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

Alzheimer's Disease Clinical Trial

— ACTION  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00948766
• Other study ID #: CENA713DUS44
• Status: Completed
• Phase: Phase 4
• First received: July 28, 2009
• Last updated: August 19, 2013
• Start date: July 2009
• Est. completion date: June 2012

Study information

• Verified date: August 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT01054755

Recruitment information / eligibility

• Status: Completed
• Enrollment: 716
• Est. completion date: June 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Puerto Rico	Metro Medical Center	Bayamon
Puerto Rico	INSPIRA Clinical Research	San Juan
United States	Upstate Clinical Research, LLC	Albany	New York
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	Dent Neurological Institute	Amherst	New York
United States	TLC Neurology, P.L.L.C	Arlington	Virginia
United States	Senior Care of Colorado	Aurora	Colorado
United States	Pharmasite Research	Baltimore	Maryland
United States	Jacinto Medical Group, PA	Baytown	Texas
United States	The Memory Clinic	Bennington	Vermont
United States	East Bay Physicians Medical Group	Berkeley	California
United States	Clinical Research Studies Dept. of Clinical Science and Medical Education	Boca Raton	Florida
United States	Paramount Clinical Research	Bridgeville	Pennsylvania
United States	Valley Medical Research	Centerville	Ohio
United States	Alzheimer's Memory Center	Charlotte	North Carolina
United States	UVA Neurology	Charlottesville	Virginia
United States	University Neurology, Inc.	Cincinnati	Ohio
United States	Michigan Neurology Associates, P.C.	Clinton Township	Michigan
United States	Department of Veterans Affairs Medical Center	Coatesville	Pennsylvania
United States	IHS Research Center Inc.	Conway	Arkansas
United States	ATP Clinical Research, Inc.	Costa Mesa	California
United States	Future Search Trials	Dallas	Texas
United States	Quantum Laboratories Memory Disorder Center	Deerfield Beach	Florida
United States	Brain Matters Research, Inc.	Delray Beach	Florida
United States	Wayne State University/Detroit Medical center	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island
United States	The Samuel and Alexia Bratton Memory Clinic, William Hill Inc	Easton	Maryland
United States	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey
United States	Alexian Brothers Neuroscience Institute	Elk Grove Village	Illinois
United States	Elkhart Clinic, LLC	Elkhart	Indiana
United States	Neurologic Consultants, PA	Fort Lauderdale	Florida
United States	White-Wilson Medical Center	Fort Walton Beach	Florida
United States	Psychiatric Consultants, PC	Franklin	Tennessee
United States	Margolin Brain Institute	Fresno	California
United States	Neuro Pain Medical Center	Fresno	California
United States	University of Texas Medical Branch	Galveston	Texas
United States	Collaborative Neuroscience Network Inc.	Garden Grove	California
United States	Westmoreland Neurology associates, Inc.	Greensburg	Pennsylvania
United States	MD Clinical	Hallandale Beach	Florida
United States	Neurological Research Clinic, Hattiesburg Clinic	Hattiesburg	Mississippi
United States	Sunrise Clinical Research, Inc	Hollywood	Florida
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Volunteer Research Group	Knoxville	Tennessee
United States	MidAmerica Neuroscience Reseach Institute	Lenexa	Kansas
United States	Premier Psychiatric Research Institute, LLC	Lincoln	Nebraska
United States	Neurological Care of Central NY	Liverpool	New York
United States	Alzheimer's Research Corporation	Manchester	New Jersey
United States	Precise Clinical Research Solutions	Manhattan	Kansas
United States	NeuroCognitive Institute	Mt. Arlington	New Jersey
United States	West Michigan Clinical Research	Muskegon	Michigan
United States	UMDNJ-Robert Wood Johnson Medical Center	New Brunswick	New Jersey
United States	Eastside Comprehensive medical Center, LLC	New York	New York
United States	The Neuroscience Center	Ocean Springs	Mississippi
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Nathan S. Kline Institute for Psychiatric Research	Orangeburg	New York
United States	Compass Research, LLC	Orlando	Florida
United States	Integrity Research, LLC	Pensacola	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Research Protocol Management Specialists	Pittsburg	Pennsylvania
United States	Neuroscience Research of the Berkshires	Pittsfield	Massachusetts
United States	Neurostudies, Inc.	Port Charlotte	Florida
United States	Cognitive Assessment Clinic	Portland	Oregon
United States	PCND Neuroscience Research Institute Inc./The Center for Memory and Aging	Poway	California
United States	Anderson Clinical Research	Redlands	California
United States	Alliance Research Group, LLC	Richmond	Virginia
United States	Neurological Associates, Inc.	Richmond	Virginia
United States	Innovative Clinical Trials	San Antonio	Texas
United States	Radiant Research Inc.	San Antonio	Texas
United States	San Francisco Clinical Research Center	San Francisco	California
United States	Neuropsychiatric Research Center of Orange County	Santa Ana	California
United States	California Neuroscience Research Medical Group, Inc.	Sherman Oaks	California
United States	J. Gary Booker, MD APMC	Shreveport	Louisiana
United States	LSU Health Sciences Center/Department of Psychiatry Psychopharmacology Research Clinic	Shreveport	Louisiana
United States	Sky, LLC.	St Louis	Missouri
United States	St. Louis University	St. Louis	Missouri
United States	Orr & Associates Memory and Geriatric Behavioral Health Clinic	St. Paul	Minnesota
United States	Behavioral Medical Research of Staten Island	Staten Island	New York
United States	Richmond Behavioral Associates	Staten Island	New York
United States	UMDNJ-School of Osteopathic Medicine Center	Stratford	New Jersey
United States	Internal Medicine Northwest	Tacoma	Washington
United States	Stedman Clinical Trials, LLC	Tampa	Florida
United States	Viking Clinical Research Center	Temecula	California
United States	Clinical Research Advantage Inc./Neurological. Physicians of Arizona, Inc	Tempe	Arizona
United States	Memory Enhancement Center of NJ	Toms River	New Jersey
United States	Collaborative Neuroscience Network, Inc	Torrance	California
United States	Northwest Neuro Specialist, PLLC	Tucson	Arizona
United States	Center for Clinical Trials	Venice	Florida
United States	Independent Psychiatric Consultants, SC	Waukesha	Wisconsin
United States	Premiere Research Institute	West Palm Beach	Florida
United States	The Burke Rehabilitation Hospital	White Plains	New York
United States	Grayline Clinical Drug Trials	Wichita Falls	Texas
United States	The Center for Excellence in Aging and Geriatric Health	Williamsburg	Virginia
United States	Clinical Trials of America, Inc.	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24	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.	Baseline of the core study to Week 24 of the core study	No
Secondary	Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24	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.	Baseline of the core study to Week 24 of the core study	No
Secondary	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	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 extension study	No
Secondary	Extension 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 extension study	No
Secondary	Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24	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.	Baseline of the core study to Week 24 of the extension study	No

External Links

•   Online Screening Questionnaire is available