Safety and Cognitive Function Study of EVP-6124 in Patients With Mild to Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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This study is being conducted to determine the safety and effect on cognitive function of the investigational medication, EVP-6124, in individuals with mild to moderate probable Alzheimer's disease.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, parallel, 24-week, Phase 2 safety/efficacy study in which three dose levels of EVP-6124 or placebo will be evaluated. Eligible for enrollment will be patients who meet clinical criteria for mild to moderate probable Alzheimer's disease who are either receiving treatment with AChEI medication at a stable dose or who are not presently taking any AChEI or memantine co-medication. Patients will be randomized to one of the following groups: 0.3 mg, 1 mg or 2 mg or Placebo. Approximately 400 subjects will be randomized to the 4 treatment groups. Study drug will be supplied as capsules and will be orally administered once daily for a total of 24 weeks.

Official Title
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A Randomized, Double-blind, Placebo-Controlled, Parallel, 24-Week, Phase 2 Study of Three Different Doses of an Alpha-7 Nicotinic Acetylcholine Receptor Agonist (EVP-6124) or Placebo in Subjects With Mild to Moderate Probable Alzheimer's Disease

Conditions
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Alzheimer's Disease, Central Nervous System Diseases, Cognition

Intervention / Treatment
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* Drug: EVP-6124
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with Probable Alzheimer's disease Mini-Mental State Examination (MMSE) score of 14 to 24 inclusive at screening and a CDR-SB score ≥2 at the screening assessment Modified Hachinski Ischemic Score (mHIS) ≤4 at screening Female subjects are ≥1 year post-menopausal or are surgically sterile Caregiver available; if not living in the same household, caregiver sees subject at least four times each week Subject living at home, senior residential setting, or an institutional setting without the need for continuous nursing care General health status acceptable for participation in a 24 week clinical trial be administered Exclusion Criteria: General Participation in another therapeutic clinical trial within 30 days before Baseline Prior participation in an amyloid vaccination clinical study Inability to swallow capsules Likely inability to complete 24 week study Inability to be ≥75% compliant with single-blind placebo run-in medication Inability to adequately perform cognitive tests History of significant cardiovascular disease Major depression Psychosis History of stroke within 18 months of screening Head trauma Inability to perform any screening or baseline evaluations

Ages Eligible for Study
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Minimum Age: 50 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 |
| --- | --- |
| Active Comparator: EVP-6124 0.3 mg<br>one 0.3 mg capsule every day for 183 days | Drug: EVP-6124<br> <br> |
| Active Comparator: EVP-6124 1 mg<br>one 1 mg capsule every day for 183 days | Drug: EVP-6124<br> <br> |
| Active Comparator: EVP-6124 2 mg<br>one 2 mg capsule every day for 183 days | Drug: EVP-6124<br> <br> |
| Placebo Comparator: Placebo<br>Placebo every day for 183 days | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale-Cognitive subscale-13 (ADAS-cog-13) |  | Day -7, Baseline, 4, 12, 18, 23 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale-Cognitive subscale-11 |  | 4, 12, 18, 23 Weeks | 
| Controlled Oral Word Association Test |  | Day -7, Baseline, 4, 12, 18, 23 Weeks | 
| Category Fluency Test |  | Day -7, Baseline, 4, 12, 18, 23 Weeks | 
| Clinical Dementia Rating Scale Sum of Boxes |  | Day -7, Baseline, 4, 12, 18, 23 Weeks | 
| Alzheimer's Disease Cooperative Study-Activities of Daily Living |  | Baseline, 4, 12, 18, 23 Weeks | 
| Neuropsychiatric Inventory |  | Baseline, 12, 23 Weeks | 
| Mini-Mental State Exam |  | Day -7, Baseline, 4, 12, 18, 23 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, Central Nervous System diseases, Cognition