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
  Purpose

The purpose of this study was to investigate the 5cm^2 and 10cm^2 doses of rivastigmine transdermal patch in terms of efficacy and safety in patients with probable Alzheimer's Disease (MMSE [Mini Mental State Examination] 10-20). A 52-week extension phase evaluated the safety and tolerability of long-term treatment by rivastigmine transdermal patch in patients with probable Alzheimer's Disease (AD).


Condition Intervention Phase
Alzheimer's Disease
Drug: Rivastigmine transdermal patch
Drug: Placebo
Phase 3

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
Official Title: A 24-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-finding Evaluation of the Efficacy, Safety, and Tolerability of the Once-daily Rivastigmine Transdermal Patch in Patients With Probable Alzheimer's Disease (MMSE 10-20)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The Alzheimer's Disease Assessment Scale - Japan cognitive subscale (ADAS-J cog) was used to measure change in cognitive function. The ADAS-J cog score ranges from 0-70, with higher total scores indicating more impairment. A negative change score indicates improvement from baseline.

  • 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 ] [ Designated as safety issue: No ]

    The overall clinical rating of change from baseline to week 24 measured by the 7-point CIBIC plus-J scale. The Clinician's Interview-Based Impression of Change plus Caregiver Input consists of 3 subscales: Disability Assessment of Dementia Scale, Behavioral Pathology in Alzheimer's Disease Rating Scale and Mental Function Impairment Scale, as well as the Clinician's Global Impression of Change (CGIC). Participants are scored according to the following:

    1. Markedly improved
    2. Moderately improved
    3. Minimally improved
    4. Unchanged
    5. Minimally worse
    6. Moderately worse
    7. Markedly worse


Secondary Outcome Measures:
  • Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The Disability Assessment for Dementia (DAD) was used to assess levels of difficulty in activities of daily living (ADL). The DAD is administered through an interview with the caregiver. A total score is obtained by adding the rating for each question and converting this to a total score out of 100 (%). Higher scores represent less disability in ADL while lower scores indicate more dysfunction. A positive change score indicates an improvement from baseline.

  • Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    BEHAVE-AD was used to assess patient behavior and psychiatric symptoms. It covers symptoms in seven categories: paranoid and delusional ideation, hallucinations, activity disturbances, diurnal rhythm disturbances, aggressiveness, affective disorders and anxieties, and phobias. Caregivers rate behavioral symptoms on a 0-3 scale. The total score can range from 0 to 66, with a lower score indicating better function. A negative change score indicates an improvement from baseline.

  • Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    MENFIS was used to assess patient cognitive and psychiatric function, and evaluates core symptoms of dementia including cognitive, motivational and emotional aspects. The total score ranges from 0 to 78. The higher the score, the greater the functional deficit. A negative change score indicates an improvement from baseline.

  • Change From Baseline in Mini-Mental State Examination (MMSE) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The MMSE is a 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 from baseline.

  • 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 ] [ Designated as safety issue: No ]
    The MMSE is a 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. This outcome measured the change in MMSE from the beginning of the open-label extension phase through to Week 52 of the extension phase.

  • 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 ] [ Designated as safety issue: No ]
    The Disability Assessment for Dementia (DAD) was used to assess levels of difficulty in activities of daily living. The DAD is administered through an interview with the caregiver. A total score is obtained by adding the rating for each question and converting this to a total score out of 100 (%). Higher scores represent less disability in activities of daily living while lower scores indicate more dysfunction. A positive change score indicates an improvement from baseline.

  • 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 ] [ Designated as safety issue: No ]
    The Modified Crichton Scale includes a total of seven items evaluated in eight grades that assess basic activities of daily living, communication functions, psychiatric symptoms and quality of life; the total score can range from 0 to 56, with a lower score indicating better function. A negative change score indicates an improvement from baseline.


Enrollment: 859
Study Start Date: January 2007
Study Completion Date: April 2010
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Participants received daily matching placebo patch for the duration of the 24-week double-blind treatment phase of the study.
Drug: Placebo
Placebo transdermal patch was provided in the following sizes: 2.5 cm^2, 5 cm^2, 7.5 cm^2 and 10 cm^2. The caregiver applied one patch on the back of a patient, placed alternately from the right to the left side at approximately the same time each day.
Experimental: 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 thereafter 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.
Drug: Rivastigmine transdermal patch

Rivastigmine transdermal patch was provided in the following sizes and doses:

2.5 cm^2 (4.5 mg), 5 cm^2 (9 mg), 7.5 cm^2 (13.5 mg), and 10 cm^2 (18 mg). The caregiver applied one patch on the back of a patient, placed alternately from the right to the left side at approximately the same time each day.

Experimental: 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 patch 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.
Drug: Rivastigmine transdermal patch

Rivastigmine transdermal patch was provided in the following sizes and doses:

2.5 cm^2 (4.5 mg), 5 cm^2 (9 mg), 7.5 cm^2 (13.5 mg), and 10 cm^2 (18 mg). The caregiver applied one patch on the back of a patient, placed alternately from the right to the left side at approximately the same time each day.


Detailed Description:

Patients 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. During the Double-blind treatment phase, patients entered a 16-week Titration Period followed by an 8-week Maintenance Period. During the open-label extension phase, all patients started treatment with a 2.5 cm^2 patch and the dose was increased to 10 cm^2 over a 16-week titration period, followed by a maintenance period of 36 weeks.

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A diagnosis of dementia of the Alzheimer's type according to the DSM-IV criteria
  • A clinical diagnosis of probable AD according to NINCDS/ADRDA criteria
  • An MMSE score of > or = 10 and < or = 20

Exclusion Criteria:

  • A current DSM-IV diagnosis of major depression
  • Taken rivastigmine in the past
  • A score of > 5 on the Modified Hachinski Ischemic Scale (MHIS) Other protocol-defined inclusion/exclusion criteria may apply

Other protocol-defined inclusion/exclusion criteria may apply

Extension Phase Eligibility Criteria

Inclusion Criteria:

  • Patients who have completed the Double-blind Treatment Phase on study medication

Exclusion Criteria

  • Patients who have any important protocol deviations until the completion of the Double-blind Treatment Phase
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00423085

Locations
Japan
Novartis Investigative Site
Hokkaido region, Hokkaido, Japan
Sponsors and Collaborators
Novartis Pharmaceuticals
Ono Pharmaceutical Co. Ltd
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

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

Keywords provided by Novartis:
rivastigmine,Alzheimer's Disease, transdermal patch

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Rivastigmine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014