Open-label, PK and Safety Study in Mild-to-moderate Alzheimer's Disease Patients

Inclusion Criteria:

- Ages ≥ 50 and ≤ 85 years

- Informed consent form (ICF) signed by the subject or legally acceptable
representative. If a legally acceptable representative signs the ICF, a notation of
capacity of the subject must be noted.

- Clinical diagnosis of dementia due to possible or probable AD consistent with criteria
established by a workgroup of the National Institute on Aging and the Alzheimer's
Disease Association.

- MMSE 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-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 (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 for the PK assessments, laboratory assessments and PTI-125DX and with a lumbar
puncture and the drawing of CSF samples for biomarker assessments.

- The patient has an Aβ/tau Index in CSF that indicates AD. This value (total tau/Aβ42)
will be ≥ 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 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 QTc 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 AD (eg, Huntington's disease,
Creutzfeld-Jacob disease, Down's syndrome, Frontotemporal Dementia, Parkinson's
disease)

- Wernicke's encephalopathy

- Active acute or chronic CNS infection

- Donepezil 23 mg or greater QD 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. PTI-125 is a marginal/weak inhibitor of the multidrug and
toxin extrusion protein 1 (MATE1) transporter.