Back to resultsSafety of Switching From Donepezil to Rivastigmine Patch in Patients With Probable Alzheimer's Disease
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Rivastigmine 5 cm^2 transdermal patch
Rivastigmine 10 cm^2 transdermal patch
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring Dementia, Alzheimer's, Rivastigmine, donepezil
Eligibility Criteria
Inclusion Criteria:
- Be at least 50 years of age;
- Have a diagnosis of probable Alzheimer's Disease;
- Have an MMSE score of > or = 10 and < or = 24;
- Must have a caregiver who is able to attend all study visits;
- Have received continuous treatment with donepezil for at least 6 months prior to screening, and received a stable dose of 5 mg/day or 10 mg/day for at least the last 3 of these 6 months.
Exclusion Criteria:
- Have an advanced, severe, progressive, or unstable disease of any type that may interfere with efficacy and safety assessments or put the patient at special risk;
- Have a history of malignancy of any organ system, treated or untreated, within the past 5 years;
- Have a history within the past year or current diagnosis of cerebrovascular disease;
- Have a current diagnosis of severe or unstable cardiovascular disease; Have a history of myocardial infarction (MI) in the last six months;
- Severe or unstable respiratory conditions (e.g., severe asthma , severe pulmonary (lung) disease);
- Digestive problems related to peptic ulcer;
- Urinary obstruction or current severe urinary tract infection;
- Abnormal thyroid function tests;
- Low folate or Vitamin B12;
- Have a disability that may prevent the patient from completing all study requirements;
- Have a current diagnosis of an active skin lesion/disorder that would prevent adhesion of a patch;
Other protocol-defined inclusion/exclusion criteria may apply
Sites / Locations
- Dedicated Clinical Research
- ATP Clinical Research
- Margolin Brain Institute
- Investigative site
- Berma Research Group
- Sunrise Clinical Research
- Center for Clinical Trials
- Premiere Research Institute @ Palm Beach Neurology
- Medical Associates of North Georgia
- Medical Associates of North Georgia
- Witham Health Services
- Investigative site
- Rochester Center For Behavioral Medicine
- Alzheimer's Research Corporation
- Investigative site
- Neurobehavioral Research, Inc
- Eastside Comprehensive Medical Center
- Investigative site
- The Ohio State University
- Investigative site
- The Clinical Trial Center
- Senior Adults Specialty Research
- Investigative site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Immediate Switch
Delayed Switch
Arm Description
Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm^2 patch and continued on their best tolerated dose for the remainder of the study.
Patients randomized to the delayed switch group were switched to 5 cm^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm^2 patch and continued on their best tolerated dose for the remainder of the study.
Outcomes
Primary Outcome Measures
Number of Participants Who Discontinued From the Study Due to Any Reason During the Core Phase of the Study
The primary objective of the study was to evaluate the safety and tolerability of 2 paradigms for switching from donepezil to rivastigmine patch in patients with Alzheimer's disease (AD). The primary variable to assess tolerability of switching was the number of participants who discontinued from the study due to any reason during the core phase.
Secondary Outcome Measures
Number of Participants Who Discontinued From the Study Due to Any Adverse Event (AE) During the Combined Core and Extension Phases of the Study
A secondary assessment of the safety and tolerability of 2 paradigms for switching from donepezil to rivastigmine patch in patients with Alzheimer's disease (AD) was the number of participants who discontinued from the study due to an AE during the combined core and extension phases of the study.
Number of Participants Who Discontinued From Study Due to Any Reason During Extension Phase
A secondary assessment of the safety and tolerability of 2 paradigms for switching from donepezil to rivastigmine patch in patients with Alzheimer's disease (AD) was the number of participants who discontinued from the study due to any reason during extension phases of the study.
Mean Change From Baseline in the Clinical Global Impression of Change (CGIC) Score at Week 5 and Week 25
The CGIC is an assessment tool used by a skilled clinician to make a judgment of the severity or a change of a patient's condition. The clinician relies solely on information obtained from the patient at the Baseline visit as well as clinical information obtained throughout the study period. The clinician does not have access to any post-baseline cognitive testing data. The CGIC is rated on a seven-point scale, ranging from (1) "very much improved" to (4) "no change" to (7) "very much worse".
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 25 and at the End of Study
The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.
Mean Change From Baseline in Neuropsychiatric Inventory - 10 Item (NPI-10) Score at Week 25 and at the End of Study.
The NPI-10 assesses a wide range of behavior problems encountered in dementia patients. The 10 behavioral domains comprising the NPI-10 are evaluated through an interview of the caregiver by a mental health professional. The scale includes both frequency and severity ratings of each domain as well as a composite domain score (frequency x severity). The sum of the composite scores for the 10 domains yields the NPI total score, which ranges from 0 to 120, the lower the score the less severe the symptoms. A negative change score from baseline indicates improvement.
Mean Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score at Week 25 and at the End of Study
The ADCS-ADL scale is composed of 23 items to assess the 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, making judgments and decisions. Responses for each item are obtained through a caregiver interview. The total score is the sum of all items and sub-questions. The range for the total ADCS-ADL score is 0 to 78; a higher score indicates a more self-sufficient individual. A positive change from baseline indicates improvement.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00428389
Brief Title
Safety of Switching From Donepezil to Rivastigmine Patch in Patients With Probable Alzheimer's Disease
Official Title
A Prospective, 5-Week, Open-Label, Randomized, Multi-Center, Parallel-Group Study With a 20-Week, Open-Label Extension Evaluating the Tolerability and Safety of Switching From Donepezil to an Initial Dose of 5 cm2 Rivastigmine Patch Formulation in Patients With Probable Alzheimer's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
February 2008 (Actual)
Study Completion Date
February 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis
4. Oversight
5. Study Description
Brief Summary
This study was designed to evaluate the safety and tolerability of switching from donepezil to an initial dose of 5cm^2 rivastigmine patch formulation in patients with probable Alzheimer's Disease (MMSE 10-24). The study included a 5-week, open-label, randomized period followed by a 20-week open-label extension period. Patients were randomized to either an immediate switch from donepezil to rivastigmine patch formulation or to a switch to rivastigmine patch formulation following a 7-day withdrawal period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Dementia, Alzheimer's, Rivastigmine, donepezil
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
262 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Immediate Switch
Arm Type
Experimental
Arm Description
Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm^2 patch and continued on their best tolerated dose for the remainder of the study.
Arm Title
Delayed Switch
Arm Type
Experimental
Arm Description
Patients randomized to the delayed switch group were switched to 5 cm^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm^2 patch and continued on their best tolerated dose for the remainder of the study.
Intervention Type
Drug
Intervention Name(s)
Rivastigmine 5 cm^2 transdermal patch
Intervention Description
Rivastigmine 5 cm^2 patch size, loaded with 9 mg and providing 4.6 mg rivastigmine per 24 hours.
Intervention Type
Drug
Intervention Name(s)
Rivastigmine 10 cm^2 transdermal patch
Intervention Description
Rivastigmine 10 cm^2 patch size loaded with 18 mg and providing 9.5 mg rivastigmine per 24 hours.
Primary Outcome Measure Information:
Title
Number of Participants Who Discontinued From the Study Due to Any Reason During the Core Phase of the Study
Description
The primary objective of the study was to evaluate the safety and tolerability of 2 paradigms for switching from donepezil to rivastigmine patch in patients with Alzheimer's disease (AD). The primary variable to assess tolerability of switching was the number of participants who discontinued from the study due to any reason during the core phase.
Time Frame
Baseline through the end of the core phase of the study (Week 5)
Secondary Outcome Measure Information:
Title
Number of Participants Who Discontinued From the Study Due to Any Adverse Event (AE) During the Combined Core and Extension Phases of the Study
Description
A secondary assessment of the safety and tolerability of 2 paradigms for switching from donepezil to rivastigmine patch in patients with Alzheimer's disease (AD) was the number of participants who discontinued from the study due to an AE during the combined core and extension phases of the study.
Time Frame
Baseline through the end of study (25 weeks)
Title
Number of Participants Who Discontinued From Study Due to Any Reason During Extension Phase
Description
A secondary assessment of the safety and tolerability of 2 paradigms for switching from donepezil to rivastigmine patch in patients with Alzheimer's disease (AD) was the number of participants who discontinued from the study due to any reason during extension phases of the study.
Time Frame
From week 5 through the end of extension phase (25 weeks)
Title
Mean Change From Baseline in the Clinical Global Impression of Change (CGIC) Score at Week 5 and Week 25
Description
The CGIC is an assessment tool used by a skilled clinician to make a judgment of the severity or a change of a patient's condition. The clinician relies solely on information obtained from the patient at the Baseline visit as well as clinical information obtained throughout the study period. The clinician does not have access to any post-baseline cognitive testing data. The CGIC is rated on a seven-point scale, ranging from (1) "very much improved" to (4) "no change" to (7) "very much worse".
Time Frame
Baseline, Week 5 (end of the core phase) and Week 25 (end of the extension phase)
Title
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 25 and at the End of Study
Description
The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.
Time Frame
Baseline and Week 25 (end of the extension phase) and at the end of study
Title
Mean Change From Baseline in Neuropsychiatric Inventory - 10 Item (NPI-10) Score at Week 25 and at the End of Study.
Description
The NPI-10 assesses a wide range of behavior problems encountered in dementia patients. The 10 behavioral domains comprising the NPI-10 are evaluated through an interview of the caregiver by a mental health professional. The scale includes both frequency and severity ratings of each domain as well as a composite domain score (frequency x severity). The sum of the composite scores for the 10 domains yields the NPI total score, which ranges from 0 to 120, the lower the score the less severe the symptoms. A negative change score from baseline indicates improvement.
Time Frame
Baseline, Week 25 (end of the extension phase) and at End of Study
Title
Mean Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score at Week 25 and at the End of Study
Description
The ADCS-ADL scale is composed of 23 items to assess the 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, making judgments and decisions. Responses for each item are obtained through a caregiver interview. The total score is the sum of all items and sub-questions. The range for the total ADCS-ADL score is 0 to 78; a higher score indicates a more self-sufficient individual. A positive change from baseline indicates improvement.
Time Frame
Baseline, Week 25 (end of the extension phase) and at the end of Study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Be at least 50 years of age;
Have a diagnosis of probable Alzheimer's Disease;
Have an MMSE score of > or = 10 and < or = 24;
Must have a caregiver who is able to attend all study visits;
Have received continuous treatment with donepezil for at least 6 months prior to screening, and received a stable dose of 5 mg/day or 10 mg/day for at least the last 3 of these 6 months.
Exclusion Criteria:
Have an advanced, severe, progressive, or unstable disease of any type that may interfere with efficacy and safety assessments or put the patient at special risk;
Have a history of malignancy of any organ system, treated or untreated, within the past 5 years;
Have a history within the past year or current diagnosis of cerebrovascular disease;
Have a current diagnosis of severe or unstable cardiovascular disease; Have a history of myocardial infarction (MI) in the last six months;
Severe or unstable respiratory conditions (e.g., severe asthma , severe pulmonary (lung) disease);
Digestive problems related to peptic ulcer;
Urinary obstruction or current severe urinary tract infection;
Abnormal thyroid function tests;
Low folate or Vitamin B12;
Have a disability that may prevent the patient from completing all study requirements;
Have a current diagnosis of an active skin lesion/disorder that would prevent adhesion of a patch;
Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Dedicated Clinical Research
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85351
Country
United States
Facility Name
ATP Clinical Research
City
Costa Mesa
State/Province
California
ZIP/Postal Code
92626
Country
United States
Facility Name
Margolin Brain Institute
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
Investigative site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80209
Country
United States
Facility Name
Berma Research Group
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Facility Name
Sunrise Clinical Research
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Center for Clinical Trials
City
Venice
State/Province
Florida
ZIP/Postal Code
34285
Country
United States
Facility Name
Premiere Research Institute @ Palm Beach Neurology
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
Medical Associates of North Georgia
City
Canton
State/Province
Georgia
ZIP/Postal Code
30114
Country
United States
Facility Name
Medical Associates of North Georgia
City
Cumming
State/Province
Georgia
ZIP/Postal Code
30040
Country
United States
Facility Name
Witham Health Services
City
Lebanon
State/Province
Indiana
ZIP/Postal Code
46052
Country
United States
Facility Name
Investigative site
City
Pittsfield
State/Province
Massachusetts
ZIP/Postal Code
01201
Country
United States
Facility Name
Rochester Center For Behavioral Medicine
City
Rochester Hills
State/Province
Michigan
ZIP/Postal Code
48307
Country
United States
Facility Name
Alzheimer's Research Corporation
City
Manchester
State/Province
New Hampshire
ZIP/Postal Code
08759
Country
United States
Facility Name
Investigative site
City
Long Branch
State/Province
New Jersey
ZIP/Postal Code
07740
Country
United States
Facility Name
Neurobehavioral Research, Inc
City
Cedarhurst
State/Province
New York
ZIP/Postal Code
11516
Country
United States
Facility Name
Eastside Comprehensive Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Investigative site
City
Centerville
State/Province
Ohio
ZIP/Postal Code
45459
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Investigative site
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
The Clinical Trial Center
City
Jenkintown
State/Province
Pennsylvania
ZIP/Postal Code
19046
Country
United States
Facility Name
Senior Adults Specialty Research
City
Austin
State/Province
Texas
ZIP/Postal Code
78757
Country
United States
Facility Name
Investigative site
City
Bennington
State/Province
Vermont
ZIP/Postal Code
05201
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
19929593
Citation
Farlow MR, Alva G, Meng X, Olin JT. A 25-week, open-label trial investigating rivastigmine transdermal patches with concomitant memantine in mild-to-moderate Alzheimer's disease: a post hoc analysis. Curr Med Res Opin. 2010 Feb;26(2):263-9. doi: 10.1185/03007990903434914.
Results Reference
derived
Learn more about this trial
Safety of Switching From Donepezil to Rivastigmine Patch in Patients With Probable Alzheimer's Disease
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