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
- Conditions
- Alzheimer's Disease
- Interventions
- Registration Number
- NCT00948766
- Lead Sponsor
- Novartis
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 716
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rivastigmine 13.3 mg/24 h transdermal patch Rivastigmine 13.3 mg/24 h (15 cm^2) 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. Rivastigmine 4.6 mg/24 h transdermal patch Rivastigmine 4.6 mg/24 h (5 cm^2) 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. Rivastigmine 13.3 mg/24 h transdermal patch Rivastigmine 4.6 mg/24 h (5 cm^2) 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. Rivastigmine 13.3 mg/24 h transdermal patch Rivastigmine 9.5 mg/24 h (10 cm^2) 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. Rivastigmine 13.3 mg/24 h transdermal patch Placebo 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. Rivastigmine 4.6 mg/24 h transdermal patch Placebo 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.
- Primary Outcome Measures
Name Time Method 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 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 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
Name Time Method 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 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 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 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 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 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.
Trial Locations
- Locations (95)
University Neurology, Inc.
🇺🇸Cincinnati, Ohio, United States
MidAmerica Neuroscience Reseach Institute
🇺🇸Lenexa, Kansas, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, 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
Wayne State University/Detroit Medical center
🇺🇸Detroit, Michigan, United States
Psychiatric Consultants, PC
🇺🇸Franklin, Tennessee, United States
Volunteer Research Group
🇺🇸Knoxville, Tennessee, United States
NeuroCognitive Institute
🇺🇸Mt. Arlington, New Jersey, United States
Anderson Clinical Research
🇺🇸Redlands, California, United States
Neuropsychiatric Research Center of Orange County
🇺🇸Santa Ana, California, United States
Center for Clinical Trials
🇺🇸Venice, Florida, United States
Precise Clinical Research Solutions
🇺🇸Manhattan, Kansas, United States
IHS Research Center Inc.
🇺🇸Conway, Arkansas, United States
ATP Clinical Research, Inc.
🇺🇸Costa Mesa, California, United States
East Bay Physicians Medical Group
🇺🇸Berkeley, California, United States
PCND Neuroscience Research Institute Inc./The Center for Memory and Aging
🇺🇸Poway, California, United States
Neuro Pain Medical Center
🇺🇸Fresno, California, United States
Memory Enhancement Center of NJ
🇺🇸Toms River, New Jersey, United States
Neurologic Consultants, PA
🇺🇸Fort Lauderdale, Florida, United States
UMDNJ-School of Osteopathic Medicine Center
🇺🇸Stratford, New Jersey, United States
White-Wilson Medical Center
🇺🇸Fort Walton Beach, Florida, United States
Clinical Research Studies Dept. of Clinical Science and Medical Education
🇺🇸Boca Raton, Florida, United States
Sky, LLC.
🇺🇸St Louis, Missouri, United States
Neuroscience Research of the Berkshires
🇺🇸Pittsfield, Massachusetts, United States
Sunrise Clinical Research, Inc
🇺🇸Hollywood, Florida, United States
Neurological Care of Central NY
🇺🇸Liverpool, New York, United States
MD Clinical
🇺🇸Hallandale Beach, Florida, United States
Pharmasite Research
🇺🇸Baltimore, Maryland, United States
Neurological Research Clinic, Hattiesburg Clinic
🇺🇸Hattiesburg, Mississippi, United States
Clinical Trials of America, Inc.
🇺🇸Winston Salem, North Carolina, United States
UVA Neurology
🇺🇸Charlottesville, Virginia, United States
Jacinto Medical Group, PA
🇺🇸Baytown, Texas, United States
Lehigh Center for Clinical Research
🇺🇸Allentown, Pennsylvania, United States
Future Search Trials
🇺🇸Dallas, Texas, United States
Valley Medical Research
🇺🇸Centerville, Ohio, United States
Research Protocol Management Specialists
🇺🇸Pittsburg, Pennsylvania, United States
Neurological Associates, Inc.
🇺🇸Richmond, Virginia, United States
INSPIRA Clinical Research
🇵🇷San Juan, Puerto Rico
The Memory Clinic
🇺🇸Bennington, Vermont, United States
Metro Medical Center
🇵🇷Bayamon, Puerto Rico
Eastside Comprehensive medical Center, LLC
🇺🇸New York, New York, United States
Grayline Clinical Drug Trials
🇺🇸Wichita Falls, Texas, United States
Neurostudies, Inc.
🇺🇸Port Charlotte, Florida, United States
Northwest Neuro Specialist, PLLC
🇺🇸Tucson, Arizona, United States
Department of Veterans Affairs Medical Center
🇺🇸Coatesville, Pennsylvania, United States
Westmoreland Neurology associates, Inc.
🇺🇸Greensburg, Pennsylvania, United States
TLC Neurology, P.L.L.C
🇺🇸Arlington, Virginia, United States
California Neuroscience Research Medical Group, Inc.
🇺🇸Sherman Oaks, California, United States
Indiana University Medical Center
🇺🇸Indianapolis, Indiana, United States
LSU Health Sciences Center/Department of Psychiatry Psychopharmacology Research Clinic
🇺🇸Shreveport, Louisiana, United States
The Neuroscience Center
🇺🇸Ocean Springs, Mississippi, United States
The Burke Rehabilitation Hospital
🇺🇸White Plains, New York, United States
Viking Clinical Research Center
🇺🇸Temecula, California, United States
Clinical Research Advantage Inc./Neurological. Physicians of Arizona, Inc
🇺🇸Tempe, Arizona, United States
Collaborative Neuroscience Network Inc.
🇺🇸Garden Grove, California, United States
Collaborative Neuroscience Network, Inc
🇺🇸Torrance, California, United States
Margolin Brain Institute
🇺🇸Fresno, California, United States
Integrity Research, LLC
🇺🇸Pensacola, Florida, United States
Alexian Brothers Neuroscience Institute
🇺🇸Elk Grove Village, Illinois, United States
The Samuel and Alexia Bratton Memory Clinic, William Hill Inc
🇺🇸Easton, Maryland, United States
J. Gary Booker, MD APMC
🇺🇸Shreveport, Louisiana, United States
Orr & Associates Memory and Geriatric Behavioral Health Clinic
🇺🇸St. Paul, Minnesota, United States
West Michigan Clinical Research
🇺🇸Muskegon, Michigan, United States
UMDNJ-Robert Wood Johnson Medical Center
🇺🇸New Brunswick, New Jersey, United States
Alzheimer's Research Corporation
🇺🇸Manchester, New Jersey, United States
Upstate Clinical Research, LLC
🇺🇸Albany, New York, United States
Nathan S. Kline Institute for Psychiatric Research
🇺🇸Orangeburg, New York, United States
Alzheimer's Memory Center
🇺🇸Charlotte, North Carolina, United States
Paramount Clinical Research
🇺🇸Bridgeville, Pennsylvania, United States
Behavioral Medical Research of Staten Island
🇺🇸Staten Island, New York, United States
Rhode Island Mood & Memory Research Institute
🇺🇸East Providence, Rhode Island, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
The Center for Excellence in Aging and Geriatric Health
🇺🇸Williamsburg, Virginia, United States
Alliance Research Group, LLC
🇺🇸Richmond, Virginia, United States
Internal Medicine Northwest
🇺🇸Tacoma, Washington, United States
Independent Psychiatric Consultants, SC
🇺🇸Waukesha, Wisconsin, United States
Quantum Laboratories Memory Disorder Center
🇺🇸Deerfield Beach, Florida, United States
Brain Matters Research, Inc.
🇺🇸Delray Beach, Florida, United States
St. Louis University
🇺🇸St. Louis, Missouri, United States
Richmond Behavioral Associates
🇺🇸Staten Island, New York, United States
Elkhart Clinic, LLC
🇺🇸Elkhart, Indiana, United States
Premiere Research Institute
🇺🇸West Palm Beach, Florida, United States
Premier Psychiatric Research Institute, LLC
🇺🇸Lincoln, Nebraska, United States
Senior Care of Colorado
🇺🇸Aurora, Colorado, United States
Compass Research, LLC
🇺🇸Orlando, Florida, United States
Stedman Clinical Trials, LLC
🇺🇸Tampa, Florida, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Cognitive Assessment Clinic
🇺🇸Portland, Oregon, United States
Michigan Neurology Associates, P.C.
🇺🇸Clinton Township, Michigan, United States
Memory Enhancement Center of America, Inc.
🇺🇸Eatontown, New Jersey, United States
Dent Neurological Institute
🇺🇸Amherst, New York, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States