Safety of Switching From Donepezil to Rivastigmine Patch in Patients With Probable Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Registration Number
- NCT00428389
- Lead Sponsor
- Novartis
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 262
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Immediate Switch Rivastigmine 5 cm^2 transdermal patch 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. Immediate Switch Rivastigmine 10 cm^2 transdermal patch 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. Delayed Switch Rivastigmine 5 cm^2 transdermal patch 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. Delayed Switch Rivastigmine 10 cm^2 transdermal patch 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.
- Primary Outcome Measures
Name Time Method Number of Participants Who Discontinued From the Study Due to Any Reason During the Core Phase of the Study Baseline through the end of the core phase of the study (Week 5) 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
Name Time Method Number of Participants Who Discontinued From the Study Due to Any Adverse Event (AE) During the Combined Core and Extension Phases of the Study Baseline through the end of study (25 weeks) 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 From week 5 through the end of extension phase (25 weeks) 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 Baseline, Week 5 (end of the core phase) and Week 25 (end of the extension phase) 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 Baseline and Week 25 (end of the extension phase) 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. Baseline, Week 25 (end of the extension phase) and at 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 Baseline, Week 25 (end of the extension phase) 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.
Trial Locations
- Locations (17)
Margolin Brain Institute
🇺🇸Fresno, California, United States
Sunrise Clinical Research
🇺🇸Hollywood, Florida, United States
Premiere Research Institute @ Palm Beach Neurology
🇺🇸West Palm Beach, Florida, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Neurobehavioral Research, Inc
🇺🇸Cedarhurst, New York, United States
Medical Associates of North Georgia
🇺🇸Cumming, Georgia, United States
ATP Clinical Research
🇺🇸Costa Mesa, California, United States
Eastside Comprehensive Medical Center
🇺🇸New York, New York, United States
Investigative site
🇺🇸Bennington, Vermont, United States
Witham Health Services
🇺🇸Lebanon, Indiana, United States
Alzheimer's Research Corporation
🇺🇸Manchester, New Hampshire, United States
The Clinical Trial Center
🇺🇸Jenkintown, Pennsylvania, United States
Rochester Center For Behavioral Medicine
🇺🇸Rochester Hills, Michigan, United States
Center for Clinical Trials
🇺🇸Venice, Florida, United States
Berma Research Group
🇺🇸Hialeah, Florida, United States
Dedicated Clinical Research
🇺🇸Sun City, Arizona, United States
Senior Adults Specialty Research
🇺🇸Austin, Texas, United States