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Trial record 12 of 19 for:    ADL | BUTYRYLCHOLINESTERASE

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) (EXTRA)

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ClinicalTrials.gov Identifier: NCT00622713
Recruitment Status : Completed
First Posted : February 25, 2008
Results First Posted : July 26, 2011
Last Update Posted : July 26, 2011
Sponsor:
Information provided by:
Novartis

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Intervention Drug: Rivastigmine transdermal patch
Enrollment 228

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rivastigmine Transdermal Patch
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 228
Exposed to Study Drug 226
Intent to Treat (ITT) Population 218
Completed 169
Not Completed 59
Reason Not Completed
Adverse Event             35
Administrative problems             4
Withdrawal by Subject             11
Lost to Follow-up             5
Death             2
Subject no longer required study drug             1
Did not meet eligibility criteria             1
Arm/Group Title Rivastigmine Transdermal Patch
Hide Arm/Group Description 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 Number of Baseline Participants 218
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 218 participants
78.7  (6.59)
[1]
Measure Description: Baseline Measures are provided for the ITT population.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 218 participants
Female
131
  60.1%
Male
87
  39.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
France Number Analyzed 218 participants
218
1.Primary Outcome
Title 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
Hide Description 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.
Time Frame 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide 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 Transdermal Patch
Hide Arm/Group Description:
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 Number of Participants Analyzed 218
Measure Type: Number
Unit of Measure: Percentage of participants
70.6
2.Secondary Outcome
Title Clinical Global Impression of Change (CGI-C) by Physician
Hide Description 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".
Time Frame Baseline and week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide 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. Last observation carried forward (LOCF) was used for missing values.
Arm/Group Title Rivastigmine Transdermal Patch
Hide Arm/Group Description:
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 Number of Participants Analyzed 208
Measure Type: Number
Unit of Measure: Percentage of participants
Very much improved 4.3
Much improved 13.0
Slightly improved 23.1
Unchanged 32.2
Slightly worsened 19.2
Much worsened 5.8
Very much worsened 2.4
3.Secondary Outcome
Title Mean Change From Baseline to Week 24 in the 4-item Instrumental Activities of Daily Living (4-IADL) Score
Hide Description 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.
Time Frame Baseline to week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide 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 Transdermal Patch
Hide Arm/Group Description:
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 Number of Participants Analyzed 218
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline (n= 198) 3.2  (1.18)
Week 24 (n= 181) 3.2  (1.16)
Change from Baseline to week 24 (n= 172) 0.1  (0.74)
4.Secondary Outcome
Title Mean Change From Baseline to Week 24 in the Mini-Mental State Examination (MMSE) Score
Hide 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) 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.
Time Frame Baseline to week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide 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 Transdermal Patch
Hide Arm/Group Description:
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 Number of Participants Analyzed 218
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline (n = 216) 19.2  (4.11)
Week 24 (n = 203) 19.2  (5.19)
Change from baseline to week 24 (n = 203) 0.0  (3.18)
5.Secondary Outcome
Title Mean Change From Baseline to Week 24 in the Mini-Zarit Inventory Score
Hide 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.
Time Frame Baseline to week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide 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 Transdermal Patch
Hide Arm/Group Description:
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 Number of Participants Analyzed 218
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline (n= 211) 2.8  (1.76)
Week 24 (n= 199) 2.9  (1.85)
Change from baseline to week 24 (n= 197) 0.1  (1.35)
Time Frame [Not Specified]
Adverse Event Reporting Description Safety population.
 
Arm/Group Title Rivastigmine Transdermal Patch
Hide Arm/Group Description 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.
All-Cause Mortality
Rivastigmine Transdermal Patch
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Rivastigmine Transdermal Patch
Affected / at Risk (%)
Total   21/218 (9.63%) 
Blood and lymphatic system disorders   
LYMPHADENOPATHY  1  1/218 (0.46%) 
Cardiac disorders   
ACUTE CORONARY SYNDROME  1  1/218 (0.46%) 
BRADYCARDIA  1  2/218 (0.92%) 
CARDIAC ARREST  1  1/218 (0.46%) 
Gastrointestinal disorders   
NAUSEA  1  1/218 (0.46%) 
SIGMOIDITIS  1  1/218 (0.46%) 
VOMITING  1  1/218 (0.46%) 
General disorders   
MALAISE  1  1/218 (0.46%) 
OEDEMA PERIPHERAL  1  1/218 (0.46%) 
Hepatobiliary disorders   
CHOLECYSTITIS  1  1/218 (0.46%) 
CHOLELITHIASIS  1  1/218 (0.46%) 
HEPATOMEGALY  1  1/218 (0.46%) 
Immune system disorders   
HYPERSENSITIVITY  1  1/218 (0.46%) 
Infections and infestations   
BRONCHITIS  1  1/218 (0.46%) 
LUNG INFECTION  1  1/218 (0.46%) 
VIRAL INFECTION  1  1/218 (0.46%) 
Injury, poisoning and procedural complications   
FALL  1  5/218 (2.29%) 
FEMORAL NECK FRACTURE  1  1/218 (0.46%) 
FOREARM FRACTURE  1  1/218 (0.46%) 
WRIST FRACTURE  1  1/218 (0.46%) 
Investigations   
BIOPSY PROSTATE  1  1/218 (0.46%) 
Metabolism and nutrition disorders   
DIABETES MELLITUS  1  1/218 (0.46%) 
Musculoskeletal and connective tissue disorders   
MUSCULOSKELETAL CHEST PAIN  1  1/218 (0.46%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
METASTATIC NEOPLASM  1  1/218 (0.46%) 
PROSTATIC ADENOMA  1  1/218 (0.46%) 
SQUAMOUS CELL CARCINOMA  1  1/218 (0.46%) 
Nervous system disorders   
AUTONOMIC NERVOUS SYSTEM IMBALANCE  1  1/218 (0.46%) 
DYSSTASIA  1  1/218 (0.46%) 
EPILEPSY  1  1/218 (0.46%) 
Psychiatric disorders   
APATHY  1  1/218 (0.46%) 
Respiratory, thoracic and mediastinal disorders   
DYSPNOEA EXERTIONAL  1  1/218 (0.46%) 
PULMONARY EMBOLISM  1  1/218 (0.46%) 
Skin and subcutaneous tissue disorders   
DERMATITIS ALLERGIC  1  1/218 (0.46%) 
PRURITUS  1  1/218 (0.46%) 
RASH  1  1/218 (0.46%) 
Social circumstances   
SOCIAL STAY HOSPITALISATION  1  1/218 (0.46%) 
Surgical and medical procedures   
HIP ARTHROPLASTY  1  1/218 (0.46%) 
MALIGNANT TUMOUR EXCISION  1  1/218 (0.46%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rivastigmine Transdermal Patch
Affected / at Risk (%)
Total   13/218 (5.96%) 
Skin and subcutaneous tissue disorders   
ERYTHEMA  1  13/218 (5.96%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00622713     History of Changes
Other Study ID Numbers: CENA713DFR08
N° EudraCT : 2007-003405-27
First Submitted: February 14, 2008
First Posted: February 25, 2008
Results First Submitted: December 10, 2010
Results First Posted: July 26, 2011
Last Update Posted: July 26, 2011