A Phase II, Multicenter, Double Blind, Placebo-Controlled Safety, Tolerability Study of BMS-708163 in Patients 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 determine the safety and tolerability of BMS-708163 in patients with mild to moderate Alzheimer's disease over a treatment period of 12-weeks and the course of any potential effects during a 12-week wash-out period

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 Mild to Moderate Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: BMS-708163
* Drug: BMS-708163
* Drug: BMS-708163
* Drug: BMS-708163
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Mild to Moderate Alzheimer's disease (MMSE 16-26) 6 Month cognitive decline Stable marketed AD therapy x2 months or additional marketed AD therapy during study Score of <=4 on the Modified Hachinski Ischemia Scale CT results consistent with Alzheimer's disease Medically stable 6 years education Reliable study partner (caregiver) Must be able to swallow capsules Exclusion Criteria: Premenopausal women Dementia due to other causes than Alzheimer's disease 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 Alzheimer's disease modification experimental therapy with 12 months of study entry 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: 50 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 |
| --- | --- |
| Active Comparator: A1<br> | Drug: BMS-708163<br>* Capsules, Oral, 25 mg, once daily, 24 weeks<br>|
| Active Comparator: A2<br> | Drug: BMS-708163<br>* Capsules, Oral, 50 mg, once daily, 24 weeks<br>|
| Active Comparator: A3<br> | Drug: BMS-708163<br>* Capsules, Oral, 100 mg, once daily, 24 weeks<br>|
| Active Comparator: A4<br> | Drug: BMS-708163<br>* Capsules, Oral, 125 mg, once daily, 24 weeks<br>|
| Placebo Comparator: A5<br> | Drug: Placebo<br>* Capsules, Oral, 0 mg, once daily, 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events |  | Weekly for the first 12-weeks of the 24-Week dosing period (Baseline-Week-12) and every 2 weeks during the second 12-weeks of the 24-Week dosing period (Weeks 14-24) and during the subsequent 12-week washout period (Weeks 28, 32, & 36) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics effects of Cerebral Spinal Fluid |  | Baseline, Week 12 and Week 24 | 
| Pharmacodynamics effects of the Alzheimer's Disease Assessment Scale - Cognitive Subscale |  | Baseline, Week 12, Week 24 and Week 36 | 
| Pharmacodynamics effects of the Alzheimer's Disease Collaborative Study - Activities of Daily Living scale |  | Baseline, Week 12, Week 24 and Week 36 | 
| Pharmacodynamics effects of the Global clinical impression as assessed with the Clinical Dementia Rating-Sum of Boxes |  | Baseline, Week 12, Week 24 and Week 36 | 
| Characterize Pharmacodynamics/Pharmacokinetics effects of the plasma exposure of BMS-708163 and variability in a population with Alzheimer's disease |  | Baseline, Week 12 and Week 24 | 
| Characterize Pharmacodynamics/Pharmacokinetics effects in refining the Pharmacokinetics/Pharmacodynamics model with Phase 2 data |  | Baseline, Week 12 and Week 24 | 
| Characterize Pharmacodynamics/Pharmacokinetics effects by exploring correlations between exposure, biomarkers, and clinical effects |  | Baseline, Week 12 and Week 24 | 
| Characterize Pharmacodynamics/Pharmacokinetics effects by exploring Pharmacokinetics variability, including the correlation between polymorphisms of CYP enzymes |  | Baseline, Week 12 and Week 24 |