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

Phase 3

Completed

Conditions: Alzheimer's Disease

Interventions: Drug: Placebo
Drug: Rivastigmine transdermal patch

Registration Number: NCT00423085

Lead Sponsor: Novartis Pharmaceuticals

Brief 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).

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 859

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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	Rivastigmine transdermal patch	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.
Rivastigmine 10 cm^2	Rivastigmine transdermal patch	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)	Baseline and Week 24	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)	Baseline and Week 24	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

Name	Time	Method
Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS)	Baseline and Week 24	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)	Baseline and Week 24	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.
Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)	Baseline and Week 24	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)	Baseline and Week 24	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.
Extension Phase: Change From Extension Phase Baseline to End of Extension in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)	Extension Phase Baseline and Week 52 of extension phase	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 Mini-Mental State Examination (MMSE)	Extension Phase Baseline and Week 52 of extension phase	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 Modified Crichton Scale	Extension Phase Baseline and Week 52 of extension phase	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.