Trial Outcomes & Findings for A 24 Week, Multicenter, Open, Evaluation of the Clinical Effectiveness of the Once-daily 10 cm^2 Rivastigmine Patch Formulation in Patients With Probable Alzheimer's Disease (EXTRA) (NCT NCT00622713)
NCT ID: NCT00622713
Last Updated: 2011-07-26
Results Overview
The primary endpoint was the percentage of patients who were able to tolerate (and stay on for at least 8 weeks) rivastigmine target patch size 10 cm\^2.
COMPLETED
PHASE4
228 participants
24 weeks
2011-07-26
Participant Flow
Participant milestones
| Measure |
Rivastigmine Transdermal Patch
During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2.
|
|---|---|
|
Overall Study
STARTED
|
228
|
|
Overall Study
Exposed to Study Drug
|
226
|
|
Overall Study
Intent to Treat (ITT) Population
|
218
|
|
Overall Study
COMPLETED
|
169
|
|
Overall Study
NOT COMPLETED
|
59
|
Reasons for withdrawal
| Measure |
Rivastigmine Transdermal Patch
During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2.
|
|---|---|
|
Overall Study
Adverse Event
|
35
|
|
Overall Study
Administrative problems
|
4
|
|
Overall Study
Withdrawal by Subject
|
11
|
|
Overall Study
Lost to Follow-up
|
5
|
|
Overall Study
Death
|
2
|
|
Overall Study
Subject no longer required study drug
|
1
|
|
Overall Study
Did not meet eligibility criteria
|
1
|
Baseline Characteristics
A 24 Week, Multicenter, Open, Evaluation of the Clinical Effectiveness of the Once-daily 10 cm^2 Rivastigmine Patch Formulation in Patients With Probable Alzheimer's Disease (EXTRA)
Baseline characteristics by cohort
| Measure |
Rivastigmine Transdermal Patch
n=218 Participants
During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2.
|
|---|---|
|
Age Continuous
|
78.7 years
STANDARD_DEVIATION 6.59 • n=5 Participants
|
|
Sex: Female, Male
Female
|
131 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
87 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
218 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 weeksPopulation: 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 primary endpoint was the percentage of patients who were able to tolerate (and stay on for at least 8 weeks) rivastigmine target patch size 10 cm\^2.
Outcome measures
| Measure |
Rivastigmine Transdermal Patch
n=218 Participants
During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2.
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|---|---|
|
Percentage of Patients Who Achieved and Maintained the Maximum Dose of 10 cm^2 Rivastigmine Patch for at Least 8 Weeks During 24 Weeks Study
|
70.6 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: 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. Last observation carried forward (LOCF) was used for missing values.
The CGIC is an assessment tool used by a clinician to make a judgment of the severity or a change of a patient's condition. The clinician relies solely on information obtained from the patient at the Baseline visit as well as clinical information obtained throughout the study period. The CGIC is rated on the following seven-point scale:"very much improved", "much improved", "slightly improved", "unchanged", "slightly worsened", "much worsened" and "very much worsened".
Outcome measures
| Measure |
Rivastigmine Transdermal Patch
n=208 Participants
During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2.
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|---|---|
|
Clinical Global Impression of Change (CGI-C) by Physician
Very much improved
|
4.3 Percentage of participants
5.2
|
|
Clinical Global Impression of Change (CGI-C) by Physician
Much improved
|
13.0 Percentage of participants
|
|
Clinical Global Impression of Change (CGI-C) by Physician
Slightly improved
|
23.1 Percentage of participants
|
|
Clinical Global Impression of Change (CGI-C) by Physician
Unchanged
|
32.2 Percentage of participants
|
|
Clinical Global Impression of Change (CGI-C) by Physician
Slightly worsened
|
19.2 Percentage of participants
|
|
Clinical Global Impression of Change (CGI-C) by Physician
Much worsened
|
5.8 Percentage of participants
|
|
Clinical Global Impression of Change (CGI-C) by Physician
Very much worsened
|
2.4 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to week 24Population: 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 4-IADL assesses the ability of a patient to autonomously perform 4 activities of daily living: Use the telephone, take medications, use public transport, and manage their own budget. Each activity is assessed by a series of questions and rated on a scale of 1 to 4. Scores on the 4 activities are combined for a total score ranging from 1 to 16. A lower score indicates a more self-sufficient individual. A positive change from baseline score indicates worsening.
Outcome measures
| Measure |
Rivastigmine Transdermal Patch
n=218 Participants
During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2.
|
|---|---|
|
Mean Change From Baseline to Week 24 in the 4-item Instrumental Activities of Daily Living (4-IADL) Score
Baseline (n= 198)
|
3.2 scores on a scale
Standard Deviation 1.18
|
|
Mean Change From Baseline to Week 24 in the 4-item Instrumental Activities of Daily Living (4-IADL) Score
Week 24 (n= 181)
|
3.2 scores on a scale
Standard Deviation 1.16
|
|
Mean Change From Baseline to Week 24 in the 4-item Instrumental Activities of Daily Living (4-IADL) Score
Change from Baseline to week 24 (n= 172)
|
0.1 scores on a scale
Standard Deviation 0.74
|
SECONDARY outcome
Timeframe: Baseline to week 24Population: 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 MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and results in a total possible score from 0 to 30, with higher scores indicating better function. A positive change score indicates improvement from baseline.
Outcome measures
| Measure |
Rivastigmine Transdermal Patch
n=218 Participants
During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2.
|
|---|---|
|
Mean Change From Baseline to Week 24 in the Mini-Mental State Examination (MMSE) Score
Baseline (n = 216)
|
19.2 scores on a scale
Standard Deviation 4.11
|
|
Mean Change From Baseline to Week 24 in the Mini-Mental State Examination (MMSE) Score
Week 24 (n = 203)
|
19.2 scores on a scale
Standard Deviation 5.19
|
|
Mean Change From Baseline to Week 24 in the Mini-Mental State Examination (MMSE) Score
Change from baseline to week 24 (n = 203)
|
0.0 scores on a scale
Standard Deviation 3.18
|
SECONDARY outcome
Timeframe: Baseline to week 24Population: 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 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.
Outcome measures
| Measure |
Rivastigmine Transdermal Patch
n=218 Participants
During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2.
|
|---|---|
|
Mean Change From Baseline to Week 24 in the Mini-Zarit Inventory Score
Baseline (n= 211)
|
2.8 Scores on a scale
Standard Deviation 1.76
|
|
Mean Change From Baseline to Week 24 in the Mini-Zarit Inventory Score
Week 24 (n= 199)
|
2.9 Scores on a scale
Standard Deviation 1.85
|
|
Mean Change From Baseline to Week 24 in the Mini-Zarit Inventory Score
Change from baseline to week 24 (n= 197)
|
0.1 Scores on a scale
Standard Deviation 1.35
|
Adverse Events
Rivastigmine Transdermal Patch
Serious adverse events
| Measure |
Rivastigmine Transdermal Patch
n=218 participants at risk
During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2.
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|---|---|
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Blood and lymphatic system disorders
LYMPHADENOPATHY
|
0.46%
1/218
Safety population.
|
|
Cardiac disorders
ACUTE CORONARY SYNDROME
|
0.46%
1/218
Safety population.
|
|
Cardiac disorders
BRADYCARDIA
|
0.92%
2/218
Safety population.
|
|
Cardiac disorders
CARDIAC ARREST
|
0.46%
1/218
Safety population.
|
|
Gastrointestinal disorders
NAUSEA
|
0.46%
1/218
Safety population.
|
|
Gastrointestinal disorders
SIGMOIDITIS
|
0.46%
1/218
Safety population.
|
|
Gastrointestinal disorders
VOMITING
|
0.46%
1/218
Safety population.
|
|
General disorders
MALAISE
|
0.46%
1/218
Safety population.
|
|
General disorders
OEDEMA PERIPHERAL
|
0.46%
1/218
Safety population.
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.46%
1/218
Safety population.
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.46%
1/218
Safety population.
|
|
Hepatobiliary disorders
HEPATOMEGALY
|
0.46%
1/218
Safety population.
|
|
Immune system disorders
HYPERSENSITIVITY
|
0.46%
1/218
Safety population.
|
|
Infections and infestations
BRONCHITIS
|
0.46%
1/218
Safety population.
|
|
Infections and infestations
LUNG INFECTION
|
0.46%
1/218
Safety population.
|
|
Infections and infestations
VIRAL INFECTION
|
0.46%
1/218
Safety population.
|
|
Injury, poisoning and procedural complications
FALL
|
2.3%
5/218
Safety population.
|
|
Injury, poisoning and procedural complications
FEMORAL NECK FRACTURE
|
0.46%
1/218
Safety population.
|
|
Injury, poisoning and procedural complications
FOREARM FRACTURE
|
0.46%
1/218
Safety population.
|
|
Injury, poisoning and procedural complications
WRIST FRACTURE
|
0.46%
1/218
Safety population.
|
|
Investigations
BIOPSY PROSTATE
|
0.46%
1/218
Safety population.
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
0.46%
1/218
Safety population.
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
0.46%
1/218
Safety population.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTATIC NEOPLASM
|
0.46%
1/218
Safety population.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATIC ADENOMA
|
0.46%
1/218
Safety population.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA
|
0.46%
1/218
Safety population.
|
|
Nervous system disorders
AUTONOMIC NERVOUS SYSTEM IMBALANCE
|
0.46%
1/218
Safety population.
|
|
Nervous system disorders
DYSSTASIA
|
0.46%
1/218
Safety population.
|
|
Nervous system disorders
EPILEPSY
|
0.46%
1/218
Safety population.
|
|
Psychiatric disorders
APATHY
|
0.46%
1/218
Safety population.
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA EXERTIONAL
|
0.46%
1/218
Safety population.
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.46%
1/218
Safety population.
|
|
Skin and subcutaneous tissue disorders
DERMATITIS ALLERGIC
|
0.46%
1/218
Safety population.
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
0.46%
1/218
Safety population.
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.46%
1/218
Safety population.
|
|
Social circumstances
SOCIAL STAY HOSPITALISATION
|
0.46%
1/218
Safety population.
|
|
Surgical and medical procedures
HIP ARTHROPLASTY
|
0.46%
1/218
Safety population.
|
|
Surgical and medical procedures
MALIGNANT TUMOUR EXCISION
|
0.46%
1/218
Safety population.
|
Other adverse events
| Measure |
Rivastigmine Transdermal Patch
n=218 participants at risk
During the first 4 weeks of the study, patients applied a new rivastigmine 5 cm\^2 patch once daily. At the end of the 4 weeks, if tolerability was satisfactory, the dosage was increased and patients applied rivastigmine 10 cm\^2 patch once daily for an additional 4 weeks. Thereafter, and until the end of the study, patients remained at the maximum tolerated dose, either 5 or 10 cm\^2.
|
|---|---|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
6.0%
13/218
Safety population.
|
Additional Information
Study Director
Novartis Pharmaceuticals
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