Sleep Efficiency Assessed by Polysomnography (PSG Sleep Lab Testing) in Advanced Parkinson's Disease

Study Overview
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Brief Summary
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This is a phase 4 study to evaluate with Polysomnography (PSG) and subjective measures the effect of Rotigotine on sleep efficiency, maintenance, insomnia, nocturnal akinesia and night-time movement in bed, in patients with advanced Parkinson's disease.

Official Title
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A Multi-Centre, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Effects of Rotigotine on Sleep Efficiency in Patients With Advanced Parkinson's Disease.

Conditions
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Advanced Idiopathic Parkinson's Disease

Intervention / Treatment
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* Other: Placebo
* Other: Rotigotine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced Parkinson's disease (ie, takes Levodopa (L-DOPA)) Hoehn and Yahr stage score of 2 to 4 Subject has sleep-maintenance insomnia Exclusion Criteria: Significant skin disease that would make transdermal drug use inappropriate Subject received therapy with controlled-release Levodopa (L-DOPA), entacapone or Stalevo® within 28 days prior to the Baseline Visit or has received therapy with Tolcapone Atypical Parkinsonian syndromes Previous diagnosis of Narcolepsy, Sleep Apnoea Syndrome, significant Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD), moderate to severe Restless Legs Syndrome (RLS) or Periodic Limb Movement Disorder

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo Transdermal Patches | Other: Placebo<br>* Placebo patches size equivalent to 4, 6 & 8 mg/24 h. Daily application of Placebo patches starting at 4 mg/24 h. Dose will be up-titrated weekly by increments of 2 mg/24 h until optimal or maximal dose is reached. Maximal dose is 16 mg/24 h. Optimal or maximal dose will be maintained for 4 Weeks followed by a de-escalation by 2 mg/24 h every other day.<br>|
| Experimental: Rotigotine<br>Rotigotine Transdermal Patches | Other: Rotigotine<br>* Rotigotine patches of 4,6 & 8 mg/24 h. Daily application of Rotigotine patches starting at 4 mg/24 h. Dose will be up-titrated weekly by increments of 2 mg/24 h until optimal or maximal dose is reached. Maximal dose is 16 mg/24 h. Optimal or maximal dose will be maintained for 4 weeks followed by a de-escalation by 2 mg/24 h every other day.<br>* Other names: (6S)-6-propyl-[2-(2-thienyl)ethyl]amino-5,6,7,8-tetrahydro-1-naphthalenol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Sleep Efficiency Index (SEI) to Week 4 of the Maintenance Period | The Sleep Efficiency Index in percent is the ratio of total sleep time (based on Polysomnography recordings) to time in bed (period between lights off and lights on). | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Parkinson's Disease Sleep Scale Score Version 2 (PDSS2) to Day 1 of the Maintenance Period | The PDSS is a scale to assess sleep and nocturnal disability in Parkinson's Disease during the previous 7 days, and is designed for self-completion by the subject. The updated version (PDSS2) contains 15 questions to be answered using a 5-point Likert scale, where 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, and 4 = very often. Thus, PDSS2 score ranges from 0-60, with higher scores indicating worse sleep and higher nocturnal disability. A negative value in Change from Baseline indicates improved sleep and less nocturnal disability. | From Baseline to Day 1 of the Maintenance Period (up to 7 weeks post-baseline) | 
| Change From Baseline in the Parkinson's Disease Sleep Scale Score Version 2 (PDSS2) to Week 4 of the Maintenance Period | The PDSS2 is a scale to assess sleep and nocturnal disability in Parkinson's Disease during the previous 7 days, and is designed for self-completion by the subject. The updated version (PDSS2) contains 15 questions to be answered using a 5-point Likert scale, where 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, and 4 = very often. Thus, PDSS2 score ranges from 0-60, with higher scores indicating worse sleep and higher nocturnal disability. A negative value in Change from Baseline indicates improved sleep and less nocturnal disability. | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | 
| Change From Baseline in the Epworth Sleepiness Score (ESS) to Day 1 of the Maintenance Period | The ESS measures the subject's general level of daytime sleepiness. The 8 items of this scale assess the probability of falling asleep in a variety of situations. Each item is scored by the subject using the following categories: 0 = would never doze, 1 = slight chance of dozing, 2 = moderate chance of dozing, and 4 = high chance of dozing. The ESS score ranges from 0 to 32, with higher values indicating a higher level of daytime sleepiness. A negative value in Change from Baseline indicates a decrease in daytime sleepiness. | From Baseline to Day 1 of the Maintenance Period (up to 7 weeks post-baseline) | 
| Change From Baseline in the Epworth Sleepiness Score (ESS) to Week 4 of the Maintenance Period | The ESS measures the subject's general level of daytime sleepiness. The 8 items of this scale assess the probability of falling asleep in a variety of situations. Each item is scored by the subject using the following categories: 0 = would never doze, 1 = slight chance of dozing, 2 = moderate chance of dozing, and 4 = high chance of dozing. The ESS score ranges from 0 to 32, with higher values indicating a higher level of daytime sleepiness. A negative value in Change from Baseline indicates a decrease in daytime sleepiness. | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | 
| Change From Baseline in the Sleep Period Time in Non-Rapid Eye Movement (Non-REM) Sleep to Week 4 of the Maintenance Period | Polysomnography (PSG) was performed for the 2 consecutive nights prior to Day 1 and the 2 consecutive nights prior Week 4 of the Maintenance Period. Readings from the first night of the PSG will not be used for analysis as this is considered an adaptation night. The subject was not allowed to sleep during the daytime on the day of a PSG reading. The PSG was recorded for a minimum of 6 h and a maximum of 8 h. The sleep period time in stage 3 non-REM was derived from the hypnogram, based on Electroencephalogram (EEG), Electro-myogram (EMG), Electro-oculogram (EOG) and Electrocardiogram (ECG). Change from Baseline is calculated by: (Stage 3 non-REM time (in minutes) at Baseline)- (Stage 3 non-REM time (in minutes) at Week 4 of the MP). | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | 
| Change From Baseline in the Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS) to Day 1 of the Maintenance Period | The NADCS assesses nocturnal akinesia, dystonia, and cramps using an ordinal severity scale. While a score of 0 = normal and 4 = maximal severity, subjects can also rate their symptoms with values of 0.5, 1.5, 2.5, and 3.5. The nocturnal akinesia score was used to evaluate motor performance while the dystonia and cramps score was used to evaluate pain. A negative value in Change from Baseline indicates an improvement. | From Baseline to Day 1 of the Maintenance Period (up to 7 weeks post-baseline) | 
| Change From Baseline in the Nocturnal Akinesia, Dystonia and Cramps Score (NADCS) to Week 4 of the Maintenance Period | The NADCS assesses nocturnal akinesia, dystonia, and cramps using an ordinal severity scale. While a score of 0 = normal and 4 = maximal severity, subjects can also rate their symptoms with values of 0.5, 1.5, 2.5, and 3.5. The nocturnal akinesia score was used to evaluate motor performance while the dystonia and cramps score was used to evaluate pain. A negative value in Change from Baseline indicates an improvement. | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | 
| Change From Baseline in the Total Wake Time After Sleep Onset (WASO) to Week 4 of the Maintenance Period | Polysomnography (PSG) was performed for the 2 consecutive nights prior to Day 1 and the 2 consecutive nights prior Week 4 of the Maintenance Period. Readings from the first night of the PSG will not be used for analysis as this is considered an adaptation night. The subject was not allowed to sleep during the daytime on the day of a PSG reading. The PSG was recorded for a minimum of 6 h and a maximum of 8 h. Sleep stages and time spent in each sleep stage were determined from EEG readings. WASO was calculated by: (Time in bed (Period between lights off and lights on))-(Sleep time). | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | 
| Change From Baseline in the Total Number of Turnings in Bed to Week 4 of the Maintenance Period | Polysomnography (PSG) was performed for the 2 consecutive nights prior to Day 1 and the 2 consecutive nights prior Week 4 of the Maintenance Period. Readings from the first night of the PSG will not be used for analysis as this is considered an adaptation night. The subject was not allowed to sleep during the daytime on the day of a PSG reading. The PSG was recorded for a minimum of 6 h and a maximum of 8 h. The number of turnings in bed was determined via a postural sensor placed on the subject's chest. | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rotigotine, Neupro, Polysomnography, Sleep efficiency, Advanced Idiopathic Parkinson's Disease, Sleep Disorder