Alzheimer's DiseasePhase 3NCT00428389
Safety of Switching From Donepezil to Rivastigmine Patch in Patients With Probable Alzheimer's Disease
A Phase 3 study testing Rivastigmine 5 cm^2 transdermal patch and Rivastigmine 10 cm^2 transdermal patch in people with Alzheimer's Disease, run by Novartis at 23 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Rivastigmine 5 cm^2 transdermal patch and Rivastigmine 10 cm^2 transdermal patch
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 262 participants
- Where
- 23 sitesUnited States
- Study dates
- Jan 2007to Feb 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 12Show fewer
- 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
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
United States23 sites
Senior Adults Specialty Research
Austin, Texas, 78757
Investigative site
Bennington, Vermont, 05201
Medical Associates of North Georgia
Canton, Georgia, 30114
Neurobehavioral Research, Inc
Cedarhurst, New York, 11516
Investigative site
Centerville, Ohio, 45459
The Ohio State University
Columbus, Ohio, 43210
ATP Clinical Research
Costa Mesa, California, 92626
Medical Associates of North Georgia
Cumming, Georgia, 30040
Investigative site
Denver, Colorado, 80209
Investigative site
Eugene, Oregon, 97401
Margolin Brain Institute
Fresno, California, 93720
Berma Research Group
Hialeah, Florida, 33016
Sunrise Clinical Research
Hollywood, Florida, 33021
The Clinical Trial Center
Jenkintown, Pennsylvania, 19046
Witham Health Services
Lebanon, Indiana, 46052
Investigative site
Long Branch, New Jersey, 07740
Alzheimer's Research Corporation
Manchester, New Hampshire, 08759
Eastside Comprehensive Medical Center
New York, New York, 10021
Investigative site
Pittsfield, Massachusetts, 01201
Rochester Center For Behavioral Medicine
Rochester Hills, Michigan, 48307
Dedicated Clinical Research
Sun City, Arizona, 85351
Center for Clinical Trials
Venice, Florida, 34285
Premiere Research Institute @ Palm Beach Neurology
West Palm Beach, Florida, 33407
About this study
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
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.
- Conditions
- Alzheimer's Disease
- Being tested
- Rivastigmine 5 cm^2 transdermal patch, Rivastigmine 10 cm^2 transdermal patch
- Keywords
- Dementia, Alzheimer's, Rivastigmine, donepezil
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rivastigmine 5 cm^2 transdermal patchDrug
Rivastigmine 5 cm^2 patch size, loaded with 9 mg and providing 4.6 mg rivastigmine per 24 hours.
Rivastigmine 10 cm^2 transdermal patchDrug
Rivastigmine 10 cm^2 patch size loaded with 18 mg and providing 9.5 mg rivastigmine per 24 hours.
| Study group | Role | What they receive |
|---|---|---|
| Immediate Switch | Experimental | 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. Receives: Drug: Rivastigmine 5 cm^2 transdermal patch; Drug: Rivastigmine 10 cm^2 transdermal patch |
| Delayed Switch | Experimental | 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. Receives: Drug: Rivastigmine 5 cm^2 transdermal patch; Drug: Rivastigmine 10 cm^2 transdermal patch |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: Baseline through the end of study (25 weeks)
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.
Measured: 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
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".
Measured: 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
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.
Measured: 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.
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.
Measured: Baseline, Week 25 (end of the extension phase) and at End of Study
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.
Measured: Baseline, Week 25 (end of the extension phase) and at the end of Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2007 (estimated)
- Study startJan 2007
- Primary completionFeb 2008
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 262 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00428389
- Sponsor's protocol ID
- CENA713DUS38
- Other IDs
- CENA713DUS38E1
- Status last verified
- Jun 2014
- First submitted
- 26 Jan 2007
- Last updated
- 11 Jun 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 19929593
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00428389
- Acronym / sponsor ID
- CENA713DUS38
- Conditions
- Alzheimer's Disease
- Keywords
- Dementia, Alzheimer's, Rivastigmine, donepezil
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 262 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Jan 2007
- Primary completion
- Feb 2008 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 30 Jan 2007 (estimated)
- Results
- Posted 27 Jun 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immediate Switch | Experimental | Drug: Rivastigmine 5 cm^2 transdermal patch, Drug: Rivastigmine 10 cm^2 transdermal patchPatients 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 | Experimental | Drug: Rivastigmine 5 cm^2 transdermal patch, Drug: Rivastigmine 10 cm^2 transdermal patchPatients 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rivastigmine 5 cm^2 transdermal patchRivastigmine 5 cm^2 patch size, loaded with 9 mg and providing 4.6 mg rivastigmine per 24 hours. | Drug | Delayed Switch, Immediate Switch |
| Rivastigmine 10 cm^2 transdermal patchRivastigmine 10 cm^2 patch size loaded with 18 mg and providing 9.5 mg rivastigmine per 24 hours. | Drug | Delayed Switch, Immediate Switch |
Primary outcome
Number of Participants Who Discontinued From the Study Due to Any Reason During the Core Phase of the Study
Time frame: 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.
6 secondary outcomes
Number of Participants Who Discontinued From the Study Due to Any Adverse Event (AE) During the Combined Core and Extension Phases of the Study
Time frame: Baseline through the end of study (25 weeks)
Number of Participants Who Discontinued From Study Due to Any Reason During Extension Phase
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: Baseline, Week 25 (end of the extension phase) and at End of Study
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
Time frame: Baseline, Week 25 (end of the extension phase) and at the end of Study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 19929593Farlow 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rivastigmine 5 cm^2 transdermal patch and Rivastigmine 10 cm^2 transdermal patch in people with Alzheimer's Disease, run by Novartis at 23 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Discontinued From the Study Due to Any Reason During the Core Phase of the Study (time frame: Baseline through the end of the core phase of the study (Week 5)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00428389, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2014.