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”

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.

Intervention(s) in this Clinical Trial

• 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.
• Drug: 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Immediate Switch
  • 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.
• Experimental: Delayed Switch
  • 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 Measures

• 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)
    Safety Issue?: Yes

Secondary 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
  • Time Frame: Baseline through the end of study (25 weeks)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novartis Industry

Overall Clinical Trial Officials and Contacts

Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00428389

Study ID Number: CENA713DUS38

ClinicalTrials.gov Identifier: NCT00428389

Health Authority: United States: Food and Drug Administration