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

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00857233
• Other study ID #: 10252
• Status: Terminated
• Phase: Phase 3
• First received: March 5, 2009
• Last updated: July 26, 2012
• Start date: June 2004
• Est. completion date: October 2010

Study information

• Verified date: July 2012
• 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 the study was to examine the safety and tolerability of memantine in outpatients with moderate to severe Alzheimer's Disease.

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 information / eligibility

• Status: Terminated
• Enrollment: 297
• Est. completion date: October 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Memantine
20 mg oral tablets once daily

Locations

Country	Name	City	State
Canada	CA005	Beauport	Quebec
Canada	CA032	Burlington	Ontario
Canada	CA044	Chatham
Canada	CA019	Edmonton	Alberta
Canada	CA023	Greenfield Park	Quebec
Canada	CA033	Kelowna	British Columbia
Canada	CA043	Kelowna	British Columbia
Canada	CA007	Kentville
Canada	CA046	Kentville
Canada	CA001	Kingston
Canada	CA002	London
Canada	CA003	London
Canada	CA016	Moncton
Canada	CA011	Montreal
Canada	CA013	Montreal	Quebec
Canada	CA014	Montreal
Canada	CA024	Montreal
Canada	CA029	Orangeville	Ontario
Canada	CA004	Ottawa	Ontario
Canada	CA042	Penticton	British Columbia
Canada	CA038	Peterborough	Ontario
Canada	CA045	Pictou	Nova Scotia
Canada	CA015	Regina	Saskatchewan
Canada	CA040	Saskatoon	Saskatchewan
Canada	CA012	Sherbrooke	Quebec
Canada	CA031	Sherbrooke
Canada	CA022	St. John	New Brunswick
Canada	CA006	Toronto
Canada	CA009	Toronto	Ontario
Canada	CA030	Vanier	Quebec
Canada	CA017	Verdun	Quebec
Canada	CA037	Windsor
Canada	CA034	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Adverse Events (AEs)	Overview of AEs	Baseline to Week 24	Yes
Primary	Percentage of Patients Who Withdrew Due to Intolerance to Treatment		Baseline to Week 24	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No