Efficacy and Safety Study of ABT-384 in Subjects With Mild-to-Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to test if the investigational medication, ABT-384, is a safe and effective treatment for adults with mild-to-moderate Alzheimer's Disease.

Detailed Description
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This is a Phase 2 study designed to evaluate the safety and efficacy of ABT-384 in approximately 260 adults with mild-to-moderate Alzheimer's Disease (AD). Subjects will be randomized to one of four treatment groups (ABT-384, donepezil, or placebo) for a 12-week Treatment Period.

Official Title
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A Randomized, Double-Blind, Placebo and Active-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of ABT-384 in Subjects With Mild-to-Moderate Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: ABT-384
* Drug: donepezil
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject and caregiver must voluntarily sign and date and informed consent. If the subject is not fully competent, full informed consent must be obtained from a legal representative and assent must be obtained from the subject. Subject is male or female between the ages of 55 and 90 years of age, inclusive, at Day-1. Subject meets the NINCDS/ADRDA criteria for probable AD. Subject has a Mini-Mental Status Examination (MMSE) score of 10 to 24, inclusive, at Screening Visit 1. Subject has a Cornell Scale for Depression in Dementia (CSDD) score ≤ 10 at Screening Visit 1. With the exception of a diagnosis of mild-to-moderate AD and the presence of stable medical conditions, the subject is generally in good health based on medical history, physical examination, vital signs, clinical lab tests and 12-lead ECG. If female, subject must be postmenopausal for at least 2 years or surgically sterile. If male, the subject is surgically sterile (vasectomy), is sexually inactive, or is using a barrier method of birth control. Subject has an identified reliable, caregiver (e.g., family member, social worker, nurse), who will provide support and ensure compliance with the study medication and procedures. Subject and caregiver are fluent in the language used for administration of the rating scales or cognitive tests and have sufficient visual, hearing and graphomotor skills to complete procedures. Exclusion Criteria: Subject has a known hypersensitivity or intolerance to donepezil that led to discontinuation or a known reported history of donepezil treatment failure. Subject is currently taking or has taken a medication for the treatment of AD or dementia within 60 days of Screening Visit 1, or is participating in cognitive therapy for the treatment of AD or dementia. Subject has a history of a drug or alcohol disorder (abuse/dependence), based on either DSM-IV-TR or ICD-10 criteria, excluding nicotine, within 2 years prior to Screening Visit 1. In the opinion of the investigator, the subject has any clinically significant uncontrolled medical or psychiatric illness that would affect the safety of the subject. The subject has a current thyroid disease or history of thyroid disease, and is not currently being treated with a stable dose of thyroid replacement medication. For any reason the investigator considers the subject to be an unsuitable candidate to receive ABT-384 or donepezil.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 90 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-384 Dose 1<br> | Drug: ABT-384<br>* Subjects will take study drug once daily for 12 weeks<br>|
| Experimental: ABT-384 Dose 2<br> | Drug: ABT-384<br>* Subjects will take study drug once daily for 12 weeks<br>|
| Active Comparator: donepezil<br> | Drug: donepezil<br>* Subjects will take study drug once daily for 12 weeks.<br>* Other names: Aricept;|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* Subjects will take study drug once daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to final observation in the Alzheimer's Disease Assessment Scale-Cognition portion (ADAS-cog) total score |  | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mini Mental Status Examination (MMSE) score at Baseline, Weeks 4, 8, and 12 |  | 12 Weeks | 
| Clinician's Interview Based Impression of Change-plus (CIBIC-plus) score at Baseline, Weeks 4, 8, and 12 |  | 12 Weeks | 
| Neuropsychiatric Inventory (NPI) score at Baseline, Weeks 4, 8, and 12 |  | 12 Weeks | 
| Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) score at Baseline, Weeks 4, 8, and 12 |  | 12 Weeks |