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Informed consent form (ICF) signed by the subject or legally acceptable representative |
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Patient has a caregiver or legal respresentative responsible for administering the drug and recording the time |
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Ages >= 50 and <= 85 years (upper limit waived for prior PTI-125 study participants) |
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Clinical diagnosis of dementia due to possible or probable Alzheimer's disease |
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If female, postmenopausal for at least 1 year |
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Patient living at home, senior residential setting, or an institutional setting without the need for continuous (i.e. 24-h) nursing care |
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General health status acceptable for participation in the study |
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Fluency (oral and written) in English or Spanish |
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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 |
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The patient is a non-smoker for at least 3 years |
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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 |
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Additional Criteria for NEW patients |
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The patient has a ratio of total tau/A42 in cerebrospinal fluid >= 0.28 |
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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 |
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Anything in the opinion of the Investigator would preclude participation in a 1-year study
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Positive urine drug test at screening
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Positive HIV, HCV or HbsAg screen
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Suicidality on C-SSRS
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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
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A medical condition that would interfere with a lumbar puncture
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Residence in a skilled nursing facility and requiring 24 h care
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Clinically significant laboratory test results
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Clinically significant untreated hypothyroidism
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Insufficiently controlled diabetes mellitus
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Renal insufficiency (serum creatinine > ULN and clinically signigicant in the opinion of PI and/or Sponsor)
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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)
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History of ischemic colitis or ischemic enterocolitis
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Unstable medical condition that is clinically significant in the judgment of the investigator
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Alanine transaminase (ALT) or aspartate transaminase (AST) > ULN or total bilirubin > ULN and clinically significant in the opinion of PI and/or Sponsor
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History of myocardial infarction or unstable angina within 6 months before screening
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History of more than 1 myocardial infarction within 5 years before screening
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Clinically significant cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (patients with a pacemaker are acceptable)
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Symptomatic hypotension, or uncontrolled hypertension
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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
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Stroke within 18 months before screening, or history of a stroke concomitant with onset of dementia
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History of brain tumor or other clinically significant space-occupying lesion on CT or MRI
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Head trauma with clinically significant loss of consciousness within 12 months before screening or concurrent with the onset of dementia
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Onset of dementia secondary to cardiac arrest, surgery with general anesthesia, or resuscitation
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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)
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Wernicke's encephalopathy
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Active acute or chronic Central Nervous System infection
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Donepezil 23 mg or greater QD currently or within 3 months prior to randomization
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Discontinued AChEI < 30 days prior to randomization
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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
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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
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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
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Immunosuppressants, including systemic corticosteroids, if taken in clinically immunosuppressive doses (Steroid use for allergy or other inflammation is permitted.)
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Antiepileptic medications if taken for control of seizures
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Chronic intake of opioid-containing analgesics
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Sedating H1 antihistamines
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Nicotine therapy (all dosage forms including a patch), varenicline (Chantix), or similar therapeutic agent within 30 days before screening
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Clinically significant illness within 30 days of enrollment
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History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease
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Loss of a significant volume of blood (> 450 mL) within 4 weeks prior to the study
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COVID-19 infection
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