Rotigotine Versus Placebo, A Study To Evaluate The Effica... | NCT01646255

NCT01646255

Status Module

Sponsor/Collaborators Module

Name	Class
UCB Trading (Shanghai) Co. Ltd.	UNKNOWN

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Rotigotine	Experimental	Rotigotine, daily doses, treatment group	Drug: Rotigotine Drug: L-dopa
Placebo	Placebo Comparator	Placebo, daily doses, placebo group	Drug: Placebo Patch Drug: L-dopa

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Rotigotine	Drug	Transdermal Patch Content: 4 mg /24 h (20 cm^2), 6 mg /24 h (30 cm^2), 8 mg /24 h (40 cm^2) For advanced-stage Parkinson's Disease, subjects received Rotigotine patches in escalating weekly dose (starting with daily doses 4 mg/24 h to 16 mg/24 h) for a maximum 7-week Titration Period, then 12 week maintenance period

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Absolute Change in Absolute Time Spent 'Off' From Baseline to the End of Double-blind Maintenance Period	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	From Baseline (Week 0) to end of Maintenance Period (up to Week 12)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Responders From Baseline to the End of the Doubleblind Maintenance Period	A Responder is defined as a subject with an ≥ 30 % decrease in absolute time spent 'off'	From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Percent Change in Absolute Time Spent "Off" From Baseline to the End of Double-blind Maintenance Period

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

An Independent Ethics Committee (IEC)-approved written informed consent is signed and dated by the subject or by the legal representative
Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, and medication application according to the judgment of the investigator
Subject has Idiopathic Parkinson's Disease of more than 3 years' duration, defined by the cardinal sign, Bradykinesia, plus the presence of at least 1 of the following: resting tremor, rigidity, or impairment of postural reflexes, and without any other known or suspected cause of Parkinsonism
The investigator must observe the subject in both the 'on' and 'off' state and determine that the subject is Hoehn & Yahr stage 2 through 4 in both the 'on' and 'off' state
Subject is male or female and aged ≥30 years at Screening (Visit 1)
Subject has a Mini Mental State Examination (MMSE) score of ≥25 at Screening (Visit 1)
Subject must be on a stable dose of L-dopa (either short-acting or sustained release [in combination with Benserazide or Carbidopa]) of at least 200 mg/day, administered in at least 2 intakes, for at least 28 days prior to Baseline (Visit 2)
Subject is not adequately controlled on a L-dopa dose (in combination with Benserazide or Carbidopa) which was judged by the treating physician to be optimal
Subject must be willing and able to accurately complete a subject diary on designated days (with assistance from caregivers, if required), recording periods when they are 'on without troublesome Dyskinesia', 'on with troublesome Dyskinesia', 'off', and sleeping
As part of the Screening (pretreatment) assessments, the subject must complete a diary over a period of 6 days, with 4 of the 6 diaries being 'valid' as determined by the investigator (see Section 9.1.1)
It must be clear to the investigator that the subject is able to differentiate between the 'on' and 'off' state and the 'valid' diaries confirm that the subject has an average of ≥2.5 h/day spent in the 'off' state
If the subject is receiving an Anticholinergic agent (eg, Benztropine, Trihexyphenidyl, Parsitan, Procyclidine, Biperiden), a monoamine oxidase (MAO)-B inhibitor (eg, Selegiline), and/or an N-methyl-d-aspartate (NMDA) antagonist (eg, Amantadine), he/she must have been on a stable dose for at least 28 days prior to Baseline (Visit 2) and be maintained on that dose for the duration of the study
Subject must be on a stable dose of all anti-Parkinsonian medications for at least 20 days prior to completing the 6 Baseline diaries

Exclusion Criteria:

Subject has previously participated in this study or subject has previously received the study medication under investigation in this study
Subject is participating in another study of an investigational drug or has done so within 28 days prior to the Baseline Visit (Visit 2)
Subject has a history of significant skin hypersensitivity to adhesive or other transdermal preparations, or recent unresolved contact dermatitis
Subject has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening (Visit 1)
Subject has atypical Parkinson's syndrome(s) due to drugs (eg, Metoclopramide, Flunarizine), Metabolic Neurogenetic Disorders (eg, Wilson's Disease), Encephalitis, Cerebrovascular Disease, or Degenerative Disease (eg, Progressive Supranuclear Palsy)
Subject has a history of Pallidotomy, Thalamotomy, deep brain stimulation, or fetal tissue transplant
Subject has dementia, active psychosis or hallucinations, or severe depression
Subject is receiving therapy with a Dopamine agonist either concurrently or has done so within 28 days prior to the Baseline Visit (Visit 2)
Subject is receiving therapy with 1 of the following drugs either concurrently or within 28 days prior to Baseline (Visit 2): Alpha-methyl dopa, Metoclopramide, Reserpine, Neuroleptics (except specific atypical neuroleptics: Olanzapine, Ziprasidone, Aripiprazole, Clozapine, quetiapine), MAO-A inhibitors, Methylphenidate, or Amphetamine
Subject is currently receiving central nervous system (CNS) active therapy (eg, sedatives, hypnotics, antidepressants, anxiolytics), unless the dose has been stable for at least 28 days prior to Baseline (Visit 2) and is likely to remain stable for the duration of the study
Subject has a current diagnosis of Epilepsy, has a history of seizures as an adult, has a history of stroke, or has had a transient ischemic attack within 1 year prior to Screening (Visit 1)
Subject has clinically relevant hepatic dysfunction (as defined as a total bilirubin >2.0 mg/dL, or Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) >2 times the upper limit of the reference range)
Subject has clinically relevant renal dysfunction (serum creatinine >2.0 mg/dL [>178 μmol/L])
Subject has clinically relevant cardiac dysfunction (any cardiac disorder which in the opinion of the investigator would put the subject at risk of clinically relevant arrhythmia) and/or myocardial infarction within the last 12 months
Subject has a QT interval corrected for heart rate according to Bazett's formula (QTcB) of ≥500 ms at Screening (Visit 1)
Subject has a history of only symptomatic (not asymptomatic) orthostatic hypotension, with a decrease of systolic blood pressure (SBP) from supine to standing position of ≥2 0 mmHg or of ≥10 mmHg in DBP after 1 or 3 minutes within 28 days prior to Baseline (Visit 2), or SBP <105 mmHg at study entry 17. Subject has evidence of an impulse control disorder (ICD) at Screening (Visit 1)
Subject has a history of known intolerance/hypersensitivity to the following Antiemetics: Domperidone, Trimethobenzamide, Ondansetron, Tropisetron, Granisetron, and Glycopyrrolate
Subject has a history of chronic alcohol or drug abuse within the last 5 years
Subject is pregnant or nursing, or is of childbearing potential but (i) not surgically sterile or (ii) not using adequate birth control methods (including at least a double barrier method) or (iii) not sexually abstinent or (iv) not at least 2 years post-menopausal
Subject has any other clinically relevant medical condition, psychiatric condition, or laboratory abnormality which would, in the judgment of the investigator, interfere with the subject's ability to participate in the study

Exclusion Criteria:

Contacts/Locations Module

Name	Affiliation	Role
UCB Clinical Trial Call Center	1 877 822 9493	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28827011	Result	Zhang ZX, Liu CF, Tao EX, Shao M, Liu YM, Wang J, Asgharnejad M, Xue HB, Surmann E, Bauer L. Rotigotine transdermal patch in Chinese patients with advanced Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study. Parkinsonism Relat Disord. 2017 Nov;44:6-12. doi: 10.1016/j.parkreldis.2017.08.015. Epub 2017 Aug 10.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Subjects randomized to placebo received matching placebo patches.
FG001	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

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

Arm/Group Information

ID	Title	Description
BG000	Placebo	Subjects randomized to placebo received matching placebo patches.
BG001	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.
BG002	Total Title

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

mean (standard deviation)

Title	Measurements
	BG00062.8± 9.1 BG00161.7± 8.8 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00062 BG00181 BG002

Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00061.83± 10.18 BG00160.38± 10.15 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Absolute Change in Absolute Time Spent 'Off' From Baseline to the End of Double-blind Maintenance Period

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

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.

Posted

Mean

Standard Deviation

hours

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	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.

Units	Counts
Participants	OG000168 OG001170

Title

Denominators

Categories

Title	Measurements
	OG000-1.13± 3.20 OG001-2.36± 2.83

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Estimate of treatment effect has been obtained from an analysis of covariance (ANCOVA) model to the change from Baseline value in absolute time spent "off". The ANCOVA model contained treatment and (pooled) site as factors and Baseline "off" time as covariate. A last observation carried forward (LOCF) imputation approach was used for missing values (during both Titration and Maintenance Periods) for the primary efficacy analysis.	ANCOVA		=0.0002	Primary efficacy analyses was made with confirmatory 2-sided test with significance level 0.05.	Least Square Mean	-1.20			2-Sided	95	-1.83	-0.57

Secondary

Percentage of Responders From Baseline to the End of the Doubleblind Maintenance Period

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

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Units	Counts
Participants

Secondary

Percent Change in Absolute Time Spent "Off" From Baseline to the End of Double-blind Maintenance Period

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.

Posted

Mean

Standard Deviation

percent change

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Units	Counts

Secondary

Percent Change in Relative Time Spent "Off" From Baseline to the End of Double-blind Maintenance Period

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.

Posted

Mean

Standard Deviation

percent change

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Secondary

Change in Absolute Time Spent "on" From Baseline to the End of Double-blind Maintenance Period

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.

Posted

Mean

Standard Deviation

hours

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Secondary

Change in Relative Time Spent "on" From Baseline to the End of Double-blind Maintenance Period

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.

Posted

Mean

Standard Deviation

hours

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Secondary

Percent Change in Absolute Time Spent "on" From Baseline to the End of Double-blind Maintenance Period

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.

Posted

Mean

Standard Deviation

percent change

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Secondary

Percent Change in Relative Time Spent "on" From Baseline to the End of Double-blind Maintenance Period

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.

Posted

Mean

Standard Deviation

percent change

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)

Secondary

Change in the Number of "Off" Periods From Baseline to the End of Double-blind Maintenance Period

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

Posted

Mean

Standard Deviation

Number of 'off' Periods

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Units	Counts
Participants

Secondary

Change in Status of the Subject (on) After Wake-up With Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period

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.

Posted

Mean

Standard Deviation

percentage of days

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Secondary

Change in Status of the Subject (on) After Wake-up Without Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period

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.

Posted

Mean

Standard Deviation

percentage of days

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Secondary

Change in Status of the Subject (Off) After Wake-up From Baseline to the End of Double-blind Maintenance Period

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.

Posted

Mean

Standard Deviation

percentage of days

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Units

Secondary

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

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.

Posted

Mean

Standard Deviation

units on a scale

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

ID	Title	Description
OG000	Full Analysis Set (Placebo Treated Subjects)	Subjects randomized to placebo received matching placebo patches.
OG001	Full Analysis Set (Rotigotine Treated Subjects)	Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo, daily doses, placebo Group Subjects randomized to placebo will receive matching placebo patches.			6	172	24	172
EG001	Rotigotine	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.			6	174	54	174

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Mitral valve prolapse	Cardiac disorders	MedDRA16.0	Non-systematic Assessment	EG0001 events1 affected172 at risk EG0010 events0 affected174 at risk
Atrial fibrillation	Cardiac disorders	MedDRA16.0	Non-systematic Assessment	EG0001 events1 affected172 at risk EG0010 events0 affected174 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA16.0	Non-systematic Assessment	EG0001 events1 affected172 at risk EG0010 events0 affected174 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA16.0	Non-systematic Assessment	EG0000 events0 affected172 at risk EG0011 events1 affected174 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA16.0	Non-systematic Assessment	EG0000 events0 affected172 at risk EG0011 events1 affected174 at risk
Skin infection	Infections and infestations	MedDRA16.0	Non-systematic Assessment	EG0000 events0 affected172 at risk EG0011 events1 affected174 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA16.0	Non-systematic Assessment	EG0000 events0 affected172 at risk EG0011 events1 affected174 at risk
Syncope	Nervous system disorders	MedDRA16.0	Non-systematic Assessment	EG0000 events0 affected172 at risk EG0012 events2 affected174 at risk
Parkinson's disease	Nervous system disorders	MedDRA16.0	Non-systematic Assessment	EG0001 events1 affected172 at risk EG0010 events0 affected174 at risk
Urinary retention	Renal and urinary disorders	MedDRA16.0	Non-systematic Assessment	EG0001 events1 affected172 at risk EG0010 events0 affected174 at risk
Vasculitis	Vascular disorders	MedDRA16.0	Non-systematic Assessment	EG0001 events1 affected172 at risk EG0010 events0 affected174 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA16.0	Non-systematic Assessment	EG0002 events2 affected172 at risk EG00123 events16 affected174 at risk
Dyskinesia	Nervous system disorders	MedDRA16.0	Non-systematic Assessment	EG0007 events7 affected172 at risk EG00113 events11 affected174 at risk
Dizziness	Nervous system disorders	MedDRA16.0	Non-systematic Assessment	EG0008 events7 affected172 at risk EG00121 events19 affected174 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA16.0	Non-systematic Assessment	EG00011 events10 affected172 at risk EG00115 events14 affected174 at risk

ID	Term
D010300	Parkinson Disease

Ancestor Terms

ID	Term
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009069	Movement Disorders
D000080874	Synucleinopathies
D019636	Neurodegenerative Diseases

ID	Term
C047508	rotigotine
D007980	Levodopa

Ancestor Terms

ID	Term
D004295	Dihydroxyphenylalanine
D002395	Catecholamines
D000588	Amines
D009930	Organic Chemicals
D002396	Catechols
D010636	Phenols
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D010649	Phenylalanine
D024322	Amino Acids, Aromatic
D000598	Amino Acids, Cyclic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D014443	Tyrosine

Superiority or Other

Units	Counts
Participants	OG000168 OG001170

Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week.

Facility	Status	City	State	ZIP	Country	Contacts
Sp1037 001		Beijing			China
Sp1037 002