search
Back to results

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

Primary Purpose

Alzheimer's Disease

Status
Terminated
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Memantine
Placebo
Sponsored by
H. Lundbeck A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's Disease

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CA019
  • CA033
  • CA034
  • CA022
  • CA046
  • CA045
  • CA032
  • CA029
  • CA004
  • CA038
  • CA009
  • CA037
  • CA005
  • CA023
  • CA013
  • CA031
  • CA012
  • CA030
  • CA017
  • CA015
  • CA040
  • CA043
  • CA042

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Memantine

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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.
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.
Efficacy of Memantine on Cognition in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the SIB Total Score.
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.

Secondary Outcome Measures

Efficacy of Memantine on Global Condition Using CIBIC-plus.
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.
Efficacy of Memantine on Functioning Using ADCS-ADL - 19 Items Total Score.
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.
Efficacy of Memantine on Functioning Using CMAI - Long Form Total Score.
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.

Full Information

First Posted
March 5, 2009
Last Updated
November 12, 2013
Sponsor
H. Lundbeck A/S
search

1. Study Identification

Unique Protocol Identification Number
NCT00857649
Brief Title
Efficacy and Safety of Memantine in Moderate to Severe Alzheimer's Disease
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2013
Overall Recruitment Status
Terminated
Study Start Date
December 2003 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
September 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lundbeck A/S

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Alzheimer's Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
369 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Memantine
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Memantine
Other Intervention Name(s)
Ebixa®
Intervention Description
20 mg Oral Tablets Once Daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral Tablets Once Daily
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
Baseline to Week 24
Title
Efficacy of Memantine on Cognition in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the SIB Total Score.
Description
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.
Time Frame
Baseline to Week 24
Secondary Outcome Measure Information:
Title
Efficacy of Memantine on Global Condition Using CIBIC-plus.
Description
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.
Time Frame
Baseline to Week 24
Title
Efficacy of Memantine on Functioning Using ADCS-ADL - 19 Items Total Score.
Description
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.
Time Frame
Baseline to Week 24
Title
Efficacy of Memantine on Functioning Using CMAI - Long Form Total Score.
Description
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.
Time Frame
Baseline to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Email contact via H. Lundbeck A/S
Organizational Affiliation
LundbeckClinicalTrials@lundbeck.com
Official's Role
Study Director
Facility Information:
Facility Name
CA019
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T5G 0B7
Country
Canada
Facility Name
CA033
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1W 4V5
Country
Canada
Facility Name
CA034
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3M 0X9
Country
Canada
Facility Name
CA022
City
St. John
State/Province
New Brunswick
Country
Canada
Facility Name
CA046
City
Kentville
State/Province
Nova Scotia
ZIP/Postal Code
B4N 4K9
Country
Canada
Facility Name
CA045
City
Pictou
State/Province
Nova Scotia
ZIP/Postal Code
B0K 1H0
Country
Canada
Facility Name
CA032
City
Burlington
State/Province
Ontario
ZIP/Postal Code
L7M 4Y1
Country
Canada
Facility Name
CA029
City
Orangeville
State/Province
Ontario
ZIP/Postal Code
L9W 2E1
Country
Canada
Facility Name
CA004
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1N 5C8
Country
Canada
Facility Name
CA038
City
Peterborough
State/Province
Ontario
ZIP/Postal Code
K9H 2P4
Country
Canada
Facility Name
CA009
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3B 2W7
Country
Canada
Facility Name
CA037
City
Windsor
State/Province
Ontario
ZIP/Postal Code
N8X 5A6
Country
Canada
Facility Name
CA005
City
Beauport
State/Province
Quebec
ZIP/Postal Code
G1J 2G3
Country
Canada
Facility Name
CA023
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2J2
Country
Canada
Facility Name
CA013
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
CA031
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1J 2B8
Country
Canada
Facility Name
CA012
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1J 3H5
Country
Canada
Facility Name
CA030
City
Vanier
State/Province
Quebec
ZIP/Postal Code
G1M 2R9
Country
Canada
Facility Name
CA017
City
Verdun
State/Province
Quebec
ZIP/Postal Code
H4H 1R3
Country
Canada
Facility Name
CA015
City
Regina
State/Province
Saskatchewan
ZIP/Postal Code
S4T 1A5
Country
Canada
Facility Name
CA040
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 0W8
Country
Canada
Facility Name
CA043
City
Kelowna
ZIP/Postal Code
V1Y 3G8
Country
Canada
Facility Name
CA042
City
Penticton
ZIP/Postal Code
V2A 5C8
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
23472619
Citation
Herrmann N, Gauthier S, Boneva N, Lemming OM; 10158 Investigators. A randomized, double-blind, placebo-controlled trial of memantine in a behaviorally enriched sample of patients with moderate-to-severe Alzheimer's disease. Int Psychogeriatr. 2013 Jun;25(6):919-27. doi: 10.1017/S1041610213000239. Epub 2013 Mar 8.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs