Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics Study of Bryostatin 1 in Patients With Alzheimer's Disease

Inclusion Criteria:

- Male or female, age 50 yrs or older. Females must be of non-childbearing potential
(surgically sterilized or at least 2 yrs post-menopausal)

- Must have a cognitive deficit present for at least 1 yr & meet DSM-IV-TRTM criteria
for AD & meet NINCDS/ADRDA criteria for the presence of probable AD

- Severity of AD must be mild to moderate, documented with a MMSE score of 12-26

- Has a CT scan or MRI scan within the prior 12 months, which is compatible with a
diagnosis of probable AD

- Ability to walk, at least with an assistive device

- Vision & hearing sufficient to comply with testing

- Normal cognitive & social functioning prior to onset of dementia

- Consistent caregiver to accompany patient to assessment visits

- Sufficient basic education to be able to complete the cognitive assessments

- Living outside an institution

- Informed consent signed & dated by patient or legal representative

- Has provided written authorization for the use & disclosure of protected health
information

Exclusion Criteria:

- Dementia due to any condition other than AD, including vascular dementia (modified
Hachinski Ischemic Scale ≥ 5; positive NINDS-AIREN criteria)

- Evidence of clinically significant unstable cardiovascular, renal, hepatic,
gastrointestinal, neurological, or metabolic disease within the past 6 months (as
determined by medical history, ECG results, chest x-ray, or physical examination)

- Use of any drug within 14 days prior to randomization unless the dose of the drug &
the condition being treated have been stable for at least 30 days & are expected to
remain stable during the study & neither the drug nor the condition being treated is
expected to interfere with the study endpoints

- Any medical or psychiatric condition that may require medication or surgical
treatment during the study

- Life expectancy less than 6 months

- Any other screening laboratory values outside the normal ranges that are deemed
clinically significant by the investigator

- Use of an investigational drug within 30 days prior to the screening visit or during
the entire study

- Significant neurological disease other than AD, including cerebral tumor,
Huntington's Disease, Parkinson's Disease, normal pressure hydrocephalus, & other
entities

- Major depression according to DSM-IV

- Psychotic episodes requiring hospitalization or antipsychotic therapy for more than 2
weeks within the past 10 yrs, not linked to AD

- Agitation sufficient to preclude participation in this trial

- Alcohol or drug dependence diagnosed within the past 10 yrs

- Epilepsy or anti-epileptic drug therapy

- Abnormal laboratory tests that might point to another etiology for dementia: serum
B12, folate, thyroid functions, electrolytes, syphilis serology

- Musculoskeletal diseases that could interfere with assessment

- Acute or poorly controlled medical illness: blood pressure> 180 mmHg systolic or 100
mmHg diastolic; myocardial infarction within 6 months; uncompensated congestive heart
failure (NYHA Class III or IV), severe renal, hepatic or gastrointestinal disease
that could alter drug pharmacokinetics; blood glucose > 180 mg/dl on repeated testing
at entry into study or need for insulin therapy

- Previous randomization in this trial or participation in another investigational
trial < 2 months prior to randomization

- Likelihood, according to clinical judgment, of being transferred to a nursing home
within 6 months

- Change in dosage of any concomitant antidepressant within 30 days prior to
randomization

- Lack of caregiver

- Pregnant or lactating females

- Patients who in the judgment of the Investigator may be unreliable or uncooperative
with the evaluation procedures outlined in this protocol

- HIV positive

- Hepatitis B or C positive

- Concomitant use of medications other than AD or antidepressant medications for which
the dose regimens are stabilized for at least 30 days prior to enrollment in study