Safety, Tolerability, and Pharmacokinetics of ABT-354 in Subjects With Mild-to-Moderate Alzheimer's Disease on Stable Doses of Acetylcholinesterase Inhibitors

Study Overview
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Brief Summary
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This study will investigate safety, tolerability and pharmacokinetics of ABT-354 in up to 20 male and female subjects, between 55 to 90 years of age with mild to moderate Alzheimer's disease on stable doses of acetylcholinesterase inhibitors.

Detailed Description
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This is a double-blind, placebo-controlled, randomized, multiple-dose, multicenter study. Up to 20 male and female subjects with mild to moderate Alzheimer's disease (AD) who are taking stable doses of acetylcholinesterase inhibitors will be enrolled in this study. Within 28 days prior to study drug administration, subjects will be screened based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD, Mini-Mental State Examination (MMSE) and Modified Hachinski Ischemic Scale (MHIS) scores, medical history, physical examination, neurological examination, vital signs, ECG, laboratory tests and response to Columbia-Suicide Severity Rating Scale (C-SSRS). The study will be performed in two groups of 10 subjects each. In each group of 10 subjects, 7 subjects will be randomly assigned to receive ABT-354 and 3 subjects to receive matching placebo.

Official Title
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A Multiple-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ABT-354 in Subjects With Mild-to-Moderate Alzheimer's Disease on Stable Doses of Acetylcholinesterase Inhibitors

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: ABT-354
* Drug: ABT-354
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's Disease Has a Mini-Mental State Examination total score of 16 to 26, inclusive, at Screening Has a Modified Hachinski Ischemia Scale score of ≤ 4 at Screening On a stable dose of - donepezil, galantamine or rivastigmine for at least 30 days prior to study drug administration Has had a computerized tomography or magnetic resonance imaging scan, interpreted by a radiologist or neurologist, within 36 months prior to randomization Exclusion Criteria: Receipt of any depot drug by injection within 30 days prior to study drug administration Receipt of an investigational product within a time period equal to 10 half-lives, if known, or within 6 weeks prior to study drug administration History of any significant neurological disease other than Alzheimer's Disease History of significant sensitivity or allergy to multiple drugs based on medical records and/or the opinion of the investigator Significant current - suicidal ideation within 1 month prior to study drug administration as evidenced by answering yes to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale completed at Screening or any history of suicide attempts

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: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1, low dose<br>ABT-354 | Drug: ABT-354<br>* ABT-354 Low Dose<br>Drug: Placebo<br>* Placebo<br>|
| Experimental: Group 2, high dose<br>ABT-354 | Drug: ABT-354<br>* ABT-354 High Dose<br>Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital signs |  | Up to Day 10 | 
| ECG (electrocardiogram) |  | Up to Day 10 | 
| Neurological exam |  | Up to Day 10 | 
| Laboratory tests | Hematology, Chemistry, Urinalysis | Up to Day 10 | 
| Number of subject with adverse events |  | Up to Day 10 | 
| C-SSRS (Columbia-Suicide Severity Rating Scale) |  | Up to Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters | Cmax, Cmin, Tmax, AUC, t-1/2, CL/F | Up to Day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease