Safety of Switching From Donepezil to Rivastigmine Patch in Patients With Probable Alzheimer's Disease

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00428389
• Other study ID #: CENA713DUS38
• Secondary ID: CENA713DUS38E1
• Status: Completed
• Phase: Phase 3
• First received: January 26, 2007
• Last updated: June 5, 2014
• Start date: January 2007
• Est. completion date: February 2008

Study information

• Verified date: June 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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). 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 262
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Rivastigmine 5 cm^2 transdermal patch
Rivastigmine 5 cm^2 patch size, loaded with 9 mg and providing 4.6 mg rivastigmine per 24 hours.
• Rivastigmine 10 cm^2 transdermal patch
Rivastigmine 10 cm^2 patch size loaded with 18 mg and providing 9.5 mg rivastigmine per 24 hours.

Locations

Country	Name	City	State
United States	Senior Adults Specialty Research	Austin	Texas
United States	Investigative site	Bennington	Vermont
United States	Medical Associates of North Georgia	Canton	Georgia
United States	Neurobehavioral Research, Inc	Cedarhurst	New York
United States	Investigative site	Centerville	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	ATP Clinical Research	Costa Mesa	California
United States	Medical Associates of North Georgia	Cumming	Georgia
United States	Investigative site	Denver	Colorado
United States	Investigative site	Eugene	Oregon
United States	Margolin Brain Institute	Fresno	California
United States	Berma Research Group	Hialeah	Florida
United States	Sunrise Clinical Research	Hollywood	Florida
United States	The Clinical Trial Center	Jenkintown	Pennsylvania
United States	Witham Health Services	Lebanon	Indiana
United States	Investigative site	Long Branch	New Jersey
United States	Alzheimer's Research Corporation	Manchester	New Hampshire
United States	Eastside Comprehensive Medical Center	New York	New York
United States	Investigative site	Pittsfield	Massachusetts
United States	Rochester Center For Behavioral Medicine	Rochester Hills	Michigan
United States	Dedicated Clinical Research	Sun City	Arizona
United States	Center for Clinical Trials	Venice	Florida
United States	Premiere Research Institute @ Palm Beach Neurology	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Secondary	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.	Baseline through the end of study (25 weeks)	No
Secondary	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.	From week 5 through the end of extension phase (25 weeks)	No
Secondary	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".	Baseline, Week 5 (end of the core phase) and Week 25 (end of the extension phase)	No
Secondary	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.	Baseline and Week 25 (end of the extension phase) and at the end of study	No
Secondary	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.	Baseline, Week 25 (end of the extension phase) and at End of Study	No
Secondary	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.	Baseline, Week 25 (end of the extension phase) and at the end of Study	No