Safety and Tolerability of Memantine in Moderate to Severe Alzheimer's Disease

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study was to examine the safety and tolerability of memantine in outpatients with moderate to severe Alzheimer's Disease.

Detailed Description
-----------------
Memantine is a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Pre-clinical studies have demonstrated that memantine can decrease the neuronal toxicity associated with excessive glutamate release and calcium overload in neurons. Results from clinical trials in patients with moderate to severe Alzheimer's Disease (AD) have demonstrated memantine's efficacy and safety by showing positive treatment effects on cognitive, global and functional decline. The purpose of this 24-week open-label extension study was to collect additional long-term safety and tolerability data on memantine in patients who completed the lead-in double-blind placebo-controlled Study 10158. In agreement with Health Canada the study was prematurely terminated due to recruitment difficulties in the lead-in Study 10158. Patients ongoing in the study when the decision to terminate was taken were allowed to complete it.

Official Title
-----------------
An Open-label Extension Study Examining the Safety and Tolerability of Memantine in Patients With Moderate to Severe Dementia of the Alzheimer's Type Having Completed Study 10158

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: Memantine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ambulatory outpatients with moderate to severe dementia of the Alzheimer's type who have completed the 24-week Study 10158 and who have a knowledgeable and reliable caregiver who will accompany the patient to all clinic visits during the course of the study. Exclusion Criteria: Diseases/medication which judged by the investigator could interfere with the assessments of safety, tolerability or efficacy.

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

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Memantine<br> | Drug: Memantine<br>* 20 mg oral tablets once daily<br>* Other names: Ebixa®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events (AEs) | Overview of AEs | Baseline to Week 24 | 
| Percentage of Patients Who Withdrew Due to Intolerance to Treatment |  | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term Efficacy of Memantine on Behavioural Symptoms Using the Neuropsychiatric Inventory (NPI) - 12 Items Version Total Score. | Change from Baseline in the NPI total score. Analysed by descriptive methods only. NPI is a validated scale that assesses behavioural disturbances in patients with dementia. The 12 item version consists of 10 behavioural and 2 neurovegetative areas. It provides both a total score as well as scores for a number of sub-scales. The frequency, severity and caregiver distress for each domain are measured. The NPI is based upon responses obtained from the caregiver. The total score is from 0 to 144. A higher score reflects more frequency and severity of the disturbances. | Baseline and Week 24 | 
| Long-term Efficacy of Memantine on Cognition Using the Severe Impairment Battery (SIB) Total Score. | Change from Baseline in the SIB total score. Analysed by descriptive methods only. SIB is a validated scale used to assess cognitive function in patients with moderate to severe dementia. Items are single words or one-step commands combined with gestures. Nine domains are assessed, and the total score is between 0 and 100. A lower total score reflects the loss of cognitive function. | Baseline and Week 24 | 
| Long-term Efficacy of Memantine on Global Condition Using the Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus). | CIBIC-plus. Improvement evaluated with reference to Baseline. Analysed by descriptive methods only. CIBIC-plus is a global rating that is derived through an independent, comprehensive interview with the patient and caregiver by a rater who is barred from knowledge of all other psychometric test scores conducted as part of this protocol as well as from reported safety data. The rating is made on a 7-point scale ranging from 1 = marked improvement to 7 = marked worsening. A score of 4 indicates no change. | Week 24 | 
| Long-term Efficacy of Memantine on Functioning Using the Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) 19-item Version Total Score | Change from Baseline on the ADCS-ADL 19-item version total score. Analysed by descriptive methods only. ADCS-ADL- 19 items version for moderate to severe AD will measure patient's functioning. This battery of ADL questions is used here to measure the functional capabilities of patients with dementia. The inventory is done by interviewing a person in close contact with the patient and covers the most usual and consistent performance of the patient over the preceding 4 weeks. Total score is from 0 to 54. The higher score, the lower impairment. | Baseline and Week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alzheimer's Disease