Safety Study of PPI-1019 in Subjects With Mild-Moderate Alzheimer’s Disease

This is a single-center, double-blind, inpatient study followed by an outpatient, placebo-controlled, multiple-IV injection evaluation of the safety and tolerability of PPI-1019 in subjects with mild-moderate Alzheimer’s disease (AD). The primary objective of the study is to assess the safety of multiple IV injections of PPI-1019 in subjects with mild-moderate Alzheimer’s disease.

Inclusion Criteria:

• Subject has the ability to understand the requirements of the study, provide written informed consent, and abide by the requirements of the study. In addition, a member of the subject’s family or a legally authorized representative must consent to the subject’s participation in the study.
• Subject has a caregiver willing to assist the subject’s involvement in the study.
• Subject is a male or female between the ages of 50 and 80 with a body mass index (BMI) below 31. Females must be post-menopausal at least 1 year or surgically sterilized.
• Subject must have a cognitive deficit present for at least 1 year and meet DSM –IV criteria for Alzheimer’s disease and meet National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) criteria for the presence of probable Alzheimer’s disease.
• Subject’s severity of Alzheimer’s disease must be mild-moderate, documented with a Mini Mental State Exam (MMSE) score of 12-26.
• Subject has a computerized tomography (CT) scan or magnetic resonance imaging (MRI) within the prior 12 months which is compatible with a diagnosis of probable AD.
• If a subject is being treated for Alzheimer’s disease, it must be with a single cholinesterase inhibitor (donepezil, rivastigmine, or galantamine), with or without memantine, and with a dose which has been stable for at least 3 months prior to dosing.
• Subject performance status is ≤ 3 on items 1 through 5 and ≤ 2 on item 6 from the Degree of Disability Section of the “Rapid Disability Scale-2”
• Subject agrees not to donate blood or blood products while participating in this study and for at least 60 days after discontinuing from the study.

Exclusion Criteria:

• Subject has participated in a clinical trial of another investigational drug or device, or has taken any experimental drug within 30 days prior to admission to the Phase 1 unit. (Subjects previously enrolled in 1019-03-01 may be enrolled in 1019-04-01, only after a wash-out period of 45 days.)
• Subject has a history compatible with vascular dementia as evidenced by a score of 5 or greater on the modified Hachinski Ischemia Scale.
• Subject has evidence of clinically significant unstable cardiovascular, renal, hepatic, gastrointestinal, neurological, or metabolic disease within the past 6 months (as determined by medical history, ECG results, chest x-ray, or physical examination).
• Subject performance status is > 3 on items 1 through 5 and > 2 on item 6 from the Degree of Disability Section of the “Rapid Disability Scale-2.”
• Subject has diabetes that requires oral antidiabetic therapy or insulin.
• Subject has a systolic blood pressure (sitting) of greater than 160 mmHg, a diastolic (sitting) greater than 95 mmHg, a decrease in systolic blood pressure of more than 30 mmHg upon standing for 2 minutes from a sitting or supine position, a pulse (sitting or supine) less than 50 or greater than 85.
• Subject has any visual, hearing, or communication disabilities impairing his/her ability to participate in the study.
• Subject is being treated with anticholinergics and/or clinically relevant cytochrome P450 3A4 inducers/inhibitors. The use of other concomitant medications for stable medical conditions is acceptable provided drug and dosage are stable for at least 4 weeks prior to dosing.
• Subject is currently taking herbal supplements which interfere with drug metabolism, e.g. St. John’s wort, ginkgo biloba.
• Subject has tested positive for drugs of abuse (amphetamines, barbiturates, cocaine, phencyclidine, or cannabinoids) on screening or Day -1
• Subject has a current or past medical history of alcohol abuse.
• Subject has any elevations (> 1.2 x ULN) on screening or Day -1 for ALT, AST, bilirubin, creatinine, blood urea nitrogen, or alkaline phosphatase.
• Subject has any other screening or Day -1 laboratory values outside the normal ranges that are deemed clinically significant by the investigator.