |  | Information on these will be collected from the time of informed consent is signed, throughout the study. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase II, Alzheimer's disease, EEG, cognition, pharmacodynamic