Randomized, Double-blind Study to Evaluate the Tolerability of 2 Different Titration Methods of Rivastigmine Patch in AD Patients (MMSE 10-20)

Study Overview
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Brief Summary
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To evaluate the tolerability, safety and efficacy of 3-step titration versus 1-step titration of Rivastigmine patch in the Japanese population.

Official Title
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A 24-week, Multicenter, Parallel-group, Randomized,Double-blind Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Methods of Rivastigmine Patch (ENA713D/ONO-2540) in Patients With Mild to Moderate Alzheimer's Disease (MMSE 10-20)

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Active Comparator
* Drug: ENA713


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of dementia of the Alzheimer's type according to the DSM-IV criteria A clinical diagnosis of probable AD according to NINCDS/ADRDA criteria An MMSE score of ≥ 10 and ≤ 20 at baseline Exclusion Criteria: Any medical or neurological conditions other than AD that could explain the patient's dementia A current diagnosis of probable or possible vascular dementia A score of > 5 on the Modified Hachinski Ischemic Scale (MHIS) A current DSM-IV Axis 1 diagnosis that may interfere with the evaluation of the patient's response to study medication. Treated with donepezil or galantamine within last 4 weeks before the efficacy assessment at baseline. an advanced severe progressive or unstable disease of any type that may interfere with efficacy and safety assessments or put the patient's at special risk Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 step<br> | Drug: Active Comparator<br>* 1-step titration group begin treatment with a rivastigmine patch 9 mg/day for 4 weeks, followed by a dose increase to 18 mg/day.<br>|
| Active Comparator: 3 step<br> | Drug: ENA713<br>* -3-step titration group will begin treatment with a rivastigmine patch 4.5 mg/day for 4 weeks, followed by a further dose increase of 4.5 mg/day at 4-week intervals up to the maintenance dose of 18 mg/day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Adverse Events Leading to Study Drug Discontinuation | The primary variable of this study is the percentage of patients having an AE leading to study drug discontinuation during the 24-week double-blind treatment period. | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | The Alzheimer's Disease Assessment Scale - Japan cognitive subscale (ADAS-J cog) was used to measure change in cognitive function. The ADAS-J cog score ranges from 0-70, with higher total scores indicating more impairment. A negative change score indicates improvement from baseline. | Baseline, 8,16, and 24 weeks | 
| Change From Baseline in Mini-Mental State Examination (MMSE) | The MMSE was used to measure severity of Alzheimer's disease. The test consists of 2 parts: language (time orientation, registration and attention) and performance (recall, response to written/verbal commands, sriting ability and reproduction of complex polygons); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement from baseline. | Baseline and 24 weeks | 
| Number of Participants With Improvement in Japanese Clinical Global Impression of Change (J-CGIC). Patients With Improvement: a Total of 1. Markedly Improved, 2. Improved, and 3. Slightly | The J-CGIC is simple 7 grade investigator's impression scale (1. Markedly improved, 2. Improved, 3. Slightly improved, 4. No change, 5. Slightly aggravated, 6. Aggravated, 7. Markedly aggravated) and a patient is defined to have improvement if J-CGIC tool the values 1, 2, or 3. | 4, 8, 12,16, 20 and 24 weeks | 
| The Percentage of Treatment Retention. | Treatment retention rate at effective dose is defined as the proportion of patients who met all the followings - 1) completed the study, 2) received rivastigmine patch 18 mg/day throughout the last 8 weeks 3) received 18 mg/day for ≥75% of the days during the last 8 weeks | Up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rivastigmine, Alzheimer's disease, Transdermal patch