Trial Outcomes & Findings for Rotigotine Versus Placebo, A Study To Evaluate The Efficacy In Advanced Stage Idiopathic Parkinson's Disease Patients (NCT NCT01646255)

NCT ID: NCT01646255

Last Updated: 2018-04-04

Results Overview

A subject has been considered "off" when he/she began to lose the optimum effects of anti-Parkinson's medication. A negative mean indicates a reduction of the time off during the conduct of the study

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 346 participants
• Primary outcome timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
• Results posted on: 2018-04-04

Participant Flow

This multicenter, randomized, double-blind, parallel-group, placebo-controlled study started recruiting in August 2012.

Participant Flow refers to the Safety Set (SS), consisting of all randomized subjects who received at least 1 dose of study medication.

Participant milestones

Measure	Placebo Subjects randomized to placebo received matching placebo patches.	Rotigotine Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Overall Study STARTED	172	174
Overall Study COMPLETED	151	160
Overall Study NOT COMPLETED	21	14

Reasons for withdrawal

Measure	Placebo Subjects randomized to placebo received matching placebo patches.	Rotigotine Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Overall Study Adverse Event	7	8
Overall Study Lack of Efficacy	2	0
Overall Study Withdrawal by Subject	10	6
Overall Study Compliance is not well	1	0
Overall Study Inclusion Criteria Deviation	1	0

Baseline Characteristics

Rotigotine Versus Placebo, A Study To Evaluate The Efficacy In Advanced Stage Idiopathic Parkinson's Disease Patients

Baseline characteristics by cohort

Measure	Placebo n=172 Participants Subjects randomized to placebo received matching placebo patches.	Rotigotine n=174 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.	Total Title n=346 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	96 Participants n=5 Participants	111 Participants n=7 Participants	207 Participants n=5 Participants
Age, Categorical >=65 years	76 Participants n=5 Participants	63 Participants n=7 Participants	139 Participants n=5 Participants
Age, Continuous mean (standard deviation)	62.8 years STANDARD_DEVIATION 9.1 • n=5 Participants	61.7 years STANDARD_DEVIATION 8.8 • n=7 Participants	62.2 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	81 Participants n=7 Participants	143 Participants n=5 Participants
Sex: Female, Male Male	110 Participants n=5 Participants	93 Participants n=7 Participants	203 Participants n=5 Participants
Weight	61.83 kg STANDARD_DEVIATION 10.18 • n=5 Participants	60.38 kg STANDARD_DEVIATION 10.15 • n=7 Participants	61.10 kg STANDARD_DEVIATION 10.18 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A subject has been considered "off" when he/she began to lose the optimum effects of anti-Parkinson's medication. A negative mean indicates a reduction of the time off during the conduct of the study

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Absolute Change in Absolute Time Spent 'Off' From Baseline to the End of Double-blind Maintenance Period	-1.13 hours Standard Deviation 3.20	-2.36 hours Standard Deviation 2.83

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A Responder is defined as a subject with an ≥ 30 % decrease in absolute time spent 'off'

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Percentage of Responders From Baseline to the End of the Doubleblind Maintenance Period	36.9 percentage of participants	48.8 percentage of participants

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A subject has been considered "off" when he/she began to lose the optimum effects of anti-Parkinson's medication.

Absolute time "off" is defined as the mean number of hours marked "off" during a 24-hour period from all valid daily diary cards.

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Percent Change in Absolute Time Spent "Off" From Baseline to the End of Double-blind Maintenance Period	-15.0 percent change Standard Deviation 56.56	-36.03 percent change Standard Deviation 43.03

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A subject has been considered "off" when he/she began to lose the optimum effects of anti-Parkinson's medication.

Relative time spent "off" will be calculated in two stages. Each valid daily diary will have an associated relative time "off" calculated as relative time "off" for day = 100*[total absolute time "off" for day/ absolute time awake for day]. Relative time spent "off" is then calculated by averaging the daily relative time "off" for the valid days of that visit.

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Percent Change in Relative Time Spent "Off" From Baseline to the End of Double-blind Maintenance Period	-14.86 percent change Standard Deviation 53.26	-34.97 percent change Standard Deviation 43.87

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A subject has been considered "on" when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'.

Absolute time "on" is defined as the mean number of hours marked "on" during a 24-hour period from all valid daily diary cards.

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Change in Absolute Time Spent "on" From Baseline to the End of Double-blind Maintenance Period	0.94 hours Standard Deviation 3.08	2.05 hours Standard Deviation 2.98

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A subject has been considered "on" when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was "off" when taking his/her L-dopa, he/she recorded the exact time their status changed to "on".

Relative time spent "on" will be calculated in two stages. Each valid daily diary will have an associated relative time "on" calculated as relative time "on" for day = 100*[total absolute time "on" for day/ absolute time awake for day]. Relative time spent "on" is then calculated by averaging the daily relative time "on" for the valid days of that visit.

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Change in Relative Time Spent "on" From Baseline to the End of Double-blind Maintenance Period	6.78 hours Standard Deviation 19.61	14.49 hours Standard Deviation 18.70

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A subject has been considered "on" when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'.

Note for percent change calculations: when absolute time at Baseline was 0 hours, the absolute Baseline value was assumed to be 1 minute for calculation purposes.

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Percent Change in Absolute Time Spent "on" From Baseline to the End of Double-blind Maintenance Period	13.53 percent change Standard Deviation 42.74	368.55 percent change Standard Deviation 4446.55

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A subject has been considered "on" when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was "off" when taking his/her L-dopa, he/she recorded the exact time their status changed to "on".

Note for percent change calculations: when relative time at Baseline was 0%, the relative Baseline value was assumed to be 0.1 for calculation purposes.

Relative time spent "on" will be calculated in two stages. Each valid daily diary will have an associated relative time "on" calculated as relative time "on" for day = 100*[total absolute time "on" for day/ absolute time awake for day]. Relative time spent "on" is then calculated by averaging the daily relative time "on" for the valid days of that visit.

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Percent Change in Relative Time Spent "on" From Baseline to the End of Double-blind Maintenance Period	14.99 percent change Standard Deviation 42.60	616.80 percent change Standard Deviation 7667.58

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A subject has been considered "off" when he/she began to lose the optimum effects of anti-Parkinson's medication.

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Change in the Number of "Off" Periods From Baseline to the End of Double-blind Maintenance Period	-0.61 Number of 'off' Periods Standard Deviation 1.59	-0.89 Number of 'off' Periods Standard Deviation 1.32

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A subject has been considered "on" when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'.

The percentage of days from Baseline to the end of the double-blind Maintenance Period in which the subject woke in the "on with troublesome dyskinesia" state is presented below.

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Change in Status of the Subject (on) After Wake-up With Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period	2.42 percentage of days Standard Deviation 21.70	1.24 percentage of days Standard Deviation 16.90

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A subject has been considered "on" when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'.

The percentage of days from Baseline to the end of the double-blind Maintenance Period in which the subject woke in the "on without troublesome dyskinesia" state is presented below.

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Change in Status of the Subject (on) After Wake-up Without Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period	7.92 percentage of days Standard Deviation 43.29	22.55 percentage of days Standard Deviation 45.41

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

A subject has been considered "off" when he/she began to lose the optimum effects of anti-Parkinson's medication.

The percentage of days from Baseline to the end of the double-blind Maintenance Period in which the subject woke in the "off" state is presented below.

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Change in Status of the Subject (Off) After Wake-up From Baseline to the End of Double-blind Maintenance Period	-10.34 percentage of days Standard Deviation 47.81	-21.14 percentage of days Standard Deviation 48.49

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

The UPDRS Part III (motor subscale) assessment consists of 27 questions, measured on a 5-Point scale (0 to 4). The sum score is calculated as sum of these 27 individual questions. This score ranges from 0 to 108, higher scores denote greater disability.

A subject has been considered "on" when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'.

Outcome measures

Measure	Full Analysis Set (Placebo Treated Subjects) n=168 Participants Subjects randomized to placebo received matching placebo patches.	Full Analysis Set (Rotigotine Treated Subjects) n=170 Participants Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week.
Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III Motor Examination) During "on" Periods From Baseline to the End of Double-blind Maintenance Period	-3.6 units on a scale Standard Deviation 9.8	-10.4 units on a scale Standard Deviation 10.4

Adverse Events

Placebo

Serious events: 6 serious events

Other events: 24 other events

Deaths: 0 deaths

Rotigotine

Serious events: 6 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=172 participants at risk Placebo, daily doses, placebo Group Subjects randomized to placebo will receive matching placebo patches.	Rotigotine n=174 participants at risk Rotigotine, daily doses, treatment Group Subjects will receive rotigotine or placebo patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo is achieved. A combination of patches (rotigotine or matching placebo) will be applied for subjects who require a dose \> 8 mg/ 24 h. Each dose level is maintained for 1 week.
Cardiac disorders Mitral valve prolapse	0.58% 1/172 • Number of events 1 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	0.00% 0/174 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Cardiac disorders Atrial fibrillation	0.58% 1/172 • Number of events 1 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	0.00% 0/174 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Intestinal obstruction	0.58% 1/172 • Number of events 1 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	0.00% 0/174 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Inguinal hernia	0.00% 0/172 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	0.57% 1/174 • Number of events 1 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/172 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	0.57% 1/174 • Number of events 1 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Infections and infestations Skin infection	0.00% 0/172 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	0.57% 1/174 • Number of events 1 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/172 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	0.57% 1/174 • Number of events 1 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Nervous system disorders Syncope	0.00% 0/172 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	1.1% 2/174 • Number of events 2 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Nervous system disorders Parkinson's disease	0.58% 1/172 • Number of events 1 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	0.00% 0/174 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Renal and urinary disorders Urinary retention	0.58% 1/172 • Number of events 1 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	0.00% 0/174 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Vascular disorders Vasculitis	0.58% 1/172 • Number of events 1 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	0.00% 0/174 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.

Other adverse events

Measure	Placebo n=172 participants at risk Placebo, daily doses, placebo Group Subjects randomized to placebo will receive matching placebo patches.	Rotigotine n=174 participants at risk Rotigotine, daily doses, treatment Group Subjects will receive rotigotine or placebo patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo is achieved. A combination of patches (rotigotine or matching placebo) will be applied for subjects who require a dose \> 8 mg/ 24 h. Each dose level is maintained for 1 week.
Gastrointestinal disorders Nausea	1.2% 2/172 • Number of events 2 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	9.2% 16/174 • Number of events 23 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Nervous system disorders Dyskinesia	4.1% 7/172 • Number of events 7 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	6.3% 11/174 • Number of events 13 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Nervous system disorders Dizziness	4.1% 7/172 • Number of events 8 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	10.9% 19/174 • Number of events 21 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	5.8% 10/172 • Number of events 11 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.	8.0% 14/174 • Number of events 15 • Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication.

Additional Information

Study Director

UCB

Phone: +1877 822

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