Effects of Rivastigmine Patch on Activities of Daily Livi... | NCT00948766

NCT00948766

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Rivastigmine 13.3 mg/24 h transdermal patch	Experimental	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) Drug: Rivastigmine 9.5 mg/24 h (10 cm^2) Drug: Rivastigmine 13.3 mg/24 h (15 cm^2) Drug: Placebo
Rivastigmine 4.6 mg/24 h transdermal patch	Active Comparator	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) Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Rivastigmine 4.6 mg/24 h (5 cm^2)	Drug	Rivastigmine was supplied in a 5 cm^2 patch which released 4.6 mg/24 h. Patches were changed daily.	Rivastigmine 13.3 mg/24 h transdermal patch

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Measure	Description	Time Frame
Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24	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 Module

Eligibility Criteria

Core study

Inclusion Criteria:

Diagnosis of probable Alzheimer's disease (AD) according to National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria.
A Mini-Mental State Examination (MMSE) score of ≥ 3 and ≤ 12.
Be able to complete at least 1 item on the Severe Impairment Battery (SIB).
Residing with someone in the community or in regular contact with the primary caregiver.
Be ambulatory or ambulatory with aid.

Exclusion Criteria:

An advanced, severe, progressive, or unstable disease of any type that may interfere with efficacy and safety assessments or put the patient at special risk.
Patients currently residing in a nursing home.
Any current medical or neurological condition other than AD that could explain the patient's dementia.
A current diagnosis of probable or possible vascular dementia.
A current diagnosis of severe or unstable cardiovascular disease.
A current diagnosis of bradycardia (< 50 beats per minute [bpm]), sick-sinus syndrome, or conduction defects.
Clinically significant urinary obstruction.
History of malignancy of any organ system within the past 5 years unless patient is verified to be in stable condition with no active metastasis.
Current diagnosis of an active skin lesion/disorder that would prevent the patient from using a transdermal patch every day.
A known exaggerated pharmacological sensitivity or hypersensitivity to drugs similar to rivastigmine, or to other cholinergic compounds.
Taken any of the following substances (at the time of the Baseline Visit [Visit 2]).
Succinylcholine-type muscle relaxants during the previous 2 weeks.
Lithium during the previous 2 weeks.
An investigational drug during the previous 4 weeks.
A drug or treatment known to cause major organ system toxicity during the previous 4 weeks.
Rivastigmine (oral or transdermal patch), donepezil, galantamine, other cholinesterase inhibitors (eg, tacrine, physostigmine, or pyridostigmine), or other approved treatments for Alzheimer's disease during the previous 2 weeks, with exception of stable treatment with memantine for at least 3 months before study entry (Visit 1).
Centrally acting anticholinergic drugs including tricyclic and tetracyclic antidepressants during the previous 4 weeks.
Selegiline unless taken at a stable dose during the previous 4 weeks.
Peripheral anticholinergics not taken at a stable dose during the previous 4 weeks.

Extension study

Inclusion Criteria:

Complete the double-blind phase (Week 24) of the core study.
Provide, if mentally competent, a separate written informed consent prior to participation in the extension study. In addition, the patient's caregiver, will provide written informed consent prior to the patient's participation in the open-label extension study. If the patient is not able to provide written informed consent, written informed consent must be obtained from the legally authorized representative on the patient's behalf.
Continue to reside with someone in the community or in regular contact with the primary caregiver; patients who reside in an assisted living facility are eligible to participate.
Continue to have a primary caregiver willing to accept responsibility for supervising treatment (eg, application and removal of the patch daily at approximately the same time of day), assessing the condition of the patient throughout the extension study.
Must be medically stable and tolerating the current dose of rivastigmine patch as determined by the investigator.

Exclusion Criteria:

Refer to the core study protocol for full details of the exclusion criteria.

Patients who discontinued the core study due to any reason are excluded.
No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Research Advantage Inc./Neurological. Physicians of Arizona, Inc		Tempe	Arizona	85282	United States

PubMed Identifier	Type	Citation	Retractions
25523430	Derived	Grossberg GT, Farlow MR, Meng X, Velting DM. Evaluating high-dose rivastigmine patch in severe Alzheimer's disease: analyses with concomitant memantine usage as a factor. Curr Alzheimer Res. 2015;12(1):53-60. doi: 10.2174/1567205011666141218122835.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Rivastigmine 13.3 mg/24 h Transdermal Patch	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
FG001	Rivastigmine 4.6 mg/24 h Transdermal Patch	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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.

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.

Posted

Mean

Standard Deviation

Units on a scale

Baseline of the core study to Week 24 of the core study

ID	Title	Description
OG000	Rivastigmine 13.3 mg/24 h Transdermal Patch	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
OG001	Rivastigmine 4.6 mg/24 h Transdermal Patch	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).

Units	Counts
Participants	OG000310 OG001303

Title

Denominators

Categories

Title	Measurements
	OG000-2.6± 6.82 OG001-3.6± 7.68

Primary

Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24

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.

Posted

Mean

Standard Deviation

Units on a scale

Baseline of the core study to Week 24 of the core study

ID	Title	Description
OG000	Rivastigmine 13.3 mg/24 h Transdermal Patch	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
OG001	Rivastigmine 4.6 mg/24 h Transdermal Patch	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).

Secondary

Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24

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.

Posted

Number

Percentage of patients

Baseline of the core study to Week 24 of the core study

ID	Title	Description
OG000	Rivastigmine 13.3 mg/24 h Transdermal Patch	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
OG001	Rivastigmine 4.6 mg/24 h Transdermal Patch

Secondary

Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24

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.

Posted

Mean

Standard Deviation

Units on a scale

Baseline of the core study to Week 24 of the core study

ID	Title	Description
OG000	Rivastigmine 13.3 mg/24 h Transdermal Patch	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
OG001	Rivastigmine 4.6 mg/24 h Transdermal Patch	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).

Secondary

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

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.

Posted

Mean

Standard Deviation

Units on a scale

Baseline of the core study to Week 24 of the extension study

ID	Title	Description
OG000	Rivastigmine 13.3 mg/24 h Transdermal Patch	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).

Secondary

Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24

Posted

Mean

Standard Deviation

Units on a scale

Baseline of the core study to Week 24 of the extension study

ID	Title	Description
OG000	Rivastigmine 13.3 mg/24 h Transdermal Patch	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).

Units	Counts
Participants

Secondary

Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24

Posted

Number

Percentage of patients

Baseline of the core study to Week 24 of the extension study

ID	Title	Description
OG000	Rivastigmine 13.3 mg/24 h Transdermal Patch	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Angina pectoris	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Arrhythmia	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0012 affected359 at risk EG0022 affected396 at risk
Bradycardia	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0003 affected355 at risk EG0011 affected359 at risk EG0022 affected396 at risk
Bundle branch block left	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Cardiac arrest	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0013 affected359 at risk EG0022 affected396 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Coronary artery disease	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Myocardial infarction	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0011 affected359 at risk EG0022 affected396 at risk
Ascites	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Colitis	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0012 affected359 at risk EG0021 affected396 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0003 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Diverticulum	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Faecaloma	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0004 affected355 at risk EG0011 affected359 at risk EG0022 affected396 at risk
Asthenia	General disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0012 affected359 at risk EG0022 affected396 at risk
Chest discomfort	General disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Chest pain	General disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0014 affected359 at risk EG0025 affected396 at risk
Fatigue	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Gait disturbance	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0012 affected359 at risk EG0020 affected396 at risk
Malaise	General disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Non-cardiac chest pain	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Oedema peripheral	General disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Biliary dyskinesia	Hepatobiliary disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Bronchitis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0012 affected359 at risk EG0023 affected396 at risk
Cellulitis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0012 affected359 at risk EG0021 affected396 at risk
Gastroenteritis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Herpes zoster	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Intestinal gangrene	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Kidney infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Lobar pneumonia	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Pneumonia	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0004 affected355 at risk EG0015 affected359 at risk EG0025 affected396 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Sepsis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0005 affected355 at risk EG0017 affected359 at risk EG0028 affected396 at risk
Back injury	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Chemical poisoning	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Excoriation	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0007 affected355 at risk EG0017 affected359 at risk EG0025 affected396 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0012 affected359 at risk EG0021 affected396 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Fractured sacrum	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0004 affected355 at risk EG0011 affected359 at risk EG0022 affected396 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Incorrect dose administered	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0011 affected359 at risk EG0022 affected396 at risk
Jaw fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Pubis fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0014 affected359 at risk EG0022 affected396 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Skull fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0004 affected355 at risk EG0013 affected359 at risk EG0024 affected396 at risk
Ulna fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Blood pressure increased	Investigations	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Blood pressure systolic decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Cardiac enzymes increased	Investigations	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Electrocardiogram T wave inversion	Investigations	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
White blood cell count increased	Investigations	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0003 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0006 affected355 at risk EG0014 affected359 at risk EG0026 affected396 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Colon cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Aphasia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Balance disorder	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0004 affected355 at risk EG0011 affected359 at risk EG0024 affected396 at risk
Convulsion	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0013 affected359 at risk EG0022 affected396 at risk
Coordination abnormal	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Dementia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Dementia Alzheimer's type	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0003 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Dizziness	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Dysstasia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Grand mal convulsion	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Headache	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Hypokinesia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Lethargy	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Loss of consciousness	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Mental impairment	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0012 affected359 at risk EG0022 affected396 at risk
Pneumocephalus	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Presyncope	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0013 affected359 at risk EG0021 affected396 at risk
Somnolence	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0012 affected359 at risk EG0022 affected396 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Syncope	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0007 affected355 at risk EG0016 affected359 at risk EG0027 affected396 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0004 affected355 at risk EG0011 affected359 at risk EG0024 affected396 at risk
Unresponsive to stimuli	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0011 affected359 at risk EG0022 affected396 at risk
VIIth nerve paralysis	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Aggression	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0013 affected359 at risk EG0020 affected396 at risk
Agitation	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0016 affected359 at risk EG0021 affected396 at risk
Anxiety	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Confusional state	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0003 affected355 at risk EG0011 affected359 at risk EG0022 affected396 at risk
Delirium	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Depression	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0012 affected359 at risk EG0021 affected396 at risk
Major depression	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Mental status changes	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0003 affected355 at risk EG0016 affected359 at risk EG0025 affected396 at risk
Mutism	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Psychotic disorder	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Psychotic disorder due to a general medical condition	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Stress	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Acute prerenal failure	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Azotaemia	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0003 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Rectocele	Reproductive system and breast disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Scrotal oedema	Reproductive system and breast disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0012 affected359 at risk EG0022 affected396 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0012 affected359 at risk EG0023 affected396 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0012 affected359 at risk EG0020 affected396 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0012 affected359 at risk EG0022 affected396 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Pulmonary cavitation	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Cystopexy	Surgical and medical procedures	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Hip arthroplasty	Surgical and medical procedures	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Hospitalisation	Surgical and medical procedures	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk
Hysterectomy	Surgical and medical procedures	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Arteriosclerosis	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Bloody discharge	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0020 affected396 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Haematoma	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0011 affected359 at risk EG0020 affected396 at risk
Haemorrhage	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected355 at risk EG0010 affected359 at risk EG0021 affected396 at risk
Hypertension	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0011 affected359 at risk EG0023 affected396 at risk
Hypotension	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0013 affected359 at risk EG0022 affected396 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected355 at risk EG0011 affected359 at risk EG0022 affected396 at risk
Shock	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected355 at risk EG0011 affected359 at risk EG0021 affected396 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00025 affected355 at risk EG00127 affected359 at risk EG00236 affected396 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00023 affected355 at risk EG00117 affected359 at risk EG00219 affected396 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00027 affected355 at risk EG00124 affected359 at risk EG00230 affected396 at risk
Application site dermatitis	General disorders	MedDRA 14.1	Systematic Assessment	EG00030 affected355 at risk EG00136 affected359 at risk EG00243 affected396 at risk
Application site erythema	General disorders	MedDRA 14.1	Systematic Assessment	EG00048 affected355 at risk EG00144 affected359 at risk EG00252 affected396 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG00042 affected355 at risk EG00143 affected359 at risk EG00258 affected396 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG00030 affected355 at risk EG00126 affected359 at risk EG00242 affected396 at risk
Weight decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG00037 affected355 at risk EG00126 affected359 at risk EG00247 affected396 at risk
Agitation	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG00047 affected355 at risk EG00155 affected359 at risk EG00258 affected396 at risk
Anxiety	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG00018 affected355 at risk EG00119 affected359 at risk EG00219 affected396 at risk
Depression	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG00019 affected355 at risk EG00116 affected359 at risk EG00218 affected396 at risk
Hallucination	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0009 affected355 at risk EG00119 affected359 at risk EG00216 affected396 at risk
Insomnia	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG00027 affected355 at risk EG00124 affected359 at risk EG00230 affected396 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG00013 affected355 at risk EG00114 affected359 at risk EG00221 affected396 at risk

ID	Title	Description
BG000	Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
BG001	Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).
BG002	Total	Total of all reporting groups

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D024801	Tauopathies
D019636	Neurodegenerative Diseases
D019965	Neurocognitive Disorders
D001523	Mental Disorders

ID	Term
D048448	Phenylcarbamates
D002219	Carbamates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).	82	355	216	355
EG001	Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch	Patients received rivastigmine 4.6 mg/24 h (5 cm^2).	74	359	210	359
EG002	Extension Study: Rivastigmine 13.3 mg/24 h Transdermal Patch	Patients received rivastigmine 13.3 mg/24 h (15 cm^2).	79	396	248	396