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

NCT00948766 | Completed Phase 4 Results

• 1 other identifier: CENA713DUS44
• Study Type: interventional
• Target: 716
• Locations: 2 countries
• Sites: 95

Brief Summary

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.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's disease; dementia; Alzheimer's type

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  Baseline of the core study to Week 24 of the core study

• Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24

  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.

  Baseline of the core study to Week 24 of the core study

Secondary Outcomes (5)

• Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24

  Baseline of the core study to Week 24 of the core study

• Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24

  Baseline of the core study to Week 24 of the core study

• 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

  Baseline of the core study to Week 24 of the extension study

• Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24

  Baseline of the core study to Week 24 of the extension study

• Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24

  Baseline of the core study to Week 24 of the extension study

Study Arms (2)

Rivastigmine 13.3 mg/24 h transdermal patch

EXPERIMENTAL

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); Drug: Rivastigmine 9.5 mg/24 h (10 cm^2); Drug: Rivastigmine 13.3 mg/24 h (15 cm^2); Drug: Placebo

Rivastigmine 4.6 mg/24 h transdermal patch

ACTIVE COMPARATOR

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); Drug: Placebo

Interventions

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

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

Also known as: ENA713D, Exelon, Exelon patch

Rivastigmine 13.3 mg/24 h transdermal patch; Rivastigmine 4.6 mg/24 h transdermal patch

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

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

Also known as: ENA713D, Exelon, Exelon path

Rivastigmine 13.3 mg/24 h transdermal patch

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

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

Also known as: ENA713D, Exelon, Exelon patch

Rivastigmine 13.3 mg/24 h transdermal patch

Placebo 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 13.3 mg/24 h transdermal patch; Rivastigmine 4.6 mg/24 h transdermal patch

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis: lead

Study Sites (95)

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

Tempe, Arizona, 85282, United States

Location

Northwest Neuro Specialist, PLLC

Tucson, Arizona, 86741, United States

Location

IHS Research Center Inc.

Conway, Arkansas, 72034, United States

Location

East Bay Physicians Medical Group

Berkeley, California, 94705, United States

Location

ATP Clinical Research, Inc.

Costa Mesa, California, 92626, United States

Location

Neuro Pain Medical Center

Fresno, California, 90502, United States

Location

Margolin Brain Institute

Fresno, California, 93720, United States

Location

Collaborative Neuroscience Network Inc.

Garden Grove, California, 92845, United States

Location

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

Poway, California, 92064, United States

Location

Anderson Clinical Research

Redlands, California, 92374, United States

Location

San Francisco Clinical Research Center

San Francisco, California, 94109, United States

Location

Neuropsychiatric Research Center of Orange County

Santa Ana, California, 92701, United States

Location

California Neuroscience Research Medical Group, Inc.

Sherman Oaks, California, 91403, United States

Location

Viking Clinical Research Center

Temecula, California, 92591, United States

Location

Collaborative Neuroscience Network, Inc

Torrance, California, 90502, United States

Location

Senior Care of Colorado

Aurora, Colorado, 80014, United States

Location

Clinical Research Studies Dept. of Clinical Science and Medical Education

Boca Raton, Florida, 33431, United States

Location

Quantum Laboratories Memory Disorder Center

Deerfield Beach, Florida, 33064, United States

Location

Brain Matters Research, Inc.

Delray Beach, Florida, 33445, United States

Location

Neurologic Consultants, PA

Fort Lauderdale, Florida, 33308, United States

Location

White-Wilson Medical Center

Fort Walton Beach, Florida, 32547, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

Sunrise Clinical Research, Inc

Hollywood, Florida, 33021, United States

Location

Compass Research, LLC

Orlando, Florida, 32806, United States

Location

Integrity Research, LLC

Pensacola, Florida, 32514, United States

Location

Neurostudies, Inc.

Port Charlotte, Florida, 33952, United States

Location

Stedman Clinical Trials, LLC

Tampa, Florida, 33613, United States

Location

Center for Clinical Trials

Venice, Florida, 34285, United States

Location

Premiere Research Institute

West Palm Beach, Florida, 33407, United States

Location

Alexian Brothers Neuroscience Institute

Elk Grove Village, Illinois, 60007, United States

Location

Elkhart Clinic, LLC

Elkhart, Indiana, 46514, United States

Location

Indiana University Medical Center

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

MidAmerica Neuroscience Reseach Institute

Lenexa, Kansas, 66214, United States

Location

Precise Clinical Research Solutions

Manhattan, Kansas, 66502, United States

Location

LSU Health Sciences Center/Department of Psychiatry Psychopharmacology Research Clinic

Shreveport, Louisiana, 71103, United States

Location

J. Gary Booker, MD APMC

Shreveport, Louisiana, 71104, United States

Location

Pharmasite Research

Baltimore, Maryland, 21208, United States

Location

The Samuel and Alexia Bratton Memory Clinic, William Hill Inc

Easton, Maryland, 21601, United States

Location

Neuroscience Research of the Berkshires

Pittsfield, Massachusetts, 01201, United States

Location

Michigan Neurology Associates, P.C.

Clinton Township, Michigan, 48035, United States

Location

Wayne State University/Detroit Medical center

Detroit, Michigan, 48201, United States

Location

West Michigan Clinical Research

Muskegon, Michigan, 49442, United States

Location

Orr & Associates Memory and Geriatric Behavioral Health Clinic

Saint Paul, Minnesota, 55114, United States

Location

Neurological Research Clinic, Hattiesburg Clinic

Hattiesburg, Mississippi, 39401, United States

Location

The Neuroscience Center

Ocean Springs, Mississippi, 39564, United States

Location

St. Louis University

St Louis, Missouri, 63104, United States

Location

Sky, LLC.

St Louis, Missouri, 63117, United States

Location

Premier Psychiatric Research Institute, LLC

Lincoln, Nebraska, 68510, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68105, United States

Location

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, 07724, United States

Location

NeuroCognitive Institute

Mount Arlington, New Jersey, 07856, United States

Location

UMDNJ-Robert Wood Johnson Medical Center

New Brunswick, New Jersey, 08903, United States

Location

Alzheimer's Research Corporation

Paterson, New Jersey, 08759, United States

Location

UMDNJ-School of Osteopathic Medicine Center

Stratford, New Jersey, 08084, United States

Location

Memory Enhancement Center of NJ

Toms River, New Jersey, 08755, United States

Location

Upstate Clinical Research, LLC

Albany, New York, 12205, United States

Location

Dent Neurological Institute

Amherst, New York, 14226, United States

Location

Neurological Care of Central NY

Liverpool, New York, 13088, United States

Location

Eastside Comprehensive medical Center, LLC

New York, New York, 10021, United States

Location

Nathan S. Kline Institute for Psychiatric Research

Orangeburg, New York, 10962, United States

Location

Behavioral Medical Research of Staten Island

Staten Island, New York, 10305, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

The Burke Rehabilitation Hospital

White Plains, New York, 10605, United States

Location

Alzheimer's Memory Center

Charlotte, North Carolina, 28211, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Clinical Trials of America, Inc.

Winston-Salem, North Carolina, 27103, United States

Location

Valley Medical Research

Centerville, Ohio, 45459, United States

Location

University Neurology, Inc.

Cincinnati, Ohio, 45219, United States

Location

Cognitive Assessment Clinic

Portland, Oregon, 97225, United States

Location

Lehigh Center for Clinical Research

Allentown, Pennsylvania, 18104, United States

Location

Paramount Clinical Research

Bridgeville, Pennsylvania, 15017, United States

Location

Department of Veterans Affairs Medical Center

Coatesville, Pennsylvania, 19320, United States

Location

Westmoreland Neurology associates, Inc.

Greensburg, Pennsylvania, 15601, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Research Protocol Management Specialists

Pittsburgh, Pennsylvania, 15243, United States

Location

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, 02914, United States

Location

Psychiatric Consultants, PC

Franklin, Tennessee, 37067, United States

Location

Volunteer Research Group

Knoxville, Tennessee, 37920, United States

Location

Jacinto Medical Group, PA

Baytown, Texas, 77521, United States

Location

Future Search Trials

Dallas, Texas, 75231, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

Innovative Clinical Trials

San Antonio, Texas, 78229, United States

Location

Radiant Research Inc.

San Antonio, Texas, 78229, United States

Location

Grayline Clinical Drug Trials

Wichita Falls, Texas, 76309, United States

Location

The Memory Clinic

Bennington, Vermont, 05201, United States

Location

TLC Neurology, P.L.L.C

Arlington, Virginia, 22205, United States

Location

UVA Neurology

Charlottesville, Virginia, 22903, United States

Location

Neurological Associates, Inc.

Richmond, Virginia, 23226, United States

Location

Alliance Research Group, LLC

Richmond, Virginia, 23230, United States

Location

The Center for Excellence in Aging and Geriatric Health

Williamsburg, Virginia, 23185, United States

Location

Internal Medicine Northwest

Tacoma, Washington, 98405, United States

Location

Independent Psychiatric Consultants, SC

Waukesha, Wisconsin, 53188, United States

Location

Metro Medical Center

Bayamón, 00959, Puerto Rico

Location

INSPIRA Clinical Research

San Juan, 00918, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 25523430 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

Rivastigmine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylcarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2009
• First Posted: July 29, 2009
• Study Start: July 1, 2009
• Primary Completion: January 1, 2012
• Study Completion: June 1, 2012
• Last Updated: August 28, 2013
• Results First Posted: February 11, 2013

Record last verified: 2013-08

Locations

PR (2); US (93)