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

NCT00322153 | Completed Phase 3 Results

• 1 other identifier: MEM-MD-50
• Study Type: interventional
• Target: 677
• Locations: 4 countries
• Sites: 83

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).

Conditions

Dementia of the Alzheimer's Type

Keywords

memantine; Alzheimer's disease; moderate to severe Alzheimer's disease

Outcome Measures

Primary Outcomes (2)

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

  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.

  Baseline to week 24

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

  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."

  Week 24

Secondary Outcomes (1)

• 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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Oral administration, once daily.

Drug: Placebo

Memantine ER

ACTIVE COMPARATOR

28mg, once daily. Oral administration for 24 weeks.

Drug: memantine ER

Interventions

memantine ER DRUG

28mg(7mg capsules) once daily and oral administration for 24 weeks.

Also known as: Namenda XR

Memantine ER

Placebo DRUG

Matching placebo oral administration once daily.

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Forest Laboratories: lead

Study Sites (83)

Forest Investigative Site 010

Phoenix, Arizona, 85004, United States

Location

Forest Investigative Site 062

Costa Mesa, California, 92626, United States

Location

Forest Investigative Site 050

Fresno, California, 93720, United States

Location

Forest Investigative Site 024

San Francisco, California, 94118, United States

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Forest Investigative Site 071

Santa Ana, California, 92705, United States

Location

Forest Investigative Site 002

Denver, Colorado, 80262, United States

Location

Forest Investigative Site 021

Boca Raton, Florida, 33486, United States

Location

Forest Investigative Site 052

Boynton Beach, Florida, 33426, United States

Location

Forest Investigative Site 070

Delray Beach, Florida, 33445, United States

Location

Forest Investigative Site 065

Fort Myers, Florida, 33912, United States

Location

Forest Investigative Site 043

Hallandale, Florida, 33009, United States

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Forest Investigative Site 044

Hallandale, Florida, 33009, United States

Location

Forest Investigative Site 001

Miami, Florida, 33137, United States

Location

Forest Investigative Site 034

North Miami, Florida, 33161, United States

Location

Forest Investigative Site 068

Orlando, Florida, 32806, United States

Location

Forest Investigative Site 038

Palm Beach Gardens, Florida, 33410, United States

Location

Forest Investigative Site 008

St. Petersburg, Florida, 33709, United States

Location

Forest Investigative Site 028

Tampa, Florida, 33617, United States

Location

Forest Investigative Site 009

Snellville, Georgia, 30078, United States

Location

Forest Investigative Site 069

Joliet, Illinois, 60435, United States

Location

Forest Investigative Site 045

Kalamazoo, Michigan, 49048, United States

Location

Forest Investigative Site 014

Saint Loius, Missouri, 63104, United States

Location

Forest Investigative Site 064

Long Branch, New Jersey, 07742, United States

Location

Forest Investigative Site 011

Morristown, New Jersey, 07960, United States

Location

Forest Investigative Site 003

New Brunswick, New Jersey, 08903, United States

Location

Forest Investigative Site 048

Albany, New York, 12205, United States

Location

Forest Investigative Site 006

Buffalo, New York, 14215, United States

Location

Forest Investigative Site 004

White Plains, New York, 10605, United States

Location

Forest Investigative Site 027

Centerville, Ohio, 45459, United States

Location

Forest Investigative Site 012

Toledo, Ohio, 43623, United States

Location

Forest Investigative Site 020

Portland, Oregon, 97210, United States

Location

Forest Investigative Site 032

Greensburg, Pennsylvania, 15601, United States

Location

Forest Investigative Site 018

Jenkintown, Pennsylvania, 19046, United States

Location

Forest Investigative Site 067

East Providence, Rhode Island, 02914, United States

Location

Forest Investigative Site 041

Austin, Texas, 78757, United States

Location

Forest Investigative Site 017

San Antonio, Texas, 78229, United States

Location

Forest Investigative Site 013

Richmond, Virginia, 23229, United States

Location

Forest Investigative Site 026

Tacoma, Washington, 98405, United States

Location

Forest Investigative Site 103

Banfield, Buenos Aires, B1828CKR, Argentina

Location

Forest Investigative Site 102

Buenos Aires, Buenos Aires, 1419HDN, Argentina

Location

Forest Investigative Site 118

Buenos Aires, Buenos Aires, C1062ABF, Argentina

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Forest Investigative Site 109

Buenos Aires, Buenos Aires, C1117ABE, Argentina

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Forest Investigative Site 104

Buenos Aires, Buenos Aires, C1122AAJ, Argentina

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Forest Investigative Site 108

Buenos Aires, Buenos Aires, C1126AAB, Argentina

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Forest Investigative Site 114

Buenos Aires, Buenos Aires, C1181ACH, Argentina

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Forest Investigative Site 106

Buenos Aires, Buenos Aires, C1209AAB, Argentina

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Forest Investigative Site 119

Buenos Aires, Buenos Aires, C1405CNF, Argentina

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Forest Investigative Site 122

Buenos Aires, Buenos Aires, C1413FWO, Argentina

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Forest Investigative Site 107

Buenos Aires, Buenos Aires, C1419AHN, Argentina

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Forest Investigative Site 111

Buenos Aires, Buenos Aires, C1425AGP, Argentina

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Forest Investigative Site 121

Buenos Aires, Buenos Aires, C1425BPK, Argentina

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Forest Investigative Site 115

Buenos Aires, Buenos Aires, C1428AQK, Argentina

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Forest Investigative Site 116

Buenos Aires, Buenos Aires, C1428AQK, Argentina

Location

Forest Investigative Site 105

La Plata, Buenos Aires, B1900AVG, Argentina

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Forest Investigative Site 123

Lanús, Buenos Aires, C1824IBR, Argentina

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Forest Investigative Site 112

Córdoba, Córdoba Province, X5000ALB, Argentina

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Forest Investigative Site 124

Córdoba, Córdoba Province, X5004AOA, Argentina

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Forest Investigative Site 110

Mendoza, Mendoza Province, M5500HYF, Argentina

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Forest Investigative Site 125

Mendoza, Mendoza Province, M5504FMI, Argentina

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Forest Investigative Site 113

Rosario, Santa Fe Province, S2000DSV, Argentina

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Forest Investigative Site 120

Santa Fe, Santa Fe Province, S3000FWO, Argentina

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Forest Investigative Site 302

Antofagasta, Antofagasta, Chile

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Forest Investigative Site 308

Coquimbo, Elqui, Chile

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Forest Investigative Site 301

Las Condes, Santiago Metropolitan, Chile

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Forest Investigative Site 309

Las Condes, Santiago Metropolitan, Chile

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Forest Investigative Site 303

Providencia, Santiago Metropolitan, Chile

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Forest Investigative Site 310

Providencia, Santiago Metropolitan, Chile

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Forest Investigative Site 313

Recoleta, Santiago Metropolitan, Chile

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Forest Investigative Site 305

San Ramón, Santiago Metropolitan, Chile

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Forest Investigative Site 304

Santiago, Santiago Metropolitan, Chile

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Forest Investigative Site 312

Santiago, Santiago Metropolitan, Chile

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Forest Investigative Site 306

Valdivia, Valdivia, Chile

Location

Forest Investigative Site 206

Aguascalientes, Aguascalientes, 20230, Mexico

Location

Forest Investigative Site 212

Saltillo, Coahuila, 25000, Mexico

Location

Forest Investigative Site 202

Mexico City, Federal District, 14000, Mexico

Location

Forest Investigative Site 207

Mexico City, Federal District, 14050, Mexico

Location

Forest Investigative Site 211

León, Guanajuato, 37000, Mexico

Location

Forest Investigative Site 205

Guadalajara, Jalisco, 44610, Mexico

Location

Forest Investigative Site 203

Zapopan, Jalisco, 45200, Mexico

Location

Forest Investigative Site 208

Monterrey, Nuevo León, 44610, Mexico

Location

Forest Investigative Site 204

Monterrey, Nuevo León, 64710, Mexico

Location

Forest Investigative Site 210

San Luis Potosí City, San Luis Potosí, 78090, Mexico

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Forest Investigative Site 213

Culiacán, Sinaloa, 80400, Mexico

Location

Related Publications (1)

• 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.

  PMID: 29771687 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Memantine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Stephen M Graham, PhD
• Organization: Forest Research Institute

Stephen.Graham@frx.com

201-427-8156

Study Officials

• Stephen M Graham, PhD

  Forest Laboratories

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 3, 2006
• First Posted: May 5, 2006
• Study Start: June 1, 2005
• Primary Completion: October 1, 2007
• Study Completion: January 1, 2008
• Last Updated: September 16, 2010
• Results First Posted: September 16, 2010

Record last verified: 2010-08

Locations

AR (23); CL (11); ME (11); US (38)