ADEPT: Clinical Effectiveness of 10 cm^2 Rivastigmine Patch in Patients With Alzheimer's Disease

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00561392
• Collaborator: (none)
• Enrollment: 208
• Location: 1
• Arm: 1
• Duration (Months): 12
• Patients Per Site Per Month: 17.3

Study Details

Study Description

Brief Summary

This study evaluated the safety and efficacy of 10 cm^{2 rivastigmine patch in patients with Alzheimer Disease (MMSE 10-26). The primary objective was the percentage of patients who stayed on the target size of 10 cm}2 for at least 8 weeks. This proportion was then compared to historical data of the percentage of patients who could reach a rivastigmine capsule target dose of 12 mg and stay on it at least 8 weeks.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: Rivastigmine 5 and 10 cm^2 patch	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 208 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 24-week, Multi-center, Open, Evaluation of the Clinical Effectiveness of the Once-daily 10 cm^2 Rivastigmine Patch Formulation in Patients With Probable Alzheimer's Disease (MMSE10-26)
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rivastigmine 5 and 10 cm^2 patch For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.	Drug: Rivastigmine 5 and 10 cm^2 patch

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Treated by Rivastigmine 10 cm^2 Patch for at Least 8 Weeks Who Completed the Study [Baseline to Week 24]

   Dosages of study medication prescribed to and taken by the patient was assessed in a "Drug Administration Record" with start date, end date, dosage and reason for dose adjustment (if applicable). Data was amended by counting the returned medication at the study visits and information by the caregiver.

2. Percentage of Participants Treated by Rivastigmine 10 cm^2 Patch for at Least 8 Weeks Regardless Whether They Completed the Study [Baseline to Week 24]

   Dosages of study medication prescribed to and taken by the patient was assessed in a "Drug Administration Record" with start date, end date, dosage and reason for dose adjustment (if applicable). Data was amended by counting the returned medication at the study visits and information by the caregiver.

3. Percentage of Participants Who Were Compliant to the 10 cm^2 Patch [Baseline to Week 24]

   Dosages of study medication prescribed to and taken by the patient was assessed in a "Drug Administration Record" with start date, end date, dosage and reason for dose adjustment (if applicable). Data was amended by counting the returned medication at the study visits and information by the caregiver.

Secondary Outcome Measures

1. Mean Change From Baseline in the Mini-Mental State Examination (MMSE) Score at Week 24 [Baseline and 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); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.

2. Mean Change From Baseline in the Trail-making Test Part A Score at Week 24 [Baseline to Week 24]

   The Trail-making test is a neuropsychological test of visual attention and task switching. The task requires a subject to 'connect-the-dots' of 25 consecutive numbers (1,2,3, etc.) on a sheet of paper or computer screen. The goal of the subject is to finish the test as quickly as possible, and the time taken to complete the test is used as the primary performance metric (in seconds). The maximum time allowed is 300 seconds. A negative change score indicates improvement.

3. Mean Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score at Week 24 [Baseline to Week 24]

   The ADCS-ADL scale is composed of 23 items developed to assess a 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, as well as making judgments and decisions. Responses for each item will be obtained from the caregiver through an interview. The range for the total ADCS-ADL score is 0 to 78; a higher score indicates a more self-sufficient individual. A positive change score indicates improvement.

4. Change From Baseline in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) at Week 24 Assessed by the Physician [Baseline to Week 24]

   The ADCS-CGIC is an assessment tool to make a judgment of change in a patient's condition. Change is derived from comparing an assessment performed at baseline versus an assessment at the end of the study. Change is categorized into 1 of 7 categories: No change; minimal, moderate, or marked improvement; or minimal, moderate, or marked decline. Results are reported as number of patients in the indicated change category.

5. Mean Change From Baseline in the Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (ADCS-CGIC) at Week 24 Assessed by the Caregiver [Baseline t0 Week 24]

   The ADCS-CGIC is an assessment tool to make a judgment of change in a patient's condition. Change is derived from comparing an assessment performed at baseline versus an assessment at the end of the study. Change is categorized into 1 of 7 categories: No change; minimal, moderate, or marked improvement; or minimal, moderate, or marked decline.

6. Mean Change From Baseline in the Mini-Zarit Inventory Score of Caregiver Burden at Week 24 [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. A negative change score indicates reduced burden.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males, and females not of child-bearing potential (surgically sterile or at least one year postmenopausal), of at least 50 years of age

• Probable Alzheimer's disease according to the NINCDS-ADRDA (National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) and DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) criteria

• MMSE (Mini-Mental State Examination) score of > 10 and < 26

• Patients initiating therapy for the first time with a cholinesterase inhibitor (patients prescribed both rivastigmine and memantine are allowed)

• Patients who failed to benefit from previous cholinesterase inhibitor treatment

Exclusion Criteria:

• Patients not treated according to the product monograph for rivastigmine capsules

• patients involved in a clinical trial

• 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)

Other protocol-defined exclusion criteria applied to the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Munich		Germany

Sponsors and Collaborators

• Novartis

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00561392
• Other Study ID Numbers: CENA713DDE15
• First Posted: Nov 21, 2007
• Last Update Posted: Apr 16, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by , ,: Alzheimer's Disease; Rivastigmine; Patch
• Additional relevant MeSH terms: Alzheimer Disease; Rivastigmine

Study Results

Participant Flow

Arm/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
Period Title: Overall Study
STARTED	208
COMPLETED	155
NOT COMPLETED	53

Baseline Characteristics

Arm/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
Overall Participants	208
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74 (7.7)
Sex: Female, Male (Count of Participants)
Female	110 52.9%
Male	98 47.1%
Region of Enrollment (participants) [Number]
Germany	208 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Treated by Rivastigmine 10 cm^2 Patch for at Least 8 Weeks Who Completed the Study
Description	Dosages of study medication prescribed to and taken by the patient was assessed in a "Drug Administration Record" with start date, end date, dosage and reason for dose adjustment (if applicable). Data was amended by counting the returned medication at the study visits and information by the caregiver.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population was defined as all randomized patients who were administered at least one dose of study medication and were assessed at baseline and post-baseline for efficacy at least 1 time.

Arm/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
Measure Participants	182
Number (95% Confidence Interval) [Percentage of participants]	74.2 35.7%

2. Secondary Outcome

Title	Mean Change From Baseline in the Mini-Mental State Examination (MMSE) Score at Week 24
Description	The MMSE is a brief, practical 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.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population was defined as all randomized patients who were administered at least one dose of study medication and were assessed at baseline and post-baseline for efficacy at least 1 time.

Arm/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
Measure Participants	182
Mean (Standard Deviation) [Units on a scale]	1.3 (3.8)

3. Secondary Outcome

Title	Mean Change From Baseline in the Trail-making Test Part A Score at Week 24
Description	The Trail-making test is a neuropsychological test of visual attention and task switching. The task requires a subject to 'connect-the-dots' of 25 consecutive numbers (1,2,3, etc.) on a sheet of paper or computer screen. The goal of the subject is to finish the test as quickly as possible, and the time taken to complete the test is used as the primary performance metric (in seconds). The maximum time allowed is 300 seconds. A negative change score indicates improvement.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population was defined as all randomized patients who were administered at least one dose of study medication and were assessed at baseline and post-baseline for efficacy at least 1 time.

Arm/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
Measure Participants	182
Mean (Standard Deviation) [Seconds]	-8.9 (109.45)

4. Secondary Outcome

Title	Mean Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score at Week 24
Description	The ADCS-ADL scale is composed of 23 items developed to assess a 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, as well as making judgments and decisions. Responses for each item will be obtained from the caregiver through an interview. The range for the total ADCS-ADL score is 0 to 78; a higher score indicates a more self-sufficient individual. A positive change score indicates improvement.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

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/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
Measure Participants	182
Mean (Standard Deviation) [Units on a scale]	1.3 (12.02)

5. Secondary Outcome

Title	Change From Baseline in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) at Week 24 Assessed by the Physician
Description	The ADCS-CGIC is an assessment tool to make a judgment of change in a patient's condition. Change is derived from comparing an assessment performed at baseline versus an assessment at the end of the study. Change is categorized into 1 of 7 categories: No change; minimal, moderate, or marked improvement; or minimal, moderate, or marked decline. Results are reported as number of patients in the indicated change category.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population was defined as all randomized patients who were administered at least one dose of study medication and were assessed at baseline and post-baseline for efficacy at least 1 time.

Arm/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
Measure Participants	182
No change	47 22.6%
Minimal improvement	25 12%
Moderate improvement	23 11.1%
Marked improvement	15 7.2%
Minimal decline	37 17.8%
Moderate decline	12 5.8%
Marked decline	5 2.4%

6. Secondary Outcome

Title	Mean Change From Baseline in the Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (ADCS-CGIC) at Week 24 Assessed by the Caregiver
Description	The ADCS-CGIC is an assessment tool to make a judgment of change in a patient's condition. Change is derived from comparing an assessment performed at baseline versus an assessment at the end of the study. Change is categorized into 1 of 7 categories: No change; minimal, moderate, or marked improvement; or minimal, moderate, or marked decline.
Time Frame	Baseline t0 Week 24

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population was defined as all randomized patients who were administered at least one dose of study medication and were assessed at baseline and post-baseline for efficacy at least 1 time.

Arm/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
Measure Participants	182
No change	21 10.1%
Minimal improvement	23 11.1%
Moderate improvement	16 7.7%
Marked improvement	15 7.2%
Minimal decline	56 26.9%
Moderate decline	20 9.6%
Marked decline	14 6.7%

7. Primary Outcome

Title	Percentage of Participants Treated by Rivastigmine 10 cm^2 Patch for at Least 8 Weeks Regardless Whether They Completed the Study
Description	Dosages of study medication prescribed to and taken by the patient was assessed in a "Drug Administration Record" with start date, end date, dosage and reason for dose adjustment (if applicable). Data was amended by counting the returned medication at the study visits and information by the caregiver.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population was defined as all randomized patients who were administered at least one dose of study medication and were assessed at baseline and post-baseline for efficacy at least 1 time.

Arm/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
Measure Participants	182
Number (95% Confidence Interval) [Percentage of participants]	80.8 38.8%

8. Primary Outcome

Title	Percentage of Participants Who Were Compliant to the 10 cm^2 Patch
Description	Dosages of study medication prescribed to and taken by the patient was assessed in a "Drug Administration Record" with start date, end date, dosage and reason for dose adjustment (if applicable). Data was amended by counting the returned medication at the study visits and information by the caregiver.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population was defined as all randomized patients who were administered at least one dose of study medication and were assessed at baseline and post-baseline for efficacy at least 1 time.

Arm/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
Measure Participants	182
Mean (Standard Deviation) [Percentage of participants]	95.0 (28.3) 45.7%

9. Secondary Outcome

Title	Mean Change From Baseline in the Mini-Zarit Inventory Score of Caregiver Burden at Week 24
Description	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. A negative change score indicates reduced burden.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population was defined as all randomized patients who were administered at least one dose of study medication and were assessed at baseline and post-baseline for efficacy at least 1 time.

Arm/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
Measure Participants	182
Mean (Standard Deviation) [Units on a scale]	0.4 (1.58)

Adverse Events

Arm/Group Title	Rivastigmine 5 and 10 cm^2 Patch
Arm/Group Description	For the 1st 4 weeks of this 24 week study, patients were administered rivastigmine transdermally once daily via a 5 cm^2 patch. After the Week 4 assessment, patients were administered rivastigmine transdermally once daily via a 10 cm^2 patch, with adjustments as necessary for safety and tolerability.
All Cause Mortality
	Rivastigmine 5 and 10 cm^2 Patch
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rivastigmine 5 and 10 cm^2 Patch
	Affected / at Risk (%)	# Events
Total	18/208 (8.7%)
Cardiac disorders
Bradycardia	1/208 (0.5%)
General disorders
Death	1/208 (0.5%)
Fatigue	1/208 (0.5%)
Malaise	1/208 (0.5%)
Infections and infestations
Bronchitis	1/208 (0.5%)
Injury, poisoning and procedural complications
Fall	1/208 (0.5%)
Femoral neck fracture	1/208 (0.5%)
Investigations
Blood glucose abnormal	1/208 (0.5%)
Metabolism and nutrition disorders
Dehydration	1/208 (0.5%)
Musculoskeletal and connective tissue disorders
Back pain	1/208 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm	1/208 (0.5%)
Nervous system disorders
Cerebrovascular accident	1/208 (0.5%)
Cognitive disorder	1/208 (0.5%)
Dementia Alzheimer's type	3/208 (1.4%)
Dysstasis	1/208 (0.5%)
Grand mal convulsion	1/208 (0.5%)
Syncope	1/208 (0.5%)
Psychiatric disorders
Aggression	1/208 (0.5%)
Confusional state	2/208 (1%)
Disorientation	1/208 (0.5%)
Psychotic disorder	1/208 (0.5%)
Renal and urinary disorders
Incontinence	1/208 (0.5%)
Vascular disorders
Circulatory collapse	1/208 (0.5%)
Deep vein thrombosis	1/208 (0.5%)
Hypertensive crisis	1/208 (0.5%)
Other (Not Including Serious) Adverse Events
	Rivastigmine 5 and 10 cm^2 Patch
	Affected / at Risk (%)	# Events
Total	49/208 (23.6%)
Gastrointestinal disorders
Nausea	21/208 (10.1%)
Vomiting	15/208 (7.2%)
Skin and subcutaneous tissue disorders
Erythema	18/208 (8.7%)
Pruritus	17/208 (8.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.