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

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

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.

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.

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 <=18. 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