Efficacy and Safety of Rivastigmine Transdermal Patch in Patients With Mild to Moderate Alzheimer's Disease

This study has been completed.
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00423085
First received: January 11, 2007
Last updated: January 14, 2014
Last verified: January 2014
Results First Received: April 27, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Alzheimer's Disease
Interventions: Drug: Rivastigmine transdermal patch
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants 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. Following the 24-week double-blind treatment phase, participants could enroll in the open-label extension phase, where all participants were titrated up to the 10 cm^2 patch dose.

Reporting Groups
  Description
Placebo Participants received daily matching placebo patch for the duration of the 24-week double-blind treatment phase of the study.
Rivastigmine 5 cm^2 During the 16-week titration period patients received daily rivastigmine 2.5 cm^2 patch for the first 4 weeks and then 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.
Rivastigmine 10 cm^2 During the 16-week titration period patients received daily rivastigmine 2.5 cm^2 patch for the first 4 weeks, rivastigmine 5 cm^2 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.
Open-label Extension All participants started treatment with daily rivastigmine 2.5 cm^2 patch. The dose was increased to 5, 7.5, and 10 cm^2 after 4 weeks of treatment at each dose level. One patch was applied once daily. The dose level reached by each individual patient at the end of this 16 weeks was maintained for the rest of the study duration (Maintenance Period). A predetermined "allowed adjustment" scheme was followed in patients who required dose adjustment due to low tolerability.

Participant Flow for 2 periods

Period 1:   24-Week Double-Blind Treatment Phase
    Placebo     Rivastigmine 5 cm^2     Rivastigmine 10 cm^2     Open-label Extension  
STARTED     288     284     287     0  
COMPLETED     242     220     228     0  
NOT COMPLETED     46     64     59     0  
Adverse Event                 21                 38                 34                 0  
Withdrawal by Subject                 8                 16                 11                 0  
Unsatisfactory therapeutic effect                 7                 6                 7                 0  
Protocol Violation                 8                 3                 7                 0  
Death                 1                 1                 0                 0  
Lost to Follow-up                 1                 0                 0                 0  

Period 2:   52-Week Open-Label Extension Phase
    Placebo     Rivastigmine 5 cm^2     Rivastigmine 10 cm^2     Open-label Extension  
STARTED     0     0     0     637 [1]
COMPLETED     0     0     0     474  
NOT COMPLETED     0     0     0     163  
Adverse Event                 0                 0                 0                 97  
Withdrawal by Subject                 0                 0                 0                 37  
Unsatisfactory therapeutic effect                 0                 0                 0                 18  
Protocol deviation                 0                 0                 0                 9  
Death                 0                 0                 0                 2  
[1] Patients who completed the 24-wk treatment phase were eligible to enroll in the open-label extension



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Participants received daily matching placebo patch for the duration of the 24-week double-blind treatment phase of the study.
Rivastigmine 5 cm^2 During the 16-week titration period patients received daily rivastigmine 2.5 cm^2 patch for the first 4 weeks and then 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.
Rivastigmine 10 cm^2 During the 16-week titration period patients received daily rivastigmine 2.5 cm^2 patch for the first 4 weeks, rivastigmine 5 cm^2 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.
Total Total of all reporting groups

Baseline Measures
    Placebo     Rivastigmine 5 cm^2     Rivastigmine 10 cm^2     Total  
Number of Participants  
[units: participants]
  286     282     287     855  
Age [1]
[units: years]
Mean ± Standard Deviation
  74.5  ± 7.36     74.3  ± 7.46     75.1  ± 6.85     74.6  ± 7.22  
Gender  
[units: participants]
       
Female     195     194     195     584  
Male     91     88     92     271  
[1] Demographic data for the double-blind treatment phase is provided for the safety population. This population consists of all randomized patients who received at least one dose of study medication and had at least one safety assessment after baseline.



  Outcome Measures
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1.  Primary:   Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)   [ Time Frame: Baseline and Week 24 ]

2.  Primary:   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)   [ Time Frame: Baseline and Week 24 ]

3.  Secondary:   Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)   [ Time Frame: Baseline and Week 24 ]

4.  Secondary:   Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)   [ Time Frame: Baseline and Week 24 ]

5.  Secondary:   Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS)   [ Time Frame: Baseline and Week 24 ]

6.  Secondary:   Change From Baseline in Mini-Mental State Examination (MMSE)   [ Time Frame: Baseline and Week 24 ]

7.  Secondary:   Extension Phase: Change From Extension Phase Baseline to End of Extension in Mini-Mental State Examination (MMSE)   [ Time Frame: Extension Phase Baseline and Week 52 of extension phase ]

8.  Secondary:   Extension Phase: Change From Extension Phase Baseline to End of Extension in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)   [ Time Frame: Extension Phase Baseline and Week 52 of extension phase ]

9.  Secondary:   Extension Phase: Change From Extension Phase Baseline to End of Extension in Modified Crichton Scale   [ Time Frame: Extension Phase Baseline and Week 52 of extension phase ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided


Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00423085     History of Changes
Obsolete Identifiers: NCT00531609
Other Study ID Numbers: CENA713D1301, CENA713D1301E1
Study First Received: January 11, 2007
Results First Received: April 27, 2011
Last Updated: January 14, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare