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.