Trial Outcomes & Findings for Clinical Effectiveness of 10 cm^2 Rivastigmine Patch in Patients With Alzheimer's Disease (NCT NCT00561392)

NCT ID: NCT00561392

Last Updated: 2012-04-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

208 participants

Primary outcome timeframe

Baseline to Week 24

Results posted on

2012-04-16

Participant Flow

Participant milestones

Participant milestones
Measure
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.
Overall Study
STARTED
208
Overall Study
COMPLETED
155
Overall Study
NOT COMPLETED
53

Reasons for withdrawal

Reasons for withdrawal
Measure
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.
Overall Study
Adverse Event
38
Overall Study
Lack of Efficacy
2
Overall Study
Protocol Violation
1
Overall Study
Withdrawal by Subject
8
Overall Study
Administrative problems
4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=208 Participants
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.
Age Continuous
74 years
STANDARD_DEVIATION 7.7 • n=5 Participants
Sex: Female, Male
Female
110 Participants
n=5 Participants
Sex: Female, Male
Male
98 Participants
n=5 Participants
Region of Enrollment
Germany
208 participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=182 Participants
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.
Percentage of Participants Treated by Rivastigmine 10 cm^2 Patch for at Least 8 Weeks Who Completed the Study
74.2 Percentage of participants
Interval 67.8 to 80.5

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=182 Participants
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.
Percentage of Participants Treated by Rivastigmine 10 cm^2 Patch for at Least 8 Weeks Regardless Whether They Completed the Study
80.8 Percentage of participants
Interval 75.0 to 86.5

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=182 Participants
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.
Percentage of Participants Who Were Compliant to the 10 cm^2 Patch
95.0 Percentage of participants
Standard Deviation 28.3

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=182 Participants
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.
Mean Change From Baseline in the Mini-Mental State Examination (MMSE) Score at Week 24
1.3 Units on a scale
Standard Deviation 3.8

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=182 Participants
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.
Mean Change From Baseline in the Trail-making Test Part A Score at Week 24
-8.9 Seconds
Standard Deviation 109.45

SECONDARY outcome

Timeframe: Baseline to Week 24

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

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.

Outcome measures

Outcome measures
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=182 Participants
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.
Mean Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score at Week 24
1.3 Units on a scale
Standard Deviation 12.02

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=182 Participants
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.
Change From Baseline in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) at Week 24 Assessed by the Physician
No change
47 Participants
Change From Baseline in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) at Week 24 Assessed by the Physician
Minimal improvement
25 Participants
Change From Baseline in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) at Week 24 Assessed by the Physician
Moderate improvement
23 Participants
Change From Baseline in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) at Week 24 Assessed by the Physician
Marked improvement
15 Participants
Change From Baseline in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) at Week 24 Assessed by the Physician
Minimal decline
37 Participants
Change From Baseline in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) at Week 24 Assessed by the Physician
Moderate decline
12 Participants
Change From Baseline in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) at Week 24 Assessed by the Physician
Marked decline
5 Participants

SECONDARY outcome

Timeframe: Baseline t0 Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=182 Participants
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.
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
No change
21 Participants
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
Minimal improvement
23 Participants
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
Moderate improvement
16 Participants
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
Marked improvement
15 Participants
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
Minimal decline
56 Participants
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
Moderate decline
20 Participants
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
Marked decline
14 Participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=182 Participants
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.
Mean Change From Baseline in the Mini-Zarit Inventory Score of Caregiver Burden at Week 24
0.4 Units on a scale
Standard Deviation 1.58

Adverse Events

Rivastigmine 5 and 10 cm^2 Patch

Serious events: 18 serious events
Other events: 49 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=208 participants at risk
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.
Cardiac disorders
Bradycardia
0.48%
1/208
General disorders
Death
0.48%
1/208
General disorders
Fatigue
0.48%
1/208
General disorders
Malaise
0.48%
1/208
Infections and infestations
Bronchitis
0.48%
1/208
Injury, poisoning and procedural complications
Fall
0.48%
1/208
Injury, poisoning and procedural complications
Femoral neck fracture
0.48%
1/208
Investigations
Blood glucose abnormal
0.48%
1/208
Metabolism and nutrition disorders
Dehydration
0.48%
1/208
Musculoskeletal and connective tissue disorders
Back pain
0.48%
1/208
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm
0.48%
1/208
Nervous system disorders
Cerebrovascular accident
0.48%
1/208
Nervous system disorders
Cognitive disorder
0.48%
1/208
Nervous system disorders
Dementia Alzheimer's type
1.4%
3/208
Nervous system disorders
Dysstasis
0.48%
1/208
Nervous system disorders
Grand mal convulsion
0.48%
1/208
Nervous system disorders
Syncope
0.48%
1/208
Psychiatric disorders
Aggression
0.48%
1/208
Psychiatric disorders
Confusional state
0.96%
2/208
Psychiatric disorders
Disorientation
0.48%
1/208
Psychiatric disorders
Psychotic disorder
0.48%
1/208
Renal and urinary disorders
Incontinence
0.48%
1/208
Vascular disorders
Circulatory collapse
0.48%
1/208
Vascular disorders
Deep vein thrombosis
0.48%
1/208
Vascular disorders
Hypertensive crisis
0.48%
1/208

Other adverse events

Other adverse events
Measure
Rivastigmine 5 and 10 cm^2 Patch
n=208 participants at risk
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.
Gastrointestinal disorders
Nausea
10.1%
21/208
Gastrointestinal disorders
Vomiting
7.2%
15/208
Skin and subcutaneous tissue disorders
Erythema
8.7%
18/208
Skin and subcutaneous tissue disorders
Pruritus
8.2%
17/208

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 778-8300

Results disclosure agreements

  • Principal investigator is a sponsor employee 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.
  • Publication restrictions are in place

Restriction type: OTHER