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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
H. Lundbeck A/S
ClinicalTrials.gov Identifier:
NCT00857649
First received: March 5, 2009
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: Memantine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by H. Lundbeck A/S:

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. [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

    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. [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

    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. [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

    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. [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

    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. [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

    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.



Enrollment: 369
Study Start Date: December 2003
Study Completion Date: September 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Memantine Drug: Memantine
20 mg Oral Tablets Once Daily
Other Name: Ebixa®
Placebo Comparator: Placebo Drug: Placebo
Oral Tablets Once Daily

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00857649

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

No publications provided by H. Lundbeck A/S

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT00857649     History of Changes
Other Study ID Numbers: 10158
Study First Received: March 5, 2009
Results First Received: October 26, 2011
Last Updated: November 12, 2013
Health Authority: Canada: Health Canada

Keywords provided by H. Lundbeck A/S:
Alzheimer's Disease

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Memantine
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014