pti-125 for mild-to-moderate alzheimer's disease patients

Conditions: Alzheimer Disease

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.

this is a phase 2b, randomized, double-blind, placebo-controlled, multiple dose study of pti-125 in mild-to-moderate alzheimer's disease patients. a total of sixty (60) patients will be enrolled in the study. patients will receive placebo, 50 mg or 100 mg b.i.d. of pti-125. the objective of this study are to investigate the safety, and biomarkers of pti-125 following 28-day repeat oral administration.

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