Clinical trial NCT00948766: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alzheimer's Disease
Keywords: Alzheimer's disease
dementia
Alzheimer's type
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-07-29
Enrollment: 716
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: Baseline of the core study to Week 24 of the core study
measure: Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24
timeFrame: Baseline of the core study to Week 24 of the core study
Secondary outcomes:
measure: Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24
timeFrame: Baseline of the core study to Week 24 of the core study
measure: Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24
timeFrame: Baseline of the core study to Week 24 of the core study
measure: 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
timeFrame: Baseline of the core study to Week 24 of the extension study
measure: Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24
timeFrame: Baseline of the core study to Week 24 of the extension study
measure: Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24
timeFrame: Baseline of the core study to Week 24 of the extension study
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Clinical Research Advantage Inc./Neurological. Physicians of Arizona, Inc
state: Arizona
city: Tucson
country: United States
facility: Northwest Neuro Specialist, PLLC
state: Arizona
city: Conway
country: United States
facility: IHS Research Center Inc.
state: Arkansas
city: Berkeley
country: United States
facility: East Bay Physicians Medical Group
state: California
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: Fresno
country: United States
facility: Neuro Pain Medical Center
state: California
city: Fresno
country: United States
facility: Margolin Brain Institute
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network Inc.
state: California
city: Poway
country: United States
facility: PCND Neuroscience Research Institute Inc./The Center for Memory and Aging
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research
state: California
city: San Francisco
country: United States
facility: San Francisco Clinical Research Center
state: California
city: Santa Ana
country: United States
facility: Neuropsychiatric Research Center of Orange County
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group, Inc.
state: California
city: Temecula
country: United States
facility: Viking Clinical Research Center
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network, Inc
state: California
city: Aurora
country: United States
facility: Senior Care of Colorado
state: Colorado
city: Boca Raton
country: United States
facility: Clinical Research Studies Dept. of Clinical Science and Medical Education
state: Florida
city: Deerfield Beach
country: United States
facility: Quantum Laboratories Memory Disorder Center
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research, Inc.
state: Florida
city: Fort Lauderdale
country: United States
facility: Neurologic Consultants, PA
state: Florida
city: Fort Walton Beach
country: United States
facility: White-Wilson Medical Center
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Hollywood
country: United States
facility: Sunrise Clinical Research, Inc
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Pensacola
country: United States
facility: Integrity Research, LLC
state: Florida
city: Port Charlotte
country: United States
facility: Neurostudies, Inc.
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials, LLC
state: Florida
city: Venice
country: United States
facility: Center for Clinical Trials
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neuroscience Institute
state: Illinois
city: Elkhart
country: United States
facility: Elkhart Clinic, LLC
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lenexa
country: United States
facility: MidAmerica Neuroscience Reseach Institute
state: Kansas
city: Manhattan
country: United States
facility: Precise Clinical Research Solutions
state: Kansas
city: Shreveport
country: United States
facility: LSU Health Sciences Center/Department of Psychiatry Psychopharmacology Research Clinic
state: Louisiana
city: Shreveport
country: United States
facility: J. Gary Booker, MD APMC
state: Louisiana
city: Baltimore
country: United States
facility: Pharmasite Research
state: Maryland
city: Easton
country: United States
facility: The Samuel and Alexia Bratton Memory Clinic, William Hill Inc
state: Maryland
city: Pittsfield
country: United States
facility: Neuroscience Research of the Berkshires
state: Massachusetts
city: Clinton Township
country: United States
facility: Michigan Neurology Associates, P.C.
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Detroit Medical center
state: Michigan
city: Muskegon
country: United States
facility: West Michigan Clinical Research
state: Michigan
city: St. Paul
country: United States
facility: Orr & Associates Memory and Geriatric Behavioral Health Clinic
state: Minnesota
city: Hattiesburg
country: United States
facility: Neurological Research Clinic, Hattiesburg Clinic
state: Mississippi
city: Ocean Springs
country: United States
facility: The Neuroscience Center
state: Mississippi
city: St Louis
country: United States
facility: Sky, LLC.
state: Missouri
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: Lincoln
country: United States
facility: Premier Psychiatric Research Institute, LLC
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Eatontown
country: United States
facility: Memory Enhancement Center of America, Inc.
state: New Jersey
city: Manchester
country: United States
facility: Alzheimer's Research Corporation
state: New Jersey
city: Mt. Arlington
country: United States
facility: NeuroCognitive Institute
state: New Jersey
city: New Brunswick
country: United States
facility: UMDNJ-Robert Wood Johnson Medical Center
state: New Jersey
city: Stratford
country: United States
facility: UMDNJ-School of Osteopathic Medicine Center
state: New Jersey
city: Toms River
country: United States
facility: Memory Enhancement Center of NJ
state: New Jersey
city: Albany
country: United States
facility: Upstate Clinical Research, LLC
state: New York
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: Liverpool
country: United States
facility: Neurological Care of Central NY
state: New York
city: New York
country: United States
facility: Eastside Comprehensive medical Center, LLC
state: New York
city: Orangeburg
country: United States
facility: Nathan S. Kline Institute for Psychiatric Research
state: New York
city: Staten Island
country: United States
facility: Behavioral Medical Research of Staten Island
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: White Plains
country: United States
facility: The Burke Rehabilitation Hospital
state: New York
city: Charlotte
country: United States
facility: Alzheimer's Memory Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston Salem
country: United States
facility: Clinical Trials of America, Inc.
state: North Carolina
city: Centerville
country: United States
facility: Valley Medical Research
state: Ohio
city: Cincinnati
country: United States
facility: University Neurology, Inc.
state: Ohio
city: Portland
country: United States
facility: Cognitive Assessment Clinic
state: Oregon
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Bridgeville
country: United States
facility: Paramount Clinical Research
state: Pennsylvania
city: Coatesville
country: United States
facility: Department of Veterans Affairs Medical Center
state: Pennsylvania
city: Greensburg
country: United States
facility: Westmoreland Neurology associates, Inc.
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburg
country: United States
facility: Research Protocol Management Specialists
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Mood & Memory Research Institute
state: Rhode Island
city: Franklin
country: United States
facility: Psychiatric Consultants, PC
state: Tennessee
city: Knoxville
country: United States
facility: Volunteer Research Group
state: Tennessee
city: Baytown
country: United States
facility: Jacinto Medical Group, PA
state: Texas
city: Dallas
country: United States
facility: Future Search Trials
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: San Antonio
country: United States
facility: Innovative Clinical Trials
state: Texas
city: San Antonio
country: United States
facility: Radiant Research Inc.
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Clinical Drug Trials
state: Texas
city: Bennington
country: United States
facility: The Memory Clinic
state: Vermont
city: Arlington
country: United States
facility: TLC Neurology, P.L.L.C
state: Virginia
city: Charlottesville
country: United States
facility: UVA Neurology
state: Virginia
city: Richmond
country: United States
facility: Neurological Associates, Inc.
state: Virginia
city: Richmond
country: United States
facility: Alliance Research Group, LLC
state: Virginia
city: Williamsburg
country: United States
facility: The Center for Excellence in Aging and Geriatric Health
state: Virginia
city: Tacoma
country: United States
facility: Internal Medicine Northwest
state: Washington
city: Waukesha
country: United States
facility: Independent Psychiatric Consultants, SC
state: Wisconsin
city: Bayamon
country: Puerto Rico
facility: Metro Medical Center
city: San Juan
country: Puerto Rico
facility: INSPIRA Clinical Research
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.