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

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)”

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.

Intervention(s) in this Clinical Trial

• Drug: Rivastigmine capsule
  • Rivastigmine capsules orally twice a day. Target dose 12 mg/day.
• 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.

Arms, Groups and Cohorts in this Clinical Trial

• 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.
• 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.

Primary 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes

Secondary 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
    Safety Issue?: Yes
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novartis Industry

Overall Clinical Trial Officials and Contacts

Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00623103

Study ID Number: CENA713B2315

ClinicalTrials.gov Identifier: NCT00623103

Health Authority: United States: Food and Drug Administration