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

This study has been terminated.
(Please see explanation in the Detailed Description field.)
Sponsor:
Information provided by (Responsible Party):
H. Lundbeck A/S
ClinicalTrials.gov Identifier:
NCT00857233
First received: March 5, 2009
Last updated: July 26, 2012
Last verified: July 2012
  Purpose

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


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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Patients With Adverse Events (AEs) [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    Overview of AEs

  • Percentage of Patients Who Withdrew Due to Intolerance to Treatment [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Long-term Efficacy of Memantine on Behavioural Symptoms Using the Neuropsychiatric Inventory (NPI) - 12 Items Version Total Score. [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

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

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

    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 Score [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    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.



Enrollment: 297
Study Start Date: June 2004
Study Completion Date: October 2010
Primary Completion Date: July 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®

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00857233

  Show 33 Study Locations
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

Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT00857233     History of Changes
Other Study ID Numbers: 10252
Study First Received: March 5, 2009
Results First Received: July 26, 2012
Last Updated: July 26, 2012
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
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on September 22, 2014