CompletedPhase 3Results posted

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

A Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Memantine in Patients With Moderate-to-Severe Dementia of the Alzheimer's Type

Lead sponsor

Forest Laboratories

Asset

Memantine

Listed sites

Recruiting sites

Enrollment

677

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 3•AD symptomatic therapy: stable ≥3 months

Primary endpoints

•Severe Impairment Battery (SIB)•Clinician's Interview-Based Impression of Change With Caregiver Input

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDMEM-MD-50

NCT IDNCT00322153

Timeline

Milestones

Study start2005-06 (month precision)

Study first posted2006-05-05estimated

Primary completion2007-10actual (month precision)

Study completion2008-01actual (month precision)

Last update posted2010-09-16estimated

Results first posted2010-09-16estimated

Assets

Drug assets

Memantine

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Ambulatory patients aged >/= 50 years

•Diagnostic evidence of probable Alzheimer's disease consistent with criteria from the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)

•Confirmatory magnetic resonance imaging (MRI) or computed tomographic (CT) scan within the prior 12 months.

•Mini-Mental State Examination (MMSE) scores >/= 3 and </= 14 at Screening (Visit 1) and Baseline (Visit 2)

•Ongoing daily acetylcholinesterase inhibitor (AChEI) therapy at a stable dose for at least 3 months prior to Screening (Visit 1). It is preferred that patients continue to receive the same AChEI therapy for the duration of the study

Exclusion criteria

•Patients with a modified Hachinski Ischemia Score greater than 4 at Screening.

•Patients who have taken memantine within one month of Screening (Visit 1)

•Patients who have a known hypersensitivity to memantine, neramexane, rimantadine, or amantadine.

•Patients whose AChEI therapy is likely to be interrupted or discontinued during the course of the study.

•Patients who are receiving therapy with more than one AChEI.

•Patients with computed tomography (CT) or magnetic resonance imaging (MRI) evidence of hydrocephalus, stroke, a space-occupying lesion, cerebral infection, or any clinically significant central nervous system disease other than Alzheimer's disease.

•Patients with a DSM-IV Axis I disorder other than Alzheimer's disease, including amnestic disorders, schizophrenia or schizoaffective disorder, bipolar disorder, current major depressive episode, psychosis, panic, or post-traumatic stress disorder.

•Patients who, in the clinician's judgement, are likely to be placed in a nursing home within the next 6 months.

•Patients who had evidence of other neurological disorders that included, but were not limited to, stroke, Parkinson's disease, seizure disorder, or head injury with loss of consciousness within the prior 5 years

•Patients who had dementia that was complicated by other organic disease

•Patients who had dementia complicated by the presence of predominant delusions

Endpoints (6)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Function / daily living

Global cognition

2 endpoints

Primary/protocol endpoint

Change From Baseline in Severe Impairment Battery (SIB) at Week 24 (LOCF)

Time frame:Baseline to week 24

change from baseline, improvement

Primary/registry result

Change From Baseline in Severe Impairment Battery (SIB) at Week 24 (LOCF)

Time frame:Baseline to week 24

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
Placebon=327 Participants	-0.4	0.65
Memantine ERn=332 Participants	2.2	0.65

Mean Difference (Final Values)2.695% CI1.0 - 4.2p0.001ANCOVA

The co-primary efficacy parameter was change from Baseline to Week 24 in SIB total score. Missing SIB total scores at Week 24 were imputed using the last-observation-carried-forward (LOCF) approach.

Function / daily living

4 endpoints

Primary/protocol endpoint

Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC-plus) at Week 24 (LOCF)

Time frame:Week 24

categorical status, descriptive

Primary/registry result

Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC-plus) at Week 24 (LOCF)

Time frame:Week 24

categorical status, descriptive

Posted result

Group	Value (mean), Units on a scale	Standard error
Placebon=328 Participants	4.1	0.07
Memantine ERn=333 Participants	3.8	0.07

p0.008Cochran-Mantel-Haenszel

The co-primary efficacy parameter was CIBIC-Plus total score at week 24. Missing CIBIC-Plus total scores at Week 24 were imputed using the last-observation-carried-forward (LOCF) approach.

Secondary/protocol endpoint

Change From Baseline in the 19-Item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19) Scale at Week 24 (LOCF)

Time frame:Baseline to week 24

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Change From Baseline in the 19-Item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19) Scale at Week 24 (LOCF)

Time frame:Baseline to week 24

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
Placebon=328 Participants	-1.7	0.44
Memantine ERn=331 Participants	-1.0	0.44

Mean Difference (Final Values)0.795% CI-0.3 - 1.8p0.177ANCOVA

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Grossberg GT, Alva G, Hendrix S, Ellison N, Kane MC, Edwards J. Memantine ER Maintains Patient Response in Moderate to Severe Alzheimer's Disease: Post Hoc Analyses From a Randomized, Controlled, Clinical Trial of Patients Treated With Cholinesterase Inhibitors. Alzheimer Dis Assoc Disord. 2018 Jul-Sep;32(3):173-178. doi: 10.1097/WAD.0000000000000261.
PMID29771687via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.