PTI-125 for Mild-to-moderate Alzheimer's Disease Patients

Exclusion Criteria

• •Exposure to an experimental drug, experimental biologic or experimental medical device within the longer of 5 half-lives or 3 months before screening
• •Enrollment in the previous PTI-125 trial
• •A medical condition that would interfere with a lumbar puncture
• •Residence in a skilled nursing facility and requiring 24 h care.
• •Clinically significant laboratory test results
• •Clinically significant untreated hypothyroidism
• •Insufficiently controlled diabetes mellitus
• •Renal insufficiency (serum creatinine \> ULN)
• •Malignant tumor within 3 years before screening (except squamous and basal cell carcinoma or cervical carcinoma in situ or localized prostate cancer or localized stage 1 bladder cancer)
• •History of ischemic colitis or ischemic enterocolitis
• •Unstable medical condition that is clinically significant in the judgment of the investigator
• •Alanine transaminase (ALT) or aspartate transaminase (AST) \> ULN or total bilirubin \> ULN.
• •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 cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (patients with a pacemaker are acceptable)
• •Symptomatic hypotension, or uncontrolled hypertension
• •Clinically significant abnormality on screening electrocardiogram (ECG), including but not necessarily limited to a confirmed corrected QT interval value \>= 450 msec for males or \>= 470 msec for females.
• •Stroke within 18 months before screening, or history of a stroke concomitant with onset of dementia
• •History of brain tumor or other clinically significant space-occupying lesion on CT or MRI
• •Head trauma with clinically significant loss of consciousness within 12 months before screening or concurrent with the onset of dementia
• •Onset of dementia secondary to cardiac arrest, surgery with general anesthesia, or resuscitation
• •Specific degenerative Central Nervous System disease diagnosis other than Alzheimer's disease (eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Frontotemporal Dementia, Parkinson's disease)
• •Wernicke's encephalopathy
• •Active acute or chronic Central Nervous System infection
• •Donepezil 23 mg quaque die currently or within 3 months prior to randomization
• •Discontinued AChEI \< 30 days prior to randomization
• •Antipsychotics; low doses are allowed only if the subject has received a stable dose for at least 3 months before randomization
• •Tricyclic antidepressants and monoamine oxidase inhibitors
• •Anxiolytics or sedative-hypnotics, including barbiturates (unless given in low doses for benign tremor); low doses of benzodiazepines and zolpidem are allowed
• •Immunosuppressants, including systemic corticosteroids, if taken in clinically immunosuppressive doses (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 illness within 30 days of enrollment
• •History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease
• •Positive serum hepatitis B surface antigen (HBsAg) or positive hepatitis C virus HCV antibody test at screening
• •Positive HIV test at screening
• •Positive urine drug test at screening
• •Loss of a significant volume of blood (\> 450 mL) within 4 weeks prior to the study
• •Suicidality on C-SSRS at screening