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
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Alzheimer's Disease
- Sponsor
- H. Lundbeck A/S
- Enrollment
- 369
- Locations
- 23
- Primary Endpoint
- 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.
- Status
- Terminated
- Last Updated
- 12 years ago
Overview
Brief 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.
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. 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.
Investigators
Eligibility Criteria
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 \<=
- •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
Arms & Interventions
Placebo
Intervention: Placebo
Memantine
Intervention: Memantine
Outcomes
Primary Outcomes
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.
Time Frame: Baseline to Week 24
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.
Efficacy of Memantine on Cognition in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the SIB Total Score.
Time Frame: Baseline to Week 24
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.
Secondary Outcomes
- Efficacy of Memantine on Global Condition Using CIBIC-plus.(Baseline to Week 24)
- Efficacy of Memantine on Functioning Using ADCS-ADL - 19 Items Total Score.(Baseline to Week 24)
- Efficacy of Memantine on Functioning Using CMAI - Long Form Total Score.(Baseline to Week 24)