Efficacy, Safety, & Tolerability of AZD3480 Patients With Mild to Moderate Dementia of the Alzheimer's Type (AD)

Study Overview
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Brief Summary
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Alzheimer's disease is the most common form of dementia and is the fourth leading cause of death among people 65 years of age and older. The global prevalence of the disease will increase significantly as the population ages, unless preventative treatments can be identified and marketed. The present study seeks to evaluate AZD3480 (TC-1734) compared to an approved medication (donepezil) shown to improve cognition and function in patients with Alzheimer's disease.

Detailed Description
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This is a double blind, positive comparator, randomized, multicenter, parallel group study to assess the efficacy, safety, and tolerability of AZD3480 as monotherapy in patients with mild to moderate dementia of the Alzheimer's type (AD). Approximately 300 subjects will be randomized and divided into 2 cohorts. Actual randomization was 293 subjects.

Official Title
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Double-Blind, Positive Comparator, Randomized, Parallel Study of Efficacy, Safety, and Tolerability of AZD3480 (TC-1734-226) as Monotherapy in Patients With Mild to Moderate Dementia of the Alzheimer's Type

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Donepezil
* Drug: AZD3480


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A clinical diagnosis of AD per NINCDS-ADRDA criteria; mild to moderate severity as defined by Mini-Mental State Examination (MMSE) scores of 12 to 22. AD diagnosed at least 12 months prior to Screening, and supported by brain imaging studies within 6 months prior to Screening. Absence of vascular dementia both per AIRENS criteria and as defined by modified Hachinski ischemia score (HIS) of </= 4. Presence of a caregiver with significant proportion of time in contact with subject and who will oversee administration of study drug during the trial Able to complete test assessments and to sign informed consent with the help of a caregiver if needed Exclusion Criteria: Diagnosis or presence of other dementing illnesses Use of mood stabilizers, antidepressants, anxiolytics, antipsychotics or hypnotics Treatment within 1 month prior to Screening using cognition-affecting agents (e.g. CNS stimulants) Tobacco user within 4 months prior to Screening Use of smoking cessation therapy within 4 months prior to Screening History within past 6 months of alcohol abuse or illicit drug abuse Unable, even with caregiver assistance, to comply with study procedures in opinion of investigator Myocardial infarction within the 12 months prior to Screening Hypothyroidism, vitamin B12 or folic acid deficiency Known systemic infection (HBV, HCV, HIV, TB) Vascular dementia per NINDS-AIRENS criteria and as defined by a modified Hachinski ischemia score (HIS, Appendix 4) score of > 4 (i.e., vascular dementia is consistent with a modified HIS > 4).

Ages Eligible for Study
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Minimum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD3480<br> | Drug: AZD3480<br>* Subjects taking 30 mg AZD3480 will take one capsule of AZD3480 and two capsules of placebo for donepezil (to maintain blind) orally once a day.<br>* Other names: TC-1734;|
| Active Comparator: Donepezil<br>Donepezil will be administered at 5 mg daily for 4 weeks and escalated to 10 mg daily for the remainder of the study. | Drug: Donepezil<br>* Subjects taking donepezil will take 1-2 capsules of 5 mg donepezil and a placebo for AZD3480 (to maintain blind) orally once a day.<br>* Other names: Aricept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) |  | 52 weeks | 
| Change from baseline in the Clinician Interview-Based Impression of Change plus carer interview [CIBIC-(+)] | The CIBIC-(+) is a co-primary endpoint with the ADAS-Cog in the United States. | 52 Weeks | 
| Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) | The ADCS-ADL is the co-primary endpoint with the ADAS-Cog in Europe. | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Neuropsychiatric Inventory (NPI) |  | 52 Weeks | 
| Change from baseline in the Mini-Mental State Examination (MMSE) |  | 52 Weeks | 
| Change from baseline in the Alzheimer's Disease Related Quality of Life (ADRQL) |  | 52 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, AD, Dementia