- Subjects and caregivers must provide written Informed Consent and be willing to
comply with scheduled visits, treatment plan, laboratory tests, and other trial
procedures.
- AD: Diagnostic evidence of probable AD consistent with Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition (DSM-IV) and National Institute of
Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and
Related Disorders Association (NINCDS-ADRDA) criteria met by the site Physician at
the time of the Screening visit. This evidence must be fully documented in the
participant's file prior to the Baseline Visit.
- For amnestic Mild Cognitive Impairment (MCI): A Clinical Dementia Rating (CDR) of 0.5
(with memory box score of at least 0.5) and a memory complaint that is objectively
verified using a test of episodic memory: Delayed recall from one paragraph of the
Wechsler Logical Memory scale (cutoff scores by education - maximum score of 25).
- Less than or equal to 8 for 16 or more years of education; Less than or equal to 4
for 8-15 years of education; Less than or equal to 2 for 0-7 years of education.
- Mini Mental State Exam (MMSE) score of 21-30
- Male and female subjects of non child-bearing potential (or using appropriate birth
control measures) who are at least 50 years of age.
- In generally good health, in the opinion of the Principal Investigator (PI), based on
medical history, Body Mass Index (BMI), physical examination, vital signs, 12-lead
ECG, and laboratory values, including hematology and chemistry values.
- No known genetic AD causes for early onset memory impairment (e.g., presenilin
mutation), participants from a family with known autosomal dominant AD associated
with mutations in APP, PS1, or PS2 genes or strongly suspected, but not yet
identified mutations in APP, PS1 or PS2 genes or Down's syndrome are not eligible to
enroll. Individuals from families with late onset AD with 2 or more affected family
members may participate.
Type II diabetic subjects may be included provided that their disease and serum glucose
values are controlled and being actively managed, as assessed by the PI using a fasting
blood sugar and/or HgbA1C (per the PI's medical judgment in consultation with the
Sponsor).
- Rosen-Modified Hachinski Ischemia Score less than or equal to 4.
- Diagnosis or history of other possible cause for or significant contributor to
dementia, including but not limited to other neurodegenerative disorders (eg,
frontotemporal dementia, Lewy body disease, vascular dementia), vitamin B12
deficiency (reflex Methylmalonic Acid (MMA) and folate if B12 is low), untreated
thyroid disease, syphilis, alcoholism, severe or recurrent head injury that is
clinically relevant to the disease under study, or onset of dementia following heart
surgery or cardiac arrest.
- Diagnosis or history of cerebrovascular disease (eg, stroke, transient ischemic
attack), severe carotid stenosis, cerebral hemorrhage, intracranial tumor,
subarachnoid hemorrhage, or subdural hematoma that could contribute to the subject's
current cognitive or functional status, impair ability to fully participate in the
trial or that may impact status during the one week study.
- Specific exclusionary brain MRI findings identified prior to study or at baseline as
determined by the investigator that could either contribute to the subject's current
cognitive or functional decline impair ability to fully participate in the trial or
that may impact status during the trial:
- History of cancer within the last year (except for cutaneous basal cell, squamous
cell cancer resolved by excision, colon polyp resolved by excision, or
non-progressive prostate cancer per investigator's judgment).
- History of clinically significant cardiovascular or renal events.
- Subjects with uncontrolled hypertension even with therapeutic intervention
- History of clinically significant (as determined by the PI in consultation with the
Sponsor) syncope, seizure, head trauma, or clinically significant unexplained loss of
consciousness within the last 5 years.
- A diagnosis of major depressive disorder or other psychiatric illness as the primary
diagnosis per the DSM-IV text revision (TR) criteria per the investigator's judgment.
- History of schizophrenia, bipolar disorder, or other severe mental illness.
- Known history of alcohol or drug abuse (as defined by the DSM-IV-TR) within 5 years
prior to dosing or a positive result regarding use of illicit drugs on the drug
screening test.
- History of clinically significant symptoms of pulmonary disease that requires
treatment (eg. asthma, COPD, or other chronic respiratory conditions).
- Known positive Human immunodeficiency virus (HIV) status.
- Unwilling or unable to comply with the Life Style guidelines described in this
protocol.
Exclusions Related to Medications or Procedures
- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
longer) of Study Day 1.
- Use of tobacco- or nicotine-containing products within three months of study Day 1.
Use of medication(s) for cognitive enhancement ? 90 days before the first dose of study
medication.
- Prescription: including but not limited to donepezil, galantamine, rivastigmine,
tacrine, memantine, Axona?;
- Reason for stoppage of donepezil may not be related to tolerability issues or to gain
entry in this study.
- Non-prescription treatments for cognitive enhancement.
- Subjects with either non-removable ferromagnetic implants (such as cardiac
pacemaker), aneurysm clips or other foreign bodies that would contraindicate a
brain MRI scan.
- A clinically significant (as determined by the PI) abnormality in the 12-lead
ECG, including complete heart block, bradycardia (heart rate sinus pauses >2 seconds, second or third degree heart block, QTc >450 or other
abnormalities judged clinically significant by the PI.