A Phase 3b, Open-Label, Safety and Efficacy Study of Rotigotine as Add-On Therapy With Low Doses of Pramipexole or Ropinirole in Patients With Advanced Parkinson's Disease

Study Overview
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Brief Summary
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This study is to investigate the safety and efficacy of Rotigotine add-on therapy with low doses of Pramipexole or Ropinirole in patients with advanced-stage Parkinson's Disease (PD) who have insufficient response to L-dopa and low doses dopamine receptor agonists.

Official Title
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An Open-Label Study to Investigate the Safety and Efficacy of Rotigotine Add-On Therapy With Low Doses of Pramipexole or Ropinirole in Patients With Advanced Parkinson's Disease Phase 3B

Conditions
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Advanced Parkinson's Disease

Intervention / Treatment
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* Drug: Rotigotine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is male or female, aged ≥ 30 and < 80 years at informed consent Subject has idiopathic Parkinson's Disease, of more than 3 years duration, as defined by the cardinal sign, bradykinesia, and the presence of at least 1 of the following: resting tremor, rigidity, impairment of postural reflexes, and without any known or suspected cause of Parkinsonism Subject has motor fluctuations such as wearing, dyskinesia Subject has experienced nocturias for at least 3 nights within 7 days prior to Baseline Subject is taking levodopa (L-DOPA, immediate and/or controlled release) in combination with benserazide or carbidopa and has been on a stable dose of L-DOPA for at least 28 days prior to Baseline (Visit 2) Subject is taking a non-ergot dopamine agonist (pramipexole ≤ 1.5 mg/day or ropinirole ≤ 6.0 mg/day) and has been on a stable dose of non-ergot dopamine agonist for at least 28 days prior to Baseline (Visit 2) Exclusion Criteria: Subject is receiving therapy with tolcapone or budipine Subject is receiving therapy with one of the following drugs either concurrently or within 28 days prior to Baseline (Visit 2): alpha-methyl dopa, metoclopramide, reserpine, neuroleptics (except specific atypical neuroleptics: olanzapine, ziprasidone, aripiprazole, clozapine, quetiapine), monoamine oxidase A (MAO-A) inhibitors, methylphenidate, or amphetamine Subject has a history of symptomatic (not asymptomatic) orthostatic hypotension within the 6 months prior to Baseline (Visit 2) Subject has a known hypersensitivity to any components of the study medication, such as a history of significant skin hypersensitivity to adhesives, known hypersensitivity to other transdermal medications, or has unresolved contact dermatitis Subject is pregnant or nursing, or is of child-bearing potential (ie, is (i) not surgically sterile, or, (ii) not using adequate birth control methods [including at least one barrier method] or, (iii) not sexually abstinent, or (iv) not at least 2 years post menopausal) Subject had a previous diagnosis of narcolepsy, sleep apnea syndrome, restless legs syndrome, or periodic limb movement disorder

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rotigotine<br>- Titration Period: Weekly titration to the subject's optimal dose of Rotigotine between 2 mg/24 h and 8 mg/24 h. In case of intolerable Adverse Events (AEs) one back-titration is allowed during the Titration Period. Duration of the Titration Period: Between 1 week and 5 weeks. - Maintenance Period: Starts once subject reached either optimal or maximal dose of Rotigotine. Subjects receive stable dose of Rotigotine throughout the Maintenance Period. No back-titration is allowed during the Maintenance Period. Duration of the Maintenance Period: Between 3 weeks and 7 weeks. | Drug: Rotigotine<br>* Application of Rotigotine up to 8 mg/24 h patches for 24 hours.<br>* Other names: Neupro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression (CGI) Item 4 (Side Effects) at the End of the Treatment Period | The CGI Item 4 was used to assess side effects. It ranges from 0 to 4 as follows: 0 = Side effects not assessable = No side effects = Side effects do not significantly interfere with subject's functioning = Side effects significantly interfere with the subject's functioning = Side effects outweigh therapeutic efficacy. | Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period) | 
| Change From Baseline to the End of the Treatment Period in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (on State) Total Score | The Unified Parkinson´s Disease Rating Scale Part III is an accepted and validated scale for the assessment of motor function in Parkinson´s disease. Each of the 27 sub-items in the UPDRS III is measured on a scale of 0 to 4, where 0 is normal and 4 represents severe abnormalities. The total scores therefore ranges from 0 to 108. A negative value in Change from Baseline to Week 8 indicates an improvement in motor functions from Baseline. | From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period) | 
| Change From Baseline to the End of the Treatment Period in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Average of on and Off State) Total Score | UPDRS Part II measures 'Activities in Daily Living'. The total score ranges from 0 (Best score possible) to 52 (Worst score possible). UPDRS Part II total score (average of on and off state) is the average of UPDRS Part II total score (on state) and Part II total score (off state). A negative value in Change from Baseline to Week 8 indicates an improvement in activities in daily living from Baseline. | From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period) | 
| Change From Baseline to the End of the Treatment Period in Absolute Time Spent Off | Absolute time spent off is measured in hours per day. A negative value in Change from Baseline to Week 8 indicates that the time spent off decreased from Baseline and therefore indicates an improvement from Baseline. Only subjects with time spent off at Baseline (subset of the Full Analysis Set (FAS)) are included in the analysis of this outcome measure. | From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to the End of the Treatment Period in Time Spent on Without Troublesome Dyskinesia | Absolute time spent on without troublesome dyskinesia is measured in hours per day. A positive value in Change from Baseline to Week 8 indicates that the time spent on without troublesome dyskinesia increased from Baseline and therefore indicates an improvement from Baseline. | From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period) | 
| Change From Baseline to the End of Treatment Period in Parkinson's Disease Sleep Scale 2 (PDSS-2) Total Score | The Parkinson´s Disease Sleep Scale (PDSS) is a questionnaire with 15 questions to assess sleep disturbance and nocturnal disability in Parkinson´s disease. The item- scores can range between 0= never and 4= very often. The PDSS score is a sum score of all 15 questions. A negative value in Change from Baseline to Week 8 indicates an improvement from Baseline. | From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period) | 
| Change From Baseline to the End of Treatment Period in the Pittsburgh Sleep Quality Index (PSQI) Global Score | The Pittsburgh Sleep Quality Index (PSQI) is a questionnaire with 18 questions to assess sleep quality. The 18 questions are distributed to 7 elements with each element ranging from 0-3. The global score is the sum score of all 7 elements and ranges from 0-21 with higher values indicating worse sleep quality. A negative value in Change from Baseline to Week 8 indicates an improvement in sleep quality from Baseline. | From Baseline (Week 0) to Week 8 (Visit 8) of the 8 weeks Treatment Period (Titration and Maintenance Period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rotigotine, Neupro