Study of the Safety and Effectiveness of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer's Disease
Study of the Safety and Effectiveness of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer's Disease
The purpose of this study is to evaluate the safety and efficacy of 2 fixed doses of EVP-6124
 compared to placebo for 26 weeks in subjects with mild to moderate Alzheimer's disease
 currently receiving stable treatment or previously treated with an acetylcholinesterase
 inhibitor.
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 probable AD consistent with criteria established
 by a workgroup of the National Institute on Aging and the Alzheimer's Disease
 Association

 -  Clinical decline within 12 months before screening and onset of symptoms at least 12
 months or longer before screening, which may include any documented cognition,
 functional, or other objective assessment or the clinical judgment of the investigator
 or the subject's referring physician that the subject has experienced a clinical
 decline within the last 12 months

 -  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 ≥14 and ≤24 at screening and confirmed on
 Day 1 prior to randomization (fluctuations of ±2 points are acceptable on Day
 1/baseline)

 -  Clinical Dementia Rating Global score (CDR-GS) ≥1 (at least mild dementia) at
 screening and confirmed on Day 1 prior to randomization

 -  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 approximately 4 times per week and will be
 available to attend clinic visits in person when possible

 -  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 26-week study

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

 -  Receiving a stable dose of an acetylcholinesterase inhibitor (AChEI) (donepezil,
 rivastigmine or galantamine) for at least 3 months (90 days) before screening and with
 continuous dosing for at least 6 months OR not presently receiving an AChEI (at least
 30 days before screening), but with a history of previous AChEI treatment (subjects
 receiving donepezil 23 mg currently or within 3 months before screening are
 ineligible)

 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 or the support
 person/caregiver to complete a 26-week study

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

 -  Inability to adequately cooperate or complete the cognitive testing procedures or any
 study assessment

 -  Residence in a skilled nursing facility

 -  Untreated vitamin B12 or folate deficiency (if treated, must be stably treated for at
 least 6 months before screening)

 -  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)

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

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

 -  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 hypertension (supine diastolic blood pressure >95 mmHg) (in
 the judgment of the investigator)

 -  Clinically significant abnormality on screening or baseline electrocardiogram (ECG),
 including but not necessarily limited to a confirmed corrected QT interval (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 central nervous system (CNS) disease diagnosis other than AD
 (eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Fronto-Temporal
 Dementia, Parkinson's disease)

 -  Subjects with no history of prior treatment with an AChEI (donepezil, rivastigmine, or
 galantamine)

 -  Memantine currently or within 30 days before screening

 -  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 screening (but not
 within 8 hours before any cognitive test)

 -  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 screening

 -  Antiepileptic medications if taken for control of seizures

 -  Chronic intake of opioid-containing analgesics

 -  Sedating H1 antihistamines

 -  Nicotine therapy (including the patch), varenicline (Chantix), or similar therapeutic
 agent within 30 days before screening

 -  Clinically significant urine drug screen or serum alcohol test result in the judgment
 of the investigator

 -  History of ischemic colitis or ischemic enterocolitis