Effects of Rivastigmine Patch on Activities of Daily Living and Cognition in Patients With Severe Dementia of the Alzheimer's Type (ACTION) (Study Protocol CENA713DUS44, NCT00948766) and a 24 Week Open-label Extension to Study CENA713DUS44

NCT ID: NCT00948766

Last Updated: 2013-08-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

716 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-31

Study Completion Date

2012-06-30

Brief Summary

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The core study assessed the efficacy of a higher dose of rivastigmine 13.3 mg/24 h transdermally (15 cm\^2 patch) compared to a lower dose of the rivastigmine 4.6 mg/24 h transdermally (5 cm\^2 patch) in patients with Severe Dementia of the Alzheimer's Type in a 24-week study. The extension study obtained additional safety and efficacy data, as well as provided the higher dose rivastigmine patch to all patients who completed the core study for an additional 24 weeks.

Detailed Description

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Conditions

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Alzheimer's Disease

Keywords

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Alzheimer's disease dementia Alzheimer's type

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Rivastigmine 13.3 mg/24 h transdermal patch

In the core study, patients were titrated to the rivastigmine 13.3 mg/24 h dose in 2 steps. For Weeks 1-4, patients received rivastigmine 4.6 mg/24 h. For Weeks 5-8, patients received rivastigmine 9.5 mg/24 h and placebo. For Weeks 9-24, patients received rivastigmine 13.3 mg/24 h and placebo. In the extension study, all patients were switched to rivastigmine 9.5 mg/24 h for a 4-week titration period and were then titrated up to 13.3 mg/24 h for a further 20 weeks of treatment.

Group Type EXPERIMENTAL

Rivastigmine 4.6 mg/24 h (5 cm^2)

Intervention Type DRUG

Rivastigmine was supplied in a 5 cm\^2 patch which released 4.6 mg/24 h. Patches were changed daily.

Rivastigmine 9.5 mg/24 h (10 cm^2)

Intervention Type DRUG

Rivastigmine was supplied in a 10 cm\^2 patch which released 9.5 mg/24 h. Patches were changed daily.

Rivastigmine 13.3 mg/24 h (15 cm^2)

Intervention Type DRUG

Rivastigmine was supplied in a 15 cm\^2 patch which released 13.3 mg/24 h. Patches were changed daily.

Placebo

Intervention Type DRUG

Placebo patches were identical in size and composition to the corresponding rivastigmine patches, except that they did not contain rivastigmine. Patches were changed daily.

Rivastigmine 4.6 mg/24 h transdermal patch

In the core study, patients received rivastigmine 4.6 mg/24 h daily. For Weeks 1-4, patients received rivastigmine 4.6 mg/24 h. For Weeks 5-24, patients received rivastigmine 4.6 mg/24 h and placebo. No patients received this treatment in the extension study.

Group Type ACTIVE_COMPARATOR

Rivastigmine 4.6 mg/24 h (5 cm^2)

Intervention Type DRUG

Rivastigmine was supplied in a 5 cm\^2 patch which released 4.6 mg/24 h. Patches were changed daily.

Placebo

Intervention Type DRUG

Placebo patches were identical in size and composition to the corresponding rivastigmine patches, except that they did not contain rivastigmine. Patches were changed daily.

Interventions

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Rivastigmine 4.6 mg/24 h (5 cm^2)

Rivastigmine was supplied in a 5 cm\^2 patch which released 4.6 mg/24 h. Patches were changed daily.

Intervention Type DRUG

Rivastigmine 9.5 mg/24 h (10 cm^2)

Rivastigmine was supplied in a 10 cm\^2 patch which released 9.5 mg/24 h. Patches were changed daily.

Intervention Type DRUG

Rivastigmine 13.3 mg/24 h (15 cm^2)

Rivastigmine was supplied in a 15 cm\^2 patch which released 13.3 mg/24 h. Patches were changed daily.

Intervention Type DRUG

Placebo

Placebo patches were identical in size and composition to the corresponding rivastigmine patches, except that they did not contain rivastigmine. Patches were changed daily.

Intervention Type DRUG

Other Intervention Names

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ENA713D Exelon Exelon patch ENA713D Exelon Exelon path ENA713D Exelon Exelon patch

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of probable Alzheimer's disease (AD) according to National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria.
* A Mini-Mental State Examination (MMSE) score of ≥ 3 and ≤ 12.
* Be able to complete at least 1 item on the Severe Impairment Battery (SIB).
* Residing with someone in the community or in regular contact with the primary caregiver.
* Be ambulatory or ambulatory with aid.


* Complete the double-blind phase (Week 24) of the core study.
* Provide, if mentally competent, a separate written informed consent prior to participation in the extension study. In addition, the patient's caregiver, will provide written informed consent prior to the patient's participation in the open-label extension study. If the patient is not able to provide written informed consent, written informed consent must be obtained from the legally authorized representative on the patient's behalf.
* Continue to reside with someone in the community or in regular contact with the primary caregiver; patients who reside in an assisted living facility are eligible to participate.
* Continue to have a primary caregiver willing to accept responsibility for supervising treatment (eg, application and removal of the patch daily at approximately the same time of day), assessing the condition of the patient throughout the extension study.
* Must be medically stable and tolerating the current dose of rivastigmine patch as determined by the investigator.

Exclusion Criteria

* 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.
* Patients currently residing in a nursing home.
* Any current medical or neurological condition other than AD that could explain the patient's dementia.
* A current diagnosis of probable or possible vascular dementia.
* A current diagnosis of severe or unstable cardiovascular disease.
* A current diagnosis of bradycardia (\< 50 beats per minute \[bpm\]), sick-sinus syndrome, or conduction defects.
* Clinically significant urinary obstruction.
* History of malignancy of any organ system within the past 5 years unless patient is verified to be in stable condition with no active metastasis.
* Current diagnosis of an active skin lesion/disorder that would prevent the patient from using a transdermal patch every day.
* A known exaggerated pharmacological sensitivity or hypersensitivity to drugs similar to rivastigmine, or to other cholinergic compounds.
* Taken any of the following substances (at the time of the Baseline Visit \[Visit 2\]).
* Succinylcholine-type muscle relaxants during the previous 2 weeks.
* Lithium during the previous 2 weeks.
* An investigational drug during the previous 4 weeks.
* A drug or treatment known to cause major organ system toxicity during the previous 4 weeks.
* Rivastigmine (oral or transdermal patch), donepezil, galantamine, other cholinesterase inhibitors (eg, tacrine, physostigmine, or pyridostigmine), or other approved treatments for Alzheimer's disease during the previous 2 weeks, with exception of stable treatment with memantine for at least 3 months before study entry (Visit 1).
* Centrally acting anticholinergic drugs including tricyclic and tetracyclic antidepressants during the previous 4 weeks.
* Selegiline unless taken at a stable dose during the previous 4 weeks.
* Peripheral anticholinergics not taken at a stable dose during the previous 4 weeks.

Extension study



* Patients who discontinued the core study due to any reason are excluded.
* No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Clinical Research Advantage Inc./Neurological. Physicians of Arizona, Inc

Tempe, Arizona, United States

Site Status

Northwest Neuro Specialist, PLLC

Tucson, Arizona, United States

Site Status

IHS Research Center Inc.

Conway, Arkansas, United States

Site Status

East Bay Physicians Medical Group

Berkeley, California, United States

Site Status

ATP Clinical Research, Inc.

Costa Mesa, California, United States

Site Status

Neuro Pain Medical Center

Fresno, California, United States

Site Status

Margolin Brain Institute

Fresno, California, United States

Site Status

Collaborative Neuroscience Network Inc.

Garden Grove, California, United States

Site Status

PCND Neuroscience Research Institute Inc./The Center for Memory and Aging

Poway, California, United States

Site Status

Anderson Clinical Research

Redlands, California, United States

Site Status

San Francisco Clinical Research Center

San Francisco, California, United States

Site Status

Neuropsychiatric Research Center of Orange County

Santa Ana, California, United States

Site Status

California Neuroscience Research Medical Group, Inc.

Sherman Oaks, California, United States

Site Status

Viking Clinical Research Center

Temecula, California, United States

Site Status

Collaborative Neuroscience Network, Inc

Torrance, California, United States

Site Status

Senior Care of Colorado

Aurora, Colorado, United States

Site Status

Clinical Research Studies Dept. of Clinical Science and Medical Education

Boca Raton, Florida, United States

Site Status

Quantum Laboratories Memory Disorder Center

Deerfield Beach, Florida, United States

Site Status

Brain Matters Research, Inc.

Delray Beach, Florida, United States

Site Status

Neurologic Consultants, PA

Fort Lauderdale, Florida, United States

Site Status

White-Wilson Medical Center

Fort Walton Beach, Florida, United States

Site Status

MD Clinical

Hallandale, Florida, United States

Site Status

Sunrise Clinical Research, Inc

Hollywood, Florida, United States

Site Status

Compass Research, LLC

Orlando, Florida, United States

Site Status

Integrity Research, LLC

Pensacola, Florida, United States

Site Status

Neurostudies, Inc.

Port Charlotte, Florida, United States

Site Status

Stedman Clinical Trials, LLC

Tampa, Florida, United States

Site Status

Center for Clinical Trials

Venice, Florida, United States

Site Status

Premiere Research Institute

West Palm Beach, Florida, United States

Site Status

Alexian Brothers Neuroscience Institute

Elk Grove Village, Illinois, United States

Site Status

Elkhart Clinic, LLC

Elkhart, Indiana, United States

Site Status

Indiana University Medical Center

Indianapolis, Indiana, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

MidAmerica Neuroscience Reseach Institute

Lenexa, Kansas, United States

Site Status

Precise Clinical Research Solutions

Manhattan, Kansas, United States

Site Status

LSU Health Sciences Center/Department of Psychiatry Psychopharmacology Research Clinic

Shreveport, Louisiana, United States

Site Status

J. Gary Booker, MD APMC

Shreveport, Louisiana, United States

Site Status

Pharmasite Research

Baltimore, Maryland, United States

Site Status

The Samuel and Alexia Bratton Memory Clinic, William Hill Inc

Easton, Maryland, United States

Site Status

Neuroscience Research of the Berkshires

Pittsfield, Massachusetts, United States

Site Status

Michigan Neurology Associates, P.C.

Clinton Township, Michigan, United States

Site Status

Wayne State University/Detroit Medical center

Detroit, Michigan, United States

Site Status

West Michigan Clinical Research

Muskegon, Michigan, United States

Site Status

Orr & Associates Memory and Geriatric Behavioral Health Clinic

Saint Paul, Minnesota, United States

Site Status

Neurological Research Clinic, Hattiesburg Clinic

Hattiesburg, Mississippi, United States

Site Status

The Neuroscience Center

Ocean Springs, Mississippi, United States

Site Status

St. Louis University

St Louis, Missouri, United States

Site Status

Sky, LLC.

St Louis, Missouri, United States

Site Status

Premier Psychiatric Research Institute, LLC

Lincoln, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, United States

Site Status

NeuroCognitive Institute

Mount Arlington, New Jersey, United States

Site Status

UMDNJ-Robert Wood Johnson Medical Center

New Brunswick, New Jersey, United States

Site Status

Alzheimer's Research Corporation

Paterson, New Jersey, United States

Site Status

UMDNJ-School of Osteopathic Medicine Center

Stratford, New Jersey, United States

Site Status

Memory Enhancement Center of NJ

Toms River, New Jersey, United States

Site Status

Upstate Clinical Research, LLC

Albany, New York, United States

Site Status

Dent Neurological Institute

Amherst, New York, United States

Site Status

Neurological Care of Central NY

Liverpool, New York, United States

Site Status

Eastside Comprehensive medical Center, LLC

New York, New York, United States

Site Status

Nathan S. Kline Institute for Psychiatric Research

Orangeburg, New York, United States

Site Status

Behavioral Medical Research of Staten Island

Staten Island, New York, United States

Site Status

Richmond Behavioral Associates

Staten Island, New York, United States

Site Status

The Burke Rehabilitation Hospital

White Plains, New York, United States

Site Status

Alzheimer's Memory Center

Charlotte, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Clinical Trials of America, Inc.

Winston-Salem, North Carolina, United States

Site Status

Valley Medical Research

Centerville, Ohio, United States

Site Status

University Neurology, Inc.

Cincinnati, Ohio, United States

Site Status

Cognitive Assessment Clinic

Portland, Oregon, United States

Site Status

Lehigh Center for Clinical Research

Allentown, Pennsylvania, United States

Site Status

Paramount Clinical Research

Bridgeville, Pennsylvania, United States

Site Status

Department of Veterans Affairs Medical Center

Coatesville, Pennsylvania, United States

Site Status

Westmoreland Neurology associates, Inc.

Greensburg, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Research Protocol Management Specialists

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, United States

Site Status

Psychiatric Consultants, PC

Franklin, Tennessee, United States

Site Status

Volunteer Research Group

Knoxville, Tennessee, United States

Site Status

Jacinto Medical Group, PA

Baytown, Texas, United States

Site Status

Future Search Trials

Dallas, Texas, United States

Site Status

University of Texas Medical Branch

Galveston, Texas, United States

Site Status

Innovative Clinical Trials

San Antonio, Texas, United States

Site Status

Radiant Research Inc.

San Antonio, Texas, United States

Site Status

Grayline Clinical Drug Trials

Wichita Falls, Texas, United States

Site Status

The Memory Clinic

Bennington, Vermont, United States

Site Status

TLC Neurology, P.L.L.C

Arlington, Virginia, United States

Site Status

UVA Neurology

Charlottesville, Virginia, United States

Site Status

Neurological Associates, Inc.

Richmond, Virginia, United States

Site Status

Alliance Research Group, LLC

Richmond, Virginia, United States

Site Status

The Center for Excellence in Aging and Geriatric Health

Williamsburg, Virginia, United States

Site Status

Internal Medicine Northwest

Tacoma, Washington, United States

Site Status

Independent Psychiatric Consultants, SC

Waukesha, Wisconsin, United States

Site Status

Metro Medical Center

Bayamón, , Puerto Rico

Site Status

INSPIRA Clinical Research

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Grossberg GT, Farlow MR, Meng X, Velting DM. Evaluating high-dose rivastigmine patch in severe Alzheimer's disease: analyses with concomitant memantine usage as a factor. Curr Alzheimer Res. 2015;12(1):53-60. doi: 10.2174/1567205011666141218122835.

Reference Type DERIVED
PMID: 25523430 (View on PubMed)

Other Identifiers

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CENA713DUS44

Identifier Type: -

Identifier Source: org_study_id

NCT01054755

Identifier Type: -

Identifier Source: nct_alias