Trial Outcomes & Findings for Study to Evaluate the Efficacy of Rotigotine on Parkinson's Disease-Associated Pain (NCT NCT01744496)

NCT ID: NCT01744496

Last Updated: 2015-05-01

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 68 participants
• Primary outcome timeframe: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after an up to 7 weeks Titration Period)
• Results posted on: 2015-05-01

Participant Flow

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.

The Participant Flow population refers to the Randomized Set (RS). The RS includes all subjects who were randomized.

Participant milestones

Measure	Placebo 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 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.
Titration Period STARTED	33	35
Titration Period COMPLETED	31	33
Titration Period NOT COMPLETED	2	2
Maintenance Period STARTED	31	33
Maintenance Period COMPLETED	27	29
Maintenance Period NOT COMPLETED	4	4

Reasons for withdrawal

Measure	Placebo 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 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.
Titration Period Adverse Event	2	1
Titration Period Personal reasons	0	1
Maintenance Period Adverse Event	1	3
Maintenance Period Protocol Violation	1	0
Maintenance Period Withdrawal by Subject	1	1
Maintenance Period Subject left town	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=33 Participants 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 n=35 Participants 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 n=68 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	15 Participants n=5 Participants	12 Participants n=7 Participants	27 Participants n=5 Participants
Age, Categorical >=65 years	18 Participants n=5 Participants	23 Participants n=7 Participants	41 Participants n=5 Participants
Age, Continuous	65.3 years STANDARD_DEVIATION 13.8 • n=5 Participants	66.5 years STANDARD_DEVIATION 11.9 • n=7 Participants	65.9 years STANDARD_DEVIATION 12.8 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized American Indian / Alaskan native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Black	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized White	32 participants n=5 Participants	35 participants n=7 Participants	67 participants n=5 Participants
Race/Ethnicity, Customized Other / mixed	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Weight	80.15 kilograms STANDARD_DEVIATION 20.00 • n=5 Participants	77.80 kilograms STANDARD_DEVIATION 13.71 • n=7 Participants	78.94 kilograms STANDARD_DEVIATION 16.97 • n=5 Participants
Height	167.17 centimeters STANDARD_DEVIATION 9.92 • n=5 Participants	168.63 centimeters STANDARD_DEVIATION 9.87 • n=7 Participants	167.92 centimeters STANDARD_DEVIATION 9.85 • n=5 Participants
Body Mass Index (BMI)	28.54 kilogram per squaremeter STANDARD_DEVIATION 6.21 • n=5 Participants	27.42 kilogram per squaremeter STANDARD_DEVIATION 4.74 • n=7 Participants	27.96 kilogram per squaremeter STANDARD_DEVIATION 5.49 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after an up to 7 weeks Titration Period)

Population: 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.

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.

Outcome measures

Measure	Placebo n=30 Participants 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 n=30 Participants 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.
Change From Baseline to the End of the Maintenance Period in Pain Severity Assessed Using an 11-point Likert Pain Scale	-2.2 scores on a scale Standard Deviation 2.78	-2.8 scores on a scale Standard Deviation 1.84

SECONDARY outcome

Timeframe: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Population: 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.

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).

Outcome measures

Measure	Placebo n=30 Participants 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 n=30 Participants 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.
Percentage of Responders at the End of the Maintenance Period	46.7 percentage of responders	60 percentage of responders

SECONDARY outcome

Timeframe: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Population: 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.

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.

Outcome measures

Measure	Placebo n=29 Participants 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 n=30 Participants 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.
Change From Baseline to the End of the Maintenance Period in the Sum Score of the 8-Item Parkinson's Disease Questionnaire (PDQ-8)	-3.77 scores on a scale Standard Deviation 13.93	-12.40 scores on a scale Standard Deviation 19.25

SECONDARY outcome

Timeframe: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Population: 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.

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.

Outcome measures

Measure	Placebo n=28 Participants 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 n=28 Participants 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.
Change From Baseline to the End of the Maintenance Period in the 7-Item Depression Subscore of the Hospital Anxiety and Depression Scale (HADS)	-1.7 scores on a scale Standard Deviation 4.3	-1.9 scores on a scale Standard Deviation 4.1

SECONDARY outcome

Timeframe: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Population: 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.

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.

Outcome measures

Measure	Placebo n=28 Participants 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 n=28 Participants 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.
Change From Baseline to the End of the Maintenance Period in the 7-Item Anxiety Subscore of the Hospital Anxiety and Depression Scale (HADS)	-1.0 scores on a scale Standard Deviation 3.2	-1.8 scores on a scale Standard Deviation 3.7

SECONDARY outcome

Timeframe: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Population: 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.

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.

Outcome measures

Measure	Placebo n=29 Participants 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 n=30 Participants 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.
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)	-5.1 scores on a scale Standard Deviation 11.7	-8.3 scores on a scale Standard Deviation 11.2

SECONDARY outcome

Timeframe: Baseline (Visit 2) until End of the Maintenance Period (Maintenance Period lasts 12 weeks ± 5 days after up to 7 weeks Titration Period)

Population: 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.

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.

Outcome measures

Measure	Placebo n=29 Participants 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 n=30 Participants 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.
Change From Baseline to the End of the Maintenance Period in the 7 Domain Scores of Classification of Pain in Parkinson's Disease Nocturnal Pain	-2.9 scores on a scale Standard Deviation 6.1	-2.4 scores on a scale Standard Deviation 5.3
Change From Baseline to the End of the Maintenance Period in the 7 Domain Scores of Classification of Pain in Parkinson's Disease Musculoskeletal Pain	-1.4 scores on a scale Standard Deviation 3.6	-1.5 scores on a scale Standard Deviation 4.2
Change From Baseline to the End of the Maintenance Period in the 7 Domain Scores of Classification of Pain in Parkinson's Disease Chronic Pain	-3.1 scores on a scale Standard Deviation 5.6	-0.7 scores on a scale Standard Deviation 2.9
Change From Baseline to the End of the Maintenance Period in the 7 Domain Scores of Classification of Pain in Parkinson's Disease Fluctuation-Related Pain	-2.2 scores on a scale Standard Deviation 4.6	-4.2 scores on a scale Standard Deviation 6.8
Change From Baseline to the End of the Maintenance Period in the 7 Domain Scores of Classification of Pain in Parkinson's Disease Oro-Facial Pain	-0.4 scores on a scale Standard Deviation 2.5	-0.6 scores on a scale Standard Deviation 2.3
Change From Baseline to the End of the Maintenance Period in the 7 Domain Scores of Classification of Pain in Parkinson's Disease Discoloration; Edema/Swelling	-1.8 scores on a scale Standard Deviation 4.9	-1.7 scores on a scale Standard Deviation 3.4
Change From Baseline to the End of the Maintenance Period in the 7 Domain Scores of Classification of Pain in Parkinson's Disease Radicular Pain	-1.3 scores on a scale Standard Deviation 3.8	-1.1 scores on a scale Standard Deviation 3.7

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Rotigotine

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=33 participants at risk 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 n=35 participants at risk 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.
Injury, poisoning and procedural complications Hip fracture	3.0% 1/33 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	0.00% 0/35 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
General disorders Oedema peripheral	0.00% 0/33 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Nervous system disorders Cerebrovascular accident	0.00% 0/33 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.

Other adverse events

Measure	Placebo n=33 participants at risk 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 n=35 participants at risk 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.
Gastrointestinal disorders Diarrhoea	6.1% 2/33 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	0.00% 0/35 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Gastrointestinal disorders Nausea	6.1% 2/33 • Number of events 3 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	22.9% 8/35 • Number of events 11 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
General disorders Application site erythema	0.00% 0/33 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	8.6% 3/35 • Number of events 3 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
General disorders Fatigue	3.0% 1/33 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	5.7% 2/35 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Infections and infestations Upper respiratory tract infection	6.1% 2/33 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Infections and infestations Urinary tract infection	0.00% 0/33 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	5.7% 2/35 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Fall	0.00% 0/33 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	5.7% 2/35 • Number of events 3 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	6.1% 2/33 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Nervous system disorders Dyskinesia	6.1% 2/33 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	5.7% 2/35 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Nervous system disorders Hyperkinesia	6.1% 2/33 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	0.00% 0/35 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Nervous system disorders Headache	12.1% 4/33 • Number of events 11 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	17.1% 6/35 • Number of events 7 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Nervous system disorders Dizziness	9.1% 3/33 • Number of events 3 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	8.6% 3/35 • Number of events 3 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Psychiatric disorders Insomnia	3.0% 1/33 • Number of events 1 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	8.6% 3/35 • Number of events 3 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Rash	6.1% 2/33 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.	5.7% 2/35 • Number of events 2 • Treatment Emergent Adverse Events were reported from Baseline up to the Safety Follow-up Visit (approximately during 25 weeks). Adverse Events refer to the Safety Set (SS). The SS includes all randomized subjects who received at least 1 dose of study medication.

Additional Information

UCB Clinical Trial Call Center

UCB

Phone: +1 877 822 9493

Results disclosure agreements

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

Restriction type: GT60