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

NCT00623103 | Completed Phase 3 Results

• 1 other identifier: CENA713B2315
• Study Type: interventional
• Target: 583
• Locations: 12 countries
• Sites: 122

Brief 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.

Conditions

Parkinson's Disease Dementia

Keywords

Parkinson's disease dementia; cholinesterase inhibitor; rivastigmine

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (6)

• 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

  From Baseline to Weeks 8, 16, 24, 52 and 76

• Change in Mattis Dementia Rating Scale (Mattis DRS-2) Scores at Weeks 16, 24, 52 and 76 Compared to Baseline

  From Baseline to Weeks 16, 24, 52 and 76

• Change in Ten Point Clock Test (TPCT) Scores at Weeks 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline

  From Baseline to Weeks 16, 24, 52 and 76

• Change in Neuropsychiatric Inventory-10 (NPI-10) Scores at Weeks 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline

  At Week 16, 24, 52 and 76 (or early discontinuation)

• 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

  From Baseline to Week 16, 24, 52 and 76 (or early discontinuation)

Study Arms (2)

Rivastigmine capsule

EXPERIMENTAL

Rivastigmine capsules starting at a total dose of 3 mg/day (1.5 mg twice daily orally) titrated up in 3 mg/day increments every 4 weeks to a final dose of 12 mg/day (6 mg twice daily orally). The 12 mg/day dose or the highest dose tolerated was maintained until week 76.

Drug: Rivastigmine capsule

Rivastigmine patch

EXPERIMENTAL

Rivastigmine patch once a day in the morning, worn for 24 hours, starting at 5 cm\^2 (delivering 4.6 mg rivastigmine over a 24 hour period) for 4 weeks then titrated up to 10 cm\^2 daily (delivering 9.5 mg rivastigmine over a 24 hour period). The 10 cm\^2 patch or the highest well tolerated dose was maintained until week 76.

Drug: Rivastigmine transdermal patch

Interventions

Rivastigmine capsule DRUG

Rivastigmine capsules orally twice a day. Target dose 12 mg/day.

Also known as: Exelon®

Rivastigmine capsule

Rivastigmine transdermal patch DRUG

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.

Also known as: Exelon®

Rivastigmine patch

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (127)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

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21st Century Neurology

Phoenix, Arizona, 85004, United States

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Neurosearch, Inc.

Reseda, California, 91335, United States

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Neurosearch II, Inc.

Ventura, California, 93003, United States

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Sunrise Clinical Research, Inc.

Hollywood, Florida, 33021, United States

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Collier Neurologic Specialists

Naples, Florida, 34102, United States

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Comprehensive Neurology Specialists, PC

Suwanee, Georgia, 30024, United States

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Neurological Associates

Meridian, Idaho, 83646, United States

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Evanstan Northwestern Healthcare Medical Group

Glenview, Illinois, 60026, United States

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University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

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Neurological Care of Central NY

Syracuse, New York, 13210-1853, United States

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Neurology & Neuroscience Associates, Inc.

Akron, Ohio, 44302, United States

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Square 1 Clinical Research

Erie, Pennsylvania, 16506, United States

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Research Protocol Management Solutions

Pittsburgh, Pennsylvania, 15243, United States

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Neurology Specialists of Dallas

Dallas, Texas, 75231, United States

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Progressive Clinical Research

Bountiful, Utah, 84010, United States

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Veterans Affairs Puget Sound Health Care System

Seattle, Washington, 98108, United States

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Novartis Investigative Site

Buenos Aires, Buenos Aires, C1425CDC, Argentina

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Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, C1122AAL, Argentina

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Novartis Investigative Site

Buenos Aires, Buenos Aires F.D., C1429DUC, Argentina

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Rosario, Santa Fe Province, S2000BZL, Argentina

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Kogarah, New South Wales, 2217, Australia

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Heidelberg, Victoria, 3084, Australia

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Malvern, Victoria, 3144, Australia

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Novartis Investigative Site

Melbourne, Victoria, 3050, Australia

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Novartis Investigative Site

Prahran, Victoria, 3181, Australia

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Graz, 8036, Austria

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Innsbruck, 6020, Austria

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Linz, 4020, Austria

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Novartis Investigative site

Linz, A-4020, Austria

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Vienna, 1220, Austria

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Antwerp, 2018, Belgium

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Brussels, 1200, Belgium

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Novartis Investigative Site

Edegem, 2650, Belgium

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Jette, 1090, Belgium

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Kortrijk, 8500, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Wilrijk, 2610, Belgium

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Calgary, Alberta, T2N 4N1, Canada

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Vancouver, British Columbia, V6T 2B5, Canada

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Halifax, Nova Scotia, B3J 3T1, Canada

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Kitchener, Ontario, N2H 5Z8, Canada

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London, Ontario, N6A 5A5, Canada

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Ottawa, Ontario, K1G 4G3, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Windsor, Ontario, N8X 5A6, Canada

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Greenfield Park, Quebec, J4V 2J2, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Montreal, Quebec, H3G 1A4, Canada

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Québec, Quebec, G1R 3X5, Canada

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Regina, Saskatchewan, S4T 1A5, Canada

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Amiens, 80054, France

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Clermont, 63003, France

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Lille, 59037, France

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Marseille, 13385, France

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Montpellier, 34295, France

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Paris, 75651, France

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Pessac, 33604, France

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Rennes, F-35043, France

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Roanne, 42328, France

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Bad Nauheim, 61231, Germany

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Beelitz-Heilstätten, 14547, Germany

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Berlin, 10713, Germany

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Berlin, 13353, Germany

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Bonn, 53105, Germany

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Dresden, 01307, Germany

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Göttingen, 37075, Germany

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Hamburg, 21075, Germany

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Kassel, 34128, Germany

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Leipzig, 04103, Germany

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Leun-Biskirchen, 35638, Germany

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Lubin, 15907, Germany

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Mainz, D-55131, Germany

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Marburg, 35032, Germany

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München, 80804, Germany

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München, 81675, Germany

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Nuremberg, 90402, Germany

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Ulm, 89073, Germany

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Ulm, 89081, Germany

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Wolfach, 77709, Germany

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Novartis Investigative Site

Bari, BA, 70121, Italy

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Bologna, BO, 40138, Italy

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Brescia, BS, 25123, Italy

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Foggia, FG, 71100, Italy

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Pozzilli, IS, 86077, Italy

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Lido di Camaiore, LU, 55041, Italy

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Milan, MI, 20100, Italy

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Roma, RM, 00133, Italy

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Roma, RM, 00163, Italy

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Roma, RM, 00179, Italy

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Roma, RM, 00185, Italy

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Trieste, TS, 34149, Italy

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Arcugnano, VI, 36057, Italy

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Cassino, 03043, Italy

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Napoli, 80131, Italy

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Novartis Investigative Site

Napoli, 80138, Italy

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Novartis Investigative Site

Zwolle, AB, 8025, Netherlands

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Blaricum, AN, 1261, Netherlands

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Maastricht, AZ, 6202, Netherlands

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Breda, CK, 4818, Netherlands

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Enschede, ER, 7513, Netherlands

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Tilburg, GC, 5022, Netherlands

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Groningen, GZ, 9713, Netherlands

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's-Hertogenbosch, JL, 5232, Netherlands

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Heerlen, PC, 6419, Netherlands

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Sittard, 6131 BK, Netherlands

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Novartis Investigative Site

Barcelona, 08014, Spain

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Novartis Investigative Site

Barcelona, 08028, Spain

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Novartis Investigative Site

Barcelona, 08035, Spain

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Novartis Investigative Site

Barcelona, 08190, Spain

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Madrid, 28034, Spain

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Novartis Investigative Site

Adana, 01330, Turkey (Türkiye)

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Antalya, 07059, Turkey (Türkiye)

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Istanbul, 34093, Turkey (Türkiye)

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Izmir, 35340, Turkey (Türkiye)

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Kocaeli, 41380, Turkey (Türkiye)

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Sihhiye/Ankara, 06100, Turkey (Türkiye)

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Novartis Investigative Site

Yenisehir/Izmir, 35120, Turkey (Türkiye)

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Blackburn, BB2 3HH, United Kingdom

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Blandford Forum, Dorset, United Kingdom

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Christchurch, Dorset, BH 232JX, United Kingdom

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Newcastle, NE4 5PL, United Kingdom

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Oxford, OX3 9DU, United Kingdom

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Peterborough, PE3 6DA, United Kingdom

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Novartis Investigative Site

Southampton, SO30 3JB, United Kingdom

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Novartis Investigative Site

Vale of Glamorgan, CF64 2XX, United Kingdom

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MeSH Terms

Interventions

Rivastigmine

Intervention Hierarchy (Ancestors)

Phenylcarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2008
• First Posted: February 25, 2008
• Study Start: January 1, 2008
• Primary Completion: November 1, 2010
• Last Updated: November 28, 2011
• Results First Posted: November 28, 2011

Record last verified: 2011-10

Locations

IT (16); FR (9); ES (5); TU (7); US (17); BE (8); NL (10); AR (4); AU (5); CA (13); DE (20); GB (8)