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

Dementia of the Alzheimer's Type Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00322153
• Other study ID #: MEM-MD-50
• Status: Completed
• Phase: Phase 3
• First received: May 3, 2006
• Last updated: August 25, 2010
• Start date: June 2005
• Est. completion date: January 2008

Study information

• Verified date: August 2010
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaArgentina: Human Research Bioethics CommitteeArgentina: Ministry of HealthChile: Instituto de Salud Pública de ChileMexico: Ethics CommitteeMexico: Ministry of HealthMexico: Secretaria de Salud
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 677
• Est. completion date: January 2008
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Dementia
• Dementia of the Alzheimer's Type

Intervention

Drug:
• memantine ER
28mg(7mg capsules) once daily and oral administration for 24 weeks.
• Placebo
Matching placebo oral administration once daily.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Forest Laboratories

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Change From Baseline in the 19-Item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19) Scale at Week 24 (LOCF)	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).	Baseline to week 24	No