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

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00948766
• Collaborator: (none)
• Enrollment: 716
• Locations: 95
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	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	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 716 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: Jul 1, 2009
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rivastigmine 13.3 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.	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.; Other Names: ENA713D Exelon Exelon patch ; Drug: 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.; Other Names: ENA713D Exelon Exelon path ; Drug: 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.; Other Names: ENA713D Exelon Exelon patch ; Drug: 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.
Active Comparator: Rivastigmine 4.6 mg/24 h transdermal patch 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); Rivastigmine was supplied in a 5 cm^2 patch which released 4.6 mg/24 h. Patches were changed daily.; Other Names: ENA713D Exelon Exelon patch ; Drug: 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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Advantage Inc./Neurological. Physicians of Arizona, Inc	Tempe	Arizona	United States	85282
2	Northwest Neuro Specialist, PLLC	Tucson	Arizona	United States	86741
3	IHS Research Center Inc.	Conway	Arkansas	United States	72034
4	East Bay Physicians Medical Group	Berkeley	California	United States	94705
5	ATP Clinical Research, Inc.	Costa Mesa	California	United States	92626
6	Neuro Pain Medical Center	Fresno	California	United States	90502
7	Margolin Brain Institute	Fresno	California	United States	93720
8	Collaborative Neuroscience Network Inc.	Garden Grove	California	United States	92845
9	PCND Neuroscience Research Institute Inc./The Center for Memory and Aging	Poway	California	United States	92064
10	Anderson Clinical Research	Redlands	California	United States	92374
11	San Francisco Clinical Research Center	San Francisco	California	United States	94109
12	Neuropsychiatric Research Center of Orange County	Santa Ana	California	United States	92701
13	California Neuroscience Research Medical Group, Inc.	Sherman Oaks	California	United States	91403
14	Viking Clinical Research Center	Temecula	California	United States	92591
15	Collaborative Neuroscience Network, Inc	Torrance	California	United States	90502
16	Senior Care of Colorado	Aurora	Colorado	United States	80014
17	Clinical Research Studies Dept. of Clinical Science and Medical Education	Boca Raton	Florida	United States	33431
18	Quantum Laboratories Memory Disorder Center	Deerfield Beach	Florida	United States	33064
19	Brain Matters Research, Inc.	Delray Beach	Florida	United States	33445
20	Neurologic Consultants, PA	Fort Lauderdale	Florida	United States	33308
21	White-Wilson Medical Center	Fort Walton Beach	Florida	United States	32547
22	MD Clinical	Hallandale Beach	Florida	United States	33009
23	Sunrise Clinical Research, Inc	Hollywood	Florida	United States	33021
24	Compass Research, LLC	Orlando	Florida	United States	32806
25	Integrity Research, LLC	Pensacola	Florida	United States	32514
26	Neurostudies, Inc.	Port Charlotte	Florida	United States	33952
27	Stedman Clinical Trials, LLC	Tampa	Florida	United States	33613
28	Center for Clinical Trials	Venice	Florida	United States	34285
29	Premiere Research Institute	West Palm Beach	Florida	United States	33407
30	Alexian Brothers Neuroscience Institute	Elk Grove Village	Illinois	United States	60007
31	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514
32	Indiana University Medical Center	Indianapolis	Indiana	United States	46202
33	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
34	MidAmerica Neuroscience Reseach Institute	Lenexa	Kansas	United States	66214
35	Precise Clinical Research Solutions	Manhattan	Kansas	United States	66502
36	LSU Health Sciences Center/Department of Psychiatry Psychopharmacology Research Clinic	Shreveport	Louisiana	United States	71103
37	J. Gary Booker, MD APMC	Shreveport	Louisiana	United States	71104
38	Pharmasite Research	Baltimore	Maryland	United States	21208
39	The Samuel and Alexia Bratton Memory Clinic, William Hill Inc	Easton	Maryland	United States	21601
40	Neuroscience Research of the Berkshires	Pittsfield	Massachusetts	United States	01201
41	Michigan Neurology Associates, P.C.	Clinton Township	Michigan	United States	48035
42	Wayne State University/Detroit Medical center	Detroit	Michigan	United States	48201
43	West Michigan Clinical Research	Muskegon	Michigan	United States	49442
44	Orr & Associates Memory and Geriatric Behavioral Health Clinic	St. Paul	Minnesota	United States	55114
45	Neurological Research Clinic, Hattiesburg Clinic	Hattiesburg	Mississippi	United States	39401
46	The Neuroscience Center	Ocean Springs	Mississippi	United States	39564
47	Sky, LLC.	St Louis	Missouri	United States	63117
48	St. Louis University	St. Louis	Missouri	United States	63104
49	Premier Psychiatric Research Institute, LLC	Lincoln	Nebraska	United States	68510
50	University of Nebraska Medical Center	Omaha	Nebraska	United States	68105
51	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey	United States	07724
52	Alzheimer's Research Corporation	Manchester	New Jersey	United States	08759
53	NeuroCognitive Institute	Mt. Arlington	New Jersey	United States	07856
54	UMDNJ-Robert Wood Johnson Medical Center	New Brunswick	New Jersey	United States	08903
55	UMDNJ-School of Osteopathic Medicine Center	Stratford	New Jersey	United States	08084
56	Memory Enhancement Center of NJ	Toms River	New Jersey	United States	08755
57	Upstate Clinical Research, LLC	Albany	New York	United States	12205
58	Dent Neurological Institute	Amherst	New York	United States	14226
59	Neurological Care of Central NY	Liverpool	New York	United States	13088
60	Eastside Comprehensive medical Center, LLC	New York	New York	United States	10021
61	Nathan S. Kline Institute for Psychiatric Research	Orangeburg	New York	United States	10962
62	Behavioral Medical Research of Staten Island	Staten Island	New York	United States	10305
63	Richmond Behavioral Associates	Staten Island	New York	United States	10312
64	The Burke Rehabilitation Hospital	White Plains	New York	United States	10605
65	Alzheimer's Memory Center	Charlotte	North Carolina	United States	28211
66	Duke University Medical Center	Durham	North Carolina	United States	27710
67	Clinical Trials of America, Inc.	Winston Salem	North Carolina	United States	27103
68	Valley Medical Research	Centerville	Ohio	United States	45459
69	University Neurology, Inc.	Cincinnati	Ohio	United States	45219
70	Cognitive Assessment Clinic	Portland	Oregon	United States	97225
71	Lehigh Center for Clinical Research	Allentown	Pennsylvania	United States	18104
72	Paramount Clinical Research	Bridgeville	Pennsylvania	United States	15017
73	Department of Veterans Affairs Medical Center	Coatesville	Pennsylvania	United States	19320
74	Westmoreland Neurology associates, Inc.	Greensburg	Pennsylvania	United States	15601
75	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
76	Research Protocol Management Specialists	Pittsburg	Pennsylvania	United States	15243
77	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island	United States	02914
78	Psychiatric Consultants, PC	Franklin	Tennessee	United States	37067
79	Volunteer Research Group	Knoxville	Tennessee	United States	37920
80	Jacinto Medical Group, PA	Baytown	Texas	United States	77521
81	Future Search Trials	Dallas	Texas	United States	75231
82	University of Texas Medical Branch	Galveston	Texas	United States	77555
83	Innovative Clinical Trials	San Antonio	Texas	United States	78229
84	Radiant Research Inc.	San Antonio	Texas	United States	78229
85	Grayline Clinical Drug Trials	Wichita Falls	Texas	United States	76309
86	The Memory Clinic	Bennington	Vermont	United States	05201
87	TLC Neurology, P.L.L.C	Arlington	Virginia	United States	22205
88	UVA Neurology	Charlottesville	Virginia	United States	22903
89	Neurological Associates, Inc.	Richmond	Virginia	United States	23226
90	Alliance Research Group, LLC	Richmond	Virginia	United States	23230
91	The Center for Excellence in Aging and Geriatric Health	Williamsburg	Virginia	United States	23185
92	Internal Medicine Northwest	Tacoma	Washington	United States	98405
93	Independent Psychiatric Consultants, SC	Waukesha	Wisconsin	United States	53188
94	Metro Medical Center	Bayamon		Puerto Rico	00959
95	INSPIRA Clinical Research	San Juan		Puerto Rico	00918

Sponsors and Collaborators

• Novartis

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Online Screening Questionnaire is available

Publications

None provided.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT00948766
• Other Study ID Numbers: CENA713DUS44; NCT01054755
• First Posted: Jul 29, 2009
• Last Update Posted: Aug 28, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Novartis: Alzheimer's disease; dementia; Alzheimer's type
• Additional relevant MeSH terms: Alzheimer Disease; Dementia; Rivastigmine

Study Results

Participant Flow

Pre-assignment Detail	One patient in each treatment group in the core study and one patient in the treatment group in the extension study did not receive study medication; they were not included in the safety set.

Arm/Group Title	Rivastigmine 13.3 mg/24 h Transdermal Patch	Rivastigmine 4.6 mg/24 h Transdermal Patch
Arm/Group Description	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).
Period Title: Core Study
STARTED	356	360
Exposed to Study Medication	355	359
COMPLETED	229	234
NOT COMPLETED	127	126
Period Title: Core Study
STARTED	397	0
Exposed to Study Medication	396	0
COMPLETED	306	0
NOT COMPLETED	91	0

Baseline Characteristics

Arm/Group Title	Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch	Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch	Total
Arm/Group Description	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).	Total of all reporting groups
Overall Participants	356	360	716
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	77.6 (8.69)	76.5 (9.35)	77.0 (9.04)
Sex: Female, Male (Count of Participants)
Female	227 63.8%	234 65%	461 64.4%
Male	129 36.2%	126 35%	255 35.6%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
Time Frame	Baseline of the core study to Week 24 of the core study

Outcome Measure Data

Analysis Population Description

Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.

Arm/Group Title	Rivastigmine 13.3 mg/24 h Transdermal Patch	Rivastigmine 4.6 mg/24 h Transdermal Patch
Arm/Group Description	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).
Measure Participants	310	303
Mean (Standard Deviation) [Units on a scale]	-2.6 (6.82)	-3.6 (7.68)

2. Primary Outcome

Title	Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24
Description	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.
Time Frame	Baseline of the core study to Week 24 of the core study

Outcome Measure Data

Analysis Population Description

Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.

Arm/Group Title	Rivastigmine 13.3 mg/24 h Transdermal Patch	Rivastigmine 4.6 mg/24 h Transdermal Patch
Arm/Group Description	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).
Measure Participants	313	316
Mean (Standard Deviation) [Units on a scale]	-1.6 (13.54)	-6.4 (14.01)

3. Secondary Outcome

Title	Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24
Description	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.
Time Frame	Baseline of the core study to Week 24 of the core study

Outcome Measure Data

Analysis Population Description

Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.

Arm/Group Title	Rivastigmine 13.3 mg/24 h Transdermal Patch	Rivastigmine 4.6 mg/24 h Transdermal Patch
Arm/Group Description	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).
Measure Participants	313	315
Marked improvement	1.0	1.3
Moderate improvement	3.5	3.5
Minimal improvement	20.1	11.4
No change	34.2	29.2
Minimal worsening	24.3	31.4
Moderate worsening	14.1	19.0
Marked worsening	2.9	4.1

4. Secondary Outcome

Title	Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24
Description	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.
Time Frame	Baseline of the core study to Week 24 of the core study

Outcome Measure Data

Analysis Population Description

Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.

Arm/Group Title	Rivastigmine 13.3 mg/24 h Transdermal Patch	Rivastigmine 4.6 mg/24 h Transdermal Patch
Arm/Group Description	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).
Measure Participants	313	313
Mean (Standard Deviation) [Units on a scale]	-0.4 (14.01)	1.2 (16.79)

5. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline of the core study to Week 24 of the extension study

Outcome Measure Data

Analysis Population Description

Modified full analysis set: All patients who received at least 1 application of study medication and had at least 1 efficacy assessment in the extension study. Only patients with available data were included in the analysis.

Arm/Group Title	Rivastigmine 13.3 mg/24 h Transdermal Patch
Arm/Group Description	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
Measure Participants	372
Mean (Standard Deviation) [Units on a scale]	-4.3 (8.37)

6. Secondary Outcome

Title	Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24
Description	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.
Time Frame	Baseline of the core study to Week 24 of the extension study

Outcome Measure Data

Analysis Population Description

Modified full analysis set: All patients who received at least 1 application of study medication and had at least 1 efficacy assessment in the extension study. Only patients with available data were included in the analysis.

Arm/Group Title	Rivastigmine 13.3 mg/24 h Transdermal Patch
Arm/Group Description	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
Measure Participants	379
Mean (Standard Deviation) [Units on a scale]	-5.9 (16.72)

7. Secondary Outcome

Title	Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24
Description	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.
Time Frame	Baseline of the core study to Week 24 of the extension study

Outcome Measure Data

Analysis Population Description

Modified full analysis set: All patients who received at least 1 application of study medication and had at least 1 efficacy assessment in the extension study. Only patients with available data were included in the analysis.

Arm/Group Title	Rivastigmine 13.3 mg/24 h Transdermal Patch
Arm/Group Description	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
Measure Participants	381
Marked improvement	1.8
Moderate improvement	5.0
Minimal improvement	9.7
No change	26.2
Minimal worsening	31.5
Moderate worsening	21.5
Marked worsening	4.2

Adverse Events

Time Frame	Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks).
Adverse Event Reporting Description	Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
Arm/Group Title	Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch		Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch		Extension Study: Rivastigmine 13.3 mg/24 h Transdermal Patch
Arm/Group Description	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).		Patients received rivastigmine 4.6 mg/24 h (5 cm^2).		Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
All Cause Mortality
	Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch		Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch		Extension Study: Rivastigmine 13.3 mg/24 h Transdermal Patch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch		Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch		Extension Study: Rivastigmine 13.3 mg/24 h Transdermal Patch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	82/355 (23.1%)		74/359 (20.6%)		79/396 (19.9%)
Blood and lymphatic system disorders
Anaemia	2/355 (0.6%)		0/359 (0%)		1/396 (0.3%)
Disseminated intravascular coagulation	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Cardiac disorders
Acute myocardial infarction	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Angina pectoris	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Arrhythmia	1/355 (0.3%)		1/359 (0.3%)		1/396 (0.3%)
Atrial fibrillation	0/355 (0%)		2/359 (0.6%)		2/396 (0.5%)
Bradycardia	3/355 (0.8%)		1/359 (0.3%)		2/396 (0.5%)
Bundle branch block left	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Cardiac arrest	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Cardiac failure acute	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Cardiac failure congestive	0/355 (0%)		3/359 (0.8%)		2/396 (0.5%)
Cardio-respiratory arrest	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Cardiopulmonary failure	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Coronary artery disease	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Myocardial infarction	2/355 (0.6%)		1/359 (0.3%)		1/396 (0.3%)
Sinus bradycardia	2/355 (0.6%)		0/359 (0%)		1/396 (0.3%)
Supraventricular tachycardia	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Ear and labyrinth disorders
Vertigo positional	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Gastrointestinal disorders
Abdominal pain	2/355 (0.6%)		1/359 (0.3%)		2/396 (0.5%)
Ascites	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Colitis	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Colitis ischaemic	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Constipation	0/355 (0%)		2/359 (0.6%)		1/396 (0.3%)
Diarrhoea	3/355 (0.8%)		1/359 (0.3%)		1/396 (0.3%)
Diverticulum	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Duodenal ulcer	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Dysphagia	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Faecaloma	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Gastrointestinal haemorrhage	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Hiatus hernia	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Intestinal obstruction	1/355 (0.3%)		1/359 (0.3%)		1/396 (0.3%)
Nausea	2/355 (0.6%)		0/359 (0%)		0/396 (0%)
Small intestinal obstruction	2/355 (0.6%)		0/359 (0%)		1/396 (0.3%)
Vomiting	4/355 (1.1%)		1/359 (0.3%)		2/396 (0.5%)
General disorders
Asthenia	2/355 (0.6%)		2/359 (0.6%)		2/396 (0.5%)
Chest discomfort	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Chest pain	2/355 (0.6%)		4/359 (1.1%)		5/396 (1.3%)
Fatigue	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Gait disturbance	0/355 (0%)		2/359 (0.6%)		0/396 (0%)
Malaise	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Non-cardiac chest pain	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Oedema peripheral	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Hepatobiliary disorders
Bile duct obstruction	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Biliary dyskinesia	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Hepatic cirrhosis	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Infections and infestations
Bronchitis	1/355 (0.3%)		2/359 (0.6%)		3/396 (0.8%)
Cellulitis	0/355 (0%)		2/359 (0.6%)		1/396 (0.3%)
Gastroenteritis	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Herpes zoster	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Intestinal gangrene	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Kidney infection	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Lobar pneumonia	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Pneumonia	4/355 (1.1%)		5/359 (1.4%)		5/396 (1.3%)
Pneumonia bacterial	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Sepsis	2/355 (0.6%)		1/359 (0.3%)		1/396 (0.3%)
Urinary tract infection	5/355 (1.4%)		7/359 (1.9%)		8/396 (2%)
Injury, poisoning and procedural complications
Back injury	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Chemical poisoning	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Contusion	1/355 (0.3%)		1/359 (0.3%)		1/396 (0.3%)
Excoriation	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Fall	7/355 (2%)		7/359 (1.9%)		5/396 (1.3%)
Femoral neck fracture	0/355 (0%)		2/359 (0.6%)		1/396 (0.3%)
Femur fracture	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Fractured sacrum	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Hip fracture	4/355 (1.1%)		1/359 (0.3%)		2/396 (0.5%)
Humerus fracture	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Incorrect dose administered	1/355 (0.3%)		1/359 (0.3%)		2/396 (0.5%)
Jaw fracture	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Joint dislocation	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Laceration	1/355 (0.3%)		1/359 (0.3%)		1/396 (0.3%)
Pubis fracture	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Rib fracture	0/355 (0%)		4/359 (1.1%)		2/396 (0.5%)
Road traffic accident	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Skull fracture	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Spinal compression fracture	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Subdural haematoma	4/355 (1.1%)		3/359 (0.8%)		4/396 (1%)
Ulna fracture	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Upper limb fracture	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Investigations
Blood pressure increased	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Blood pressure systolic decreased	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Cardiac enzymes increased	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Electrocardiogram T wave inversion	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
White blood cell count increased	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Metabolism and nutrition disorders
Decreased appetite	3/355 (0.8%)		0/359 (0%)		1/396 (0.3%)
Dehydration	6/355 (1.7%)		4/359 (1.1%)		6/396 (1.5%)
Failure to thrive	2/355 (0.6%)		0/359 (0%)		1/396 (0.3%)
Hypoglycaemia	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Hypovolaemia	1/355 (0.3%)		1/359 (0.3%)		1/396 (0.3%)
Malnutrition	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Rhabdomyolysis	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer metastatic	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Gastric cancer	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Nervous system disorders
Aphasia	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Balance disorder	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Carotid artery stenosis	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Cerebrovascular accident	4/355 (1.1%)		1/359 (0.3%)		4/396 (1%)
Convulsion	1/355 (0.3%)		3/359 (0.8%)		2/396 (0.5%)
Coordination abnormal	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Dementia	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Dementia Alzheimer's type	3/355 (0.8%)		0/359 (0%)		1/396 (0.3%)
Dizziness	2/355 (0.6%)		0/359 (0%)		1/396 (0.3%)
Dysstasia	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Grand mal convulsion	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Headache	2/355 (0.6%)		0/359 (0%)		1/396 (0.3%)
Hepatic encephalopathy	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Hypokinesia	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Ischaemic stroke	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Lethargy	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Loss of consciousness	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Mental impairment	0/355 (0%)		2/359 (0.6%)		2/396 (0.5%)
Pneumocephalus	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Presyncope	1/355 (0.3%)		3/359 (0.8%)		1/396 (0.3%)
Somnolence	0/355 (0%)		2/359 (0.6%)		2/396 (0.5%)
Subarachnoid haemorrhage	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Syncope	7/355 (2%)		6/359 (1.7%)		7/396 (1.8%)
Transient ischaemic attack	4/355 (1.1%)		1/359 (0.3%)		4/396 (1%)
Unresponsive to stimuli	1/355 (0.3%)		1/359 (0.3%)		2/396 (0.5%)
VIIth nerve paralysis	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Psychiatric disorders
Aggression	0/355 (0%)		3/359 (0.8%)		0/396 (0%)
Agitation	2/355 (0.6%)		6/359 (1.7%)		1/396 (0.3%)
Anxiety	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Confusional state	3/355 (0.8%)		1/359 (0.3%)		2/396 (0.5%)
Delirium	1/355 (0.3%)		1/359 (0.3%)		1/396 (0.3%)
Depression	0/355 (0%)		2/359 (0.6%)		1/396 (0.3%)
Major depression	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Mental status changes	3/355 (0.8%)		6/359 (1.7%)		5/396 (1.3%)
Mutism	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Psychotic disorder	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Psychotic disorder due to a general medical condition	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Stress	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Renal and urinary disorders
Acute prerenal failure	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Azotaemia	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Renal failure acute	3/355 (0.8%)		1/359 (0.3%)		1/396 (0.3%)
Reproductive system and breast disorders
Rectocele	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Scrotal oedema	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Chronic obstructive pulmonary disease	1/355 (0.3%)		2/359 (0.6%)		2/396 (0.5%)
Dyspnoea	2/355 (0.6%)		2/359 (0.6%)		3/396 (0.8%)
Emphysema	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Pleural effusion	0/355 (0%)		2/359 (0.6%)		0/396 (0%)
Pneumonia aspiration	2/355 (0.6%)		2/359 (0.6%)		2/396 (0.5%)
Pneumothorax	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Pulmonary cavitation	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Pulmonary embolism	2/355 (0.6%)		0/359 (0%)		1/396 (0.3%)
Respiratory distress	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Respiratory failure	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Surgical and medical procedures
Cystopexy	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Hip arthroplasty	0/355 (0%)		1/359 (0.3%)		0/396 (0%)
Hospitalisation	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Hysterectomy	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Vascular disorders
Arteriosclerosis	2/355 (0.6%)		0/359 (0%)		1/396 (0.3%)
Bloody discharge	1/355 (0.3%)		0/359 (0%)		0/396 (0%)
Deep vein thrombosis	1/355 (0.3%)		1/359 (0.3%)		0/396 (0%)
Haematoma	1/355 (0.3%)		1/359 (0.3%)		0/396 (0%)
Haemorrhage	1/355 (0.3%)		0/359 (0%)		1/396 (0.3%)
Hypertension	2/355 (0.6%)		1/359 (0.3%)		3/396 (0.8%)
Hypotension	0/355 (0%)		3/359 (0.8%)		2/396 (0.5%)
Orthostatic hypotension	2/355 (0.6%)		1/359 (0.3%)		2/396 (0.5%)
Shock	0/355 (0%)		1/359 (0.3%)		1/396 (0.3%)
Other (Not Including Serious) Adverse Events
	Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch		Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch		Extension Study: Rivastigmine 13.3 mg/24 h Transdermal Patch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	216/355 (60.8%)		210/359 (58.5%)		248/396 (62.6%)
Gastrointestinal disorders
Diarrhoea	25/355 (7%)		27/359 (7.5%)		36/396 (9.1%)
Nausea	23/355 (6.5%)		17/359 (4.7%)		19/396 (4.8%)
Vomiting	27/355 (7.6%)		24/359 (6.7%)		30/396 (7.6%)
General disorders
Application site dermatitis	30/355 (8.5%)		36/359 (10%)		43/396 (10.9%)
Application site erythema	48/355 (13.5%)		44/359 (12.3%)		52/396 (13.1%)
Infections and infestations
Urinary tract infection	42/355 (11.8%)		43/359 (12%)		58/396 (14.6%)
Injury, poisoning and procedural complications
Fall	30/355 (8.5%)		26/359 (7.2%)		42/396 (10.6%)
Investigations
Weight decreased	37/355 (10.4%)		26/359 (7.2%)		47/396 (11.9%)
Psychiatric disorders
Agitation	47/355 (13.2%)		55/359 (15.3%)		58/396 (14.6%)
Anxiety	18/355 (5.1%)		19/359 (5.3%)		19/396 (4.8%)
Depression	19/355 (5.4%)		16/359 (4.5%)		18/396 (4.5%)
Hallucination	9/355 (2.5%)		19/359 (5.3%)		16/396 (4%)
Insomnia	27/355 (7.6%)		24/359 (6.7%)		30/396 (7.6%)
Renal and urinary disorders
Urinary incontinence	13/355 (3.7%)		14/359 (3.9%)		21/396 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.