Trial Outcomes & Findings for Safety of Switching From Donepezil to Rivastigmine Patch in Patients With Probable Alzheimer's Disease (NCT NCT00428389)

Last Updated: 2014-06-11

Results Overview

The primary objective of the study was to evaluate the safety and tolerability of 2 paradigms for switching from donepezil to rivastigmine patch in patients with Alzheimer's disease (AD). The primary variable to assess tolerability of switching was the number of participants who discontinued from the study due to any reason during the core phase.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

262 participants

Primary outcome timeframe

Baseline through the end of the core phase of the study (Week 5)

Results posted on

2014-06-11

Participant Flow

Participant milestones

Participant milestones
Measure	Immediate Switch Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.
Core Phase STARTED	131	131
Core Phase Intent-to-treat Population	131	130
Core Phase COMPLETED	120	120
Core Phase NOT COMPLETED	11	11
Extension Phase STARTED	117	117
Extension Phase COMPLETED	85	91
Extension Phase NOT COMPLETED	32	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Immediate Switch Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.
Core Phase Adverse Event	6	4
Core Phase Lack of Efficacy	2	0
Core Phase Abnormal test procedure result(s)	0	1
Core Phase Withdrawal by Subject	3	4
Core Phase Protocol deviation	0	2
Extension Phase Adverse Event	17	11
Extension Phase Lack of Efficacy	4	3
Extension Phase Withdrawal by Subject	6	6
Extension Phase Lost to Follow-up	0	3
Extension Phase Death	1	0
Extension Phase Protocol Violation	3	2
Extension Phase Administrative problems	1	1

Baseline Characteristics

Safety of Switching From Donepezil to Rivastigmine Patch in Patients With Probable Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Immediate Switch n=131 Participants Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch n=130 Participants Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Total n=261 Participants Total of all reporting groups
Age, Continuous	77.8 years STANDARD_DEVIATION 7.66 • n=99 Participants	76.7 years STANDARD_DEVIATION 8.41 • n=107 Participants	77.3 years STANDARD_DEVIATION 8.04 • n=206 Participants
Sex: Female, Male Female	79 Participants n=99 Participants	72 Participants n=107 Participants	151 Participants n=206 Participants
Sex: Female, Male Male	52 Participants n=99 Participants	58 Participants n=107 Participants	110 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline through the end of the core phase of the study (Week 5)

Population: The Safety population consisted of all randomized patients who had at least 1 post-baseline safety assessment. Patients were analyzed according to the treatment received.

Outcome measures

Outcome measures
Measure	Immediate Switch n=131 Participants Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch n=130 Participants Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.
Number of Participants Who Discontinued From the Study Due to Any Reason During the Core Phase of the Study	11 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline through the end of study (25 weeks)

Population: The Safety population consisted of all randomized patients who had at least 1 post-baseline safety assessment. Patients were analyzed according to the treatment received.

A secondary assessment of the safety and tolerability of 2 paradigms for switching from donepezil to rivastigmine patch in patients with Alzheimer's disease (AD) was the number of participants who discontinued from the study due to an AE during the combined core and extension phases of the study.

Outcome measures

Outcome measures
Measure	Immediate Switch n=131 Participants Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch n=130 Participants Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.
Number of Participants Who Discontinued From the Study Due to Any Adverse Event (AE) During the Combined Core and Extension Phases of the Study	23 Participants	15 Participants

SECONDARY outcome

Timeframe: From week 5 through the end of extension phase (25 weeks)

Population: The Safety population consisted of all randomized patients who had at least 1 post-baseline safety assessment. Patients were analyzed according to the treatment received.

Outcome measures

Outcome measures
Measure	Immediate Switch n=117 Participants Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch n=117 Participants Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.
Number of Participants Who Discontinued From Study Due to Any Reason During Extension Phase	32 Participants	26 Participants

SECONDARY outcome

Timeframe: Baseline, Week 5 (end of the core phase) and Week 25 (end of the extension phase)

Population: The Intent-to-Treat (ITT) population included all randomized patients who entered the switch period for at least 1 day and had at least 1 post-baseline assessment of tolerability/safety. This outcome used observed cases without imputation (OC).

The CGIC is an assessment tool used by a skilled clinician to make a judgment of the severity or a change of a patient's condition. The clinician relies solely on information obtained from the patient at the Baseline visit as well as clinical information obtained throughout the study period. The clinician does not have access to any post-baseline cognitive testing data. The CGIC is rated on a seven-point scale, ranging from (1) "very much improved" to (4) "no change" to (7) "very much worse".

Outcome measures

Outcome measures
Measure	Immediate Switch n=131 Participants Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch n=130 Participants Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.
Mean Change From Baseline in the Clinical Global Impression of Change (CGIC) Score at Week 5 and Week 25 At Week 25 (n= 105, 109)	4.1 Scores on a scale Standard Deviation 1.16	4.3 Scores on a scale Standard Deviation 0.96
Mean Change From Baseline in the Clinical Global Impression of Change (CGIC) Score at Week 5 and Week 25 At Week 5 (n= 116, 114)	3.9 Scores on a scale Standard Deviation 0.85	4.0 Scores on a scale Standard Deviation 0.84

SECONDARY outcome

Timeframe: Baseline and Week 25 (end of the extension phase) and at the end of study

The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.

Outcome measures

Outcome measures
Measure	Immediate Switch n=131 Participants Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch n=130 Participants Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 25 and at the End of Study At Week 25 (n= 96, 106)	-0.7 Scores on a scale Standard Deviation 3.58	-0.4 Scores on a scale Standard Deviation 3.94
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 25 and at the End of Study At the End of Study (n= 115, 118)	-0.5 Scores on a scale Standard Deviation 3.62	-0.3 Scores on a scale Standard Deviation 4.11

SECONDARY outcome

Timeframe: Baseline, Week 25 (end of the extension phase) and at End of Study

The NPI-10 assesses a wide range of behavior problems encountered in dementia patients. The 10 behavioral domains comprising the NPI-10 are evaluated through an interview of the caregiver by a mental health professional. The scale includes 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 10 domains yields the NPI total score, which ranges from 0 to 120, the lower the score the less severe the symptoms. A negative change score from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Immediate Switch n=131 Participants Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch n=130 Participants Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.
Mean Change From Baseline in Neuropsychiatric Inventory - 10 Item (NPI-10) Score at Week 25 and at the End of Study. At week 25 (n= 95, 107)	-0.1 Scores on a scale Standard Deviation 9.53	0.4 Scores on a scale Standard Deviation 12.92
Mean Change From Baseline in Neuropsychiatric Inventory - 10 Item (NPI-10) Score at Week 25 and at the End of Study. At the End of Study (n= 114, 118)	-0.8 Scores on a scale Standard Deviation 11.22	0.5 Scores on a scale Standard Deviation 12.36

SECONDARY outcome

Timeframe: Baseline, Week 25 (end of the extension phase) and at the end of Study

The ADCS-ADL scale is composed of 23 items to assess the 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, making judgments and decisions. Responses for each item are obtained through a caregiver interview. The total score is the sum of all items and sub-questions. The range for the total ADCS-ADL score is 0 to 78; a higher score indicates a more self-sufficient individual. A positive change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Immediate Switch n=131 Participants Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch n=130 Participants Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.
Mean Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score at Week 25 and at the End of Study At Week 25 (n= 95, 107)	-3.9 Scores on a scale Standard Deviation 8.72	-4.2 Scores on a scale Standard Deviation 9.91
Mean Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score at Week 25 and at the End of Study At the End of Study (n= 113, 117)	-3.1 Scores on a scale Standard Deviation 9.44	-4.2 Scores on a scale Standard Deviation 9.65

Adverse Events

Immediate Switch

Serious events: 14 serious events

Other events: 51 other events

Deaths: 0 deaths

Delayed Switch

Serious events: 9 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Immediate Switch n=131 participants at risk Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch n=130 participants at risk Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.
Blood and lymphatic system disorders Anaemia	0.00% 0/131	0.77% 1/130
Cardiac disorders Bradycardia	0.76% 1/131	0.77% 1/130
Cardiac disorders Coronary artery disease	0.76% 1/131	0.00% 0/130
Cardiac disorders Myocardial infarction	0.76% 1/131	0.00% 0/130
Gastrointestinal disorders Gastritis	0.00% 0/131	0.77% 1/130
General disorders Asthenia	0.00% 0/131	0.77% 1/130
Infections and infestations Abscess limb	0.76% 1/131	0.00% 0/130
Infections and infestations Gastroenteritis	0.00% 0/131	0.77% 1/130
Infections and infestations Pneumonia	0.00% 0/131	0.77% 1/130
Infections and infestations Sepsis	0.00% 0/131	0.77% 1/130
Injury, poisoning and procedural complications Fall	0.76% 1/131	0.77% 1/130
Injury, poisoning and procedural complications Hip fracture	0.00% 0/131	0.77% 1/130
Metabolism and nutrition disorders Dehydration	0.76% 1/131	0.77% 1/130
Metabolism and nutrition disorders Hyperglycaemia	0.76% 1/131	0.00% 0/130
Metabolism and nutrition disorders Hyponatraemia	0.76% 1/131	0.00% 0/130
Metabolism and nutrition disorders Oral intake reduced	0.76% 1/131	0.00% 0/130
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.76% 1/131	0.00% 0/130
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign vaginal neoplasm	0.00% 0/131	0.77% 1/130
Nervous system disorders Cerebellar infarction	0.76% 1/131	0.00% 0/130
Nervous system disorders Cerebrovascular accident	0.76% 1/131	0.00% 0/130
Nervous system disorders Lethargy	0.76% 1/131	0.00% 0/130
Nervous system disorders Syncope	1.5% 2/131	0.77% 1/130
Psychiatric disorders Anxiety	0.76% 1/131	0.00% 0/130
Psychiatric disorders Major depression	0.76% 1/131	0.00% 0/130
Psychiatric disorders Mental status changes	1.5% 2/131	0.00% 0/130
Psychiatric disorders Psychotic disorder	0.76% 1/131	0.00% 0/130
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/131	0.77% 1/130
Respiratory, thoracic and mediastinal disorders Hyperventilation	0.76% 1/131	0.00% 0/130
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.76% 1/131	0.00% 0/130

Other adverse events

Other adverse events
Measure	Immediate Switch n=131 participants at risk Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.	Delayed Switch n=130 participants at risk Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.
Gastrointestinal disorders Constipation	0.00% 0/131	5.4% 7/130
Gastrointestinal disorders Nausea	6.9% 9/131	0.77% 1/130
Gastrointestinal disorders Vomiting	5.3% 7/131	3.1% 4/130
General disorders Application site reaction	13.0% 17/131	17.7% 23/130
Infections and infestations Urinary tract infection	5.3% 7/131	3.1% 4/130
Injury, poisoning and procedural complications Fall	5.3% 7/131	3.8% 5/130
Psychiatric disorders Agitation	6.1% 8/131	7.7% 10/130
Psychiatric disorders Anxiety	1.5% 2/131	6.2% 8/130
Psychiatric disorders Confusional state	5.3% 7/131	3.1% 4/130
Psychiatric disorders Depression	3.1% 4/131	5.4% 7/130

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER