Trial Outcomes & Findings for Tolerability of Rivastigmine Before and After Switching From Oral Formulation to Transdermal Patch in Alzheimer's Dementia (NCT NCT01585272)
NCT ID: NCT01585272
Last Updated: 2018-04-18
Results Overview
The overall rate of adverse events reported from initiation through the first 28-week treatment period
COMPLETED
PHASE4
121 participants
Baseline through week 28
2018-04-18
Participant Flow
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
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
121
|
|
Overall Study
Safety Set
|
102
|
|
Overall Study
Exelon Patch 5 cm2
|
114
|
|
Overall Study
Exelon Patch 10 cm2
|
96
|
|
Overall Study
COMPLETED
|
82
|
|
Overall Study
NOT COMPLETED
|
39
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Adverse Event
|
22
|
|
Overall Study
Protocol Violation
|
7
|
|
Overall Study
Withdrawal by Subject
|
10
|
Baseline Characteristics
Tolerability of Rivastigmine Before and After Switching From Oral Formulation to Transdermal Patch in Alzheimer's Dementia
Baseline characteristics by cohort
| Measure |
Rivastigmine
n=102 Participants
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.
|
|---|---|
|
Age, Continuous
|
74.8 Years
STANDARD_DEVIATION 7.93 • n=93 Participants
|
|
Sex: Female, Male
Female
|
52 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
50 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Baseline through week 28Population: 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.
The overall rate of adverse events reported from initiation through the first 28-week treatment period
Outcome measures
| Measure |
Rivastigmine
n=102 Participants
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.
|
|---|---|
|
Number of Patients With Adverse Events, Serious Adverse Events, and Death
Patients with at least one SAEs
|
16 Participants
|
|
Number of Patients With Adverse Events, Serious Adverse Events, and Death
Patients with at least one AE
|
94 Participants
|
|
Number of Patients With Adverse Events, Serious Adverse Events, and Death
Death
|
0 Participants
|
SECONDARY outcome
Timeframe: Baselin, week 16, 28 and 52Population: 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
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).
Outcome measures
| Measure |
Rivastigmine
n=102 Participants
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.
|
|---|---|
|
Change From Baseline in Mini-Mental Status Examination (MMSE)
Week 16 (n=90)
|
-0.1 Score
Standard Deviation 2.62
|
|
Change From Baseline in Mini-Mental Status Examination (MMSE)
Week 28 (n=82)
|
0.1 Score
Standard Deviation 2.62
|
|
Change From Baseline in Mini-Mental Status Examination (MMSE)
Week 52 (n=93)
|
-1.0 Score
Standard Deviation 3.48
|
SECONDARY outcome
Timeframe: Baseline, week 16, 28 and 52Population: 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.
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).
Outcome measures
| Measure |
Rivastigmine
n=102 Participants
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.
|
|---|---|
|
Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Week 16 (n=90)
|
0.0 Score
Standard Deviation 4.92
|
|
Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Week 28 (n=82)
|
0.4 Score
Standard Deviation 5.20
|
|
Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Week 52 (n=93)
|
0.8 Score
Standard Deviation 7.37
|
SECONDARY outcome
Timeframe: Baseline through week 52Population: 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)
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.
Outcome measures
| Measure |
Rivastigmine
n=114 Participants
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.
|
|---|---|
|
The Discontinuation Rate Due to the Treatment Switching From Oral Capsule to Rivastigmine Patch Treatment
Exelon patch 5 cm 2:Week 4 - Week 28
|
18 Participants
|
|
The Discontinuation Rate Due to the Treatment Switching From Oral Capsule to Rivastigmine Patch Treatment
Exelon patch 10 cm 2: Week 28 - Week 52
|
14 Participants
|
SECONDARY outcome
Timeframe: Baseline through week 52Population: 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.
The percentage of patients successfully titrated to rivastigmine patch 10 cm2
Outcome measures
| Measure |
Rivastigmine
n=102 Participants
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.
|
|---|---|
|
Percentage of Patients Successfully Titrated to Rivastigmine Patch 10 cm^2
|
85.3 Percentage of participants
|
Adverse Events
Rivastigmine
Serious adverse events
| Measure |
Rivastigmine
n=102 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Cardiac failure chronic
|
0.98%
1/102 • 52 weeks
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.98%
1/102 • 52 weeks
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.98%
1/102 • 52 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.98%
1/102 • 52 weeks
|
|
Hepatobiliary disorders
Cholecystitis
|
0.98%
1/102 • 52 weeks
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.98%
1/102 • 52 weeks
|
|
Infections and infestations
Arthritis infective
|
0.98%
1/102 • 52 weeks
|
|
Infections and infestations
Cellulitis
|
0.98%
1/102 • 52 weeks
|
|
Infections and infestations
Escherichia sepsis
|
0.98%
1/102 • 52 weeks
|
|
Infections and infestations
Pneumonia
|
2.9%
3/102 • 52 weeks
|
|
Infections and infestations
Pyuria
|
0.98%
1/102 • 52 weeks
|
|
Infections and infestations
Tertiary syphilis
|
0.98%
1/102 • 52 weeks
|
|
Infections and infestations
Urinary tract infection
|
2.0%
2/102 • 52 weeks
|
|
Injury, poisoning and procedural complications
Open fracture
|
0.98%
1/102 • 52 weeks
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.98%
1/102 • 52 weeks
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.98%
1/102 • 52 weeks
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.98%
1/102 • 52 weeks
|
|
Musculoskeletal and connective tissue disorders
Neck mass
|
0.98%
1/102 • 52 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of prostate
|
0.98%
1/102 • 52 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.98%
1/102 • 52 weeks
|
|
Nervous system disorders
Headache
|
0.98%
1/102 • 52 weeks
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.98%
1/102 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.98%
1/102 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary fibrosis
|
0.98%
1/102 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.98%
1/102 • 52 weeks
|
|
Surgical and medical procedures
Knee arthroplasty
|
0.98%
1/102 • 52 weeks
|
|
Vascular disorders
Venous thrombosis limb
|
0.98%
1/102 • 52 weeks
|
Other adverse events
| Measure |
Rivastigmine
n=102 participants at risk
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.
|
|---|---|
|
Eye disorders
Cataract
|
2.9%
3/102 • 52 weeks
|
|
Eye disorders
Dry eye
|
2.9%
3/102 • 52 weeks
|
|
Gastrointestinal disorders
Abdominal discomfort
|
3.9%
4/102 • 52 weeks
|
|
Gastrointestinal disorders
Constipation
|
3.9%
4/102 • 52 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
5.9%
6/102 • 52 weeks
|
|
Gastrointestinal disorders
Mouth ulceration
|
2.9%
3/102 • 52 weeks
|
|
Gastrointestinal disorders
Nausea
|
11.8%
12/102 • 52 weeks
|
|
Gastrointestinal disorders
Vomiting
|
10.8%
11/102 • 52 weeks
|
|
General disorders
Application site erosion
|
2.9%
3/102 • 52 weeks
|
|
General disorders
Application site erythema
|
17.6%
18/102 • 52 weeks
|
|
General disorders
Application site pruritus
|
33.3%
34/102 • 52 weeks
|
|
General disorders
Application site rash
|
13.7%
14/102 • 52 weeks
|
|
General disorders
Chest discomfort
|
2.9%
3/102 • 52 weeks
|
|
General disorders
Pyrexia
|
2.9%
3/102 • 52 weeks
|
|
Infections and infestations
Bronchitis
|
2.9%
3/102 • 52 weeks
|
|
Infections and infestations
Conjunctivitis
|
2.9%
3/102 • 52 weeks
|
|
Infections and infestations
Nasopharyngitis
|
5.9%
6/102 • 52 weeks
|
|
Infections and infestations
Periodontitis
|
2.9%
3/102 • 52 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
6.9%
7/102 • 52 weeks
|
|
Infections and infestations
Urinary tract infection
|
2.9%
3/102 • 52 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
4.9%
5/102 • 52 weeks
|
|
Investigations
Weight decreased
|
27.5%
28/102 • 52 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.8%
12/102 • 52 weeks
|
|
Musculoskeletal and connective tissue disorders
Myofascial pain syndrome
|
2.9%
3/102 • 52 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.9%
3/102 • 52 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of prostate
|
2.9%
3/102 • 52 weeks
|
|
Nervous system disorders
Dizziness
|
23.5%
24/102 • 52 weeks
|
|
Nervous system disorders
Headache
|
2.9%
3/102 • 52 weeks
|
|
Psychiatric disorders
Agitation
|
4.9%
5/102 • 52 weeks
|
|
Psychiatric disorders
Insomnia
|
3.9%
4/102 • 52 weeks
|
|
Psychiatric disorders
Irritability
|
2.9%
3/102 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.9%
5/102 • 52 weeks
|
|
Skin and subcutaneous tissue disorders
Eczema
|
2.9%
3/102 • 52 weeks
|
|
Skin and subcutaneous tissue disorders
Papule
|
2.9%
3/102 • 52 weeks
|
|
Vascular disorders
Hypertension
|
2.9%
3/102 • 52 weeks
|
Additional Information
Study Director
Novartis Pharmaceutical
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 or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER