Alzheimer's Disease
Conditions
Keywords
Alzheimer's disease, cholinesterase inhibitor, rivastigmine
Brief summary
This study is designed to confirm the efficacy, the tolerability, the patient compliance and the caregiver satisfaction with rivastigmine target patch size 10 cm\^2 in patients with probable Alzheimer's Disease (Mini-Mental State Examination 10-26) in the community setting
Interventions
The study treatment was delivered as a patch sizes 5 and 10 cm\^2 containing respectively 9 and 18 mg of rivastigmine. During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2.
Sponsors
Novartis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Inclusion criteria
* Males, and females of at least 50 years old with a primary caregiver * Probable Alzheimer's disease * Mini-Mental State Examination (MMSE) score of ≥ 10 and ≤ 26 * Patients initiating therapy for the first time with a Cholinesterase (ChE) inhibitor (patients prescribed both rivastigmine and memantine are allowed) or patients who failed to benefit from previous ChE inhibitor treatment * Residing with someone in the community throughout the study or, if living alone, in contact with the responsible caregiver everyday
Exclusion criteria
* Patients not treated according to the product monograph for capsules * Current diagnosis of an active skin lesion/disorder that would prevent accurate assessment of the adhesion and potential skin irritation of the patch (e.g., atopic dermatitis, wounded or scratched skin in the area of the patch application) * History of allergy to topical products containing any of the constituents of the patches Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Achieved and Maintained the Maximum Dose of 10 cm^2 Rivastigmine Patch for at Least 8 Weeks During 24 Weeks Study | 24 weeks | The primary endpoint was the percentage of patients who were able to tolerate (and stay on for at least 8 weeks) rivastigmine target patch size 10 cm\^2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Change (CGI-C) by Physician | Baseline and week 24 | The CGIC is an assessment tool used by a 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 CGIC is rated on the following seven-point scale:very much improved, much improved, slightly improved, unchanged, slightly worsened, much worsened and very much worsened. |
| Mean Change From Baseline to Week 24 in the 4-item Instrumental Activities of Daily Living (4-IADL) Score | Baseline to week 24 | The 4-IADL assesses the ability of a patient to autonomously perform 4 activities of daily living: Use the telephone, take medications, use public transport, and manage their own budget. Each activity is assessed by a series of questions and rated on a scale of 1 to 4. Scores on the 4 activities are combined for a total score ranging from 1 to 16. A lower score indicates a more self-sufficient individual. A positive change from baseline score indicates worsening. |
| Mean Change From Baseline to Week 24 in the Mini-Mental State Examination (MMSE) Score | Baseline to week 24 | The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and results in a total possible score from 0 to 30, with higher scores indicating better function. A positive change score indicates improvement from baseline. |
| Mean Change From Baseline to Week 24 in the Mini-Zarit Inventory Score | Baseline to week 24 | The Mini-Zarit Inventory assesses the burden of a caregiver in caring for a patient. The inventory is composed of 5 questions which are rated according to the following answers: 0 = never, ½ = sometimes, 1 = often. The ratings on the 5 questions are added together resulting in a total score of 0 to 7 with a higher score indicating greater caregiver burden. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rivastigmine Transdermal Patch During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2. | 218 |
| Total | 218 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative problems | 4 |
| Overall Study | Adverse Event | 35 |
| Overall Study | Death | 2 |
| Overall Study | Did not meet eligibility criteria | 1 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Subject no longer required study drug | 1 |
| Overall Study | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | Rivastigmine Transdermal Patch |
|---|---|
| Age Continuous | 78.7 years STANDARD_DEVIATION 6.59 |
| Region of Enrollment France | 218 participants |
| Sex: Female, Male Female | 131 Participants |
| Sex: Female, Male Male | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 218 |
| serious Total, serious adverse events | 21 / 218 |
Outcome results
Primary
Percentage of Patients Who Achieved and Maintained the Maximum Dose of 10 cm^2 Rivastigmine Patch for at Least 8 Weeks During 24 Weeks Study
The primary endpoint was the percentage of patients who were able to tolerate (and stay on for at least 8 weeks) rivastigmine target patch size 10 cm\^2.
Time frame: 24 weeks
Population: The Intent-to-Treat (ITT) population was defined as all patients who were administered at least one dose of study medication and were assessed for efficacy at least 1 time.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivastigmine Transdermal Patch | Percentage of Patients Who Achieved and Maintained the Maximum Dose of 10 cm^2 Rivastigmine Patch for at Least 8 Weeks During 24 Weeks Study | 70.6 Percentage of participants |
Secondary
Clinical Global Impression of Change (CGI-C) by Physician
The CGIC is an assessment tool used by a 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 CGIC is rated on the following seven-point scale:very much improved, much improved, slightly improved, unchanged, slightly worsened, much worsened and very much worsened.
Time frame: Baseline and week 24
Population: The Intent-to-Treat (ITT) population was defined as all patients who were administered at least one dose of study medication and were assessed for efficacy at least 1 time. Last observation carried forward (LOCF) was used for missing values.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Rivastigmine Transdermal Patch | Clinical Global Impression of Change (CGI-C) by Physician | Slightly worsened | 19.2 Percentage of participants | — |
| Rivastigmine Transdermal Patch | Clinical Global Impression of Change (CGI-C) by Physician | Very much improved | 4.3 Percentage of participants | 5.2 |
| Rivastigmine Transdermal Patch | Clinical Global Impression of Change (CGI-C) by Physician | Much improved | 13.0 Percentage of participants | — |
| Rivastigmine Transdermal Patch | Clinical Global Impression of Change (CGI-C) by Physician | Slightly improved | 23.1 Percentage of participants | — |
| Rivastigmine Transdermal Patch | Clinical Global Impression of Change (CGI-C) by Physician | Unchanged | 32.2 Percentage of participants | — |
| Rivastigmine Transdermal Patch | Clinical Global Impression of Change (CGI-C) by Physician | Much worsened | 5.8 Percentage of participants | — |
| Rivastigmine Transdermal Patch | Clinical Global Impression of Change (CGI-C) by Physician | Very much worsened | 2.4 Percentage of participants | — |
Secondary
Mean Change From Baseline to Week 24 in the 4-item Instrumental Activities of Daily Living (4-IADL) Score
The 4-IADL assesses the ability of a patient to autonomously perform 4 activities of daily living: Use the telephone, take medications, use public transport, and manage their own budget. Each activity is assessed by a series of questions and rated on a scale of 1 to 4. Scores on the 4 activities are combined for a total score ranging from 1 to 16. A lower score indicates a more self-sufficient individual. A positive change from baseline score indicates worsening.
Time frame: Baseline to week 24
Population: The Intent-to-Treat (ITT) population was defined as all patients who were administered at least one dose of study medication and were assessed for efficacy at least 1 time.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivastigmine Transdermal Patch | Mean Change From Baseline to Week 24 in the 4-item Instrumental Activities of Daily Living (4-IADL) Score | Baseline (n= 198) | 3.2 scores on a scale | Standard Deviation 1.18 |
| Rivastigmine Transdermal Patch | Mean Change From Baseline to Week 24 in the 4-item Instrumental Activities of Daily Living (4-IADL) Score | Week 24 (n= 181) | 3.2 scores on a scale | Standard Deviation 1.16 |
| Rivastigmine Transdermal Patch | Mean Change From Baseline to Week 24 in the 4-item Instrumental Activities of Daily Living (4-IADL) Score | Change from Baseline to week 24 (n= 172) | 0.1 scores on a scale | Standard Deviation 0.74 |
Secondary
Mean Change From Baseline to Week 24 in the Mini-Mental State Examination (MMSE) Score
The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and results in a total possible score from 0 to 30, with higher scores indicating better function. A positive change score indicates improvement from baseline.
Time frame: Baseline to week 24
Population: The Intent-to-Treat (ITT) population was defined as all patients who were administered at least one dose of study medication and were assessed for efficacy at least 1 time.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivastigmine Transdermal Patch | Mean Change From Baseline to Week 24 in the Mini-Mental State Examination (MMSE) Score | Change from baseline to week 24 (n = 203) | 0.0 scores on a scale | Standard Deviation 3.18 |
| Rivastigmine Transdermal Patch | Mean Change From Baseline to Week 24 in the Mini-Mental State Examination (MMSE) Score | Baseline (n = 216) | 19.2 scores on a scale | Standard Deviation 4.11 |
| Rivastigmine Transdermal Patch | Mean Change From Baseline to Week 24 in the Mini-Mental State Examination (MMSE) Score | Week 24 (n = 203) | 19.2 scores on a scale | Standard Deviation 5.19 |
Secondary
Mean Change From Baseline to Week 24 in the Mini-Zarit Inventory Score
The Mini-Zarit Inventory assesses the burden of a caregiver in caring for a patient. The inventory is composed of 5 questions which are rated according to the following answers: 0 = never, ½ = sometimes, 1 = often. The ratings on the 5 questions are added together resulting in a total score of 0 to 7 with a higher score indicating greater caregiver burden.
Time frame: Baseline to week 24
Population: The Intent-to-Treat (ITT) population was defined as all patients who were administered at least one dose of study medication and were assessed for efficacy at least 1 time.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivastigmine Transdermal Patch | Mean Change From Baseline to Week 24 in the Mini-Zarit Inventory Score | Baseline (n= 211) | 2.8 Scores on a scale | Standard Deviation 1.76 |
| Rivastigmine Transdermal Patch | Mean Change From Baseline to Week 24 in the Mini-Zarit Inventory Score | Week 24 (n= 199) | 2.9 Scores on a scale | Standard Deviation 1.85 |
| Rivastigmine Transdermal Patch | Mean Change From Baseline to Week 24 in the Mini-Zarit Inventory Score | Change from baseline to week 24 (n= 197) | 0.1 Scores on a scale | Standard Deviation 1.35 |