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

Alzheimer's Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00423085
• Other study ID #: CENA713D1301
• Secondary ID: CENA713D1301E1
• Status: Completed
• Phase: Phase 3
• First received: January 11, 2007
• Last updated: January 14, 2014
• Start date: January 2007
• Est. completion date: April 2010

Study information

• Verified date: January 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

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).

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.

Other known NCT identifiers

• NCT00531609

Recruitment information / eligibility

• Status: Completed
• Enrollment: 859
• Est. completion date: April 2010
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

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.
• 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.

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Hokkaido region	Hokkaido

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Ono Pharmaceutical Co. Ltd

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)	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.	Baseline and Week 24	No
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)	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: Markedly improved; Moderately improved; Minimally improved; Unchanged; Minimally worse; Moderately worse; Markedly worse	Baseline and Week 24	No
Secondary	Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)	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.	Baseline and Week 24	No
Secondary	Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)	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.	Baseline and Week 24	No
Secondary	Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS)	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.	Baseline and Week 24	No
Secondary	Change From Baseline in Mini-Mental State Examination (MMSE)	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.	Baseline and Week 24	No
Secondary	Extension Phase: Change From Extension Phase Baseline to End of Extension in Mini-Mental State Examination (MMSE)	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 Baseline and Week 52 of extension phase	No
Secondary	Extension Phase: Change From Extension Phase Baseline to End of Extension in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)	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 Baseline and Week 52 of extension phase	No
Secondary	Extension Phase: Change From Extension Phase Baseline to End of Extension in Modified Crichton Scale	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.	Extension Phase Baseline and Week 52 of extension phase	No