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

An Open-label Extension Study Examining the Safety and Tolerability of Memantine in Patients With Moderate to Severe Dementia of the Alzheimer's Type Having Completed Study 10158

The primary objective of the study was to examine the safety and tolerability of memantine in outpatients with moderate to severe Alzheimer's Disease.

Study Overview

• Status: Terminated
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Memantine

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.

• Study Type: Interventional
• Enrollment (Actual): 297
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Chatham, Canada, N7L 1B7
    • CA044
  • Kentville, Canada, B4N 4K9
    • CA007
  • Kentville, Canada, B4N 4K9
    • CA046
  • Kingston, Canada, K7L 2V7
    • CA001
  • London, Canada, N6A 4V2
    • CA003
  • London, Canada, N6C5J1
    • CA002
  • Moncton, Canada, E1C 4B7
    • CA016
  • Montreal, Canada, H2X 3J4
    • CA024
  • Montreal, Canada, H3T 1E2
    • CA014
  • Montreal, Canada, H4H 1R3
    • CA011
  • Sherbrooke, Canada, J1J 2B8
    • CA031
  • Toronto, Canada, M6M 3Z5
    • CA006
  • Windsor, Canada, N8X 5A6
    • CA037
  • Alberta
    • Edmonton, Alberta, Canada, T5G 0B7
      • CA019
  • British Columbia
    • Kelowna, British Columbia, Canada, V1W 4V5
      • CA033
    • Kelowna, British Columbia, Canada, V1Y 3G8
      • CA043
    • Penticton, British Columbia, Canada, V2A 5C8
      • CA042
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3M 0X9
      • CA034
  • New Brunswick
    • St. John, New Brunswick, Canada
      • CA022
  • Nova Scotia
    • 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
  • Quebec
    • Beauport, Quebec, Canada, G1J 2G3
      • CA005
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • CA023
    • Montreal, Quebec, Canada, H1T 2M4
      • CA013
    • 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

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:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
Number of Patients With Adverse Events (AEs)	Overview of AEs	Baseline to Week 24
Percentage of Patients Who Withdrew Due to Intolerance to Treatment		Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term Efficacy of Memantine on Behavioural Symptoms Using the Neuropsychiatric Inventory (NPI) - 12 Items Version Total Score.	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.	Baseline and Week 24
Long-term Efficacy of Memantine on Cognition Using the Severe Impairment Battery (SIB) Total Score.	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.	Baseline and Week 24
Long-term Efficacy of Memantine on Global Condition Using the Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus).	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.	Week 24
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 Score	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.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): October 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): August 29, 2012
• Last Update Submitted That Met QC Criteria: July 26, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Alzheimer's Disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: 10252