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

Study Overview
=================
Brief Summary
-----------------
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

Official Title
-----------------
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.

Conditions
-----------------
Mild Cognitive Impairment

Intervention / Treatment
-----------------
* Drug: AL-208
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females (of non-childbearing potential), 50 to 79 years of age. Undergoing CABG surgery with the use of extracorporeal circulation. Willing and able to complete cognitive testing. Score < 16 on the Center for Epidemiological Studies in Depression scale (CES-D). Score > or = 28 on the Mini-Mental State Examination (MMSE). Willing and able to provide informed consent to participate in this study Fluency in written and spoken English. Exclusion Criteria: 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. History of stroke or other significant neurological disorder Transient ischemic attack (TIA) with ongoing cognitive sequelae Chronic atrial fibrillation or uncontrolled atrial fibrillation prior to surgery Myocardial infarction (MI) within the last 8 weeks and/or previous history of more than 3 MIs History of liver dysfunction with ongoing sequelae (including but not limited to liver enzymes > 2.5 x upper limit or normal (ULN) at screening). History of renal dysfunction with ongoing sequelae (including but not limited to creatinine value > 2.5 mg/dL at screening). Known active alcohol or drug abuse. Concurrent use of prescription medications known to enhance memory General anesthesia (defined as anesthesia requiring intubation or ventilatory support) within 3 months prior to randomization. Cardiopulmonary bypass or thoracotomy within 2 years prior to randomization. Undergoing valvular repair or replacement during scheduled CABG surgery. Chronic obstructive pulmonary disease (COPD) requiring oxygen therapy. Decompensating congestive heart disease Subjects on immunosuppressive drugs, such as azathioprine, chemotherapeutic agents, mycophenolate, monoclonal antibodies, or more than 20 mg/day prednisone, within the previous 3 months Receipt of any investigational agent or device within 30 days of screening.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AL-208<br>1 dose of 300 mg | Drug: AL-208<br>* 1 dose of 300 mg<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 1 dose of placebo<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MCI following CABG surgery