Back to resultsEfficacy and Safety of Rivastigmine Transdermal Patch in Patients With Mild to Moderate Alzheimer's Disease
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Rivastigmine transdermal patch
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring rivastigmine，Alzheimer's Disease, transdermal patch
Eligibility Criteria
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/exclusion criteria may apply
Other protocol-defined inclusion/exclusion criteria may apply
Extension Phase Eligibility Criteria
Inclusion Criteria:
- Patients who have completed the Double-blind Treatment Phase on study medication
Exclusion Criteria
- Patients who have any important protocol deviations until the completion of the Double-blind Treatment Phase
Sites / Locations
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
rivastigmine 5 cm^2
Rivastigmine 10 cm^2
Arm Description
Participants received daily matching placebo patch for the duration of the 24-week double-blind treatment phase of the study.
During the 16-week titration period patients received daily rivastigmine 2.5 cm^2 patch for the first 4 weeks and thereafter 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.
During the 16-week titration period patients received daily rivastigmine 2.5 cm^2 patch for the first 4 weeks, rivastigmine 5 cm^2 patch 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.
Outcomes
Primary Outcome Measures
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.
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:
Markedly improved
Moderately improved
Minimally improved
Unchanged
Minimally worse
Moderately worse
Markedly worse
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT00423085
First Posted
January 11, 2007
Last Updated
January 14, 2014
Sponsor
Novartis Pharmaceuticals
Collaborators
Ono Pharmaceutical Co. Ltd
1. Study Identification
Unique Protocol Identification Number
NCT00423085
Brief Title
Efficacy and Safety of Rivastigmine Transdermal Patch in Patients With Mild to Moderate Alzheimer's Disease
Official Title
A 24-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-finding Evaluation of the Efficacy, Safety, and Tolerability of the Once-daily Rivastigmine Transdermal Patch in Patients With Probable Alzheimer's Disease (MMSE 10-20)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
April 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
Collaborators
Ono Pharmaceutical Co. Ltd
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
rivastigmine，Alzheimer's Disease, transdermal patch
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
859 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received daily matching placebo patch for the duration of the 24-week double-blind treatment phase of the study.
Arm Title
rivastigmine 5 cm^2
Arm Type
Experimental
Arm Description
During the 16-week titration period patients received daily rivastigmine 2.5 cm^2 patch for the first 4 weeks and thereafter 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.
Arm Title
Rivastigmine 10 cm^2
Arm Type
Experimental
Arm Description
During the 16-week titration period patients received daily rivastigmine 2.5 cm^2 patch for the first 4 weeks, rivastigmine 5 cm^2 patch 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.
Intervention Type
Drug
Intervention Name(s)
Rivastigmine transdermal patch
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)
Description
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
Title
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)
Description
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:
Markedly improved
Moderately improved
Minimally improved
Unchanged
Minimally worse
Moderately worse
Markedly worse
Time Frame
Baseline and Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)
Description
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
Title
Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)
Description
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
Title
Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS)
Description
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
Title
Change From Baseline in Mini-Mental State Examination (MMSE)
Description
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
Title
Extension Phase: Change From Extension Phase Baseline to End of Extension in Mini-Mental State Examination (MMSE)
Description
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
Title
Extension Phase: Change From Extension Phase Baseline to End of Extension in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)
Description
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
Title
Extension Phase: Change From Extension Phase Baseline to End of Extension in Modified Crichton Scale
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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/exclusion criteria may apply
Other protocol-defined inclusion/exclusion criteria may apply
Extension Phase Eligibility Criteria
Inclusion Criteria:
Patients who have completed the Double-blind Treatment Phase on study medication
Exclusion Criteria
Patients who have any important protocol deviations until the completion of the Double-blind Treatment Phase
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Hokkaido region
State/Province
Hokkaido
Country
Japan
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety of Rivastigmine Transdermal Patch in Patients With Mild to Moderate Alzheimer's Disease
We'll reach out to this number within 24 hrs