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

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00857649
• Other study ID #: 10158
• Status: Terminated
• Phase: Phase 3
• First received: March 5, 2009
• Last updated: November 12, 2013
• Start date: December 2003
• Est. completion date: September 2010

Study information

• Verified date: November 2013
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 369
• Est. completion date: September 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Memantine
20 mg Oral Tablets Once Daily
• Placebo
Oral Tablets Once Daily

Locations

Country	Name	City	State
Canada	CA005	Beauport	Quebec
Canada	CA032	Burlington	Ontario
Canada	CA019	Edmonton	Alberta
Canada	CA023	Greenfield Park	Quebec
Canada	CA033	Kelowna	British Columbia
Canada	CA043	Kelowna
Canada	CA046	Kentville	Nova Scotia
Canada	CA013	Montreal	Quebec
Canada	CA029	Orangeville	Ontario
Canada	CA004	Ottawa	Ontario
Canada	CA042	Penticton
Canada	CA038	Peterborough	Ontario
Canada	CA045	Pictou	Nova Scotia
Canada	CA015	Regina	Saskatchewan
Canada	CA040	Saskatoon	Saskatchewan
Canada	CA012	Sherbrooke	Quebec
Canada	CA031	Sherbrooke	Quebec
Canada	CA022	St. John	New Brunswick
Canada	CA009	Toronto	Ontario
Canada	CA030	Vanier	Quebec
Canada	CA017	Verdun	Quebec
Canada	CA037	Windsor	Ontario
Canada	CA034	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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( — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to Week 24	No
Primary	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.	Baseline to Week 24	No
Secondary	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.	Baseline to Week 24	No
Secondary	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.	Baseline to Week 24	No
Secondary	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.	Baseline to Week 24	No