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

Phase 3
Terminated
Conditions
Alzheimer's Disease
Interventions
Registration Number
NCT00857233
Lead Sponsor
H. Lundbeck A/S
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
297
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
MemantineMemantine-
Primary Outcome Measures
NameTimeMethod
Number of Patients With Adverse Events (AEs)Baseline to Week 24

Overview of AEs

Percentage of Patients Who Withdrew Due to Intolerance to TreatmentBaseline to Week 24
Secondary Outcome Measures
NameTimeMethod
Long-term Efficacy of Memantine on Behavioural Symptoms Using the Neuropsychiatric Inventory (NPI) - 12 Items Version Total Score.Baseline and Week 24

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.

Long-term Efficacy of Memantine on Cognition Using the Severe Impairment Battery (SIB) Total Score.Baseline and Week 24

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.

Long-term Efficacy of Memantine on Global Condition Using the Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus).Week 24

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.

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 ScoreBaseline and Week 24

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.

Trial Locations

Locations (33)

CA022

🇨🇦

St. John, New Brunswick, Canada

CA043

🇨🇦

Kelowna, British Columbia, Canada

CA009

🇨🇦

Toronto, Ontario, Canada

CA019

🇨🇦

Edmonton, Alberta, Canada

CA001

🇨🇦

Kingston, Canada

CA037

🇨🇦

Windsor, Canada

CA045

🇨🇦

Pictou, Nova Scotia, Canada

CA013

🇨🇦

Montreal, Quebec, Canada

CA004

🇨🇦

Ottawa, Ontario, Canada

CA034

🇨🇦

Winnipeg, Manitoba, Canada

CA007

🇨🇦

Kentville, Canada

CA006

🇨🇦

Toronto, Canada

CA033

🇨🇦

Kelowna, British Columbia, Canada

CA042

🇨🇦

Penticton, British Columbia, Canada

CA023

🇨🇦

Greenfield Park, Quebec, Canada

CA005

🇨🇦

Beauport, Quebec, Canada

CA012

🇨🇦

Sherbrooke, Quebec, Canada

CA015

🇨🇦

Regina, Saskatchewan, Canada

CA044

🇨🇦

Chatham, Canada

CA017

🇨🇦

Verdun, Quebec, Canada

CA040

🇨🇦

Saskatoon, Saskatchewan, Canada

CA003

🇨🇦

London, Canada

CA002

🇨🇦

London, Canada

CA024

🇨🇦

Montreal, Canada

CA014

🇨🇦

Montreal, Canada

CA011

🇨🇦

Montreal, Canada

CA032

🇨🇦

Burlington, Ontario, Canada

CA016

🇨🇦

Moncton, Canada

CA029

🇨🇦

Orangeville, Ontario, Canada

CA038

🇨🇦

Peterborough, Ontario, Canada

CA030

🇨🇦

Vanier, Quebec, Canada

CA046

🇨🇦

Kentville, Canada

CA031

🇨🇦

Sherbrooke, Canada

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