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

Novartis

Status and phase: Completed; Phase 3

Conditions: Alzheimer's Disease

Treatments: Drug: Rivastigmine 10 cm^2 transdermal patch; Drug: Rivastigmine 5 cm^2 transdermal patch

Study type: Interventional

Funder types: Industry

Identifiers

NCT00428389

CENA713DUS38

CENA713DUS38E1 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 262 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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262 participants in 2 patient groups

Immediate Switch

Experimental group

Description:

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.

Treatment:

Drug: Rivastigmine 5 cm^2 transdermal patch

Drug: Rivastigmine 10 cm^2 transdermal patch

Delayed Switch

Experimental group

Description:

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.

Treatment:

Drug: Rivastigmine 5 cm^2 transdermal patch

Drug: Rivastigmine 10 cm^2 transdermal patch