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

This study has been completed.
Sponsor:
Information provided by:
Forest Laboratories
ClinicalTrials.gov Identifier:
NCT00322153
First received: May 3, 2006
Last updated: August 25, 2010
Last verified: August 2010
  Purpose

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).


Condition Intervention Phase
Dementia of the Alzheimer's Type
Drug: memantine ER
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Forest Laboratories:

Primary Outcome Measures:
  • Change From Baseline in Severe Impairment Battery (SIB) at Week 24 (LOCF) [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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).


Enrollment: 677
Study Start Date: June 2005
Study Completion Date: January 2008
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Oral administration, once daily.
Drug: Placebo
Matching placebo oral administration once daily.
Active Comparator: Memantine ER
28mg, once daily. Oral administration for 24 weeks.
Drug: memantine ER
28mg(7mg capsules) once daily and oral administration for 24 weeks.
Other Name: Namenda XR

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

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00322153

  Hide Study Locations
Locations
United States, Arizona
Forest Investigative Site 010
Phoenix, Arizona, United States, 85004
United States, California
Forest Investigative Site 062
Costa Mesa, California, United States, 92626
Forest Investigative Site 050
Fresno, California, United States, 93720
Forest Investigative Site 024
San Francisco, California, United States, 94118
Forest Investigative Site 071
Santa Ana, California, United States, 92705
United States, Colorado
Forest Investigative Site 002
Denver, Colorado, United States, 80262
United States, Florida
Forest Investigative Site 021
Boca Raton, Florida, United States, 33486
Forest Investigative Site 052
Boynton Beach, Florida, United States, 33426
Forest Investigative Site 070
Delray Beach, Florida, United States, 33445
Forest Investigative Site 065
Fort Myers, Florida, United States, 33912
Forest Investigative Site 043
Hallandale Beach, Florida, United States, 33009
Forest Investigative Site 044
Hallandale Beach, Florida, United States, 33009
Forest Investigative Site 001
Miami, Florida, United States, 33137
Forest Investigative Site 034
North Miami, Florida, United States, 33161
Forest Investigative Site 068
Orlando, Florida, United States, 32806
Forest Investigative Site 038
Palm Beach Gardens, Florida, United States, 33410
Forest Investigative Site 008
Saint Petersburg, Florida, United States, 33709
Forest Investigative Site 028
Tampa, Florida, United States, 33617
United States, Georgia
Forest Investigative Site 009
Snellville, Georgia, United States, 30078
United States, Illinois
Forest Investigative Site 069
Joliet, Illinois, United States, 60435
United States, Michigan
Forest Investigative Site 045
Kalamazoo, Michigan, United States, 49048
United States, Missouri
Forest Investigative Site 014
Saint Loius, Missouri, United States, 63104
United States, New Jersey
Forest Investigative Site 064
Long Branch, New Jersey, United States, 07742
Forest Investigative Site 011
Morristown, New Jersey, United States, 07960
Forest Investigative Site 003
New Brunswick, New Jersey, United States, 08903
United States, New York
Forest Investigative Site 048
Albany, New York, United States, 12205
Forest Investigative Site 006
Buffalo, New York, United States, 14215
Forest Investigative Site 004
White Plains, New York, United States, 10605
United States, Ohio
Forest Investigative Site 027
Centerville, Ohio, United States, 45459
Forest Investigative Site 012
Toledo, Ohio, United States, 43623
United States, Oregon
Forest Investigative Site 020
Portland, Oregon, United States, 97210
United States, Pennsylvania
Forest Investigative Site 032
Greensburg, Pennsylvania, United States, 15601
Forest Investigative Site 018
Jenkintown, Pennsylvania, United States, 19046
United States, Rhode Island
Forest Investigative Site 067
East Providence, Rhode Island, United States, 02914
United States, Texas
Forest Investigative Site 041
Austin, Texas, United States, 78757
Forest Investigative Site 017
San Antonio, Texas, United States, 78229
United States, Virginia
Forest Investigative Site 013
Richmond, Virginia, United States, 23229
United States, Washington
Forest Investigative Site 026
Tacoma, Washington, United States, 98405
Argentina
Forest Investigative Site 103
Banfield, Buenos Aires, Argentina, B1828CKR
Forest Investigative Site 105
La Plata, Buenos Aires, Argentina, B1900AVG
Forest Investigative Site 123
Lanus, Buenos Aires, Argentina, C1824IBR
Forest Investigative Site 113
Rosario, Santa Fe, Argentina, S2000DSV
Forest Investigative Site 102
Buenos Aires, Argentina, 1419HDN
Forest Investigative Site 107
Buenos Aires, Argentina, C1419AHN
Forest Investigative Site 106
Buenos Aires, Argentina, C1209AAB
Forest Investigative Site 109
Buenos Aires, Argentina, C1117ABE
Forest Investigative Site 111
Buenos Aires, Argentina, C1425AGP
Forest Investigative Site 122
Buenos Aires, Argentina, C1413FWO
Forest Investigative Site 115
Buenos Aires, Argentina, C1428AQK
Forest Investigative Site 116
Buenos Aires, Argentina, C1428AQK
Forest Investigative Site 118
Buenos Aires, Argentina, C1062ABF
Forest Investigative Site 108
Buenos Aires, Argentina, C1126AAB
Forest Investigative Site 104
Buenos Aires, Argentina, C1122AAJ
Forest Investigative Site 114
Buenos Aires, Argentina, C1181ACH
Forest Investigative Site 121
Buenos Aires, Argentina, C1425BPK
Forest Investigative Site 119
Buenos Aires, Argentina, C1405CNF
Forest Investigative Site 112
Cordoba, Argentina, X5000ALB
Forest Investigative Site 124
Cordoba, Argentina, X5004AOA
Forest Investigative Site 110
Mendoza, Argentina, M5500HYF
Forest Investigative Site 125
Mendoza, Argentina, M5504FMI
Forest Investigative Site 120
Santa Fe, Argentina, S3000FWO
Chile
Forest Investigative Site 308
Coquimbo, Elqui, Chile
Forest Investigative Site 309
Las Condes, Santiago, Chile
Forest Investigative Site 301
Las Condes, Santiago, Chile
Forest Investigative Site 310
Providencia, Santiago, Chile
Forest Investigative Site 303
Providencia, Santiago, Chile
Forest Investigative Site 313
Recoleta, Santiago, Chile
Forest Investigative Site 305
San Ramon, Santiago, Chile
Forest Investigative Site 302
Antofagasta, Chile
Forest Investigative Site 304
Santiago, Chile
Forest Investigative Site 312
Santiago, Chile
Forest Investigative Site 306
Valdivia, Chile
Mexico
Forest Investigative Site 212
Saltillo, Coahuila, Mexico, 25000
Forest Investigative Site 202
Mexico City, Federal District, Mexico, 14000
Forest Investigative Site 207
Mexico City, Federal District, Mexico, 14050
Forest Investigative Site 211
Leon, Guanajuato, Mexico, 37000
Forest Investigative Site 205
Guadalajara, Jalisco, Mexico, 44610
Forest Investigative Site 203
Zapopan, Jalisco, Mexico, 45200
Forest Investigative Site 204
Monterrey, Nuevo Leon, Mexico, 64710
Forest Investigative Site 208
Monterrey, Nuevo Leon, Mexico, 44610
Forest Investigative Site 213
Culiacan, Sinaloa, Mexico, 80400
Forest Investigative Site 206
Aguascalientes, Mexico, 20230
Forest Investigative Site 210
San Luis Potosi, Mexico, 78090
Sponsors and Collaborators
Forest Laboratories
Investigators
Study Director: Stephen M Graham, PhD Forest Laboratories
  More Information

No publications provided

Responsible Party: Stephen M Graham, PhD, Senior Director, Clinical Development, Neurology, Forest Research Institute, a subsidiary of Forest Laboratories, Inc
ClinicalTrials.gov Identifier: NCT00322153     History of Changes
Other Study ID Numbers: MEM-MD-50
Study First Received: May 3, 2006
Results First Received: July 20, 2010
Last Updated: August 25, 2010
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Argentina: Human Research Bioethics Committee
Argentina: Ministry of Health
Chile: Instituto de Salud Pública de Chile
Mexico: Ethics Committee
Mexico: Ministry of Health
Mexico: Secretaria de Salud

Keywords provided by Forest Laboratories:
memantine
Alzheimer's disease
moderate to severe Alzheimer's disease

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Memantine
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on October 19, 2014