Tetra PICASSO AD Trial: Study to Evaluate Effects of BPN14770 in Early Alzheimer's Subjects

Inclusion Criteria

• Males or females between the ages of 55 and 85 years with a clinical diagnosis of early stage AD, defined according to the following criteria assessed during Screening and at Baseline :
• Clinical Dementia Rating (CDR) score of 0.5 or 1, with Memory Box score of 0.5 or greater
• MMSE score of 20 or greater
• RBANS DMI score ≤ 85 Note: PET imaging for amyloid is not required for diagnosis, which will be made on clinical grounds.
• Currently receiving a stable (at least 2 months) dose regimen of donepezil or another cholinesterase inhibitor for treatment of Alzheimer's disease. Doses of these drugs may not be changed during the trial.

Note: Memantine is not permitted during the trial and must be discontinued at least 3 weeks prior to Baseline.

• Modified Hachinski Ischemia score 48 kg (105 pounds) at screening.
• Female subjects must be at least two years post-menopausal (subjected reported menopausal status), surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months prior to first study drug administration), or willing to either (1) utilize hormonal contraception plus one barrier method or (2) use two barrier methods of contraception (e.g. diaphragm and spermicide) from initial screening until one month after taking the final dose. An intrauterine device (IUD) is considered a barrier method of contraception in this study. Male subjects must be willing to inform female partners of their participation in the study and must agree to use adequate contraceptive methods (vasectomy performed at least 6 months prior to first study drug administration, or use at least one barrier method of birth control).
• Able to understand and comply with the study procedures, voluntarily agree to participate in this study, and provide written informed consent prior to start of any study-specific procedures.
• All subjects must have a caregiver who is willing and able to ensure compliance with study medications, visits, and study procedures.

Exclusion Criteria

• Any medical or neurological condition (other than early stage AD) that might be a contributing cause to the subject's cognitive impairment.
• History of stroke or multiple (>3 discreet episodes) Transient Ischemic Attacks (TIAs), severe head trauma with cognitive sequelae, uncontrolled seizures, or unexplained prolonged loss of consciousness (> 1 minute) during the past year.
• Clinically significant major psychiatric illness during the past 6 months.
• History of unstable angina, myocardial infarction, chronic heart failure, or clinically significant conduction abnormalities during the past year.
• Clinically significant liver or renal disease.
• Clinically significant abnormality, in the Investigator's judgment, in hematology, chemistry, or urinalysis.
• Positive serology results for hepatitis B surface antigen (HbsAg) or hepatitis C virus (HCV).
• Abnormal liver function test at the Screening Visit (aspartate aminotransferase or alanine aminotransferase >2

× the upper limit of normal [ULN], or total bilirubin >1.7 × ULN, based on appropriate age and gender normal values). Subjects may be re-screened once.

• Marked hypotension (systolic blood pressure [BP] ˂90 mmHg or diastolic BP ˂50 mmHg) or hypertension (systolic BP ˃160 mmHg or diastolic BP ˃100 mmHg) based on sitting values. O ut-of-range results may be repeated once at Screening, and eligibility must be confirmed at Baseline.
• Marked bradycardia (heart rate ˂45 beats per minute [bpm]) or tachycardia (heart rate ˃115 bpm) based on supine ECG values. Out-of-range results may be repeated once at Screening, and eligibility must be confirmed at Baseline.
• Clinically important conduction abnormalities on ECG, or evidence or history of long QT syndrome based on supine ECG values obtained at Screening. Out-of-range results may be repeated once and eligibility confirmed at Baseline.
• Active gastric or duodenal ulcers or other diseases of the g