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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: PPI-1019 (APAN)

• Study Type: Interventional
• Enrollment: 125
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Department of Psychiatry & Human Behavior at the University California, Irvine
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Clinical (adverse events, vital signs, ECG) and laboratory (chemistry, hematology) parameters
Single dose pharmacokinetic parameters

Collaborators and Investigators

• Sponsor: PRAECIS Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Study Completion: June 1, 2005

Study Registration Dates

• First Submitted: December 27, 2004
• First Submitted That Met QC Criteria: December 27, 2004
• First Posted (Estimate): December 28, 2004

Study Record Updates

• Last Update Posted (Estimate): September 19, 2006
• Last Update Submitted That Met QC Criteria: September 18, 2006
• Last Verified: September 1, 2006

More Information

Terms related to this study

• Keywords: Mild-moderate Alzheimer's disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 1019-03-01