| Eligibility |
Inclusion Criteria:
1. Written informed consent from caregiver and subject (if possible) or legally
acceptable representative if different from caregiver
2. Male and female subjects 55-85 years of age inclusive
3. Cognitive deficit present for at least 2 years that meet the diagnostic criteria for
probable Alzheimer's dementia. The diagnosis must be confirmed at the time of the
screening visit
4. MMSE-2 score of 10-18 inclusive (applies to Screening Visit only)
5. Patients must have a baseline SIB total score of at least 60 and may not have a SIB
score >93 at screening
6. Neuroimaging computerized tomography (CT) or Magnetic Resonance Imaging (MRI) within
the last 24 months consistent with a diagnosis of probable AD without any other
clinically significant co-morbid pathologies. If there has been a significant change
in the subject's clinical status since the last imaging study that is not consistent
with progression of the subject's AD, an imaging study should be performed to confirm
eligibility
7. Reliable caregiver(s) or informant(s) who attends the subject at least an average of 3
hours or more per day for 3 or more days per week and who will agree to accompany the
subject to the clinic visits and reliably complete the caregiver questions
8. Adequate vision and motor function to comply with testing
9. If taking an approved cholinesterase inhibitor for treatment of Alzheimer's disease,
must be on a stable dose for at least 3 months prior to entry into study and the dose
must not change during the study unless a change is required due to an adverse effect
of the prescribed medication or a clinically significant change in the patient's
status
10. Subjects who are memantine naïve or have been off memantine for at least 90 days prior
to initial treatment with study drug
11. Subjects on neuroleptic medications must be on a stable dose for =4 weeks at screening
(dose adjustments will be permitted if medically necessary at the discretion of the
PI)
12. Females participating in the study must meet one the following criteria:
1. Surgically sterilized (e.g., hysterectomy, bilateral oophorectomy or tubal
ligation) for at least 6 months or postmenopausal (postmenopausal females must
have no menstrual bleeding for at least 1 year) or
2. If not postmenopausal, agree to use a double method of contraception, one of
which is a barrier method (e.g., intrauterine device plus condom, spermicidal gel
plus condom) 30 days prior to dosing until 30 days after last dose and have
negative human chorionic gonadotropin (ß-hCG) test for pregnancy at screening
13. Males who have not had a vasectomy must use appropriate contraception methods (barrier
or abstinence) from 30 days prior to dosing until 30 days after last dose
14. In the opinion of the PI subjects should be in reasonably good health over the last 6
months and any chronic disease should be stable -
Exclusion Criteria:
Eligibility Criteria:
Inclusion
1. Written informed consent from caregiver and subject (if possible) or legally acceptable
representative if different from caregiver 2. Male and female subjects 55-85 years of age
inclusive 3. Cognitive deficit present for at least 2 years that meet the diagnostic
criteria for probable Alzheimer's dementia. The diagnosis must be confirmed at the time of
the screening visit 4. MMSE-2 score of 10-18 inclusive (applies to Screening Visit only) 5.
Patients must have a baseline SIB total score of at least 60 and may not have a SIB score
>93 at screening 6. Neuroimaging computerized tomography (CT) or Magnetic Resonance Imaging
(MRI) within the last 24 months consistent with a diagnosis of probable AD without any
other clinically significant co-morbid pathologies. If there has been a significant change
in the subject's clinical status since the last imaging study that is not consistent with
progression of the subject's AD, an imaging study should be performed to confirm
eligibility 7. Reliable caregiver(s) or informant(s) who attends the subject at least an
average of 3 hours or more per day for 3 or more days per week and who will agree to
accompany the subject to the clinic visits and reliably complete the caregiver questions 8.
Adequate vision and motor function to comply with testing 9. If taking an approved
cholinesterase inhibitor for treatment of Alzheimer's disease, must be on a stable dose for
at least 3 months prior to entry into study and the dose must not change during the study
unless a change is required due to an adverse effect of the prescribed medication or a
clinically significant change in the patient's status 10. Subjects who are memantine naïve
or have been off memantine for at least 90 days prior to initial treatment with study drug
11. Subjects on neuroleptic medications must be on a stable dose for =4 weeks at screening
(dose adjustments will be permitted if medically necessary at the discretion of the PI) 12.
Females participating in the study must meet one the following criteria:
1. Surgically sterilized (e.g., hysterectomy, bilateral oophorectomy or tubal ligation)
for at least 6 months or postmenopausal (postmenopausal females must have no menstrual
bleeding for at least 1 year) or
2. If not postmenopausal, agree to use a double method of contraception, one of which is
a barrier method (e.g., intrauterine device plus condom, spermicidal gel plus condom)
30 days prior to dosing until 30 days after last dose and have negative human
chorionic gonadotropin (ß-hCG) test for pregnancy at screening 13. Males who have not
had a vasectomy must use appropriate contraception methods (barrier or abstinence)
from 30 days prior to dosing until 30 days after last dose 14. In the opinion of the
PI subjects should be in reasonably good health over the last 6 months and any chronic
disease should be stable Exclusion
1. Dementia due to any condition other than AD, including vascular dementia
(Rosen-Modified Hachinski Ischemic score = 5)
2. Evidence of significant central nervous system (CNS) vascular disease on previous
neuroimaging including but not limited to: cortical stroke, multiple infarcts,
localized single infarcts in the thalamus, angular gyrus, multiple lacunar
infarcts or extensive white matter injury
3. Clinically significant neurologic disease or condition other than AD, such as
cerebral tumor, chronic subdural fluid collections, Huntington's Disease,
Parkinson's Disease, normal pressure hydrocephalus, or any other diagnosis that
could interfere with assessment of safety and efficacy
4. Evidence of clinically significant unstable cardiovascular, pulmonary, renal,
hepatic, gastrointestinal, neurologic, or metabolic disease within the 6 months
prior to enrollment. If there is a history of cancer the subject should be clear
of cancer for at least 2 years prior to screening. More recent history of basal
cell or squamous cell carcinoma and melanoma in situ (Stage 0) may be acceptable
after review by the Medical Monitor.
5. Creatinine clearance (CL) of <45ml/min
6. Poorly controlled diabetes, at the discretion of the Principal Investigator
7. Concomitant treatment with NMDA receptor antagonists such as but not limited to
memantine or drug combinations containing memantine, dextromethorphan (a cough
suppressant), ketamine, phencyclidine (PCP), methoxetamine (MXE), nitrous oxide
(N2O) and the following synthetic opioids: penthidine, levorphanol, methadone,
dextrpropoxyphene, tramadol, and ketobemidone.
8. Use of vitamin E > 400 International Units (IU) per day within 14 days prior to
screening
9. Use of acetaminophen within 14 days prior to screening
10. Use of gabapentin within 14 days prior to screening
11. Use of valproic acid within 14 days prior to screening
12. Use of an active Alzheimer's vaccine within 2 years prior to screening
13. Use of a monoclonal antibody for treatment of AD within 1 year prior to screening
14. Any medical or psychiatric condition that is likely to require initiation of
additional medication or surgical intervention during the course of the study
15. Any screening laboratory values outside the reference ranges that are deemed
clinically significant by the PI
16. Use of an investigational drug within 90 days prior to screening
17. Suicidality defined as active suicidal thoughts during the 6 months prior to
screening or at Baseline [Type 4 or 5 on C-SSRS], or history of suicide attempt
in previous 2 years, or at serious suicide risk in PI's judgment
18. Major psychiatric illness such as current major depression according to
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition , current or
past diagnosis of bipolar disorder, schizophrenia, or any other psychiatric
disorder that might interfere with the assessments of safety or efficacy at the
discretion of the PI
19. Diagnosis of alcohol or drug abuse within the last 2 years
20. Abnormal laboratory tests that suggest an alternate etiology for dementia. If the
patient has prior history of serum B12 abnormality, anemia with hemoglobin
=10g/dl, thyroid function abnormality, electrolyte abnormality, or positive
syphilis serology the patient should be revaluated to determine if these
potential causes of dementia have been addressed. Only if these causes have been
ruled out as the cause of the dementia can the patient be enrolled.
21. History of prolonged QT or prolonged QT on screening ECG (QTcB or QTcF >499 per
central reader)
22. Acute or poorly controlled medical illness: blood pressure > 180 mmHg systolic or
100 mmHg diastolic; myocardial infarction within 6 months; uncompensated
congestive heart failure [New York Heart Association (NYHA) Class III or IV]
23. Known to be seropositive for human immunodeficiency virus (HIV)
24. Known to be seropositive for Hepatitis B or C, unless successful curative
treatment for Hepatitis C (e.g., Harvoni) has been received and there is
documentation that there is no Hep B/C virus detected 3 months after completion
of treatment
25. AST or ALT >3x upper limit of normal (ULN) and total bilirubin >2x ULN or
International Normalized Ratio (INR) >1.5
26. Prior exposure to bryostatin, or known sensitivity to bryostatin or any
ingredient in the study drug
27. Any other concurrent medical condition, which in the opinion of the PI makes the
subject unsuitable for the clinical study -
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