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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00623103
First received: February 14, 2008
Last updated: October 19, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Parkinson's Disease Dementia
Drug: Rivastigmine capsule
Drug: Rivastigmine transdermal patch
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events (AEs) Due, or Potentially Due, to Worsening of Parkinson Disease (PD) Motor Symptoms (Tremor, Muscle Rigidity, Bradykinesia, Fall) [ Time Frame: 76 Weeks ] [ Designated as safety issue: Yes ]
    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.

  • 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) [ Time Frame: 76 Weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 [ Time Frame: From Baseline to Weeks 8, 16, 24, 52 and 76 ] [ Designated as safety issue: Yes ]
    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.

  • Change in Mattis Dementia Rating Scale (Mattis DRS-2) Scores at Weeks 16, 24, 52 and 76 Compared to Baseline [ Time Frame: From Baseline to Weeks 16, 24, 52 and 76 ] [ Designated as safety issue: No ]
    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.

  • Change in Ten Point Clock Test (TPCT) Scores at Weeks 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline [ Time Frame: From Baseline to Weeks 16, 24, 52 and 76 ] [ Designated as safety issue: No ]
    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.

  • Change in Neuropsychiatric Inventory-10 (NPI-10) Scores at Weeks 16, 24, 52 and 76 (or Early Discontinuation) Compared to Baseline [ Time Frame: At Week 16, 24, 52 and 76 (or early discontinuation) ] [ Designated as safety issue: No ]
    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).

  • 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 [ Time Frame: From Baseline to Week 16, 24, 52 and 76 (or early discontinuation) ] [ Designated as safety issue: No ]

    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.


  • UPDRS Part V Stage (Modified Hoehn and Yahr Staging)at Baseline, Week 8,16,24,52 and 76 (or Early Discontinuation) [ Time Frame: From Baseline to Week 8, 16, 24, 52 and 76 (or early discontinuation) ] [ Designated as safety issue: No ]
    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).


Enrollment: 583
Study Start Date: January 2008
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivastigmine capsule
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 capsules orally twice a day. Target dose 12 mg/day.
Other Name: Exelon®
Experimental: Rivastigmine patch
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
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.
Other Name: Exelon®

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00623103

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Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Arizona
21st Century Neurology
Phoenix, Arizona, United States, 85004
United States, California
Neurosearch, Inc.
Reseda, California, United States, 91335
Neurosearch II, Inc.
Ventura, California, United States, 93003
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Sunrise Clinical Research, Inc.
Hollywood, Florida, United States, 33021
Collier Neurologic Specialists
Naples, Florida, United States, 34102
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Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00623103     History of Changes
Other Study ID Numbers: CENA713B2315
Study First Received: February 14, 2008
Results First Received: October 19, 2011
Last Updated: October 19, 2011
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Spain: Spanish Agency of Medicines
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Parkinson's disease dementia
cholinesterase inhibitor
rivastigmine

Additional relevant MeSH terms:
Parkinson Disease
Dementia
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Rivastigmine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014