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This phase IIIb study is intended to implement a consistent treatment way for switching to Exelon transdermal patch from oral formulation of rivastigmine to stress the importance of (1) advantages of transdermal patch over conventional oral therapies: smooth drug delivery with reduced side effects;(2) encourage treatment compliance in the Alzheimer's dementia setting.
This study is a single-arm, treatment-switched design. Eligible patients, who are under Exelon capsule 3 mg b.i.d. treatment for 4 weeks before Visit 2, will be recruited, followed by treatment switch from oral capsule to patch for 48 weeks maintenance treatment. During the maintenance period, the treatment will be initiated with Exelon Patch 4.6 mg/24 hours (Exelon Patch 5 cm^2) for the first 24 weeks and the dose will be escalated to Exelon Patch 9.5 mg/24 hours (Exelon Patch 10 cm^2) for another 24 weeks if well tolerated. Visits to assess safety are scheduled at baseline, 3 days, 1 week and 2 weeks after the first treatment switch, every 4 weeks until Week 40, and at the end of study (Week 52). The assessment to address the primary objective will focus on the safety of treatment switching (Week 0~28); however the safety assessment will be performed during the whole study period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rivastigmine | Experimental | Eligible patients, who are under rivastigmine capsule 3 mg b.i.d. treatment for 4 weeks before Visit 2, will be recruited, followed by treatment switch from oral capsule to transdermal patch for 48 weeks maintenance treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ENA713 | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Adverse Events, Serious Adverse Events, and Death | The overall rate of adverse events reported from initiation through the first 28-week treatment period | Baseline through week 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Mini-Mental Status Examination (MMSE) | The changes in Mini-Mental Status Examination (MMSE) of patients with Alzheimer's disease treated with Exelon 5 cm^2 Patch at Week 28 and Exelon 10 cm2 Patch at Week 52 versus baseline, the treatment-switching day at Week 4. MMSE is a multi-item instrument that examines orientation, registration, attention, calculation, recall, visuospatial ability and language. The total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement from baseline. The assessments will be conducted at Visit 1, 2, 8, 11 and 17 (screening, Week 4 (baseline), 16, 28 and 52). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Taichung | Taiwan ROC | Taiwan | |||
| Novartis Investigative Site |
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Patients receiving Exelon patch 5 cm^2 were more than those receiving Exelon capsule for 4 weeks as least, because some patients had interrupted Exelon capsule for few days in the middle of 4-week Exelon capsule treatment, but still switched to Exelon patch 5 cm2
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| ID | Title | Description |
|---|---|---|
| FG000 | Rivastigmine | Eligible patients, who are under rivastigmine capsule 3 mg b.i.d. treatment for 4 weeks before Visit 2, will be recruited, followed by treatment switch from oral capsule to transdermal patch for 48 weeks maintenance treatment. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Rivastigmine | Eligible patients, who are under rivastigmine capsule 3 mg b.i.d. treatment for 4 weeks before Visit 2, will be recruited, followed by treatment switch from oral capsule to transdermal patch for 48 weeks maintenance treatment. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients With Adverse Events, Serious Adverse Events, and Death | The overall rate of adverse events reported from initiation through the first 28-week treatment period | Safety population: All enrolled subjects who received 3 mg b.i.d Exelon capsule for more than 4 weeks and used at least one dose of Exelon patch therapy. | Posted | Number | Participants | Baseline through week 28 |
|
52 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rivastigmine | Eligible patients, who are under rivastigmine capsule 3 mg b.i.d. treatment for 4 weeks before Visit 2, will be recruited, followed by treatment switch from oral capsule to transdermal patch for 48 weeks maintenance treatment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure chronic | Cardiac disorders | 18.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cataract | Eye disorders | 18.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceutical | 862-778-8300 |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000068836 | Rivastigmine |
| ID | Term |
|---|---|
| D048448 | Phenylcarbamates |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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| Baselin, week 16, 28 and 52 |
| Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) | The changes in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) of patients with Alzheimer's disease treated with Exelon 5 cm^2 Patch at Week 28 and Exelon 10 cm^2 Patch at Week 52 versus baseline, the treatment-switching day at Week 4. ADAS-Cog has been used as the major cognitive measure of anti-dementia drugs. The total score range is 0 to 70 points, with higher scores indicating greater cognitive impairment. The assessments will be conducted at Visit, 2, 8, 11 and 17 (Week 4 (baseline), 16, 28 and 52). | Baseline, week 16, 28 and 52 |
| The Discontinuation Rate Due to the Treatment Switching From Oral Capsule to Rivastigmine Patch Treatment | The discontinuation rate due to the treatment switching from oral capsule to patch treatment. For patients who discontinue earlier due to intolerance of patch treatment, the proportion will be analyzed. Both the discontinuation rate of 5 cm2 and 10 cm^2 patch therapy will be presented. | Baseline through week 52 |
| Percentage of Patients Successfully Titrated to Rivastigmine Patch 10 cm^2 | The percentage of patients successfully titrated to rivastigmine patch 10 cm2 | Baseline through week 52 |
| Taipei |
| Taiwan, ROC |
| 112 |
| Taiwan |
| Novartis Investigative Site | Taichung | 40447 | Taiwan |
| Novartis Investigative Site | Taipei | 10002 | Taiwan |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | Change From Baseline in Mini-Mental Status Examination (MMSE) | The changes in Mini-Mental Status Examination (MMSE) of patients with Alzheimer's disease treated with Exelon 5 cm^2 Patch at Week 28 and Exelon 10 cm2 Patch at Week 52 versus baseline, the treatment-switching day at Week 4. MMSE is a multi-item instrument that examines orientation, registration, attention, calculation, recall, visuospatial ability and language. The total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement from baseline. The assessments will be conducted at Visit 1, 2, 8, 11 and 17 (screening, Week 4 (baseline), 16, 28 and 52). | ITT population: All enrolled subjects who received 3 mg b.i.d Exelon capsule orally for 4 weeks and at least one dose of Exelon patch therapy | Posted | Mean | Standard Deviation | Score | Baselin, week 16, 28 and 52 |
|
|
|
| Secondary | Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) | The changes in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) of patients with Alzheimer's disease treated with Exelon 5 cm^2 Patch at Week 28 and Exelon 10 cm^2 Patch at Week 52 versus baseline, the treatment-switching day at Week 4. ADAS-Cog has been used as the major cognitive measure of anti-dementia drugs. The total score range is 0 to 70 points, with higher scores indicating greater cognitive impairment. The assessments will be conducted at Visit, 2, 8, 11 and 17 (Week 4 (baseline), 16, 28 and 52). | ITT population: All enrolled subjects who received 3 mg b.i.d Exelon capsule orally for 4 weeks and at least one dose of Exelon patch therapy. | Posted | Mean | Standard Deviation | Score | Baseline, week 16, 28 and 52 |
|
|
|
| Secondary | The Discontinuation Rate Due to the Treatment Switching From Oral Capsule to Rivastigmine Patch Treatment | The discontinuation rate due to the treatment switching from oral capsule to patch treatment. For patients who discontinue earlier due to intolerance of patch treatment, the proportion will be analyzed. Both the discontinuation rate of 5 cm2 and 10 cm^2 patch therapy will be presented. | Of the patients treated, N=121, number of patients analyzied were those who received 5cm patch (n=114) and those who received 10cm patch (n=96) | Posted | Number | Participants | Baseline through week 52 |
|
|
|
| Secondary | Percentage of Patients Successfully Titrated to Rivastigmine Patch 10 cm^2 | The percentage of patients successfully titrated to rivastigmine patch 10 cm2 | Safety population: All enrolled subjects who received 3 mg b.i.d Exelon capsule for more than 4 weeks and used at least one dose of Exelon patch therapy. | Posted | Number | Percentage of participants | Baseline through week 52 |
|
|
|
| 16 |
| 102 |
| 83 |
| 102 |
| Supraventricular tachycardia | Cardiac disorders | 18.1 | Systematic Assessment |
|
| Inguinal hernia | Gastrointestinal disorders | 18.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | 18.1 | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | 18.1 | Systematic Assessment |
|
| Cholelithiasis | Hepatobiliary disorders | 18.1 | Systematic Assessment |
|
| Arthritis infective | Infections and infestations | 18.1 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | 18.1 | Systematic Assessment |
|
| Escherichia sepsis | Infections and infestations | 18.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | 18.1 | Systematic Assessment |
|
| Pyuria | Infections and infestations | 18.1 | Systematic Assessment |
|
| Tertiary syphilis | Infections and infestations | 18.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | 18.1 | Systematic Assessment |
|
| Open fracture | Injury, poisoning and procedural complications | 18.1 | Systematic Assessment |
|
| Pelvic fracture | Injury, poisoning and procedural complications | 18.1 | Systematic Assessment |
|
| Wrist fracture | Injury, poisoning and procedural complications | 18.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | 18.1 | Systematic Assessment |
|
| Neck mass | Musculoskeletal and connective tissue disorders | 18.1 | Systematic Assessment |
|
| Benign neoplasm of prostate | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 18.1 | Systematic Assessment |
|
| Lung adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 18.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | 18.1 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | 18.1 | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 18.1 | Systematic Assessment |
|
| Idiopathic pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | 18.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 18.1 | Systematic Assessment |
|
| Knee arthroplasty | Surgical and medical procedures | 18.1 | Systematic Assessment |
|
| Venous thrombosis limb | Vascular disorders | 18.1 | Systematic Assessment |
|
| Dry eye | Eye disorders | 18.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | 18.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | 18.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | 18.1 | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | 18.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | 18.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | 18.1 | Systematic Assessment |
|
| Application site erosion | General disorders | 18.1 | Systematic Assessment |
|
| Application site erythema | General disorders | 18.1 | Systematic Assessment |
|
| Application site pruritus | General disorders | 18.1 | Systematic Assessment |
|
| Application site rash | General disorders | 18.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | 18.1 | Systematic Assessment |
|
| Pyrexia | General disorders | 18.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | 18.1 | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | 18.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | 18.1 | Systematic Assessment |
|
| Periodontitis | Infections and infestations | 18.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | 18.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | 18.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | 18.1 | Systematic Assessment |
|
| Weight decreased | Investigations | 18.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | 18.1 | Systematic Assessment |
|
| Myofascial pain syndrome | Musculoskeletal and connective tissue disorders | 18.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | 18.1 | Systematic Assessment |
|
| Benign neoplasm of prostate | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 18.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | 18.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | 18.1 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | 18.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | 18.1 | Systematic Assessment |
|
| Irritability | Psychiatric disorders | 18.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | 18.1 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | 18.1 | Systematic Assessment |
|
| Papule | Skin and subcutaneous tissue disorders | 18.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | 18.1 | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D009930 |
| Organic Chemicals |
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|