Exelon Patch and Combination With Memantine Comparative Trial

Study Overview
=================
Brief Summary
-----------------
The primary objective is to compare the tolerability between rivastigmine patch monotherapy and combination therapy with memantine in patients with Alzheimer's disease (AD). The secondary objective is to compare the efficacy and safety between rivastigmine patch monotherapy and combination therapy with memantine in patients with AD. The study hypothesis is that the tolerability of the combination therapy with memantine is not inferior to that of rivastigmine patch monotherapy in AD patients.

Detailed Description
-----------------
Recently, the rivastigmine patch demonstrated efficacy comparable to the highest doses of rivastigmine capsules, with markedly improved tolerability profile. We hypothesized that combination of memantine and rivastigmine patch will be safe and well tolerated and result in more clinical benefit in patients with AD in comparison with rivastigmine patch monotherapy, for the mechanisms of the drugs are different.

Official Title
-----------------
A Multicenter, Randomized, Open-label Study to Compare the Tolerability Between Rivastigmine Patch Monotherapy and Combination Therapy With Memantine in Patients With Alzheimer's Disease

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

Intervention / Treatment
-----------------
* Drug: Rivastigmine transdermal patch (Exelon patch), memantine
* Drug: Rivastigmine transdermal patch


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Dementia by DSM-IV and probable AD by NINCDS-ADRDA Age of 50 to 90 years Mini-Mental State Examination (MMSE) score of 10 to 20 Brain MRI or CT scan consistent with a diagnosis of probable AD The caregiver must meet the patient at least once a week and be sufficiently familiar with the patient to provide accurate data. Ambulatory or ambulatory-aided (is, walker or cane) ability Written informed consent will be obtained from the patient (if possible) and from the patient's legally acceptable representative. Even if unable to provide written informed consent, the patient must assent verbally to participating in the study. Exclusion Criteria: Patients with evidence of severe or unstable physical illness, i.e., acute and severe asthmatic conditions, severe or unstable cardiovascular disease, active peptic ulcer disease, severe hepatic or renal disease, or any medical condition which would prohibit them from completing the study Any psychiatric or primary neurodegenerative disorder other than AD Any patients with hearing or visual problem that can disturb the efficient evaluation of the patients. Any patients with a history of drug addiction or alcohol addiction for the past 10 years Patients with bradycardia (bpm less than 50) or sick sinus syndrome or conduction defects (sino-atrial block, second ot third degree A-V blocks Clinically significant laboratory abnormalities to affect cognitive function (i.e.abnormal thyroid function test, abnormal low level of vitamin B12 or folate, or syphilis, etc) History of allergy to topical products containing any of the constitution of the patches Current diagnosis of an active skin lesion Involved in other clinical trials or treated by experimental drug within 4 weeks Patients with hypersensitivity to cholinesterase inhibitors

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 90 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 |
| --- | --- |
| Active Comparator: rivastigmine patch monotherapy<br> | Drug: Rivastigmine transdermal patch<br>* All patients start on a 5-cm2 rivastigmine patch and their dose is increased to a 10-cm2 patch after 4 weeks. Patients will be randomly allocated to 1 of 2 treatment groups of rivastigmine patch monotherapy and combination therapy with memantine at the baseline visit (week 9)and treated with the drugs for 16 weeks.<br>* Other names: exelon patch;|
| Active Comparator: Combination therapy with memantine<br> | Drug: Rivastigmine transdermal patch (Exelon patch), memantine<br>* All patients start on a 5-cm2 rivastigmine patch and their dose is increased to a 10-cm2 patch after 4 weeks. Patients will be randomly allocated to 1 of 2 treatment groups of rivastigmine patch monotherapy and combination therapy with memantine at the baseline visit (week 9)and treated with the drugs for 16 weeks.<br>* Other names: exelon patch, ebixa;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention rate at week 16 after randomization |  | End point (16 weeks after randomization) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline at week 16 in Alzheimer's Disease Assessment Scale-Cognitive subscale |  | 16 weeks after randomization | 
| Change from baseline at week 16 in Mini-Mental State Examination |  | 16 weeks after randomization | 
| Change from baseline at week 16 in Frontal Assessment Battery |  | 16 weeks after randomization | 
| Change from baseline at week 16 in Alzheimer's Disease Cooperative Study - Activities of Daily Living |  | 16 weeks after randomization | 
| Change from baseline at week 16 in Caregiver-Administered Neuropsychiatric Inventory |  | 16 weeks after randomization | 
| Change from baseline at week 16 in Cohen Mansfield Agitation Inventory |  | 16 weeks after randomization | 
| Change from baseline at week 16 in Clinical Dementia Rating Scale-Sum of Boxes |  | 16 weeks after randomization | 
| Safety |  | from baseline to end-point |