Alzheimer's Disease
Conditions
Keywords
Alzheimer's disease, dementia, Alzheimer's type
Brief summary
The core study assessed the efficacy of a higher dose of rivastigmine 13.3 mg/24 h transdermally (15 cm\^2 patch) compared to a lower dose of the rivastigmine 4.6 mg/24 h transdermally (5 cm\^2 patch) in patients with Severe Dementia of the Alzheimer's Type in a 24-week study. The extension study obtained additional safety and efficacy data, as well as provided the higher dose rivastigmine patch to all patients who completed the core study for an additional 24 weeks.
Interventions
DRUGRivastigmine 4.6 mg/24 h (5 cm^2)
Rivastigmine was supplied in a 5 cm\^2 patch which released 4.6 mg/24 h. Patches were changed daily.
DRUGRivastigmine 9.5 mg/24 h (10 cm^2)
Rivastigmine was supplied in a 10 cm\^2 patch which released 9.5 mg/24 h. Patches were changed daily.
DRUGRivastigmine 13.3 mg/24 h (15 cm^2)
Rivastigmine was supplied in a 15 cm\^2 patch which released 13.3 mg/24 h. Patches were changed daily.
DRUGPlacebo
Placebo patches were identical in size and composition to the corresponding rivastigmine patches, except that they did not contain rivastigmine. Patches were changed daily.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Core study Inclusion Criteria: * Diagnosis of probable Alzheimer's disease (AD) according to National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria. * A Mini-Mental State Examination (MMSE) score of ≥ 3 and ≤ 12. * Be able to complete at least 1 item on the Severe Impairment Battery (SIB). * Residing with someone in the community or in regular contact with the primary caregiver. * Be ambulatory or ambulatory with aid.
Exclusion criteria
* An advanced, severe, progressive, or unstable disease of any type that may interfere with efficacy and safety assessments or put the patient at special risk. * Patients currently residing in a nursing home. * Any current medical or neurological condition other than AD that could explain the patient's dementia. * A current diagnosis of probable or possible vascular dementia. * A current diagnosis of severe or unstable cardiovascular disease. * A current diagnosis of bradycardia (\< 50 beats per minute \[bpm\]), sick-sinus syndrome, or conduction defects. * Clinically significant urinary obstruction. * History of malignancy of any organ system within the past 5 years unless patient is verified to be in stable condition with no active metastasis. * Current diagnosis of an active skin lesion/disorder that would prevent the patient from using a transdermal patch every day. * A known exaggerated pharmacological sensitivity or hypersensitivity to drugs similar to rivastigmine, or to other cholinergic compounds. * Taken any of the following substances (at the time of the Baseline Visit \[Visit 2\]). * Succinylcholine-type muscle relaxants during the previous 2 weeks. * Lithium during the previous 2 weeks. * An investigational drug during the previous 4 weeks. * A drug or treatment known to cause major organ system toxicity during the previous 4 weeks. * Rivastigmine (oral or transdermal patch), donepezil, galantamine, other cholinesterase inhibitors (eg, tacrine, physostigmine, or pyridostigmine), or other approved treatments for Alzheimer's disease during the previous 2 weeks, with exception of stable treatment with memantine for at least 3 months before study entry (Visit 1). * Centrally acting anticholinergic drugs including tricyclic and tetracyclic antidepressants during the previous 4 weeks. * Selegiline unless taken at a stable dose during the previous 4 weeks. * Peripheral anticholinergics not taken at a stable dose during the previous 4 weeks. Extension study Inclusion Criteria: * Complete the double-blind phase (Week 24) of the core study. * Provide, if mentally competent, a separate written informed consent prior to participation in the extension study. In addition, the patient's caregiver, will provide written informed consent prior to the patient's participation in the open-label extension study. If the patient is not able to provide written informed consent, written informed consent must be obtained from the legally authorized representative on the patient's behalf. * Continue to reside with someone in the community or in regular contact with the primary caregiver; patients who reside in an assisted living facility are eligible to participate. * Continue to have a primary caregiver willing to accept responsibility for supervising treatment (eg, application and removal of the patch daily at approximately the same time of day), assessing the condition of the patient throughout the extension study. * Must be medically stable and tolerating the current dose of rivastigmine patch as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24 | Baseline of the core study to Week 24 of the core study | The ADCS-ADL-SIV is designed to assess the patient's performance of both 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, and making judgments and decisions. For each of the 19 questions in the ADCS-ADL-SIV, there was either a forced choice of best response or a yes or no question with additional sub-questions. Responses for each item were obtained from the caregiver through an interview. Higher numbered scores and answers of yes reflected a more self-sufficient individual. The total score was calculated as the sum of all items and sub-questions and ranged from 0 to 54. A higher total score represented a higher functioning patient. A positive change score indicates improvement. |
| Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24 | Baseline of the core study to Week 24 of the core study | The SIB is a 40-item scale developed for the evaluation of the severity of cognitive dysfunction in more advanced Alzheimer Disease patients. The domains assessed included social interaction, memory, language, attention, orientation, praxis, visuo-spatial ability, construction, and orienting to name. The items of the SIB were developed as simple 1-step commands which are presented by a trained rater with gestural cues and repeated if necessary. The SIB was scored from 0 to 100, with higher scores reflecting higher levels of cognitive ability. A positive change score indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extension Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24 | Baseline of the core study to Week 24 of the extension study | The ADCS-ADL-SIV is designed to assess the patient's performance of both 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, and making judgments and decisions. For each of the 19 questions in the ADCS-ADL-SIV, there was either a forced choice of best response or a yes or no question with additional sub-questions. Responses for each item were obtained from the caregiver through an interview. Higher numbered scores and answers of yes reflected a more self-sufficient individual. The total score was calculated as the sum of all items and sub-questions and ranged from 0 to 54. A higher total score represented a higher functioning patient. A positive change score indicates improvement. |
| Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Baseline of the core study to Week 24 of the core study | The ADCS-CGIC assesses the clinical meaningfulness of a treatment based on the clinician's rating of change. The rating is provided by a trained clinician or psychometrician blinded to the patient's treatment. The rater interviewed the patient and caregiver separately at Baseline using a worksheet that provided space for notes and comments. At baseline, raters had access to all of the patient's available records and evaluations. The rater used a similar worksheet at follow-up visits, and referred to the baseline worksheet prior to making a rating of change. The worksheets were divided into 3 domains: mental/cognitive state, behavior, and functioning. Change ratings were based on a 7-point scale: Marked (1), moderate (2), and minimal improvement (3), no change (4), and marked (5), moderate (6), and minimal worsening (7). The percentage of patients in each of the 7 categories is reported. |
| Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Baseline of the core study to Week 24 of the extension study | The ADCS-CGIC assesses the clinical meaningfulness of a treatment based on the clinician's rating of change. The rating is provided by a trained clinician or psychometrician blinded to the patient's treatment. The rater interviewed the patient and caregiver separately at Baseline using a worksheet that provided space for notes and comments. At baseline, raters had access to all of the patient's available records and evaluations. The rater used a similar worksheet at follow-up visits, and referred to the baseline worksheet prior to making a rating of change. The worksheets were divided into 3 domains: mental/cognitive state, behavior, and functioning. Change ratings were based on a 7-point scale: Marked (1), moderate (2), and minimal improvement (3), no change (4), and marked (5), moderate (6), and minimal worsening (7). The percentage of patients in each of the 7 categories is reported. |
| Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24 | Baseline of the core study to Week 24 of the extension study | The SIB is a 40-item scale developed for the evaluation of the severity of cognitive dysfunction in more advanced Alzheimer Disease patients. The domains assessed included social interaction, memory, language, attention, orientation, praxis, visuo-spatial ability, construction, and orienting to name. The items of the SIB were developed as simple 1-step commands which are presented by a trained rater with gestural cues and repeated if necessary. The SIB was scored from 0 to 100, with higher scores reflecting higher levels of cognitive ability. A positive change score indicates improvement. |
| Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24 | Baseline of the core study to Week 24 of the core study | The NPI-12 assesses a wide range of behaviors encountered in patients with dementia to provide a means of distinguishing the frequency and severity of behavioral changes over time. Ten behavioral and 2 neurovegetative domains were evaluated in an interview with the caregiver given by a mental health professional. The scale included 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 12 domains yielded the NPI-12 total score. The NPI-12 was scored from 0 to 144, with lower scores reflecting improvement in psychiatric behavior. A negative change score indicates improvement. |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
One patient in each treatment group in the core study and one patient in the treatment group in the extension study did not receive study medication; they were not included in the safety set.
Participants by arm
| Arm | Count |
|---|---|
| Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch Patients received rivastigmine 13.3 mg/24 h (15 cm\^2). | 356 |
| Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch Patients received rivastigmine 4.6 mg/24 h (5 cm\^2). | 360 |
| Total | 716 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Core Study | Administrative Problems | 2 | 2 |
| Core Study | Adverse Event | 73 | 51 |
| Core Study | Death | 1 | 1 |
| Core Study | Lost to Follow-up | 3 | 2 |
| Core Study | Patient Withdrew Consent | 27 | 46 |
| Core Study | Protocol Deviation | 8 | 10 |
| Core Study | Unsatisfactory Therapeutic Effect | 13 | 14 |
| Extension Study | Administrative Problems | 1 | 0 |
| Extension Study | Adverse Event | 43 | 0 |
| Extension Study | Death | 4 | 0 |
| Extension Study | Lost to Follow-up | 8 | 0 |
| Extension Study | Patient Withdrew Consent | 32 | 0 |
| Extension Study | Study Drug No Longer Required | 1 | 0 |
| Extension Study | Unsatisfactory Therapeutic Effect | 2 | 0 |
Baseline characteristics
| Characteristic | Core Study: Rivastigmine 13.3 mg/24 h Transdermal Patch | Core Study: Rivastigmine 4.6 mg/24 h Transdermal Patch | Total |
|---|---|---|---|
| Age Continuous | 77.6 years STANDARD_DEVIATION 8.69 | 76.5 years STANDARD_DEVIATION 9.35 | 77.0 years STANDARD_DEVIATION 9.04 |
| Sex: Female, Male Female | 227 Participants | 234 Participants | 461 Participants |
| Sex: Female, Male Male | 129 Participants | 126 Participants | 255 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 216 / 355 | 210 / 359 | 248 / 396 |
| serious Total, serious adverse events | 82 / 355 | 74 / 359 | 79 / 396 |
Outcome results
Primary
Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24
The ADCS-ADL-SIV is designed to assess the patient's performance of both 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, and making judgments and decisions. For each of the 19 questions in the ADCS-ADL-SIV, there was either a forced choice of best response or a yes or no question with additional sub-questions. Responses for each item were obtained from the caregiver through an interview. Higher numbered scores and answers of yes reflected a more self-sufficient individual. The total score was calculated as the sum of all items and sub-questions and ranged from 0 to 54. A higher total score represented a higher functioning patient. A positive change score indicates improvement.
Time frame: Baseline of the core study to Week 24 of the core study
Population: Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24 | -2.6 Units on a scale | Standard Deviation 6.82 |
| Rivastigmine 4.6 mg/24 h Transdermal Patch | Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24 | -3.6 Units on a scale | Standard Deviation 7.68 |
Primary
Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24
The SIB is a 40-item scale developed for the evaluation of the severity of cognitive dysfunction in more advanced Alzheimer Disease patients. The domains assessed included social interaction, memory, language, attention, orientation, praxis, visuo-spatial ability, construction, and orienting to name. The items of the SIB were developed as simple 1-step commands which are presented by a trained rater with gestural cues and repeated if necessary. The SIB was scored from 0 to 100, with higher scores reflecting higher levels of cognitive ability. A positive change score indicates improvement.
Time frame: Baseline of the core study to Week 24 of the core study
Population: Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24 | -1.6 Units on a scale | Standard Deviation 13.54 |
| Rivastigmine 4.6 mg/24 h Transdermal Patch | Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24 | -6.4 Units on a scale | Standard Deviation 14.01 |
Secondary
Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24
The ADCS-CGIC assesses the clinical meaningfulness of a treatment based on the clinician's rating of change. The rating is provided by a trained clinician or psychometrician blinded to the patient's treatment. The rater interviewed the patient and caregiver separately at Baseline using a worksheet that provided space for notes and comments. At baseline, raters had access to all of the patient's available records and evaluations. The rater used a similar worksheet at follow-up visits, and referred to the baseline worksheet prior to making a rating of change. The worksheets were divided into 3 domains: mental/cognitive state, behavior, and functioning. Change ratings were based on a 7-point scale: Marked (1), moderate (2), and minimal improvement (3), no change (4), and marked (5), moderate (6), and minimal worsening (7). The percentage of patients in each of the 7 categories is reported.
Time frame: Baseline of the core study to Week 24 of the core study
Population: Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | No change | 34.2 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Moderate improvement | 3.5 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Minimal improvement | 20.1 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Minimal worsening | 24.3 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Moderate worsening | 14.1 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Marked worsening | 2.9 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Marked improvement | 1.0 Percentage of patients |
| Rivastigmine 4.6 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Moderate worsening | 19.0 Percentage of patients |
| Rivastigmine 4.6 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Marked improvement | 1.3 Percentage of patients |
| Rivastigmine 4.6 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Minimal worsening | 31.4 Percentage of patients |
| Rivastigmine 4.6 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Moderate improvement | 3.5 Percentage of patients |
| Rivastigmine 4.6 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Marked worsening | 4.1 Percentage of patients |
| Rivastigmine 4.6 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Minimal improvement | 11.4 Percentage of patients |
| Rivastigmine 4.6 mg/24 h Transdermal Patch | Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | No change | 29.2 Percentage of patients |
Secondary
Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24
The NPI-12 assesses a wide range of behaviors encountered in patients with dementia to provide a means of distinguishing the frequency and severity of behavioral changes over time. Ten behavioral and 2 neurovegetative domains were evaluated in an interview with the caregiver given by a mental health professional. The scale included 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 12 domains yielded the NPI-12 total score. The NPI-12 was scored from 0 to 144, with lower scores reflecting improvement in psychiatric behavior. A negative change score indicates improvement.
Time frame: Baseline of the core study to Week 24 of the core study
Population: Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24 | -0.4 Units on a scale | Standard Deviation 14.01 |
| Rivastigmine 4.6 mg/24 h Transdermal Patch | Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24 | 1.2 Units on a scale | Standard Deviation 16.79 |
Secondary
Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24
The ADCS-CGIC assesses the clinical meaningfulness of a treatment based on the clinician's rating of change. The rating is provided by a trained clinician or psychometrician blinded to the patient's treatment. The rater interviewed the patient and caregiver separately at Baseline using a worksheet that provided space for notes and comments. At baseline, raters had access to all of the patient's available records and evaluations. The rater used a similar worksheet at follow-up visits, and referred to the baseline worksheet prior to making a rating of change. The worksheets were divided into 3 domains: mental/cognitive state, behavior, and functioning. Change ratings were based on a 7-point scale: Marked (1), moderate (2), and minimal improvement (3), no change (4), and marked (5), moderate (6), and minimal worsening (7). The percentage of patients in each of the 7 categories is reported.
Time frame: Baseline of the core study to Week 24 of the extension study
Population: Modified full analysis set: All patients who received at least 1 application of study medication and had at least 1 efficacy assessment in the extension study. Only patients with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Marked improvement | 1.8 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Moderate improvement | 5.0 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Minimal improvement | 9.7 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | No change | 26.2 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Minimal worsening | 31.5 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Moderate worsening | 21.5 Percentage of patients |
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24 | Marked worsening | 4.2 Percentage of patients |
Secondary
Extension Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24
The ADCS-ADL-SIV is designed to assess the patient's performance of both 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, and making judgments and decisions. For each of the 19 questions in the ADCS-ADL-SIV, there was either a forced choice of best response or a yes or no question with additional sub-questions. Responses for each item were obtained from the caregiver through an interview. Higher numbered scores and answers of yes reflected a more self-sufficient individual. The total score was calculated as the sum of all items and sub-questions and ranged from 0 to 54. A higher total score represented a higher functioning patient. A positive change score indicates improvement.
Time frame: Baseline of the core study to Week 24 of the extension study
Population: Modified full analysis set: All patients who received at least 1 application of study medication and had at least 1 efficacy assessment in the extension study. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Extension Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24 | -4.3 Units on a scale | Standard Deviation 8.37 |
Secondary
Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24
The SIB is a 40-item scale developed for the evaluation of the severity of cognitive dysfunction in more advanced Alzheimer Disease patients. The domains assessed included social interaction, memory, language, attention, orientation, praxis, visuo-spatial ability, construction, and orienting to name. The items of the SIB were developed as simple 1-step commands which are presented by a trained rater with gestural cues and repeated if necessary. The SIB was scored from 0 to 100, with higher scores reflecting higher levels of cognitive ability. A positive change score indicates improvement.
Time frame: Baseline of the core study to Week 24 of the extension study
Population: Modified full analysis set: All patients who received at least 1 application of study medication and had at least 1 efficacy assessment in the extension study. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rivastigmine 13.3 mg/24 h Transdermal Patch | Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24 | -5.9 Units on a scale | Standard Deviation 16.72 |