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

NCT ID: NCT00428389

Last Updated: 2014-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 262 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2008-02-29

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.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Rivastigmine 5 cm^2 transdermal patch

Intervention Type: DRUG

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

Intervention Type: DRUG

Rivastigmine 10 cm\^2 patch size loaded with 18 mg and providing 9.5 mg rivastigmine per 24 hours.

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.

Group Type: EXPERIMENTAL

Rivastigmine 5 cm^2 transdermal patch

Intervention Type: DRUG

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

Intervention Type: DRUG

Rivastigmine 10 cm\^2 patch size loaded with 18 mg and providing 9.5 mg rivastigmine per 24 hours.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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;

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Dedicated Clinical Research

Sun City, Arizona, United States

ATP Clinical Research

Costa Mesa, California, United States

Margolin Brain Institute

Fresno, California, United States

Investigative site

Denver, Colorado, United States

Berma Research Group

Hialeah, Florida, United States

Sunrise Clinical Research

Hollywood, Florida, United States

Center for Clinical Trials

Venice, Florida, United States

Premiere Research Institute @ Palm Beach Neurology

West Palm Beach, Florida, United States

Medical Associates of North Georgia

Canton, Georgia, United States

Medical Associates of North Georgia

Cumming, Georgia, United States

Witham Health Services

Lebanon, Indiana, United States

Investigative site

Pittsfield, Massachusetts, United States

Rochester Center For Behavioral Medicine

Rochester Hills, Michigan, United States

Alzheimer's Research Corporation

Manchester, New Hampshire, United States

Investigative site

Long Branch, New Jersey, United States

Neurobehavioral Research, Inc

Cedarhurst, New York, United States

Eastside Comprehensive Medical Center

New York, New York, United States

Investigative site

Centerville, Ohio, United States

The Ohio State University

Columbus, Ohio, United States

Investigative site

Eugene, Oregon, United States

The Clinical Trial Center

Jenkintown, Pennsylvania, United States

Senior Adults Specialty Research

Austin, Texas, United States

Investigative site

Bennington, Vermont, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 19929593 (View on PubMed)

Other Identifiers

CENA713DUS38E1

Identifier Type: OTHER

Identifier Source: secondary_id

CENA713DUS38

Identifier Type: -

Identifier Source: org_study_id