Comparative Efficacy, Safety, and Tolerability of Rivastigmine 10 and 15 cm^2 Patch in Patients With Alzheimer's Disease (AD) Showing Cognitive Decline

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00506415
• Collaborator: (none)
• Enrollment: 1,584
• Locations: 145
• Arms: 4
• Duration (Months): 47
• Patients Per Site: 10.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study was to support the optimal use of rivastigmine patch in long-term treatment of Alzheimer's Disease in patients demonstrating functional and cognitive decline at the target maintenance dose of rivastigmine patch 10 cm^2.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: Rivastigmine 5 cm^2; Drug: Rivastigmine 10 cm^2; Drug: Rivastigmine 15 cm^2; Drug: Placebo to 15 cm^2 patch; Drug: Placebo to 10 cm^2 patch	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1584 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A 48-Week, Multicenter, Randomized, Double-Blind, Parallel-Group Evaluation of the Comparative Efficacy, Safety, and Tolerability of Exelon® 10 and 15 cm^2 Patch in Patients With Mild to Moderate Alzheimer's Disease (AD) Showing Functional and Cognitive Decline
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open label: Rivastigmine (5 cm^2 / 10 cm^2) Rivastigmine 5 cm^2 transdermal patch once a day during the first 4 weeks of open label treatment followed by rivastigmine 10 cm^2 transdermal patch once a day from week 4 to week 24, 36 or 48.	Drug: Rivastigmine 5 cm^2; 5 cm^2 transdermal patch; Other Names: Exelon® ; Drug: Rivastigmine 10 cm^2; 10 cm^2 transdermal patch.; Other Names: Exelon®
Experimental: Double blind: Rivastigmine (10 cm^2) Rivastigmine transdermal patch 10 cm^2 and placebo to rivastigmine 15 cm^2 once daily for 48 weeks during the double blind period.	Drug: Rivastigmine 10 cm^2; 10 cm^2 transdermal patch.; Other Names: Exelon® ; Drug: Placebo to 15 cm^2 patch; Placebo of rivastigmine transdermal patch 15 cm^2.
Experimental: Double blind: Rivastigmine (15 cm^2) Rivastigmine transdermal patch 15 cm^2 and placebo to rivastigmine 10 cm^2 once daily for 48 weeks during double blind period.	Drug: Rivastigmine 15 cm^2; 15 cm^2 transdermal patch.; Other Names: Exelon® ; Drug: Placebo to 10 cm^2 patch; Placebo of rivastigmine transdermal patch 10 cm^2.
Experimental: Extended open label Rivastigmine (10 cm^2) Rivastigmine 10 cm^2 transdermal patch once a day during 48 weeks open label treatment running in parallel to the double blind period.	Drug: Rivastigmine 10 cm^2; 10 cm^2 transdermal patch.; Other Names: Exelon®

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) Subscale at Week 48 of Double Blind Period [Baseline and week 48 of double blind period]

   The Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog) subscale comprises 11 items summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. A negative change indicates an improvement from baseline.

2. Change in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) Subscale Score From Baseline to Week 48 of Double Blind Period [Baseline and week 48 of double blind period]

   The Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) is a 16 item subscale of the caregiver-based ADCS-IADL scale, developed for the use in dementia studies. The ADCS-IADL total score ranges from 0 to 56, with higher scores indicating less severe impairment. A positive change indicates an improvement from baseline.

Secondary Outcome Measures

1. Time to Functional Decline as Measured by Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) Subscale During the Double Blind Period [390 days was the maximum]

   Functional decline was defined by either an at least 1 point decrease in the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) subscale score in a visit and confirmed by the following visit/assessment or at least 2 points decrease from the double blind randomization baseline.

2. Change in Attention and Executive Function as Assessed by the Trail Making Test (Part A) at Week 48 of the Double Blind Period [Baseline and week 48 of double blind period]

   Change from baseline to week 48 in total time to perform Trail Making Test (TMT) part A. This test provides information on visual search, scanning, speed of processing, mental flexibility, and executive functions. The TMT part A requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. The score represents the amount of time required to complete the task. Total values for TMT part A range between 0 and 300 seconds. A negative change indicates an improvement from baseline.

3. Change in Attention and Executive Function as Assessed by the Trail Making Test (Part B) at Week 48 of Double Blind Period [Baseline and week 48 of double blind period]

   Change from baseline to week 48 in total time to perform Trail Making Test (TMT) part B. This test provides information on visual search, scanning, speed of processing, mental flexibility, and executive functions. TMT has two parts: Part A requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for TMT-Part B except the person must alternate between numbers and letters. Total values for TMT part B range between 0 and 420 seconds. A negative change from baseline indicates an improvement in condition.

4. Change From Baseline in Neuropsychiatric Inventory (NPI)-10 Score at Week 48 of Double Blind Period [Baseline and week 48 of double blind period]

   Change from baseline to week 48 as assessed by the Neuropsychiatric Inventory (NPI)-10 total score. The scale consists of 10 domains that are rated for both frequency (range 1-4) and severity (range 1-3). A composite score for each domain is calculated (frequency x severity) which ranges from 1 to 12. There is a leading question for each item. If the symptom is not present then the frequency, severity and distress scores are not completed. In this case the score is 0 for the item. The sum of the composite scores yields the NPI-10 total score (range 0-120). A negative change in score indicates an improvement from baseline (symptom reduction).

5. Number of Patients With Adverse Events, Serious Adverse Events and Discontinuations Due to Adverse Events [30 days after a maximum of 96 weeks treatment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female patients between 50 and 85 years of age with a diagnosis of probable Alzheimers Disease,

• Baseline Mini-Mental State Examination (MMSE) score 10-24 inclusive,

• A primary caregiver willing to accept responsibility for supervising treatment, assessing the patient's condition throughout the study, and for providing input into efficacy assessments.

• For double blind only: Meet the decline criteria of functional (as assessed by the investigator) and cognitive (assessed by a 1 point reduction in Mini-Mental State Examination) score between visits or a 3 point reduction from baseline) decline at weeks 23, 36 or 48.

Exclusion Criteria:

• Presence of an advanced, severe, progressive, or unstable disease of any type that could interfere with efficacy and safety assessments or put the patient at particular risk,

• Any medical or neurological condition other than Alzheimers Disease that could explain the patient's dementia,

• A diagnosis of probable or possible vascular dementia,

• A current diagnosis of unsuccessfully-treated depression, or any other mental disorder that may interfere with the evaluation of the patient's response to study medication,

• A history or current diagnosis of cerebrovascular disease (e.g. stroke),

• A current diagnosis of severe or unstable cardiovascular disease (e.g. unstable coronary artery disease).

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis investigative site	Birmingham	Alabama	United States	35294
2	Novartis investigative site	Gilbert	Arizona	United States	85234
3	Novartis investigative site	Phoenix	Arizona	United States	85004
4	Novartis investigative site	Sun City	Arizona	United States	85351
5	Novartis investigative site	Anaheim	California	United States	92804
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13	Novartis investigative site	San Francisco	California	United States	94115
14	Novartis investigative site	Fort Collins	Colorado	United States	80524
15	Novartis investigative site	Longmont	Colorado	United States	80501
16	Novartis investigative site	Boca Raton	Florida	United States	33431
17	Novartis investigative site	Bradenton	Florida	United States	32405
18	Novartis investigative site	Deerfield Beach	Florida	United States	33064
19	Novartis investigative site	Delray Beach	Florida	United States	33445
20	Novartis investigative site	Fort Lauderdale	Florida	United States	33308
21	Novartis investigative site	Gainesville	Florida	United States	32610
22	Novartis investigative site	Miami Beach	Florida	United States	33140
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50	Novartis investigative site	Columbus	Ohio	United States	43220
51	Novartis investigative site	Corvallis	Oregon	United States	97330
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66	Novartis investigative site	Toronto	Ontario	Canada
67	Novartis investigative site	Calgary		Canada
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89	Novartis investigative site	Montpellier		France
90	Novartis investigative site	Nice		France
91	Novartis investigative site	Paris		France
92	Novartis investigative site	Rennes		France
93	Novartis investigative site	Rodez		France
94	Novartis investigative site	Bad Neustadt/Saale		Germany
95	Novartis investigative site	Berlin		Germany
96	Novartis investigative site	Bonn		Germany
97	Novartis investigative site	Burg		Germany
98	Novartis investigative site	Duesseldorf		Germany
99	Novartis investigative site	Frankfurt		Germany
100	Novartis investigative site	Giessen		Germany
101	Novartis investigative site	Koln		Germany
102	Novartis investigative site	Krefeld		Germany
103	Novartis investigative site	Leipzig		Germany
104	Novartis investigative site	Magdeburg		Germany
105	Novartis investigative site	Mannheim		Germany
106	Novartis investigative site	Marburg		Germany
107	Novartis investigative site	Muenchen		Germany
108	Novartis investigative site	Muenster		Germany
109	Novartis investigative site	Nuernberg		Germany
110	Novartis investigative site	Stralsund		Germany
111	Novartis investigative site	Stuttgart		Germany
112	Novartis investigative site	Wurzburg		Germany
113	Novartis investigative site	Milano	Milan	Italy
114	Novartis investigative site	Ancona		Italy
115	Novartis investigative site	Arcugnano		Italy
116	Novartis investigative site	Arezzo		Italy
117	Novartis investigative site	Bari		Italy
118	Novartis investigative site	Bologna		Italy
119	Novartis investigative site	Brescia		Italy
120	Novartis investigative site	Cagliari		Italy
121	Novartis investigative site	Catania		Italy
122	Novartis investigative site	Città di Castello		Italy
123	Novartis investigative site	Cremona		Italy
124	Novartis investigative site	Ferrara		Italy
125	Novartis investigative site	Firenze		Italy
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130	Novartis investigative site	Milan		Italy
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136	Novartis investigative site	Pisa		Italy
137	Novartis investigative site	Rho		Italy
138	Novartis investigative site	Rome		Italy
139	Novartis investigative site	Torino		Italy
140	Novartis investigative site	Verona		Italy
141	Novartis investigative site	Barcelona		Spain
142	Novartis investigative site	Palma de Mallorca		Spain
143	Novartis investigative site	Basel		Switzerland
144	Novartis investigative site	Biel		Switzerland
145	Novartis investigative site	Mendrisio		Switzerland

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00506415
• Other Study ID Numbers: CENA713D2340
• First Posted: Jul 25, 2007
• Last Update Posted: Sep 19, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by Novartis Pharmaceuticals: Alzheimer's; Patch; Cognitive; Decline
• Additional relevant MeSH terms: Alzheimer Disease; Cognitive Dysfunction; Rivastigmine

Study Results

Participant Flow

Pre-assignment Detail	1,584 participants were enrolled, 1582 received study drug during the initial open label period; of these, 567 were qualified to enter a double blind randomized period.

Arm/Group Title	Initial Open Label: Rivastigmine (5 cm^2 / 10 cm^2)	Double Blind: Rivastigmine (10 cm^2)	Double Blind: Rivastigmine (15 cm^2)	Extended Open Label (10 cm^2)
Arm/Group Description	Rivastigmine 5 cm^2 transdermal patch once a day during the first 4 weeks of open label treatment followed by rivastigmine 10 cm^2 transdermal patch once a day from week 4 to week 24, 36 or 48.	Rivastigmine transdermal patch 10 cm^2 and placebo to rivastigmine 15 cm^2 once daily for 48 weeks during the double blind period.	Rivastigmine transdermal patch 15 cm^2 and placebo to rivastigmine 10 cm^2 once daily for 48 weeks during double blind period.	Rivastigmine 10 cm^2 transdermal patch once a day during 48 weeks (from week 48 to week 96) open label treatment.
Period Title: Initial Open Label (Maximum 48 Weeks)
STARTED	1584	0	0	0
Exposed to Study Drug	1582	0	0	0
COMPLETED	1085	0	0	0
NOT COMPLETED	499	0	0	0
Period Title: Initial Open Label (Maximum 48 Weeks)
STARTED	0	286	280	0
COMPLETED	0	203	207	0
NOT COMPLETED	0	83	73	0
Period Title: Initial Open Label (Maximum 48 Weeks)
STARTED	0	0	0	457
COMPLETED	0	0	0	395
NOT COMPLETED	0	0	0	62

Baseline Characteristics

Arm/Group Title	Total Patients
Arm/Group Description	Total number of patients enrolled in the initial open label period that may have been randomized in the double blind period or may have continued in the extended open label period.
Overall Participants	1584
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.93 (7.131)
Sex: Female, Male (Count of Participants)
Female	992 62.6%
Male	592 37.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) Subscale at Week 48 of Double Blind Period
Description	The Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog) subscale comprises 11 items summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. A negative change indicates an improvement from baseline.
Time Frame	Baseline and week 48 of double blind period

Outcome Measure Data

Analysis Population Description

Intent to treat population double blind (ITT-DB): included all randomized patients who received at least 1 dose of double blind study drug, and had at least 1 post-randomization assessment for both co-primary efficacy variables: Alzheimer's Disease Assessment Scale-Cognitive and Disease Cooperative Study-Instrumental Activities of Daily Living.

Arm/Group Title	Double Blind: Rivastigmine (10 cm^2)	Double Blind: Rivastigmine (15 cm^2)
Arm/Group Description	Rivastigmine transdermal patch 10 cm^2 and placebo to rivastigmine 15 cm^2 once daily for 48 weeks during the double blind period.	Rivastigmine transdermal patch 15 cm^2 and placebo to rivastigmine 10 cm^2 once daily for 48 weeks during double blind period.
Measure Participants	268	264
Mean (Standard Deviation) [units on a scale]	4.9 (7.49)	4.1 (8.00)

2. Primary Outcome

Title	Change in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) Subscale Score From Baseline to Week 48 of Double Blind Period
Description	The Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) is a 16 item subscale of the caregiver-based ADCS-IADL scale, developed for the use in dementia studies. The ADCS-IADL total score ranges from 0 to 56, with higher scores indicating less severe impairment. A positive change indicates an improvement from baseline.
Time Frame	Baseline and week 48 of double blind period

Outcome Measure Data

Analysis Population Description

Intent to treat population double blind (ITT-DB): included all randomized patients who received at least 1 dose of double blind study drug, and had at least 1 post-randomization assessment for both co-primary efficacy variables: Alzheimer's Disease Assessment Scale-Cognitive and Disease Cooperative Study-Instrumental Activities of Daily Living.

Arm/Group Title	Double Blind: Rivastigmine (10 cm^2)	Double Blind: Rivastigmine (15 cm^2)
Arm/Group Description	Rivastigmine transdermal patch 10 cm^2 and placebo to rivastigmine 15 cm^2 once daily for 48 weeks during the double blind period.	Rivastigmine transdermal patch 15 cm^2 and placebo to rivastigmine 10 cm^2 once daily for 48 weeks during double blind period.
Measure Participants	271	265
Mean (Standard Deviation) [units on a scale]	-6.2 (8.78)	-4.4 (8.21)

3. Secondary Outcome

Title	Time to Functional Decline as Measured by Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) Subscale During the Double Blind Period
Description	Functional decline was defined by either an at least 1 point decrease in the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) subscale score in a visit and confirmed by the following visit/assessment or at least 2 points decrease from the double blind randomization baseline.
Time Frame	390 days was the maximum

Outcome Measure Data

Analysis Population Description

Intent to treat population double blind (ITT-DB): included all randomized patients who received at least 1 dose of double blind study drug, and had at least 1 post-randomization assessment for both co-primary efficacy variables: Alzheimer's Disease Assessment Scale-Cognitive and Disease Cooperative Study-Instrumental Activities of Daily Living.

Arm/Group Title	Double Blind: Rivastigmine (10 cm^2)	Double Blind: Rivastigmine (15 cm^2)
Arm/Group Description	Rivastigmine transdermal patch 10 cm^2 and placebo to rivastigmine 15 cm^2 once daily for 48 weeks during the double blind period.	Rivastigmine transdermal patch 15 cm^2 and placebo to rivastigmine 10 cm^2 once daily for 48 weeks during double blind period.
Measure Participants	271	265
Median (95% Confidence Interval) [Time in days]	90	91

4. Secondary Outcome

Title	Change in Attention and Executive Function as Assessed by the Trail Making Test (Part A) at Week 48 of the Double Blind Period
Description	Change from baseline to week 48 in total time to perform Trail Making Test (TMT) part A. This test provides information on visual search, scanning, speed of processing, mental flexibility, and executive functions. The TMT part A requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. The score represents the amount of time required to complete the task. Total values for TMT part A range between 0 and 300 seconds. A negative change indicates an improvement from baseline.
Time Frame	Baseline and week 48 of double blind period

Outcome Measure Data

Analysis Population Description

Intent to treat population (ITT-DB): included all randomized patients with an assessment at baseline and week 48 who received at least 1 dose of double blind study drug, and had at least 1 post-randomization assessment for both co-primary efficacy variables (ADAS-cog and ADCS-IADL).

Arm/Group Title	Double Blind: Rivastigmine (10 cm^2)	Double Blind: Rivastigmine (15 cm^2)
Arm/Group Description	Rivastigmine transdermal patch 10 cm^2 and placebo to rivastigmine 15 cm^2 once daily for 48 weeks during the double blind period.	Rivastigmine transdermal patch 15 cm^2 and placebo to rivastigmine 10 cm^2 once daily for 48 weeks during double blind period.
Measure Participants	258	254
Mean (Standard Deviation) [Time in seconds]	18.2 (62.57)	16.3 (66.09)

5. Secondary Outcome

Title	Change in Attention and Executive Function as Assessed by the Trail Making Test (Part B) at Week 48 of Double Blind Period
Description	Change from baseline to week 48 in total time to perform Trail Making Test (TMT) part B. This test provides information on visual search, scanning, speed of processing, mental flexibility, and executive functions. TMT has two parts: Part A requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for TMT-Part B except the person must alternate between numbers and letters. Total values for TMT part B range between 0 and 420 seconds. A negative change from baseline indicates an improvement in condition.
Time Frame	Baseline and week 48 of double blind period

Outcome Measure Data

Analysis Population Description

Intent to treat population (ITT-DB): included all randomized patients with an assessment at baseline and week 48 who received at least 1 dose of double blind study drug, and had at least 1 post-randomization assessment for both co-primary efficacy variables (ADAS-cog, ADCS-IADL).

Arm/Group Title	Double Blind: Rivastigmine (15 cm^2)	Double Blind: Rivastigmine (10 cm^2)
Arm/Group Description	Rivastigmine transdermal patch 15 cm^2 and placebo to rivastigmine 10 cm^2 once daily for 48 weeks during the double blind period.	Rivastigmine transdermal patch 10 cm^2 and placebo to rivastigmine 15 cm^2 once daily for 48 weeks during the double blind period.
Measure Participants	235	236
Mean (Standard Deviation) [Time in seconds]	9.3 (68.80)	5.8 (65.38)

6. Secondary Outcome

Title	Change From Baseline in Neuropsychiatric Inventory (NPI)-10 Score at Week 48 of Double Blind Period
Description	Change from baseline to week 48 as assessed by the Neuropsychiatric Inventory (NPI)-10 total score. The scale consists of 10 domains that are rated for both frequency (range 1-4) and severity (range 1-3). A composite score for each domain is calculated (frequency x severity) which ranges from 1 to 12. There is a leading question for each item. If the symptom is not present then the frequency, severity and distress scores are not completed. In this case the score is 0 for the item. The sum of the composite scores yields the NPI-10 total score (range 0-120). A negative change in score indicates an improvement from baseline (symptom reduction).
Time Frame	Baseline and week 48 of double blind period

Outcome Measure Data

Analysis Population Description

Intent to treat population double blind (ITT-DB): included all randomized patients with an assessment at baseline and week 48, who received at least 1 dose of double blind study drug, and had at least 1 post-randomization assessment for both co-primary efficacy variables (ADAS-cog, ADCS-IADL).

Arm/Group Title	Double Blind: Rivastigmine (10 cm^2)	Double Blind: Rivastigmine (15 cm^2)
Arm/Group Description	Rivastigmine transdermal patch 10 cm^2 and placebo to rivastigmine 15 cm^2 once daily for 48 weeks during the double blind period.	Rivastigmine transdermal patch 15 cm^2 and placebo to rivastigmine 10 cm^2 once daily for 48 weeks during double blind period.
Measure Participants	271	265
Mean (Standard Deviation) [units on a scale]	0.9 (10.98)	1.4 (11.51)

7. Secondary Outcome

Title	Number of Patients With Adverse Events, Serious Adverse Events and Discontinuations Due to Adverse Events
Time Frame	30 days after a maximum of 96 weeks treatment

Outcome Measure Data

Analysis Population Description

The safety set included all patients who received at least one dose of study medication and who had at least one post-baseline safety assessment.

Arm/Group Title	Initial Open Label: Rivastigmine (5 cm^2 / 10 cm^2)	Double Blind: Rivastigmine (10 cm^2)	Double Blind: Rivastigmine (15 cm^2)	Extended Open Label (10 cm^2)
Arm/Group Description	Rivastigmine 5 cm^2 transdermal patch once a day during the first 4 weeks of open label treatment followed by rivastigmine 10 cm^2 transdermal patch once a day from week 4 to week 24, 36 or 48.	Rivastigmine transdermal patch 10 cm^2 and placebo to rivastigmine 15 cm^2 once daily for 48 weeks during the double blind period.	Rivastigmine transdermal patch 15c m^2 and placebo to rivastigmine 10 cm^2 once daily for 48 weeks during double blind period.	Rivastigmine 10 cm^2 transdermal patch once a day during 48 weeks open label treatment running in parallel to the double blind period.
Measure Participants	1582	283	280	457
Number [Participants]	1135 71.7%	193 NaN	210 NaN	263 NaN

Adverse Events

Time Frame	30 days after a maximum of 96 weeks treatment
Adverse Event Reporting Description	The safety set included all patients who received at least one dose of study medication and who had at least one post-baseline safety assessment.
Arm/Group Title	Initial Open Label: Rivastigmine (5 cm^2 / 10 cm^2)		Double Blind: Rivastigmine (10 cm^2)		Double Blind: Rivastigmine (15 cm^2)		Extended Open Label: Rivastigmine (10 cm^2)
Arm/Group Description	Safety population Initial Open Label (Safety-IOL) - This population consisted of all patients who received at least 1 dose of study drug during the initial open label phase and had at least 1 post baseline safety assessment during the same phase.		Safety population Double Blind (Safety-DB) - This population included all patients who were randomized, received at least 1 dose of study drug during the double blind phase and had at least 1 post-randomization safety assessment during the double blind phase. Patients were analyzed according to treatment received.		Safety population Double Blind (Safety-DB) - This population included all patients who were randomized, received at least 1 dose of study drug during the double blind phase and had at least 1 post-randomization safety assessment during the double blind phase. Patients were analyzed according to treatment received.		Safety population Extended Open Label (Safety-EOL) - This population consisted of all patients who received at least 1 dose of study drug during the extended open label phase and had at least 1 post baseline safety assessment during the same phase.
All Cause Mortality
	Initial Open Label: Rivastigmine (5 cm^2 / 10 cm^2)		Double Blind: Rivastigmine (10 cm^2)		Double Blind: Rivastigmine (15 cm^2)		Extended Open Label: Rivastigmine (10 cm^2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Initial Open Label: Rivastigmine (5 cm^2 / 10 cm^2)		Double Blind: Rivastigmine (10 cm^2)		Double Blind: Rivastigmine (15 cm^2)		Extended Open Label: Rivastigmine (10 cm^2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	227/1582 (14.3%)		44/283 (15.5%)		44/280 (15.7%)		59/457 (12.9%)
Blood and lymphatic system disorders
Anaemia	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Coagulopathy	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Haemorrhagic anaemia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Lymphadenopathy	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Cardiac disorders
Acute coronary syndrome	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Acute myocardial infarction	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Angina pectoris	2/1582 (0.1%)		2/283 (0.7%)		0/280 (0%)		1/457 (0.2%)
Aortic valve calcification	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Arrhythmia	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Atrial fibrillation	9/1582 (0.6%)		2/283 (0.7%)		0/280 (0%)		3/457 (0.7%)
Atrial thrombosis	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Atrioventricular block complete	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Bradyarrhythmia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Bradycardia	3/1582 (0.2%)		1/283 (0.4%)		2/280 (0.7%)		0/457 (0%)
Bundle branch block left	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Cardiac arrest	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Cardiac failure	8/1582 (0.5%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Cardiac failure congestive	2/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		1/457 (0.2%)
Cardio-respiratory arrest	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Cardiomyopathy	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Coronary artery disease	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Coronary artery stenosis	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Left ventricular failure	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Myocardial infarction	6/1582 (0.4%)		2/283 (0.7%)		0/280 (0%)		0/457 (0%)
Myocardial ischaemia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Sick sinus syndrome	1/1582 (0.1%)		2/283 (0.7%)		1/280 (0.4%)		1/457 (0.2%)
Sinus bradycardia	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Tachyarrhythmia	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Tachycardia	0/1582 (0%)		1/283 (0.4%)		1/280 (0.4%)		0/457 (0%)
Tachycardia paroxysmal	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Ear and labyrinth disorders
Vertigo	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Endocrine disorders
Adrenal insufficiency	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Hyperthyroidism	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Thyroid disorder	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Eye disorders
Cataract	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Visual acuity reduced	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Abdominal pain	5/1582 (0.3%)		0/283 (0%)		2/280 (0.7%)		0/457 (0%)
Abdominal pain upper	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		1/457 (0.2%)
Colitis	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Colonic polyp	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Diarrhoea	5/1582 (0.3%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Duodenal ulcer haemorrhage	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Gastric ulcer haemorrhage	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Gastritis	4/1582 (0.3%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Gastrointestinal disorder	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Gastrointestinal inflammation	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Gastrooesophageal reflux disease	1/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Hernial eventration	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Hiatus hernia	2/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Inguinal hernia	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Intestinal mass	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Intestinal obstruction	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		2/457 (0.4%)
Irritable bowel syndrome	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Nausea	7/1582 (0.4%)		1/283 (0.4%)		1/280 (0.4%)		1/457 (0.2%)
Pancreatitis	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Pancreatitis acute	2/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Rectal haemorrhage	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		1/457 (0.2%)
Reflux oesophagitis	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Sigmoiditis	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Small intestinal obstruction	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Vomiting	12/1582 (0.8%)		2/283 (0.7%)		3/280 (1.1%)		1/457 (0.2%)
General disorders
Abasia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Asthenia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		2/457 (0.4%)
Catheter site haemorrhage	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Complication of device removal	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Device malfunction	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Fatigue	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Gait disturbance	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
General physical health deterioration	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Malaise	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Non-cardiac chest pain	1/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Oedema peripheral	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Pyrexia	1/1582 (0.1%)		1/283 (0.4%)		1/280 (0.4%)		0/457 (0%)
Hepatobiliary disorders
Cholecystitis	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Cholecystitis acute	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Cholelithiasis	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		2/457 (0.4%)
Cryptogenic cirrhosis	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Infections and infestations
Abdominal sepsis	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Bacteraemia	0/1582 (0%)		2/283 (0.7%)		0/280 (0%)		0/457 (0%)
Catheter site infection	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Cellulitis	1/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Cholecystitis infective	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Cystitis	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Diverticulitis	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Febrile infection	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Gastritis viral	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Gastroenteritis	1/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Gastroenteritis viral	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Herpes zoster	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Infected skin ulcer	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Infection	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Lobar pneumonia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Meningitis	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Osteomyelitis	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Pneumonia	7/1582 (0.4%)		2/283 (0.7%)		4/280 (1.4%)		2/457 (0.4%)
Pyelonephritis	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Renal abscess	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Respiratory tract infection	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Sepsis	2/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Sinusitis	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Urinary tract infection	7/1582 (0.4%)		4/283 (1.4%)		4/280 (1.4%)		2/457 (0.4%)
Urosepsis	0/1582 (0%)		0/283 (0%)		2/280 (0.7%)		0/457 (0%)
Viral infection	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Injury, poisoning and procedural complications
Accidental overdose	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Anastomotic leak	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Cerebral haemorrhage traumatic	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Chest injury	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Concussion	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Facial bones fracture	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Fall	12/1582 (0.8%)		1/283 (0.4%)		3/280 (1.1%)		0/457 (0%)
Femoral neck fracture	4/1582 (0.3%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Femur fracture	2/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		2/457 (0.4%)
Foot fracture	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Forearm fracture	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Fractured sacrum	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Head injury	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Hip fracture	7/1582 (0.4%)		2/283 (0.7%)		0/280 (0%)		1/457 (0.2%)
Humerus fracture	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Injury	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Joint dislocation	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		2/457 (0.4%)
Joint sprain	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Ligament rupture	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Lower limb fracture	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Mental status changes postoperative	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Multiple injuries	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Patella fracture	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Pelvic fracture	1/1582 (0.1%)		3/283 (1.1%)		0/280 (0%)		0/457 (0%)
Radius fracture	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		1/457 (0.2%)
Rib fracture	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Soft tissue injury	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Spinal compression fracture	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Spinal fracture	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Subdural haematoma	2/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Thoracic vertebral fracture	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Tibia fracture	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Traumatic brain injury	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Traumatic fracture	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Traumatic haematoma	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Upper limb fracture	4/1582 (0.3%)		0/283 (0%)		1/280 (0.4%)		1/457 (0.2%)
Investigations
Cardiac enzymes increased	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Heart rate increased	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
International normalised ratio increased	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Prostatic specific antigen increased	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/1582 (0.1%)		0/283 (0%)		2/280 (0.7%)		1/457 (0.2%)
Dehydration	5/1582 (0.3%)		3/283 (1.1%)		3/280 (1.1%)		1/457 (0.2%)
Diabetes mellitus	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Failure to thrive	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		1/457 (0.2%)
Hyperglycaemia	1/1582 (0.1%)		2/283 (0.7%)		0/280 (0%)		0/457 (0%)
Hyperkalaemia	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Hypoglycaemia	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Hypokalaemia	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Hyponatraemia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Malnutrition	1/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Musculoskeletal and connective tissue disorders
Bursitis	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Groin pain	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Intervertebral disc protrusion	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Muscle spasms	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Muscular weakness	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Musculoskeletal chest pain	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Neck pain	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Osteoarthritis	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Osteoporotic fracture	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Pain in extremity	0/1582 (0%)		0/283 (0%)		0/280 (0%)		2/457 (0.4%)
Periarthritis	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Spinal osteoarthritis	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Synovial cyst	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Angiomyolipoma	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
B-cell lymphoma	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Basal cell carcinoma	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Benign breast neoplasm	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Bladder cancer	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Bladder neoplasm	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Breast cancer	2/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Breast cancer metastatic	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Bronchial carcinoma	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Cholesteatoma	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Colon cancer	0/1582 (0%)		2/283 (0.7%)		0/280 (0%)		2/457 (0.4%)
Colon neoplasm	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Colorectal cancer	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Gastric cancer	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Hepatic neoplasm malignant	1/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Leiomyosarcoma	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		1/457 (0.2%)
Lip and/or oral cavity cancer	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Lung adenocarcinoma	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Lung neoplasm	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Lung neoplasm malignant	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Lymphoma	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Malignant melanoma	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Malignant melanoma in situ	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Metastases to liver	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Metastases to lung	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Metastases to meninges	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Metastatic neoplasm	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Oesophageal carcinoma	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Prostate cancer	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Skin cancer	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Squamous cell carcinoma of skin	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Thyroid cancer	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Nervous system disorders
Balance disorder	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Brain oedema	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Cerebellar haemorrhage	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Cerebral haemorrhage	1/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		1/457 (0.2%)
Cerebral ischaemia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Cerebrovascular accident	5/1582 (0.3%)		1/283 (0.4%)		2/280 (0.7%)		0/457 (0%)
Cognitive disorder	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Coma	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Convulsion	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Crying	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Dementia	3/1582 (0.2%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Dementia Alzheimer's type	3/1582 (0.2%)		2/283 (0.7%)		0/280 (0%)		1/457 (0.2%)
Dizziness	0/1582 (0%)		0/283 (0%)		2/280 (0.7%)		1/457 (0.2%)
Dizziness postural	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Embolic cerebral infarction	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Encephalopathy	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Epilepsy	2/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Extrapyramidal disorder	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Lethargy	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Loss of consciousness	2/1582 (0.1%)		1/283 (0.4%)		2/280 (0.7%)		0/457 (0%)
Mental impairment	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Multiple system atrophy	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Neuroleptic malignant syndrome	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Neurological decompensation	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Paraesthesia	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Presyncope	1/1582 (0.1%)		0/283 (0%)		2/280 (0.7%)		1/457 (0.2%)
Psychomotor hyperactivity	3/1582 (0.2%)		1/283 (0.4%)		1/280 (0.4%)		2/457 (0.4%)
Sciatica	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Senile dementia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Status epilepticus	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Syncope	14/1582 (0.9%)		3/283 (1.1%)		2/280 (0.7%)		3/457 (0.7%)
Transient ischaemic attack	3/1582 (0.2%)		1/283 (0.4%)		0/280 (0%)		1/457 (0.2%)
VIIth nerve paralysis	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Psychiatric disorders
Abnormal behaviour	1/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		1/457 (0.2%)
Aggression	5/1582 (0.3%)		2/283 (0.7%)		2/280 (0.7%)		0/457 (0%)
Agitation	6/1582 (0.4%)		2/283 (0.7%)		3/280 (1.1%)		0/457 (0%)
Anxiety	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Confusional state	3/1582 (0.2%)		0/283 (0%)		1/280 (0.4%)		1/457 (0.2%)
Delirium	4/1582 (0.3%)		2/283 (0.7%)		0/280 (0%)		0/457 (0%)
Delusion	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Depressed mood	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Depression	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Disorientation	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Fear	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Hallucination	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Hallucination, visual	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Insomnia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Mental status changes	4/1582 (0.3%)		1/283 (0.4%)		0/280 (0%)		3/457 (0.7%)
Panic attack	0/1582 (0%)		0/283 (0%)		1/280 (0.4%)		0/457 (0%)
Paranoia	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Psychotic disorder	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Restlessness	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Suicidal ideation	0/1582 (0%)		2/283 (0.7%)		0/280 (0%)		0/457 (0%)
Suicide attempt	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Renal and urinary disorders
Dysuria	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Haematuria	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Nephrolithiasis	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Obstructive uropathy	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Renal failure	2/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Renal failure acute	1/1582 (0.1%)		1/283 (0.4%)		1/280 (0.4%)		2/457 (0.4%)
Renal infarct	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Urinary incontinence	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Urinary retention	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Reproductive system and breast disorders
Prostatitis	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Asthma	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Dyspnoea	5/1582 (0.3%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Dyspnoea exertional	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Foreign body aspiration	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Haemothorax	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Pleurisy	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Pleuritic pain	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Pneumonia aspiration	2/1582 (0.1%)		0/283 (0%)		1/280 (0.4%)		1/457 (0.2%)
Pneumonitis	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Pulmonary embolism	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		2/457 (0.4%)
Respiratory distress	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Respiratory failure	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Wheezing	0/1582 (0%)		0/283 (0%)		0/280 (0%)		1/457 (0.2%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Hyperhidrosis	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Psoriasis	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Skin ulcer	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Vascular disorders
Aortic aneurysm rupture	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Deep vein thrombosis	1/1582 (0.1%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Hypertension	2/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Hypertensive crisis	1/1582 (0.1%)		0/283 (0%)		0/280 (0%)		0/457 (0%)
Hypotension	3/1582 (0.2%)		1/283 (0.4%)		2/280 (0.7%)		1/457 (0.2%)
Peripheral arterial occlusive disease	0/1582 (0%)		1/283 (0.4%)		0/280 (0%)		0/457 (0%)
Other (Not Including Serious) Adverse Events
	Initial Open Label: Rivastigmine (5 cm^2 / 10 cm^2)		Double Blind: Rivastigmine (10 cm^2)		Double Blind: Rivastigmine (15 cm^2)		Extended Open Label: Rivastigmine (10 cm^2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	732/1582 (46.3%)		110/283 (38.9%)		151/280 (53.9%)		112/457 (24.5%)
Gastrointestinal disorders
Abdominal pain upper	17/1582 (1.1%)		3/283 (1.1%)		9/280 (3.2%)		4/457 (0.9%)
Diarrhoea	73/1582 (4.6%)		13/283 (4.6%)		18/280 (6.4%)		4/457 (0.9%)
Nausea	90/1582 (5.7%)		13/283 (4.6%)		33/280 (11.8%)		11/457 (2.4%)
Vomiting	68/1582 (4.3%)		12/283 (4.2%)		27/280 (9.6%)		1/457 (0.2%)
General disorders
Application site erythema	184/1582 (11.6%)		16/283 (5.7%)		18/280 (6.4%)		10/457 (2.2%)
Application site pruritus	139/1582 (8.8%)		11/283 (3.9%)		11/280 (3.9%)		5/457 (1.1%)
Application site rash	56/1582 (3.5%)		5/283 (1.8%)		6/280 (2.1%)		2/457 (0.4%)
Infections and infestations
Urinary tract infection	45/1582 (2.8%)		8/283 (2.8%)		11/280 (3.9%)		11/457 (2.4%)
Injury, poisoning and procedural complications
Fall	53/1582 (3.4%)		16/283 (5.7%)		19/280 (6.8%)		24/457 (5.3%)
Investigations
Weight decreased	44/1582 (2.8%)		8/283 (2.8%)		19/280 (6.8%)		12/457 (2.6%)
Metabolism and nutrition disorders
Decreased appetite	36/1582 (2.3%)		7/283 (2.5%)		16/280 (5.7%)		5/457 (1.1%)
Nervous system disorders
Dizziness	37/1582 (2.3%)		2/283 (0.7%)		10/280 (3.6%)		8/457 (1.8%)
Headache	62/1582 (3.9%)		11/283 (3.9%)		11/280 (3.9%)		7/457 (1.5%)
Psychiatric disorders
Agitation	42/1582 (2.7%)		14/283 (4.9%)		12/280 (4.3%)		5/457 (1.1%)
Anxiety	56/1582 (3.5%)		7/283 (2.5%)		10/280 (3.6%)		10/457 (2.2%)
Depression	65/1582 (4.1%)		13/283 (4.6%)		14/280 (5%)		15/457 (3.3%)
Insomnia	40/1582 (2.5%)		7/283 (2.5%)		11/280 (3.9%)		6/457 (1.3%)
Renal and urinary disorders
Urinary incontinence	25/1582 (1.6%)		5/283 (1.8%)		9/280 (3.2%)		6/457 (1.3%)
Vascular disorders
Hypertension	53/1582 (3.4%)		8/283 (2.8%)		9/280 (3.2%)		8/457 (1.8%)

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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.