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)
Alzheimer's Disease
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's disease, dementia, Alzheimer's type
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.
Sites / Locations
- Clinical Research Advantage Inc./Neurological. Physicians of Arizona, Inc
- Northwest Neuro Specialist, PLLC
- IHS Research Center Inc.
- East Bay Physicians Medical Group
- ATP Clinical Research, Inc.
- Neuro Pain Medical Center
- Margolin Brain Institute
- Collaborative Neuroscience Network Inc.
- PCND Neuroscience Research Institute Inc./The Center for Memory and Aging
- Anderson Clinical Research
- San Francisco Clinical Research Center
- Neuropsychiatric Research Center of Orange County
- California Neuroscience Research Medical Group, Inc.
- Viking Clinical Research Center
- Collaborative Neuroscience Network, Inc
- Senior Care of Colorado
- Clinical Research Studies Dept. of Clinical Science and Medical Education
- Quantum Laboratories Memory Disorder Center
- Brain Matters Research, Inc.
- Neurologic Consultants, PA
- White-Wilson Medical Center
- MD Clinical
- Sunrise Clinical Research, Inc
- Compass Research, LLC
- Integrity Research, LLC
- Neurostudies, Inc.
- Stedman Clinical Trials, LLC
- Center for Clinical Trials
- Premiere Research Institute
- Alexian Brothers Neuroscience Institute
- Elkhart Clinic, LLC
- Indiana University Medical Center
- University of Kansas Medical Center
- MidAmerica Neuroscience Reseach Institute
- Precise Clinical Research Solutions
- LSU Health Sciences Center/Department of Psychiatry Psychopharmacology Research Clinic
- J. Gary Booker, MD APMC
- Pharmasite Research
- The Samuel and Alexia Bratton Memory Clinic, William Hill Inc
- Neuroscience Research of the Berkshires
- Michigan Neurology Associates, P.C.
- Wayne State University/Detroit Medical center
- West Michigan Clinical Research
- Orr & Associates Memory and Geriatric Behavioral Health Clinic
- Neurological Research Clinic, Hattiesburg Clinic
- The Neuroscience Center
- Sky, LLC.
- St. Louis University
- Premier Psychiatric Research Institute, LLC
- University of Nebraska Medical Center
- Memory Enhancement Center of America, Inc.
- Alzheimer's Research Corporation
- NeuroCognitive Institute
- UMDNJ-Robert Wood Johnson Medical Center
- UMDNJ-School of Osteopathic Medicine Center
- Memory Enhancement Center of NJ
- Upstate Clinical Research, LLC
- Dent Neurological Institute
- Neurological Care of Central NY
- Eastside Comprehensive medical Center, LLC
- Nathan S. Kline Institute for Psychiatric Research
- Behavioral Medical Research of Staten Island
- Richmond Behavioral Associates
- The Burke Rehabilitation Hospital
- Alzheimer's Memory Center
- Duke University Medical Center
- Clinical Trials of America, Inc.
- Valley Medical Research
- University Neurology, Inc.
- Cognitive Assessment Clinic
- Lehigh Center for Clinical Research
- Paramount Clinical Research
- Department of Veterans Affairs Medical Center
- Westmoreland Neurology associates, Inc.
- Thomas Jefferson University
- Research Protocol Management Specialists
- Rhode Island Mood & Memory Research Institute
- Psychiatric Consultants, PC
- Volunteer Research Group
- Jacinto Medical Group, PA
- Future Search Trials
- University of Texas Medical Branch
- Innovative Clinical Trials
- Radiant Research Inc.
- Grayline Clinical Drug Trials
- The Memory Clinic
- TLC Neurology, P.L.L.C
- UVA Neurology
- Neurological Associates, Inc.
- Alliance Research Group, LLC
- The Center for Excellence in Aging and Geriatric Health
- Internal Medicine Northwest
- Independent Psychiatric Consultants, SC
- Metro Medical Center
- INSPIRA Clinical Research
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Rivastigmine 13.3 mg/24 h transdermal patch
Rivastigmine 4.6 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.
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.