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

Phase 3

Completed

Conditions: Dementia of the Alzheimer's Type

Interventions: Drug: Placebo
Drug: memantine ER

Registration Number: NCT00322153

Lead Sponsor: Forest Laboratories

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 677

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Oral administration, once daily.
Memantine ER	memantine ER	28mg, once daily. Oral administration for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Severe Impairment Battery (SIB) at Week 24 (LOCF)	Baseline to week 24	The SIB was developed for the evaluation of cognitive function in patients with more advanced dementia, and evaluates the areas of memory, language, praxis, orientation, and attention. The SIB test items consist of simple, one-step commands presented with gestural cues that are repeated if necessary. The test contains 51 items, and the range of possible scores is 0 to 100 (with 0 being the worst result). The SIB has been shown to be a valid and reliable instrument sensitive to longitudinal change.
Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC-plus) at Week 24 (LOCF)	Week 24	The CIBIC-Plus is a measure of an overall clinical effect and is based on a comprehensive evaluation at Baseline and later visits of four domains: general (overall clinical status), functional (including activities of daily living), cognitive, and behavioral. A skilled clinician interviews the patient, and includes information supplied by a knowledgeable caregiver. The CIBIC-Plus is a rating of the patient's global status relative to Baseline, ranging from a score of 1, indicating "marked improvement" to a score of 4, indicating "no change" to a score of 7, indicating "marked worsening."

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the 19-Item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19) Scale at Week 24 (LOCF)	Baseline to week 24	The ADCS-ADL19 modified inventory consists of 19 items used to measure the functional capabilities of patients with moderate to severe dementia. Each activity-of-daily-living (ADL) item comprises a series of hierarchical subquestions ranging from the highest level of independent performance to complete loss of ability to perform the ADL Inventory. The inventory is performed 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. Response range is 0 (total disability) to 54 (total independence).

Trial Locations

Locations (83): Forest Investigative Site 308
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Coquimbo, Elqui, Chile
Forest Investigative Site 213
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Culiacan, Sinaloa, Mexico
Forest Investigative Site 045
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Kalamazoo, Michigan, United States
Forest Investigative Site 065
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Fort Myers, Florida, United States
Forest Investigative Site 071
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Santa Ana, California, United States
Forest Investigative Site 111
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Buenos Aires, Argentina
Forest Investigative Site 110
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Mendoza, Argentina
Forest Investigative Site 120
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Santa Fe, Argentina
Forest Investigative Site 202
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Mexico City, Federal District, Mexico
Forest Investigative Site 010
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Phoenix, Arizona, United States
Forest Investigative Site 024
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San Francisco, California, United States
Forest Investigative Site 211
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Leon, Guanajuato, Mexico
Forest Investigative Site 002
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Denver, Colorado, United States
Forest Investigative Site 020
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Portland, Oregon, United States
Forest Investigative Site 121
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Buenos Aires, Argentina
Forest Investigative Site 062
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Costa Mesa, California, United States
Forest Investigative Site 050
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Fresno, California, United States
Forest Investigative Site 070
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Delray Beach, Florida, United States
Forest Investigative Site 021
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Boca Raton, Florida, United States
Forest Investigative Site 052
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Boynton Beach, Florida, United States
Forest Investigative Site 001
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Miami, Florida, United States
Forest Investigative Site 034
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North Miami, Florida, United States
Forest Investigative Site 044
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Hallandale Beach, Florida, United States
Forest Investigative Site 043
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Hallandale Beach, Florida, United States
Forest Investigative Site 038
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Palm Beach Gardens, Florida, United States
Forest Investigative Site 008
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Saint Petersburg, Florida, United States
Forest Investigative Site 069
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Joliet, Illinois, United States
Forest Investigative Site 009
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Snellville, Georgia, United States
Forest Investigative Site 014
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Saint Loius, Missouri, United States
Forest Investigative Site 048
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Albany, New York, United States
Forest Investigative Site 004
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White Plains, New York, United States
Forest Investigative Site 006
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Buffalo, New York, United States
Forest Investigative Site 027
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Centerville, Ohio, United States
Forest Investigative Site 012
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Toledo, Ohio, United States
Forest Investigative Site 067
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East Providence, Rhode Island, United States
Forest Investigative Site 018
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Jenkintown, Pennsylvania, United States
Forest Investigative Site 032
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Greensburg, Pennsylvania, United States
Forest Investigative Site 017
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San Antonio, Texas, United States
Forest Investigative Site 102
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Buenos Aires, Argentina
Forest Investigative Site 026
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Tacoma, Washington, United States
Forest Investigative Site 105
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La Plata, Buenos Aires, Argentina
Forest Investigative Site 123
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Lanus, Buenos Aires, Argentina
Forest Investigative Site 108
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Buenos Aires, Argentina
Forest Investigative Site 106
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Buenos Aires, Argentina
Forest Investigative Site 114
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Buenos Aires, Argentina
Forest Investigative Site 119
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Buenos Aires, Argentina
Forest Investigative Site 122
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Buenos Aires, Argentina
Forest Investigative Site 112
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Cordoba, Argentina
Forest Investigative Site 116
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Buenos Aires, Argentina
Forest Investigative Site 115
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Buenos Aires, Argentina
Forest Investigative Site 124
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Cordoba, Argentina
Forest Investigative Site 125
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Mendoza, Argentina
Forest Investigative Site 312
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Santiago, Chile
Forest Investigative Site 306
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Valdivia, Chile
Forest Investigative Site 212
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Saltillo, Coahuila, Mexico
Forest Investigative Site 304
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Santiago, Chile
Forest Investigative Site 208
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Monterrey, Nuevo Leon, Mexico
Forest Investigative Site 203
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Zapopan, Jalisco, Mexico
Forest Investigative Site 205
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Guadalajara, Jalisco, Mexico
Forest Investigative Site 210
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San Luis Potosi, Mexico
Forest Investigative Site 003
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New Brunswick, New Jersey, United States
Forest Investigative Site 064
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Long Branch, New Jersey, United States
Forest Investigative Site 011
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Morristown, New Jersey, United States
Forest Investigative Site 103
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Banfield, Buenos Aires, Argentina
Forest Investigative Site 118
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Buenos Aires, Argentina
Forest Investigative Site 109
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Buenos Aires, Argentina
Forest Investigative Site 104
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Buenos Aires, Argentina
Forest Investigative Site 107
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Buenos Aires, Argentina
Forest Investigative Site 301
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Las Condes, Santiago, Chile
Forest Investigative Site 309
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Las Condes, Santiago, Chile
Forest Investigative Site 303
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Providencia, Santiago, Chile
Forest Investigative Site 310
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Providencia, Santiago, Chile
Forest Investigative Site 313
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Recoleta, Santiago, Chile
Forest Investigative Site 305
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San Ramon, Santiago, Chile
Forest Investigative Site 302
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Antofagasta, Chile
Forest Investigative Site 113
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Rosario, Santa Fe, Argentina
Forest Investigative Site 207
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Mexico City, Federal District, Mexico
Forest Investigative Site 204
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Monterrey, Nuevo Leon, Mexico
Forest Investigative Site 206
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Aguascalientes, Mexico
Forest Investigative Site 041
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Austin, Texas, United States
Forest Investigative Site 028
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Tampa, Florida, United States
Forest Investigative Site 068
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Orlando, Florida, United States
Forest Investigative Site 013
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Richmond, Virginia, United States