A Phase IIa Multi-Center Study of 18F-FDG PET, Safety, and Tolerability of AZD0530 in Mild Alzheimer's Disease
A Phase IIa Multi-Center Study of 18F-FDG PET, Safety, and Tolerability of AZD0530 in Mild Alzheimer's Disease
AZD0530 is an inhibitor of Src and Abl family kinases1. It has been developed as treatment
 for malignancies because these kinases play a role in tumor invasion and proliferation.
 However, the Src family kinases (SFKs) are highly expressed in brain and have major effects
 on synaptic plasticity2. Moreover, the investigators have recently shown that a specific SFK,
 namely Fyn, is aberrantly activated by specific conformations of the Amyloid Beta (Aß)
 peptide from Alzheimer's disease (AD). Genetic deletion of Fyn rescues AD deficits in
 preclinical models. This clinical trial will test the potential benefit of AZD0530 for
 Alzheimer's disease modification.
Inclusion Criteria

 1. NIA-Alzheimer's Association core clinical criteria for probable AD

 2. 18F-Florbetapir scan with evidence of elevated Aβ (based on central review)

 3. Age between 55-85 (inclusive)

 4. MMSE score between 18 and 26 (inclusive)

 5. Stability of permitted medications for 4 weeks. In particular:

 -  Stable doses of antidepressants lacking significant anticholinergic side effects
 (if they are not currently depressed and do not have a history of major
 depression within the past 1 year)

 -  Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks
 prior to screen

 6. Geriatric Depression Scale less than 6 [Note: a score ≥6 on this screening scale may
 be permissible, if the subject is examined by a site clinician and judged not to be
 depressed.]

 7. Study partner is available who has frequent contact with the subject (e.g., average of
 10 hours per week or more), and can accompany the subject to most visits to answer
 questions about the subject

 8. Visual and auditory acuity adequate for neuropsychological testing

 9. Good general health with no disease expected to interfere with the study

 10. Subject is not pregnant, lactating, or of childbearing potential (i.e., women must be
 two years post-menopausal or surgically sterile)

 11. Modified Hachinski less than or equal to 4

 12. Completed six grades of education or has a good work history

 13. Must speak English or Spanish fluently

 Exclusion Criteria

 1. Any significant neurologic disease other than AD, such as Parkinson's disease,
 multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain
 tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple
 sclerosis, or history of significant head trauma followed by persistent neurologic
 defaults or known structural brain abnormalities

 2. Screening/baseline MRI scan with evidence of infection, infarction, or other focal
 lesions or multiple lacunes or lacunes in a critical memory structure

 3. Subjects that have any contraindications for MRI studies, including claustrophobia,
 the presence of metal (ferromagnetic) implants, or cardiac pacemaker

 4. Major depression, bipolar disorder as described in DSM-IV within the past 1 year or
 psychotic features, agitation or behavioral problems within 3 months, which could lead
 to difficulty complying with the protocol

 5. History of schizophrenia (DSM V criteria)

 6. History of alcohol or substance abuse or dependence within the past 2 years (DSM V
 criteria)

 7. Clinically significant or unstable medical condition, including uncontrolled
 hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal,
 hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may
 either put the subject at risk because of participation in the study, or influence the
 results, or the subject's ability to participate in the study.

 8. Has had a history within the last 5 years of a primary or recurrent malignant disease
 with the exception of non-melanoma skin cancers, resected cutaneous squamous cell
 carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ
 prostate cancer with normal prostate-specific antigen post-treatment

 9. Clinically significant abnormalities in B12 or TFTs that might interfere with the
 study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and
 methylmalonic acid (MMA)) indicate that it is not physiologically significant.

 10. Residence in skilled nursing facility.

 11. Use of any excluded medication as described in study protocol

 12. Current or recent participation in any procedures involving radioactive agents,
 including current, past, or anticipated exposure to radiation in the workplace, such
 that the total radiation dose exposure to the subject in a given year would exceed the
 limits of annual and total dose commitment set forth in the US Code of Federal
 Regulations (CFR) Title 21 Section 361.1. This guideline is an effective dose of 5 rem
 received per year.

 13. Neutropenia defined as absolute neutrophils count of <1,800/microliter

 14. Thrombocytopenia defined as platelet count <120x103/microliter

 15. For CSF sub-study participants, a current blood clotting or bleeding disorder, or
 significantly abnormal PT or PTT at screening

 16. Clinically significant abnormalities in screening laboratories, including:

 -  Aspartate aminotransferase (AST) >1.5 times ULN

 -  Alanine aminotransferase (ALT) > 1.5 times ULN

 -  Total bilirubin >1.5 times ULN

 -  Serum creatinine >2.0 times ULN

 17. History of interstitial lung disease

 18. Patients whom the PI deems to be otherwise ineligible