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

Sponsor:	Forest Laboratories
Information provided by:	Forest Laboratories
ClinicalTrials.gov Identifier:	NCT00322153

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 III

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:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease Dementia

Drug Information available for: Memantine Memantine hydrochloride

U.S. FDA Resources

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

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

Show 83 Study Locations

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 Publica 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
Dopamine Agents

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 12, 2012