A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamic (PD) Effects of Posiphen® in Subjects With Early Alzheimer’s Disease (AD)
when compared to a placebo, in adult male and female patients with early Alzheimer’s disease
1. Male or female aged 55 to 85 years (inclusive).
2. Female participants must be post-menopausal for at least 2 consecutive years or
surgically sterile (bilateral tubal ligation, hysterectomy or bilateral oophorectomy)
for at least 6 months prior to screening.
3. Female participants will be given a urine pregnancy test at the screening visit for
which they should test negative.
4. Diagnosis of amnestic MCI or probable mild AD according to the core clinical criteria
outlined in the NIA-AA Guidelines.
5. MMSE score between the range of 21 to 27.
6. CDR score of 0.5 or 1.0.
7. A score on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only)
from the Wechsler Memory Scale-Revised within the following education-adjusted ranges:
– Less than or equal to 11 for 16 or more years of education
– Less than or equal to 9 for 8-15 years of education
– Less than or equal to 6 for 0-7 years of education
8. To qualify for entry, subjects will have CSF Aβ42 levels that are consistent with
Alzheimer’s disease as measured via mass spectrometry by C2N.
9. General cognition and functional performance sufficiently preserved that the subject
can provide written informed consent.
10. A minimum of 6 years of education or good work history.
11. 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. Study partner (or other individual) should also oversee
study drug administration if needed to ensure compliance with dose regimen.
12. No evidence of current suicidal ideation or previous suicide attempt in the past month
as evaluated in the Columbia Suicide Severity Rating Scale.
13. MRI scan within the 12 months prior to screening without evidence of infection,
infarction, or other focal lesions and without clinical symptoms suggestive of
intervening neurological disease. Lacunes that are not believed to contribute to the
subject’s cognitive impairment are permissible. If there is no MRI available within a
12-month timeframe, then an MRI must be performed as part of the screening procedures
14. Stability of permitted medications for 4 weeks prior to baseline. NOTE: Cholinesterase
inhibitors and or memantine are allowable only if stable for 12 weeks prior to screen.
If taking Aricept (donepezil), no more than 10 mg/day is permitted during the course
of the study.
15. Adequate visual and hearing ability (physical ability to perform all the study
16. Good general health with no disease expected to interfere with the study. Subjects may
have common age-related disorders (i.e., hypertension, type II diabetes, dyslipidemia,
and hypothyroidism) as long as these disorders are being controlled by diet or
17. Must speak English fluently.
1. Has a history of a psychiatric disorder such as schizophrenia, bipolar disorder or
major depression according to the criteria of the most current version of the
Diagnostic and Statistical Manual of Mental Disorders (DSM). Mild depression or
history of depression that is stable on treatment with a tricyclic antidepressant SSRI
or SNRI medication at a stable dose is acceptable.
2. Other neurodegenerative diseases, including Parkinson’s disease and Huntington’s
disease, or cerebral tumor.
3. Dementia other than AD, such as Acquired Immunodeficiency Syndrome (AIDS),
Creutzfeldt-Jakob disease (CJD), Lewy Bodies dementia (LBD), Cerebrovascular dementia
(CVD), Progressive Supranuclear Palsy (PSP), or normal pressure hydrocephalus (NPH).
4. History of a seizure disorder.
5. Clinically significant abnormalities in screening laboratory or ECG results.
6. Has current serious or unstable illness including cardiovascular, hepatic, renal,
gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic,
or hematologic disease or other conditions that, in the investigator’s opinion, makes
them ineligible for participation in this study.
7. Has four or more microinfarcts as noted in the MRI scan.
8. Has cancer or has had a malignant tumor within the past 3 years, except patients who
underwent potentially curative therapy with no evidence of recurrence. (Patients with
stable untreated prostate cancer or skin cancers are not excluded).
9. According to the criteria of the most current version of the DSM, alcohol abuse,
alcohol dependence, or drug abuse in the past 5 years.
10. Participation in another clinical trial with an investigational agent and have taken
at least one dose of study medication, unless unblinded on placebo, within 16 weeks
prior to screening. (The end of a previous investigational trial is the date the last
dose of an investigational agent was taken).
11. Resides in a skilled nursing facility.
12. Subjects with infection or inflammation of the skin or skin disease at or in proximity
to the lumbar puncture site.
13. History of lumbar spine surgery or chronic low back pain (CLBP).
14. Subjects whom the site PI deems to be otherwise ineligible.
- UCSD Alzheimer’s Disease Research Center, La Jolla, California, United States, 92037