Overview

An Open-label study for patients who completed the previous studies, PTI-125-02 or PTI-125-03. Additional new patients will be included for a total of 100 patients enrolled for this study.

Eligibility

Inclusion Criteria:

• Informed consent form (ICF) signed by the subject or legally acceptable representative.
• Patient has a caregiver or legal respresentative responsible for administering the drug and recording the time.
• Ages >= 50 and <= 85 years (upper limit waived for prior PTI-125 study participants)
• Clinical diagnosis of dementia due to possible or probable Alzheimer's disease
• If female, postmenopausal for at least 1 year
• Patient living at home, senior residential setting, or an institutional setting without the need for continuous (i.e. 24-h) nursing care
• General health status acceptable for participation in the study
• Fluency (oral and written) in English or Spanish
• If receiving memantine, rivastigmine, galantamine or an AChEI, receiving a stable dose for at least 3 months. If receiving donepezil, any dose lower than 23 mg once daily. Multiple medications are allowed.
• The patient is a non-smoker for at least 3 years.
• The patient or legal representative must agree to comply with the drawing of blood samples, laboratory assessments and for new patients or patients starting < 30 days form the last PTI-125 study, with a lumbar puncture and the drawing of cerebrospinal fluid samples for biomarker assessments.

Additional Criteria for NEW patients:

• The patient has a ratio of total tau/A42 in cerebrospinal fluid >= 0.28.
• MMSE score >= 16 and <=26 at screening, OR if > 26, must have evidence of AD pathology such as a prior CSF total tau/AB42 ratio >=0.28, an amyloid positive PET scan or hippocampal volume loss consistent with AD.

Exclusion Criteria:

• Anything in the opinion of the Investigator would preclude participation in a 1-year study.
• Positive urine drug test at screening
• Positive HIV, HCV or HbsAg screen
• Suicidality on C-SSRS
• Exposure to an experimental drug other than PTI-125, experimental biologic or experimental medical device within the longer of 5 half-lives or 3 months before screening
• 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 and clinically signigicant in the opinion of PI and/or Sponsor)
• 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 and clinically significant in the opinion of PI and/or Sponsor.
• 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 or greater QD currently or within 3 months prior to randomization
• Discontinued AChEI < 30 days prior to randomization
• Antipsychotics; low doses 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 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.
• 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
• Loss of a significant volume of blood (> 450 mL) within 4 weeks prior to the study
• COVID-19 infection