A Sleep Laboratory Study to Investigate the Safety and Efficacy of the Rotigotine Skin Patch in Subjects With Restless Legs Syndrome and End-Stage Renal Disease Requiring Hemodialysis

• Sponsor: UCB BIOSCIENCES GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01537042
• Collaborator: (none)
• Enrollment: 30
• Locations: 15
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a sleep laboratory study to evaluate the efficacy and safety of Rotigotine in subjects with Restless Legs Syndrome and End-Stage Renal Disease requiring hemodialysis.

The objectives are to demonstrate superiority of Rotigotine against Placebo as well as to investigate the effect of Rotigotine on quality of life and sleep.

Condition or Disease	Intervention/Treatment	Phase
Restless Legs Syndrome; End-Stage Renal Disease	Drug: Rotigotine; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group, Polysomnography Study to Investigate Safety and Efficacy of the Rotigotine Transdermal Patch in Subjects With Restless Legs Syndrome and End-Stage Renal Disease Requiring Hemodialysis
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rotigotine Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.	Drug: Rotigotine; Transdermal patch; Dose: 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h. Subjects start with a Rotigotine dose of 1 mg/24 h for 1 week. The dose can be increased weekly during Up-Titration Period until either the optimal or the maximal dose of 3 mg/24 h has been reached. Subjects will maintain the optimal/maximal dose during the 2-week Maintenance Period. Following the Maintenance Period, subjects will be de-escalated from their optimal dose by decreasing the dose by 1 mg/24 h every other day during Taper Period until complete withdrawal.; Other Names: Neupro
Placebo Comparator: Placebo Transdermal patch matched according to patch size and appearance.	Drug: Placebo; Transdermal patch; Patches matching to active treatment patches in size and appearance. Up to 3 weeks of Titration, 2 weeks of Maintenance, Up to 4 days of Taper Period.

Outcome Measures

Primary Outcome Measures

1. Ratio From Baseline to the End of the 2-week Maintenance Period in Periodic Limb Movement Index (PLMI) [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

   The PLMI is defined as Periodic Limb Movements (PLMs)/ total time in bed in hours. PLMs are measured by Polysomnography (PSG). The reduction of the PLMI is reflected in terms of the ratio from Baseline to the end of the Maintenance Period and was calculated as [PLMI at end of Maintenance Period (MP)] / [PLMI at Baseline]. A PLMI Ratio <1 indicates an improvement from Baseline to the end of the 2-week MP.

Secondary Outcome Measures

1. Change From Baseline in the Periodic Limb Movements Index (PLMI) to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

   The PLMI is defined as Periodic Limb Movements (PLMs)/ total time in bed in hours. PLMs are measured by Polysomnography (PSG). A negative value in change from Baseline indicates an improvement from Baseline to the end of the Maintenance Period.

2. Change From Baseline in the International Restless Legs Syndrome Study Group Rating Scale (IRLS) Sum Score to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

   The IRLS is a subject based scale that consists of 10 items to evaluate the severity of major RLS symptoms and the impact of the disease on subjects' functioning in daytime activities. Each of the 10 items is measured on a scale that ranges from 0 (not present) to 4 (severe). A sum score between 0 (no RLS symptoms present at all) and 40 (maximum severity in all symptoms) across all 10 items will be calculated. A negative value in Change from Baseline indicates an improvement from Baseline in IRLS.

3. Change From Baseline in Clinical Global Impressions (CGI) Item 1 Score [Visit 2 (Baseline); Visit 6 (End of Maintence Period)]

   The CGI Item 1 score measures the severity of illness on a scale that ranges from 0 (Not assessed) to 7 (Among the most extremely ill).

4. Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 1 to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

   The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 1 measures satisfaction with sleep during the last seven nights on an 11-point scale that ranges between 0 (completely satisfied) to 10 (completely dissatisfied). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.

5. Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 2 to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

   The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 2 measures the severity of RLS symptoms during the last 7 nights in the situation of falling asleep. This is measured on an 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.

6. Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 3 to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

   The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 3 measures the severity of RLS symptoms during the last seven nights on an 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.

7. Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 4 to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

   The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 4 measures the severity of RLS symptoms during the last seven days at rest on an 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.

8. Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 5 to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

   The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 5 measures the severity of RLS symptoms during the last seven days engaged in activities on an 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.

9. Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 6 to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

   The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 6 measures the severity of daytime tiredness/ sleepiness on an 11-point scale that ranges between 0 (not at all) to 10 (very severe). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.

10. Change From Baseline in the Periodic Limb Movement During Sleep Arousal Index (PLMSAI) to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

    The Periodic Limb Movement during Sleep Arousal Index (PLMSAI) reflects the influence of the PLM on subject's sleep. Arousal is defined as sudden change in the Electroencephalogram (EEG) activity and the index illustrates to what degree the PLMs contribute to arousal from sleep. A negative value in Change from Baseline indicates an improvement from Baseline.

11. Change From Baseline in Sleep Efficiency to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

    Sleep stages and time spent in each sleep stage are determined from Electroencephalogram (EEG) readings. Sleep stage data will be used to calculate sleep efficiency. Sleep efficiency will be presented as percentages. Sleep efficiency is the percentage of time in bed spent asleep. A postive value in Change from Baseline indicates an improvement from Baseline.

12. Change From Baseline in the Restless Legs-Quality of Life (RLS-QoL) Total Score to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

    The RLS-QoL is a disease-specific questionnaire to evaluate quality of life. It consists of 12 items. A total score will be calculated from all of the 12 items. The overall sum score can be from 0 (highest QoL) to 60 (lowest QoL). A negative value in Change from Baseline indicates an improvement from Baseline.

13. Change From Baseline in the Short-Form-36 (SF-36) Item Questionnaire Mental Component Summary (MCS) to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

    The SF-36 is a 36 item generic human research quality of life instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General Health (5 items), Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), Mental Health (5 items), and a further unscaled single item (question 2) for perceived stability or change in health (Health Transition) during the last year. The norm based scores (based on the US general population) were used for analysis. For the MCS, the lowest and highest possible scores are -9 and 82 (rounded). The SF-36 domains (subscores) are scored so that a higher score indicates a better health state.

14. Change From Baseline in the Short-Form-36 (SF-36) Item Questionnaire Physical Component Summary (PCS) to the End of the Maintenance Period [From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period]

    The SF-36 is a 36 item generic human research quality of life instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General Health (5 items), Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), Mental Health (5 items), and a further unscaled single item (question 2) for perceived stability or change in health (Health Transition) during the last year. The norm-based scores (based on the US general population) were used for analysis. For the PCS, the lowest and highest possible scores are 1 and 81 (rounded). The SF-36 domains (subscores) are scored so that a higher score indicates a better health state.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• End-Stage Renal Disease (ESRD) requiring hemodialysis and regular dialysis schedule

• Fulfillment of pre-defined criteria of hematology parameters

• Diagnosis of Restless Legs (RLS) based on the 4 cardinal diagnostic clinical features according to the International Restless Legs Syndrome Study Group

• Initial response to previous dopaminergic treatment for RLS, or has had no previous dopaminergic treatment (ie, de novo)

• Score of ≥ 15 points on the IRLS (indicating moderate to severe RLS) at Baseline

• Score of ≥ 11 points on the RLS-DI (Diagnostic Index) at Baseline

• Score of ≥ 4 points on the Clinical Global Impressions (CGI) Item 1 assessment (indicating moderately ill) at Baseline

• Scores ≥ 15 Periodic Limb Movements (PLMs) per hour on the Periodic Limb Movement Index (PLMI) based on Polysomnography (PSG) (recorded during the second night) as assessed by the investigator at Baseline

Exclusion Criteria:

• Clinically relevant Polyneuropathy or Varicosis which cannot be clearly differentiated from RLS symptoms in the opinion of the investigator

• Clinically relevant concomitant diseases, such as Attention Deficit Hyperactivity Disorder, Painful Legs, and Moving Toes

• Other central nervous system diseases

• Evidence of an impulse control disorder according to the modified Minnesota Impulsive Disorders Interview (mMIDI)

• 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 Columbia-Suicidality Severity Rating Scale (C-SSRS) at Screening (Visit 1) or Baseline (Visit 2)

• Prior history of psychotic episodes

• History of symptomatic (not asymptomatic) Orthostatic Hypotension

• Clinically relevant Cardiovascular Disease

• Clinically relevant Venous or Arterial Peripheral Vascular Disease

• Malignant Neoplastic Disease requiring therapy within 12 months prior to Screening (Visit 1)

• Treatment with any of the following drug classes: neuroleptics, norepinephrine and dopamine reuptake inhibitors (bupropion), gabapentin, budipine, dopamine antagonist antiemetics (except domperidone), opioids, monoamine oxidase (MAO) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, or psychostimulants (eg, amphetamines)

• Subject is pregnant, nursing, or is a woman of childbearing potential who is not surgically sterile, 2 years postmenopausal, or does not consistently use 2 combined effective methods of contraception (including at least 1 barrier method), unless sexually abstinent

• Previous treatment with dopamine agonists within a period of 14 days prior to Baseline (Visit 2), or L-dopa within 7 days prior to Baseline (Visit 2)

• Medical history indicating intolerability to dopaminergic therapy (if pretreated) or has experienced Augmentation (Garcia-Borreguero and Williams, 2010) when previously treated with any dopaminergic agent

• Subject has received previous treatment with Rotigotine

• Known hypersensitivity to any of the components of the study medication, such as a history of significant Skin Hypersensitivity to adhesives, known Hypersensitivity to other transdermal medications, or unresolved Contact Dermatitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	606	Brandon	Florida	United States
2	604	Newton	Massachusetts	United States
3	603	West Seneca	New York	United States
4	607	Dublin	Ohio	United States
5	605	West Chester	Pennsylvania	United States
6	601	Austin	Texas	United States
7	101	Innsbruck		Austria
8	201	Helsinki		Finland
9	203	Tampere		Finland
10	302	Bordeaux Cedex		France
11	301	Montpellier Cédex 5		France
12	404	Berlin		Germany
13	401	Marburg		Germany
14	402	Schwerin		Germany
15	502	Pisa		Italy

Sponsors and Collaborators

• UCB BIOSCIENCES GmbH

Investigators

• Study Director: UCB Clinical Trial Call Center, [phone] (UCB)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: UCB BIOSCIENCES GmbH
• ClinicalTrials.gov Identifier: NCT01537042
• Other Study ID Numbers: SP0934; 2011-003486-15
• First Posted: Feb 22, 2012
• Last Update Posted: Nov 2, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by UCB BIOSCIENCES GmbH: Rotigotine; Neupro; Restless Legs Syndrome; RLS; End-Stage Renal Disease
• Additional relevant MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Kidney Diseases; Kidney Failure, Chronic; Syndrome; Rotigotine

Study Results

Participant Flow

Recruitment Details	The recruitment for the SP0934 study began in April 2012. It concluded in October 2013. This was a multicenter study with subjects enrolled by 9 sites across Europe and 6 sites across the United States.
Pre-assignment Detail	The participant flow consists of the Randomized Set (RS), which is all subjects randomized into SP0934.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance. Up to 3 weeks of Titration, 2 weeks of Maintenance, Up to 4 days of Taper Period.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h. Subjects start with a Rotigotine dose of 1 mg/24 h for 1 week. The dose can be increased weekly during Up-Titration Period until either the optimal or the maximal dose of 3 mg/24 h has been reached. Subjects will maintain the optimal/maximal dose during the 2-week Maintenance Period. Following the Maintenance Period, subjects will be de-escalated from their optimal dose by decreasing the dose by 1 mg/24 h every other day during Taper Period until complete withdrawal.
Period Title: Overall Study
STARTED	10	20
COMPLETED	10	15
NOT COMPLETED	0	5

Baseline Characteristics

Arm/Group Title	Placebo	Rotigotine	Total
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.	Total of all reporting groups
Overall Participants	10	20	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.7 (16.3)	57.2 (12.6)	55.0 (14.0)
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 80%	15 75%	23 76.7%
>=65 years	2 20%	5 25%	7 23.3%
Sex: Female, Male (Count of Participants)
Female	3 30%	7 35%	10 33.3%
Male	7 70%	13 65%	20 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 20%	6 30%	8 26.7%
White	4 40%	13 65%	17 56.7%
More than one race	1 10%	0 0%	1 3.3%
Unknown or Not Reported	3 30%	1 5%	4 13.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 20%	3 15%	5 16.7%
Not Hispanic or Latino	5 50%	16 80%	21 70%
Unknown or Not Reported	3 30%	1 5%	4 13.3%
Region of Enrollment (participants) [Number]
United States	6 60%	12 60%	18 60%
Europe	4 40%	8 40%	12 40%
Weight (Kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms]	85.38 (20.99)	89.42 (15.34)	88.07 (17.17)
Height (Centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Centimeters]	171.77 (8.59)	171.50 (11.99)	171.59 (10.82)
BMI (kg/ m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/ m^2]	28.850 (6.182)	30.405 (4.262)	29.887 (4.931)

Outcome Measures

1. Primary Outcome

Title	Ratio From Baseline to the End of the 2-week Maintenance Period in Periodic Limb Movement Index (PLMI)
Description	The PLMI is defined as Periodic Limb Movements (PLMs)/ total time in bed in hours. PLMs are measured by Polysomnography (PSG). The reduction of the PLMI is reflected in terms of the ratio from Baseline to the end of the Maintenance Period and was calculated as [PLMI at end of Maintenance Period (MP)] / [PLMI at Baseline]. A PLMI Ratio <1 indicates an improvement from Baseline to the end of the 2-week MP.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15
Least Squares Mean (95% Confidence Interval) [ratio]	1.16	0.51

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rotigotine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0232
	Comments
	Method	ANCOVA
	Comments	An analysis of covariance (ANCOVA) was performed for the log-transformed PLMI ratio with treatment and region as factors and Baseline as a covariate.
Method of Estimation	Estimation Parameter	Treatment Ratio
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95%; 0.22 to 0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in the Periodic Limb Movements Index (PLMI) to the End of the Maintenance Period
Description	The PLMI is defined as Periodic Limb Movements (PLMs)/ total time in bed in hours. PLMs are measured by Polysomnography (PSG). A negative value in change from Baseline indicates an improvement from Baseline to the end of the Maintenance Period.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15
Mean (Standard Deviation) [movement/ hour]	10.3 (21)	-23.7 (38.7)

3. Secondary Outcome

Title	Change From Baseline in the International Restless Legs Syndrome Study Group Rating Scale (IRLS) Sum Score to the End of the Maintenance Period
Description	The IRLS is a subject based scale that consists of 10 items to evaluate the severity of major RLS symptoms and the impact of the disease on subjects' functioning in daytime activities. Each of the 10 items is measured on a scale that ranges from 0 (not present) to 4 (severe). A sum score between 0 (no RLS symptoms present at all) and 40 (maximum severity in all symptoms) across all 10 items will be calculated. A negative value in Change from Baseline indicates an improvement from Baseline in IRLS.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15
Mean (Standard Deviation) [units on a scale]	-8.6 (7.2)	-15.9 (9.1)

4. Secondary Outcome

Title	Change From Baseline in Clinical Global Impressions (CGI) Item 1 Score
Description	The CGI Item 1 score measures the severity of illness on a scale that ranges from 0 (Not assessed) to 7 (Among the most extremely ill).
Time Frame	Visit 2 (Baseline); Visit 6 (End of Maintence Period)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo (Visit 2)	Rotigotine (Visit 2)	Placebo (Visit 6)	Rotigotine (Visit 6)
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15	10	15
Not assessed	0 0%	0 0%	0 0%	0 NaN
Normal, not ill at all	0 0%	0 0%	1 3.3%	5 NaN
Borderline ill	0 0%	0 0%	1 3.3%	4 NaN
Mildly ill	0 0%	0 0%	3 10%	3 NaN
Moderately ill	3 30%	3 15%	5 16.7%	1 NaN
Markedly ill	5 50%	9 45%	0 0%	2 NaN
Severely ill	2 20%	2 10%	0 0%	0 NaN
Among the most extremely ill subjects	0 0%	1 5%	0 0%	0 NaN

5. Secondary Outcome

Title	Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 1 to the End of the Maintenance Period
Description	The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 1 measures satisfaction with sleep during the last seven nights on an 11-point scale that ranges between 0 (completely satisfied) to 10 (completely dissatisfied). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15
Mean (Standard Deviation) [units on a scale]	-1.1 (3.5)	-2.8 (3.2)

6. Secondary Outcome

Title	Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 2 to the End of the Maintenance Period
Description	The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 2 measures the severity of RLS symptoms during the last 7 nights in the situation of falling asleep. This is measured on an 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15
Mean (Standard Deviation) [units on a scale]	-2.8 (2.9)	-4.4 (2.9)

7. Secondary Outcome

Title	Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 3 to the End of the Maintenance Period
Description	The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 3 measures the severity of RLS symptoms during the last seven nights on an 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15
Mean (Standard Deviation) [units on a scale]	-3.2 (2.6)	-4.7 (3.1)

8. Secondary Outcome

Title	Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 4 to the End of the Maintenance Period
Description	The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 4 measures the severity of RLS symptoms during the last seven days at rest on an 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15
Mean (Standard Deviation) [units on a scale]	-1.6 (3.2)	-2.6 (2.2)

9. Secondary Outcome

Title	Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 5 to the End of the Maintenance Period
Description	The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 5 measures the severity of RLS symptoms during the last seven days engaged in activities on an 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15
Mean (Standard Deviation) [units on a scale]	-1.6 (2.1)	-1.6 (2.7)

10. Secondary Outcome

Title	Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 6 to the End of the Maintenance Period
Description	The RLS-6 consists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness. Scale 6 measures the severity of daytime tiredness/ sleepiness on an 11-point scale that ranges between 0 (not at all) to 10 (very severe). The ratings are given by the subjects. A negative value in Change from Baseline indicates an improvement from Baseline.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15
Mean (Standard Deviation) [units on a scale]	-1.6 (2.0)	-3.4 (2.3)

11. Secondary Outcome

Title	Change From Baseline in the Periodic Limb Movement During Sleep Arousal Index (PLMSAI) to the End of the Maintenance Period
Description	The Periodic Limb Movement during Sleep Arousal Index (PLMSAI) reflects the influence of the PLM on subject's sleep. Arousal is defined as sudden change in the Electroencephalogram (EEG) activity and the index illustrates to what degree the PLMs contribute to arousal from sleep. A negative value in Change from Baseline indicates an improvement from Baseline.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15
Mean (Standard Deviation) [movement per hour]	4.634 (7.162)	-1.609 (14.412)

12. Secondary Outcome

Title	Change From Baseline in Sleep Efficiency to the End of the Maintenance Period
Description	Sleep stages and time spent in each sleep stage are determined from Electroencephalogram (EEG) readings. Sleep stage data will be used to calculate sleep efficiency. Sleep efficiency will be presented as percentages. Sleep efficiency is the percentage of time in bed spent asleep. A postive value in Change from Baseline indicates an improvement from Baseline.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	10	15
Mean (Standard Deviation) [sleep time/ total time in bed]	-2.850 (10.347)	7.668 (12.317)

13. Secondary Outcome

Title	Change From Baseline in the Restless Legs-Quality of Life (RLS-QoL) Total Score to the End of the Maintenance Period
Description	The RLS-QoL is a disease-specific questionnaire to evaluate quality of life. It consists of 12 items. A total score will be calculated from all of the 12 items. The overall sum score can be from 0 (highest QoL) to 60 (lowest QoL). A negative value in Change from Baseline indicates an improvement from Baseline.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	9	15
Mean (Standard Deviation) [scores on a scale]	-10.2 (10.8)	-10.7 (10.9)

14. Secondary Outcome

Title	Change From Baseline in the Short-Form-36 (SF-36) Item Questionnaire Mental Component Summary (MCS) to the End of the Maintenance Period
Description	The SF-36 is a 36 item generic human research quality of life instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General Health (5 items), Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), Mental Health (5 items), and a further unscaled single item (question 2) for perceived stability or change in health (Health Transition) during the last year. The norm based scores (based on the US general population) were used for analysis. For the MCS, the lowest and highest possible scores are -9 and 82 (rounded). The SF-36 domains (subscores) are scored so that a higher score indicates a better health state.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	9	14
Mean (Standard Deviation) [units on a scale]	6.4 (6.6)	2.2 (10.1)

15. Secondary Outcome

Title	Change From Baseline in the Short-Form-36 (SF-36) Item Questionnaire Physical Component Summary (PCS) to the End of the Maintenance Period
Description	The SF-36 is a 36 item generic human research quality of life instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General Health (5 items), Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), Mental Health (5 items), and a further unscaled single item (question 2) for perceived stability or change in health (Health Transition) during the last year. The norm-based scores (based on the US general population) were used for analysis. For the PCS, the lowest and highest possible scores are 1 and 81 (rounded). The SF-36 domains (subscores) are scored so that a higher score indicates a better health state.
Time Frame	From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), which included all randomized subjects with at least 1 patch applied during the Treatment Period, and had evaluable PSG data at Baseline and at the end of the 2-week Maintenance Period.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Measure Participants	9	14
Mean (Standard Deviation) [units on a scale]	-0.3 (8.7)	3.8 (6.3)

Adverse Events

Time Frame	Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013.
Adverse Event Reporting Description	Adverse Events reporting refers to the Safety Set (SS). All subjects who are randomized and have at least 1 patch applied during the Treatment Period were included in the SS.
Arm/Group Title	Placebo		Rotigotine
Arm/Group Description	Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.		Rotigotine Transdermal Patch 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
All Cause Mortality
	Placebo		Rotigotine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Rotigotine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		3/20 (15%)
Gastrointestinal disorders
Abdominal pain	0/10 (0%)	0	1/20 (5%)	2
General disorders
Chest pain	0/10 (0%)	0	1/20 (5%)	1
Infections and infestations
Gastrointestinal infection	1/10 (10%)	1	0/20 (0%)	0
Injury, poisoning and procedural complications
Foot fracture	0/10 (0%)	0	1/20 (5%)	1
Psychiatric disorders
Anxiety	0/10 (0%)	0	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/10 (0%)	0	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Rotigotine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/10 (40%)		12/20 (60%)
Eye disorders
Eye haemorrhage	0/10 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders
Diarrhoea	2/10 (20%)	2	1/20 (5%)	1
Constipation	0/10 (0%)	0	1/20 (5%)	1
Gastrooesophageal reflux disease	0/10 (0%)	0	1/20 (5%)	1
Nausea	0/10 (0%)	0	4/20 (20%)	5
Vomiting	0/10 (0%)	0	3/20 (15%)	3
General disorders
Application site pruritus	0/10 (0%)	0	1/20 (5%)	1
Fatigue	1/10 (10%)	1	0/20 (0%)	0
Oedema peripheral	1/10 (10%)	1	0/20 (0%)	0
Injury, poisoning and procedural complications
Dialysis device complication	0/10 (0%)	0	1/20 (5%)	1
Back injury	0/10 (0%)	0	1/20 (5%)	1
Investigations
Electrocardiogram PR prolongation	0/10 (0%)	0	1/20 (5%)	1
Electrocardiogram ST segment abnormal	0/10 (0%)	0	1/20 (5%)	1
Metabolism and nutrition disorders
Anorexia	0/10 (0%)	0	1/20 (5%)	1
Diabetic ketoacidosis	0/10 (0%)	0	1/20 (5%)	2
Hyperglycaemia	0/10 (0%)	0	1/20 (5%)	2
Fluid overload	0/10 (0%)	0	1/20 (5%)	3
Musculoskeletal and connective tissue disorders
Muscle spasms	0/10 (0%)	0	1/20 (5%)	1
Pain in extremity	0/10 (0%)	0	1/20 (5%)	1
Nervous system disorders
Somnolence	0/10 (0%)	0	1/20 (5%)	1
Headache	0/10 (0%)	0	2/20 (10%)	3
Paraesthesia	0/10 (0%)	0	1/20 (5%)	1
Psychiatric disorders
Confusional state	0/10 (0%)	0	1/20 (5%)	1
Depression	0/10 (0%)	0	1/20 (5%)	1
Dysphoria	0/10 (0%)	0	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/10 (0%)	0	2/20 (10%)	2
Sleep apnoea syndrome	0/10 (0%)	0	1/20 (5%)	1
Vascular disorders
Hypertension	0/10 (0%)	0	2/20 (10%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

UCB has > 60 but <= 180 days to review results communications prior to public release and may delete information that is confidential and compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that the results shall be published regardless of outcome.