Alzheimer's Disease
Conditions
Keywords
rivastigmine，Alzheimer's Disease, transdermal patch
Brief summary
The purpose of this study was to investigate the 5cm\^2 and 10cm\^2 doses of rivastigmine transdermal patch in terms of efficacy and safety in patients with probable Alzheimer's Disease (MMSE \[Mini Mental State Examination\] 10-20). A 52-week extension phase evaluated the safety and tolerability of long-term treatment by rivastigmine transdermal patch in patients with probable Alzheimer's Disease (AD).
Detailed description
Patients were randomly assigned in a double-blind manner to one of the 3 treatment arms (placebo, rivastigmine 5 cm\^2 and rivastigmine 10 cm\^2) in a ratio of 1:1:1. During the Double-blind treatment phase, patients entered a 16-week Titration Period followed by an 8-week Maintenance Period. During the open-label extension phase, all patients started treatment with a 2.5 cm\^2 patch and the dose was increased to 10 cm\^2 over a 16-week titration period, followed by a maintenance period of 36 weeks.
Interventions
Rivastigmine transdermal patch was provided in the following sizes and doses: 2.5 cm\^2 (4.5 mg), 5 cm\^2 (9 mg), 7.5 cm\^2 (13.5 mg), and 10 cm\^2 (18 mg). The caregiver applied one patch on the back of a patient, placed alternately from the right to the left side at approximately the same time each day.
DRUGPlacebo
Placebo transdermal patch was provided in the following sizes: 2.5 cm\^2, 5 cm\^2, 7.5 cm\^2 and 10 cm\^2. The caregiver applied one patch on the back of a patient, placed alternately from the right to the left side at approximately the same time each day.
Sponsors
Ono Pharmaceutical Co. Ltd
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* A diagnosis of dementia of the Alzheimer's type according to the DSM-IV criteria * A clinical diagnosis of probable AD according to NINCDS/ADRDA criteria * An MMSE score of \> or = 10 and \< or = 20
Exclusion criteria
* A current DSM-IV diagnosis of major depression * Taken rivastigmine in the past * A score of \> 5 on the Modified Hachinski Ischemic Scale (MHIS) Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | Baseline and Week 24 | The Alzheimer's Disease Assessment Scale - Japan cognitive subscale (ADAS-J cog) was used to measure change in cognitive function. The ADAS-J cog score ranges from 0-70, with higher total scores indicating more impairment. A negative change score indicates improvement from baseline. |
| Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Baseline and Week 24 | The overall clinical rating of change from baseline to week 24 measured by the 7-point CIBIC plus-J scale. The Clinician's Interview-Based Impression of Change plus Caregiver Input consists of 3 subscales: Disability Assessment of Dementia Scale, Behavioral Pathology in Alzheimer's Disease Rating Scale and Mental Function Impairment Scale, as well as the Clinician's Global Impression of Change (CGIC). Participants are scored according to the following: 1. Markedly improved 2. Moderately improved 3. Minimally improved 4. Unchanged 5. Minimally worse 6. Moderately worse 7. Markedly worse |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Baseline and Week 24 | The Disability Assessment for Dementia (DAD) was used to assess levels of difficulty in activities of daily living (ADL). The DAD is administered through an interview with the caregiver. A total score is obtained by adding the rating for each question and converting this to a total score out of 100 (%). Higher scores represent less disability in ADL while lower scores indicate more dysfunction. A positive change score indicates an improvement from baseline. |
| Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) | Baseline and Week 24 | BEHAVE-AD was used to assess patient behavior and psychiatric symptoms. It covers symptoms in seven categories: paranoid and delusional ideation, hallucinations, activity disturbances, diurnal rhythm disturbances, aggressiveness, affective disorders and anxieties, and phobias. Caregivers rate behavioral symptoms on a 0-3 scale. The total score can range from 0 to 66, with a lower score indicating better function. A negative change score indicates an improvement from baseline. |
| Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) | Baseline and Week 24 | MENFIS was used to assess patient cognitive and psychiatric function, and evaluates core symptoms of dementia including cognitive, motivational and emotional aspects. The total score ranges from 0 to 78. The higher the score, the greater the functional deficit. A negative change score indicates an improvement from baseline. |
| Change From Baseline in Mini-Mental State Examination (MMSE) | Baseline and Week 24 | The MMSE is a 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 from baseline. |
| Extension Phase: Change From Extension Phase Baseline to End of Extension in Mini-Mental State Examination (MMSE) | Extension Phase Baseline and Week 52 of extension phase | The MMSE is a 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. This outcome measured the change in MMSE from the beginning of the open-label extension phase through to Week 52 of the extension phase. |
| Extension Phase: Change From Extension Phase Baseline to End of Extension in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Extension Phase Baseline and Week 52 of extension phase | The Disability Assessment for Dementia (DAD) was used to assess levels of difficulty in activities of daily living. The DAD is administered through an interview with the caregiver. A total score is obtained by adding the rating for each question and converting this to a total score out of 100 (%). Higher scores represent less disability in activities of daily living while lower scores indicate more dysfunction. A positive change score indicates an improvement from baseline. |
| Extension Phase: Change From Extension Phase Baseline to End of Extension in Modified Crichton Scale | Extension Phase Baseline and Week 52 of extension phase | The Modified Crichton Scale includes a total of seven items evaluated in eight grades that assess basic activities of daily living, communication functions, psychiatric symptoms and quality of life; the total score can range from 0 to 56, with a lower score indicating better function. A negative change score indicates an improvement from baseline. |
Countries
Japan
Participant flow
Pre-assignment details
Participants were randomly assigned in a double-blind manner to one of the 3 treatment arms (placebo, rivastigmine 5 cm\^2 and rivastigmine 10 cm\^2) in a ratio of 1:1:1. Following the 24-week double-blind treatment phase, participants could enroll in the open-label extension phase, where all participants were titrated up to the 10 cm\^2 patch dose.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received daily matching placebo patch for the duration of the 24-week double-blind treatment phase of the study. | 286 |
| Rivastigmine 5 cm^2 During the 16-week titration period patients received daily rivastigmine 2.5 cm\^2 patch for the first 4 weeks and then daily rivastigmine 5 cm\^2 patch. For patients who experienced intolerability, the dose was adjusted to rivastigmine 2.5 cm\^2 daily. Patients then entered the 8-week maintenance period during which time they continued to receive the dose of rivastigmine they were taking at the end of the titration period. | 282 |
| Rivastigmine 10 cm^2 During the 16-week titration period patients received daily rivastigmine 2.5 cm\^2 patch for the first 4 weeks, rivastigmine 5 cm\^2 for the next 4 weeks, rivastigmine 7.5 cm\^2 patch for the next 4 weeks and then rivastigmine 10 cm\^2 patch for the final 4 weeks. For patients who experienced intolerability, the dose was adjusted downward. Patients then entered the 8-week maintenance period during which time they continued to receive the dose of rivastigmine they were taking at the end of the titration period. | 287 |
| Total | 855 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 24-Week Double-Blind Treatment Phase | Adverse Event | 21 | 38 | 34 | 0 |
| 24-Week Double-Blind Treatment Phase | Death | 1 | 1 | 0 | 0 |
| 24-Week Double-Blind Treatment Phase | Lost to Follow-up | 1 | 0 | 0 | 0 |
| 24-Week Double-Blind Treatment Phase | Protocol Violation | 8 | 3 | 7 | 0 |
| 24-Week Double-Blind Treatment Phase | Unsatisfactory therapeutic effect | 7 | 6 | 7 | 0 |
| 24-Week Double-Blind Treatment Phase | Withdrawal by Subject | 8 | 16 | 11 | 0 |
| 52-Week Open-Label Extension Phase | Adverse Event | 0 | 0 | 0 | 97 |
| 52-Week Open-Label Extension Phase | Death | 0 | 0 | 0 | 2 |
| 52-Week Open-Label Extension Phase | Protocol deviation | 0 | 0 | 0 | 9 |
| 52-Week Open-Label Extension Phase | Unsatisfactory therapeutic effect | 0 | 0 | 0 | 18 |
| 52-Week Open-Label Extension Phase | Withdrawal by Subject | 0 | 0 | 0 | 37 |
Baseline characteristics
| Characteristic | Placebo | Rivastigmine 5 cm^2 | Rivastigmine 10 cm^2 | Total |
|---|---|---|---|---|
| Age, Continuous | 74.5 years STANDARD_DEVIATION 7.36 | 74.3 years STANDARD_DEVIATION 7.46 | 75.1 years STANDARD_DEVIATION 6.85 | 74.6 years STANDARD_DEVIATION 7.22 |
| Sex: Female, Male Female | 195 Participants | 194 Participants | 195 Participants | 584 Participants |
| Sex: Female, Male Male | 91 Participants | 88 Participants | 92 Participants | 271 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 157 / 286 | 206 / 282 | 214 / 287 | 491 / 637 |
| serious Total, serious adverse events | 20 / 286 | 14 / 282 | 18 / 287 | 74 / 637 |
Outcome results
Primary
Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)
The Alzheimer's Disease Assessment Scale - Japan cognitive subscale (ADAS-J cog) was used to measure change in cognitive function. The ADAS-J cog score ranges from 0-70, with higher total scores indicating more impairment. A negative change score indicates improvement from baseline.
Time frame: Baseline and Week 24
Population: The Intent-to-treat population: This population includes all randomized patients who received at least one dose of study drug and had at least a baseline and any post-baseline assessment on treatment (i.e. not more than 2 days after the last known date of study drug) for one of the primary efficacy variables. LOCF was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | Baseline Score | 24.8 units on a scale | Standard Deviation 9.46 |
| Placebo | Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | Change from Baseline | 1.3 units on a scale | Standard Deviation 5.07 |
| Placebo | Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | Week 24 Score | 26.1 units on a scale | Standard Deviation 11.49 |
| Rivastigmine 5 cm^2 | Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | Change from Baseline | 0.5 units on a scale | Standard Deviation 4.96 |
| Rivastigmine 5 cm^2 | Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | Baseline Score | 25.2 units on a scale | Standard Deviation 9.62 |
| Rivastigmine 5 cm^2 | Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | Week 24 Score | 25.7 units on a scale | Standard Deviation 11.7 |
| Rivastigmine 10 cm^2 | Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | Change from Baseline | 0.1 units on a scale | Standard Deviation 5.04 |
| Rivastigmine 10 cm^2 | Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | Week 24 Score | 25.1 units on a scale | Standard Deviation 11.25 |
| Rivastigmine 10 cm^2 | Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) | Baseline Score | 25.0 units on a scale | Standard Deviation 9.93 |
Primary
Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J)
The overall clinical rating of change from baseline to week 24 measured by the 7-point CIBIC plus-J scale. The Clinician's Interview-Based Impression of Change plus Caregiver Input consists of 3 subscales: Disability Assessment of Dementia Scale, Behavioral Pathology in Alzheimer's Disease Rating Scale and Mental Function Impairment Scale, as well as the Clinician's Global Impression of Change (CGIC). Participants are scored according to the following: 1. Markedly improved 2. Moderately improved 3. Minimally improved 4. Unchanged 5. Minimally worse 6. Moderately worse 7. Markedly worse
Time frame: Baseline and Week 24
Population: Intent-to-treat population utilizing LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Markedly worse | 2 Participants |
| Placebo | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Minimally worse | 84 Participants |
| Placebo | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Minimally improved | 36 Participants |
| Placebo | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Markedly improved | 0 Participants |
| Placebo | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Unchanged | 111 Participants |
| Placebo | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Moderately improved | 5 Participants |
| Placebo | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Moderately worse | 29 Participants |
| Rivastigmine 5 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Markedly worse | 0 Participants |
| Rivastigmine 5 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Unchanged | 109 Participants |
| Rivastigmine 5 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Markedly improved | 0 Participants |
| Rivastigmine 5 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Moderately improved | 12 Participants |
| Rivastigmine 5 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Minimally improved | 45 Participants |
| Rivastigmine 5 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Minimally worse | 82 Participants |
| Rivastigmine 5 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Moderately worse | 21 Participants |
| Rivastigmine 10 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Moderately improved | 6 Participants |
| Rivastigmine 10 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Markedly worse | 2 Participants |
| Rivastigmine 10 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Markedly improved | 0 Participants |
| Rivastigmine 10 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Minimally worse | 78 Participants |
| Rivastigmine 10 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Moderately worse | 22 Participants |
| Rivastigmine 10 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Minimally improved | 53 Participants |
| Rivastigmine 10 cm^2 | Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) | Unchanged | 109 Participants |
Secondary
Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)
BEHAVE-AD was used to assess patient behavior and psychiatric symptoms. It covers symptoms in seven categories: paranoid and delusional ideation, hallucinations, activity disturbances, diurnal rhythm disturbances, aggressiveness, affective disorders and anxieties, and phobias. Caregivers rate behavioral symptoms on a 0-3 scale. The total score can range from 0 to 66, with a lower score indicating better function. A negative change score indicates an improvement from baseline.
Time frame: Baseline and Week 24
Population: Intent-to-treat population. Only patients with a valid baseline and post-baseline score were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) | Week 24 Score | 4.8 units on a scale | Standard Deviation 5.41 |
| Placebo | Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) | Change from Baseline | -0.1 units on a scale | Standard Deviation 3.76 |
| Placebo | Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) | Baseline Score | 4.8 units on a scale | Standard Deviation 4.5 |
| Rivastigmine 5 cm^2 | Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) | Week 24 Score | 4.6 units on a scale | Standard Deviation 5.03 |
| Rivastigmine 5 cm^2 | Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) | Baseline Score | 4.7 units on a scale | Standard Deviation 4.96 |
| Rivastigmine 5 cm^2 | Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) | Change from Baseline | -0.1 units on a scale | Standard Deviation 4.17 |
| Rivastigmine 10 cm^2 | Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) | Baseline Score | 5.4 units on a scale | Standard Deviation 5.15 |
| Rivastigmine 10 cm^2 | Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) | Change from Baseline | -0.3 units on a scale | Standard Deviation 4.7 |
| Rivastigmine 10 cm^2 | Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) | Week 24 Score | 5.1 units on a scale | Standard Deviation 5.89 |
Secondary
Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)
The Disability Assessment for Dementia (DAD) was used to assess levels of difficulty in activities of daily living (ADL). The DAD is administered through an interview with the caregiver. A total score is obtained by adding the rating for each question and converting this to a total score out of 100 (%). Higher scores represent less disability in ADL while lower scores indicate more dysfunction. A positive change score indicates an improvement from baseline.
Time frame: Baseline and Week 24
Population: Intent-to-treat population. Only patients with a valid baseline and post-baseline score were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Baseline Score | 66.70 units on a scale | Standard Deviation 19.902 |
| Placebo | Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Change from Baseline | -4.16 units on a scale | Standard Deviation 12.443 |
| Placebo | Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Week 24 Score | 62.54 units on a scale | Standard Deviation 22.395 |
| Rivastigmine 5 cm^2 | Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Baseline Score | 64.19 units on a scale | Standard Deviation 20.571 |
| Rivastigmine 5 cm^2 | Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Week 24 Score | 61.19 units on a scale | Standard Deviation 22.415 |
| Rivastigmine 5 cm^2 | Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Change from Baseline | -2.99 units on a scale | Standard Deviation 10.259 |
| Rivastigmine 10 cm^2 | Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Change from Baseline | -1.88 units on a scale | Standard Deviation 10.657 |
| Rivastigmine 10 cm^2 | Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Week 24 Score | 62.27 units on a scale | Standard Deviation 23.691 |
| Rivastigmine 10 cm^2 | Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Baseline Score | 64.15 units on a scale | Standard Deviation 21.921 |
Secondary
Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS)
MENFIS was used to assess patient cognitive and psychiatric function, and evaluates core symptoms of dementia including cognitive, motivational and emotional aspects. The total score ranges from 0 to 78. The higher the score, the greater the functional deficit. A negative change score indicates an improvement from baseline.
Time frame: Baseline and Week 24
Population: Intent-to-treat population. Only patients with a valid baseline and post-baseline score were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) | Change from Baseline | 2.9 units on a scale | Standard Deviation 6.18 |
| Placebo | Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) | Week 24 Score | 26.1 units on a scale | Standard Deviation 12.68 |
| Placebo | Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) | Baseline Score | 23.2 units on a scale | Standard Deviation 11.13 |
| Rivastigmine 5 cm^2 | Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) | Change from Baseline | 2.2 units on a scale | Standard Deviation 5.86 |
| Rivastigmine 5 cm^2 | Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) | Baseline Score | 24.3 units on a scale | Standard Deviation 11.72 |
| Rivastigmine 5 cm^2 | Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) | Week 24 Score | 26.5 units on a scale | Standard Deviation 13.43 |
| Rivastigmine 10 cm^2 | Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) | Change from Baseline | 1.6 units on a scale | Standard Deviation 5.82 |
| Rivastigmine 10 cm^2 | Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) | Baseline Score | 24.6 units on a scale | Standard Deviation 11.36 |
| Rivastigmine 10 cm^2 | Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) | Week 24 Score | 26.2 units on a scale | Standard Deviation 12.69 |
Secondary
Change From Baseline in Mini-Mental State Examination (MMSE)
The MMSE is a 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 from baseline.
Time frame: Baseline and Week 24
Population: Intent-to-treat population. Only patients with a valid baseline and post-baseline score were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mini-Mental State Examination (MMSE) | Week 24 Score | 16.4 units on a scale | Standard Deviation 4.21 |
| Placebo | Change From Baseline in Mini-Mental State Examination (MMSE) | Baseline Score | 16.7 units on a scale | Standard Deviation 2.87 |
| Placebo | Change From Baseline in Mini-Mental State Examination (MMSE) | Change from Baseline | -0.3 units on a scale | Standard Deviation 2.82 |
| Rivastigmine 5 cm^2 | Change From Baseline in Mini-Mental State Examination (MMSE) | Week 24 Score | 16.6 units on a scale | Standard Deviation 4.62 |
| Rivastigmine 5 cm^2 | Change From Baseline in Mini-Mental State Examination (MMSE) | Baseline Score | 16.9 units on a scale | Standard Deviation 2.88 |
| Rivastigmine 5 cm^2 | Change From Baseline in Mini-Mental State Examination (MMSE) | Change from Baseline | -0.3 units on a scale | Standard Deviation 3.05 |
| Rivastigmine 10 cm^2 | Change From Baseline in Mini-Mental State Examination (MMSE) | Baseline Score | 16.4 units on a scale | Standard Deviation 3.09 |
| Rivastigmine 10 cm^2 | Change From Baseline in Mini-Mental State Examination (MMSE) | Change from Baseline | 0.0 units on a scale | Standard Deviation 2.87 |
| Rivastigmine 10 cm^2 | Change From Baseline in Mini-Mental State Examination (MMSE) | Week 24 Score | 16.4 units on a scale | Standard Deviation 4.47 |
Secondary
Extension Phase: Change From Extension Phase Baseline to End of Extension in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)
The Disability Assessment for Dementia (DAD) was used to assess levels of difficulty in activities of daily living. The DAD is administered through an interview with the caregiver. A total score is obtained by adding the rating for each question and converting this to a total score out of 100 (%). Higher scores represent less disability in activities of daily living while lower scores indicate more dysfunction. A positive change score indicates an improvement from baseline.
Time frame: Extension Phase Baseline and Week 52 of extension phase
Population: Intent-to-treat population utilizing last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Extension Phase: Change From Extension Phase Baseline to End of Extension in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Extension Baseline | 61.99 units on a scale | Standard Deviation 22.939 |
| Placebo | Extension Phase: Change From Extension Phase Baseline to End of Extension in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | End of Extension | 51.95 units on a scale | Standard Deviation 25.407 |
| Placebo | Extension Phase: Change From Extension Phase Baseline to End of Extension in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) | Change from Baseline | -10.04 units on a scale | Standard Deviation 14.089 |
Secondary
Extension Phase: Change From Extension Phase Baseline to End of Extension in Mini-Mental State Examination (MMSE)
The MMSE is a 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. This outcome measured the change in MMSE from the beginning of the open-label extension phase through to Week 52 of the extension phase.
Time frame: Extension Phase Baseline and Week 52 of extension phase
Population: Intent-to-treat population utilizing last observation carried forward. This population includes all patients who received at least one dose of open-label study medication and had at least one efficacy assessment on treatment in the open-label extension Phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Extension Phase: Change From Extension Phase Baseline to End of Extension in Mini-Mental State Examination (MMSE) | Extension Baseline | 16.6 units on a scale | Standard Deviation 4.43 |
| Placebo | Extension Phase: Change From Extension Phase Baseline to End of Extension in Mini-Mental State Examination (MMSE) | End of Extension | 14.9 units on a scale | Standard Deviation 5.58 |
| Placebo | Extension Phase: Change From Extension Phase Baseline to End of Extension in Mini-Mental State Examination (MMSE) | Change from Baseline | -1.7 units on a scale | Standard Deviation 3.28 |
Secondary
Extension Phase: Change From Extension Phase Baseline to End of Extension in Modified Crichton Scale
The Modified Crichton Scale includes a total of seven items evaluated in eight grades that assess basic activities of daily living, communication functions, psychiatric symptoms and quality of life; the total score can range from 0 to 56, with a lower score indicating better function. A negative change score indicates an improvement from baseline.
Time frame: Extension Phase Baseline and Week 52 of extension phase
Population: Intent-to-treat population utilizing last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Extension Phase: Change From Extension Phase Baseline to End of Extension in Modified Crichton Scale | Extension Baseline | 20.0 units on a scale | Standard Deviation 10.04 |
| Placebo | Extension Phase: Change From Extension Phase Baseline to End of Extension in Modified Crichton Scale | End of Extension | 24.0 units on a scale | Standard Deviation 11.3 |
| Placebo | Extension Phase: Change From Extension Phase Baseline to End of Extension in Modified Crichton Scale | Change from Baseline | 4.0 units on a scale | Standard Deviation 6.74 |