Comparative Efficacy, Safety, and Tolerability of Rivastigmine 10 and 15 cm^2 Patch in Patients With Alzheimer's Disease (AD) Showing Cognitive Decline

Alzheimer Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00506415
• Other study ID #: CENA713D2340
• Status: Completed
• Phase: Phase 3
• First received: July 20, 2007
• Last updated: September 17, 2012
• Start date: June 2007
• Est. completion date: May 2011

Study information

• Verified date: September 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyGermany: Federal Institute for Drugs and Medical DevicesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: Agenzia Italiana del Farmaco (AIFA)Spain: Agencia Española del Medicamento y Productos Sanitarios (AEMPS)Canada: Therapeutic Products Directorate (TPD)Switzerland: SwissmedicUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1584
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 85 Years

Eligibility

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.

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

Intervention

Drug:
• Rivastigmine 5 cm^2
5 cm^2 transdermal patch
• Rivastigmine 10 cm^2
10 cm^2 transdermal patch.
• Rivastigmine 15 cm^2
15 cm^2 transdermal patch.
• Placebo to 15 cm^2 patch
Placebo of rivastigmine transdermal patch 15 cm^2.
• Placebo to 10 cm^2 patch
Placebo of rivastigmine transdermal patch 10 cm^2.

Locations

Country	Name	City	State
Canada	Novartis investigative site	Calgary
Canada	Novartis investigative site	Edmonton
Canada	Novartis investigative site	Greenfield Park
Canada	Novartis investigative site	Halifax
Canada	Novartis investigative site	London
Canada	Novartis investigative site	Montreal
Canada	Novartis investigative site	Ottawa
Canada	Novartis investigative site	Peterborough
Canada	Novartis investigative site	Quebec
Canada	Novartis investigative site	Regina
Canada	Novartis investigative site	Toronto
Canada	Novartis investigative site	Toronto	Ontario
Canada	Novartis investigative site	Vancouver
Canada	Novartis investigative site	Winnipeg
France	Novartis investigative site	Bordeaux
France	Novartis investigative site	Bourg en Bresse
France	Novartis investigative site	Caen
France	Novartis investigative site	Cherbourg
France	Novartis investigative site	Dijon
France	Novartis investigative site	Dijon	Burgundy
France	Novartis investigative site	Fains Veel	Alsace Lorraine
France	Novartis investigative site	Limoges
France	Novartis investigative site	Montpellier
France	Novartis investigative site	Nice
France	Novartis investigative site	Paris
France	Novartis investigative site	Reims	Champagne-Ardenne
France	Novartis investigative site	Rennes
France	Novartis investigative site	Rodez
Germany	Novartis investigative site	Bad Neustadt/Saale
Germany	Novartis investigative site	Berlin
Germany	Novartis investigative site	Bonn
Germany	Novartis investigative site	Burg
Germany	Novartis investigative site	Duesseldorf
Germany	Novartis investigative site	Frankfurt
Germany	Novartis investigative site	Giessen
Germany	Novartis investigative site	Koln
Germany	Novartis investigative site	Krefeld
Germany	Novartis investigative site	Leipzig
Germany	Novartis investigative site	Magdeburg
Germany	Novartis investigative site	Mannheim
Germany	Novartis investigative site	Marburg
Germany	Novartis investigative site	Muenchen
Germany	Novartis investigative site	Muenster
Germany	Novartis investigative site	Nuernberg
Germany	Novartis investigative site	Stralsund
Germany	Novartis investigative site	Stuttgart
Germany	Novartis investigative site	Wurzburg
Italy	Novartis investigative site	Ancona
Italy	Novartis investigative site	Arcugnano
Italy	Novartis investigative site	Arezzo
Italy	Novartis investigative site	Bari
Italy	Novartis investigative site	Bologna
Italy	Novartis investigative site	Brescia
Italy	Novartis investigative site	Cagliari
Italy	Novartis investigative site	Catania
Italy	Novartis investigative site	Città di Castello
Italy	Novartis investigative site	Cremona
Italy	Novartis investigative site	Ferrara
Italy	Novartis investigative site	Firenze
Italy	Novartis investigative site	Foggia
Italy	Novartis investigative site	Genova
Italy	Novartis investigative site	La Spezia
Italy	Novartis investigative site	Milan
Italy	Novartis investigative site	Milano
Italy	Novartis investigative site	Milano	Milan
Italy	Novartis investigative site	Modena
Italy	Novartis investigative site	Napoli
Italy	Novartis investigative site	Padova
Italy	Novartis investigative site	Pavia
Italy	Novartis investigative site	Perugia
Italy	Novartis investigative site	Pisa
Italy	Novartis investigative site	Rho
Italy	Novartis investigative site	Rome
Italy	Novartis investigative site	Torino
Italy	Novartis investigative site	Verona
Spain	Novartis investigative site	Barcelona
Spain	Novartis investigative site	Palma de Mallorca
Switzerland	Novartis investigative site	Basel
Switzerland	Novartis investigative site	Biel
Switzerland	Novartis investigative site	Mendrisio
United States	Novartis investigative site	Albany	New York
United States	Novartis investigative site	Anaheim	California
United States	Novartis investigative site	Atlanta	Georgia
United States	Novartis investigative site	Beaufort	South Carolina
United States	Novartis investigative site	Beaver	Pennsylvania
United States	Novartis investigative site	Birmingham	Alabama
United States	Novartis investigative site	Boca Raton	Florida
United States	Novartis investigative site	Bradenton	Florida
United States	Novartis investigative site	Brentwood	Tennessee
United States	Novartis investigative site	Canton	Ohio
United States	Novartis investigative site	Carson	California
United States	Novartis investigative site	Charleston	West Virginia
United States	Novartis investigative site	Chicago	Illinois
United States	Novartis investigative site	Columbia	Missouri
United States	Novartis investigative site	Columbus	Ohio
United States	Novartis investigative site	Corvallis	Oregon
United States	Novartis investigative site	Costa Mesa	California
United States	Novartis investigative site	Dallas	Texas
United States	Novartis investigative site	Deerfield Beach	Florida
United States	Novartis investigative site	Delray Beach	Florida
United States	Novartis investigative site	Erie	Pennsylvania
United States	Novartis investigative site	Flemington	New Jersey
United States	Novartis investigative site	Flint	Michigan
United States	Novartis investigative site	Flushing	Michigan
United States	Novartis investigative site	Fort Collins	Colorado
United States	Novartis investigative site	Fort Lauderdale	Florida
United States	Novartis investigative site	Fort Worth	Texas
United States	Novartis investigative site	Fullerton	California
United States	Novartis investigative site	Gainesville	Florida
United States	Novartis investigative site	Gilbert	Arizona
United States	Novartis investigative site	Greensboro	North Carolina
United States	Novartis investigative site	Greensburg	Pennsylvania
United States	Novartis investigative site	Hattiesburg	Mississippi
United States	Novartis Investigative Site	Honolulu	Hawaii
United States	Novartis investigative site	Huntington	West Virginia
United States	Novartis investigative site	Irving	Texas
United States	Novartis investigative site	La Habra	California
United States	Novartis investigative site	La Jolla	California
United States	Novartis investigative site	Longmont	Colorado
United States	Novartis investigative site	Macon	Georgia
United States	Novartis investigative site	Miami Beach	Florida
United States	Novartis investigative site	Morganton	North Carolina
United States	Novartis investigative site	Nashville	Tennessee
United States	Novartis investigative site	National City	California
United States	Novartis investigative site	Nutley	New Jersey
United States	Novartis investigative site	Ocean Springs	Mississippi
United States	Novartis investigative site	Phoenix	Arizona
United States	Novartis investigative site	Pittsburgh	Pennsylvania
United States	Novartis investigative site	Pompano Beach	Florida
United States	Novartis investigative site	Port Charlotte	Florida
United States	Novartis investigative site	Portland	Oregon
United States	Novartis investigative site	Redlands	California
United States	Novartis investigative site	Roseville	Michigan
United States	Novartis investigative site	San Francisco	California
United States	Novartis investigative site	Somerset	New Jersey
United States	Novartis investigative site	Springfield	Massachusetts
United States	Novartis investigative site	St. Louis	Missouri
United States	Novartis investigative site	Summerville	South Carolina
United States	Novartis investigative site	Sun City	Arizona
United States	Novartis investigative site	Sunrise	Florida
United States	Novartis investigative site	Syracuse	New York
United States	Novartis investigative site	Traverse City	Michigan
United States	Novartis investigative site	West Palm Beach	Florida
United States	Novartis investigative site	Winston-Salem	North Carolina
United States	Novartis investigative site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) Subscale at 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.	Baseline and week 48 of double blind period	No
Primary	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	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.	Baseline and week 48 of double blind period	No
Secondary	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	Functional decline was defined by either an at least 1 point decrease in the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-IADL) subscale score in a visit and confirmed by the following visit/assessment or at least 2 points decrease from the double blind randomization baseline.	390 days was the maximum	No
Secondary	Change in Attention and Executive Function as Assessed by the Trail Making Test (Part A) at Week 48 of the Double Blind Period	Change from baseline to week 48 in total time to perform Trail Making Test (TMT) part A. This test provides information on visual search, scanning, speed of processing, mental flexibility, and executive functions. The TMT part A requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. The score represents the amount of time required to complete the task. Total values for TMT part A range between 0 and 300 seconds. A negative change indicates an improvement from baseline.	Baseline and week 48 of double blind period	No
Secondary	Change in Attention and Executive Function as Assessed by the Trail Making Test (Part B) at Week 48 of Double Blind Period	Change from baseline to week 48 in total time to perform Trail Making Test (TMT) part B. This test provides information on visual search, scanning, speed of processing, mental flexibility, and executive functions. TMT has two parts: Part A requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for TMT-Part B except the person must alternate between numbers and letters. Total values for TMT part B range between 0 and 420 seconds. A negative change from baseline indicates an improvement in condition.	Baseline and week 48 of double blind period	No
Secondary	Change From Baseline in Neuropsychiatric Inventory (NPI)-10 Score at Week 48 of Double Blind Period	Change from baseline to week 48 as assessed by the Neuropsychiatric Inventory (NPI)-10 total score. The scale consists of 10 domains that are rated for both frequency (range 1-4) and severity (range 1-3). A composite score for each domain is calculated (frequency x severity) which ranges from 1 to 12. There is a leading question for each item. If the symptom is not present then the frequency, severity and distress scores are not completed. In this case the score is 0 for the item. The sum of the composite scores yields the NPI-10 total score (range 0-120). A negative change in score indicates an improvement from baseline (symptom reduction).	Baseline and week 48 of double blind period	No
Secondary	Number of Patients With Adverse Events, Serious Adverse Events and Discontinuations Due to Adverse Events		30 days after a maximum of 96 weeks treatment	Yes