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Effects of Rivastigmine Patch on Activities of Daily Living and Cognition in Patients With Severe Dementia of the Alzheimer's Type (ACTION) (Study Protocol CENA713DUS44, NCT00948766) and a 24 Week Open-label Extension to Study CENA713DUS44 (ACTION)

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ClinicalTrials.gov Identifier: NCT00948766
Recruitment Status : Completed
First Posted : July 29, 2009
Results First Posted : February 11, 2013
Last Update Posted : August 28, 2013
Sponsor:
Information provided by (Responsible Party):
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions 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
Enrollment 716
Recruitment Details  
Pre-assignment Details One patient in each treatment group in the core study and one patient in the treatment group in the extension study did not receive study medication; they were not included in the safety set.
Arm/Group Title Rivastigmine 13.3 mg/24 h Transdermal Patch Rivastigmine 4.6 mg/24 h Transdermal Patch
Hide Arm/Group Description Patients received rivastigmine 13.3 mg/24 h (15 cm^2). Patients received rivastigmine 4.6 mg/24 h (5 cm^2).
Period Title: Core Study
Started 356 360
Exposed to Study Medication 355 359
Completed 229 234
Not Completed 127 126
Reason Not Completed
Adverse Event             73             51
Unsatisfactory Therapeutic Effect             13             14
Patient Withdrew Consent             27             46
Lost to Follow-up             3             2
Administrative Problems             2             2
Death             1             1
Protocol Deviation             8             10
Period Title: Extension Study
Started 397 [1] 0 [2]
Exposed to Study Medication 396 0
Completed 306 0
Not Completed 91 0
Reason Not Completed
Adverse Event             43             0
Unsatisfactory Therapeutic Effect             2             0
Study Drug No Longer Required             1             0
Patient Withdrew Consent             32             0
Lost to Follow-up             8             0
Administrative Problems             1             0
Death             4             0
[1]
397 of the 463 patients who completed the core study entered the extension study.
[2]
No patients received this treatment in the extension study.
Arm/Group Title Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch Total
Hide Arm/Group Description Patients received rivastigmine 13.3 mg/24 h (15 cm^2). Patients received rivastigmine 4.6 mg/24 h (5 cm^2). Total of all reporting groups
Overall Number of Baseline Participants 356 360 716
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 356 participants 360 participants 716 participants
77.6  (8.69) 76.5  (9.35) 77.0  (9.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 356 participants 360 participants 716 participants
Female
227
  63.8%
234
  65.0%
461
  64.4%
Male
129
  36.2%
126
  35.0%
255
  35.6%
1.Primary Outcome
Title Core Study: Change From Baseline in the Alzheimer’s Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24
Hide Description The ADCS-ADL-SIV is designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests, and making judgments and decisions. For each of the 19 questions in the ADCS-ADL-SIV, there was either a forced choice of best response or a "yes" or "no" question with additional sub-questions. Responses for each item were obtained from the caregiver through an interview. Higher numbered scores and answers of "yes" reflected a more self-sufficient individual. The total score was calculated as the sum of all items and sub-questions and ranged from 0 to 54. A higher total score represented a higher functioning patient. A positive change score indicates improvement.
Time Frame Baseline of the core study to Week 24 of the core study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.
Arm/Group Title Rivastigmine 13.3 mg/24 h Transdermal Patch Rivastigmine 4.6 mg/24 h Transdermal Patch
Hide Arm/Group Description:
Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
Patients received rivastigmine 4.6 mg/24 h (5 cm^2).
Overall Number of Participants Analyzed 310 303
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-2.6  (6.82) -3.6  (7.68)
2.Primary Outcome
Title Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24
Hide Description The SIB is a 40-item scale developed for the evaluation of the severity of cognitive dysfunction in more advanced Alzheimer Disease patients. The domains assessed included social interaction, memory, language, attention, orientation, praxis, visuo-spatial ability, construction, and orienting to name. The items of the SIB were developed as simple 1-step commands which are presented by a trained rater with gestural cues and repeated if necessary. The SIB was scored from 0 to 100, with higher scores reflecting higher levels of cognitive ability. A positive change score indicates improvement.
Time Frame Baseline of the core study to Week 24 of the core study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.
Arm/Group Title Rivastigmine 13.3 mg/24 h Transdermal Patch Rivastigmine 4.6 mg/24 h Transdermal Patch
Hide Arm/Group Description:
Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
Patients received rivastigmine 4.6 mg/24 h (5 cm^2).
Overall Number of Participants Analyzed 313 316
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-1.6  (13.54) -6.4  (14.01)
3.Secondary Outcome
Title Core Study: Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24
Hide Description The ADCS-CGIC assesses the clinical meaningfulness of a treatment based on the clinician’s rating of change. The rating is provided by a trained clinician or psychometrician blinded to the patient’s treatment. The rater interviewed the patient and caregiver separately at Baseline using a worksheet that provided space for notes and comments. At baseline, raters had access to all of the patient’s available records and evaluations. The rater used a similar worksheet at follow-up visits, and referred to the baseline worksheet prior to making a rating of change. The worksheets were divided into 3 domains: mental/cognitive state, behavior, and functioning. Change ratings were based on a 7-point scale: Marked (1), moderate (2), and minimal improvement (3), no change (4), and marked (5), moderate (6), and minimal worsening (7). The percentage of patients in each of the 7 categories is reported.
Time Frame Baseline of the core study to Week 24 of the core study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.
Arm/Group Title Rivastigmine 13.3 mg/24 h Transdermal Patch Rivastigmine 4.6 mg/24 h Transdermal Patch
Hide Arm/Group Description:
Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
Patients received rivastigmine 4.6 mg/24 h (5 cm^2).
Overall Number of Participants Analyzed 313 315
Measure Type: Number
Unit of Measure: Percentage of patients
Marked improvement 1.0 1.3
Moderate improvement 3.5 3.5
Minimal improvement 20.1 11.4
No change 34.2 29.2
Minimal worsening 24.3 31.4
Moderate worsening 14.1 19.0
Marked worsening 2.9 4.1
4.Secondary Outcome
Title Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24
Hide Description The NPI-12 assesses a wide range of behaviors encountered in patients with dementia to provide a means of distinguishing the frequency and severity of behavioral changes over time. Ten behavioral and 2 neurovegetative domains were evaluated in an interview with the caregiver given by a mental health professional. The scale included both frequency and severity ratings of each domain as well as a composite domain score (frequency x severity). The sum of the composite scores for the 12 domains yielded the NPI-12 total score. The NPI-12 was scored from 0 to 144, with lower scores reflecting improvement in psychiatric behavior. A negative change score indicates improvement.
Time Frame Baseline of the core study to Week 24 of the core study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.
Arm/Group Title Rivastigmine 13.3 mg/24 h Transdermal Patch Rivastigmine 4.6 mg/24 h Transdermal Patch
Hide Arm/Group Description:
Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
Patients received rivastigmine 4.6 mg/24 h (5 cm^2).
Overall Number of Participants Analyzed 313 313
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-0.4  (14.01) 1.2  (16.79)
5.Secondary Outcome
Title Extension Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24
Hide Description The ADCS-ADL-SIV is designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests, and making judgments and decisions. For each of the 19 questions in the ADCS-ADL-SIV, there was either a forced choice of best response or a "yes" or "no" question with additional sub-questions. Responses for each item were obtained from the caregiver through an interview. Higher numbered scores and answers of "yes" reflected a more self-sufficient individual. The total score was calculated as the sum of all items and sub-questions and ranged from 0 to 54. A higher total score represented a higher functioning patient. A positive change score indicates improvement.
Time Frame Baseline of the core study to Week 24 of the extension study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified full analysis set: All patients who received at least 1 application of study medication and had at least 1 efficacy assessment in the extension study. Only patients with available data were included in the analysis.
Arm/Group Title Rivastigmine 13.3 mg/24 h Transdermal Patch
Hide Arm/Group Description:
Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
Overall Number of Participants Analyzed 372
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-4.3  (8.37)
6.Secondary Outcome
Title Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24
Hide Description The SIB is a 40-item scale developed for the evaluation of the severity of cognitive dysfunction in more advanced Alzheimer Disease patients. The domains assessed included social interaction, memory, language, attention, orientation, praxis, visuo-spatial ability, construction, and orienting to name. The items of the SIB were developed as simple 1-step commands which are presented by a trained rater with gestural cues and repeated if necessary. The SIB was scored from 0 to 100, with higher scores reflecting higher levels of cognitive ability. A positive change score indicates improvement.
Time Frame Baseline of the core study to Week 24 of the extension study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified full analysis set: All patients who received at least 1 application of study medication and had at least 1 efficacy assessment in the extension study. Only patients with available data were included in the analysis.
Arm/Group Title Rivastigmine 13.3 mg/24 h Transdermal Patch
Hide Arm/Group Description:
Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
Overall Number of Participants Analyzed 379
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-5.9  (16.72)
7.Secondary Outcome
Title Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24
Hide Description The ADCS-CGIC assesses the clinical meaningfulness of a treatment based on the clinician’s rating of change. The rating is provided by a trained clinician or psychometrician blinded to the patient’s treatment. The rater interviewed the patient and caregiver separately at Baseline using a worksheet that provided space for notes and comments. At baseline, raters had access to all of the patient’s available records and evaluations. The rater used a similar worksheet at follow-up visits, and referred to the baseline worksheet prior to making a rating of change. The worksheets were divided into 3 domains: mental/cognitive state, behavior, and functioning. Change ratings were based on a 7-point scale: Marked (1), moderate (2), and minimal improvement (3), no change (4), and marked (5), moderate (6), and minimal worsening (7). The percentage of patients in each of the 7 categories is reported.
Time Frame Baseline of the core study to Week 24 of the extension study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified full analysis set: All patients who received at least 1 application of study medication and had at least 1 efficacy assessment in the extension study. Only patients with available data were included in the analysis.
Arm/Group Title Rivastigmine 13.3 mg/24 h Transdermal Patch
Hide Arm/Group Description:
Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
Overall Number of Participants Analyzed 381
Measure Type: Number
Unit of Measure: Percentage of patients
Marked improvement 1.8
Moderate improvement 5.0
Minimal improvement 9.7
No change 26.2
Minimal worsening 31.5
Moderate worsening 21.5
Marked worsening 4.2
Time Frame Adverse events were reported from randomization in the core study through the end of the extension study (48 weeks).
Adverse Event Reporting Description Safety set: All patients who received at least 1 dose of study medication and had at least 1 safety assessment after baseline. One patient in each treatment group did not receive study medication and were not included in the safety set.
 
Arm/Group Title Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch Extension Study: Rivastigmine 13.3 mg/24 h Transdermal Patch
Hide Arm/Group Description Patients received rivastigmine 13.3 mg/24 h (15 cm^2). Patients received rivastigmine 4.6 mg/24 h (5 cm^2). Patients received rivastigmine 13.3 mg/24 h (15 cm^2).
All-Cause Mortality
Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch Extension Study: Rivastigmine 13.3 mg/24 h Transdermal Patch
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch Extension Study: Rivastigmine 13.3 mg/24 h Transdermal Patch
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   82/355 (23.10%)   74/359 (20.61%)   79/396 (19.95%) 
Blood and lymphatic system disorders       
Anaemia  1  2/355 (0.56%)  0/359 (0.00%)  1/396 (0.25%) 
Disseminated intravascular coagulation  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Cardiac disorders       
Acute myocardial infarction  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Angina pectoris  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Arrhythmia  1  1/355 (0.28%)  1/359 (0.28%)  1/396 (0.25%) 
Atrial fibrillation  1  0/355 (0.00%)  2/359 (0.56%)  2/396 (0.51%) 
Bradycardia  1  3/355 (0.85%)  1/359 (0.28%)  2/396 (0.51%) 
Bundle branch block left  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Cardiac arrest  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Cardiac failure acute  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Cardiac failure congestive  1  0/355 (0.00%)  3/359 (0.84%)  2/396 (0.51%) 
Cardio-respiratory arrest  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Cardiopulmonary failure  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Coronary artery disease  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Myocardial infarction  1  2/355 (0.56%)  1/359 (0.28%)  1/396 (0.25%) 
Sinus bradycardia  1  2/355 (0.56%)  0/359 (0.00%)  1/396 (0.25%) 
Supraventricular tachycardia  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Ear and labyrinth disorders       
Vertigo positional  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  2/355 (0.56%)  1/359 (0.28%)  2/396 (0.51%) 
Ascites  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Colitis  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Colitis ischaemic  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Constipation  1  0/355 (0.00%)  2/359 (0.56%)  1/396 (0.25%) 
Diarrhoea  1  3/355 (0.85%)  1/359 (0.28%)  1/396 (0.25%) 
Diverticulum  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Duodenal ulcer  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Dysphagia  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Faecaloma  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Gastrointestinal haemorrhage  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Hiatus hernia  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Intestinal obstruction  1  1/355 (0.28%)  1/359 (0.28%)  1/396 (0.25%) 
Nausea  1  2/355 (0.56%)  0/359 (0.00%)  0/396 (0.00%) 
Small intestinal obstruction  1  2/355 (0.56%)  0/359 (0.00%)  1/396 (0.25%) 
Vomiting  1  4/355 (1.13%)  1/359 (0.28%)  2/396 (0.51%) 
General disorders       
Asthenia  1  2/355 (0.56%)  2/359 (0.56%)  2/396 (0.51%) 
Chest discomfort  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Chest pain  1  2/355 (0.56%)  4/359 (1.11%)  5/396 (1.26%) 
Fatigue  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Gait disturbance  1  0/355 (0.00%)  2/359 (0.56%)  0/396 (0.00%) 
Malaise  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Non-cardiac chest pain  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Oedema peripheral  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Hepatobiliary disorders       
Bile duct obstruction  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Biliary dyskinesia  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Hepatic cirrhosis  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Infections and infestations       
Bronchitis  1  1/355 (0.28%)  2/359 (0.56%)  3/396 (0.76%) 
Cellulitis  1  0/355 (0.00%)  2/359 (0.56%)  1/396 (0.25%) 
Gastroenteritis  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Herpes zoster  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Intestinal gangrene  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Kidney infection  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Lobar pneumonia  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Pneumonia  1  4/355 (1.13%)  5/359 (1.39%)  5/396 (1.26%) 
Pneumonia bacterial  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Sepsis  1  2/355 (0.56%)  1/359 (0.28%)  1/396 (0.25%) 
Urinary tract infection  1  5/355 (1.41%)  7/359 (1.95%)  8/396 (2.02%) 
Injury, poisoning and procedural complications       
Back injury  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Chemical poisoning  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Contusion  1  1/355 (0.28%)  1/359 (0.28%)  1/396 (0.25%) 
Excoriation  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Fall  1  7/355 (1.97%)  7/359 (1.95%)  5/396 (1.26%) 
Femoral neck fracture  1  0/355 (0.00%)  2/359 (0.56%)  1/396 (0.25%) 
Femur fracture  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Fractured sacrum  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Hip fracture  1  4/355 (1.13%)  1/359 (0.28%)  2/396 (0.51%) 
Humerus fracture  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Incorrect dose administered  1  1/355 (0.28%)  1/359 (0.28%)  2/396 (0.51%) 
Jaw fracture  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Joint dislocation  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Laceration  1  1/355 (0.28%)  1/359 (0.28%)  1/396 (0.25%) 
Pubis fracture  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Rib fracture  1  0/355 (0.00%)  4/359 (1.11%)  2/396 (0.51%) 
Road traffic accident  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Skull fracture  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Spinal compression fracture  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Subdural haematoma  1  4/355 (1.13%)  3/359 (0.84%)  4/396 (1.01%) 
Ulna fracture  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Upper limb fracture  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Investigations       
Blood pressure increased  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Blood pressure systolic decreased  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Cardiac enzymes increased  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Electrocardiogram T wave inversion  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
White blood cell count increased  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  3/355 (0.85%)  0/359 (0.00%)  1/396 (0.25%) 
Dehydration  1  6/355 (1.69%)  4/359 (1.11%)  6/396 (1.52%) 
Failure to thrive  1  2/355 (0.56%)  0/359 (0.00%)  1/396 (0.25%) 
Hypoglycaemia  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Hypovolaemia  1  1/355 (0.28%)  1/359 (0.28%)  1/396 (0.25%) 
Malnutrition  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Musculoskeletal and connective tissue disorders       
Muscular weakness  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Rhabdomyolysis  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Colon cancer metastatic  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Gastric cancer  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Nervous system disorders       
Aphasia  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Balance disorder  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Carotid artery stenosis  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Cerebrovascular accident  1  4/355 (1.13%)  1/359 (0.28%)  4/396 (1.01%) 
Convulsion  1  1/355 (0.28%)  3/359 (0.84%)  2/396 (0.51%) 
Coordination abnormal  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Dementia  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Dementia Alzheimer's type  1  3/355 (0.85%)  0/359 (0.00%)  1/396 (0.25%) 
Dizziness  1  2/355 (0.56%)  0/359 (0.00%)  1/396 (0.25%) 
Dysstasia  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Grand mal convulsion  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Headache  1  2/355 (0.56%)  0/359 (0.00%)  1/396 (0.25%) 
Hepatic encephalopathy  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Hypokinesia  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Ischaemic stroke  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Lethargy  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Loss of consciousness  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Mental impairment  1  0/355 (0.00%)  2/359 (0.56%)  2/396 (0.51%) 
Pneumocephalus  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Presyncope  1  1/355 (0.28%)  3/359 (0.84%)  1/396 (0.25%) 
Somnolence  1  0/355 (0.00%)  2/359 (0.56%)  2/396 (0.51%) 
Subarachnoid haemorrhage  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Syncope  1  7/355 (1.97%)  6/359 (1.67%)  7/396 (1.77%) 
Transient ischaemic attack  1  4/355 (1.13%)  1/359 (0.28%)  4/396 (1.01%) 
Unresponsive to stimuli  1  1/355 (0.28%)  1/359 (0.28%)  2/396 (0.51%) 
VIIth nerve paralysis  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Psychiatric disorders       
Aggression  1  0/355 (0.00%)  3/359 (0.84%)  0/396 (0.00%) 
Agitation  1  2/355 (0.56%)  6/359 (1.67%)  1/396 (0.25%) 
Anxiety  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Confusional state  1  3/355 (0.85%)  1/359 (0.28%)  2/396 (0.51%) 
Delirium  1  1/355 (0.28%)  1/359 (0.28%)  1/396 (0.25%) 
Depression  1  0/355 (0.00%)  2/359 (0.56%)  1/396 (0.25%) 
Major depression  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Mental status changes  1  3/355 (0.85%)  6/359 (1.67%)  5/396 (1.26%) 
Mutism  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Psychotic disorder  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Psychotic disorder due to a general medical condition  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Stress  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Renal and urinary disorders       
Acute prerenal failure  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Azotaemia  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Renal failure acute  1  3/355 (0.85%)  1/359 (0.28%)  1/396 (0.25%) 
Reproductive system and breast disorders       
Rectocele  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Scrotal oedema  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Chronic obstructive pulmonary disease  1  1/355 (0.28%)  2/359 (0.56%)  2/396 (0.51%) 
Dyspnoea  1  2/355 (0.56%)  2/359 (0.56%)  3/396 (0.76%) 
Emphysema  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Pleural effusion  1  0/355 (0.00%)  2/359 (0.56%)  0/396 (0.00%) 
Pneumonia aspiration  1  2/355 (0.56%)  2/359 (0.56%)  2/396 (0.51%) 
Pneumothorax  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Pulmonary cavitation  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Pulmonary embolism  1  2/355 (0.56%)  0/359 (0.00%)  1/396 (0.25%) 
Respiratory distress  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Respiratory failure  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Surgical and medical procedures       
Cystopexy  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Hip arthroplasty  1  0/355 (0.00%)  1/359 (0.28%)  0/396 (0.00%) 
Hospitalisation  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Hysterectomy  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Vascular disorders       
Arteriosclerosis  1  2/355 (0.56%)  0/359 (0.00%)  1/396 (0.25%) 
Bloody discharge  1  1/355 (0.28%)  0/359 (0.00%)  0/396 (0.00%) 
Deep vein thrombosis  1  1/355 (0.28%)  1/359 (0.28%)  0/396 (0.00%) 
Haematoma  1  1/355 (0.28%)  1/359 (0.28%)  0/396 (0.00%) 
Haemorrhage  1  1/355 (0.28%)  0/359 (0.00%)  1/396 (0.25%) 
Hypertension  1  2/355 (0.56%)  1/359 (0.28%)  3/396 (0.76%) 
Hypotension  1  0/355 (0.00%)  3/359 (0.84%)  2/396 (0.51%) 
Orthostatic hypotension  1  2/355 (0.56%)  1/359 (0.28%)  2/396 (0.51%) 
Shock  1  0/355 (0.00%)  1/359 (0.28%)  1/396 (0.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch Extension Study: Rivastigmine 13.3 mg/24 h Transdermal Patch
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   216/355 (60.85%)   210/359 (58.50%)   248/396 (62.63%) 
Gastrointestinal disorders       
Diarrhoea  1  25/355 (7.04%)  27/359 (7.52%)  36/396 (9.09%) 
Nausea  1  23/355 (6.48%)  17/359 (4.74%)  19/396 (4.80%) 
Vomiting  1  27/355 (7.61%)  24/359 (6.69%)  30/396 (7.58%) 
General disorders       
Application site dermatitis  1  30/355 (8.45%)  36/359 (10.03%)  43/396 (10.86%) 
Application site erythema  1  48/355 (13.52%)  44/359 (12.26%)  52/396 (13.13%) 
Infections and infestations       
Urinary tract infection  1  42/355 (11.83%)  43/359 (11.98%)  58/396 (14.65%) 
Injury, poisoning and procedural complications       
Fall  1  30/355 (8.45%)  26/359 (7.24%)  42/396 (10.61%) 
Investigations       
Weight decreased  1  37/355 (10.42%)  26/359 (7.24%)  47/396 (11.87%) 
Psychiatric disorders       
Agitation  1  47/355 (13.24%)  55/359 (15.32%)  58/396 (14.65%) 
Anxiety  1  18/355 (5.07%)  19/359 (5.29%)  19/396 (4.80%) 
Depression  1  19/355 (5.35%)  16/359 (4.46%)  18/396 (4.55%) 
Hallucination  1  9/355 (2.54%)  19/359 (5.29%)  16/396 (4.04%) 
Insomnia  1  27/355 (7.61%)  24/359 (6.69%)  30/396 (7.58%) 
Renal and urinary disorders       
Urinary incontinence  1  13/355 (3.66%)  14/359 (3.90%)  21/396 (5.30%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862 778-8300
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00948766     History of Changes
Obsolete Identifiers: NCT01054755
Other Study ID Numbers: CENA713DUS44
First Submitted: July 28, 2009
First Posted: July 29, 2009
Results First Submitted: January 8, 2013
Results First Posted: February 11, 2013
Last Update Posted: August 28, 2013