Study to Evaluate the Efficacy of Rotigotine on Parkinson's Disease-Associated Pain (DOLORES)

• ClinicalTrials.gov Identifier: NCT01744496
• Recruitment Status: Completed
• First Posted: December 6, 2012
• Results First Posted: December 2, 2014
• Last Update Posted: May 1, 2015
• Sponsor: UCB BIOSCIENCES GmbH
• Information provided by (Responsible Party): UCB Pharma ( UCB BIOSCIENCES GmbH )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Advanced Idiopathic Parkinson's Disease
• Interventions: Drug: Rotigotine; Drug: Placebo
• Enrollment: 68

Participant Flow

Recruitment Details	The study was conducted in Europe and USA. Recruitment was planned to continue until approximately 64 patients were randomized in the study. Subjects were randomized in a 1:1 ratio to either Rotigotine or Placebo. To achieve this, approximately 28 investigational sites were planned to participate in this hypothesis-generating pilot study.
Pre-assignment Details	The Participant Flow population refers to the Randomized Set (RS). The RS includes all subjects who were randomized.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description	Placebo Transdermal Patches Placebo: Placebo patches matched the size of active patches 20 cm^2, 30 cm^2, or 40 cm^2 and contained Placebo. Application of Placebo patches started at the Baseline Visit. Placebo patches were administered once daily starting with the equivalent of 4 mg / 24 h. Doses were then up-titrated in weekly equivalents to 2 mg / 24 h until either optimal dose or maximum dose was reached. The maximum dose was the equivalent to 16 mg / 24 h. The duration of the Titration Period varied from 1 to 7 weeks. The Maintenance Period lasted 12 weeks ± 5 days. During the De-Escalation Period, the dose of Placebo will be decreased by the equivalent to 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.	Rotigotine Transdermal Patches Rotigotine: Patches contained 4 mg / 24 h (20 cm^2), 6 mg/ 24 h (30 cm^2), or 8 mg /24 h (40 cm^2) of Rotigotine. Application of study medication started at the Baseline Visit. Rotigotine was administered once daily starting at 4 mg / 24 h. Doses were then up-titrated in weekly increments of 2 mg / 24 h until optimal or maximum dose (16 mg / 24 h) was reached and the Maintenance Period could be started. The duration of the Titration Period varied from 1 to 7 weeks ± 3 days. The Maintenance Period lasted 12 weeks ± 5 days. Thereafter, during the De-Escalation Period, the dose of study medication was decreased by 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.
Period Title: Titration Period
Started	33	35
Completed	31	33
Not Completed	2	2
Reason Not Completed
Adverse Event	2	1
Personal reasons	0	1
Period Title: Maintenance Period
Started	31	33
Completed	27	29
Not Completed	4	4
Reason Not Completed
Adverse Event	1	3
Protocol Violation	1	0
Withdrawal by Subject	1	1
Subject left town	1	0

Baseline Characteristics

Arm/Group Title		Placebo	Rotigotine	Total
Arm/Group Description		Placebo Transdermal Patches Placebo: Placebo patches matched the size of active patches 20 cm^2, 30 cm^2, or 40 cm^2 and contained Placebo. Application of Placebo patches started at the Baseline Visit. Placebo patches were administered once daily starting with the equivalent of 4 mg / 24 h. Doses were then up-titrated in weekly equivalents to 2 mg / 24 h until either optimal dose or maximum dose was reached. The maximum dose was the equivalent to 16 mg / 24 h. The duration of the Titration Period varied from 1 to 7 weeks. The Maintenance Period lasted 12 weeks ± 5 days. During the De-Escalation Period, the dose of Placebo was decreased by the equivalent to 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.	Rotigotine Transdermal Patches Rotigotine: Patches contained 4 mg / 24 h (20 cm^2), 6 mg/ 24 h (30 cm^2), or 8 mg /24 h (40 cm^2) of Rotigotine. Application of study medication started at the Baseline Visit. Rotigotine was administered once daily starting at 4 mg / 24 h. Doses were then up-titrated in weekly increments of 2 mg / 24 h until optimal or maximum dose (16 mg / 24 h) was reached and the Maintenance Period could be started. The duration of the Titration Period varied from 1 to 7 weeks ± 3 days. The Maintenance Period lasted 12 weeks ± 5 days. Thereafter, during the De-Escalation Period, the dose of study medication was decreased by 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.	Total of all reporting groups
Overall Number of Baseline Participants		33	35	68
Baseline Analysis Population Description		The Baseline Analysis Population refers to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants	35 participants	68 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	15 45.5%	12 34.3%	27 39.7%
	>=65 years	18 54.5%	23 65.7%	41 60.3%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	33 participants	35 participants	68 participants
		65.3 (13.8)	66.5 (11.9)	65.9 (12.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants	35 participants	68 participants
	Female	16 48.5%	16 45.7%	32 47.1%
	Male	17 51.5%	19 54.3%	36 52.9%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	33 participants	35 participants	68 participants
American Indian / Alaskan native		0	0	0
Asian		1	0	1
Black		0	0	0
Native Hawaiian or other Pacific Islander		0	0	0
White		32	35	67
Other / mixed		0	0	0
Weight; Mean (Standard Deviation); Unit of measure: Kilograms
	Number Analyzed	33 participants	35 participants	68 participants
		80.15 (20.00)	77.80 (13.71)	78.94 (16.97)
Height; Mean (Standard Deviation); Unit of measure: Centimeters
	Number Analyzed	33 participants	35 participants	68 participants
		167.17 (9.92)	168.63 (9.87)	167.92 (9.85)
Body Mass Index (BMI); Mean (Standard Deviation); Unit of measure: Kilogram per squaremeter
	Number Analyzed	33 participants	35 participants	68 participants
		28.54 (6.21)	27.42 (4.74)	27.96 (5.49)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to the End of the Maintenance Period in Pain Severity Assessed Using an 11-point Likert Pain Scale
Description	An 11-Point Likert Scale was used to assess patients' average daily pain. The subject rated his/her average pain from 0 (no pain) to 10 (worst pain ever experienced). The average pain experienced in the last 7 days was calculated by the mean of the daily Likert Pain Scores within the 7 days prior to the respective visit (ie, Likert Pain Scores with a date of assessment before the date of visit and on or after the date of visit - 7 days). A negative value indicates an improvement.
Time Frame	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after an up to 7 weeks Titration Period)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and includes all subjects who were randomized, received at least 1 dose of study medication, and had a valid primary efficacy Baseline measurement and at least 1 valid post-Baseline Maintenance or valid Withdrawal primary efficacy measurement.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description:	Placebo Transdermal Patches Placebo: Placebo patches matched the size of active patches 20 cm^2, 30 cm^2, or 40 cm^2 and contained Placebo. Application of Placebo patches started at the Baseline Visit. Placebo patches were administered once daily starting with the equivalent of 4 mg / 24 h. Doses were then up-titrated in weekly equivalents to 2 mg / 24 h until either optimal dose or maximum dose was reached. The maximum dose was the equivalent to 16 mg / 24 h. The duration of the Titration Period varied from 1 to 7 weeks. The Maintenance Period lasted 12 weeks ± 5 days. During the De-Escalation Period, the dose of Placebo was decreased by the equivalent to 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.	Rotigotine Transdermal Patches Rotigotine: Patches contained 4 mg / 24 h (20 cm^2), 6 mg/ 24 h (30 cm^2), or 8 mg /24 h (40 cm^2) of Rotigotine. Application of study medication started at the Baseline Visit. Rotigotine was administered once daily starting at 4 mg / 24 h. Doses were then up-titrated in weekly increments of 2 mg / 24 h until optimal or maximum dose (16 mg / 24 h) was reached and the Maintenance Period could be started. The duration of the Titration Period varied from 1 to 7 weeks ± 3 days. The Maintenance Period lasted 12 weeks ± 5 days. Thereafter, during the De-Escalation Period, the dose of study medication was decreased by 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.
Overall Number of Participants Analyzed	30	30
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-2.2 (2.78)	-2.8 (1.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rotigotine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.172
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	ANCOVA model for the change from Baseline to the End of Treatment containing treatment and region as factors and Baseline value as a covariate.
Method of Estimation	Estimation Parameter	Least Square Mean
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95%; -1.87 to 0.34
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.55
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Responders at the End of the Maintenance Period
Description	Responders are defined as patients experiencing a 2-Point or more Reduction on an 11-Point Likert Pain Scale from Baseline to the End of the Maintenance Period. An 11-Point Likert Scale was used to assess patients' average daily pain. The patient rated his/her average pain from 0 (no pain) to 10 (worst pain ever experienced).
Time Frame	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and includes all subjects who were randomized, received at least 1 dose of study medication, and had a valid primary efficacy Baseline measurement and at least 1 valid post-Baseline Maintenance or valid Withdrawal primary efficacy measurement.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description:	Placebo Transdermal Patches Placebo: Placebo patches matched the size of active patches 20 cm^2, 30 cm^2, or 40 cm^2 and contained Placebo. Application of Placebo patches started at the Baseline Visit. Placebo patches were administered once daily starting with the equivalent of 4 mg / 24 h. Doses were then up-titrated in weekly equivalents to 2 mg / 24 h until either optimal dose or maximum dose was reached. The maximum dose was the equivalent to 16 mg / 24 h. The duration of the Titration Period varied from 1 to 7 weeks. The Maintenance Period lasted 12 weeks ± 5 days. During the De-Escalation Period, the dose of Placebo was decreased by the equivalent to 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.	Rotigotine Transdermal Patches Rotigotine: Patches contained 4 mg / 24 h (20 cm^2), 6 mg/ 24 h (30 cm^2), or 8 mg /24 h (40 cm^2) of Rotigotine. Application of study medication started at the Baseline Visit. Rotigotine was administered once daily starting at 4 mg / 24 h. Doses were then up-titrated in weekly increments of 2 mg / 24 h until optimal or maximum dose (16 mg / 24 h) was reached and the Maintenance Period could be started. The duration of the Titration Period varied from 1 to 7 weeks ± 3 days. The Maintenance Period lasted 12 weeks ± 5 days. Thereafter, during the De-Escalation Period, the dose of study medication was decreased by 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.
Overall Number of Participants Analyzed	30	30
Measure Type: Number; Unit of Measure: percentage of responders
	46.7	60

3. Secondary Outcome

Title	Change From Baseline to the End of the Maintenance Period in the Sum Score of the 8-Item Parkinson's Disease Questionnaire (PDQ-8)
Description	The 8-Item Parkinson's Disease Questionnaire (PDQ-8) (Peto et al, 1998) is a self-administered questionnaire that provides a reliable measure of overall health status. The PDQ-8 contains 8 items of daily living, with 1 item selected from each of the following 8 scales: mobility, Activities of Daily Living (ADL), emotional well being, stigma, social support, cognitions, communication, and bodily discomfort. The total PDQ-8 score is the sum of all the individual items converted to a summary index score between 0 and 100, with lower scores indicating better health. A negative value indicates an improvement.
Time Frame	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and includes all subjects who were randomized, received at least 1 dose of study medication, and had a valid primary efficacy Baseline measurement and at least 1 valid post-Baseline Maintenance or valid Withdrawal primary efficacy measurement.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description:	Placebo Transdermal Patches Placebo: Placebo patches matched the size of active patches 20 cm^2, 30 cm^2, or 40 cm^2 and contained Placebo. Application of Placebo patches started at the Baseline Visit. Placebo patches were administered once daily starting with the equivalent of 4 mg / 24 h. Doses were then up-titrated in weekly equivalents to 2 mg / 24 h until either optimal dose or maximum dose was reached. The maximum dose was the equivalent to 16 mg / 24 h. The duration of the Titration Period varied from 1 to 7 weeks. The Maintenance Period lasted 12 weeks ± 5 days. During the De-Escalation Period, the dose of Placebo was decreased by the equivalent to 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.	Rotigotine Transdermal Patches Rotigotine: Patches contained 4 mg / 24 h (20 cm^2), 6 mg/ 24 h (30 cm^2), or 8 mg /24 h (40 cm^2) of Rotigotine. Application of study medication started at the Baseline Visit. Rotigotine was administered once daily starting at 4 mg / 24 h. Doses were then up-titrated in weekly increments of 2 mg / 24 h until optimal or maximum dose (16 mg / 24 h) was reached and the Maintenance Period could be started. The duration of the Titration Period varied from 1 to 7 weeks ± 3 days. The Maintenance Period lasted 12 weeks ± 5 days. Thereafter, during the De-Escalation Period, the dose of study medication was decreased by 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.
Overall Number of Participants Analyzed	29	30
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-3.77 (13.93)	-12.40 (19.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rotigotine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.038
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	ANCOVA model for the change from Baseline to the End of Treatment containing treatment and region as factors and Baseline value as a covariate.
Method of Estimation	Estimation Parameter	Least Square Mean
	Estimated Value	-8.01
	Confidence Interval	(2-Sided) 95%; -15.56 to -0.46
	Parameter Dispersion	Type: Standard Error of the mean; Value: 3.77
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change From Baseline to the End of the Maintenance Period in the 7-Item Depression Subscore of the Hospital Anxiety and Depression Scale (HADS)
Description	The Hospital Anxiety and Depression Scale (HADS) (Zigmond and Snaith, 1983) is a 14-item self-assessment scale for detecting states of depression and anxiety in the setting of a hospital medical outpatient clinic. It comprises a 7-item anxiety subscale and a 7-item depressive subscale that are also measures of severity of the emotional disorder. The 14 items are scored between 0 and 3. The 7-item depression subscore and 7-item anxiety subscore were calculated as the sum of the 7 corresponding individual scores. A negative value indicates an improvement.
Time Frame	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and includes all subjects who were randomized, received at least 1 dose of study medication, and had a valid primary efficacy Baseline measurement and at least 1 valid post-Baseline Maintenance or valid Withdrawal primary efficacy measurement.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description:	Placebo Transdermal Patches Placebo: Placebo patches matched the size of active patches 20 cm^2, 30 cm^2, or 40 cm^2 and contained Placebo. Application of Placebo patches started at the Baseline Visit. Placebo patches were administered once daily starting with the equivalent of 4 mg / 24 h. Doses were then up-titrated in weekly equivalents to 2 mg / 24 h until either optimal dose or maximum dose was reached. The maximum dose was the equivalent to 16 mg / 24 h. The duration of the Titration Period varied from 1 to 7 weeks. The Maintenance Period lasted 12 weeks ± 5 days. During the De-Escalation Period, the dose of Placebo was decreased by the equivalent to 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.	Rotigotine Transdermal Patches Rotigotine: Patches contained 4 mg / 24 h (20 cm^2), 6 mg/ 24 h (30 cm^2), or 8 mg /24 h (40 cm^2) of Rotigotine. Application of study medication started at the Baseline Visit. Rotigotine was administered once daily starting at 4 mg / 24 h. Doses were then up-titrated in weekly increments of 2 mg / 24 h until optimal or maximum dose (16 mg / 24 h) was reached and the Maintenance Period could be started. The duration of the Titration Period varied from 1 to 7 weeks ± 3 days. The Maintenance Period lasted 12 weeks ± 5 days. Thereafter, during the De-Escalation Period, the dose of study medication was decreased by 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.
Overall Number of Participants Analyzed	28	28
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-1.7 (4.3)	-1.9 (4.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rotigotine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.247
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	ANCOVA model for the change from Baseline to the End of Treatment containing treatment and region as factors and Baseline value as a covariate.
Method of Estimation	Estimation Parameter	Least Square Mean
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95%; -2.76 to 0.73
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.87
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change From Baseline to the End of the Maintenance Period in the 7-Item Anxiety Subscore of the Hospital Anxiety and Depression Scale (HADS)
Description	The Hospital Anxiety and Depression Scale (HADS) (Zigmond and Snaith, 1983) is a 14-item self-assessment scale for detecting states of depression and anxiety in the setting of a hospital medical outpatient clinic. It comprises a 7-item anxiety subscale and a 7-item depressive subscale that are also measures of severity of the emotional disorder. The 14 items are scored between 0 and 3. The 7-item depression subscore and 7-item anxiety subscore were calculated as the sum of the 7 corresponding individual scores. A negative value indicates an improvement.
Time Frame	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and includes all subjects who were randomized, received at least 1 dose of study medication, and had a valid primary efficacy Baseline measurement and at least 1 valid post-Baseline Maintenance or valid Withdrawal primary efficacy measurement.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description:	Placebo Transdermal Patches Placebo: Placebo patches matched the size of active patches 20 cm^2, 30 cm^2, or 40 cm^2 and contained Placebo. Application of Placebo patches started at the Baseline Visit. Placebo patches were administered once daily starting with the equivalent of 4 mg / 24 h. Doses were then up-titrated in weekly equivalents to 2 mg / 24 h until either optimal dose or maximum dose was reached. The maximum dose was the equivalent to 16 mg / 24 h. The duration of the Titration Period varied from 1 to 7 weeks. The Maintenance Period lasted 12 weeks ± 5 days. During the De-Escalation Period, the dose of Placebo was decreased by the equivalent to 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.	Rotigotine Transdermal Patches Rotigotine: Patches contained 4 mg / 24 h (20 cm^2), 6 mg/ 24 h (30 cm^2), or 8 mg /24 h (40 cm^2) of Rotigotine. Application of study medication started at the Baseline Visit. Rotigotine was administered once daily starting at 4 mg / 24 h. Doses were then up-titrated in weekly increments of 2 mg / 24 h until optimal or maximum dose (16 mg / 24 h) was reached and the Maintenance Period could be started. The duration of the Titration Period varied from 1 to 7 weeks ± 3 days. The Maintenance Period lasted 12 weeks ± 5 days. Thereafter, during the De-Escalation Period, the dose of study medication was decreased by 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.
Overall Number of Participants Analyzed	28	28
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-1.0 (3.2)	-1.8 (3.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rotigotine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.371
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	ANCOVA model for the change from Baseline to the End of Treatment containing treatment and region as factors and Baseline value as a covariate.
Method of Estimation	Estimation Parameter	Least Square Mean
	Estimated Value	-0.58
	Confidence Interval	(2-Sided) 95%; -1.85 to 0.70
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.64
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Change From Baseline to the End of the Maintenance Period in the Combined Score of the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II (Activities of Daily Living [ADL] Subscale) and III (Motor Subscale)
Description	Part II of the Unified Parkinson's Disease Rating Scale (UPDRS) assesses the subject's activities of daily living. Part III assesses motor function. The UPDRS is completed by questioning the subject about his/her general state in conjunction with any observations made by the investigator (or designee) since the previous visit. Part II is subject-rated and Part III is physician-rated. The UPDRS Part II (Activities of Daily Living) consists of 13 items scored between 0 and 4. The sum score was calculated as the sum of these 13 individual scores. The UPDRS Part III (motor subscale) consists of 27 items and sub items scored between 0 and 4. The sum score was calculated as sum of these 27 individual scores. The sum score of UPDRS Parts II and III is the sum of the corresponding single sum scores. A negative value indicates an improvement.
Time Frame	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and includes all subjects who were randomized, received at least 1 dose of study medication, and had a valid primary efficacy Baseline measurement and at least 1 valid post-Baseline Maintenance or valid Withdrawal primary efficacy measurement.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description:	Placebo Transdermal Patches Placebo: Placebo patches matched the size of active patches 20 cm^2, 30 cm^2, or 40 cm^2 and contained Placebo. Application of Placebo patches started at the Baseline Visit. Placebo patches were administered once daily starting with the equivalent of 4 mg / 24 h. Doses were then up-titrated in weekly equivalents to 2 mg / 24 h until either optimal dose or maximum dose was reached. The maximum dose was the equivalent to 16 mg / 24 h. The duration of the Titration Period varied from 1 to 7 weeks. The Maintenance Period lasted 12 weeks ± 5 days. During the De-Escalation Period, the dose of Placebo was decreased by the equivalent to 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.	Rotigotine Transdermal Patches Rotigotine: Patches contained 4 mg / 24 h (20 cm^2), 6 mg/ 24 h (30 cm^2), or 8 mg /24 h (40 cm^2) of Rotigotine. Application of study medication started at the Baseline Visit. Rotigotine was administered once daily starting at 4 mg / 24 h. Doses were then up-titrated in weekly increments of 2 mg / 24 h until optimal or maximum dose (16 mg / 24 h) was reached and the Maintenance Period could be started. The duration of the Titration Period varied from 1 to 7 weeks ± 3 days. The Maintenance Period lasted 12 weeks ± 5 days. Thereafter, during the De-Escalation Period, the dose of study medication was decreased by 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.
Overall Number of Participants Analyzed	29	30
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-5.1 (11.7)	-8.3 (11.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rotigotine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.346
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	ANCOVA model for the change from Baseline to the End of Treatment containing treatment and region as factors and Baseline value as a covariate.
Method of Estimation	Estimation Parameter	Least Square Mean
	Estimated Value	-2.82
	Confidence Interval	(2-Sided) 95%; -8.76 to 3.13
	Parameter Dispersion	Type: Standard Error of the mean; Value: 2.97
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Change From Baseline to the End of the Maintenance Period in the 7 Domain Scores of Classification of Pain in Parkinson's Disease
Description	The classification of pain in Parkinson's disease scale classifies pain in the following domains: musculoskeletal pain (item 1), chronic pain (items 2 and 3), fluctuation related pain (items 4, 5 and 6), nocturnal pain (items 7 and 8), oro-facial pain (items 9, 10 and 11), discoloration; edema/swelling (items 12 and 13), and radicular pain (item 14). Severity of the pain is measured on a scale from none (0) to severe (3) and frequency is measured on a scale from never (0) to very frequent (4). A score of a single item was calculated by multiplying severity with frequency. A domain score was calculated as the sum of every individual score related to the respective domain. A negative value indicates an improvement.
Time Frame	Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and includes all subjects who were randomized, received at least 1 dose of study medication, and had a valid primary efficacy Baseline measurement and at least 1 valid post-Baseline Maintenance or valid Withdrawal primary efficacy measurement.

Arm/Group Title	Placebo	Rotigotine
Arm/Group Description:	Placebo Transdermal Patches Placebo: Placebo patches matched the size of active patches 20 cm^2, 30 cm^2, or 40 cm^2 and contained Placebo. Application of Placebo patches started at the Baseline Visit. Placebo patches were administered once daily starting with the equivalent of 4 mg / 24 h. Doses were then up-titrated in weekly equivalents to 2 mg / 24 h until either optimal dose or maximum dose was reached. The maximum dose was the equivalent to 16 mg / 24 h. The duration of the Titration Period varied from 1 to 7 weeks. The Maintenance Period lasted 12 weeks ± 5 days. During the De-Escalation Period, the dose of Placebo was decreased by the equivalent to 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.	Rotigotine Transdermal Patches Rotigotine: Patches contained 4 mg / 24 h (20 cm^2), 6 mg/ 24 h (30 cm^2), or 8 mg /24 h (40 cm^2) of Rotigotine. Application of study medication started at the Baseline Visit. Rotigotine was administered once daily starting at 4 mg / 24 h. Doses were then up-titrated in weekly increments of 2 mg / 24 h until optimal or maximum dose (16 mg / 24 h) was reached and the Maintenance Period could be started. The duration of the Titration Period varied from 1 to 7 weeks ± 3 days. The Maintenance Period lasted 12 weeks ± 5 days. Thereafter, during the De-Escalation Period, the dose of study medication was decreased by 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.
Overall Number of Participants Analyzed	29	30
Mean (Standard Deviation); Unit of Measure: scores on a scale
Musculoskeletal Pain	-1.4 (3.6)	-1.5 (4.2)
Chronic Pain	-3.1 (5.6)	-0.7 (2.9)
Fluctuation-Related Pain	-2.2 (4.6)	-4.2 (6.8)
Nocturnal Pain	-2.9 (6.1)	-2.4 (5.3)
Oro-Facial Pain	-0.4 (2.5)	-0.6 (2.3)
Discoloration; Edema/Swelling	-1.8 (4.9)	-1.7 (3.4)
Radicular Pain	-1.3 (3.8)	-1.1 (3.7)

Adverse Events

Time Frame	Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks).
Adverse Event Reporting Description	Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Arm/Group Title	Placebo		Rotigotine
Arm/Group Description	Placebo Transdermal Patches Placebo: Placebo patches matched the size of active patches 20 cm^2, 30 cm^2, or 40 cm^2 and contained Placebo. Application of Placebo patches started at the Baseline Visit. Placebo patches were administered once daily starting with the equivalent of 4 mg / 24 h. Doses were then up-titrated in weekly equivalents to 2 mg / 24 h until either optimal dose or maximum dose was reached. The maximum dose was the equivalent to 16 mg / 24 h. The duration of the Titration Period varied from 1 to 7 weeks. The Maintenance Period lasted 12 weeks ± 5 days. During the De-Escalation Period, the dose of Placebo was decreased by the equivalent to 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.		Rotigotine Transdermal Patches Rotigotine: Patches contained 4 mg / 24 h (20 cm^2), 6 mg/ 24 h (30 cm^2), or 8 mg /24 h (40 cm^2) of Rotigotine. Application of study medication started at the Baseline Visit. Rotigotine was administered once daily starting at 4 mg / 24 h. Doses were then up-titrated in weekly increments of 2 mg / 24 h until optimal or maximum dose (16 mg / 24 h) was reached and the Maintenance Period could be started. The duration of the Titration Period varied from 1 to 7 weeks ± 3 days. The Maintenance Period lasted 12 weeks ± 5 days. Thereafter, during the De-Escalation Period, the dose of study medication was decreased by 2 mg / 24 h every other day. The De-Escalation Period might have lasted up to 12 days.
All-Cause Mortality
	Placebo		Rotigotine
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Placebo		Rotigotine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/33 (3.03%)		2/35 (5.71%)
General disorders
Oedema peripheral * 1	0/33 (0.00%)	0	1/35 (2.86%)	1
Injury, poisoning and procedural complications
Hip fracture * 1	1/33 (3.03%)	1	0/35 (0.00%)	0
Nervous system disorders
Cerebrovascular accident * 1	0/33 (0.00%)	0	1/35 (2.86%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDra 16.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Rotigotine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/33 (51.52%)		20/35 (57.14%)
Gastrointestinal disorders
Diarrhoea * 1	2/33 (6.06%)	2	0/35 (0.00%)	0
Nausea * 1	2/33 (6.06%)	3	8/35 (22.86%)	11
General disorders
Application site erythema * 1	0/33 (0.00%)	0	3/35 (8.57%)	3
Fatigue * 1	1/33 (3.03%)	1	2/35 (5.71%)	2
Infections and infestations
Upper respiratory tract infection * 1	2/33 (6.06%)	2	1/35 (2.86%)	1
Urinary tract infection * 1	0/33 (0.00%)	0	2/35 (5.71%)	2
Injury, poisoning and procedural complications
Fall * 1	0/33 (0.00%)	0	2/35 (5.71%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma * 1	2/33 (6.06%)	2	1/35 (2.86%)	1
Nervous system disorders
Dyskinesia * 1	2/33 (6.06%)	2	2/35 (5.71%)	2
Hyperkinesia * 1	2/33 (6.06%)	2	0/35 (0.00%)	0
Headache * 1	4/33 (12.12%)	11	6/35 (17.14%)	7
Dizziness * 1	3/33 (9.09%)	3	3/35 (8.57%)	3
Psychiatric disorders
Insomnia * 1	1/33 (3.03%)	1	3/35 (8.57%)	3
Skin and subcutaneous tissue disorders
Rash * 1	2/33 (6.06%)	2	2/35 (5.71%)	2
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDra 16.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: UCB Clinical Trial Call Center
• Organization: UCB
• Phone: +1 877 822 9493

• Responsible Party: UCB Pharma ( UCB BIOSCIENCES GmbH )
• ClinicalTrials.gov Identifier: NCT01744496
• Other Study ID Numbers: PD0004; 2012-002608-42 ( EudraCT Number )
• First Submitted: December 5, 2012
• First Posted: December 6, 2012
• Results First Submitted: November 24, 2014
• Results First Posted: December 2, 2014
• Last Update Posted: May 1, 2015