Trial Outcomes & Findings for 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 (NCT NCT01537042)

Last Updated: 2014-11-03

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

30 participants

Primary outcome timeframe

From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Results posted on

2014-11-03

Participant Flow

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.

The participant flow consists of the Randomized Set (RS), which is all subjects randomized into SP0934.

Participant milestones

Participant milestones
Measure	Placebo 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 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.
Overall Study STARTED	10	20
Overall Study COMPLETED	10	15
Overall Study NOT COMPLETED	0	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 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 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.
Overall Study Adverse Event	0	2
Overall Study Lack of Efficacy	0	1
Overall Study Protocol Violation	0	1
Overall Study Other	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=20 Participants 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 n=30 Participants Total of all reporting groups
Age, Continuous	50.7 years STANDARD_DEVIATION 16.3 • n=5 Participants	57.2 years STANDARD_DEVIATION 12.6 • n=7 Participants	55.0 years STANDARD_DEVIATION 14.0 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	15 Participants n=7 Participants	23 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	13 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	16 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	12 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Europe	4 participants n=5 Participants	8 participants n=7 Participants	12 participants n=5 Participants
Weight	85.38 Kilograms STANDARD_DEVIATION 20.99 • n=5 Participants	89.42 Kilograms STANDARD_DEVIATION 15.34 • n=7 Participants	88.07 Kilograms STANDARD_DEVIATION 17.17 • n=5 Participants
Height	171.77 Centimeters STANDARD_DEVIATION 8.59 • n=5 Participants	171.50 Centimeters STANDARD_DEVIATION 11.99 • n=7 Participants	171.59 Centimeters STANDARD_DEVIATION 10.82 • n=5 Participants
BMI	28.850 kg/ m^2 STANDARD_DEVIATION 6.182 • n=5 Participants	30.405 kg/ m^2 STANDARD_DEVIATION 4.262 • n=7 Participants	29.887 kg/ m^2 STANDARD_DEVIATION 4.931 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Ratio From Baseline to the End of the 2-week Maintenance Period in Periodic Limb Movement Index (PLMI)	1.16 ratio Interval 0.68 to 1.99	0.51 ratio Interval 0.33 to 0.8	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the Periodic Limb Movements Index (PLMI) to the End of the Maintenance Period	10.3 movement/ hour Standard Deviation 21	-23.7 movement/ hour Standard Deviation 38.7	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the International Restless Legs Syndrome Study Group Rating Scale (IRLS) Sum Score to the End of the Maintenance Period	-8.6 units on a scale Standard Deviation 7.2	-15.9 units on a scale Standard Deviation 9.1	—	—

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) n=15 Participants 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.
Change From Baseline in Clinical Global Impressions (CGI) Item 1 Score Not assessed	0 participants	0 participants	0 participants	0 participants
Change From Baseline in Clinical Global Impressions (CGI) Item 1 Score Normal, not ill at all	0 participants	0 participants	1 participants	5 participants
Change From Baseline in Clinical Global Impressions (CGI) Item 1 Score Borderline ill	0 participants	0 participants	1 participants	4 participants
Change From Baseline in Clinical Global Impressions (CGI) Item 1 Score Mildly ill	0 participants	0 participants	3 participants	3 participants
Change From Baseline in Clinical Global Impressions (CGI) Item 1 Score Moderately ill	3 participants	3 participants	5 participants	1 participants
Change From Baseline in Clinical Global Impressions (CGI) Item 1 Score Markedly ill	5 participants	9 participants	0 participants	2 participants
Change From Baseline in Clinical Global Impressions (CGI) Item 1 Score Severely ill	2 participants	2 participants	0 participants	0 participants
Change From Baseline in Clinical Global Impressions (CGI) Item 1 Score Among the most extremely ill subjects	0 participants	1 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 1 to the End of the Maintenance Period	-1.1 units on a scale Standard Deviation 3.5	-2.8 units on a scale Standard Deviation 3.2	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 2 to the End of the Maintenance Period	-2.8 units on a scale Standard Deviation 2.9	-4.4 units on a scale Standard Deviation 2.9	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 3 to the End of the Maintenance Period	-3.2 units on a scale Standard Deviation 2.6	-4.7 units on a scale Standard Deviation 3.1	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 4 to the End of the Maintenance Period	-1.6 units on a scale Standard Deviation 3.2	-2.6 units on a scale Standard Deviation 2.2	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 5 to the End of the Maintenance Period	-1.6 units on a scale Standard Deviation 2.1	-1.6 units on a scale Standard Deviation 2.7	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the Restless Legs-6 (RLS-6) Rating Scale 6 to the End of the Maintenance Period	-1.6 units on a scale Standard Deviation 2.0	-3.4 units on a scale Standard Deviation 2.3	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the Periodic Limb Movement During Sleep Arousal Index (PLMSAI) to the End of the Maintenance Period	4.634 movement per hour Standard Deviation 7.162	-1.609 movement per hour Standard Deviation 14.412	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in Sleep Efficiency to the End of the Maintenance Period	-2.850 sleep time/ total time in bed Standard Deviation 10.347	7.668 sleep time/ total time in bed Standard Deviation 12.317	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=15 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the Restless Legs-Quality of Life (RLS-QoL) Total Score to the End of the Maintenance Period	-10.2 scores on a scale Standard Deviation 10.8	-10.7 scores on a scale Standard Deviation 10.9	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=14 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the Short-Form-36 (SF-36) Item Questionnaire Mental Component Summary (MCS) to the End of the Maintenance Period	6.4 units on a scale Standard Deviation 6.6	2.2 units on a scale Standard Deviation 10.1	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=14 Participants 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.	Placebo (Visit 6) Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine (Visit 6) 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.
Change From Baseline in the Short-Form-36 (SF-36) Item Questionnaire Physical Component Summary (PCS) to the End of the Maintenance Period	-0.3 units on a scale Standard Deviation 8.7	3.8 units on a scale Standard Deviation 6.3	—	—

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Rotigotine

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=10 participants at risk Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=20 participants at risk 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.
Gastrointestinal disorders Abdominal pain	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 2 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
General disorders Chest pain	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Infections and infestations Gastrointestinal infection	10.0% 1/10 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	0.00% 0/20 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Psychiatric disorders Anxiety	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.

Other adverse events

Additional Information

Study Director

UCB Clinical Trial Call Center

Phone: +1 887 822 9493

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=10 participants at risk Transdermal patch matched according to patch size and appearance. Placebo: Transdermal patch; Patches matching to active treatment patches in size and appearance.	Rotigotine n=20 participants at risk 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.
Eye disorders Eye haemorrhage	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Gastrointestinal disorders Diarrhoea	20.0% 2/10 • Number of events 2 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Gastrointestinal disorders Constipation	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Gastrointestinal disorders Nausea	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	20.0% 4/20 • Number of events 5 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Gastrointestinal disorders Vomiting	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	15.0% 3/20 • Number of events 3 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
General disorders Application site pruritus	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
General disorders Fatigue	10.0% 1/10 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	0.00% 0/20 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
General disorders Oedema peripheral	10.0% 1/10 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	0.00% 0/20 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Injury, poisoning and procedural complications Dialysis device complication	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Injury, poisoning and procedural complications Back injury	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Investigations Electrocardiogram PR prolongation	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Investigations Electrocardiogram ST segment abnormal	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Metabolism and nutrition disorders Anorexia	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 2 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 2 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Metabolism and nutrition disorders Fluid overload	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 3 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Nervous system disorders Somnolence	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Nervous system disorders Headache	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	10.0% 2/20 • Number of events 3 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Nervous system disorders Paraesthesia	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Psychiatric disorders Confusional state	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Psychiatric disorders Depression	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Psychiatric disorders Dysphoria	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	10.0% 2/20 • Number of events 2 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	5.0% 1/20 • Number of events 1 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.
Vascular disorders Hypertension	0.00% 0/10 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.	10.0% 2/20 • Number of events 2 • Adverse Events were recorded during the course of the SP0934 study, which began in April 2012 and concluded in October 2013. 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.