Tolerability of Rivastigmine Before and After Switching From Oral Formulation to Transdermal Patch in Alzheimer's Dementia

Study Overview
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Brief Summary
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This phase IIIb study is intended to implement a consistent treatment way for switching to Exelon transdermal patch from oral formulation of rivastigmine to stress the importance of (1) advantages of transdermal patch over conventional oral therapies: smooth drug delivery with reduced side effects;(2) encourage treatment compliance in the Alzheimer's dementia setting. This study is a single-arm, treatment-switched design. Eligible patients, who are under Exelon capsule 3 mg b.i.d. treatment for 4 weeks before Visit 2, will be recruited, followed by treatment switch from oral capsule to patch for 48 weeks maintenance treatment. During the maintenance period, the treatment will be initiated with Exelon Patch 4.6 mg/24 hours (Exelon Patch 5 cm^2) for the first 24 weeks and the dose will be escalated to Exelon Patch 9.5 mg/24 hours (Exelon Patch 10 cm^2) for another 24 weeks if well tolerated. Visits to assess safety are scheduled at baseline, 3 days, 1 week and 2 weeks after the first treatment switch, every 4 weeks until Week 40, and at the end of study (Week 52). The assessment to address the primary objective will focus on the safety of treatment switching (Week 0 28); however the safety assessment will be performed during the whole study period.

Official Title
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A 52-week, Prospective, Multi-center, Open-label Study to Assess the Tolerability of Rivastigmine Before and After Switching From Oral Formulation to Transdermal Patch in Patients With Alzheimer's Dementia in a Controlled Titration Schedule

Conditions
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Alzheimer's Dementia

Intervention / Treatment
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* Drug: ENA713


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With diagnosis of mild to moderate Alzheimer's disease. Mini-Mental Status Examination score of 10-26 within 3 months before starting oral rivastigmine treatment. A clinical diagnosis of probable AD according to NINCDS/ADRDA criteria. The brain scan (magnetic resonance imaging (MRI) or computed tomography (CT) used for establishing that these criteria are met must have been available on the source document within one year prior to study participation. Patients who are currently taking or planned to receive Exelon 3 mg capsule twice-daily treatment. Written informed consent must be obtained before any assessment is performed. If female, must be surgically sterile or at least one year post-menopausal. Sufficient education to read, write, and communicate effectively. Capable of complying with the requirements of the study Exclusion Criteria: Any advanced, severe or unstable disease that could interfere with study evaluation or completion or put patient at special risk. Any medical or neurological condition other than AD that could explain the patient's dementia (e.g., abnormal thyroid function tests, Vitamin B12 or folate deficiency, posttraumatic conditions, Huntington's disease, Parkinson's disease, syphilis). Active uncontrolled peptic ulceration, or gastrointestinal bleeding, within the previous 3 months prior to visit 1. A current diagnosis of active, uncontrolled seizure disorder. A history within the past year or current diagnosis of cerebrovascular disease (e.g., stroke, transient ischemic attacks, aneurysms). Bradycardia (< 50 beats per minute), sick sinus syndrome, conduction deficits (S-A block, second or third degree A-V block) Severe or unstable cardiovascular disease. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes, or other components of the formulation. Current diagnosis of a systemic active skin disorder or lesion that would prevent accurate assessment of the adhesion and skin irritation potential of the patch. Previous lack of efficacy with cholinesterase inhibitors. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. Patients with history of malignancy yet have been treated and defined as complete remission for more than 5 years are not excluded from study participation. Pregnant or nursing (lactating) women. Concurrently treated with succinylcholine, similar neuromuscular blocking agents or cholinergic agonists such as bethanechol 2 weeks before the start of study drug and during the treatment period.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivastigmine<br>Eligible patients, who are under rivastigmine capsule 3 mg b.i.d. treatment for 4 weeks before Visit 2, will be recruited, followed by treatment switch from oral capsule to transdermal patch for 48 weeks maintenance treatment. | Drug: ENA713<br> <br> * Other names: Rivastigmine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events, Serious Adverse Events, and Death | The overall rate of adverse events reported from initiation through the first 28-week treatment period | Baseline through week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mini-Mental Status Examination (MMSE) | The changes in Mini-Mental Status Examination (MMSE) of patients with Alzheimer's disease treated with Exelon 5 cm^2 Patch at Week 28 and Exelon 10 cm2 Patch at Week 52 versus baseline, the treatment-switching day at Week 4. MMSE is a multi-item instrument that examines orientation, registration, attention, calculation, recall, visuospatial ability and language. The total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement from baseline. The assessments will be conducted at Visit 1, 2, 8, 11 and 17 (screening, Week 4 (baseline), 16, 28 and 52). | Baselin, week 16, 28 and 52 | 
| Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) | The changes in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) of patients with Alzheimer's disease treated with Exelon 5 cm^2 Patch at Week 28 and Exelon 10 cm^2 Patch at Week 52 versus baseline, the treatment-switching day at Week 4. ADAS-Cog has been used as the major cognitive measure of anti-dementia drugs. The total score range is 0 to 70 points, with higher scores indicating greater cognitive impairment. The assessments will be conducted at Visit, 2, 8, 11 and 17 (Week 4 (baseline), 16, 28 and 52). | Baseline, week 16, 28 and 52 | 
| The Discontinuation Rate Due to the Treatment Switching From Oral Capsule to Rivastigmine Patch Treatment | The discontinuation rate due to the treatment switching from oral capsule to patch treatment. For patients who discontinue earlier due to intolerance of patch treatment, the proportion will be analyzed. Both the discontinuation rate of 5 cm2 and 10 cm^2 patch therapy will be presented. | Baseline through week 52 | 
| Percentage of Patients Successfully Titrated to Rivastigmine Patch 10 cm^2 | The percentage of patients successfully titrated to rivastigmine patch 10 cm2 | Baseline through week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's dementia, AD