Clinical trial: Simufilam (PTI-125), 100 mg, for Mild-to-moderate Alzheimer's Disease Patients (NCT04388254)

Eligibility criteria:
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/Aβ42 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
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 50 Years old.
Subject must be at most 85 Years

Patient description (medical language): A 70-year-old man comes to the office accompanied by his wife.  The patient has experienced progressive memory loss over the last years.  He needs help with some of his routine activities, such as paying bills.  The patient's wife says, "He used to be such an independent person, but now he needs help with many things, even finding direction to home!"  Medical history includes hypertension, hyperlipidemia, and type 2 diabetes mellitus.  Family history includes Alzheimer disease in his father.  MRI reveals diffuse cortical and hippocampal atrophy. The diagnosis of AD is made using the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria.

Patient description (patient's own words): I am a 70-year-old man, and I paid a visit to the doctor with my wife the other day. I noticed that I tend to forget small things and that my memory has decreased over the past few years. I even ask my wife to help me out with my daily routine. I used to be the one paying the bills, but now she has to give me a hand. My wife mentioned to the doctor that I used to be independent and that I tend to forget where we live. I suffer from hypertension, high cholesterol, and type 2 diabetes. My poor dad was suffering from Alzheimer disease, so I hope I'm not going to end the same way! I did an MRI and they found out that some part of my brain was decreasing. I also did an Alzheimer test.

Does the patient match the trial criteria? 1