Rotigotine Versus Placebo to Evaluate the Efficacy on Depressive Symptoms in Idiopathic Parkinson's Disease Patients

Study Overview
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Brief Summary
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The purpose of this study was to show superiority of Rotigotine over placebo on improvement of depressive symptoms in subjects with idiopathic Parkinson's disease.

Detailed Description
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The study included a maximum 2-week Screening Period, a maximum 4-week Titration Period for early-stage Parkinson's disease or maximum 7-week Titration Period for advanced-stage Parkinson's disease, 8-week Maintenance Period, a maximum 6-day De-escalation Period for early-stage Parkinson's disease or maximum 12-day De-escalation Period for advanced-stage Parkinson's disease and 30-day Safety Follow-Up Period. The maximum study durations for an individual subject with early-stage Parkinson's disease and with advanced-stage Parkinson's disease were 19 weeks and 23 weeks, respectively.

Official Title
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Double Blind, Placebo-controlled, Parallel, Multicenter, Randomized Interventional Phase IV Study to Evaluate the Efficacy of Rotigotine on Depressive Symptoms in Idiopathic Parkinson's Disease Patients

Conditions
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Idiopathic Parkinson's Disease

Intervention / Treatment
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* Drug: Rotigotine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects ≥ 20 years old Subjects diagnosed with idiopathic Parkinson's disease (according to the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria for Parkinson's disease) at modified Hoehn and Yahr Scale stages I-III; do not have motor fluctuations, dyskinesia, and have stable motor symptom at least 4 weeks prior to the Screening Visit as judged by the local investigator Subject has a Beck Depression Inventory II (BDI-II) score ≥ 16 as evidenced by depression rating scale study in Parkinson's disease (Schrag A et al, 2007) Subject has a Mini-Mental State Examination (MMSE) score ≥ 24 If subject is taking Levodopa (L-DOPA) and derivatives, Monoamine Oxidase (MAO) B-inhibitors, anticholinergics agents, Catechol-O-Methyl Transferase (COMT) inhibitor or N-Methyl-D-Aspartate (NMDA) antagonist, he/she must have been on stable dose for at least 28 days prior to the Screening Visit If subject is taking an antidepressant drug such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), bupropion, tricyclic antidepressants (TCAs), he/she must have been on a stable dose for at least 28 days prior to the Screening Visit and be maintained on that dose for the duration of the trial Exclusion Criteria: Subject has any medical or psychiatric condition (ie, bipolar disorder, dementia, hallucinations or psychosis) that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the C-SSRS at Screening (Visit 1) Current psychotherapy or behavior therapy while participating in this study Subject has received electroconvulsive therapy within 12 weeks of the Screening Visit Subject who has received dopamine agonists within 28 days of the Screening Visit Subject who has received neuroleptics, methylphenidate, reserpine, alpha-methyldopa, metoclopramide, levosulpiride or amphetamine derivatives within 28 days of the Screening Visit

Ages Eligible for Study
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Minimum Age: 20 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rotigotine<br>Rotigotine, daily doses, treatment group | Drug: Rotigotine<br>* Transdermal Patch Content: 2 mg /24 h (10 cm^2), 4 mg /24 h (20 cm^2), 6 mg /24 h (30 cm^2), 8 mg /24 h (40 cm^2) For early-stage Parkinson's disease, Subjects received Rotigotine patches in escalating weekly dose (starting with daily doses 2 mg/24 h to 8 mg/24 h) for a maximum 4-week Titration Period, then 8 week Maintenance period For advanced-stage Parkinson's disease, Subjects received Rotigotine patches in escalating weekly dose (starting with daily doses 4 mg/24 h to 16 mg/24 h) for a maximum 7-week Titration Period, then 8 week Maintenance period<br>|
| Placebo Comparator: Placebo<br>Placebo, daily doses, placebo group | Drug: Placebo<br>* Transdermal Patch Size: 10 cm^2, 20 cm^2, 30 cm^2, 40 cm^2 Subjects randomized to placebo received matching placebo patches<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to the End of Maintenance Period in the Score of the Hamilton Depression Scale (HAM-D) | The HAM-D consists of 17 items. Nine of the items are scored on a 5-point scale, ranging from 0 to 4. The remaining 8 items are scored on a 3-point scale, from 0 to 2. Therefore, the total score ranges between 0 to 52, with a cutoff score of 15/16 diagnosing major depressive disorder. | From Baseline (Week 0) to end of Maintenance Period (up to Week 15) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to the End of Maintenance Period in the Score of Beck Depression Inventory (BDI-II) | The Beck Depression Inventory II (BDI-II) is a self-report instrument to measure Depression symptoms and severity. There are 21 items in the BDI-II. Scores of 0-13 are considered minimal depression; 14-19 indicates mild depression; 20-28 indicates moderate depression; and 29-63 indicates severe depression. | From Baseline (Week 0) to end of Maintenance Period (up to Week 15) | 
| Change From Baseline to the End of Maintenance Period in the Score of Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living-ADL Subscale) | The UPDRS Part II is a tool to measure Activities in Daily Living - it includes speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing, hygiene, turning in bed and adjusting clothes, falling (unrelated to freezing), freezing when walking, walking, tremor, and sensory complaints related to Parkinsonism. Each of the 13 questions is measured on a scale from 0 (normal) to 4 (severe). The total score of UPDRS part II ranges from 0 (normal) to 52 (severe). | From Baseline (Week 0) to end of Maintenance Period (up to Week 15) | 
| Change From Baseline to the End of Maintenance Period in the Score of Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Subscale) | Improvement of motor symptoms is measured by the change from Baseline in UPDRS Part III motor score. The UPDRS Part III is an accepted and validated scale for the assessment of motor function in Parkinson's disease. Each of the elements in the UPDRS Part III is measured on a scale of 0 to 4, where 0 is normal and 4 represents severe abnormalities. The total score of UPDRS part III ranges from 0 (normal) to 108 (severe abnormalities). | From Baseline (Week 0) to end of Maintenance Period (up to Week 15) | 
| Change From Baseline to the End of Maintenance Period in the Combined Score of Unified Parkinson's Disease Rating Scale (UPDRS) Part II (ADL) Plus Part III (Motor Subscale) | The combined score of UPDRS part II and UPDRS part III is the sum of the individual scores and threfore ranges from 0 (normal) to 160 (severe). | From Baseline (Week 0) to end of Maintenance Period (up to Week 15) | 
| Change From Baseline to the End of Maintenance Period in the Score of Apathy Scale (AS) | The AS is an abbreviated version of the Apathy Scale (AS). The AS consists of 14 items phrased as questions that are to be answered on a four-point Likert scale. It was developed specifically for patients with Parkinson Disease (PD). For questions 1-8, the scoring system is the following: not at all = 3 points; slightly = 2 points; some =1 point, a lot = 0 point. For questions 9-14: the scoring system is the following: not at all = 0 points; slightly = 1 point; some = 2 points; a lot = 3 points. Adding all scores provides the final score with a range from 0 to 42. | From Baseline (Week 0) to end of Maintenance Period (up to Week 15) | 
| Change From Baseline to the End of Maintenance Period in the Score of Snaith-Hamilton Pleasure Scale (SHAPS) | The SHAPS is a self-report instrument developed for the assessment of hedonic capacity. The sum of the 14 items scores ranges from 0 to 14. A higher score represents more anhedonic symptoms. | From Baseline (Week 0) to end of Maintenance Period (up to Week 15) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rotigotine, Neupro, Depressive Symptom, Idiopathic Parkinson's disease