Trial to Assess Parkinson's Disease (PD) Symptom Control to Four Doses of Rotigotine in a Transdermal Patch

Study Overview
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Brief Summary
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The purpose of this study is to show Rotigotine dose response at four doses of Rotigotine used with L-dopa in treating advanced stage Parkinson's disease.

Detailed Description
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To maintain treatment blind, two different active patch sizes were used (10 cm^2 & 20 cm^2). Placebo patches matched according to size and appearance. During the trial subjects applied up to three patches, active and placebo, to achieve their assigned daily dose.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, 5-arm, Parallel-group Trial to Assess Rotigotine Transdermal System Dose Response in Subjects With Advanced-stage Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Rotigotine
* Drug: Rotigotine
* Other: Placebo
* Drug: Rotigotine
* Drug: Rotigotine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PD greater than 3 years Stable dose L-dopa but symptoms not adequately controlled and have off time Able and willing to complete diary on specific days Exclusion Criteria: Previous use of rotigotine or Neupro Atypical Parkinson's syndrome Pallidotomy Thalamotomy Deep brain stimulation Fetal tissue transplant Dementia Psychosis Hallucinations Epilepsy Renal or hepatic dysfunction Clinically relevant cardiac dysfunction Symptomatic orthostatic hypotension Skin sensitivity to adhesives or unresolved contact dermatitis History of chronic alcohol or drug abuse Pregnant or of child-bearing potential Impulse control disorder

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rotigotine 2 mg/24 hr<br> | Drug: Rotigotine<br>* 2 mg/24 hr (one 10 cm^2) transdermal patch applied daily for titration and maintenance period - 16 weeks<br>* Other names: Neupro;|
| Experimental: Rotigotine 4 mg/24 hr<br> | Drug: Rotigotine<br>* 4 mg/24 hr (one 20 cm^2) transdermal patch applied daily for titration and maintenance period - 16 weeks<br>* Other names: Neupro;|
| Experimental: Rotigotine 6 mg/24 hr<br> | Drug: Rotigotine<br>* 6 mg/24 hr (one 10 cm^2 & one 20 cm^2) transdermal patches applied daily for titration and maintenance period - 16 weeks<br>* Other names: Neupro;|
| Experimental: Rotigotine 8 mg/24 hr<br> | Drug: Rotigotine<br>* 8 mg/24 hr (two 10 cm^2 & one 20 cm^2) transdermal patches applied daily for titration and maintenance period - 16 weeks<br>* Other names: Neupro;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo transdermal patch applied daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in the Absolute Time Spent Off From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary | Time Off is defined as when the patient does not have the effect of anti-Parkinson's medication. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in Relative Time Spent Off From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary | Time Off is defined as when the patient does not have the effect of anti-Parkinson's medication. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Absolute Time Spent on From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary | Time On is defined as when the patient has the effect of anti-Parkinson's medication. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Relative Time Spent on From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary | Time On is defined as when the patient has the effect of anti-Parkinson's medication. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Status of the Subject After Wake-Up From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary |  | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II From Baseline to the End of the Maintenance Period | The Unified Parkinson's Disease Rating Scale (UPDRS) Part II is a scale for the assessment of function in Parkinson's disease. UPDRS Part II measures Activities of Daily Living. It consists of 13 questions, each ranging from 0 to 4. The sum score of the UPDRS Part II ranges from 0 to 52. A higher score indicates greater disability. A negative change score indicates improvement. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III From Baseline to the End of the Maintenance Period | The Unified Parkinson's Disease Rating Scale (UPDRS) Part III is a scale for the assessment of function in Parkinson's disease. UPDRS Part III measures Motor Function. It consists of 14 items with 27 questions, each ranging from 0 to 4. The sum score for the UPDRS Part III ranges from 0 to 108. A higher score indicates greater disability. A negative change score indicates improvement. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - What Proportion of the Waking Day Are Dyskinesias Present? | Item = Duration (question #32) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period - What proportion of the waking day are dyskinesias present? Has a possible score of 0 - 4 points (4 = maximum). A higher score indicates more severe symptoms. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Disability: How Disabling Are the Dyskinesias? | Item = Disability (question #33) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period - How disabling are the dyskinesias? Has a possible score of 0 - 4 points (4 = maximum). A higher score indicates more severe symptoms. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Painful Dyskinesias: How Painful Are the Dyskinesias? | Item = Painful Dyskinesia (question #34) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period - How painful are the dyskinesias? Has a possible score of 0 - 4 points (4 = maximum). A higher score indicates more severe symptoms. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Presence of Early Morning Dystonia | Item = Presence of Early Morning Dystonia (question #35) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates early morning dystonia. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Are Off Periods Predictable? | Item = Are off periods predictable (question #36) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates off periods are predictable. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Are Off Periods Unpredictable? | Item = Are off periods unpredictable (question #37) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates off periods are unpredictable. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Do Off Periods Come on Suddenly? | Item = Do off periods come on suddenly, within a few seconds (question #38) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates off periods come on suddenly, within a few seconds. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - What Proportion of the Waking Day is the Subject Off, on Average? | Item = What proportion of the waking day is the subject off, on average (question #39) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 - 4 points (4 = maximum). A higher score indicates the subject is off a larger portion of the waking day. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Does the Patient Have Anorexia, Nausea, or Vomiting? | Item = Does the patient have anorexia, nausea, or vomiting (question #40) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates subject has anorexia, nausea, or vomiting. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Does the Patient Have Any Sleep Disturbances Such as Insomnia or Hypersomnolence? | Item = Does the patient have any sleep disturbances such as insomnia or hypersomnolence (question #41) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates subject has sleep disturbances such as insomnia or hypersomnolence. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV From Baseline to the End of the Maintenance Period - Does the Patient Have Symptomatic Orthostasis? | Item = Does the patient have symptomatic orthostasis (question #42) in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV from Baseline to the end of the Maintenance Period has a possible score of 0 (no) or 1 (yes). A score of 1 indicates subject has symptomatic orthostasis. Results show the number of subjects per dose group and their change over time either improving (decrease in score), worsening (increase in score), or remaining the same. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 
| The Change in Number of Off Periods From Baseline to the End of the Maintenance Period as Recorded by the Subject in a Daily Diary | Time Off is defined as when the patient does not have the effect of anti-Parkinson's medication. | From Baseline to the End of the Maintenance Period [16 Weeks Treatment Period (4 weeks Titration Period and 12 weeks Maintenance Period)]. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, rotigotine, patch, transdermal, dopamine agonist, off time, Neupro