Convenience, Tolerability, and Safety of Change in the Administration of Rivastigmine From Capsules to a Transdermal Patch in Patients With Mild to Moderate Alzheimer's Disease

Study Overview
=================
Brief Summary
-----------------
This study used two doses of rivastigmine transdermal patch (5 cm^2, 10 cm^2) to establish the feasibility of 2 switch schedules (with transdermal patch one-step dose titration or without dose titration) from rivastigmine capsules (3 mg bid (bis in die, twice a day), 4,5 mg bid, 6 mg bid) to rivastigmine transdermal patch and to assess safety, tolerability, convenience, and caregivers preferences of rivastigmine transdermal patch versus capsules.

Official Title
-----------------
A Multi-center, Randomised, Open-label Study to Evaluate Convenience and Safety of Change in the Mode of Administration of Rivastigmine (From Capsules to a Transdermal Patch) in Patients With Alzheimer's Disease

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: Rivastigmine patch (4.6 mg/day switch to 9.5 mg/day)
* Drug: Rivastigmine patch (9.5 mg/day)
* Drug: Rivastigmine capsules (6 mg to 12 mg/day)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meet DSM-IV (Diagnostic & Statistical Manual of Mental Disorders, Version IV) criteria for dementia of Alzheimer type and NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for probable Alzheimer's disease (AD), have a MMSE (Mini Mental State Examination) score > 10 and < 26 Have received continuous treatment with rivastigmine capsules at least with 3 mg bid (6 mg of total daily dose) for at least 3 months before entering in the study Cooperative, willing to complete all aspects of the study, and capable of doing so, either alone or with the aid of a responsible caregiver Have a primary caregiver willing to accept responsibility for supervising the treatment, (eg, application and removal of the patch daily at approximately the same time of day) and assessing the condition of the patient throughout the study. Exclusion Criteria: A medical or neurological condition other that AD that could explain the patients dementia (eg, Huntington's disease, Parkinson's Disease, abnormal thyroid function test, B12 or folate deficiency, post-traumatic conditions, syphilis) Current diagnosis of an active skin lesion/disorder that would prevent accurate assessment of the adhesion and potential skin irritation of the patch (e.g., atopic dermatitis, wounded or scratched skin in the area of the patch application) History of allergy to topical products containing vitamin E Taken any of the following substances prior to randomization: succinylcholine-type muscle relaxants during the previous 2 weeks an investigational drug during the previous 4 weeks Other protocol-defined inclusion/exclusion criteria applied to the study.

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivastigmine patch (4.6 mg/day switch to 9.5 mg/day)<br> | Drug: Rivastigmine patch (4.6 mg/day switch to 9.5 mg/day)<br>* Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).<br>|
| Experimental: Rivastigmine patch (9.5 mg/day)<br> | Drug: Rivastigmine patch (9.5 mg/day)<br>* Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).<br>|
| Active Comparator: Rivastigmine capsules (6 mg to 12 mg/day)<br> | Drug: Rivastigmine capsules (6 mg to 12 mg/day)<br>* Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Had a Gastrointestinal Adverse Event (AE) at Any Time During the Study | Gastrointestinal adverse events (including nausea, vomiting, and diarrhea) were coded using the medical dictionary MedDRA v11.0 and the number of patients who suffered an AE were described by system organ class (SOC) and preferred term (PT). | Baseline to end of study (Month 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With an AE Involving the Skin (Local Tolerance) Recorded Over the Course of the Study Period (Patch Groups Only) | Adverse events involving the skin included urticaria, pruritus, erythema, and pigmentation disorder. Only the groups administered rivastigmine transdermally via patch were analyzed. The adverse events were coded using the medical dictionary MedDRA v11.0 and the number of patients who suffered an AE were described by system organ class (SOC) and preferred term (PT). | Baseline to end of study (Month 3) | 
| Percentage of Patients With at Least 1 AE of Any Kind Recorded During the Period of the Study. | Adverse events were coded using the medical dictionary MedDRA v11.0 and the number of patients who suffered an AE were described by system organ class (SOC) and preferred term (PT). They were also tabulated by severity, relationship with study treatment, and action taken. | Baseline to end of study (Month 3) | 
| Overall Caregiver Satisfaction With Treatment | Caregivers were asked to rate their overall degree of satisfaction with the Alzheimer's disease treatment on a scale of 1 to 5 (1 Very good - 5 Very poor) at the end of the study (Month 3). A higher score indicates less satisfaction. | At end of study (Month 3) | 
| Overall Patient Satisfaction With Treatment | Patients were asked to rate their overall degree of satisfaction with the Alzheimer's disease treatment on a scale of 1 to 5 (1 Very good - 5 Very poor) at the end of the study (Month 3). A higher score indicates less satisfaction. | At end of study (Month 3) | 
| Change in the Total Mini-Mental State Examination (MMSE) Score From Baseline to Month 1 and Month 3 | The Mini Mental State Examination (MMSE) was used to evaluate the patient's cognitive status and how it progressed over time. The 35-point version used in this study was made up of five sections: orientation, fixation, attention and calculation, memory and language, and constructional praxis. The total score for each patient was obtained by adding the score from each of the above sections. The individual receives 1 point for each correct answer. The total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement. | Baseline to Month 1 and Month 3 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alzheimer's, rivastigmine, transdermal, safety, randomized, switch, patch