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

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)”

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).

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.

Intervention(s) in this Clinical Trial

• 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.
• 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.

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: Placebo
  • Participants received daily matching placebo patch for the duration of the 24-week double-blind treatment phase of the study.
• 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.
• 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.

Primary Measures

• Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)
  • Time Frame: Baseline and Week 24
    Safety Issue?: No
• 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
    Safety Issue?: No

Secondary Measures

• Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD)
  • Time Frame: Baseline and Week 24
    Safety Issue?: No
• Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)
  • Time Frame: Baseline and Week 24
    Safety Issue?: No
• Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS)
  • Time Frame: Baseline and Week 24
    Safety Issue?: No
• Change From Baseline in Mini-Mental State Examination (MMSE)
  • Time Frame: Baseline and Week 24
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novartis Pharmaceuticals Industry

Overall Clinical Trial Officials and Contacts

Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00423085

Study ID Number: CENA713D1301

ClinicalTrials.gov Identifier: NCT00423085

Health Authority: Japan: Ministry of Health, Labor and Welfare