Trial Outcomes & Findings for Effects of Neupro on Cardiovascular Observations in Patients With Restless Legs Syndrome (NCT NCT01455012)

NCT ID: NCT01455012

Last Updated: 2013-07-26

Results Overview

Polysomnography (PSG) recordings, including the assessment of continuous Blood Pressure and 12-lead Electrocardiogram (ECG), were obtained on 2 consecutive nights prior to Baseline Visit and prior to End of Maintenance Period (Visit 7) for up to 8 hours per night. Readings from the first night of the PSG were only used for analysis if the PSG from the second night was determined to be not valid for evaluation. Influence of Periodic Limb Movements (PLMs) on sleep is reflected in the Periodic Limb Movement-Related Arousal Index (PLMAI). Arousal is defined as sudden change in the EEG activity and the index illustrates to what degree the PLMs contribute to arousal from sleep. Sleep stages and time spent in each sleep stage were determined from Electroencephalogram (EEG) readings. A negative value in Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 81 participants
• Primary outcome timeframe: Baseline to the end of the 4-week Maintenance Period
• Results posted on: 2013-07-26

Participant Flow

This study started to enroll subjects in September 2011 in order to end up with 9 German centers with enrolled subjects.

Participant Flow refers to the Randomized Set (RS). RS consists of all subjects randomized into this study.

Participant milestones

Measure	Placebo Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Rotigotine Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Overall Study STARTED	41	40
Overall Study COMPLETED	30	36
Overall Study NOT COMPLETED	11	4

Reasons for withdrawal

Measure	Placebo Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Rotigotine Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Overall Study Adverse Event	0	2
Overall Study Lack of Efficacy	6	1
Overall Study Withdrawal by Subject	3	1
Overall Study Unknown reason	2	0

Baseline Characteristics

Effects of Neupro on Cardiovascular Observations in Patients With Restless Legs Syndrome

Baseline characteristics by cohort

Measure	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Total n=66 Participants Total of all reporting groups
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	23 Participants n=5 Participants	26 Participants n=7 Participants	49 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	11 Participants n=7 Participants	17 Participants n=5 Participants
Age Continuous	56.0 years STANDARD_DEVIATION 9.6 • n=5 Participants	57.9 years STANDARD_DEVIATION 10.2 • n=7 Participants	57.0 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	22 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment Germany	29 participants n=5 Participants	37 participants n=7 Participants	66 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

Polysomnography (PSG) recordings, including the assessment of continuous Blood Pressure and 12-lead Electrocardiogram (ECG), were obtained on 2 consecutive nights prior to Baseline Visit and prior to End of Maintenance Period (Visit 7) for up to 8 hours per night. Readings from the first night of the PSG were only used for analysis if the PSG from the second night was determined to be not valid for evaluation. Influence of Periodic Limb Movements (PLMs) on sleep is reflected in the Periodic Limb Movement-Related Arousal Index (PLMAI). Arousal is defined as sudden change in the EEG activity and the index illustrates to what degree the PLMs contribute to arousal from sleep. Sleep stages and time spent in each sleep stage were determined from Electroencephalogram (EEG) readings.

A negative value in Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Change From Baseline in the Number of Elevations of Systolic Blood Pressure (BP) During the Night That Are Associated With Periodic Limb Movements (PLMs) at the End of the 4-week Maintenance Period	-239.95 Nocturnal Elevations of Systolic BP 95% Confidence Interval 237.1 • Interval -275.34 to -204.56	-79.61 Nocturnal Elevations of Systolic BP 95% Confidence Interval 189.3 • Interval -119.25 to -39.97

SECONDARY outcome

Timeframe: Baseline to the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

Polysomnography (PSG) recordings, including the assessment of continuous Blood Pressure and 12-lead Electrocardiogram (ECG), were obtained on 2 consecutive nights prior to Baseline Visit and prior to End of Maintenance Period (Visit 7) for up to 8 hours per night. Readings from the first night of the PSG were only used for analysis if the PSG from the second night was determined to be not valid for evaluation. Influence of Periodic Limb Movements (PLMs) on sleep is reflected in the Periodic Limb Movement-Related Arousal Index (PLMAI). Arousal is defined as sudden change in the EEG activity and the index illustrates to what degree the PLMs contribute to arousal from sleep. Sleep stages and time spent in each sleep stage were determined from Electroencephalogram (EEG) readings.

A negative value in Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Change From Baseline in the Total Number of Elevations of Systolic Blood Pressure (BP) During the Night at the End of the 4-week Maintenance Period	-199.8 Nocturnal Elevations of Systolic BP Standard Deviation 262.8	-34.3 Nocturnal Elevations of Systolic BP Standard Deviation 243.4

SECONDARY outcome

Timeframe: Baseline to the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

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 PLMI Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Change From Baseline in the Periodic Limb Movements Index (PLMI) at the End of the 4-week Maintenance Period	-50.1 Periodic Limb Movements/hour Standard Deviation 44.5	-15.2 Periodic Limb Movements/hour Standard Deviation 50.3

SECONDARY outcome

Timeframe: Baseline to the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

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' daytime functioning. 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 was calculated. A negative value in IRLS Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Change From Baseline in the International Restless Legs Syndrome Rating Scale (IRLS) at the End of the 4-week Maintenance Period	-18.5 units on a scale Standard Deviation 8.0	-12.5 units on a scale Standard Deviation 9.0

SECONDARY outcome

Timeframe: Baseline to the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

The RLS-QoL is a disease-specific instrument for the evaluation of Quality of life. It consists of 12 items and the overall sum score is calculated from all 12 items and measured on a scale that ranges from 0 (lowest Quality of life) to 60 (highest level of Quality of life). A negative value in RLS-QoL Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Change From Baseline in Restless Legs Syndrome-Quality of Life (RLS-QoL) at the End of the 4-week Maintenance Period	-17.8 units on a scale Standard Deviation 13.2	-11.0 units on a scale Standard Deviation 11.9

SECONDARY outcome

Timeframe: At the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

The CGI Item 2 score measures any change in severity of RLS from Baseline on a 7-point scale consisting of the following categories:

• 1- Very much improved
• 2- Much improved
• 3- Minimally improved
• 4- No change
• 5- Minimally worse
• 6- Much worse
• 7- Very much worse

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Clinical Global Impressions (CGI) Item 2 (Change of Condition) at the End of the 4-week Maintenance Period No change	1 participants	6 participants
Clinical Global Impressions (CGI) Item 2 (Change of Condition) at the End of the 4-week Maintenance Period Minimally worse	0 participants	1 participants
Clinical Global Impressions (CGI) Item 2 (Change of Condition) at the End of the 4-week Maintenance Period Much improved	7 participants	9 participants
Clinical Global Impressions (CGI) Item 2 (Change of Condition) at the End of the 4-week Maintenance Period Much worse	0 participants	0 participants
Clinical Global Impressions (CGI) Item 2 (Change of Condition) at the End of the 4-week Maintenance Period Very much worse	0 participants	0 participants
Clinical Global Impressions (CGI) Item 2 (Change of Condition) at the End of the 4-week Maintenance Period Very much improved	26 participants	9 participants
Clinical Global Impressions (CGI) Item 2 (Change of Condition) at the End of the 4-week Maintenance Period Minimally improved	3 participants	4 participants

SECONDARY outcome

Timeframe: At the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

The CGI Item 1 score measures the severity of illness on a 7-point scale consisting of the following categories:

• 1- Normal, not ill at all
• 2- Borderline ill
• 3- Mildly ill
• 4- Moderately ill
• 5- Markedly ill
• 6- Severely ill
• 7- Among the most extremely ill subjects

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Clinical Global Impressions (CGI) Item 1 (Severity of Illness) at the End of the 4-week Maintenance Period Normal, not ill at all	6 participants	2 participants
Clinical Global Impressions (CGI) Item 1 (Severity of Illness) at the End of the 4-week Maintenance Period Borderline ill	18 participants	8 participants
Clinical Global Impressions (CGI) Item 1 (Severity of Illness) at the End of the 4-week Maintenance Period Mildly ill	9 participants	7 participants
Clinical Global Impressions (CGI) Item 1 (Severity of Illness) at the End of the 4-week Maintenance Period Moderately ill	2 participants	8 participants
Clinical Global Impressions (CGI) Item 1 (Severity of Illness) at the End of the 4-week Maintenance Period Markedly ill	2 participants	3 participants
Clinical Global Impressions (CGI) Item 1 (Severity of Illness) at the End of the 4-week Maintenance Period Severely ill	0 participants	1 participants
Clinical Global Impressions (CGI) Item 1 (Severity of Illness) at the End of the 4-week Maintenance Period Among the most extremely ill subjects	0 participants	0 participants

SECONDARY outcome

Timeframe: At the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

The CGI Item 3 score measures the therapeutic efficacy on a 4-point scale consisting of the following categories:

• 1- Very good
• 2- Moderate
• 3- Slight
• 4- Unchanged or worse

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Clinical Global Impressions (CGI) Item 3 (Therapeutic Efficacy) at the End of the 4-week Maintenance Period Very good	31 participants	11 participants
Clinical Global Impressions (CGI) Item 3 (Therapeutic Efficacy) at the End of the 4-week Maintenance Period Moderate	4 participants	10 participants
Clinical Global Impressions (CGI) Item 3 (Therapeutic Efficacy) at the End of the 4-week Maintenance Period Slight	1 participants	3 participants
Clinical Global Impressions (CGI) Item 3 (Therapeutic Efficacy) at the End of the 4-week Maintenance Period Unchanged or worse	1 participants	5 participants

SECONDARY outcome

Timeframe: Baseline to the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

The RLS-6 consists of 6 items of which four items are designed to assess severity of RLS and two items cover sleep and daytime tiredness. Item 1 measures subject's satisfaction with sleep on a 11-point scale that ranges between 0 (completely satisfied) to 10 (completely dissatisfied). The ratings are given by the subjects. A negative value in RLS-6 Item 6 Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 1 at the End of the 4-week Maintenance Period	-4.1 units on a scale Standard Deviation 3.3	-3.4 units on a scale Standard Deviation 3.1

SECONDARY outcome

Timeframe: Baseline to the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

The RLS-6 consists of 6 items of which four items are designed to assess severity of RLS and two items cover sleep and daytime tiredness. Item 2 measures the severity of RLS at time falling asleep on a 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in RLS-6 Item 2 Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 2 at the End of the 4-week Maintenance Period	-4.6 units on a scale Standard Deviation 3.8	-3.9 units on a scale Standard Deviation 3.3

SECONDARY outcome

Timeframe: Baseline to the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

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

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 3 at the End of the 4-week Maintenance Period	-4.9 units on a scale Standard Deviation 3.3	-3.7 units on a scale Standard Deviation 3.5

SECONDARY outcome

Timeframe: Baseline to the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

The RLS-6 consists of 6 items of which four items are designed to assess severity of RLS and two items cover sleep and daytime tiredness. Item 4 measures the severity of RLS during day rest on a 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in RLS-6 Item 4 Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 4 at the End of the 4-week Maintenance Period	-2.9 units on a scale Standard Deviation 2.9	-2.7 units on a scale Standard Deviation 3.4

SECONDARY outcome

Timeframe: Baseline to the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

The RLS-6 consists of 6 items of which four items are designed to assess severity of RLS and two items cover sleep and daytime tiredness. Item 5 measures the severity of RLS during day not rest on a 11-point scale that ranges between 0 (none) to 10 (very severe). The ratings are given by the subjects. A negative value in RLS-6 Item 5 Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 5 at the End of the 4-week Maintenance Period	-1.3 units on a scale Standard Deviation 2.6	-1.3 units on a scale Standard Deviation 1.9

SECONDARY outcome

Timeframe: Baseline to the end of the 4-week Maintenance Period

Population: Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.

The RLS-6 consists of 6 items of which four items are designed to assess severity of RLS and two items cover sleep and daytime tiredness. Item 6 measures subject's tiredness or sleepiness during the day on a 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 RLS-6 Item 6 Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

Outcome measures

Measure	Rotigotine n=37 Participants Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Placebo n=29 Participants Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Change From Baseline in Restless Legs Syndrome-6 Rating Scales (RLS-6) Item 6 at the End of the 4-week Maintenance Period	-3.5 units on a scale Standard Deviation 2.8	-2.5 units on a scale Standard Deviation 2.8

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Rotigotine

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=40 participants at risk Placebo Placebo : Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.	Rotigotine n=40 participants at risk Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.
Gastrointestinal disorders Nausea	7.5% 3/40 • Number of events 3 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	22.5% 9/40 • Number of events 11 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
Gastrointestinal disorders Diarrhoea	7.5% 3/40 • Number of events 3 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	0.00% 0/40 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
General disorders Fatigue	15.0% 6/40 • Number of events 6 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	12.5% 5/40 • Number of events 5 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
General disorders Application site pruritus	0.00% 0/40 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	5.0% 2/40 • Number of events 2 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
Infections and infestations Nasopharyngitis	7.5% 3/40 • Number of events 5 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	17.5% 7/40 • Number of events 8 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
Infections and infestations Influenza	5.0% 2/40 • Number of events 2 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	0.00% 0/40 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	5.0% 2/40 • Number of events 2 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	2.5% 1/40 • Number of events 1 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
Nervous system disorders Headache	17.5% 7/40 • Number of events 8 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	17.5% 7/40 • Number of events 8 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
Nervous system disorders Somnolence	10.0% 4/40 • Number of events 4 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	10.0% 4/40 • Number of events 4 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
Nervous system disorders Dizziness	2.5% 1/40 • Number of events 1 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	10.0% 4/40 • Number of events 4 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
Psychiatric disorders Restlessness	0.00% 0/40 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	5.0% 2/40 • Number of events 2 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	2.5% 1/40 • Number of events 1 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	10.0% 4/40 • Number of events 4 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/40 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.	5.0% 2/40 • Number of events 2 • Adverse Events were collected up to 16 weeks from Screening Period to the Safety Follow-Up Visit. Adverse Events refer to the Safety Set consisting of all randomized subjects who received at least one dose of study medication.

Additional Information

UCB Clinical Trial Call Center

UCB

Phone: +1 877 822 9493 (UCB)

Results disclosure agreements

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

Restriction type: GT60