An Efficacy and Safety Study of Galantamine for the Treatment of Patients With Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of two fixed doses (16mg/day and 24mg/day) of galantamine (a drug for treating dementia) versus placebo for the treatment of patients with Alzheimer's disease.

Detailed Description
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This is a randomized (study drug assigned by chance), double-blind (neither the physician nor the patient know the name of the study medication), placebo-controlled, parallel-group study to evaluate the efficacy and safety of two fixed doses of galantamine (16 and 24 milligrams per day [mg/day]) in patients with Alzheimer's disease. The study consists of a 4-week screening period during which all patients will receive placebo, and a 24-week double-blind treatment period during which patients will receive placebo, galantamine 16 mg/day, or galantamine 24 mg/day. For patients receiving galantamine treatment, the starting dose is 8 mg/day and increases at 4-week intervals in increments of 8 mg/day. The primary measures of effectiveness are the change from baseline to the end of the study (week 24) in the Alzheimer's Disease Assessment Scale - Japan cognitive subscale (ADAS-J cog) and the Clinician's Interview-Based Impression of Change plus - Japan (CIBIC plus-J). Safety assessments include the incidence of adverse events, clinical laboratory tests, vital signs, electrocardiograms (ECGs), and physical examination findings. The study hypothesis is that galantamine will be effective in the treatment of Alzheimer's disease. Study drug taken orally twice a day.

Official Title
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Placebo-controlled Confirmatory Study of Galantamine (R113675) for Alzheimer's Type Dementia

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: Galantamine 16 mg/day
* Drug: Galantamine 24 mg/day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients with a diagnosis of Alzheimer's disease according to the National Institute of Neurological and Communicative Disorders and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria Having a Mini-Mental Status Examination (MMSE) score of 10 - 22 inclusive Having an Alzheimer's Disease Assessment Scale - Japan cognitive subscale (ADAS-J cog) score of at least 18 Exhibiting an onset and progression of cognitive dysfunction during at least 6 months prior to the screening period Exclusion Criteria: Patients with neurodegenerative diseases other than Alzheimer's disease, such as Lewy bodies disease, (dementia due to tiny round structures made of proteins that develop within nerve cells in the brain), Parkinsonism, etc Patients with cognitive dysfunction due to cerebral damage resulting from a lack of oxygen, a brain injury, etc Patients with multi-infarct dementia (brought on by a series of strokes) or active cerebrovascular disease Patients with clinically significant cardiovascular disease Patients currently taking drugs such as a cholinesterase inhibitors, which improve cerebral circulation/metabolism

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Form= tablet, route= oral use. Corresponding placebo tablets confirmed to be indistinguishable from the galantamine tablets will be administered for 24 weeks.<br>|
| Experimental: Galantamine 16 mg/day<br> | Drug: Galantamine 16 mg/day<br>* Type= exact number, number= 8, 16, unit= mg/day, form= tablet, route= oral use. Patients will receive 8 mg galantamine daily for the first 4 weeks, and 16 mg galantamine daily for the remaining 20 weeks.<br>|
| Experimental: Galantamine 24 mg/day<br> | Drug: Galantamine 24 mg/day<br>* Type= exact number, number= 8, 16, 24, unit= mg/day, form= tablet, route= oral use. Patients will receive 8 mg galantamine daily for the first 4 weeks, then 16 mg galantamine daily for the following 4 weeks, and 24 mg galantamine daily for the remaining 16 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | ADAS-J cog is the Japanese version of the cognitive function subscale of the Alzheimer's disease assessment scale (ADAS). This scale is used to detect changes in cognitive function in individuals with Alzheimer disease on the basis of three domains: memory, language and behavior. The minimum score is zero (0) and means well cognitive function. The maximum total score is 70 points, and the larger the score, the more severe the degree of impairment. | Baseline and 24 weeks | 
| Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | CIBIC plus-J is the Japanese version of the Clinician's Interview-based Impression of Change plus the caregiver's input (CIBIC plus). It is a seven-point categorical assessment scale for evaluating the efficacy of antidementia drugs, ranging from markedly improved to markedly worse. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Disability Assessment for Dementia (DAD) | Each of the 40 item of the DAD is scored as 1 point= Yes, 0 point= No, or non applicable= N/A. A total score (minimum=0; maximum=40) is the sum of points for each questions converted out 100. Items rated as Not Applicable (N/A) are not considered for the total score. The final score is a percentage that gives an appreciation of global function in activity of daily life (ADL). Higher scores represent less disability in ADL while lower scores indicate more dysfunction. | Baseline and 24 weeks | 
| Change From Baseline in the Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) | Behave-AD is a CIBIC plus-J subscale that rates the patient's severity of psychotic symptoms. This four-point scale varies from 0 (=none) to 3 (= serious). | Baseline and 24 weeks | 
| Change From Baseline in the Mental Function Impairment Scale (MENFIS) | MENFIS is a Clinician's Interview-Based Impression of Change (CIBIC) plus-Japan subscale that rates the patient's severity for mental function impairment. This seven-point scale varies from 0 (= absolutely no impairment) to 6 (=complete impairment). | Baseline and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, Cognitive dysfunction, Dementia, Galantamine, R113675