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

November 12, 2013 updated by: H. Lundbeck A/S

A Randomised, Double-Blind, Parallel-Group Study Examining the Efficacy and Safety of Memantine in Patients With Moderate to Severe Dementia of the Alzheimer's Type

The primary objective of this study is to examine the efficacy of memantine on cognition and behavioural symptoms in outpatients with moderate to severe dementia of the Alzheimer's type.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

This 24-week randomised, double-blind, placebo-controlled, multicentre study examines the effect of memantine 20 mg, administered once daily, on cognitive and behavioural symptoms in outpatients diagnosed with moderate to severe AD and significant psychopathology.

Study Type

Interventional

Enrollment (Actual)

369

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Kelowna, Canada, V1Y 3G8
        • CA043
      • Penticton, Canada, V2A 5C8
        • CA042
    • Alberta
      • Edmonton, Alberta, Canada, T5G 0B7
        • CA019
    • British Columbia
      • Kelowna, British Columbia, Canada, V1W 4V5
        • CA033
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3M 0X9
        • CA034
    • New Brunswick
      • St. John, New Brunswick, Canada
        • CA022
    • Nova Scotia
      • Kentville, Nova Scotia, Canada, B4N 4K9
        • CA046
      • Pictou, Nova Scotia, Canada, B0K 1H0
        • CA045
    • Ontario
      • Burlington, Ontario, Canada, L7M 4Y1
        • CA032
      • Orangeville, Ontario, Canada, L9W 2E1
        • CA029
      • Ottawa, Ontario, Canada, K1N 5C8
        • CA004
      • Peterborough, Ontario, Canada, K9H 2P4
        • CA038
      • Toronto, Ontario, Canada, M3B 2W7
        • CA009
      • Windsor, Ontario, Canada, N8X 5A6
        • CA037
    • Quebec
      • Beauport, Quebec, Canada, G1J 2G3
        • CA005
      • Greenfield Park, Quebec, Canada, J4V 2J2
        • CA023
      • Montreal, Quebec, Canada, H1T 2M4
        • CA013
      • Sherbrooke, Quebec, Canada, J1J 2B8
        • CA031
      • Sherbrooke, Quebec, Canada, J1J 3H5
        • CA012
      • Vanier, Quebec, Canada, G1M 2R9
        • CA030
      • Verdun, Quebec, Canada, H4H 1R3
        • CA017
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 1A5
        • CA015
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • CA040

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Outpatients who:

  • had a primary diagnosis of probable Alzheimer's Disease (AD) according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria, and with Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised (DSM IV TR) criteria for dementia of the Alzheimer's type
  • had moderate to severe dementia, defined as a Mini Mental State Examination (MMSE) total score >=5 and <=15 at screening. Before substantial protocol amendment SA04 (dated 7 October 2004) was implemented, the MMSE total score range at screening was >=8 and <=18. Substantial protocol amendment SA07 (dated 4 September 2009) allowed patients who had previously had an MMSE score of 16 or 17 to be re-screened >6 months after their initial screening and, if there was documented evidence of cognitive decline, to be enrolled in the study
  • had a Neuropsychiatric Inventory (NPI) total score >=13 and an NPI agitation/aggression subitem score >=1 at screening and baseline
  • did not have vascular dementia or a modified Hachinski Ischaemia Scale score >4 at screening

Exclusion Criteria:

  • Evidence of clinically significant active disease, evidence of other neurological disorders, and previous treatment with memantine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Oral Tablets Once Daily
Experimental: Memantine
Drug: Memantine
20 mg Oral Tablets Once Daily
Other Names:
  • Ebixa®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of Memantine on Behavioural Symptoms in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the NPI - 12 Items Version Total Score.
Time Frame: Baseline to Week 24

Change from Baseline in Neuropsychiatric Inventory (NPI) total score.

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 to Week 24
Efficacy of Memantine on Cognition in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the SIB Total Score.
Time Frame: Baseline to Week 24

Change from Baseline in Severe Impairment Battery (SIB) total score.

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 to Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of Memantine on Global Condition Using CIBIC-plus.
Time Frame: Baseline to Week 24

Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus). Improvement evaluated with reference to Baseline.

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.
Baseline to Week 24
Efficacy of Memantine on Functioning Using ADCS-ADL - 19 Items Total Score.
Time Frame: Baseline to Week 24

Change from Baseline on the Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) 19-item version total score.

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 to Week 24
Efficacy of Memantine on Functioning Using CMAI - Long Form Total Score.
Time Frame: Baseline to Week 24

Change from Baseline on the Cohen-Mansfield Agitation Inventory (CMAI) - Long Form total score.

CMAI - Long Form looks specifically at agitated behaviour in patients with cognitive impairment. It is a seven-point rating scale assessing the frequency of up to 29 agitated behaviours, ranging from "1 = Never" to "7 = Several times an hour". Rating is based on responses obtained from interviews with the caregiver. The total score ranges from 29 to 203, with a higher score reflecting more frequent behavioural disturbances.
Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lundbeck A/S

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2003

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

September 1, 2010

Study Registration Dates

First Submitted

March 5, 2009

First Submitted That Met QC Criteria

March 5, 2009

First Posted (Estimate)

March 6, 2009

Study Record Updates

Last Update Posted (Estimate)

December 5, 2013

Last Update Submitted That Met QC Criteria

November 12, 2013

Last Verified

November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10158

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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