PTI-125 for Mild-to-moderate Alzheimer's Disease Patients
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Intervention: Placebo oral tablet; Simufilam 100 mg tablet; Simufilam 50 mg oral tablet
Intervention description: Oral placebo tablet; Simufilam 100 mg oral tablet; Simufilam 50 mg oral tablet
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Approximately sixty (60) patients will be enrolled into the study and randomized to one of three cohorts. Cohorts will receive placebo or PTI-125 at 50 or 100 mg b.i.d. (n=20 per group)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: The sponsor, participant, care provider, investigator including sub-investigators and outcomes assessors will be blinded to throughout the study which includes using an Integrated Web Response System (IWRS) and electronic data capture (EDC) to ensure blinding during the study.
Enrollment: 64.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This is a Phase 2b, Randomized, Double-blind, Placebo-controlled, multiple dose study of
      PTI-125 in mild-to-moderate Alzheimer's disease patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ages >= 50 and <= 85 years

          -  Informed consent form (ICF) signed by the subject or legally acceptable
             representative.

          -  Clinical diagnosis of dementia due to possible or probable Alzheimer's disease

          -  Mini-Mental State Examination score >= 16 and <= 26 at screening

          -  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.

          -  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 and with a lumbar puncture and the drawing of cerebrospinal fluid samples.

          -  The patient has a ratio of total tau/Aβ42 in cerebrospinal fluid >= 0.28.

          -  Patient has a caregiver or legal representative responsible for administering the drug
             and recording the time.

        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