A Multicenter, Double Blind, Placebo-Controlled, Safety and Tolerability Study of BMS-708163 in Patients With Prodromal Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and tolerability of BMS-708163 in patients with Prodromal Alzheimer's disease over a treatment period of a minimum of 104-weeks. In addition patients will be seen for safety visits at 4 and 12 weeks post treatment.

Official Title
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Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, Pharmacodynamic and Pharmacokinetic Effects of BMS-708163 in the Treatment of Patients With Prodromal Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Avagacestat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient meets clinical criteria for prodromal Alzheimer's disease (MMSE 24-30) Memory complaint by subject or study partner CSF aβ42 levels < 200pg/mL or Total Tau/aβ42 ratio of ≥ 0.39 Score of ≤4 on the Modified Hachinski Ischemia Scale CT results consistent with Alzheimer's disease Medically stable 6 years education Reliable study partner Must be able to swallow capsules Exclusion Criteria: Premenopausal women DSM-IV diagnosis of Dementia History of stroke Immunocompromised Active peptic ulcer, GI bleed, chronic inflammatory bowel disease, chronic diarrhea or past GI surgery that would impact drug absorption Unstable Vitamin B-12 deficiency Hematologic or solid malignancy within 5 years Geriatric Depression Scale ≥ 6 Unstable medical condition Alcohol or drug abuse history with 12-months of study entry Significant drug allergy Prisoners, compulsory psychiatric patients, or residents of nursing home or skilled nursing facility at entry Any other experimental therapy with 30-days of study entry

Ages Eligible for Study
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Minimum Age: 45 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avagacestat (50 mg)<br> | Drug: Avagacestat<br>* Capsules, Oral, 50 mg, once daily, 104 - 220 Weeks<br>* Other names: BMS-708163;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Capsules, Oral, 0 mg, once daily, 104 - 220 Weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of BMS-708163 in patients with Prodromal Alzheimer's disease as measured by adverse events, vital signs, laboratory assessments, electrocardiograms (ECGs) and Safety Head Magnetic resonance imaging (MRI) findings |  | Every 12 weeks up to week 220 | 
| Safety and tolerability of BMS-708163 in patients with Prodromal Alzheimer's disease as measured by adverse events, vital signs, laboratory assessments, electrocardiograms (ECGs) and Safety Head Magnetic resonance imaging (MRI) findings |  | Avagacestat-treated patients will be seen for safety visits at 4 Post Treatment/Study Termination | 
| Safety and tolerability of BMS-708163 in patients with Prodromal Alzheimer's disease as measured by adverse events, vital signs, laboratory assessments, electrocardiograms (ECGs) and Safety Head Magnetic resonance imaging (MRI) findings |  | Avagacestat-treated patients will be seen for safety visits at 12 Post Treatment/Study Termination | 
| Safety and tolerability of BMS-708163 in patients with Prodromal Alzheimer's disease as measured by adverse events, vital signs, laboratory assessments, electrocardiograms (ECGs) and Safety Head Magnetic resonance imaging (MRI) findings |  | Avagacestat-treated patients will have a 24 week post treatment skin examination by a dermatologist | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive value of Cerebral Spinal Fluid (CSF) biomarkers (Aβ40, and Aβ42, total Tau, total Tau/Aβ42 ratio, phosphorylated Tau) on progression to dementia |  | Baseline (Week 0), Week 2 (optional), Week 24 and Week 104 |