Comparison of 23 mg Donepezil Sustained Release (SR) to 10 mg Donepezil Immediate Release (IR) in Patients With Moderate to Severe Alzheimer's Disease
Summary
The purpose of this study is to compare 23 mg donepezil sustained release (SR) to the currently marketed formulation of 10 mg donepezil immediate release (IR) in patients with moderate to severe Alzheimer's disease.
Description
This study consists of a double-blind, double-dummy, parallel-group comparison of 23 mg donepezil SR with the currently marketed donepezil formulation (10 mg donepezil IR) in patients with moderate to severe Alzheimer's disease. Patients must have been taking 10 mg IR (or a bioequivalent generic) for at least 3 months prior to Screening. The study will consist of 24 weeks of daily administration of study medication, with clinic visits at Screening, Baseline, 3 weeks (safety only), 6 weeks, 12 weeks, 18 weeks and 24 weeks or early termination. Patients will receive either 10 mg donepezil IR in combination with the placebo corresponding to 23 mg donepezil SR, or 23 mg donepezil SR in combination with the placebo corresponding to 10 mg donepezil IR.
A total of approximately 1600 patients will be enrolled to obtain complete data from approximately 1200 completed patients (Revised per Amendment 02). During the Baseline visit, patients will be randomized in a 2:1 ratio (23 mg donepezil SR to 10 mg donepezil IR). The study will be performed at approximately 200 global sites (Asia, Oceania, Europe, India, Israel, North America, South Africa, and South America) (Revised per Amendments 01 and 02). An Independent Data Monitoring Committee (IDMC) will be established to review safety aspects of the study and to evaluate the results of a planned interim analysis.
Patients who complete the study may be eligible to undergo evaluation for enrollment into the open-label extension study, E2020-G000-328.
Study Design
Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Conditions
Alzheimer's Disease
Intervention
Aricept (donepezil SR 23 mg), Aricept (donepezil IR 10 mg)
Location
MedTrials, Inc.
Hickory
North Carolina
United States
28601
Status
Completed
Source
Eisai Inc.
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00478205
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Neuropil Threads
Abnormal structures located chiefly in distal dendrites and, along with NEUROFIBRILLARY TANGLES and SENILE PLAQUES, constitute the three morphological hallmarks of ALZHEIMER DISEASE. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease.
Alzheimer Vaccines
Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.
Aphasia, Primary Progressive
A progressive form of dementia characterized by the global loss of language abilities and initial preservation of other cognitive functions. Fluent and nonfluent subtypes have been described. Eventually a pattern of global cognitive dysfunction, similar to ALZHEIMER DISEASE, emerges. Pathologically, there are no Alzheimer or PICK DISEASE like changes, however, spongiform changes of cortical layers II and III are present in the TEMPORAL LOBE and FRONTAL LOBE. (From Brain 1998 Jan;121(Pt 1):115-26)
Amyloid Beta-protein Precursor
A precursor to the AMYLOID BETA-PROTEIN (beta/A4). Alterations in the expression of the amyloid beta-protein precursor (ABPP) gene, located on chromosome 21, plays a role in the development of the neuropathology common to both ALZHEIMER DISEASE and DOWN SYNDROME. ABPP is associated with the extensive extracellular matrix secreted by neuronal cells. Upon cleavage, this precursor produces three proteins of varying amino acid lengths: 695, 751, and 770. The beta/A4 (695 amino acids) or beta-amyloid protein is the principal component of the extracellular amyloid in senile plaques found in ALZHEIMER DISEASE; DOWN SYNDROME and, to a limited extent, in normal aging.
Down Syndrome
A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe MENTAL RETARDATION. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)
Clinical Trials
Preliminary Efficacy and Safety Study of ST101 Plus Aricept in Alzheimer's Disease
This study will investigate the ability of ST101 to improve memory in people with Alzheimer's disease who currently receive 10 mg Aricept® (donepezil) per day. This study also will examin...
Effect of Aricept on Biomarkers (Acetylcholine, sAPP Alpha) In Cerebrospinal Fluid
It is hypothesized that the acetylcholinesterase inhibitor, donepezil, will increase acute cerebrospinal fluid (CSF) actylcholine levels in healthy volunteers following a 5mg single dose o...
The purpose of this study is to determine the safety of donepezil hydrochloride (Aricept) in children with Down syndrome who have finished the preceding 10-week, double-blind study of done...
Drug-Drug Interaction Study With Aricept® (Donepezil)
The purpose of this study is to find out if the plasma concentration of donepezil is changed when BMS-708163 is administered at the same time
The purpose of the study is to evaluate the efficacy and safety of Aricept in nursing home patients with severe Alzheimer's disease.
PubMed Articles
Discontinuing donepezil or starting memantine for Alzheimer's disease.
To the Editor: In the Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO) study, Howard and coauthors (March 8 issue)(1) found that the magnitude of benefit, as assessed with th...
Discontinuing donepezil or starting memantine for Alzheimer's disease.
To the Editor: In the Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO) study, Howard and coauthors (March 8 issue)(1) found that the magnitude of benefit, as assessed with th...
Discontinuing donepezil or starting memantine for Alzheimer's disease.
To the Editor: In the Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO) study, Howard and coauthors (March 8 issue)(1) found that the magnitude of benefit, as assessed with th...
To provide healthcare professionals with a comprehensive assessment of donepezil 23 mg and its role in treating Alzheimer's disease (AD), the Donepezil 23 mg Expert Working Group (EWG) convened in Ju...
Donepezil or memantine improved cognitive functioning in moderate-to-severe Alzheimer disease.
QUESTION In community-dwelling patients with moderate-to-severe Alzheimer disease, what are the benefits of continuing donepezil and/or initiating memantine treatment? METHODS DESIGN Randomized, 2 x 2...
