Safety of Switching From Donepezil to Rivastigmine Patch in Patients With Probable Alzheimer's Disease
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
2 other identifiers
interventional
262
1 country
23
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jan 2007
Shorter than P25 for phase_3
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2007
CompletedFirst Submitted
Initial submission to the registry
January 26, 2007
CompletedFirst Posted
Study publicly available on registry
January 30, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2008
CompletedResults Posted
Study results publicly available
June 27, 2011
CompletedJune 11, 2014
June 1, 2014
1.1 years
January 26, 2007
December 22, 2010
June 5, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Baseline through the end of the core phase of the study (Week 5)
Secondary Outcomes (6)
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)
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)
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)
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
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
- +1 more secondary outcomes
Study Arms (2)
Immediate Switch
EXPERIMENTALPatients 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
EXPERIMENTALPatients 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.
Interventions
Rivastigmine 5 cm\^2 patch size, loaded with 9 mg and providing 4.6 mg rivastigmine per 24 hours.
Rivastigmine 10 cm\^2 patch size loaded with 18 mg and providing 9.5 mg rivastigmine per 24 hours.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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;
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Novartislead
Study Sites (23)
Dedicated Clinical Research
Sun City, Arizona, 85351, United States
ATP Clinical Research
Costa Mesa, California, 92626, United States
Margolin Brain Institute
Fresno, California, 93720, United States
Investigative site
Denver, Colorado, 80209, United States
Berma Research Group
Hialeah, Florida, 33016, United States
Sunrise Clinical Research
Hollywood, Florida, 33021, United States
Center for Clinical Trials
Venice, Florida, 34285, United States
Premiere Research Institute @ Palm Beach Neurology
West Palm Beach, Florida, 33407, United States
Medical Associates of North Georgia
Canton, Georgia, 30114, United States
Medical Associates of North Georgia
Cumming, Georgia, 30040, United States
Witham Health Services
Lebanon, Indiana, 46052, United States
Investigative site
Pittsfield, Massachusetts, 01201, United States
Rochester Center For Behavioral Medicine
Rochester Hills, Michigan, 48307, United States
Alzheimer's Research Corporation
Manchester, New Hampshire, 08759, United States
Investigative site
Long Branch, New Jersey, 07740, United States
Neurobehavioral Research, Inc
Cedarhurst, New York, 11516, United States
Eastside Comprehensive Medical Center
New York, New York, 10021, United States
Investigative site
Centerville, Ohio, 45459, United States
The Ohio State University
Columbus, Ohio, 43210, United States
Investigative site
Eugene, Oregon, 97401, United States
The Clinical Trial Center
Jenkintown, Pennsylvania, 19046, United States
Senior Adults Specialty Research
Austin, Texas, 78757, United States
Investigative site
Bennington, Vermont, 05201, United States
Related Publications (1)
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.
PMID: 19929593DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 26, 2007
First Posted
January 30, 2007
Study Start
January 1, 2007
Primary Completion
February 1, 2008
Study Completion
February 1, 2008
Last Updated
June 11, 2014
Results First Posted
June 27, 2011
Record last verified: 2014-06