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Long-term Safety of Rivastigmine Capsule and Patch in Patients With Mild to Moderately-severe Dementia Associated With Parkinson's Disease (PDD)

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ClinicalTrials.gov Identifier: NCT00623103
Recruitment Status : Completed
First Posted : February 25, 2008
Results First Posted : November 28, 2011
Last Update Posted : November 28, 2011
Sponsor:
Information provided by (Responsible Party):
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Parkinson's Disease Dementia
Interventions Drug: Rivastigmine capsule
Drug: Rivastigmine transdermal patch
Enrollment 583

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rivastigmine Capsule Rivastigmine Patch
Hide Arm/Group Description Rivastigmine capsules starting at a total dose of 3 mg/day (1.5 mg twice daily orally) titrated up in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day (6 mg twice daily orally0. The 12 mg/day dose or the highest dose tolerated was maintained until week 76. Rivastigmine patch once a day in the morning, worn for 24 hours, starting at 5 cm^2 (delivering 4.6 mg rivastigmine over a 24 hour period) for 4 weeks then titrated up to 10 cm^2 daily (delivering 9.5 mg rivastigmine over a 24 hour period). The 10 cm^2 patch or the highest well tolerated dose was maintained until week 76.
Period Title: Overall Study
Started 295 288
Safety Set: Received Study Drug 294 [1] 288
Completed 184 175
Not Completed 111 113
Reason Not Completed
Adverse Event             70             60
Unsatisfactory therapeutic effect             4             12
Withdrawal by Subject             18             24
Lost to Follow-up             4             1
Administrative problems             2             4
Death             11             11
Protocol deviation             2             1
[1]
One randomized participant did not receive study drug and was not included in the Safety set.
Arm/Group Title Rivastigmine Capsule Rivastigmine Patch Total
Hide Arm/Group Description Rivastigmine capsules starting at a total dose of 3 mg/day (1.5 mg twice daily orally) titrated up in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day (6 mg twice daily orally0. The 12 mg/day dose or the highest dose tolerated was maintained until week 76. Rivastigmine patch once a day in the morning, worn for 24 hours, starting at 5 cm^2 (delivering 4.6 mg rivastigmine over a 24 hour period) for 4 weeks then titrated up to 10 cm^2 daily (delivering 9.5 mg rivastigmine over a 24 hour period). The 10 cm^2 patch or the highest well tolerated dose was maintained until week 76. Total of all reporting groups
Overall Number of Baseline Participants 295 288 583
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 295 participants 288 participants 583 participants
72.35  (6.295) 72.26  (6.352) 72.31  (6.318)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 295 participants 288 participants 583 participants
Female
88
  29.8%
97
  33.7%
185
  31.7%
Male
207
  70.2%
191
  66.3%
398
  68.3%
1.Primary Outcome
Title Percentage of Participants With Adverse Events (AEs) Due, or Potentially Due, to Worsening of Parkinson Disease (PD) Motor Symptoms (Tremor, Muscle Rigidity, Bradykinesia, Fall)
Hide Description The AEs were summarized by presenting the number and percentage of patients having any of the 4 AEs or discontinued due to any of the 4 predefined AEs (tremor, muscle rigidity, bradykinesia, and fall)in each treatment group. The 95% CIs associated with the rates were also presented.
Time Frame 76 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population consisted of all participants who received at least 1 dose of study drug and had 1 post-baseline safety measurement. Participants with observation at 76 weeks were included in this analysis.
Arm/Group Title Rivastigmine Capsule Rivastigmine Patch
Hide Arm/Group Description:
Rivastigmine capsules starting at a total dose of 3 mg/day (1.5 mg twice daily orally) titrated up in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day (6 mg twice daily orally0. The 12 mg/day dose or the highest dose tolerated was maintained until week 76.
Rivastigmine patch once a day in the morning, worn for 24 hours, starting at 5 cm^2 (delivering 4.6 mg rivastigmine over a 24 hour period) for 4 weeks then titrated up to 10 cm^2 daily (delivering 9.5 mg rivastigmine over a 24 hour period). The 10 cm^2 patch or the highest well tolerated dose was maintained until week 76.
Overall Number of Participants Analyzed 294 288
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Tremor
24.5
(19.7 to 29.8)
9.7
(6.6 to 13.7)
Muscle Rigidity
4.1
(2.1 to 7.0)
5.2
(2.9 to 8.4)
Bradykinesia
5.1
(2.9 to 8.3)
6.3
(3.7 to 9.7)
Fall
17.0
(12.9 to 21.8)
20.1
(15.7 to 25.2)
2.Primary Outcome
Title Percentage of Participants With Study Drug Discontinuations Due to Predefined AEs That Are Due, or Potentially Due, to Worsening of PD Motor Symptoms (Tremor, Muscle Rigidity, Bradykinesia, Fall)
Hide Description The discontinuations due to these AEs were summarized by presenting the number and percentage of patients having any of the 4 AEs or discontinued due to any of the 4 predefined AEs (tremor, muscle rigidity, bradykinesia, and fall) in each treatment group. The 95% CIs associated with these rates were also presented.
Time Frame 76 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population consisted of all participants who received at least 1 dose of study drug and had 1 post-baseline safety measurement. Participants with observation at 76 weeks were included in this analysis.
Arm/Group Title Rivastigmine Capsule Rivastigmine Patch
Hide Arm/Group Description:
Rivastigmine capsules starting at a total dose of 3 mg/day (1.5 mg twice daily orally) titrated up in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day (6 mg twice daily orally0. The 12 mg/day dose or the highest dose tolerated was maintained until week 76.
Rivastigmine patch once a day in the morning, worn for 24 hours, starting at 5 cm^2 (delivering 4.6 mg rivastigmine over a 24 hour period) for 4 weeks then titrated up to 10 cm^2 daily (delivering 9.5 mg rivastigmine over a 24 hour period). The 10 cm^2 patch or the highest well tolerated dose was maintained until week 76.
Overall Number of Participants Analyzed 294 288
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Tremor
2.4
(1.0 to 4.8)
0.7
(0.1 to 2.5)
Muscle Rigidity
0.3
(0.0 to 1.9)
0.3
(0.0 to 1.9)
Bradykinesia
1.0
(0.2 to 3.0)
0.0
(0.0 to 0.0)
Fall
1.0
(0.2 to 3.0)
1.4
(0.4 to 3.5)
3.Secondary Outcome
Title Change in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination Scores at Weeks 8, 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline
Hide Description Unified Parkinson Disease Rating Scale (UPDRS) is a 6 part Parkinson's disease specific rating scale that estimates clinical function taking into consideration both disability (functional deficits) and impairment (objective clinical signs). Part III records the motor examination in Items 18-31 rated on a scale of 0 to 4 with (0 being absent/ normal and 4 being the worse) for a total possible score of 0 to 56.
Time Frame From Baseline to Weeks 8, 16, 24, 52 and 76
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population consisted of all participants who received at least 1 dose of study drug and had 1 post-baseline safety measurement. "n" in each of the categories is the number of participants at each time point with non-missing baseline and post-baseline measurements.
Arm/Group Title Rivastigmine Capsule Rivastigmine Patch
Hide Arm/Group Description:
Rivastigmine capsules starting at a total dose of 3 mg/day (1.5 mg twice daily orally) titrated up in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day (6 mg twice daily orally0. The 12 mg/day dose or the highest dose tolerated was maintained until week 76.
Rivastigmine patch once a day in the morning, worn for 24 hours, starting at 5 cm^2 (delivering 4.6 mg rivastigmine over a 24 hour period) for 4 weeks then titrated up to 10 cm^2 daily (delivering 9.5 mg rivastigmine over a 24 hour period). The 10 cm^2 patch or the highest well tolerated dose was maintained until week 76.
Overall Number of Participants Analyzed 294 288
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 8 (n=276,277) -0.4  (6.99) -0.9  (7.05)
Week 16 (n=254,252) 0.5  (7.72) -1.7  (7.44)
Week 24 (n=229,237) 0.1  (8.19) -1.4  (7.90)
Week 52 (n=203,206) 0.7  (8.66) 1.6  (9.57)
Week 76 (n=183,175) 2.1  (9.98) 2.1  (9.65)
4.Secondary Outcome
Title Change in Mattis Dementia Rating Scale (Mattis DRS-2) Scores at Weeks 16, 24, 52 and 76 Compared to Baseline
Hide Description Mattis DRS-2 is a measure of cognitive status. The total score is the sum of 5 subscale scores: Attention [0-37], Initiation/Perservation [0-37] (performing alternating movements), Construction [0-6] (copying designs), Conceptualization [0-39] (similarities) and Memory [0-25] (sentence recall, design recognition)for a total possible score of 0-144. Higher score is reflective of better cognitive function, lower scores associated with more pronounced cognitive deficit. The change from baseline was calculated such that a positive number indicates an improvement.
Time Frame From Baseline to Weeks 16, 24, 52 and 76
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population which included all patients who received at least 1 dose of study drug and had at least 1 pre- and post-baseline assessment for 1 of the efficacy variables. Last observation carried forward. (LOCF)
Arm/Group Title Rivastigmine Capsule Rivastigmine Patch
Hide Arm/Group Description:
Rivastigmine capsules starting at a total dose of 3 mg/day (1.5 mg twice daily orally) titrated up in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day (6 mg twice daily orally0. The 12 mg/day dose or the highest dose tolerated was maintained until week 76.
Rivastigmine patch once a day in the morning, worn for 24 hours, starting at 5 cm^2 (delivering 4.6 mg rivastigmine over a 24 hour period) for 4 weeks then titrated up to 10 cm^2 daily (delivering 9.5 mg rivastigmine over a 24 hour period). The 10 cm^2 patch or the highest well tolerated dose was maintained until week 76.
Overall Number of Participants Analyzed 273 273
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 16 5.4  (11.98) 3.4  (11.53)
Week 24 6.5  (12.98) 4.4  (12.85)
Week 52 4.6  (13.62) 1.3  (15.07)
Week 76 3.9  (16.82) -1.4  (17.43)
5.Secondary Outcome
Title Change in Ten Point Clock Test (TPCT) Scores at Weeks 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline
Hide Description The Ten Point Clock Test measures executive functioning and visuospatial skills. Participants are asked to put numbers on the face of a clock and then make the clock read 10 minutes after 11. Points are awarded on a scale of 0 to 10 for spacing of specific numbers and the positions of the hands. The change from baseline was calculated such that a positive number indicates improvement.
Time Frame From Baseline to Weeks 16, 24, 52 and 76
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population which included all patients who received at least 1 dose of study drug and had at least 1 pre- and post-baseline assessment for 1 of the efficacy variables. Last observation carried forward. (LOCF)
Arm/Group Title Rivastigmine Capsule Rivastigmine Patch
Hide Arm/Group Description:
Rivastigmine capsules starting at a total dose of 3 mg/day (1.5 mg twice daily orally) titrated up in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day (6 mg twice daily orally0. The 12 mg/day dose or the highest dose tolerated was maintained until week 76.
Rivastigmine patch once a day in the morning, worn for 24 hours, starting at 5 cm^2 (delivering 4.6 mg rivastigmine over a 24 hour period) for 4 weeks then titrated up to 10 cm^2 daily (delivering 9.5 mg rivastigmine over a 24 hour period). The 10 cm^2 patch or the highest well tolerated dose was maintained until week 76.
Overall Number of Participants Analyzed 273 273
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 16 0.5  (2.75) 0.4  (3.02)
Week 24 0.6  (3.18) 0.3  (3.40)
Week 52 0.3  (2.97) -0.1  (3.33)
Week 76 0.0  (3.2) -0.3  (3.57)
6.Secondary Outcome
Title Change in Neuropsychiatric Inventory-10 (NPI-10) Scores at Weeks 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline
Hide Description The parameter for analysis was the change from baseline of total score of 10 items on the NPI scale (NPI-10). The total score is a sum of the 10 domains, where the score for a domain is defined as the product of frequency (range: 1-4) and severity (range: 1-3). Each domain has a maximum score of 12 and all domains were equally weighted for total score(thus the range for the total score is 0 to 120 with 0 being completely healthy to 120 which is the worse score patient can get). The change from baseline was calculated such that a negative number indicates an improvement (symptom reduction).
Time Frame At Week 16, 24, 52 and 76 (or early discontinuation)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population which included all patients who received at least 1 dose of study drug and had at least 1 pre- and post-baseline assessment for 1 of the efficacy variables. Last observation carried forward. (LOCF)
Arm/Group Title Rivastigmine Capsule Rivastigmine Patch
Hide Arm/Group Description:
Rivastigmine capsules starting at a total dose of 3 mg/day (1.5 mg twice daily orally) titrated up in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day (6 mg twice daily orally0. The 12 mg/day dose or the highest dose tolerated was maintained until week 76.
Rivastigmine patch once a day in the morning, worn for 24 hours, starting at 5 cm^2 (delivering 4.6 mg rivastigmine over a 24 hour period) for 4 weeks then titrated up to 10 cm^2 daily (delivering 9.5 mg rivastigmine over a 24 hour period). The 10 cm^2 patch or the highest well tolerated dose was maintained until week 76.
Overall Number of Participants Analyzed 294 288
Mean (Standard Deviation)
Unit of Measure: Score
Week 16 -3.3  (9.75) -0.5  (10.89)
Week 24 -2.6  (10.31) -1.0  (10.27)
Week 52 -1.7  (11.40) -0.3  (11.26)
Week 76 -1.6  (11.22) 0.7  (12.62)
7.Secondary Outcome
Title Change in Alzheimer's Disease Cooperative Study-Activities Of Daily Living (ADCS-ADL) Scores at Weeks 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline
Hide Description

The 23 item caregiver-based ADL scale of the dementia Alzheimer’s disease Cooperative Study-Activities of Daily Living (ADCS-ADL) was used for analysis. This is a caregiver rated questionnaire of 23 items, with possible scores over a range of 0-78, where 78 denote full functioning with no impairment. The total score was derived by adding up the item scores of the 23 items.

The change from baseline was calculated such that a positive change indicates an improvement.

Time Frame From Baseline to Week 16, 24, 52 and 76 (or early discontinuation)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population which included all patients who received at least 1 dose of study drug and had at least 1 pre- and post-baseline assessment for 1 of the efficacy variables. Last observation carried forward. (LOCF).
Arm/Group Title Rivastigmine Capsule Rivastigmine Patch
Hide Arm/Group Description:
Rivastigmine capsules starting at a total dose of 3 mg/day (1.5 mg twice daily orally) titrated up in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day (6 mg twice daily orally0. The 12 mg/day dose or the highest dose tolerated was maintained until week 76.
Rivastigmine patch once a day in the morning, worn for 24 hours, starting at 5 cm^2 (delivering 4.6 mg rivastigmine over a 24 hour period) for 4 weeks then titrated up to 10 cm^2 daily (delivering 9.5 mg rivastigmine over a 24 hour period). The 10 cm^2 patch or the highest well tolerated dose was maintained until week 76.
Overall Number of Participants Analyzed 294 288
Mean (Standard Deviation)
Unit of Measure: Score
Week 16 (n=273, 270) -0.4  (9.60) -1.3  (10.38)
Week 24 (n=273,270) -0.6  (10.12) -1.5  (10.91)
Week 52 (n=273,270) -2.2  (11.13) -5.4  (13.57)
Week 76 (n=273, 270) -4.4  (13.13) -7.8  (15.62)
8.Secondary Outcome
Title UPDRS Part V Stage (Modified Hoehn and Yahr Staging)at Baseline, Week 8,16,24,52 and 76 (or Early Discontinuation)
Hide Description Unified Parkinson Disease Rating Scale (UPDRS) is a 6 part Parkinson's disease specific rating scale that estimates clinical function taking into consideration both disability (functional deficits) and impairment (objective clinical signs). UPDRS Part V is assessed by the modified Hoehn and Yahr Staging Scale. The scale ranges from 0 (no signs of disease) to 5 (wheelchair bound or bedridden unless aided).
Time Frame From Baseline to Week 8, 16, 24, 52 and 76 (or early discontinuation)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Safety population consisted of all patients who have received at least one dose of study drug and have had at least 1 safety measurement after baseline. n=indicates patients with observation during different timepoints.
Arm/Group Title Rivastigmine Capsule Rivastigmine Patch
Hide Arm/Group Description:
Rivastigmine capsules starting at a total dose of 3 mg/day (1.5 mg twice daily orally) titrated up in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day (6 mg twice daily orally0. The 12 mg/day dose or the highest dose tolerated was maintained until week 76.
Rivastigmine patch once a day in the morning, worn for 24 hours, starting at 5 cm^2 (delivering 4.6 mg rivastigmine over a 24 hour period) for 4 weeks then titrated up to 10 cm^2 daily (delivering 9.5 mg rivastigmine over a 24 hour period). The 10 cm^2 patch or the highest well tolerated dose was maintained until week 76.
Overall Number of Participants Analyzed 294 288
Mean (Standard Deviation)
Unit of Measure: Score
Baseline (n = 294,288) 2.7  (0.65) 2.7  (0.70)
Week 8 (n=17,18) 2.6  (0.70) 2.7  (1.05)
Week 16 (n=254,252) 2.8  (0.68) 2.7  (0.67)
Week 24 (229, 236) 2.7  (0.75) 2.7  (0.67)
Week 52 (n=202,208) 2.8  (0.73) 2.8  (0.69)
Week 76 (n=184, 175) 2.8  (0.74) 2.8  (0.79)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Exelon Capsule Exelon Patch
Hide Arm/Group Description Exelon Capsule Exelon Patch
All-Cause Mortality
Exelon Capsule Exelon Patch
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Exelon Capsule Exelon Patch
Affected / at Risk (%) Affected / at Risk (%)
Total   87/294 (29.59%)   83/288 (28.82%) 
Cardiac disorders     
Acute myocardial infarction  1  0/294 (0.00%)  1/288 (0.35%) 
Angina pectoris  1  1/294 (0.34%)  2/288 (0.69%) 
Arteriosclerosis coronary artery  1  1/294 (0.34%)  0/288 (0.00%) 
Atrial fibrillation  1  3/294 (1.02%)  0/288 (0.00%) 
Atrial flutter  1  1/294 (0.34%)  0/288 (0.00%) 
Atrioventricular block second degree  1  0/294 (0.00%)  1/288 (0.35%) 
Bradycardia  1  1/294 (0.34%)  0/288 (0.00%) 
Cardiac arrest  1  1/294 (0.34%)  0/288 (0.00%) 
Cardiac failure  1  1/294 (0.34%)  2/288 (0.69%) 
Cardiac failure acute  1  0/294 (0.00%)  1/288 (0.35%) 
Cardiac valve sclerosis  1  1/294 (0.34%)  0/288 (0.00%) 
Cardio-respiratory arrest  1  1/294 (0.34%)  1/288 (0.35%) 
Coronary artery disease  1  1/294 (0.34%)  1/288 (0.35%) 
Myocardial infarction  1  2/294 (0.68%)  2/288 (0.69%) 
Sinus arrhythmia  1  1/294 (0.34%)  0/288 (0.00%) 
Gastrointestinal disorders     
Abdominal distension  1  1/294 (0.34%)  0/288 (0.00%) 
Abdominal hernia  1  1/294 (0.34%)  0/288 (0.00%) 
Abdominal pain  1  1/294 (0.34%)  0/288 (0.00%) 
Abdominal pain upper  1  1/294 (0.34%)  0/288 (0.00%) 
Constipation  1  0/294 (0.00%)  1/288 (0.35%) 
Diarrhoea  1  1/294 (0.34%)  3/288 (1.04%) 
Duodenal ulcer haemorrhage  1  1/294 (0.34%)  0/288 (0.00%) 
Gastric ulcer haemorrhage  1  0/294 (0.00%)  1/288 (0.35%) 
Haemorrhoidal haemorrhage  1  0/294 (0.00%)  1/288 (0.35%) 
Haemorrhoids  1  0/294 (0.00%)  1/288 (0.35%) 
Ileus  1  1/294 (0.34%)  1/288 (0.35%) 
Inguinal hernia  1  1/294 (0.34%)  1/288 (0.35%) 
Inguinal hernia strangulated  1  1/294 (0.34%)  0/288 (0.00%) 
Intestinal obstruction  1  1/294 (0.34%)  1/288 (0.35%) 
Melaena  1  0/294 (0.00%)  1/288 (0.35%) 
Mesenteric occlusion  1  1/294 (0.34%)  1/288 (0.35%) 
Nausea  1  2/294 (0.68%)  1/288 (0.35%) 
Pancreatitis  1  1/294 (0.34%)  0/288 (0.00%) 
Pancreatitis acute  1  1/294 (0.34%)  0/288 (0.00%) 
Periodontitis  1  0/294 (0.00%)  1/288 (0.35%) 
Rectal haemorrhage  1  0/294 (0.00%)  1/288 (0.35%) 
Salivary hypersecretion  1  1/294 (0.34%)  0/288 (0.00%) 
Small intestinal obstruction  1  2/294 (0.68%)  0/288 (0.00%) 
Umbilical hernia  1  1/294 (0.34%)  0/288 (0.00%) 
Vomiting  1  0/294 (0.00%)  1/288 (0.35%) 
General disorders     
Asthenia  1  1/294 (0.34%)  0/288 (0.00%) 
Complication of device insertion  1  0/294 (0.00%)  1/288 (0.35%) 
Device failure  1  1/294 (0.34%)  0/288 (0.00%) 
Fatigue  1  2/294 (0.68%)  0/288 (0.00%) 
Gait disturbance  1  0/294 (0.00%)  1/288 (0.35%) 
General physical health deterioration  1  1/294 (0.34%)  0/288 (0.00%) 
Non-cardiac chest pain  1  2/294 (0.68%)  0/288 (0.00%) 
Pyrexia  1  2/294 (0.68%)  3/288 (1.04%) 
Hepatobiliary disorders     
Cholelithiasis  1  2/294 (0.68%)  1/288 (0.35%) 
Infections and infestations     
Bronchitis  1  1/294 (0.34%)  0/288 (0.00%) 
Bronchopneumonia  1  1/294 (0.34%)  1/288 (0.35%) 
Cellulitis  1  0/294 (0.00%)  1/288 (0.35%) 
Cystitis klebsiella  1  1/294 (0.34%)  0/288 (0.00%) 
Gastroenteritis viral  1  0/294 (0.00%)  1/288 (0.35%) 
Gastrointestinal infection  1  2/294 (0.68%)  0/288 (0.00%) 
Helicobacter infection  1  2/294 (0.68%)  0/288 (0.00%) 
Lung infection  1  1/294 (0.34%)  0/288 (0.00%) 
Pneumonia  1  9/294 (3.06%)  7/288 (2.43%) 
Pneumonia fungal  1  1/294 (0.34%)  0/288 (0.00%) 
Post procedural sepsis  1  0/294 (0.00%)  1/288 (0.35%) 
Rash pustular  1  1/294 (0.34%)  0/288 (0.00%) 
Respiratory tract infection  1  2/294 (0.68%)  0/288 (0.00%) 
Sepsis  1  0/294 (0.00%)  1/288 (0.35%) 
Tracheobronchitis  1  0/294 (0.00%)  1/288 (0.35%) 
Urinary tract infection  1  2/294 (0.68%)  4/288 (1.39%) 
Injury, poisoning and procedural complications     
Accidental overdose  1  0/294 (0.00%)  1/288 (0.35%) 
Brain herniation  1  1/294 (0.34%)  0/288 (0.00%) 
Concussion  1  1/294 (0.34%)  0/288 (0.00%) 
Contusion  1  2/294 (0.68%)  0/288 (0.00%) 
Fall  1  2/294 (0.68%)  9/288 (3.13%) 
Femoral neck fracture  1  2/294 (0.68%)  1/288 (0.35%) 
Femur fracture  1  6/294 (2.04%)  3/288 (1.04%) 
Hand fracture  1  1/294 (0.34%)  0/288 (0.00%) 
Head injury  1  2/294 (0.68%)  0/288 (0.00%) 
Hip fracture  1  3/294 (1.02%)  2/288 (0.69%) 
Humerus fracture  1  0/294 (0.00%)  2/288 (0.69%) 
Lower limb fracture  1  1/294 (0.34%)  2/288 (0.69%) 
Nerve root injury  1  0/294 (0.00%)  1/288 (0.35%) 
Pelvic fracture  1  0/294 (0.00%)  1/288 (0.35%) 
Post-traumatic pain  1  1/294 (0.34%)  0/288 (0.00%) 
Rib fracture  1  1/294 (0.34%)  2/288 (0.69%) 
Scapula fracture  1  1/294 (0.34%)  0/288 (0.00%) 
Skin laceration  1  1/294 (0.34%)  0/288 (0.00%) 
Spinal compression fracture  1  1/294 (0.34%)  0/288 (0.00%) 
Spinal fracture  1  1/294 (0.34%)  0/288 (0.00%) 
Upper limb fracture  1  1/294 (0.34%)  0/288 (0.00%) 
Wrist fracture  1  1/294 (0.34%)  0/288 (0.00%) 
Investigations     
Weight decreased  1  0/294 (0.00%)  1/288 (0.35%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/294 (0.00%)  1/288 (0.35%) 
Dehydration  1  3/294 (1.02%)  4/288 (1.39%) 
Hypokalaemia  1  1/294 (0.34%)  0/288 (0.00%) 
Weight loss poor  1  0/294 (0.00%)  1/288 (0.35%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/294 (0.00%)  1/288 (0.35%) 
Back pain  1  2/294 (0.68%)  0/288 (0.00%) 
Bursitis  1  1/294 (0.34%)  0/288 (0.00%) 
Mobility decreased  1  0/294 (0.00%)  1/288 (0.35%) 
Musculoskeletal discomfort  1  0/294 (0.00%)  1/288 (0.35%) 
Pathological fracture  1  1/294 (0.34%)  0/288 (0.00%) 
Spinal osteoarthritis  1  0/294 (0.00%)  1/288 (0.35%) 
Synovitis  1  1/294 (0.34%)  0/288 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder cancer  1  1/294 (0.34%)  0/288 (0.00%) 
Breast cancer  1  0/294 (0.00%)  1/288 (0.35%) 
Malignant melanoma  1  1/294 (0.34%)  0/288 (0.00%) 
Meningioma benign  1  0/294 (0.00%)  1/288 (0.35%) 
Prostate cancer  1  1/294 (0.34%)  1/288 (0.35%) 
Rectosigmoid cancer  1  0/294 (0.00%)  1/288 (0.35%) 
Waldenstrom's macroglobulinaemia  1  0/294 (0.00%)  1/288 (0.35%) 
Nervous system disorders     
Akinesia  1  2/294 (0.68%)  3/288 (1.04%) 
Aphasia  1  0/294 (0.00%)  1/288 (0.35%) 
Balance disorder  1  1/294 (0.34%)  0/288 (0.00%) 
Basilar artery thrombosis  1  0/294 (0.00%)  1/288 (0.35%) 
Bradykinesia  1  2/294 (0.68%)  3/288 (1.04%) 
Cerebral infarction  1  0/294 (0.00%)  2/288 (0.69%) 
Cerebrovascular accident  1  1/294 (0.34%)  0/288 (0.00%) 
Cognitive disorder  1  1/294 (0.34%)  0/288 (0.00%) 
Cogwheel rigidity  1  4/294 (1.36%)  2/288 (0.69%) 
Coma  1  0/294 (0.00%)  1/288 (0.35%) 
Convulsion  1  0/294 (0.00%)  1/288 (0.35%) 
Dementia  1  1/294 (0.34%)  0/288 (0.00%) 
Depressed level of consciousness  1  1/294 (0.34%)  0/288 (0.00%) 
Dizziness  1  1/294 (0.34%)  3/288 (1.04%) 
Dysarthria  1  0/294 (0.00%)  1/288 (0.35%) 
Dyskinesia  1  0/294 (0.00%)  3/288 (1.04%) 
Epilepsy  1  0/294 (0.00%)  2/288 (0.69%) 
Freezing phenomenon  1  2/294 (0.68%)  1/288 (0.35%) 
Hypokinesia  1  0/294 (0.00%)  1/288 (0.35%) 
Lacunar infarction  1  0/294 (0.00%)  1/288 (0.35%) 
Loss of consciousness  1  1/294 (0.34%)  2/288 (0.69%) 
Monoparesis  1  0/294 (0.00%)  1/288 (0.35%) 
On and off phenomenon  1  3/294 (1.02%)  0/288 (0.00%) 
Parkinson's disease  1  0/294 (0.00%)  1/288 (0.35%) 
Parkinsonian gait  1  3/294 (1.02%)  2/288 (0.69%) 
Parkinsonian rest tremor  1  3/294 (1.02%)  2/288 (0.69%) 
Psychomotor hyperactivity  1  2/294 (0.68%)  0/288 (0.00%) 
Psychomotor skills impaired  1  1/294 (0.34%)  0/288 (0.00%) 
Quadriplegia  1  1/294 (0.34%)  0/288 (0.00%) 
Somnolence  1  1/294 (0.34%)  1/288 (0.35%) 
Syncope  1  5/294 (1.70%)  1/288 (0.35%) 
Transient ischaemic attack  1  1/294 (0.34%)  4/288 (1.39%) 
Psychiatric disorders     
Agitation  1  0/294 (0.00%)  2/288 (0.69%) 
Anxiety  1  1/294 (0.34%)  1/288 (0.35%) 
Confusional state  1  3/294 (1.02%)  6/288 (2.08%) 
Delirium  1  0/294 (0.00%)  2/288 (0.69%) 
Delusion  1  1/294 (0.34%)  1/288 (0.35%) 
Depression  1  0/294 (0.00%)  1/288 (0.35%) 
Hallucination  1  1/294 (0.34%)  4/288 (1.39%) 
Hallucination, visual  1  3/294 (1.02%)  3/288 (1.04%) 
Insomnia  1  0/294 (0.00%)  2/288 (0.69%) 
Mental status changes  1  1/294 (0.34%)  0/288 (0.00%) 
Psychotic disorder  1  0/294 (0.00%)  1/288 (0.35%) 
Psychotic disorder due to a general medical condition  1  0/294 (0.00%)  1/288 (0.35%) 
Renal and urinary disorders     
Bladder trabeculation  1  0/294 (0.00%)  1/288 (0.35%) 
Calculus bladder  1  1/294 (0.34%)  0/288 (0.00%) 
Haematuria  1  1/294 (0.34%)  0/288 (0.00%) 
Micturition urgency  1  0/294 (0.00%)  1/288 (0.35%) 
Renal failure  1  1/294 (0.34%)  1/288 (0.35%) 
Urinary bladder polyp  1  1/294 (0.34%)  0/288 (0.00%) 
Urinary incontinence  1  0/294 (0.00%)  1/288 (0.35%) 
Urinary retention  1  2/294 (0.68%)  0/288 (0.00%) 
Urinary tract obstruction  1  1/294 (0.34%)  0/288 (0.00%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  1/294 (0.34%)  0/288 (0.00%) 
Prostatic obstruction  1  0/294 (0.00%)  1/288 (0.35%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  1/294 (0.34%)  0/288 (0.00%) 
Brain hypoxia  1  1/294 (0.34%)  1/288 (0.35%) 
Dyspnoea  1  3/294 (1.02%)  1/288 (0.35%) 
Lung disorder  1  0/294 (0.00%)  1/288 (0.35%) 
Pleural effusion  1  1/294 (0.34%)  0/288 (0.00%) 
Pneumonia aspiration  1  0/294 (0.00%)  1/288 (0.35%) 
Productive cough  1  0/294 (0.00%)  1/288 (0.35%) 
Pulmonary embolism  1  4/294 (1.36%)  1/288 (0.35%) 
Pulmonary oedema  1  1/294 (0.34%)  0/288 (0.00%) 
Respiratory arrest  1  1/294 (0.34%)  0/288 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin ulcer  1  0/294 (0.00%)  1/288 (0.35%) 
Urticaria  1  1/294 (0.34%)  0/288 (0.00%) 
Vascular disorders     
Haematoma  1  0/294 (0.00%)  1/288 (0.35%) 
Hypertension  1  0/294 (0.00%)  2/288 (0.69%) 
Hypertensive crisis  1  1/294 (0.34%)  1/288 (0.35%) 
Hypotension  1  3/294 (1.02%)  0/288 (0.00%) 
Orthostatic hypotension  1  1/294 (0.34%)  0/288 (0.00%) 
Peripheral arterial occlusive disease  1  0/294 (0.00%)  1/288 (0.35%) 
Phlebitis  1  1/294 (0.34%)  0/288 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Exelon Capsule Exelon Patch
Affected / at Risk (%) Affected / at Risk (%)
Total   239/294 (81.29%)   215/288 (74.65%) 
Gastrointestinal disorders     
Constipation  1  21/294 (7.14%)  21/288 (7.29%) 
Diarrhoea  1  27/294 (9.18%)  14/288 (4.86%) 
Nausea  1  117/294 (39.80%)  23/288 (7.99%) 
Vomiting  1  45/294 (15.31%)  7/288 (2.43%) 
General disorders     
Application site erythema  1  0/294 (0.00%)  40/288 (13.89%) 
Fatigue  1  19/294 (6.46%)  13/288 (4.51%) 
Infections and infestations     
Urinary tract infection  1  17/294 (5.78%)  21/288 (7.29%) 
Injury, poisoning and procedural complications     
Fall  1  48/294 (16.33%)  49/288 (17.01%) 
Investigations     
Weight decreased  1  19/294 (6.46%)  18/288 (6.25%) 
Metabolism and nutrition disorders     
Decreased appetite  1  18/294 (6.12%)  12/288 (4.17%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  13/294 (4.42%)  16/288 (5.56%) 
Nervous system disorders     
Bradykinesia  1  13/294 (4.42%)  15/288 (5.21%) 
Dizziness  1  26/294 (8.84%)  21/288 (7.29%) 
Headache  1  15/294 (5.10%)  12/288 (4.17%) 
On and off phenomenon  1  12/294 (4.08%)  16/288 (5.56%) 
Parkinsonian gait  1  15/294 (5.10%)  12/288 (4.17%) 
Parkinsonian rest tremor  1  69/294 (23.47%)  26/288 (9.03%) 
Somnolence  1  23/294 (7.82%)  18/288 (6.25%) 
Psychiatric disorders     
Anxiety  1  17/294 (5.78%)  22/288 (7.64%) 
Confusional state  1  21/294 (7.14%)  21/288 (7.29%) 
Depression  1  6/294 (2.04%)  22/288 (7.64%) 
Hallucination  1  19/294 (6.46%)  21/288 (7.29%) 
Hallucination, visual  1  12/294 (4.08%)  16/288 (5.56%) 
Insomnia  1  14/294 (4.76%)  23/288 (7.99%) 
Vascular disorders     
Hypertension  1  16/294 (5.44%)  12/288 (4.17%) 
Hypotension  1  22/294 (7.48%)  10/288 (3.47%) 
Orthostatic hypotension  1  18/294 (6.12%)  17/288 (5.90%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
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 (i.e., 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: NCT00623103     History of Changes
Other Study ID Numbers: CENA713B2315
First Submitted: February 14, 2008
First Posted: February 25, 2008
Results First Submitted: October 19, 2011
Results First Posted: November 28, 2011
Last Update Posted: November 28, 2011