Study of the Safety of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer's Disease Currently Receiving Memantine

Inclusion Criteria:

- Ages ≥55 and ≤85 years

- Informed consent form (ICF) signed by the subject or legally acceptable
representative before any study-specific procedures for the subject are performed and
an ICF signed by the support person/caregiver before any study-specific procedures
for the support person/caregiver are performed

- Clinical diagnosis of dementia due to possible or probable AD consistent with
criteria established by a workgroup of the National Institute on Aging and the
Alzheimer's Disease Association

- Magnetic resonance imaging (MRI) or computed tomography (CT) scan performed within 12
months before screening, with findings consistent with the diagnosis of dementia due
to AD without any other clinically significant comorbid pathologies. If an MRI or CT
scan is unavailable or occurred greater than 12 months before screening, this
assessment should be completed and the findings confirmed before the subject enters
the run-in period (Day -14) (copy of the report will be available at the study site)

- Mini-Mental State Examination (MMSE) score ≥12 and ≤26 at screening

- Modified Hachinski Ischemic Scale (mHIS) score ≤4 at screening

- Fertile, sexually active subjects (men and women) must use an effective method of
contraception during the study. Female subjects and the female partner of male
subjects must be surgically sterile (hysterectomy or bilateral tubal ligation),
postmenopausal for at least 1-year, or willing to practice adequate methods of
contraception if of childbearing potential (defined as consistent use of combined
effective methods of contraception [including at least 1 barrier method])

- Reliable and capable support person/caregiver, who if not living in the same
household, interacts with the subject regularly and will help facilitate clinic
visits of the study subject

- Subject living at home, senior residential setting, or an institutional setting
without the need for continuous (ie, 24-hour) nursing care

- General health status acceptable for participation in a 24-week study

- Fluency (oral and written) in the language in which the standardized tests will be
administered

- Receiving a stable dose of memantine for at least 3 months (90 days) before screening
and with continuous dosing for at least 3 months. Additional co-medication with an
AChEI (donepezil in any dose form other than 23 mg once daily (QD), rivastigmine or
galantamine) is allowed if stable for at least 3 months (90 days) before screening
with total continuous exposure for at least 3 months.

Exclusion Criteria:

- Exposure to an experimental drug, experimental biologic or experimental medical
device within 2 months (60 days) before screening

- Prior participation in an amyloid vaccination clinical study at any time in the past
or completion of a passive amyloid vaccination study within 6 months before screening

- Inability to swallow a tablet

- In the judgment of the investigator, inability of the subject to complete a 24-week
study

- Residence in a skilled nursing facility

- Inability to be ≥75% compliant with single-blind study drug

- Clinically significant (in the judgment of the investigator) abnormal serum
electrolytes (sodium, potassium, magnesium) after repeat testing

- Clinically significant untreated hypothyroidism (if treated, thyroid-stimulating
hormone level and thyroid supplementation dose must be stable for at least 6 months
before screening)

- Insufficiently controlled diabetes mellitus (in the judgment of the investigator) or
requiring insulin

- Renal insufficiency (serum creatinine >2.0 mg/dL)

- Malignant tumor within 3 years before screening (except squamous and basal cell
carcinoma or cervical carcinoma in situ or localized prostate cancer)

- History of ischemic colitis or ischemic enterocolitis

- Unstable medical condition that is clinically significant in the judgment of the
investigator

- Female subjects who are pregnant, nursing, or planning to become pregnant during the
study

- Alanine transaminase (ALT) or aspartate transaminase (AST) >2.5 times the upper limit
of normal

- History of myocardial infarction or unstable angina within 6 months before screening

- History of more than 1 myocardial infarction within 5 years before screening

- Clinically significant (in the judgment of the investigator) cardiac arrhythmia
(including atrial fibrillation), cardiomyopathy, or cardiac conduction defect
(subjects with a pacemaker are acceptable)

- Symptomatic hypotension, or uncontrolled hypertension (in the judgment of the
investigator)

- Clinically significant abnormality on screening electrocardiogram (ECG), including
but not necessarily limited to a confirmed QTc value ≥450 msec for males or ≥470 msec
for females. In subjects with a QRS value >120msec, those with a QTc value <500 msec
may be eligible following discussion with the Medical Monitor.

- Stroke within 18 months before screening, or history of a stroke concomitant with
onset of dementia

- History of brain tumor, subdural hematoma, or other clinically significant (in the
judgment of the investigator) space-occupying lesion on CT or MRI

- Head trauma with clinically significant (in the judgment of the investigator) loss of
consciousness within 12 months before screening or concurrent with the onset of
dementia

- Onset of dementia secondary (in the judgment of the investigator) to cardiac arrest,
surgery with general anesthesia, or resuscitation

- Specific degenerative CNS disease diagnosis other than AD (eg, Huntington's disease,
Creutzfeld-Jacob disease, Down's syndrome, Fronto-Temporal Dementia, Parkinson's
disease)

- Wernicke's encephalopathy

- Active acute or chronic CNS infection

- Donepezil 23 mg QD currently or within 3 months prior to randomization

- Discontinued AChEI <30 days prior to randomization

- Antipsychotics; low doses (in the judgment of the investigator, except clozapine) are
allowed only if given for sleep disturbances, agitation and/or aggression, and only
if the subject has received a stable dose for at least 3 months before randomization

- Tricyclic antidepressants and monoamine oxidase inhibitors; all other antidepressants
are allowed only if the subject has received a stable dose for at least 3 months
before randomization

- Anxiolytics or sedative-hypnotics, including barbiturates (unless given in low doses
for benign tremor); low doses of benzodiazepines and zolpidem (in the judgment of the
investigator) are allowed only if given for insomnia/sleep disturbance, and only if
the subject has received a stable dose for at least 3 months before randomization

- Peripherally acting drugs with effects on cholinergic transmission

- Immunosuppressants, including systemic corticosteroids, if taken in clinically
immunosuppressive doses in the judgment of the investigator (Note: steroid use for
allergy or other inflammation is permitted)

- Antiepileptic medications if taken for control of seizures

- Chronic intake of opioid-containing analgesics

- Sedating H1 antihistamines

- Nicotine therapy (all dosage forms including a patch), varenicline (Chantix), or
similar therapeutic agent within 30 days before screening

- Clinically significant urine drug screen (UDS) or serum alcohol test result in the
judgment of the investigator (including medical marijuana)