PTI-125 for Mild-to-moderate Alzheimer's Disease Patients
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Intervention: PTI-125, 100 mg tablets
Intervention description: PTI-125, 100 mg tablets taken twice a day for 28 days
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This is a Phase 2a, multi-center, open-label 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 <= 24 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-hour) 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 (90 days) before screening and with continuous dosing for at
             least 3 months. If receiving donepezil, receiving any dose lower than 23 mg once
             daily.

          -  The patient is a non-smoker for at least 12 months.

          -  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/Abeta42 in cerebrospinal fluid >= 0.30.

          -  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

          -  Residence in a skilled nursing facility

          -  Clinically significant laboratory test results

          -  Clinically significant untreated hypothyroidism (if treated, thyroid-stimulating
             hormone level and thyroid supplementation dose must be stable for at least 6 months
             before screening)

          -  Insufficiently controlled diabetes mellitus or requiring insulin

          -  Renal insufficiency (serum creatinine >2.0 mg/dL)

          -  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) >2 times the upper limit of
             normal or total bilirubin greater than the upper limit of normal.

          -  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 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 CNS 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 quaque die currently or within 3 months prior to enrollment
             in the study

          -  Discontinued AChEI < 30 days prior to enrollment in the study

          -  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 enrollment in the study

          -  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 enrollment in the study

          -  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 enrollment in the study

          -  Peripherally acting drugs with effects on cholinergic transmission

          -  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

          -  Loss of a significant volume of blood (> 450 mL) within 4 weeks prior to the study

          -  Metformin or cimetidine.