San Juan Capistrano,
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.
- 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
- 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
- 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.
- 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
- 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.