Effect of PF-04360365 On ABETA In Patients With Alzheimer's Disease And Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
The primary goal of this study is to evaluate the effect of PF-04360365 on the clearance of ABETA from the CSF (cerebrospinal fluid) in patients with mild Alzheimer's disease and healthy volunteers. Additionally, the study will assess the pharmacokinetics of PF-04360365, pharmacokinetic and pharmacodynamic relationships in plasma and CSF and the safety and tolerability of single doses of PF-04360365 administered to patients with Alzheimer's disease and healthy volunteers.

Official Title
-----------------
A Randomized, Investigator And Subject-Blind, Sponsor-Open, Placebo-Controlled Study To Examine The Effects Of PF-04360365 On ABETA In Patients With Alzheimer's Disease And Healthy Volunteers

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Biological: PF-04360365
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or females of non-childbearing potential (age 50 and over for Alzheimer's disease patients; 21-45 for healthy volunteers) For patients with Alzheimer's Disease: Diagnosis of probable Alzheimer's disease, consistent with criteria from both National Institute of Neurological and Communicable Disease and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and Diagnostic and Statistical Manual of Mental Disorders (DSM IV) Mini-mental status exam score greater than or equal to 20 Rosen-Modified Hachinski Ischemia Score of < or = 4 On stable dose of background cholinesterase inhibitor or memantine at least 3 months prior to enrollment Exclusion Criteria: Diagnosis or history of other demential or neurodegenerative disorders Diagnosis or history of clinically significant cerebrovascular disease Specific findings on magnetic resonance imaging (MRI); cortical infarct, micro hemorrhage, multiple white matter lacunes, extensive white matter abnormalities History of autoimmune disorders History of allergic or anaphylactic reactions

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04360365<br> | Biological: PF-04360365<br>* 10 mg/kg, single dose administered intravenously<br>|
| Placebo Comparator: Placebo<br>single dose administered intravenously | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional Clearance rate of ABeta peptide in CSF |  | 36 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the ratio of CSF labeled/unlabeled ABETA time curve from onset of clearance to 36h following start of infusion |  | 36 hours | 
| PF-04360365 concentrations and ABETA concentrations in plasma and CSF |  | 36 hours | 
| Ratio of labeled/unlabeled leucine in plasma and CSF post labeled leucine administration |  | 36 hours | 
| Adverse events, vital signs, clinical labs, electrocardiograms, physical / neurologic examinations, Columbia Suicide Severity Rating Scale, MRI |  | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alzheimer's disease antibody leucine ABeta