A 48-Week, Multicenter, Randomized, Double-Blind, Parallel-Group Evaluation of the Comparative Efficacy, Safety, and Tolerability of Exelon® 10 and 15 cm^2 Patch in Patients With Mild to Moderate Alzheimer's Disease (AD) Showing Functional and Cognitive Decline
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 1,584
- Locations
- 2
- Primary Endpoint
- Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) Subscale at Week 48 of Double Blind Period
Study Overview
Brief Summary
The purpose of this study was to support the optimal use of rivastigmine patch in long-term treatment of Alzheimer's Disease in patients demonstrating functional and cognitive decline at the target maintenance dose of rivastigmine patch 10 cm^2.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 50 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female patients between 50 and 85 years of age with a diagnosis of probable Alzheimers Disease,
- •Baseline Mini-Mental State Examination (MMSE) score 10-24 inclusive,
- •A primary caregiver willing to accept responsibility for supervising treatment, assessing the patient's condition throughout the study, and for providing input into efficacy assessments.
- •For double blind only: Meet the decline criteria of functional (as assessed by the investigator) and cognitive (assessed by a 1 point reduction in Mini-Mental State Examination) score between visits or a 3 point reduction from baseline) decline at weeks 23, 36 or 48.
Exclusion Criteria
- •Presence of an advanced, severe, progressive, or unstable disease of any type that could interfere with efficacy and safety assessments or put the patient at particular risk,
- •Any medical or neurological condition other than Alzheimers Disease that could explain the patient's dementia,
- •A diagnosis of probable or possible vascular dementia,
- •A current diagnosis of unsuccessfully-treated depression, or any other mental disorder that may interfere with the evaluation of the patient's response to study medication,
- •A history or current diagnosis of cerebrovascular disease (e.g. stroke),
- •A current diagnosis of severe or unstable cardiovascular disease (e.g. unstable coronary artery disease).
- •Other protocol-defined inclusion/exclusion criteria may apply.
Arms & Interventions
Double blind: Rivastigmine (10 cm^2)
Rivastigmine transdermal patch 10 cm^2 and placebo to rivastigmine 15 cm^2 once daily for 48 weeks during the double blind period.
Intervention: Placebo to 15 cm^2 patch (Drug)
Open label: Rivastigmine (5 cm^2 / 10 cm^2)
Rivastigmine 5 cm^2 transdermal patch once a day during the first 4 weeks of open label treatment followed by rivastigmine 10 cm^2 transdermal patch once a day from week 4 to week 24, 36 or 48.
Intervention: Rivastigmine 5 cm^2 (Drug)
Open label: Rivastigmine (5 cm^2 / 10 cm^2)
Rivastigmine 5 cm^2 transdermal patch once a day during the first 4 weeks of open label treatment followed by rivastigmine 10 cm^2 transdermal patch once a day from week 4 to week 24, 36 or 48.
Intervention: Rivastigmine 10 cm^2 (Drug)
Double blind: Rivastigmine (10 cm^2)
Rivastigmine transdermal patch 10 cm^2 and placebo to rivastigmine 15 cm^2 once daily for 48 weeks during the double blind period.
Intervention: Rivastigmine 10 cm^2 (Drug)
Double blind: Rivastigmine (15 cm^2)
Rivastigmine transdermal patch 15 cm^2 and placebo to rivastigmine 10 cm^2 once daily for 48 weeks during double blind period.
Intervention: Rivastigmine 15 cm^2 (Drug)
Double blind: Rivastigmine (15 cm^2)
Rivastigmine transdermal patch 15 cm^2 and placebo to rivastigmine 10 cm^2 once daily for 48 weeks during double blind period.
Intervention: Placebo to 10 cm^2 patch (Drug)
Extended open label Rivastigmine (10 cm^2)
Rivastigmine 10 cm^2 transdermal patch once a day during 48 weeks open label treatment running in parallel to the double blind period.
Intervention: Rivastigmine 10 cm^2 (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) Subscale at Week 48 of Double Blind Period
Time Frame: Baseline and week 48 of double blind period
The Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog) subscale comprises 11 items summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. A negative change indicates an improvement from baseline.
Change in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) Subscale Score From Baseline to Week 48 of Double Blind Period
Time Frame: Baseline and week 48 of double blind period
The Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) is a 16 item subscale of the caregiver-based ADCS-IADL scale, developed for the use in dementia studies. The ADCS-IADL total score ranges from 0 to 56, with higher scores indicating less severe impairment. A positive change indicates an improvement from baseline.
Secondary Outcomes
- Time to Functional Decline as Measured by Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) Subscale During the Double Blind Period(390 days was the maximum)
- Change in Attention and Executive Function as Assessed by the Trail Making Test (Part A) at Week 48 of the Double Blind Period(Baseline and week 48 of double blind period)
- Change in Attention and Executive Function as Assessed by the Trail Making Test (Part B) at Week 48 of Double Blind Period(Baseline and week 48 of double blind period)
- Change From Baseline in Neuropsychiatric Inventory (NPI)-10 Score at Week 48 of Double Blind Period(Baseline and week 48 of double blind period)
- Number of Patients With Adverse Events, Serious Adverse Events and Discontinuations Due to Adverse Events(30 days after a maximum of 96 weeks treatment)