safety study of ppi-1019 in subjects with mild-moderate alzheimer's disease

Conditions: Alzheimer's Disease

Summary: 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.


Eligibility criteria:
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.

Keywords: alzheimer's disease