Long-term Safety of Rivastigmine Capsule and Patch in Patients With Mild to Moderately-severe Dementia Associated With Parkinson's Disease (PDD)

Parkinson's Disease Dementia Clinical Trial

Official title:

A 76-week Prospective, Open-label, Multicenter Study to Evaluate the Long-term Effect of Rivastigmine Capsule and Transdermal Patch on Worsening of the Underlying Motor Symptoms of PD in Patients With Mild to Moderately Severe Dementia Associated With Parkinson's Disease (PDD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00623103
• Other study ID #: CENA713B2315
• Status: Completed
• Phase: Phase 3
• First received: February 14, 2008
• Last updated: October 19, 2011
• Start date: January 2008

Study information

• Verified date: October 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaAustria: Agency for Health and Food SafetyBelgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: Ministry of HealthNetherlands: Medicines Evaluation Board (MEB)Spain: Spanish Agency of MedicinesTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to provide long-term safety data for rivastigmine capsule and transdermal patch treatments, in particular the effect of rivastigmine on worsening of the underlying motor symptoms of Parkinson's Disease (PD), in patients with mild to moderately severe dementia associated with PD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 583
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 85 Years

Eligibility

Inclusion Criteria:

• Diagnosis of idiopathic Parkinson's disease, according to the UK Parkinson's disease Society Brain Bank criteria

• Diagnosis of Parkinson's disease dementia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, with onset of symptoms of dementia at least 2 years following the first diagnosis of idiopathic Parkinson's disease

• Mini Mental State Examination score of =10 and = 26 (at Screening Visit only)

Exclusion Criteria:

• An advanced, severe, or unstable disease of any type that may interfere with the primary and secondary variable evaluations

• A score of 5 (wheelchair bound or bedridden) in the "on"-state on the Modified Hoehn and Yahr Staging (UPDRS Part V)

• A current diagnosis of any primary neurodegenerative disorder other than idiopathic PD

• A current diagnosis of any treatable dementia (hypothyroidism, syphilis, vitamin B12 or folate deficiency) that is verified by the investigator to be the cause of dementia.

• A current diagnosis of probably vascular dementia according to the National Institute of Neurological Disorders and Stroke and the Association International pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria

• A current diagnosis of a major depressive episode according to DSM-IV criteria

• A history of stereotaxic brain surgery for Parkinson's disease

• A known exaggerated pharmacological sensitivity or hypersensitivity to drugs similar to rivastigmine or to other cholinergic compounds

Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dementia
• Parkinson Disease
• Parkinson's Disease Dementia

Intervention

Drug:
• Rivastigmine capsule
Rivastigmine capsules orally twice a day. Target dose 12 mg/day.
• Rivastigmine transdermal patch
Rivastigmine patch once a day in the morning, worn for 24 hours. Target dose 10 cm^2/day delivering 9.5 mg over a 24 hour period.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires	Capital Federal
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Australia	Novartis Investigative Site	Heidelberg	Victoria
Australia	Novartis Investigative Site	Kogarah	New South Wales
Australia	Novartis Investigative Site	Malvern	Victoria
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	Prahran	Victoria
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Innsbruck
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative site	Linz
Austria	Novartis Investigative Site	Vienna
Belgium	Novartis Investigative Site	Antwerpen
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Edegem
Belgium	Novartis Investigative Site	Jette
Belgium	Novartis Investigative Site	Kortrijk
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Wilrijk
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Kitchener	Ontario
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Regina	Saskatchewan
Canada	Novartis Investigative site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Windsor	Ontario
France	Novartis Investigative Site	Amiens Cedex
France	Novartis Investigative Site	Clermont
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Marseille Cedex
France	Novartis Investigative Site	Montpellier Cedex 5
France	Novartis Investigative Site	Paris Cedex
France	Novartis Investigative site	Pessac Cedex
France	Novartis Investigative site	Rennes
France	Novartis Investigative Site	Roanne
Germany	Novartis Investigative Site	Bad Nauheim
Germany	Novartis Investigative Site	Beelitz-Heilstaetten
Germany	Novartis Investigative site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Goettingen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Kassel
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leun-Biskirchen
Germany	Novartis Investigative Site	Luebben
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Munchen
Germany	Novartis Investigative Site	Nuernberg
Germany	Novartis Investigative site	Ulm
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Wolfach
Italy	Novartis Investigative Site	Arcugnano	VI
Italy	Novartis Investigative Site	Bari	BA
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative site	Cassino
Italy	Novartis Investigative Site	Foggia	FG
Italy	Novartis Investigative Site	Lido di Camaiore	LU
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Pozzilli	IS
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Trieste	TS
Netherlands	Novartis Investigative Site	Blaricum	AN
Netherlands	Novartis Investigative Site	Breda	CK
Netherlands	Novartis Investigative Site	Enschede	ER
Netherlands	Novartis Investigative Site	Groningen	GZ
Netherlands	Novartis Investigative Site	Heerlen	PC
Netherlands	Novartis Investigative Site	Hertogenbosch	JL
Netherlands	Novartis Investigative Site	Maastricht	AZ
Netherlands	Novartis Investigative Site	Sittard
Netherlands	Novartis Investigative Site	Tilburg	GC
Netherlands	Novartis Investigative Site	Zwolle	AB
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Madrid
Turkey	Novartis Investigative Site	Adana
Turkey	Novartis Investigative Site	Antalya
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Sihhiye/Ankara
Turkey	Novartis Investigative Site	Yenisehir/Izmir
United Kingdom	Novartis Investigative Site	Blackburn
United Kingdom	Novartis Investigative Site	Blandford Forum, Dorset
United Kingdom	Novartis Investigative Site	Christchurch, Dorset
United Kingdom	Novartis Investigative Site	Newcastle
United Kingdom	Novartis Investigative Site	Oxford
United Kingdom	Novartis Investigative Site	Peterborough
United Kingdom	Novartis Investigative Site	Southampton
United Kingdom	Novartis Investigative Site	Vale of Glamorgan
United States	Neurology & Neuroscience Associates, Inc.	Akron	Ohio
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Progressive Clinical Research	Bountiful	Utah
United States	Neurology Specialists of Dallas	Dallas	Texas
United States	Square 1 Clinical Research	Erie	Pennsylvania
United States	Evanstan Northwestern Healthcare Medical Group	Glenview	Illinois
United States	Sunrise Clinical Research, Inc.	Hollywood	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Neurological Associates	Meridian	Idaho
United States	Collier Neurologic Specialists	Naples	Florida
United States	21st Century Neurology	Phoenix	Arizona
United States	Research Protocol Management Solutions	Pittsburgh	Pennsylvania
United States	Neurosearch, Inc.	Reseda	California
United States	Veterans Affairs Puget Sound Health Care System	Seattle	Washington
United States	Comprehensive Neurology Specialists, PC	Suwanee	Georgia
United States	Neurological Care of Central NY	Syracuse	New York
United States	Neurosearch II, Inc.	Ventura	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (AEs) Due, or Potentially Due, to Worsening of Parkinson Disease (PD) Motor Symptoms (Tremor, Muscle Rigidity, Bradykinesia, Fall)	The AEs were summarized by presenting the number and percentage of patients having any of the 4 AEs or discontinued due to any of the 4 predefined AEs (tremor, muscle rigidity, bradykinesia, and fall)in each treatment group. The 95% CIs associated with the rates were also presented.	76 Weeks	Yes
Primary	Percentage of Participants With Study Drug Discontinuations Due to Predefined AEs That Are Due, or Potentially Due, to Worsening of PD Motor Symptoms (Tremor, Muscle Rigidity, Bradykinesia, Fall)	The discontinuations due to these AEs were summarized by presenting the number and percentage of patients having any of the 4 AEs or discontinued due to any of the 4 predefined AEs (tremor, muscle rigidity, bradykinesia, and fall) in each treatment group. The 95% CIs associated with these rates were also presented.	76 Weeks	Yes
Secondary	Change in Unified Parkinson Disease Rating Scale (UPDRS) Part III Motor Examination Scores at Weeks 8, 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline	Unified Parkinson Disease Rating Scale (UPDRS) is a 6 part Parkinson's disease specific rating scale that estimates clinical function taking into consideration both disability (functional deficits) and impairment (objective clinical signs). Part III records the motor examination in Items 18-31 rated on a scale of 0 to 4 with (0 being absent/ normal and 4 being the worse) for a total possible score of 0 to 56.	From Baseline to Weeks 8, 16, 24, 52 and 76	Yes
Secondary	Change in Mattis Dementia Rating Scale (Mattis DRS-2) Scores at Weeks 16, 24, 52 and 76 Compared to Baseline	Mattis DRS-2 is a measure of cognitive status. The total score is the sum of 5 subscale scores: Attention [0-37], Initiation/Perservation [0-37] (performing alternating movements), Construction [0-6] (copying designs), Conceptualization [0-39] (similarities) and Memory [0-25] (sentence recall, design recognition)for a total possible score of 0-144. Higher score is reflective of better cognitive function, lower scores associated with more pronounced cognitive deficit. The change from baseline was calculated such that a positive number indicates an improvement.	From Baseline to Weeks 16, 24, 52 and 76	No
Secondary	Change in Ten Point Clock Test (TPCT) Scores at Weeks 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline	The Ten Point Clock Test measures executive functioning and visuospatial skills. Participants are asked to put numbers on the face of a clock and then make the clock read 10 minutes after 11. Points are awarded on a scale of 0 to 10 for spacing of specific numbers and the positions of the hands. The change from baseline was calculated such that a positive number indicates improvement.	From Baseline to Weeks 16, 24, 52 and 76	No
Secondary	Change in Neuropsychiatric Inventory-10 (NPI-10) Scores at Weeks 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline	The parameter for analysis was the change from baseline of total score of 10 items on the NPI scale (NPI-10). The total score is a sum of the 10 domains, where the score for a domain is defined as the product of frequency (range: 1-4) and severity (range: 1-3). Each domain has a maximum score of 12 and all domains were equally weighted for total score(thus the range for the total score is 0 to 120 with 0 being completely healthy to 120 which is the worse score patient can get). The change from baseline was calculated such that a negative number indicates an improvement (symptom reduction).	At Week 16, 24, 52 and 76 (or early discontinuation)	No
Secondary	Change in Alzheimer's Disease Cooperative Study-Activities Of Daily Living (ADCS-ADL) Scores at Weeks 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline	The 23 item caregiver-based ADL scale of the dementia Alzheimer's disease Cooperative Study-Activities of Daily Living (ADCS-ADL) was used for analysis. This is a caregiver rated questionnaire of 23 items, with possible scores over a range of 0-78, where 78 denote full functioning with no impairment. The total score was derived by adding up the item scores of the 23 items.; The change from baseline was calculated such that a positive change indicates an improvement.	From Baseline to Week 16, 24, 52 and 76 (or early discontinuation)	No
Secondary	UPDRS Part V Stage (Modified Hoehn and Yahr Staging)at Baseline, Week 8,16,24,52 and 76 (or Early Discontinuation)	Unified Parkinson Disease Rating Scale (UPDRS) is a 6 part Parkinson's disease specific rating scale that estimates clinical function taking into consideration both disability (functional deficits) and impairment (objective clinical signs). UPDRS Part V is assessed by the modified Hoehn and Yahr Staging Scale. The scale ranges from 0 (no signs of disease) to 5 (wheelchair bound or bedridden unless aided).	From Baseline to Week 8, 16, 24, 52 and 76 (or early discontinuation)	No