Study to Evaluate Safety, Tolerability, and Effect of AL208 on Mild Cognitive Impairment Following Coronary Artery Bypass Graft Surgery

A Phase II Study Designed to Evaluate the Safety, Tolerability, and Effect of a Single, Rising Dose of Intravenous AL-208, Followed by a Placebo-Controlled, Double-Blind, Parallel-Group Evaluation of a Single Dose of AL-208, on Mild Cognitive Impairment Following Coronary Artery Bypass Graft Surgery.

The primary objective is to compare mild cognitive impairment in the AL-208 group with the placebo group at 14 + - 3 days after CABG surgery

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Drug: AL-208; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5G2C4
      • Toronto General Hospital
• United States
  • California
    • Laguna Hills, California, United States, 92653
      • Physicians Clinical Research Corp.
    • Sacramento, California, United States, 95825
      • Sacramento Heart and Vascular Research Center
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital Research Institute
    • Atlanta, Georgia, United States, 30342
      • The Atlanta Heart and Vascular Research Group
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Elk Grove Village, Illinois, United States, 60007
      • Chicago Heart Institute and Vein Clinic
    • Hindsdale, Illinois, United States, 60521
      • Illinois Heart and Vascular Foundation
  • Indiana
    • Ft. Wayne, Indiana, United States, 46804
      • Indiana/Ohio Heart Cardiothoracic and Vascular Surgeons
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • Michigan
    • Flint, Michigan, United States, 48532
      • Cardiothoracic Associates
  • New York
    • New York, New York, United States, 10016
      • NYU Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Raleigh, North Carolina, United States, 27610
      • Carolina Cardiovascular Surgical Associates, PA
    • Wilmington, North Carolina, United States, 28405
      • Memory Assessment and Research Services
  • Ohio
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mary Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104-5428
      • Tulsa Clinical Resesarch, LLC
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16502
      • Consultants in Cardiovascular Diseases Inc.
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Clinical Research Solutions, PC
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75226
      • Clinical Cardiovascular Research Center
    • Houston, Texas, United States, 77030
      • St. Luke's Episcopal Hospital
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Mechanicsville, Virginia, United States, 23116
      • Cardiac and Thoracic Surgical Associates, Ltd.
  • Washington
    • Tacoma, Washington, United States, 98415
      • Multicare Health Systems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females (of non-childbearing potential), 50 to 79 years of age.
2. Undergoing CABG surgery with the use of extracorporeal circulation.
3. Willing and able to complete cognitive testing.
4. Score < 16 on the Center for Epidemiological Studies in Depression scale (CES-D).
5. Score > or = 28 on the Mini-Mental State Examination (MMSE).
6. Willing and able to provide informed consent to participate in this study
7. Fluency in written and spoken English.

Exclusion Criteria:

1. Presence of any severe mental illness that could affect interpretation of efficacy data, such as schizophrenia or bipolar affective disorder; any untreated or unstable psychiatric condition including depressive disorder or anxiety disorder.
2. History of stroke or other significant neurological disorder
3. Transient ischemic attack (TIA) with ongoing cognitive sequelae
4. Chronic atrial fibrillation or uncontrolled atrial fibrillation prior to surgery
5. Myocardial infarction (MI) within the last 8 weeks and/or previous history of more than 3 MIs
6. History of liver dysfunction with ongoing sequelae (including but not limited to liver enzymes > 2.5 x upper limit or normal (ULN) at screening).
7. History of renal dysfunction with ongoing sequelae (including but not limited to creatinine value > 2.5 mg/dL at screening).
8. Known active alcohol or drug abuse.
9. Concurrent use of prescription medications known to enhance memory
10. General anesthesia (defined as anesthesia requiring intubation or ventilatory support) within 3 months prior to randomization.
11. Cardiopulmonary bypass or thoracotomy within 2 years prior to randomization.
12. Undergoing valvular repair or replacement during scheduled CABG surgery.
13. Chronic obstructive pulmonary disease (COPD) requiring oxygen therapy.
14. Decompensating congestive heart disease
15. Subjects on immunosuppressive drugs, such as azathioprine, chemotherapeutic agents, mycophenolate, monoclonal antibodies, or more than 20 mg/day prednisone, within the previous 3 months
16. Receipt of any investigational agent or device within 30 days of screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 1 dose of placebo
Active Comparator: AL-208; 1 dose of 300 mg	Drug: AL-208; 1 dose of 300 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary objective of this study was to compare mild cognitive impairment in the AL-208 group with the placebo group at 14±3 days after coronary artery bypass graft (CABG) surgery.	The primary objective of this study was to compare mild cognitive impairment in the AL-208 group with the placebo group at 14±3 days after coronary artery bypass graft (CABG) surgery.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety profile of AL-208 in subjects undergoing CABG surgery	The safety profile of AL-208 in subjects undergoing CABG surgery	14 days
The effect of treatment with AL-208 on postoperative personality changes in subjects undergoing CABG surgery	The effect of treatment with AL-208 on postoperative personality changes in subjects undergoing CABG surgery	14 days
Concentration of AL-208 in plasma in subjects undergoing CABG surgery	Concentration of AL-208 in plasma in subjects undergoing CABG surgery	14 days

Collaborators and Investigators

• Sponsor: Allon Therapeutics
• Investigators: Study Director: Elena Matthews, MD, Medical Monitor on behalf of Allon Therapeutics

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: November 24, 2006
• First Submitted That Met QC Criteria: November 24, 2006
• First Posted (Estimate): November 27, 2006

Study Record Updates

• Last Update Posted (Estimate): October 24, 2012
• Last Update Submitted That Met QC Criteria: October 18, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: MCI following CABG surgery
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: AL 208-201