Exelon Patch and Combination With Memantine Comparative Trial

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”

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.

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.

Intervention(s) in this Clinical Trial

• Drug: Rivastigmine transdermal patch (Exelon patch), memantine
  • 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.
• Drug: Rivastigmine transdermal patch
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: rivastigmine patch monotherapy
• Active Comparator: Combination therapy with memantine

Primary Measures

• Retention rate at week 16 after randomization
  • Time Frame: End point (16 weeks after randomization)
    Safety Issue?: Yes

Secondary Measures

• Change from baseline at week 16 in Alzheimer's Disease Assessment Scale-Cognitive subscale
  • Time Frame: 16 weeks after randomization
    Safety Issue?: No
• Change from baseline at week 16 in Mini-Mental State Examination
  • Time Frame: 16 weeks after randomization
    Safety Issue?: No
• Change from baseline at week 16 in Frontal Assessment Battery
  • Time Frame: 16 weeks after randomization
    Safety Issue?: No
• Change from baseline at week 16 in Alzheimer's Disease Cooperative Study - Activities of Daily Living
  • Time Frame: 16 weeks after randomization
    Safety Issue?: No
• Change from baseline at week 16 in Caregiver-Administered Neuropsychiatric Inventory
  • Time Frame: 16 weeks after randomization
    Safety Issue?: No
• Change from baseline at week 16 in Cohen Mansfield Agitation Inventory
  • Time Frame: 16 weeks after randomization
    Safety Issue?: No
• Change from baseline at week 16 in Clinical Dementia Rating Scale-Sum of Boxes
  • Time Frame: 16 weeks after randomization
    Safety Issue?: No
• Safety
  • Time Frame: from baseline to end-point
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: 90 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Inha University Hospital Other

Overall Clinical Trial Officials and Contacts

Seong Choi, MD Principal Investigator Department of Neurology, Inha University Hospital  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01025466

Study ID Number: EXPECT

ClinicalTrials.gov Identifier: NCT01025466

Health Authority: South Korea: Institutional Review Board