A 24-Week Efficacy, Safety and Tolerability of Rivastigmine Patch Study in Patients With Probable Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy, safety, and tolerability of Exelon® patch in patients with probable AD (MMSE 10-20), in order to support a planned regulatory submission and registration of Exelon transdermal patch in China. The study is designed to confirm the non-inferiority of the efficacy of Exelon patch (target 10 cm² patch size) versus Exelon capsules (target 6.0 mg bid dose) on cognition, using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog).

Official Title
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A 24-Week, Randomized, Double-blind, Double-dummy, Parallel-group, Active-controlled Study to Assess the Efficacy, Safety, and Tolerability of the Once-daily Rivastigmine Patch Formulation in Patients With Probable Alzheimer's Disease (Mini-Mental State Examination (MMSE) 10-20)

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Rivastigmine Patch
* Drug: Rivastigmine Capsules
* Drug: Placebo to Rivastigmine patch
* Drug: Placebo to Rivastigmine capsules


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: have a diagnosis of dementia of the Alzheimer's type according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria; have a clinical diagnosis of probable AD according to NINCDS/ADRDA criteria. have a brain scan (magnetic resonance imaging (MRI) or computed tomography (CT)) consistent with the diagnosis of AD. The brain scan must have been performed within one year prior to randomization; have an MMSE score of ≥ 10 and ≤ 20; have sufficient education to have been able to read, write, and communicate effectively during the premorbid state; be residing with someone in the community throughout the study or, if living alone, in contact with the primary caregiver everyday; Exclusion criteria: have an advanced, severe, progressive, or unstable infectious, metabolic, immune, endocrinologic, hepatic, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological condition that may interfere with efficacy and safety assessments or put the patient at special risk; have a history or current diagnosis of any medical or neurological condition other than AD that is identified as contributing cause of the patient's dementia; have a current diagnosis of probable or possible vascular dementia according to the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria (NINDS-AIREN); have a score of > 4 on the Modified Hachinski Ischemic Scale (MHIS); have a current DSM-IV diagnosis of major depression, unless, in the opinion of the investigator, is in remission for at least 12 weeks; 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: Rivastigmine patch<br>Once-daily target patch size 10 cm² | Drug: Rivastigmine Patch<br>* Once-daily target patch size 10 cm²<br>* Other names: ENA713, Exelon;Drug: Placebo to Rivastigmine capsules<br>* matching Placebo to Rivastigmine capsules<br>* Other names: placebo;|
| Active Comparator: Rivastigmine capsules<br>Twice-daily target dose of 6 mg oral capsule | Drug: Rivastigmine Capsules<br>* Twice-daily target dose of 6 mg oral capsule<br>* Other names: ENA713, Exelon;Drug: Placebo to Rivastigmine patch<br>* Matching placebo to Rivastigmine patch<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on Cognition, Assessed by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) | The Alzheimer's Disease Assessment Scale (ADAS) is a performance-based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. It was assessed by a mental health professional (e.g., M.D., Ph.D., Pharm.D., R.N., or other equivalent qualifications) with a minimum of 2 years research experience meeting certification requirements. | Change at 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Global Functioning, Assessed by the Alzheimer's Disease Assessment Scale Clinical Impression of Change (ADCS-CGIC) | Alzheimer's disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) scale provides a single global rating of change from baseline. It was recommended that the baseline interview be conducted by two raters, one designated as the primary rater, the other as a backup. Both raters were independent trained clinicians, experienced in the assessment of patients with dementia. Neither rater was involved in any other way with the patients' treatment or evaluation throughout the study. At baseline, both raters had access to all of the patient's available records and evaluations. Subsequently, for all ratings of change from baseline, the rater relied solely on information obtained during the baseline interview of the patient and caregiver, including written notes and, if available, the baseline interview audio- or videotape. The rater had no access to any other safety or efficacy data, including all previous post-baseline ADCS-CGIC ratings by either rater. | Change at 24 weeks | 
| Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Total Score | Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) is a caregiver-based Activities of Daily Living (ADL) scale composed of 23 items developed for use in dementia clinical studies. It was designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests, as well as making judgments and decisions. Responses for each item were obtained from the caregiver through an interview. For each basic ADL, there was a forced choice of best response or a yes or no question with additional sub questions. Higher numbered scores and answers of yes reflected a more self-sufficient individual. Therefore, the higher total score, the higher functioning the patient was. The total score was the sum of all items and sub questions. The range for the total ADCS-ADL score was 0 to 78. | Change at 24 weeks | 
| Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | NPI including Caregiver Distress Scale (NPI-D) assesses a wide range of behavior problems encountered in dementia patients to provide a means of distinguishing frequency and severity of changes in behavioral problems & facilitates rapid behavioral assessment using screening questions.10 behavioral problems & 2 neurovegetative domains were evaluated through an interview of the caregiver by a mental health professional. The scale includes both frequency & severity ratings of ea. domain as well as a composite domain score(frequency x severity). Frequency: 1(occasionally) - 4(very frequently)&severity:1(mild) - 3(marked).The sum of the composite scores of the 12 domains yields the NPI total score. The NPI-D: 0(not severe & not at all distressing) - 5 (very severe or extremely distressing) for each of the 12 domains. NPI-12 total score: from 0-144, the NPI-10 total score: from 0-120, & NPI-D score: from 0-60, all with higher scores indicating more severe behavioral disturbance. | Change at 24 weeks | 
| Change From Baseline in Mini-Mental State Examination (MMSE) Total Score | The Mini-Mental State Examination (MMSE) was used to establish patient's eligibility for the study and it was also used as an efficacy parameter in the Double-blind Treatment Period. The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and results in a total possible score of 30, with higher scores indicating betterfunction. The total MMSE score at screening was between 10 and 20, inclusive, in order forthe patient to be eligible to participate in the trial. | Change at 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's, Rivastigmine, Patch, Dementia