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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 (ACTION)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00948766
First Posted: July 29, 2009
Last Update Posted: August 28, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis
  Purpose
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.

Condition Intervention Phase
Alzheimer's Disease Drug: Rivastigmine 4.6 mg/24 h (5 cm^2) Drug: Rivastigmine 9.5 mg/24 h (10 cm^2) Drug: Rivastigmine 13.3 mg/24 h (15 cm^2) Drug: Placebo Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 24 Week, Prospective, Randomized, Parallel-group, Double-blind, Multi-center Study (ENA713DUS44) Comparing the Effects of Rivastigmine Patch 15 cm^2 vs. Rivastigmine Patch 5 cm^2 on ACTivities of Daily Living and CognitION in Patients With Severe Dementia of the Alzheimer's Type (ACTION) and a 24-week Open-label Extension to Study ENA713DUS44

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24 [ Time Frame: Baseline of the core study to Week 24 of the core study ]
    The ADCS-ADL-SIV is designed to assess the patient's performance of both 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, and making judgments and decisions. For each of the 19 questions in the ADCS-ADL-SIV, there was either a forced choice of best response or a "yes" or "no" question with additional sub-questions. Responses for each item were obtained from the caregiver through an interview. Higher numbered scores and answers of "yes" reflected a more self-sufficient individual. The total score was calculated as the sum of all items and sub-questions and ranged from 0 to 54. A higher total score represented a higher functioning patient. A positive change score indicates improvement.

  • Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24 [ Time Frame: Baseline of the core study to Week 24 of the core study ]
    The SIB is a 40-item scale developed for the evaluation of the severity of cognitive dysfunction in more advanced Alzheimer Disease patients. The domains assessed included social interaction, memory, language, attention, orientation, praxis, visuo-spatial ability, construction, and orienting to name. The items of the SIB were developed as simple 1-step commands which are presented by a trained rater with gestural cues and repeated if necessary. The SIB was scored from 0 to 100, with higher scores reflecting higher levels of cognitive ability. A positive change score indicates improvement.


Secondary Outcome Measures:
  • Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 [ Time Frame: Baseline of the core study to Week 24 of the core study ]
    The ADCS-CGIC assesses the clinical meaningfulness of a treatment based on the clinician's rating of change. The rating is provided by a trained clinician or psychometrician blinded to the patient's treatment. The rater interviewed the patient and caregiver separately at Baseline using a worksheet that provided space for notes and comments. At baseline, raters had access to all of the patient's available records and evaluations. The rater used a similar worksheet at follow-up visits, and referred to the baseline worksheet prior to making a rating of change. The worksheets were divided into 3 domains: mental/cognitive state, behavior, and functioning. Change ratings were based on a 7-point scale: Marked (1), moderate (2), and minimal improvement (3), no change (4), and marked (5), moderate (6), and minimal worsening (7). The percentage of patients in each of the 7 categories is reported.

  • Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24 [ Time Frame: Baseline of the core study to Week 24 of the core study ]
    The NPI-12 assesses a wide range of behaviors encountered in patients with dementia to provide a means of distinguishing the frequency and severity of behavioral changes over time. Ten behavioral and 2 neurovegetative domains were evaluated in an interview with the caregiver given by a mental health professional. The scale included 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 12 domains yielded the NPI-12 total score. The NPI-12 was scored from 0 to 144, with lower scores reflecting improvement in psychiatric behavior. A negative change score indicates improvement.

  • Extension Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24 [ Time Frame: Baseline of the core study to Week 24 of the extension study ]
    The ADCS-ADL-SIV is designed to assess the patient's performance of both 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, and making judgments and decisions. For each of the 19 questions in the ADCS-ADL-SIV, there was either a forced choice of best response or a "yes" or "no" question with additional sub-questions. Responses for each item were obtained from the caregiver through an interview. Higher numbered scores and answers of "yes" reflected a more self-sufficient individual. The total score was calculated as the sum of all items and sub-questions and ranged from 0 to 54. A higher total score represented a higher functioning patient. A positive change score indicates improvement.

  • Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24 [ Time Frame: Baseline of the core study to Week 24 of the extension study ]
    The SIB is a 40-item scale developed for the evaluation of the severity of cognitive dysfunction in more advanced Alzheimer Disease patients. The domains assessed included social interaction, memory, language, attention, orientation, praxis, visuo-spatial ability, construction, and orienting to name. The items of the SIB were developed as simple 1-step commands which are presented by a trained rater with gestural cues and repeated if necessary. The SIB was scored from 0 to 100, with higher scores reflecting higher levels of cognitive ability. A positive change score indicates improvement.

  • Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 [ Time Frame: Baseline of the core study to Week 24 of the extension study ]
    The ADCS-CGIC assesses the clinical meaningfulness of a treatment based on the clinician's rating of change. The rating is provided by a trained clinician or psychometrician blinded to the patient's treatment. The rater interviewed the patient and caregiver separately at Baseline using a worksheet that provided space for notes and comments. At baseline, raters had access to all of the patient's available records and evaluations. The rater used a similar worksheet at follow-up visits, and referred to the baseline worksheet prior to making a rating of change. The worksheets were divided into 3 domains: mental/cognitive state, behavior, and functioning. Change ratings were based on a 7-point scale: Marked (1), moderate (2), and minimal improvement (3), no change (4), and marked (5), moderate (6), and minimal worsening (7). The percentage of patients in each of the 7 categories is reported.


Enrollment: 716
Study Start Date: July 2009
Study Completion Date: June 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Other Names:
  • ENA713D
  • Exelon
  • Exelon patch
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.
Other Names:
  • ENA713D
  • Exelon
  • Exelon path
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.
Other Names:
  • ENA713D
  • Exelon
  • Exelon patch
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.
Active Comparator: 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.
Drug: 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.
Other Names:
  • ENA713D
  • Exelon
  • Exelon patch
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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Core study

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.

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

Inclusion Criteria:

  • 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:

Refer to the core study protocol for full details of the exclusion criteria.

  • 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.

Other protocol-defined inclusion/exclusion criteria applied to the study.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00948766


  Hide Study Locations
Locations
United States, Arizona
Clinical Research Advantage Inc./Neurological. Physicians of Arizona, Inc
Tempe, Arizona, United States, 85282
Northwest Neuro Specialist, PLLC
Tucson, Arizona, United States, 86741
United States, Arkansas
IHS Research Center Inc.
Conway, Arkansas, United States, 72034
United States, California
East Bay Physicians Medical Group
Berkeley, California, United States, 94705
ATP Clinical Research, Inc.
Costa Mesa, California, United States, 92626
Neuro Pain Medical Center
Fresno, California, United States, 90502
Margolin Brain Institute
Fresno, California, United States, 93720
Collaborative Neuroscience Network Inc.
Garden Grove, California, United States, 92845
PCND Neuroscience Research Institute Inc./The Center for Memory and Aging
Poway, California, United States, 92064
Anderson Clinical Research
Redlands, California, United States, 92374
San Francisco Clinical Research Center
San Francisco, California, United States, 94109
Neuropsychiatric Research Center of Orange County
Santa Ana, California, United States, 92701
California Neuroscience Research Medical Group, Inc.
Sherman Oaks, California, United States, 91403
Viking Clinical Research Center
Temecula, California, United States, 92591
Collaborative Neuroscience Network, Inc
Torrance, California, United States, 90502
United States, Colorado
Senior Care of Colorado
Aurora, Colorado, United States, 80014
United States, Florida
Clinical Research Studies Dept. of Clinical Science and Medical Education
Boca Raton, Florida, United States, 33431
Quantum Laboratories Memory Disorder Center
Deerfield Beach, Florida, United States, 33064
Brain Matters Research, Inc.
Delray Beach, Florida, United States, 33445
Neurologic Consultants, PA
Fort Lauderdale, Florida, United States, 33308
White-Wilson Medical Center
Fort Walton Beach, Florida, United States, 32547
MD Clinical
Hallandale Beach, Florida, United States, 33009
Sunrise Clinical Research, Inc
Hollywood, Florida, United States, 33021
Compass Research, LLC
Orlando, Florida, United States, 32806
Integrity Research, LLC
Pensacola, Florida, United States, 32514
Neurostudies, Inc.
Port Charlotte, Florida, United States, 33952
Stedman Clinical Trials, LLC
Tampa, Florida, United States, 33613
Center for Clinical Trials
Venice, Florida, United States, 34285
Premiere Research Institute
West Palm Beach, Florida, United States, 33407
United States, Illinois
Alexian Brothers Neuroscience Institute
Elk Grove Village, Illinois, United States, 60007
United States, Indiana
Elkhart Clinic, LLC
Elkhart, Indiana, United States, 46514
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
MidAmerica Neuroscience Reseach Institute
Lenexa, Kansas, United States, 66214
Precise Clinical Research Solutions
Manhattan, Kansas, United States, 66502
United States, Louisiana
LSU Health Sciences Center/Department of Psychiatry Psychopharmacology Research Clinic
Shreveport, Louisiana, United States, 71103
J. Gary Booker, MD APMC
Shreveport, Louisiana, United States, 71104
United States, Maryland
Pharmasite Research
Baltimore, Maryland, United States, 21208
The Samuel and Alexia Bratton Memory Clinic, William Hill Inc
Easton, Maryland, United States, 21601
United States, Massachusetts
Neuroscience Research of the Berkshires
Pittsfield, Massachusetts, United States, 01201
United States, Michigan
Michigan Neurology Associates, P.C.
Clinton Township, Michigan, United States, 48035
Wayne State University/Detroit Medical center
Detroit, Michigan, United States, 48201
West Michigan Clinical Research
Muskegon, Michigan, United States, 49442
United States, Minnesota
Orr & Associates Memory and Geriatric Behavioral Health Clinic
St. Paul, Minnesota, United States, 55114
United States, Mississippi
Neurological Research Clinic, Hattiesburg Clinic
Hattiesburg, Mississippi, United States, 39401
The Neuroscience Center
Ocean Springs, Mississippi, United States, 39564
United States, Missouri
Sky, LLC.
St Louis, Missouri, United States, 63117
St. Louis University
St. Louis, Missouri, United States, 63104
United States, Nebraska
Premier Psychiatric Research Institute, LLC
Lincoln, Nebraska, United States, 68510
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68105
United States, New Jersey
Memory Enhancement Center of America, Inc.
Eatontown, New Jersey, United States, 07724
Alzheimer's Research Corporation
Manchester, New Jersey, United States, 08759
NeuroCognitive Institute
Mt. Arlington, New Jersey, United States, 07856
UMDNJ-Robert Wood Johnson Medical Center
New Brunswick, New Jersey, United States, 08903
UMDNJ-School of Osteopathic Medicine Center
Stratford, New Jersey, United States, 08084
Memory Enhancement Center of NJ
Toms River, New Jersey, United States, 08755
United States, New York
Upstate Clinical Research, LLC
Albany, New York, United States, 12205
Dent Neurological Institute
Amherst, New York, United States, 14226
Neurological Care of Central NY
Liverpool, New York, United States, 13088
Eastside Comprehensive medical Center, LLC
New York, New York, United States, 10021
Nathan S. Kline Institute for Psychiatric Research
Orangeburg, New York, United States, 10962
Behavioral Medical Research of Staten Island
Staten Island, New York, United States, 10305
Richmond Behavioral Associates
Staten Island, New York, United States, 10312
The Burke Rehabilitation Hospital
White Plains, New York, United States, 10605
United States, North Carolina
Alzheimer's Memory Center
Charlotte, North Carolina, United States, 28211
Duke University Medical Center
Durham, North Carolina, United States, 27710
Clinical Trials of America, Inc.
Winston Salem, North Carolina, United States, 27103
United States, Ohio
Valley Medical Research
Centerville, Ohio, United States, 45459
University Neurology, Inc.
Cincinnati, Ohio, United States, 45219
United States, Oregon
Cognitive Assessment Clinic
Portland, Oregon, United States, 97225
United States, Pennsylvania
Lehigh Center for Clinical Research
Allentown, Pennsylvania, United States, 18104
Paramount Clinical Research
Bridgeville, Pennsylvania, United States, 15017
Department of Veterans Affairs Medical Center
Coatesville, Pennsylvania, United States, 19320
Westmoreland Neurology associates, Inc.
Greensburg, Pennsylvania, United States, 15601
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Research Protocol Management Specialists
Pittsburg, Pennsylvania, United States, 15243
United States, Rhode Island
Rhode Island Mood & Memory Research Institute
East Providence, Rhode Island, United States, 02914
United States, Tennessee
Psychiatric Consultants, PC
Franklin, Tennessee, United States, 37067
Volunteer Research Group
Knoxville, Tennessee, United States, 37920
United States, Texas
Jacinto Medical Group, PA
Baytown, Texas, United States, 77521
Future Search Trials
Dallas, Texas, United States, 75231
University of Texas Medical Branch
Galveston, Texas, United States, 77555
Innovative Clinical Trials
San Antonio, Texas, United States, 78229
Radiant Research Inc.
San Antonio, Texas, United States, 78229
Grayline Clinical Drug Trials
Wichita Falls, Texas, United States, 76309
United States, Vermont
The Memory Clinic
Bennington, Vermont, United States, 05201
United States, Virginia
TLC Neurology, P.L.L.C
Arlington, Virginia, United States, 22205
UVA Neurology
Charlottesville, Virginia, United States, 22903
Neurological Associates, Inc.
Richmond, Virginia, United States, 23226
Alliance Research Group, LLC
Richmond, Virginia, United States, 23230
The Center for Excellence in Aging and Geriatric Health
Williamsburg, Virginia, United States, 23185
United States, Washington
Internal Medicine Northwest
Tacoma, Washington, United States, 98405
United States, Wisconsin
Independent Psychiatric Consultants, SC
Waukesha, Wisconsin, United States, 53188
Puerto Rico
Metro Medical Center
Bayamon, Puerto Rico, 00959
INSPIRA Clinical Research
San Juan, Puerto Rico, 00918
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00948766     History of Changes
Obsolete Identifiers: NCT01054755
Other Study ID Numbers: CENA713DUS44
First Submitted: July 28, 2009
First Posted: July 29, 2009
Results First Submitted: January 8, 2013
Results First Posted: February 11, 2013
Last Update Posted: August 28, 2013
Last Verified: August 2013

Keywords provided by Novartis:
Alzheimer's disease
dementia
Alzheimer's type

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Rivastigmine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents