Clinical trial NCT00322153: A Study of the Safety and Efficacy of Memantine in Moderate to Severe Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dementia of the Alzheimer's Type
Keywords: memantine
Alzheimer's disease
moderate to severe Alzheimer's disease
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
First posted: 2006-05-05
Enrollment: 677
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the safety, tolerability, and efficacy of memantine compared to placebo in outpatients diagnosed with moderate-to-severe dementia of the Alzheimer's type on a concurrent acetylcholinesterase inhibitor (AChEI).

Detailed description: Memantine is a therapeutic agent that represents a unique class of Alzheimer's disease (AD) treatment options. A once daily (QD) dosing regimen in an AD population would simplify administration for the caregiver. The purpose of this study is to evaluate the safety and efficacy of modified release memantine taken once daily in outpatients with moderate-to-severe AD on a concurrent AChEI.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Severe Impairment Battery (SIB) at Week 24 (LOCF)
timeFrame: Baseline to week 24
measure: Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC-plus) at Week 24 (LOCF)
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline in the 19-Item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19) Scale at Week 24 (LOCF)
timeFrame: Baseline to week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Forest Investigative Site 010
state: Arizona
city: Costa Mesa
country: United States
facility: Forest Investigative Site 062
state: California
city: Fresno
country: United States
facility: Forest Investigative Site 050
state: California
city: San Francisco
country: United States
facility: Forest Investigative Site 024
state: California
city: Santa Ana
country: United States
facility: Forest Investigative Site 071
state: California
city: Denver
country: United States
facility: Forest Investigative Site 002
state: Colorado
city: Boca Raton
country: United States
facility: Forest Investigative Site 021
state: Florida
city: Boynton Beach
country: United States
facility: Forest Investigative Site 052
state: Florida
city: Delray Beach
country: United States
facility: Forest Investigative Site 070
state: Florida
city: Fort Myers
country: United States
facility: Forest Investigative Site 065
state: Florida
city: Hallandale Beach
country: United States
facility: Forest Investigative Site 043
state: Florida
city: Hallandale Beach
country: United States
facility: Forest Investigative Site 044
state: Florida
city: Miami
country: United States
facility: Forest Investigative Site 001
state: Florida
city: North Miami
country: United States
facility: Forest Investigative Site 034
state: Florida
city: Orlando
country: United States
facility: Forest Investigative Site 068
state: Florida
city: Palm Beach Gardens
country: United States
facility: Forest Investigative Site 038
state: Florida
city: Saint Petersburg
country: United States
facility: Forest Investigative Site 008
state: Florida
city: Tampa
country: United States
facility: Forest Investigative Site 028
state: Florida
city: Snellville
country: United States
facility: Forest Investigative Site 009
state: Georgia
city: Joliet
country: United States
facility: Forest Investigative Site 069
state: Illinois
city: Kalamazoo
country: United States
facility: Forest Investigative Site 045
state: Michigan
city: Saint Loius
country: United States
facility: Forest Investigative Site 014
state: Missouri
city: Long Branch
country: United States
facility: Forest Investigative Site 064
state: New Jersey
city: Morristown
country: United States
facility: Forest Investigative Site 011
state: New Jersey
city: New Brunswick
country: United States
facility: Forest Investigative Site 003
state: New Jersey
city: Albany
country: United States
facility: Forest Investigative Site 048
state: New York
city: Buffalo
country: United States
facility: Forest Investigative Site 006
state: New York
city: White Plains
country: United States
facility: Forest Investigative Site 004
state: New York
city: Centerville
country: United States
facility: Forest Investigative Site 027
state: Ohio
city: Toledo
country: United States
facility: Forest Investigative Site 012
state: Ohio
city: Portland
country: United States
facility: Forest Investigative Site 020
state: Oregon
city: Greensburg
country: United States
facility: Forest Investigative Site 032
state: Pennsylvania
city: Jenkintown
country: United States
facility: Forest Investigative Site 018
state: Pennsylvania
city: East Providence
country: United States
facility: Forest Investigative Site 067
state: Rhode Island
city: Austin
country: United States
facility: Forest Investigative Site 041
state: Texas
city: San Antonio
country: United States
facility: Forest Investigative Site 017
state: Texas
city: Richmond
country: United States
facility: Forest Investigative Site 013
state: Virginia
city: Tacoma
country: United States
facility: Forest Investigative Site 026
state: Washington
city: Banfield
country: Argentina
facility: Forest Investigative Site 103
state: Buenos Aires
city: La Plata
country: Argentina
facility: Forest Investigative Site 105
state: Buenos Aires
city: Lanus
country: Argentina
facility: Forest Investigative Site 123
state: Buenos Aires
city: Rosario
country: Argentina
facility: Forest Investigative Site 113
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 102
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 118
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 109
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 104
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 108
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 114
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 106
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 119
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 122
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 107
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 111
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 121
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 115
city: Buenos Aires
country: Argentina
facility: Forest Investigative Site 116
city: Cordoba
country: Argentina
facility: Forest Investigative Site 112
city: Cordoba
country: Argentina
facility: Forest Investigative Site 124
city: Mendoza
country: Argentina
facility: Forest Investigative Site 110
city: Mendoza
country: Argentina
facility: Forest Investigative Site 125
city: Santa Fe
country: Argentina
facility: Forest Investigative Site 120
city: Coquimbo
country: Chile
facility: Forest Investigative Site 308
state: Elqui
city: Las Condes
country: Chile
facility: Forest Investigative Site 301
state: Santiago
city: Las Condes
country: Chile
facility: Forest Investigative Site 309
state: Santiago
city: Providencia
country: Chile
facility: Forest Investigative Site 303
state: Santiago
city: Providencia
country: Chile
facility: Forest Investigative Site 310
state: Santiago
city: Recoleta
country: Chile
facility: Forest Investigative Site 313
state: Santiago
city: San Ramon
country: Chile
facility: Forest Investigative Site 305
state: Santiago
city: Antofagasta
country: Chile
facility: Forest Investigative Site 302
city: Santiago
country: Chile
facility: Forest Investigative Site 304
city: Santiago
country: Chile
facility: Forest Investigative Site 312
city: Valdivia
country: Chile
facility: Forest Investigative Site 306
city: Saltillo
country: Mexico
facility: Forest Investigative Site 212
state: Coahuila
city: Mexico City
country: Mexico
facility: Forest Investigative Site 202
state: Federal District
city: Mexico City
country: Mexico
facility: Forest Investigative Site 207
state: Federal District
city: Leon
country: Mexico
facility: Forest Investigative Site 211
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Forest Investigative Site 205
state: Jalisco
city: Zapopan
country: Mexico
facility: Forest Investigative Site 203
state: Jalisco
city: Monterrey
country: Mexico
facility: Forest Investigative Site 208
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Forest Investigative Site 204
state: Nuevo Leon
city: Culiacan
country: Mexico
facility: Forest Investigative Site 213
state: Sinaloa
city: Aguascalientes
country: Mexico
facility: Forest Investigative Site 206
city: San Luis Potosi
country: Mexico
facility: Forest Investigative Site 210
Study officials:
affiliation: Forest Laboratories
name: Stephen M Graham, PhD
role: STUDY_DIRECTOR
References:
citation: 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.