Safety Study of PPI-1019 in Patients With Mild-Moderate Alzheimer's Disease
Single Dose Escalation Safety Study of PPI-1019 in Patients With Mild-Moderate Alzheimer's Disease
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.
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.