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

Conditions: Alzheimer's Disease

Summary: this is a multi-center, double-blind, inpatient study followed by outpatient, placebo-controlled, single-dose, dose-escalation evaluation of the safety and tolerability of ppi-1019 in patients with mild-moderate alzheimer's disease (ad). up to 12 sequential cohorts of 8 patients (6 active and 2 placebo) will be given a single ppi-1019 dose intravenously (iv) over 1 minute in order to determine a maximum tolerated dose (mtd). the mtd will be the dose immediately below the not-tolerated dose.


Eligibility criteria:
inclusion criteria: * patient has the ability to understand the requirements of the study, provide written informed consent, and abide by the requirements of the study. * patient has a caregiver willing to assist the patient's involvement in the study. * patient 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. * patient must have a cognitive deficit present for at least one 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. * patient's severity of alzheimer's disease must be mild-moderate, documented with a mini mental state exam (mmse) score of 12-26. * patient 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 patient is being treated for alzheimer's disease, it must be with a single agent (donepezil, rivastigmine, galantamine, or memantine) and with a dose which has been stable for at least 3 months. * patient is otherwise in good general health. treatment of hypertension with no more than 2 medications and for hyperlipidemia with one agent is acceptable provided drugs and dosages have been stable for at least 30 days. * patient agrees to abstain from alcohol and not take any other drugs, dietary supplements, or herbal therapies other than mylanta®, ibuprofen, or a multivitamin for the length of the study (screening to follow-up visit day 22). * patient 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: * patient has participated in a clinical trial of another investigational drug or device, or has taken any experimental drug within 30 days prior to screening. * patient has a history compatible with vascular dementia as evidenced by a score of 5 or greater on the modified hachinski ischemia scale. * patient has evidence of clinically significant 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). findings of potential significance must be discussed with an appropriate sponsor clinician (or praecis' designee) prior to patient entry. * patient has a systolic blood pressure (sitting) of greater than 150 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, or a pulse (sitting or supine) less than 55 or greater than 85. * patient has any visual, hearing, or communication disabilities impairing his or her ability to participate in the study. * patient intends to use any concomitant medications during the study other than those described in inclusion criteria. * patient has taken any concomitant medication without the approval of the investigator within 7 days prior to day 1. * patient has tested positive for drugs of abuse (benzodiazepines, narcotics, amphetamines, barbiturates, sedatives, hypnotics, cocaine, phencyclidine, alcohol, or cannabinoids) on drug screening or day -1. * patient has any elevations (\> 1.2 x uln) on screening or day -1 for alt, ast, bilirubin, creatinine, blood urea nitrogen, or alkaline phosphatase. * patient has any other screening or day -1 laboratory values outside the normal ranges that are deemed clinically significant by the investigator.

Keywords: mild-moderate alzheimer's disease