Alzheimer's Disease
Conditions
Keywords
Alzheimer's disease antibody leucine ABeta
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.
Interventions
BIOLOGICALPF-04360365
10 mg/kg, single dose administered intravenously
DRUGPlacebo
Placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Fractional Clearance rate of ABeta peptide in CSF | 36 hours |
Secondary
| Measure | 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 |
Countries
Sweden, United States
Outcome results
None listed