Conditions: Parkinson´s Disease
Keywords: Parkinson´s Disease Kinesia-360™ Kinesia-ONE™ Biosensor
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 40
Healthy volunteers: no

Brief summary:
Evaluate the benefits of Kinesia-360™ wearable technology in addition to standard clinical practice on improving Parkinson´s disease motor symptoms, Neupro dosing regimen and adherence to Neupro compared with only standard clinical practice.

Detailed description:

Arms:
arm 1: Subjects will use the Kinesia-ONE™ wearable device in-clinic at Visit 1 and Visit 2 for recording of specific motor symptoms. The optimal dose of Neupro for any given subject will be determined by standard clinical practice. arm 2: Subjects will use the Kinesia-ONE™ wearable device in-clinic at Visit 1 and Visit 2 for recording of specific motor symptoms, and additionally subjects will use the Kinesia-360™ wearable device at home while awake for continuous measurement of motor symptoms. The Investigator will use these symptom data to provide feedback to subjects on their motor symptoms and to supplement standard of care to titrate the optimal dose of Neupro for any given subject.

Interventions: intervention 1: Kinesia-ONE™ intervention 2: Kinesia-360™ intervention 3: Rotigotine
Intervention descriptions: intervention 1: Kinesia-ONE™ wearable sensor uses a subject-worn finger sensor and iPad mini application (APP) to objectively measure specific motor tasks related to Parkinson's disease symptoms such as tremor, bradykinesia (slowed movements), and dyskinesia (involuntary movements) in the Investigator's office. Subjects should wear the Kinesia-ONE™ device on the most affected side. intervention 2: Kinesia-360™ wearable sensor includes a wrist and ankle device, along with a cell phone, which is also APP-based, and is designed for continuous day time monitoring of Parkinson's disease symptoms. Subjects will wear Kinesia-360™ while they go about their daily lives, and symptom severity is continually captured to enable objective assessment of Parkinson's disease symptoms. Subjects should wear the Kinesia-360™ device bands on the most affected side. intervention 3: All subjects will start Neupro treatment at a dose of either rotigotine 2 mg/24 h or 4 mg/24 h (according to the disease stage of the subject) which will then be adjusted based on symptom assessment either via standard care alone or via a combination of standard care and evaluation of the recordings made available by the Kinesia wearable technologies.

Protocol document:
Prot_001.pdf: 
UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 1 of 38
PROTOCOL PD0049
A MULTICENTER, OPEN-LABEL, TWO-ARM STUDY TO 
EVALUATE THE IMPACT OF USING WEARABLE DEVICES IN 
ADDITION TO STANDARD CLINICAL PRACTICE ON
PARKINSON’S SUBJECT SYMPTOMS MANAGEMENT
PHASE 4
Sponsor:
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Protocol/Amendment number
Date
Final protocol
16 Dec 2016
Confidential Material
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB.
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16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 2 of 38
STUDY CONTACT INFORMATION
Sponsor
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Sponsor Study Physician
Name:
, MD
Address:
UCB Biosciences, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES OF AMERICA
Phone:
Fax:
Clinical Project Manager
Name:
Address:
UCB Biosciences, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES OF AMERICA
Phone:
Fax:
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 3 of 38
Clinical Trial Biostatistician
Name:
, MSc
Address:
UCB Biosciences GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Clinical Monitoring Contract Research Organization
Name:
PAREXEL International
Address:
1 Federal Street
Billerica, MA 01821
UNITED STATES OF AMERICA
Phone:
+1 978 313 3900
Fax:
+1 781 768 5512
Device Manufacturer
Name:
Great Lakes Neuro Technologies, Inc. (GLNT)
Address:
10055 Sweet Valley Drive
Valley View, OH 44125
UNITED STATES OF AMERICA
Phone:
+1 855 456 3876
Fax: 
+1 216 361 5420
Device Manufacturer/Complaint Reporting
Name:
Great Lakes Neuro Technologies/
Phone:
Office:
(9:00am – 5:00pm EST)
Mobile
 (after business hours)
email: 
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16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 4 of 38
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
USA: +1 800 880 6949
or +1 866 890 3175
Email
Global: DS_ICT@ucb.com (for interventional clinical studies)
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 5 of 38
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................8
1
SUMMARY.....................................................................................................................10
2
INTRODUCTION ...........................................................................................................11
3
STUDY OBJECTIVES....................................................................................................12
3.1 Primary objectives ...........................................................................................................12
3.2 Other objectives ...............................................................................................................12
4
STUDY VARIABLES.....................................................................................................13
4.1 Efficacy variables.............................................................................................................13
4.1.1
Primary efficacy variables ...................................................................................13
4.1.2
Other efficacy variables.......................................................................................13
4.2 Safety variables................................................................................................................14
5
STUDY DESIGN.............................................................................................................14
5.1 Study description .............................................................................................................14
5.1.1
Study duration per subject ...................................................................................14
5.1.2
Planned number of subjects and sites ..................................................................14
5.1.3
Anticipated regions and countries .......................................................................15
5.2 Schedule of study assessments.........................................................................................15
5.3 Rationale for study design and selection of dose.............................................................18
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................18
6.1 Inclusion criteria ..............................................................................................................18
6.2 Exclusion criteria .............................................................................................................18
6.3 Withdrawal criteria ..........................................................................................................19
7
MEDICINAL PRODUCT AND DEVICE ......................................................................19
7.1 Description of medicinal product.....................................................................................19
7.2 Devices.............................................................................................................................19
7.2.1
Description of devices .........................................................................................20
7.2.2
Packaging and labeling of the Kinesia devices....................................................21
7.2.3
Storage requirements ...........................................................................................21
7.2.4
Device accountability ..........................................................................................21
7.3 Concomitant medications/treatments...............................................................................21
7.3.1
Rescue medication...............................................................................................21
7.4 Blinding............................................................................................................................21
7.5 Randomization and numbering of subjects......................................................................21
8
STUDY PROCEDURES BY VISIT ...............................................................................22
8.1 Visit 1 /Screening............................................................................................................22
8.2 Week 1 .............................................................................................................................22
8.3 Weeks 2, 3, and 4.............................................................................................................23
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16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 6 of 38
8.4 Week 5 up to Week 12.....................................................................................................23
8.5 Visit 2 (End of Study Visit) (Week 12 ±3 days)..............................................................24
8.6 Early Withdrawal Visit ....................................................................................................24
9
ASSESSMENT OF EFFICACY......................................................................................24
9.1 Inclusion criteria threshold related to tremor and/or bradykinesia ..................................24
9.1.1
Unified Parkinson’s Disease Rating Scale ..........................................................25
9.1.2
39-Item Parkinson’s Disease Questionnaire........................................................25
10
ASSESSMENT OF SAFETY..........................................................................................25
10.1 Adverse events.................................................................................................................25
10.1.1
Definitions ...........................................................................................................25
10.1.1.1
Adverse event............................................................................................25
10.1.1.2
Serious adverse event ................................................................................25
10.1.1.3
Adverse events of special interest .............................................................26
10.1.2
Procedures for reporting and recording adverse events and other safety related 
information ..........................................................................................................26
10.1.2.1
Description of adverse events....................................................................27
10.1.2.2
Rule for repetition of an adverse event......................................................27
10.1.2.3
Reporting of serious AEs (related or not to Neupro) ................................27
10.1.2.4
Device reporting........................................................................................27
10.1.3
Follow up of adverse events ................................................................................27
10.1.4
Pregnancy and breastfeeding ...............................................................................28
10.1.5
Overdose of medicinal product............................................................................28
10.2 Laboratory measurements................................................................................................28
10.3 Other safety measurements..............................................................................................28
10.3.1
Rate of discontinuation of treatment with Neupro ..............................................28
11
STUDY MANAGEMENT AND ADMINISTRATION.................................................29
11.1 Adherence to protocol......................................................................................................29
11.2 Monitoring .......................................................................................................................29
11.2.1
Definition of source data .....................................................................................29
11.2.2
Source data verification .......................................................................................30
11.3 Data handling...................................................................................................................30
11.3.1
Case Report form completion..............................................................................30
11.3.2
Database entry and reconciliation........................................................................30
11.3.3
Subject Screening and Enrollment log/Subject Identification Code list..............30
11.4 Termination of the study..................................................................................................30
11.5 Archiving and data retention............................................................................................31
11.6 Audit and inspection ........................................................................................................31
11.7 Good Clinical Practice .....................................................................................................31
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Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 7 of 38
12
STATISTICS ...................................................................................................................31
12.1 Definition of analysis sets................................................................................................32
12.2 General statistical considerations.....................................................................................32
12.3 Planned efficacy analyses ................................................................................................32
12.3.1
Analysis of the efficacy variables........................................................................32
12.3.2
Other efficacy analyses........................................................................................33
12.4 Planned safety analyses....................................................................................................33
12.4.1
Safety analyses.....................................................................................................33
12.5 Handling of protocol deviations.......................................................................................33
12.6 Handling of dropouts or missing data..............................................................................33
12.7 Planned interim analysis and data monitoring.................................................................33
12.8 Determination of sample size...........................................................................................34
13
ETHICS AND REGULATORY REQUIREMENTS......................................................34
13.1 Informed consent .............................................................................................................34
13.2 Subject identification cards..............................................................................................34
13.3 Institutional Review Boards.............................................................................................34
13.4 Subject privacy.................................................................................................................35
13.5 Protocol amendments.......................................................................................................35
14
FINANCE, INSURANCE, AND PUBLICATION.........................................................35
15
REFERENCES ................................................................................................................36
16
DECLARATION AND SIGNATURE OF INVESTIGATOR .......................................37
17
SPONSOR DECLARATION ..........................................................................................38
LIST OF TABLES
Table 5‒1:
Schedule of study assessments.........................................................................16
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 8 of 38
LIST OF ABBREVIATIONS
ADE
adverse device event
AE
adverse event
ANCOVA
analysis of covariance
APP
application, application software
ATC
Anatomical Therapeutic Chemical
CDMS
clinical data management system
CG
Control Group
CI
confidence interval
CRO
contract research organization
DBS
Deep Brain Stimulation
ECG
electrocardiogram
eCRF
electronic Case Report form
EG
Experimental Group
ES
Enrolled Set
FAS
Full Analysis Set
FDA
Food and Drug Administration
GLNT
Great Lakes Neuro Technologies, Inc.
H0
null hypothesis
Ha
alternative hypothesis
ICF
Informed Consent form
ICH-GCP
International Council for Harmonisation-Good Clinical Practice
IMP
investigational medicinal product
IRB
Institutional Review Board
ISO
International Organization for Standardization
MedDRA
Medical Dictionary for Regulatory Activities
n
number
PDQ-39
39-Item Parkinson’s Disease Questionnaire
PPS
Per-Protocol Set
PS
Patient Safety
RLS
restless leg syndrome
SAE
serious adverse event
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16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 9 of 38
SAP
Statistical Analysis Plan
SD
standard deviation
SOP
Standard Operating Procedure
SS
Safety Set
TEAE
treatment-emergent adverse event
UPDRS
Unified Parkinson’s Disease Rating Scale
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 10 of 38
1
SUMMARY
PD0049 is a pilot study to investigate whether motor symptoms in subjects with Parkinson’s 
disease who start treatment with Neupro® can be improved by using wearable devices. 
Specifically, this study focuses on investigating how to optimize the evaluation of motor 
symptoms in subjects with Parkinson’s disease aiming at enabling Investigators to optimize 
subjects’ Neupro dosing regimens and ensure better patient outcomes in a timelier manner.
In this study, 2 Kinesia devices (Kinesia-ONE and Kinesia-360) will be employed to record 
specific motor symptoms. Approximately 40 subjects with Parkinson’s disease of any stage will 
be randomized (1:1 ratio) to either the Control Group or the Experimental Group. Specific motor 
tasks will be measured in all subjects with Kinesia-ONE on Day 1. In contrast to subjects 
randomized to the Control Group, subjects randomized to the Experimental Group will also use 
the Kinesia-360 device for home-based self-recording of their motor symptoms.
All subjects will start Neupro treatment at a dose of either rotigotine 2mg/24h or 4mg/24h 
(according to the disease stage of the subject), which will then be adjusted based on symptom 
assessment either via standard care alone (Control Group) or via a combination of standard care 
and evaluation of the recordings made available by the Kinesia wearable technologies
(Experimental Group). The Neupro dosing regimen used in PD0049 follows standard of care, 
and is in line with the approved dosing regimen for rotigotine in the treatment of Parkinson’s 
disease (ie, up to 8mg/24h, depending on the stage of the disease).
PD0049 starts with in-clinic Screening activities, assessments (including recording of Baseline 
motor symptoms via Kinesia-One), and training in the use of Kinesia-360 devices (for subjects 
randomized to the Experimental Group only) on Day 1, followed by 3 days at home: During this 
period, subjects randomized to the Experimental Group will use the Kinesia-360 device to record 
their motor symptoms (on Days 2 and 3). Subjects allocated to the Control Group will start 
treatment with Neupro preferably on Day 1 (but no later than Day 4); subjects allocated to the 
Experimental group will start treatment with Neupro on Day 4. There are no required visits from 
Week 2 up to Week 12 (Visit 2). However, Investigators and subjects in the Experimental Group 
are encouraged to discuss by phone Kinesia-360 motor symptom reports and needs for any 
changes in Neupro dosing. Subjects of either group return to the clinic for final assessments and 
reporting of adverse events (AEs) and concomitant medications at Week 12. The individual 
duration of study participation may last up to 12 weeks.
A primary objective of PD0049 is to evaluate whether Parkinson’s disease motor symptoms in 
subjects starting Neupro can be improved by using feedback of motor symptom data from the 
Kinesia-360 wearable technology presented to subjects and Investigators in addition to standard 
clinical practice as compared with only standard clinical practice. A primary objective is to 
evaluate whether a clinician is more likely to determine a Neupro dosing regimen that improves 
a subject’s Parkinson’s disease motor symptoms when using motor symptom data collected with 
the Kinesia-360 wearable technology in addition to standard clinical practice as compared with 
only standard clinical practice. Another primary objective is to evaluate whether subjects with 
Parkinson’s disease are more likely to continue the usage of Neupro if Parkinson’s disease motor 
symptom data collected using the Kinesia wearable technology is used to provide the subjects 
with feedback on the status of their Parkinson’s disease motor symptoms and is used in addition 
to standard of care for titrating their Neupro dosing regimen. Other objectives include to evaluate 
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 11 of 38
the quality of life and engagement in the management and treatment of their disease within 
subjects in either group, as well as to evaluate the safety of Neupro. The corresponding variables 
to be assessed to meet the study objectives are described in detail in Section 4.
2
INTRODUCTION
Neupro is approved for the treatment of the signs and symptoms of early-stage idiopathic 
Parkinson’s disease as monotherapy (ie, without levodopa) or in combination with levodopa, ie, 
over the course of the disease, through to late stages when the effect of levodopa wears off or 
becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or "on-off" 
fluctuations).
Dosing in patients with early-stage Parkinson’s disease consists of a single daily dose initiated at 
rotigotine 2mg/24h and then increased in weekly increments of rotigotine 2mg/24h to an 
effective dose up to a maximum dose of rotigotine 6mg/24h. Rotigotine 4mg/24h may be an 
effective dose in some patients. For most patients an effective dose is reached within 3 or 
4 weeks at doses of rotigotine 6mg/24h. The maximum approved dose is rotigotine 6mg/24h
(NEUPRO [package insert]. 2016 [Section 15]).
Dosing in patients with advanced-stage Parkinson’s disease with fluctuations consists of a single 
daily dose that should be initiated at rotigotine 4mg/24h and the increased in weekly increments 
of rotigotine 2mg/24h to an effective dose up to a maximum dose of rotigotine 8mg/24h. 
Rotigotine 4mg/24h or rotigotine 6mg/24h may be effective doses in some patients. For most 
patients with advanced-stage Parkinson’s disease, an effective dose is reached within 3 to 
7 weeks at doses of rotigotine 8mg/24h. The maximum approved dose is rotigotine 8mg/24h
(NEUPRO [package insert]. 2016 [Section 15]).
Optimal patient outcomes may be expected only when the clinician is able to prescribe a 
customized, optimal dosing regimen for patients with Parkinson’s disease. Clinicians employ 
various measures to diagnose Parkinson’s disease and its severity in order to prescribe the 
optimal dosing regimen for the patient. Key amongst these measures is an evaluation of the 
severity of the motor symptoms (eg, dyskinesia, gait, tremor, rigidity, and posture) associated 
with Parkinson’s disease. The quality of this evaluation (ie, quantification of movement) is 
critical to an accurate diagnosis of the evaluation of severity of the motor symptoms and is 
currently limited by the ability of the Clinician (through manual manipulation and observation) 
to accurately measure the various physical manifestations of motor symptoms associated with
Parkinson’s disease. Ultimately, the quality of the evaluation of the motor symptoms may 
determine whether the Clinician is able to prescribe the optimal dosing regimen for the patient.
New, wearable technologies that allow for accurate, consistent, and ongoing measurement of 
motor activity under ambulatory conditions in patients with Parkinson’s disease may provide the 
Clinician with additional motor symptom data that the Clinician could use to make more accurate 
evaluations of the motor symptoms associated with Parkinson’s disease, thereby providing the 
patient with the optimal Neupro dosing regimen and ensuring better patient outcomes in a more 
timely manner.
The focus of this 12-week study is on optimizing patients’ response to Neupro by using a 
commercially available wearable device to optimize the evaluation of motor symptoms and to 
improve customized dosing.
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 12 of 38
3
STUDY OBJECTIVES
3.1
Primary objectives
The primary objectives of this study are to:

Evaluate whether Parkinson’s disease motor symptoms in subjects starting Neupro can be 
improved by using feedback of motor symptom data from the Kinesia-360 wearable 
technology presented to subjects and Investigators in addition to standard clinical practice as 
compared with only standard clinical practice.

Evaluate the Neupro dosing regimen when using feedback of motor symptom data collected 
with the Kinesia-360 wearable technology in addition to standard clinical practice as 
compared with only standard clinical practice.

Evaluate whether subjects with Parkinson’s disease are more likely to continue the usage of 
Neupro if Parkinson’s disease motor symptom data collected using the Kinesia-360 wearable 
technology is used to provide the subjects with feedback on the status of their Parkinson’s 
disease motor symptoms and is used in addition to standard of care for titrating their Neupro 
dosing regimen.
3.2
Other objectives
Other objectives of this study are to:

Evaluate whether the quality of life of subjects with Parkinson’s disease can be improved by 
using the Kinesia-360 wearable technology to collect motor symptom data in addition to 
standard clinical practice as compared with only standard clinical practice to titrate the 
Neupro dosing regimen.

Evaluate whether subjects with Parkinson’s disease are more actively engaged in the 
management and treatment of their disease with Neupro therapy with the use of the 
Kinesia-360 wearable technology as compared to without the use of the Kinesia-360 
wearable technology.

Evaluate the safety of Neupro.
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 13 of 38
4
STUDY VARIABLES
4.1
Efficacy variables
4.1.1
Primary efficacy variables
The efficacy variables of this study are:

Change from Baseline (Visit 1/Week 1) to Visit 2 (Week 12/3 months after start of treatment 
with Neupro) in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III Motor Score 

Change from Baseline (Visit 1/Week 1) to Visit 2 (Week 12) in Kinesia-ONE variables:

finger tapping speed score

rest tremor score

averaged finger tapping speed and resting tremor scores

postural tremor score

finger tapping amplitude score

hand grasp speed score

hand grasp amplitude score

rapid alternating movement speed score

rapid alternating amplitude score

dyskinesia score

Neupro dose per 24h at Visit 2 (Week 12)

Number of Neupro dose changes during the study (between Visit 1 and Visit 2)

Discontinuation of treatment with Neupro during the course of the study
4.1.2
Other efficacy variables

Change from Baseline to Visit 2 in the motor scores derived from the Kinesia-360 wearable 
technology by time (weekly/monthly) and by Neupro dose level (mg/24h) for the 
Experimental Group in:

average daily tremor score

average daily slowness score

average daily dyskinesia score

percent wear-time tremor detected

percent wear-time dyskinesia detected

percent wear-time user not moving

percent wear-time user was walking score

percent wear-time user active but not walking
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 14 of 38

number of steps per hour while wearing device

Change from Baseline to Visit 2 (Week 12) in the 39-Item Parkinson’s Disease 
Questionnaire (PDQ-39) scores.

Change from Baseline to Visit 2 (Week 12) in subject engagement questionnaire scores.
4.2
Safety variables
Safety variable is:

Occurrence of AEs 
5
STUDY DESIGN
5.1
Study description
PD0049 is a multicenter, open-label, two-arm, 12-week study in subjects with Parkinson’s 
disease. On Day 1, eligible subjects will be randomized to either the Control Group or the 
Experimental Group in a 1:1 fashion. In both groups, subjects will use the Kinesia-ONE 
wearable device in-clinic at Visit 1 and Visit 2 for recording of specific motor symptoms, and 
subjects randomized to the Experimental Group will also use the Kinesia-360 wearable device at 
home while awake for continuous measurement of motor symptoms. The Investigator will use 
these symptom data to provide feedback to subjects on their motor symptoms and to supplement 
standard of care to titrate the optimal dose of Neupro for any given subject. In the Control 
Group, subjects will not use any wearable device at home, and the Investigator will use only 
standard of care to titrate the optimal Neupro dose. 
Subjects in the Control Group and the Experimental Group will start treatment with Neupro 
2mg/24h or 4mg/24h (at the Investigator’s discretion and according to the disease stage of the 
subject) preferably on Day 1 (but no later than Day 4) or Day 4, respectively. Evaluations 
conclude 12 weeks after the start of treatment with Neupro (ie, at Visit 2).
The decision to prescribe Neupro must be made by the Investigator independent of his/her 
decision to include the subject in the study. The subject’s treatment/Neupro intake must be 
within the terms of the marketing authorization; Neupro will not be supplied by UCB.
A schedule of study assessments is presented in Table 5‒1; for a detailed rationale of the study 
design see Section 5.3.
5.1.1
Study duration per subject
Each subject’s participation is approximately 12 weeks.
The end of the study is defined as the date of the last visit of the last subject in the study.
5.1.2
Planned number of subjects and sites
This study will be conducted in approximately 6 sites and will include a total of approximately 
40 subjects (20 subjects in the Experimental Group and 20 subjects in the Control Group). Of 
note, a single site will not randomize more than 20 subjects.
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 15 of 38
5.1.3
Anticipated regions and countries
This study will be conducted in the US. 
5.2
Schedule of study assessments
A schedule of assessments planned for both the Control Group and the Experimental group is 
presented in Table 5‒1.
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 16 of 38
Table 5‒1:
Schedule of study assessments
In Clinic
At Home
In Clinic
SCREENING
BASELINE
EOS/EW
Visit 1
Visit 2
Assessments
Day 1
Day 
2-3
Day 
4
Week 
2
Week 
3
Week 
4
Week 
11
Week 12
(±3 days)
Written informed consent
X
Demographic data 
(incl. height and weight)
X
Xa
Kinesia-ONE subject assessments (measured in triplicate)
Xb
X
UPDRS 
X
X
Patient engagement questionnaire
X
X
PDQ-39
X
X
Verification of inclusion/exclusion criteria
X
Randomization
X
C Group: Start treatment with Neupro 2mg or 4mg 
preferably on Day 1 but no later than Day 4 (dose 
adjustments during study are performed per standard of 
care) 
X
X
C Group: Record Neupro dose
X
X
E Group: Kinesia-360 device training and distribution of 
equipment
X
E Group: Subject wears Kinesia-360 wrist and ankle 
devices on Days 2 and 3 at home for baseline
X
E Group: Start treatment with Neupro 2mg or 4mg on 
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 17 of 38
Day 4
E Group: Record Neupro dosec
X
X
E Group: Reminder phone calls from site to subject at 
beginning of Weeks 2, 3, 4 and 11 (remind subject to 
charge devices and wear devices on at least 2 consecutive 
days during Weeks 2, 3, 4 and 11)
Xd
Xd
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E Group: Subject wears Kinesia-360 wrist and ankle 
devices on at least 2 consecutive days at home
X
X
X
X
E Group: Subject and Investigator access Kinesia-360 
device reports (subjects via device app, Investigators via 
GLNT web portal)
X
X
E Group: Investigator combines standard of care with
Kinesia-360 motor symptom reports to adjust Neupro
dose and is encouraged to contact the subject by phone to 
discuss motor symptom reports and potential Neupro
dose adjustments anytime between V1 and V2 based on 
clinical judgment 
X
E Group: Subject returns Kinesia-360 device equipment to 
site
X
Record adverse events
X
X
Record concomitant medications
X
X
APP=application; C Group=Control Group; E Group=Experimental Group; EOS=End of Study; EW=Early Withdrawal; GLNT=Great Lakes Neuro 
Technologies, Inc.; PDQ-39=39-Item Parkinson’s disease questionnaire; UPDRS=Unified Parkinson’s Disease Rating Scale; V=visit
a Only weight at V2. 
b The average of the triplicate resting tremor scores and triplicate finger tapping scores from Kinesia-ONE must be >1.0 to be eligible for inclusion in this study.
c Subjects in the Experimental Group will be prompted to record Neupro dose in device app during each use of Kinesia-360 between V1 and V2. 
d Subjects in the Experimental Group are to use Kinesia-ONE on at least 2 consecutive days during Weeks 2, 3, 4 and 11, but are free to use the device as often 
as they like between these time points prior to Visit 2.
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 18 of 38
5.3
Rationale for study design and selection of dose
The Neupro dosing regimen used in PD0049 follows standard of care, and is in line with the 
approved dosing regimen for rotigotine in the treatment of Parkinson’s disease (ie, up to 
8mg/24h, depending on the stage of the disease).
As described in Section 2, the focus of this study is on optimizing the benefits of Neupro in 
patients with Parkinson’s disease by using wearable devices to help the Investigator optimize the 
evaluation of motor symptoms and improve customized dosing.
To that end, PD0049 employs Kinesia wearable technologies that allow for accurate, consistent, 
and ongoing measurement of motor activity under ambulatory conditions to provide the 
Investigator with additional information to further enhance his/her ability to evaluate subjects’ 
motor symptoms more accurately and, via providing the patient with the optimal Neupro dosing 
regimen, ensure better patient outcomes in a more timely manner. Both Kinesia devices will be 
used in accordance with their labelled instructions.
6
SELECTION AND WITHDRAWAL OF SUBJECTS
6.1
Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
1. Subject is newly prescribed Neupro and is expected to commence Neupro treatment.
Historical Neupro treatment is permitted.
2. An Institutional Review Board (IRB) approved written Informed Consent form (ICF) is 
signed and dated by the subject, before any study-related procedures.
3. Subject is considered reliable and capable of adhering to the protocol, visit schedule, 
completion of the diary, and using Kinesia devices according to the judgment of the 
Investigator.
4. Male or female subject, ≥18 years of age at the time of the Screening Visit.
5. Subject has Parkinson’s disease, defined by the cardinal sign, bradykinesia, plus the presence 
of at least 1 of the following: tremor at rest, rigidity or impairment of postural reflexes, and 
without any other known or suspected cause of Secondary Parkinsonism.
6. Subject experiences motor symptoms associated with Parkinson’s disease that are not 
sufficiently controlled by current therapy. The average of the triplicate resting tremor scores 
and triplicate finger tapping scores from Kinesia-ONE (6 scores in total) must be >1.0. 
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is met:
1. Subject is currently participating in any study with an investigational medicinal product
(IMP) or investigational device.
2. Subject has any medical, neurological or psychiatric condition (eg, previous stroke, bipolar 
disorder, dementia, hallucinations, psychosis or severe depression, and drug or alcohol 
abuse) which, in the opinion of the Investigator, could jeopardize or would compromise the 
subject’s ability to participate in this study.
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 19 of 38
3. Subject with Deep Brain Stimulation (DBS) device implant.
6.3
Withdrawal criteria
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care.
Subjects should be withdrawn from the study if any of the following events occur:
1. Subject develops an illness that would interfere with his/her continued participation.
2. Subject is noncompliant with the study procedures in the opinion of the Investigator.
3. Subject withdraws his/her consent.
4. The sponsor or a regulatory agency requests withdrawal of the subject.
For assessments to be performed in case of an Early Withdrawal, refer to Table 5‒1.
Investigators should attempt to obtain information on subjects in the case of withdrawal or 
discontinuation. For subjects considered as lost to follow up, the Investigator should make an 
effort (at least 1 phone call and 1 written message to the subject), and document his/her effort 
(date and summary of the phone call and copy of the written message in the source documents) 
to complete the final evaluation. All results of these evaluations and observations, together with a 
narrative description of the reason(s) for discontinuing the subject, including the date of 
discontinuation, must be recorded in the source documents. The electronic Case Report form 
(eCRF) must document the primary reason for withdrawal or discontinuation.
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a subject in advance.
For handling of dropouts, refer to Section 12.6. 
7
MEDICINAL PRODUCT AND DEVICE
7.1
Description of medicinal product
Neupro (rotigotine) is a nonergolinic dopamine agonist for the treatment of the signs and 
symptoms of Parkinson’s disease and Restless Legs Syndrome (RLS). Neupro elicits its 
beneficial effect on Parkinson’s diseases by activation of the D3, D2 and D1 receptors of the 
caudate-putamen in the brain. 
Neupro (Anatomical Therapeutic Chemical [ATC] code: N04BC09) is available as a transdermal 
system in six dosages. In the current study, Neupro is to be applied as prescribed by the 
Investigator and based on instructions provided in the patient leaflet/package insert (NEUPRO 
[package insert]. 2016 [Section 15]).
7.2
Devices
In the present study, all subjects will use the Kinesia-ONE device in-clinic during the Screening 
Visit for specific motor tasks/for recording of specific baseline motor symptoms. Subjects
randomized to the Experimental Group will also use the Kinesia-360 device at home for 
continuous measurement of motor symptoms.
Kinesia-360 is intended to monitor physical motion and muscle activity to quantify kinematics of 
movement disorder symptoms such as tremor, and assess activity in any instance where 
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 20 of 38
quantifiable analysis of motion and muscle activity is desired. Kinesia Regulatory Certifications: 
Kinesia-One and Kinesia-360 have received US Food and Drug Administration (FDA) 510K 
clearance to market (06 Apr 2007), Conformité Européen Mark (European Medical Device 
Directive 93/42/EEC), Canadian Medical Device Conformity Assessment Systems, Australian 
Therapeutic Goods Association Certification, and International Organization for Standardization 
(ISO) 13485 (2003). Kinesia-One and Kinesia-360 are tested to International Electrotechnical 
Commission 60601 Standards, comply with Federal Communications Commission Part 
15 Rules, and are Health Insurance Portability and Accountability Act compliant, and 
FDA Part 11 compliant for Electronic Data Capture in Clinical Trials.
7.2.1
Description of devices
Kinesia-ONE Wearable Sensor uses a subject-worn finger sensor and iPad mini application 
(APP) to objectively measure specific motor tasks related to Parkinson’s disease symptoms such 
as tremor, bradykinesia (slowed movements), and dyskinesia (involuntary movements) in the 
Investigator’s office. Subjects should wear the Kinesia-ONE device on the most affected side.
Kinesia-360 Wearable Sensor includes a wrist and ankle device, along with a cell phone, which
is also APP-based, and is designed for continuous day time monitoring of Parkinson’s disease 
symptoms. Subjects will wear Kinesia-360 while they go about their daily lives, and symptom 
severity is continually captured to enable objective assessment of Parkinson’s disease symptoms. 
Subjects should wear the Kinesia-360 device bands on the most affected side.
Symptom data recorded by either device, as well as the corresponding data reports, will be made 
available to the Investigators through a web portal.
The following variables will be derived from either Kinesia device to be used in PD0049:
Kinesia-ONE
Kinesia-360
Change from Baseline to Visit 2 (Week 12) in 
the following Kinesia-ONE measures, which 
will be averaged from triplicate repeated 
assessments at a measurement point:
Change from Baseline to Visit 2 (Week 12) in 
the following Kinesia-360 measures, which 
will be averaged from 2 consecutive days of 
wear:
Resting tremor score
Average daily tremor score
Postural tremor score
Average daily slowness score
Finger tapping speed and amplitude scores
Average daily dyskinesia score
Hand grasps speed and amplitude scores
% wear-time tremor was detected
Rapid alternating movements speed and 
amplitude scores
% wear-time dyskinesia was detected
Dyskinesia score
% wear-time user was not moving
% wear-time user was walking
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 21 of 38
% wear-time user was active, but not walking
Number of steps/h while wearing the device
7.2.2
Packaging and labeling of the Kinesia devices
The sites will receive uniquely numbered wearable sensor devices (Kinesia-ONE and 
Kinesia-360) for use in the study. The devices will be provided in the intended final packaging.
7.2.3
Storage requirements
Sensor devices must be stored in a secured area with limited access at the Investigators’ sites. 
7.2.4
Device accountability
Great Lakes Neuro Technologies, Inc. (GLNT) will supply the wearable sensor devices and 
associated equipment / software. The Investigator must ensure that the devices are used only in 
accordance with the manufacturer’s instructions. A device accountability form will be used to 
record the receipt and return dates of the wearable sensor devices and associated equipment/ 
software. In addition, dispensing and returning information on a by-subject basis will be 
completed. This form will serve as source documentation during the course of the study. Details 
of any device lost, not used, disposed of at the study site, or returned to the Sponsor must also be 
recorded. The Investigator, after completion of the study, will ensure that all devices are returned 
to GLNT.
7.3
Concomitant medications/treatments
Subjects will continue with their usual treatment. All medications/treatments (ie, Parkinson’s 
disease medications and others), including dosages, will be recorded in the appropriate study 
documents (ie, eCRF and source document).
Investigators are encouraged to adjust, if needed, the Neupro dose to optimize Parkinson’s 
disease symptoms. Back-titration of the Neupro dose in case of AEs is allowed as per standard of 
care.
Subjects are encouraged not to change the dosages of any concomitant medications during the 
study. There are no prohibited medications defined for this study.
7.3.1
Rescue medication
Not applicable.
7.4
Blinding
Not applicable.
7.5
Randomization and numbering of subjects
Subjects will be randomized (1:1) to either the Control Group (without Kinesia-360 device to 
measure motor symptoms at home) or the Experimental Group (with Kinesia-360 device to 
measure motor symptoms at home) during the Screening Visit (Visit 1). The randomization will 
be stratified by site. A randomization list for each site with a block size of 4 will be provided to 
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 22 of 38
the site. Each subject will receive a 5-digit number assigned at Screening that serves as the 
subject identifier throughout the study.
8
STUDY PROCEDURES BY VISIT
Prior to the start of any study-related examinations or procedures, the written ICF must be signed 
and personally dated by the subject. The person (Investigator [or designee]) who conducted the 
informed consent discussion will document their informed consent process with his/her 
signature.
8.1
Visit 1 /Screening
The Screening examinations will be completed within 4 days, the first of which will take place at 
the study site (in clinic) and will include the following:
Day 1, in clinic:

Sign ICF

Control Group and Experimental Group: Subject wears Kinesia-ONE sensor on the most 
affected side in the clinic to measure specific motor tasks in triplicate. Calculation of the 
average of triplicate resting tremor scores and triplicate finger tapping speed scores (ie, 
6 scores in total) must be >1.0 for subject inclusion in the study.

Verification of inclusion/exclusion criteria and collection of demographic data (including
weight and height)

PDQ-39

Investigator performs UPDRS assessment

Patient Engagement Questionnaire

Randomization (Control Group [without Kinesia-360 device use at home]/Experimental 
Group [with Kinesia-360 device use at home])

Experimental Group: Trained in-clinic on Kinesia-360 device (and sent home with the 
device)

Control Group: Start treatment with Neupro as prescribed (preferably on Day 1, but no later 
than Day 4); record date and dose

Control Group and Experimental Group: Recording of AEs and concomitant medications
8.2
Week 1
Day 2 and 3, home: 

Experimental Group: Subject wears Kinesia-360 wrist and ankle devices on Days 2 and 3 at 
home for baseline

Experimental Group: Recording of concomitant medications and Neupro dose via APP
Day 4, home: 

Experimental Group: Start treatment with Neupro as prescribed; record date and dose via 
APP
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 23 of 38

Experimental Group: Recording of concomitant medications 
8.3
Weeks 2, 3, and 4
Control Group, home:

Investigator uses standard of care to adjust Neupro dose as needed.

Phone contact initiated by subject or Investigator as needed. Documentation of any contact or 
dosage adjustment.
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
Subject uses Kinesia-360 at least on 2 consecutive days at home weekly to measure motor 
symptoms.

Subject accesses Kinesia-360 motor symptom reports on device following each day of 
measurements.

Investigator receives Kinesia-360 motor symptom reports via web portal following each day 
of measurements.

Investigator combines standard of care with weekly Kinesia-360 motor symptom reports to 
adjust Neupro dose as needed.

Phone contact initiated by subject or Investigator as needed and dispatch of Kinesia-360 
motor symptom reports. Documentation of any contact or dosage adjustment.

Recording of concomitant medications and Neupro dose via APP.

A reminder phone call from the site to the subject each week during Weeks 2, 3, and 4 to 
ensure the subject will perform the protocol-requested Kinesia-360 assessments on 2 
consecutive days per week. In addition, the subject should be reminded to charge the device 
and phone batteries the night prior to assessments.
8.4
Week 5 up to Week 12
Control Group, home:

Treatment of subjects as per standard of care.

Phone contact initiated by subject or Investigator as needed. Documentation of any contact or 
dosage adjustment.
Experimental Group, home:

A reminder phone call from the site to the subject during the week prior to Visit 2 to ensure 
the subject will perform the protocol-requested Kinesia-360 assessments on 2 consecutive 
days.  In addition, the subject should be reminded to charge the device and phone batteries 
the night prior to assessments.

Optional: Subject may use Kinesia-360 as desired between Week 5 and Visit 2 (Week 12).

Subject receives Kinesia-360 motor symptom reports on device following each day of 
measurements.
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 24 of 38

Investigator receives Kinesia-360 motor symptom reports via web portal and by email 
following each day of measurements.

Treatment of patients as per standard of care and dispatch of any Kinesia-360 motor 
symptom report.

Phone contact initiated by subject or Investigator as needed and dispatch of Kinesia-360 
motor symptom reports. Documentation of any contact or dosage adjustment.
8.5
Visit 2 (End of Study Visit) (Week 12 ±3 days)
Visit 2 represents the 3 month (from first Neupro dose) Follow-Up Visit.
Control Group and Experimental Group, in clinic:

Control Group and Experimental Group: Subject wears Kinesia-ONE sensor in the clinic on 
the same side assessed at Visit 1 to measure specific motor tasks in triplicate.

Investigator performs UPDRS assessment

Patient Engagement Questionnaire

Record Neupro dose

Complete questionnaire (PDQ-39)

Recording of AEs and concomitant medications
Experimental Group, in clinic:

Return Kinesia-360 equipment to site
8.6
Early Withdrawal Visit
In case of an Early Withdrawal Visit, the same assessments as planned for Visit 2 shall be 
performed (see Section 8.5).
9
ASSESSMENT OF EFFICACY
9.1
Inclusion criteria threshold related to tremor and/or 
bradykinesia
Based on prior experience with studies involving dopaminergic therapies, GLNT expects
bradykinesia and tremor to improve when using Neupro during PD0049. At Screening (ie, on 
Day 1), Investigators will perform the Kinesia-ONE assessment battery in triplicate on the more 
affected side of the body of each subject. As subjects will be on their individual Parkinson’s 
disease medication when entering the study, they will likely be in a relative “on” state. However, 
since these subjects will be newly prescribed Neupro as their Parkinson’s disease symptoms are 
not sufficiently controlled by their current therapy, it is likely that 1 or more symptoms will be 
present at Screening. To ensure subjects have sufficient room to improve, the inclusion criteria 
for this study include the presence of tremor and/or bradykinesia at Screening as measured by 
Kinesia-ONE. Specifically, based on experience in prior studies, the average of the 
triplicate resting tremor scores and the triplicate finger tapping scores (6 scores in total, averaged 
for 1 single score) must be >1.0 at Screening for subjects to be eligible for inclusion in this study 
(see Section 6.1, inclusion criterion #6).
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 25 of 38
9.1.1
Unified Parkinson’s Disease Rating Scale
The change from Baseline to Visit 2 (Week 12) in Part III UPDRS Motor Score will be utilized 
as a primary efficacy variable.
The UPDRS is a comprehensive assessment of symptoms in subjects with Parkinson’s disease. If 
possible, the same Investigator will perform both UPDRS assessments on a given subject. In 
PD0049, Parts I, II, and IV of the UPDRS will be used for the assessment of other efficacy 
variables.
9.1.2
39-Item Parkinson’s Disease Questionnaire
Another efficacy variable to be assessed is the change from Baseline to Visit 2 (Week 12) in 
PDQ-39 questionnaire scores.
In Parkinson’s disease, the PDQ-39 is the most widely used subject-reported rating scale 
endpoint in clinical studies.
10
ASSESSMENT OF SAFETY
10.1
Adverse events
10.1.1
Definitions
10.1.1.1
Adverse event
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the ICF), including any pretreatment and posttreatment periods required by the 
protocol, must be reported in the eCRF even if no Neupro was taken but specific study 
procedures were conducted. This includes all AEs not present prior to the initial visit and all AEs 
that recurred or worsened after the initial visit.
Signs or symptoms of the condition/disease for which Neupro is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
increases in a clinically significant manner as compared to the clinical profile known to the 
Investigator from the subject’s history or the pre-Neupro Period.
10.1.1.2
Serious adverse event
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. A serious adverse event (SAE) must meet 1 or more of the following criteria:

Death

Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.)
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 26 of 38

Significant or persistent disability/incapacity

Congenital anomaly/birth defect (including that occurring in a fetus)

Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious
(Important medical events may include, but are not limited to, potential Hy’s Law, allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse.)

Initial inpatient hospitalization or prolongation of hospitalization
(A patient admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 
admission to the hospital would also qualify for the initial inpatient hospitalization criteria. 
However, emergency room visits that do not result in admission to the hospital would not 
qualify for this criteria and, instead, should be evaluated for 1 of the other criteria in the 
definition of serious [eg, life-threatening adverse experience, important medical event].
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery 
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
this would then qualify as an AE and, if necessary, the seriousness of the event would need to 
be determined.)
10.1.1.3
Adverse events of special interest
Not applicable.
10.1.2
Procedures for reporting and recording adverse events and other 
safety related information
The Investigator is requested to instruct participating subjects of the need to inform them of any 
AE or other safety related information during the study, regardless of the relationship to 
medication, device use, or study procedures.
The subject will be given the opportunity to report AEs spontaneously. A general prompt will 
also be given at each study visit to detect AEs. For example:
“Did you notice anything unusual about your health (since your last visit)?”
In addition, the Investigator should review any self-assessment procedures (eg, diary cards) 
employed in the study.
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 27 of 38
10.1.2.1
Description of adverse events
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF 
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation.
Details for completion of the AE eCRF (including judgment of relationship to Neupro) are 
described in the eCRF Completion Guidelines.
10.1.2.2
Rule for repetition of an adverse event
An increase in the intensity of an AE should lead to the repetition of the AE being reported with:

The outcome date of the first AE that is not related to the natural course of the disease being 
the same as the start date of the repeated AE, and the outcome of “worsening”

The AE verbatim term being the same for the first and repeated AE, so that the repeated AE 
can be easily identified as the worsening of the first one
Details for completion of the AE are described in the eCRF Completion Guidelines.
10.1.2.3
Reporting of serious AEs (related or not to Neupro)
An Investigator shall submit to UCB a report of any SAE experienced by a study subject, 
whether or not considered related to the participation in the study (ie, associated or not with 
Neupro) within 24 hours after the Investigator first learns of the event using the appropriate 
form.
Every effort shall be made to report the following information: date of AE, treatment/action 
taken, resolution, assessment of both the seriousness and the relationship to Neupro.
10.1.2.4
Device reporting
Great Lakes Neuro Technologies, Inc. will follow FDA medical device reporting requirements 
per 21CFR803. Sites will report adverse device effects and device deficiencies directly to GLNT 
(
: Office: 
[9:00am – 5:00pm EST]; Mobile: 
 
[after business hours]; email: 
). An adverse device event (ADE) is 
defined as any AE related to the use of a device. A device deficiency is defined as inadequacy of 
a device with respect to its identity, quality, durability, reliability, safety, or performance. Great 
Lakes Neuro Technologies, Inc. will share this information with UCB.
10.1.3
Follow up of adverse events
An AE should be followed until it has resolved, has a stable sequelae, the Investigator 
determines that it is no longer clinically significant, or the subject is lost to follow up. This 
follow-up requirement applies to AEs and SAEs. 
If an AE is ongoing at the end of the study for a subject, follow up should be provided until 
resolution/stable level of sequelae is achieved, or until the Investigator no longer deems that it is 
clinically significant, or until the subject is lost to follow up. If no follow up is provided, the 
Investigator must provide a justification. The follow up will usually be continued for 30 days
after the subject has discontinued treatment with Neupro.
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 28 of 38
Information on SAEs obtained after clinical database lock will be captured through the Patient 
Safety (PS) database without limitation of time.
10.1.4
Pregnancy and breastfeeding
Investigators are required to report pregnancy of a subject, pregnancy of a subject’s partner, and 
a subject who is breastfeeding using the Pregnancy Report and Outcome form for postmarketing 
cases. The procedure for reporting a pregnancy or breastfeeding is identical to the procedure for 
reporting safety relevant information (see Section 10.1.2.3).
The progression of the pregnancy and the eventual birth (if applicable) must be followed up 
using the same form in which the Investigator has to report on the health of the mother and of the 
child. Every reasonable attempt should be made to follow the development and health of the 
child for at least 30 days after birth for any significant medical issues or development delay.
If the subject is lost to follow up and/or refuses to give information, written documentation of 
attempts to contact the subject needs to be provided by the Investigator and filed at the site.
In cases where the partner of a male subject enrolled in this study becomes pregnant, the 
Investigator or designee is asked to contact the subject to request consent of the partner via the 
Partner Pregnancy Consent form that should be available in the Investigator’s site file. The 
Investigator will complete the Pregnancy Report and Outcome form for postmarketing cases and 
send it to UCB only after the partner has agreed that additional information can be captured and 
has provided the signed Partner Pregnancy Consent form.
10.1.5
Overdose of medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the eCRF. Any SAE or nonserious AE associated with excessive dosing must be 
followed as any other SAE or nonserious AE. These events are only considered AEs or SAEs if 
there are associated clinical signs and symptoms or if the act of taking the excess medicine itself 
is an AE or SAE (eg, suicide attempt).
Further details on Neupro overdosing can be found in the label (NEUPRO [package insert]. 2016
[Section 15]).
10.2
Laboratory measurements
Not applicable.
10.3
Other safety measurements
10.3.1
Rate of discontinuation of treatment with Neupro
The comparison of the rate of discontinuation of treatment with Neupro during the course of the 
study for the Control Group and the Experimental Group is one of the safety variables in 
PD0049.
Subjects who discontinue treatment with Neupro are encouraged to attend an Early Withdrawal 
Visit (see Section 8.6). For subjects randomized to the Experimental Group, discontinuation of 
treatment with Neupro can also be captured via the Kinesia-360 diary medication section within 
the respective APP.
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 29 of 38
11
STUDY MANAGEMENT AND ADMINISTRATION 
11.1
Adherence to protocol
The Investigator should not deviate from the protocol. However, the Investigator should take any 
measure necessary in deviation from or not defined by the protocol in order to protect clinical 
study subjects from any immediate hazard to their health and safety. In this case, this action 
should be taken immediately, without prior notification of the regulatory authority, IRB, or 
sponsor.
After implementation of such measure, the Investigator must notify the Clinical Project Manager
of the sponsor within 24 hours and follow any local regulatory requirements.
11.2
Monitoring
UCB (or designee) will monitor the study to meet the sponsor’s monitoring Standard Operating 
Procedures (SOPs), International Council for Harmonisation-Good Clinical Practice (ICH-GCP)
guideline, and applicable regulatory requirements, and to ensure that study initiation, conduct, 
and closure are adequate. Monitoring of the study may be delegated by UCB to a Contract 
Research Organziation (CRO) or a contract monitor.
The Investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any 
missing information. The Investigator(s)/institution(s) will permit direct access to source 
data/documents for study-related monitoring, audits, IRB review, and regulatory inspection(s).
The Investigator will allow UCB (or designee) to periodically review all eCRFs and 
corresponding source documents (eg, hospital and laboratory records for each study participant). 
Monitoring visits will provide UCB (or designee) with the opportunity to evaluate the progress 
of the study, verify the accuracy and completeness of eCRFs, ensure that all protocol 
requirements, applicable authorities regulations, and Investigator’s obligations are being 
fulfilled, and resolve any inconsistencies in the study records.
11.2.1
Definition of source data 
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, electrocardiogram (ECG) or other printouts, completed scales, 
or quality of life questionnaires. Source documents should be kept in a secure, limited access 
area.
Source documents that are computer generated and stored electronically must be printed for 
review by the monitor (eg, ECG reports). Once printed, these copies should be signed and dated 
by the Investigator and become a permanent part of the subject’s source documents. The 
Investigator will facilitate the process for enabling the monitor to compare the content of the 
printout and the data stored in the computer to ensure all data are consistent.
Electronic data records, such as Holter monitor records or electroencephalogram records, must 
be saved and stored as instructed by UCB (or designee).
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16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
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11.2.2
Source data verification
Source data verification ensures accuracy and credibility of the data obtained. During monitoring 
visits, reported data are reviewed with regard to being accurate, complete, and verifiable from 
source documents (eg, subject files, recordings from automated instruments, tracings [ECG], 
x-ray films, laboratory notes). All data reported on the eCRF should be supported by source 
documents, unless otherwise specified in Section 11.2.1.
11.3
Data handling
11.3.1
Case Report form completion
The Investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
eCRFs and in all required reports.
Any change or correction to the eCRF after saving must be accompanied by a reason for the 
change.
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the Investigator.
The Investigator should maintain a list of personnel authorized to enter data into the eCRF.
Detailed instructions will be provided in the eCRF Completion Guidelines.
11.3.2
Database entry and reconciliation
Case Report forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system (CDMS). Computerized data cleaning checks 
will be used in addition to manual review to check for discrepancies and to ensure consistency of 
the data. The data are entered into the eCRFs once and are subsequently verified.
An electronic audit trail system will be maintained within the CDMS to track all data changes in 
the database once the data have been saved initially into the system or electronically loaded. 
Regular backups of the electronic data will be performed.
11.3.3
Subject Screening and Enrollment log/Subject Identification Code list
The subject’s screening and enrollment will be recorded in the Subject Screening and Enrollment 
Log.
The Investigator will keep a Subject Identification Code list. This list remains with the 
Investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation.
11.4
Termination of the study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity.
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16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
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If the study is prematurely terminated or suspended, UCB (or its representative) will inform the 
Investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory 
requirement(s). The IRB should also be informed and provided with reason(s) for the termination 
or suspension by the sponsor or by the Investigator/institution, as specified by the applicable 
regulatory requirement(s). In addition, arrangements will be made for the return of the Kinesia 
devices and other material in accordance with UCB procedures for the study.
11.5
Archiving and data retention
The Investigator will maintain adequate records for the study, including eCRFs, medical records, 
Informed Consent documents, device dispensing and disposition records, safety reports, 
information regarding participants who discontinued, device distribution, and other pertinent 
data.
All essential documents are to be retained by the Investigator for at least 5 years after the final 
study report or first publication of the study results becomes available, whichever comes later. 
These documents should be retained for a longer period, however, if required by the applicable 
regulatory requirement(s) or by an agreement with UCB. The Investigator will contact UCB for 
authorization prior to the destruction of any study records or in the event of accidental loss or 
destruction of any study records. The Investigator will also notify UCB should he/she relocate or 
move the study-related files to a location other than that specified in the sponsor’s trial master 
file.
11.6
Audit and inspection
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities.
The main purposes of an audit or inspection are to confirm that the rights and well-being of the 
subjects enrolled have been protected, that enrolled subjects (ie, signing consent and undergoing 
study procedures) are appropriate for the study, and that all data relevant for the evaluation of 
Neupro have been processed and reported in compliance with the planned arrangements, the 
protocol, investigational site, and IRB SOPs, ICH-GCP, and applicable regulatory requirements.
The Investigator will provide direct access to all study documents, source records, and source 
data. If an inspection by a regulatory authority is announced, the Investigator will immediately 
inform UCB (or designee).
11.7
Good Clinical Practice
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
Investigator, institution, institution staff, or designees of the sponsor will lead to prompt action 
by UCB to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study.
12
STATISTICS
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan (SAP).
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 32 of 38
12.1
Definition of analysis sets
Four analysis sets will be defined for this study: the Enrolled Set (ES), the Safety Set (SS), the 
Full Analysis Set (FAS), and the Per-Protocol Set (PPS).
The ES will consist of all subjects who signed the ICF.
The SS will consist of all subjects who received at least 1 dose of Neupro. The SS will be used 
for the analysis of all demographic, disposition, and safety data.
The FAS will consist of all subjects who have at least 1 valid Baseline and at least 1 valid 
post-Baseline efficacy measurement. The FAS will be used for the analysis and presentation of 
the efficacy data. In the case of misallocation, subjects will be primarily analyzed according to 
Kinesia-360 application (yes/no). However, if applicable, sensitivity analysis will also be 
performed according to the randomized group.
The PPS will consist of those subjects in the FAS who do not have any important protocol 
deviations that would have an impact on the efficacy variables. The PPS will be used for 
sensitivity analysis.
12.2
General statistical considerations
All analyses will be performed using SAS® version 9.3 or higher (SAS Institute, Cary, NC, 
USA). Continuous variables will be summarized by visit (where applicable) with the statistics 
including the number of subjects (n), mean, standard deviation (SD), median, minimum, and 
maximum. Categorical variables will be summarized by visit (where applicable) with frequency 
counts and percentages.
Unless otherwise specified, the comparisons will be for outcomes in subjects with Parkinson’s 
disease in the Experimental Group (optimal Neupro dosing regimen will be titrated using motor 
symptom data collected with the Kinesia-360 wearable technology in addition to standard 
clinical practice) versus outcomes in subjects with Parkinson’s disease in the Control Group 
(optimal Neupro dosing regimen will be titrated using only standard clinical practice). It is 
obvious that Kinesia-360 based efficacy data will be presented for the Experimental group only.
Unless otherwise specified, the level of significance for all tests will be 0.05. All statistical tests 
are 2-sided; however, they are exploratory only and p-values <0.05 do not indicate statistical 
significance, since no alpha adjustment will be performed.
All data recorded in the eCRF, APP, and questionnaires will be listed.
12.3
Planned efficacy analyses
12.3.1
Analysis of the efficacy variables
The efficacy variables, change from Baseline to Visit 2 (for all efficacy variables not based on 
Kinesia-360) will be analyzed utilizing an analysis of covariance (ANCOVA) with Baseline as a 
covariate, “center” as factor, and “group” as main factor. The 2 groups are the Experimental 
Group (EG) and the Control Group (CG).
The 2-sided null and alternative hypotheses are: 

Null hypothesis (H0): EG=CG

Alternative hypothesis (Ha): EG≠CG
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 33 of 38
EG: Represents the change from Baseline to Visit 2 for subjects in the Experimental Group.
CG: Represents the change from Baseline to Visit 2 for subjects in the Control Group.
The efficacy analysis will be performed on the FAS and observed cases will be utilized. The 
group effect will be estimated and presented with 95% 2-sided confidence intervals (CIs) and 
p-values.
The PPS will be used for sensitivity analysis on selected efficacy variables.
12.3.2
Other efficacy analyses
Kinesia-360-based efficacy data will be presented descriptively for the Experimental Group. Due 
to repeated measurements (during titration weekly and during maintenance), comparisons will be 
performed by time point and also by dose, if applicable (dependent on number of subjects in 
respective dose groups). Optional time points might also be subject to analysis (dependent on 
number of subjects at respective time points or windows for time points).
12.4
Planned safety analyses
12.4.1
Safety analyses
All analyses of safety data will be performed on the SS.
The incidence of subjects with treatment-emergent AEs (TEAEs) and/or SAEs will be 
determined. Furthermore, the absolute and relative frequencies for subjects with a given TEAE 
with respect to the preferred term according to the latest available version of the Medical 
Dictionary for Regulatory Activities (MedDRA®) will be determined within each study part and 
system organ class. Additional tables will include, but are not limited to, summaries of TEAEs 
by maximum event intensity and causal relationship to Neupro. The actions taken for each AE, 
the time of onset of the AE, and the duration of each AE will be listed.
Further details will be provided in the SAP.
12.5
Handling of protocol deviations
Important protocol deviations are identified as part of the data cleaning process in the Data 
Cleaning Plan. Ongoing data cleaning meetings will be held throughout the duration of the study. 
Objectives of these meetings include to review and update (if necessary) the important protocol 
deviations and discuss exclusion of subjects from analysis populations. Furthermore, overall 
trends in protocol deviations will be discussed at the Data Evaluation Meeting. Through this 
ongoing data cleaning and evaluation process, all decisions regarding important protocol 
deviations and exclusions from analysis populations are made on an ongoing basis.
12.6
Handling of dropouts or missing data
In general, there will be no imputation of missing data.
12.7
Planned interim analysis and data monitoring
Not applicable.
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16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 34 of 38
12.8
Determination of sample size
Due to the character of the study, no formal sample size estimation can be performed. A sample 
size of approximately 40 will be regarded to be sufficient to get an impression of the effect of the 
device on the efficacy variables.
13
ETHICS AND REGULATORY REQUIREMENTS
13.1
Informed consent
Subject’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki.
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the subject in both oral and written form by the Investigator (or 
designee). Each subject will have the opportunity to discuss the study and its alternatives with 
the Investigator.
Prior to participation in the study, the ICF should be signed and personally dated by the subject, 
or his/her legal representative, and by the person who conducted the informed consent discussion 
(Investigator or designee). The subject or his/her legal representative must receive a copy of the 
signed and dated ICF. As part of the consent process, each subject must consent to direct access 
to his/her medical records for study-related monitoring, auditing, IRB review, and regulatory 
inspection.
If the ICF is amended during the study, the Investigator (or the Sponsor, if applicable) must 
follow all applicable regulatory requirements pertaining to the approval of the amended ICF by 
the IRB and use of the amended form.
All studies conducted at centers in the US must include the use of a Health Insurance Portability 
and Accountability Act Authorization form.
The subject may withdraw his/her consent to participate in the study at any time. A subject is 
considered as enrolled in the study when he/she has signed the ICF. An eCRF must not be 
started, nor may any study specific procedure be performed for a given subject, without having 
obtained his/her written consent to participate in the study.
13.2
Subject identification cards
Upon signing the ICF, the subject or legal representative will be provided with a subject 
identification card in the language of the subject. The Investigator will fill in the subject 
identifying information and medical emergency contact information. The Investigator will 
instruct the subject to keep the card with him/her at all times.
13.3
Institutional Review Boards
The study will be conducted under the auspices of an IRB and in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki.
The Investigator(s)/UCB will ensure that an appropriately constituted IRB that complies with 
applicable country-specific regulations will be responsible for the initial and continuing review 
and approval of the clinical study. Prior to initiation of the study, the Investigator/UCB will 
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 35 of 38
forward copies of the protocol, ICF, Investigator’s Brochure, Investigator’s curriculum vitae (if 
applicable), advertisement (if applicable), and all other subject-related documents to be used for 
the study to the IRB for its review and approval.
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB for the protocol and all other documents submitted to the IRB.
The Investigator will also promptly report to the IRB all changes in the study, all unanticipated 
problems involving risks to human subjects or others, and any protocol deviations, to eliminate 
immediate hazards to subjects.
The Investigator will not make any changes in the study or study conduct without IRB approval, 
except where necessary to eliminate apparent immediate hazards to the subjects. For minor 
changes to a previously approved protocol during the period covered by the original approval, it 
may be possible for the Investigator to obtain an expedited review by the IRB as allowed.
As part of the IRB requirements for continuing review of approved studies, the Investigator will 
be responsible for submitting periodic progress reports to the IRB (based on IRB requirements), 
at intervals appropriate to the degree of subject risk involved, but no less than once per year. The 
Investigator should provide a final report to the IRB following study completion.
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active Investigators in accordance with applicable regulatory requirements. 
The appropriate IRB will also be informed by the Investigator or the Sponsor, as specified by the 
applicable regulatory requirements in each concerned country. Where applicable, Investigators 
are to provide the Sponsor (or its representative) with evidence of such IRB notification.
13.4
Subject privacy
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject number 
assigned at Screening.
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB, or representatives of regulatory authorities will be allowed to review that portion of the 
subject’s primary medical records that directly concerns this study (including, but not limited to, 
admission/discharge summaries for hospital admissions occurring during a subject’s study 
participation, and autopsy reports for deaths occurring during the study).
13.5
Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective.
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB, and the regulatory authorities (if required), prior to being 
implemented.
14
FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 36 of 38
Finance, insurance, and publication rights are addressed in the Investigator and/or CRO 
agreements, as applicable.
15
REFERENCES
NEUPRO [package insert]. Smyrna, GA: UCB Inc.; 2016
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 37 of 38
16
DECLARATION AND SIGNATURE OF INVESTIGATOR
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and local 
laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects of 
this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially, and will not be made available to third parties without prior authorization by 
UCB.
All rights of publication of the results reside with UCB, unless other agreements were made in a 
separate contract.
Investigator:
Printed name
Date/Signature
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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 38 of 38
17
SPONSOR DECLARATION
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice.
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 1 of 39
STATISTICAL ANALYSIS PLAN 
Study: PD0049
Product: Rotigotine transdermal system
A MULTICENTER, OPEN-LABEL, TWO-ARM STUDY TO EVALUATE THE IMPACT OF 
USING WEARABLE DEVICES IN ADDITION TO STANDARD CLINICAL PRACTICE ON 
PARKINSON’S SUBJECT SYMPTOMS MANAGEMENT
SAP/Amendment Number
Date
Final SAP
14 Jun 2017
Amendment 1
31 Jan 2018
Confidentiality Statement
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, reproduced, 
published, or otherwise used without the express permission of UCB.
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 2 of 39
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................5
1
INTRODUCTION .............................................................................................................7
2
PROTOCOL SUMMARY.................................................................................................7
2.1 Study objectives.................................................................................................................7
2.1.1
Primary objectives .................................................................................................7
2.1.2
Other objectives.....................................................................................................8
2.2 Study variables...................................................................................................................8
2.2.1
Efficacy variables ..................................................................................................8
2.2.1.1
Primary efficacy variables...........................................................................8
2.2.1.2
Other efficacy variables...............................................................................9
2.2.2
Safety variable .......................................................................................................9
2.3 Study design and conduct ................................................................................................10
2.4 Determination of sample size...........................................................................................13
3
DATA ANALYSIS CONSIDERATIONS......................................................................13
3.1 General presentation of summaries and analyses ............................................................13
3.2 General study level definitions ........................................................................................14
3.2.1
Analysis time points ............................................................................................14
3.2.1.1
Relative Day..............................................................................................14
3.2.1.2
End date of the Treatment Period..............................................................14
3.2.2
Study periods .......................................................................................................14
3.2.3
Mapping of assessments performed at Early Withdrawal Visit ..........................15
3.2.4
Rescreening..........................................................................................................15
3.3 Definition of Baseline values...........................................................................................15
3.4 Protocol deviations...........................................................................................................15
3.5 Analysis sets.....................................................................................................................15
3.5.1
Enrolled Set .........................................................................................................15
3.5.2
Safety Set.............................................................................................................15
3.5.3
Full Analysis Set..................................................................................................15
3.5.4
Per Protocol Set ...................................................................................................16
3.6 Treatment assignment and treatment groups ...................................................................16
3.7 Center pooling strategy....................................................................................................16
3.8 Coding dictionaries ..........................................................................................................16
3.9 Changes to protocol-defined analyses..............................................................................16
4
STATISTICAL/ANALYTICAL ISSUES.......................................................................16
4.1 Adjustments for covariates...............................................................................................16
4.2 Handling of dropouts or missing data..............................................................................17
4.3 Interim analyses and data monitoring..............................................................................17
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 3 of 39
4.4 Multicenter studies...........................................................................................................17
4.5 Multiple comparisons/multiplicity...................................................................................17
4.6 Use of an efficacy subset of subjects ...............................................................................17
4.7 Active-control studies intended to show equivalence......................................................18
4.8 Examination of subgroups ...............................................................................................18
5
STUDY POPULATION CHARACTERISTICS.............................................................18
5.1 Subject disposition...........................................................................................................18
5.2 Protocol deviations...........................................................................................................18
6
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................19
6.1 Demographics ..................................................................................................................19
6.2 Other Baseline characteristics..........................................................................................19
6.3 Medical history and concomitant diseases.......................................................................19
6.4 Prior and concomitant medications..................................................................................19
7
MEASUREMENTS OF TREATMENT COMPLIANCE...............................................20
8
EFFICACY ANALYSES ................................................................................................20
8.1 Statistical analysis of the primary efficacy variables.......................................................20
8.1.1
Derivations of primary efficacy variables ...........................................................20
8.1.1.1
Unified Parkinson’s Disease Rating Scale Part III....................................20
8.1.1.2
Kinesia-ONE variables..............................................................................20
8.1.1.3
Number of Neupro dose changes ..............................................................21
8.1.2
Primary analysis of the primary efficacy variables .............................................22
8.1.3
Secondary analyses of the primary efficacy variables.........................................22
8.1.4
Supportive and sensitivity analyses of the primary efficacy variables................22
8.2 Analysis of other efficacy variables.................................................................................22
8.2.1
Kinesia-360 motor scores ....................................................................................22
8.2.2
Parkinson’s Disease Questionnaire (PDQ-39).....................................................23
8.2.3
Patient Activation Measure (PAM-13)................................................................24
8.2.4
Unified Parkinson’s Disease Rating Scale Parts I, II, IV ....................................24
9
PHARMACOKINETICS AND PHARMACODYNAMICS..........................................25
9.1 Pharmacokinetics .............................................................................................................25
9.2 Pharmacodynamics ..........................................................................................................25
10
SAFETY ANALYSES.....................................................................................................25
10.1 Extent of exposure ...........................................................................................................25
10.2 Adverse events.................................................................................................................25
10.3 Clinical laboratory evaluations ........................................................................................26
10.4 Other observations related to safety.................................................................................26
10.4.1
Weight..................................................................................................................26
10.4.2
Other safety variables ..........................................................................................26
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 4 of 39
11
REFERENCES ................................................................................................................27
12
APPENDICES .................................................................................................................28
13
AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN (SAP) (IF 
APPLICABLE)................................................................................................................29
13.1 AMENDMENT 1.............................................................................................................29
13.2 AMENDMENT 2.............................................................................................................38
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE.....................................................39
LIST OF TABLES
Table 2‒1:
Schedule of study assessments.........................................................................10
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 5 of 39
LIST OF ABBREVIATIONS
ADaM
Analysis Data Model
AE
adverse event
ANCOVA
analysis of covariance
APP
application, application software
BMI
body mass index
BSA
body surface area
CG
Control Group
CI
confidence interval
cm
centimeters
EG
Experimental Group
EOS
end of study
ES
Enrolled Set
EW
Early withdrawal
FAS
Full Analysis Set
FDA
Food and Drug Administration
GLNT
Great Lakes NeuroTechnologies, Inc.
H0
null hypothesis
Ha
alternative hypothesis
HLT
high level term
ICF
Informed Consent form
ICH
International Council for Harmonization
in
inches
lb
pounds
kg
kilograms
MedDRA
Medical Dictionary for Regulatory Activities
PAM-13
13-Item Patient Activation Measure
PDQ-39
39-Item Parkinson’s Disease Questionnaire
PPS
Per-Protocol Set
PT
preferred term
Q1
first (25th percent) quartile
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 6 of 39
Q3
third (75th percent) quartile
SAP
Statistical Analysis Plan
SD
standard deviation
SOC
system organ class
SDTM
Study Data Tabulation Model
SS
Safety Set
TEAE
treatment-emergent adverse event
UPDRS
Unified Parkinson’s Disease Rating Scale
WHODD
World Health Organization Drug dictionary
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 7 of 39
1
INTRODUCTION
This Statistical Analysis Plan (SAP) defines the scope of statistical analyses and provides a 
detailed description of methodology for the statistical analyses to support the final clinical study 
report for PD0049.
The SAP is based on the clinical study protocol, dated 16 Dec 2016. 
The content of this SAP is in compliance with the International Council for Harmonization (ICH) 
/ Food and Drug Administration (FDA) E9 Guidance documents.
2
PROTOCOL SUMMARY
PD0049 is a pilot study to investigate whether motor symptoms in subjects with Parkinson’s 
disease who start treatment with Neupro® can be improved by using wearable devices. 
Specifically, this study focuses on investigating how to optimize the evaluation of motor 
symptoms in subjects with Parkinson’s disease aiming at enabling Investigators to optimize 
subjects’ Neupro dosing regimens and ensure better patient outcomes in a timelier manner.
In this study, 2 Kinesia devices (Kinesia-ONE and Kinesia-360) will be employed to record 
specific motor symptoms. Approximately 40 subjects with Parkinson’s disease of any stage will 
be randomized (1:1 ratio) to either the Control Group or the Experimental Group. Specific motor 
tasks will be measured in all subjects with Kinesia-ONE on Day 1. In contrast to subjects 
randomized to the Control Group, subjects randomized to the Experimental Group will also use 
the Kinesia-360 device for home-based self-recording of their motor symptoms.
All subjects will start Neupro treatment at a dose of either rotigotine 2mg/24h or 4mg/24h 
(according to the disease stage of the subject), which will then be adjusted based on symptom 
assessment either via standard care alone (Control Group) or via a combination of standard care 
and evaluation of the recordings made available by the Kinesia wearable technologies 
(Experimental Group). The Neupro dosing regimen used in PD0049 follows standard of care, 
and is in line with the approved dosing regimen for rotigotine in the treatment of Parkinson’s 
disease (ie, up to 8mg/24h, depending on the stage of the disease).
PD0049 starts with in-clinic Screening activities, assessments (including recording of Baseline 
motor symptoms via Kinesia-One), and training in the use of Kinesia-360 devices (for subjects 
randomized to the Experimental Group only) on Day 1, followed by 3 days at home: During this 
period, subjects randomized to the Experimental Group will use the Kinesia-360 device to record 
their motor symptoms (on Days 2 and 3). Subjects allocated to the Control Group will start 
treatment with Neupro preferably on Day 1 (but no later than Day 4); subjects allocated to the 
Experimental group will start treatment with Neupro on Day 4. There are no required visits from 
Week 2 up to Week 12 (Visit 2). However, Investigators and subjects in the Experimental Group 
are encouraged to discuss by phone Kinesia-360 motor symptom reports and needs for any 
changes in Neupro dosing. Subjects of either group return to the clinic for final assessments and 
reporting of adverse events (AEs) and concomitant medications at Week 12. The individual 
duration of study participation may last up to 12 weeks.
2.1
Study objectives
2.1.1
Primary objectives
The primary objectives of this study are to:
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 8 of 39

Evaluate whether Parkinson’s disease motor symptoms in subjects starting Neupro can be 
improved by using feedback of motor symptom data from the Kinesia-360 wearable 
technology presented to subjects and Investigators in addition to standard clinical practice as 
compared with only standard clinical practice.

Evaluate the Neupro dosing regimen when using feedback of motor symptom data collected 
with the Kinesia-360 wearable technology in addition to standard clinical practice as 
compared with only standard clinical practice.

Evaluate whether subjects with Parkinson’s disease are more likely to continue the usage of 
Neupro if Parkinson’s disease motor symptom data collected using the Kinesia-360 wearable 
technology is used to provide the subjects with feedback on the status of their Parkinson’s 
disease motor symptoms and is used in addition to standard of care for titrating their Neupro 
dosing regimen.
2.1.2
Other objectives
Other objectives of this study are to:

Evaluate whether the quality of life of subjects with Parkinson’s disease can be improved by 
using the Kinesia-360 wearable technology to collect motor symptom data in addition to 
standard clinical practice as compared with only standard clinical practice to titrate the 
Neupro dosing regimen.

Evaluate whether subjects with Parkinson’s disease are more actively engaged in the 
management and treatment of their disease with Neupro therapy with the use of the 
Kinesia-360 wearable technology as compared to without the use of the Kinesia-360 
wearable technology.

Evaluate the safety of Neupro.
2.2
Study variables
2.2.1
Efficacy variables
2.2.1.1
Primary efficacy variables
The primary efficacy variables of this study are:

Change from Baseline (Visit 1/Week 1) to Visit 2 (Week 12/3 months after start of treatment 
with Neupro) in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III Motor Score 

Change from Baseline (Visit 1/Week 1) to Visit 2 (Week 12) in Kinesia-ONE variables:

finger tapping speed score

rest tremor score

averaged finger tapping speed and resting tremor scores

postural tremor score

finger tapping amplitude score

hand grasp speed score
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 9 of 39

hand grasp amplitude score

rapid alternating movement speed score

rapid alternating amplitude score

dyskinesia score

kinetic tremor score

rapid alternating movement rhythm score

hand movements rhythm score

finger tapping rhythm score

average Kinesia-ONE score

Neupro dose per 24h at Visit 2 (Week 12) 

Number of Neupro dose changes during the study (between Visit 1 and Visit 2) 

Discontinuation of treatment with Neupro during the course of the study
2.2.1.2
Other efficacy variables
Other efficacy varibles are:

Change from Baseline to Visit 2 in the motor scores derived from the Kinesia-360 wearable 
technology by time (weekly/monthly) for the Experimental Group in:

average daily tremor score

average daily slowness score

average daily dyskinesia score

percent wear-time tremor detected

percent wear-time dyskinesia detected

percent wear-time user not moving

percent wear-time user was walking score

percent wear-time user active but not walking

number of steps per hour while wearing device

Number of days on Kinesia-360 device

Change from Baseline to Visit 2 (Week 12) in the 39-Item Parkinson’s Disease 
Questionnaire (PDQ-39) scores.

Change from Baseline to Visit 2 (Week 12) in subject engagement questionnaire scores.
2.2.2
Safety variable
Safety variable is:

Occurrence of AEs 
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 10 of 39
2.3
Study design and conduct
PD0049 is a multicenter, open-label, two-arm, 12-week study in subjects with Parkinson’s 
disease. On Day 1, eligible subjects will be randomized to either the Control Group or the 
Experimental Group in a 1:1 fashion. In both groups, subjects will use the Kinesia-ONE 
wearable device in-clinic at Visit 1 and Visit 2 for recording of specific motor symptoms, and 
subjects randomized to the Experimental Group will also use the Kinesia-360 wearable device at 
home while awake for continuous measurement of motor symptoms. The Investigator will use 
these symptom data to provide feedback to subjects on their motor symptoms and to supplement 
standard of care to titrate the optimal dose of Neupro for any given subject. In the Control 
Group, subjects will not use any wearable device at home, and the Investigator will use only 
standard of care to titrate the optimal Neupro dose.
Subjects in the Control Group and the Experimental Group will start treatment with Neupro 
2mg/24h or 4mg/24h (at the Investigator’s discretion and according to the disease stage of the 
subject) preferably on Day 1 (but no later than Day 4) or Day 4, respectively. Evaluations 
conclude 12 weeks after the start of treatment with Neupro (ie, at Visit 2).
The Neupro dosing regimen used in PD0049 follows standard of care, and is in line with the 
approved dosing regimen for rotigotine in the treatment of Parkinson’s disease (ie, up to 
8mg/24h, depending on the stage of the disease).
The decision to prescribe Neupro must be made by the Investigator independent of his/her 
decision to include the subject in the study. The subject’s treatment/Neupro intake must be 
within the terms of the marketing authorization; Neupro will not be supplied by UCB.
Each subject’s participation is approximately 12 weeks. The end of the study is defined as the 
date of the last visit of the last subject in the study.
This study will be conducted in the US, in approximately 6 sites and will include a total of 
approximately 40 subjects (20 subjects in the Experimental Group and 20 subjects in the Control 
Group). Of note, a single site will not randomize more than 20 subjects.
A schedule of study assessments is presented in Table 2‒1 :
Table 2‒1:
Schedule of study assessments
In Clinic
At Home
In Clinic
SCREENING
BASELINE
EOS/EW
Visit 1
Visit 2
Assessments
Day 1
Day 
2-3
Day 
4
Week 
2
Week 
3
Week 
4
Week 
11
Week 12
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 11 of 39
Table 2‒1:
Schedule of study assessments
In Clinic
At Home
In Clinic
SCREENING
BASELINE
EOS/EW
Visit 1
Visit 2
Assessments
Day 1
Day 
2-3
Day 
4
Week 
2
Week 
3
Week 
4
Week 
11
Week 12
(±3 days)
UPDRS 
X
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questionnaire
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X
X
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inclusion/exclusion criteria
X
Randomization
X
C Group: Start treatment 
with Neupro 2mg or 4mg 
preferably on Day 1 but no 
later than Day 4 (dose 
adjustments during study 
are performed per standard 
of care) 
X
X
C Group: Record Neupro 
dose
X
X
E Group: Kinesia-360 
device training and 
distribution of equipment
X
E Group: Subject wears 
Kinesia-360 wrist and 
ankle devices on Days 2 
and 3 at home for baseline
X
E Group: Start treatment 
with Neupro 2mg or 4mg 
on Day 4
X
E Group: Record Neupro 
dosec
X
X
E Group: Reminder 
phone calls from site to 
subject at beginning of 
Weeks 2, 3, 4 and 11 
(remind subject to charge 
devices and wear devices 
on at least 2 consecutive 
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 12 of 39
Table 2‒1:
Schedule of study assessments
In Clinic
At Home
In Clinic
SCREENING
BASELINE
EOS/EW
Visit 1
Visit 2
Assessments
Day 1
Day 
2-3
Day 
4
Week 
2
Week 
3
Week 
4
Week 
11
Week 12
(±3 days)
days during Weeks 2, 3, 4 
and 11)
E Group: Subject wears 
Kinesia-360 wrist and 
ankle devices on at least 2 
consecutive days at home
X
X
X
X
E Group: Subject and 
Investigator access 
Kinesia-360 device reports 
(subjects via device app, 
Investigators via GLNT 
web portal)
X
X
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combines standard of care
with Kinesia-360 motor 
symptom reports to adjust
Neupro dose and is
encouraged to contact the
subject by phone to 
discuss motor symptom 
reports and potential 
Neupro dose adjustments
anytime between V1 and
V2 based on clinical 
judgment 
X
E Group: Subject returns 
Kinesia-360 device 
equipment to site
X
Record adverse events
X
X
Record concomitant 
medications
X
X
APP=application; C Group=Control Group; E Group=Experimental Group; EOS=End of Study; EW=Early 
Withdrawal; GLNT=Great Lakes Neuro Technologies, Inc.; PDQ-39=39-Item Parkinson’s disease questionnaire; 
UPDRS=Unified Parkinson’s Disease Rating Scale; V=visit
a Only weight at V2.
b The average of the triplicate resting tremor scores and triplicate finger tapping scores from Kinesia-ONE must be 
>1.0 to be eligible for inclusion in this study.
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 13 of 39
c Subjects in the Experimental Group will be prompted to record Neupro dose in device app during each use of 
Kinesia-360 between V1 and V2.
d Subjects in the Experimental Group are to use Kinesia-360 on at least 2 consecutive days during Weeks 2, 3, 4 and 
11, but are free to use the device as often as they like between these time points prior to Visit 2.
2.4
Determination of sample size
Due to the character of the study, no formal sample size estimation can be performed. A sample 
size of approximately 40 will be regarded to be sufficient to get an impression of the effect of the 
device on the efficacy variables.
3
DATA ANALYSIS CONSIDERATIONS
3.1
General presentation of summaries and analyses
The statistical analyses will be performed by Chiltern. Computations and generation of outputs 
will be performed using SAS® (Statistical Analysis System, SAS-Institute, Cary, NC, USA) 
Version 9.3 or above. All tables and listings will use Courier New font size 9.
For continuous data in general, summary statistics (n [number of available measurements], 
arithmetic mean, standard deviation (SD), median, minimum, and maximum) will be presented 
by group. For selected variables, the first (25th percent) quartile (Q1) and the third (75th percent) 
quartile (Q3) may also be presented (for patient reported outcomes).
Mean, SD, median and quartiles will be displayed to 1 more decimal place than collected in the 
source data. Derived variables in general will display the mean, SD and median to 1 more 
decimal place than the variables used in the derivation (i.e. a change from Baseline will be 
reported to the same precision as the Baseline data). However, a special rule can be defined as 
needed for appropriate reporting.
For descriptive statistics of continuous variables by visit, the change from Baseline and actual 
value at the given time point will be displayed. The change from Baseline is the post-Baseline 
value minus the Baseline value. If the Baseline or post-Baseline value is missing, then the 
change from Baseline is set to missing. Percent change from Baseline is the change from 
Baseline divided by Baseline and multiplied by 100. If the Baseline value is 0 and the post-
Baseline value is also 0, then the percent change from Baseline is set to 0. If the Baseline value is 
0 and the post-Baseline value is non-zero, then the percent change from Baseline is set to 
missing. If the Baseline value is missing, the percent change from Baseline is set to missing.
Frequency tables (frequency counts and percentages) will be presented for categorical data. If 
there are no missing values then the missing row can be removed. If there are missing values 
(including missing a single assessment or entire visit), then include the missing row with the 
frequency count and percentage. If there are no subjects in a specific CRF category, then that 
row will be retained and 0 presented in the table. In general, percentages will be calculated based 
on the utilized analysis set. However, in the case of subgroup analyses, the N of the subgroup 
will be used as denominator.
Unless stated otherwise, all inferential statistical tests will be 2-sided and conducted at the 0.05 
alpha level. P-values will be presented to 3 decimal places. 
All data in the database (ADaM) will be presented in by-subject data listings, and sorted by 
group, site, subject number, variable (where applicable), and visit (where applicable). All listings 
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 14 of 39
will include repeated and unscheduled measurements. Such measurements will appear in 
chronological order. In all the listings dates will be presented in the format ‘YYYY-MM-DD’ 
and times will be presented in 24h clock format as ‘hh:mm’. The visit dates and phone contact 
dates will be presented in a listing. This includes the scheduled phone contacts in the 
Experimental Group and the unscheduled phone contacts in both groups. As scheduled phone 
contacts in the Experimental Group were consistently reported on both the form for scheduled 
contacts as well as on the unscheduled telephone log, duplicate phone contacts will be removed 
at the SDTM level. It will be considered at the SDTM level that the scheduled phone contacts do 
not appear twice, unless two or more phone contacts were documented as conducted on the same
day.
All tabulations will be sorted by variable and visit. Only scheduled visits will be included in the 
tabulation. Categorical data will be summarized by visit, using the number and percentage of 
subjects in each category. Percentages will be based on the corresponding population size (i.e., 
the denominator of percentages should match the sample size in the column header), unless 
otherwise noted via footnote in the applicable summary table. Percentages will be presented to 1 
decimal place. For data points with n=0 (i.e., no subjects in the applicable category), no value for 
percentage of subjects will be displayed.
3.2
General study level definitions
3.2.1
Analysis time points
3.2.1.1
Relative Day
The relative day of a visit or an event with respect to the first administration of study medication
(i.e. first patch application of Neupro) will be presented in subject data listings. Relative days 
will be calculated as follows:

If the start (stop) date occurred prior to the first application of study medication, the relative 
day is calculated as start (stop) date minus date of first patch application. That means that in 
subject data listings, relative days based on this situation will be preceded by a ‘-‘.

If the start (stop) date occurred on or after the first application of study medication but prior 
to the last patch application, the relative day is calculated as start (stop) date minus date of 
first patch application + 1.

If the start (stop) date occurred after the date of last patch application, the relative day is 
calculated as start (stop) date minus date of last patch application + 1. In subject data listings, 
relative days based on this situation will be preceded by a ‘+’.
Relative days will not be presented for partial or missing dates.
3.2.1.2
End date of the Treatment Period
The end date of the Treatment Period will be either the date of Visit 2 for subjects completing the 
Treatment Period, or the date of the Early Withdrawal for subjects who discontinued during the 
Treatment Period. If a subject does not have a Visit 2/EW, then the date of last known dose of 
study medication during the Treatment Period will define the end date of the Treatment Period.
3.2.2
Study periods
The following study periods are defined for the classification by study period:
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 15 of 39

Pretreatment Period: Prior to the date of first administration of study medication

Treatment Period: On or after the date of first administration of study medication and prior to 
or on the date of last administration of study medication during the Treatment Period.
3.2.3
Mapping of assessments performed at Early Withdrawal Visit
Efficacy and safety assessments at an Early Withdrawal Visit that correspond to a scheduled visit 
(Visit 2) will be summarized at the scheduled visit (Visit 2) if the assessment was scheduled to 
occur at that visit.
3.2.4
Rescreening
Rescreening was not foreseen in the clinical study protocol. However one subject was 
rescreened. In this case, the initial screening is documented with a different subject number than 
the second screening and following visits of this same subject. The fact that a rescreened subject 
has 2 different subject numbers is not accounted for in the analysis, which means that the subject 
will be counted twice in the tables based on the Enrolled Set. This was decided to be acceptable 
due to the exploratory nature of this study, and will not impact the efficacy and safety analysis.
3.3
Definition of Baseline values
Baseline values for efficacy and safety variables will be determined from the last available value 
on or before the day of the first patch application, unless otherwise noted for a specific type of 
data. In general, Baseline values will be the values collected at Visit 1.
3.4
Protocol deviations
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct or on the primary efficacy outcomes for an individual 
subject. The criteria for identifying important protocol deviations will be defined within the 
appropriate protocol-specific document. Important protocol deviations will be reviewed as part 
of the ongoing data cleaning process and data evaluation. All important deviations will be 
identified and documented prior to database lock to confirm exclusion from analysis sets.
3.5
Analysis sets
Four analysis sets will be defined for this study: the Enrolled Set (ES), the Safety Set (SS), the 
Full Analysis Set (FAS), and the Per-Protocol Set (PPS).
3.5.1
Enrolled Set
The ES will consist of all subjects who signed the Informed Consent form (ICF).
3.5.2
Safety Set
The SS will consist of all subjects who received at least 1 dose of Neupro. A subject who 
received Neupro after screen failing is not considered as treated within the study and therefore 
not included in the SS. The SS will be used for the analysis of all demographic, disposition, and 
safety data.
3.5.3
Full Analysis Set
The FAS will consist of all subjects who have at least 1 valid Baseline and at least 1 valid post 
Baseline efficacy measurement. That means, subjects in FAS have non-missing values at Visit 1 
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 16 of 39
and at Visit 2 either for the UPDRS Part III Motor Score or for at least one Kinesia-ONE 
variable or for Neupro dose per 24h.
The FAS will be used for the analysis and presentation of the efficacy data. In the case of 
misallocation, subjects will primarily be analyzed according to Kinesia-360 application (yes/no). 
However, if applicable, sensitivity analysis will also be performed according to the randomized 
group.
3.5.4
Per Protocol Set
The PPS will consist of those subjects in the FAS who do not have any important protocol 
deviations that would have an impact on the primary efficacy variables. The PPS will be used for 
sensitivity analysis.
3.6
Treatment assignment and treatment groups
Eligible Subjects will be randomized to either the Control Group or the Experimental Group. In 
the Control Group, optimal Neupro dosing regimen will be titrated using standard clinical 
practice only. In the Experimental Group, optimal Neupro dosing regimen will be titrated using 
motor symptom data collected with the Kinesia-360 wearable technology in addition to standard 
clinical practice.
Comparisons between Control Group and Experimental Group will be performed for outcomes 
where data are available for both groups, e.g. Kinesia-ONE data, and questionnaires. Kinesia-
360 data however are only available for subjects in the Experimental Group, and will therefore 
be presented only for this group.
3.7
Center pooling strategy
No pooling of centers is planned for this study.
3.8
Coding dictionaries
All AEs will be coded for analysis according to the Medical Dictionary for Regulatory Activities 
(MedDRA)® coding dictionary, using the latest version available. Prior and concomitant 
medications will be coded for analysis using the latest version of the World Health Organization 
Drug dictionary (WHO-DD).
3.9
Changes to protocol-defined analyses
Additional Kinesia-ONE scores which were not prespecified in the clinical study protocol are 
provided by the vendor. These will be analyzed in the same way as the prespecified variables.
4
STATISTICAL/ANALYTICAL ISSUES
4.1
Adjustments for covariates
The continuous efficacy variables, change from Baseline to Visit 2 (for all efficacy variables not 
based on Kinesia-360) will be analyzed utilizing an analysis of covariance (ANCOVA) with 
Baseline as a covariate, “center” as factor, and “group” as main factor. The adjustments for 
baseline value and center are included, as these variables may have a systematic impact on the 
efficacy outcome.
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 17 of 39
4.2
Handling of dropouts or missing data
Subjects who prematurely discontinue the study will be evaluated based on the data collected at 
the Withdrawal Visit. The Withdrawal Visit data will be used similar to Visit 2 data.
Adverse events with missing intensity will be assumed to be severe. Adverse events with missing 
relationship to study medication per the investigator will be assumed to be related.
For analyses of AEs and concomitant medication usage, a complete date must be established in 
order to correctly identify the AE or medication as occurring during treatment or not. For 
purposes of imputing missing components of partially-reported start and stop dates for AEs and 
for medication use, the algorithms listed below will be followed. Start and stop dates of AEs or 
concomitant medication will be displayed as reported in the subject data listings (i.e., no imputed 
values will be displayed in data listings).

Missing start day, but month and year present: If the start of study medication occurred in the 
same month and year as the occurrence of the AE/concomitant medication, the start day of 
the event/concomitant medication will be assigned to the day of first application of study 
medication. Otherwise the start day will be set to the 1st day of the month.

Missing start day and month, but year present: If the start of study medication occurred in the 
same year as the occurrence of the AE/concomitant medication, the start day and month will 
be assigned to the date of first application of study medication. Otherwise the start day and 
month will be set to January 1st.

Missing end day, but month and year present: The end day will be set to the last day of the 
month.

Missing end day and month, but year present: If the maximum of the subject’s date of study 
termination or the date equivalent to 30 days after the subject’s last application of study 
medication is the same year as the occurrence of the AE/Concomitant medication, then the 
end day and month will be set to the maximum of the date of study termination or the date 
equivalent to 30 days after last application of study medication. Otherwise the end day will 
be set to December 31st of the given year.
4.3
Interim analyses and data monitoring
No formal interim analysis is planned for PD0049. Also, no specific data monitoring, steering, or 
evaluation committee is planned for this study.
4.4
Multicenter studies
No multicenter analyses are planned. Therefore, this section is not applicable for this study.
4.5
Multiple comparisons/multiplicity
All statistical tests are considered exploratory, and calculated p-values <0.05 do not indicate 
statistical significance, since no alpha adjustment will be performed.
4.6
Use of an efficacy subset of subjects
The FAS will be used as primary analysis set for efficacy analyses. The primary efficacy 
analyses will be repeated for the PPS. The PPS will be used to evaluate subjects who have 
efficacy data and are reasonably compliant with the conditions of the study. This analysis set will
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 18 of 39
provide additional information on the efficacy analysis and will describe findings in a subset of 
subjects who more closely followed the intentions of the study protocol.
4.7
Active-control studies intended to show equivalence
This section is not applicable for this study.
4.8
Examination of subgroups
No subgroups are defined for this study.
5
STUDY POPULATION CHARACTERISTICS
5.1
Subject disposition
Subject disposition will be summarized on all subjects screened. The number of subjects 
screened, in addition to the number and percentage of those subjects who were screen failures, 
broken down by primary reason for screen failure, will be presented.
A summary of disposition of subjects will be provided for all screened subjects. The date of first 
subject in, date of last subject out, number of subjects screened, and the number of subjects in 
each analysis set by group and for all subjects will be summarized overall and by investigator 
site. Subjects who transferred sites will be summarized according to their original site.
A summary of disposition of analysis sets will be provided for the SS. Additionally, a summary 
of disposition and discontinuation reasons will present the number and percentage of subjects 
starting the study, completing the study, and discontinuing the study with primary reason for 
discontinuation.
A summary of discontinuations due to AEs for the SS will present the number and percentage of 
subjects who discontinued this study due to AEs broken down by type of AE. 
The following listings will be provided: study eligibility criteria text, subjects who did not meet 
study eligibility criteria, subject disposition, subject analysis sets, Neupro discontinuation and 
visit dates.
5.2
Protocol deviations
Important protocol deviations defined in the protocol-specific document, and additionally 
identified at the data evaluation meetings, will be listed. In addition, the number and percentage 
of subjects with at least 1 important protocol deviation will be summarized overall and by 
category of important protocol deviation for the SS. The number and percentage of subjects with 
no important protocol deviations will also be summarized for the SS. These will be summarized
by group and for all subjects overall. A listing of important protocol deviations will be provided.
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 19 of 39
6
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS
6.1
Demographics
Tables with descriptive statistics and listings will be given for the demographic variables age, 
gender, weight and height at Baseline, race, ethnicity, and body mass index (BMI). Demographic 
characteristics will be summarized for all study defined analysis sets, and presented in a listing.
The calculation of age is based on the date of informed consent and the date of birth. If the date 
of birth is incomplete, it will be completed with January as imputed month if month is missing 
and it will be completed with 1 as imputed day of birth if day is missing. Age is calculated as 
follows: Age (years) = ([Date of Informed Consent] – [Imputed Date of Birth]) / 365.25. It will 
be summarized as a continuous variable and as a categorical variable based on the categories: 
<65 years, 65-<85 years, ≥85 years, also based on the categories: <65 years, ≥65 years, and also 
based on the categories: <75 years, ≥75 years.
Weight recorded in pounds (lb) will be converted to kilograms (kg) as weight(lb)*0.4536kg/lb.
Height recorded in inches (in) will be converted to height in centimeters (cm) as 
height(in)*2.54cm/in.
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6.2
Other Baseline characteristics
The disease stage of Parkinson’s Disease at Baseline can be assessed by the given start dose of 
Neupro at either 2mg/24h or 4mg/24h. The start dose of Neupro is tabulated within the study 
medication summary.
6.3
Medical history and concomitant diseases
Medical history data and concomitant diseases data are not collected. Therefore this section is 
not applicable.
6.4
Prior and concomitant medications
Medications will be considered as prior if the start date of the medication is before the date of 
first patch administration. Medications will be considered as concomitant if they are taken at 
least once in the treatment period starting with the first patch administration and ending after the 
last patch administration during the study. Medications starting prior to first patch administration
and continuing into the treatment period will be considered both prior and concomitant 
medication.
In case of partial or missing dates the rules described in Section 4.2 will be applied.
Prior and concomitant medications will be summarized separately for the SS. The number and 
percentage of subjects who used prior and concomitant medications, respectively, will be 
presented according to the anatomical main group (level 1), the pharmacological subgroup 
(level 3), and the preferred term.
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 20 of 39
7
MEASUREMENTS OF TREATMENT COMPLIANCE
A calculation of treatment compliance will not be performed. This is due to the nature of this 
pilot study. Subjects in both treatment arms are treated using standard clinical practice only, 
there is no fixed mandatory dosing scheme to be followed. Also, no diary data or drug 
accountability data is collected. Data on Neupro dosing is recorded on the concomitant 
medication pages of the CRF only. Given this, an appropriate measure for treatment compliance 
could not be identified.
8
EFFICACY ANALYSES
The efficacy analysis will be performed on the FAS and observed cases will be utilized. The PPS 
will be used for sensitivity analysis on selected efficacy variables.
8.1
Statistical analysis of the primary efficacy variables
The change from Baseline to Visit 2 in the primary efficacy variables will be analyzed for 
differences among the treatment groups using analysis of covariance (ANCOVA) with treatment 
group and center as factors and the corresponding baseline variable as a covariate. The 95% 
confidence interval (CI) on the calculated least square mean difference between experimental 
group and control group in change from baseline in the primary efficacy variables will also be 
reported.
8.1.1
Derivations of primary efficacy variables
8.1.1.1
Unified Parkinson’s Disease Rating Scale Part III
The Unified Parkinson’s Disease Rating Scale (UPDRS; Movement Disorder Society Task Force 
on Rating Scales for Parkinson’s disease, 2003) consists of 4 parts: Part I of UPDRS assesses 
mentation, behavior, and mood. Part II of the UPDRS assesses the subject’s activity of daily 
living. Part III assesses motor function. Part IV assesses complications of therapy.
The UPDRS Part III (motor subscale) will be measured in the “on” state and consists of 27 items 
and sub-items scored between 0 and 4. It includes speech, facial expression, tremor at rest (face, 
right hand, left hand, right foot, left foot), action or postural tremor of hands (right and left), 
rigidity (neck, extremities), finger taps (right and left), hand movements (right and left), rapid 
alternating movements of hands (right and left), leg agility (right and left), arising from chair, 
posture, gait, postural stability, body bradykinesia, and hypokinesia (14 items, 27 questions = 
108 points maximum). The sum score will be calculated as sum of the 27 individual scores. If 
one or more items are missing, the sum score will also be missing.
8.1.1.2
Kinesia-ONE variables
The Kinesia-ONE data includes the following variables collected at Baseline and at Visit 2:

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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 21 of 39

hand grasp speed score
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hand grasp amplitude score
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rapid alternating movement speed score
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rapid alternating amplitude score

dyskinesia score
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hand movements rhythm score
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finger tapping rhythm score
These scores are all calculated as an average from triplicate repeated assessments at a 
measurement point. 
In addition, a composite Kinesia-ONE score will be calculated as the average of following 
scores: 

finger tapping speed score

rest tremor score

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
kinetic tremor score

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
finger tapping rhythm score

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
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
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
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
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
rapid alternating rhythm score
The composite score will only be calculated if at least 50% of the scores are available.
8.1.1.3
Number of Neupro dose changes
The number of Neupro dose changes is derived as the sum of all Neupro dose changes during the 
treatment period and includes any increase or decrease of dose, irrespective of the dose level. If a 
dose level change, e.g. from 2mg/24h to 4mg/24h, occurs multiple times, it is counted as often as 
it occurs. 
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 22 of 39
8.1.2
Primary analysis of the primary efficacy variables
The efficacy variables, change from Baseline to Visit 2 (for all continuous efficacy variables not 
based on Kinesia-360, i.e. UPDRS Part III and Kinesia-ONE scores) will be analyzed utilizing 
an analysis of covariance (ANCOVA) with Baseline as a covariate, “center” as factor, and 
“group” as main factor. The 2 groups are the Experimental Group (EG) and the Control Group 
(CG).
The 2-sided null and alternative hypotheses are: 

Null hypothesis (H0): EG=CG

Alternative hypothesis (Ha): EG≠CG
EG: Represents the change from Baseline to Visit 2 for subjects in the Experimental Group.
CG: Represents the change from Baseline to Visit 2 for subjects in the Control Group.
The efficacy analysis will be performed on the FAS and observed cases will be utilized. The 
group effect will be estimated and presented with 95% 2-sided CIs and p-values.
The single items of UPDRS Part III and the sum score will be presented in listings, the sum score 
will be summarized by group, and the change from Baseline to Visit 2 in UPDRS Part III score 
will be analyzed using ANCOVA.
The change from Baseline to Visit 2 in each of the Kinesia-ONE scores will be analyzed using 
ANCOVA.
The Neupro dose per 24h at Visit 2 will be summarized by group, as well as the Neupro starting 
dose per 24h. Both assessments of Neupro dose will be related in a shift table by group. In 
addition, Neupro dose and Neupro dose change will be tabulated as continuous variable.
The number of Neupro dose changes after first administration until Visit 2 will be summarized 
by group.
The comparison of the rate of discontinuation of treatment with Neupro during the course of the 
study for the control group and the experimental group will be performed using logistic 
regression with factors for treatment and center.
8.1.3
Secondary analyses of the primary efficacy variables
Not applicable.
8.1.4
Supportive and sensitivity analyses of the primary efficacy variables
The primary analyses (ANCOVA and corresponding summary statistics) will be repeated for the 
PPS on observed cases.
In case of misallocation to treatment groups, the primary analyses will be repeated for the FAS 
as randomized.
8.2
Analysis of other efficacy variables
8.2.1
Kinesia-360 motor scores
Kinesia-360-based efficacy data will be presented descriptively for the Experimental Group. Due 
to repeated measurements (during titration weekly and during maintenance), comparisons will be 
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 23 of 39
performed by time point and also by dose, if applicable (dependent on number of subjects in 
respective dose groups). Optional time points might also be subject to analysis (dependent on 
number of subjects at respective time points or windows for time points).
Change from Baseline to Week 2, Week 3, Week 4, Week 7/8, and Week 11 in the motor scores 
derived from the Kinesia-360 wearable technology by Neupro dose level (mg/24h) for the 
Experimental Group will be summarized for following scores:

average daily tremor score

average daily slowness score

average daily dyskinesia score

percent wear-time tremor detected

percent wear-time dyskinesia detected

percent wear-time user not moving

percent wear-time user was walking score

percent wear-time user active but not walking

number of steps per hour while wearing device
The average daily scores of tremor, slowness and dyskinesia will be derived from the 2-minutes 
interval data. Only those 2-minutes interval data records, when the device was not paused, will 
be considered. For each day, starting at 0:00 until 23:58, the available non-paused 2-minutes 
interval scores of tremor (and similarly for slowness and dyskinesia) will be selected and the 
arithmetic mean of these will be calculated which results in the average daily scores. 
The percent wear-times and number of steps per hour will be derived from the daily Kinesia-360 
data. Multiple records per day will be averaged and weighted by wear-time.
These daily scores will be used to derive the scores per visit week. The daily scores will be 
averaged from 2 consecutive days of wearing in the respective assessment week. Assessments on 
study day 8 to 14 are eligible for Week 2 scores, assessments on study day 15 to 21 are eligible 
for Week 3 scores, assessments on study day 22 to 28 are eligible for Week 4 scores, 
assessments on study day 43 to 56 are eligible for Week 7/8 scores, and assessments on study 
day 71 to 77 are eligible for Week 11 assessments. The Week 7/8 is an artificially added Week, 
which considers the data collected on voluntary basis during that time interval, and therefore 
might have sparse data. If more than 2 consecutive assessments are available for Week 7/8, the 
latest 2 consecutive values will be considered. The same applies for the assessments in Week 2, 
Week 3, Week 4, and Week 11: If more than 2 consecutive assessments are available per week, 
the latest 2 consecutive values will be considered.
In addition, the maximum relative day of Kinesia-360 usage will be listed, and the number of 
days the subject used the Kinesia-360 device will be calculated by subject and summarized.
8.2.2
Parkinson’s Disease Questionnaire (PDQ-39)
The Parkinson’s Disease Questionnaire (PDQ-39; Jenkinson, 1997) is a simple questionnaire that 
assesses health related quality of life in individuals with PD. The answer categories are coded as 
follows: 0=never, 1=occasionally, 2=sometimes, 3=often, 4=always or cannot do at all. It 
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 24 of 39
provides scores in 8 scales: mobility (questions 1-10), activities of daily living (questions 11-16), 
emotions (questions 17-22), stigma (questions 23-26), social support (questions 27-29), 
cognition (questions 30-33), communication (questions 34-36), and bodily discomfort (questions 
37-39). It is designed for self-completion by subjects and should take only a few minutes for the 
subject to complete. 
For each of the 8 domains a score will be calculated: The coded answer categories of the 
corresponding domain questions will be added. This domain raw value will be multiplied with 
100 and divided by the maximum domain raw value (e.g. 4*10=40 for the 10 questions of 
mobility domain). This transformation gives domain scores between 0 and 100.
Domain scores will only be calculated if at least 50% of items on the scale have been answered. 
If this is the case, the missing items, if any, will be replaced with the overall mean of the item, 
and the corresponding domain score will be calculated based on the replaced questions.  
The social support domain consists of questions 27, 28, and 29. If respondents indicate that they 
do not have a spouse or partner on question 28 then social support will be calculated as follows: 
social support = (sum of questions 27 + 29) / (4 * 2) * 100.
Individual questions will be summarized categorically, and the domain scores will be tabulated 
using continuous summary statistics by visit. 
A sum score, calculated by adding together the 8 domain scores and dividing the sum by 8, will 
also be presented using continuous summary statistics by visit (including change from baseline 
values).
8.2.3
Patient Activation Measure (PAM-13)
The Patient Activation Measure (PAM-13) quantifies the extent to which people are informed 
about and involved in their health care. The answer categories are coded as follows: 1=disagree 
strongly, 2=disagree, 3=agree, 4=agree strongly. 
A sum score will be calculated by adding together the coded answer categories of the 13 items, 
and then transforming to a scale from 0 to 100 using the formula 100*(sum of items - 13)/(52-
13). 
The sum score will only be calculated if at least nine questions have been answered. If this is the 
case, the missing items, if any, will be replaced with the overall mean of the item, and the sum 
score will be calculated based on the replaced items.
The individual questions will be summarized categorically, and the sum score will be presents 
using continuous summary statistics by visit (including change from baseline values).
8.2.4
Unified Parkinson’s Disease Rating Scale Parts I, II, IV
The UPDRS Part I (Mentation, Behavior, and Mood) includes intellectual impairment, thought 
disorder, depression, and motivation/initiative (4 questions=16 points maximum).
The UPDRS Part II (Activities in Daily Living) consists of 13 items scored between 0 and 4. It 
includes speech, salivation, swallowing, handwriting, cutting food and handling utensils, 
dressing, hygiene, turning in bed and adjusting clothes, falling (unrelated to freezing), freezing 
when walking, walking, tremor, and sensory complaints related to Parkinsonism (13 
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 25 of 39
questions=52 points maximum). The sum score will be calculated as the sum of the 13 individual 
scores. If one or more items are missing, the sum score will also be missing.
The UPDRS Part IV (Complications of Therapy) consists of 11 questions. It includes 
dyskinesias, duration, disability, painful dyskinesias, early morning dystonia, clinical 
fluctuations, presence of anorexia, nausea or vomiting, sleep disturbance, and symptomatic 
orthostasis (11 questions).
The single items of UPDRS Parts I, II, and IV, and the sum scores will be presented in listings. 
The UPDRS Part IV will be presented separately for each item, the sum scores of UPDRS Part I 
and II will be summarized by group, and the change from Baseline to Visit 2 in UPDRS Part II 
score will be analyzed using ANCOVA as described in Section 8.1.2 .
9
PHARMACOKINETICS AND PHARMACODYNAMICS 
9.1
Pharmacokinetics
Not applicable.
9.2
Pharmacodynamics
Not applicable.
10
SAFETY ANALYSES
In general, safety analyses will be conducted with the SS as randomized.
10.1
Extent of exposure
The overall duration of exposure is defined as the date of last patch administration minus the date 
of the first patch application + 1 day. The overall exposure duration will be summarized using 
descriptive statistics for the subjects. 
10.2
Adverse events
Adverse events with start date prior to first administration of study medication are defined as 
pre-treatment AEs. No summaries of these events will be provided, they are included in listings. 
Treatment emergent AEs are all AEs starting on or after the date of first study medication and up 
to 30 days after the last dose of study medication. Also AEs with an earlier onset are treatment 
emergent, if the intensity worsened during the treatment period. AEs occurring more than 30 
days after the last dose will not be considered treatment emergent.
For AEs with a partial start date, the imputation rules as described in Section 4.2 will be applied. 
If a start date is completely missing, then the AE will be considered treatment-emergent unless 
the AE end date is on or before the first date of study medication. Duration should not be 
calculated if there is missing stop date information.
Treatment emergent adverse events (TEAE) will be tabulated by MedDRA system organ class 
(SOC), high level term (HLT) and preferred term (PT). The number and percentage of subjects 
experiencing each event at least once will be summarized in addition to the number of events. In 
summaries of TEAEs by relationship and intensity, respectively, the number of events will not be 
presented.
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 26 of 39
All summaries will be sorted alphabetically by SOC and HLT and by descending frequency of 
PT in the Experimental Group within HLTs. If there is more than one PT with the same 
frequency in the Experimental Group these events will be sorted alphabetically.
Tables showing TEAEs, serious TEAEs, non-serious TEAEs, TEAEs leading to discontinuation 
of study medication, TEAEs by maximum intensity, TEAEs by maximum relationship, and 
TEAEs including subject numbers will be provided. The table showing AEs leading to study 
discontinuation will also be provided for the ES. A glossary of MedDRA terms and associated 
investigator provided terms for all adverse events will be presented. Individual subject data 
listings will be presented for all AEs, serious TEAEs, TEAEs leading to withdrawal of study 
medication, and TEAEs with fatal outcome.
10.3
Clinical laboratory evaluations
Not applicable.
10.4
Other observations related to safety
10.4.1
Weight
Weight recorded in pounds (lb) will be converted to kilograms (kg) as described in Section 6.1 . 
Summary statistics of the actual values and change from Baseline values of body weight will be 
presented by visit in the SS.
10.4.2
Other safety variables
The comparison of the rate of discontinuation of treatment with Neupro during the course of the 
study for the Control Group and the Experimental Group is one of the safety variables. This is 
described in Section 8.1.2 .
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 27 of 39
11
REFERENCES
Jenkinson C., Fitzpatrick R., Petro V., Greenhall R., and Hyman N. (1997) The Parkinson’s 
Disease Questionnaire (PDQ-39). Development and validation of a Parkinson’s Disease 
summary index score. Age Ageing, 26:353-357.
Keys A; Fidanza F; Karvonen M; Kimura N; Taylor H. Indices of relative weight and obesity. 
Journal of Chronic Diseases 1972, 25 (6–7): 329–43. 
Mosteller RD. Simplified calculation of body surface area. N Engl J Med 1987 Oct22; 
317(17):1098 (letter).
Movement Disorder Society Task Force on Rating Scales for Parkinson’s Disease. The Unified 
Parkinson’s Disease Rating Scale (UPDRS): status and recommendations. Mov Disord. 
2003;18:738-50.
NEUPRO [package insert]. Smyrna, GA: UCB Inc.; 2016
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This document cannot be used to support any marketing authorization application and any extensions
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 28 of 39
12
APPENDICES
Not applicable.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


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31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 29 of 39
13
AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN 
(SAP) (IF APPLICABLE)
13.1
AMENDMENT 1
Rationale for the amendment
The SAP was amended after the Data Evaluation Meeting, to specify the SS more precisely, to 
define the handling of question 28 of PDQ-39, to describe the derivation of Kinesia-360 scores in 
more detail, and to correct the subgroup level of concomitant medications presented. In addition, 
new Kinesia variables, and the handling of rescreened subjects and of phone contacts has been 
added.
Modifications and changes
Changes in section 2.1
Following text before section 2.1.1 was removed in order to keep this section consistent with the 
clinical study protocol:
A primary objective of PD0049 is to evaluate whether Parkinson’s disease motor symptoms in 
subjects starting Neupro can be improved by using feedback of motor symptom data from the 
Kinesia-360 wearable technology presented to subjects and Investigators in addition to standard 
clinical practice as compared with only standard clinical practice. A primary objective is to 
evaluate whether a clinician is more likely to determine a Neupro dosing regimen that improves 
a subject’s Parkinson’s disease motor symptoms when using motor symptom data collected with 
the Kinesia-360 wearable technology in addition to standard clinical practice as compared with 
only standard clinical practice. Another primary objective is to evaluate whether subjects with 
Parkinson’s disease are more likely to continue the usage of Neupro if Parkinson’s disease motor 
symptom data collected using the Kinesia wearable technology is used to provide the subjects 
with feedback on the status of their Parkinson’s disease motor symptoms and is used in addition 
to standard of care for titrating their Neupro dosing regimen. Other objectives include to evaluate 
the quality of life and engagement in the management and treatment of their disease within 
subjects in either group, as well as to evaluate the safety of Neupro.
Changes in section 2.2.1.1
The primary efficacy variables of this study are:

Change from Baseline (Visit 1/Week 1) to Visit 2 (Week 12/3 months after start of treatment 
with Neupro) in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III Motor Score 

Change from Baseline (Visit 1/Week 1) to Visit 2 (Week 12) in Kinesia-ONE variables:

finger tapping speed score

rest tremor score

averaged finger tapping speed and resting tremor scores

postural tremor score

finger tapping amplitude score

hand grasp speed score
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 30 of 39

hand grasp amplitude score

rapid alternating movement speed score

rapid alternating amplitude score

dyskinesia score

Neupro dose per 24h at Visit 2 (Week 12) 

Number of Neupro dose changes during the study (between Visit 1 and Visit 2) 

Discontinuation of treatment with Neupro during the course of the study
Has been changed to:
The primary efficacy variables of this study are:

Change from Baseline (Visit 1/Week 1) to Visit 2 (Week 12/3 months after start of treatment 
with Neupro) in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III Motor Score 

Change from Baseline (Visit 1/Week 1) to Visit 2 (Week 12) in Kinesia-ONE variables:

finger tapping speed score

rest tremor score

averaged finger tapping speed and resting tremor scores

postural tremor score

finger tapping amplitude score

hand grasp speed score

hand grasp amplitude score

rapid alternating movement speed score

rapid alternating amplitude score

dyskinesia score

kinetic tremor score

rapid alternating movement rhythm score

hand movements rhythm score

finger tapping rhythm score

average Kinesia-ONE score

Neupro dose per 24h at Visit 2 (Week 12) 

Number of Neupro dose changes during the study (between Visit 1 and Visit 2) 

Discontinuation of treatment with Neupro during the course of the study
Changes in section 2.2.1.2
Other efficacy varibles are:
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 31 of 39

Change from Baseline to Visit 2 in the motor scores derived from the Kinesia-360 wearable 
technology by time (weekly/monthly) for the Experimental Group in:

average daily tremor score

average daily slowness score

average daily dyskinesia score

percent wear-time tremor detected

percent wear-time dyskinesia detected

percent wear-time user not moving

percent wear-time user was walking score

percent wear-time user active but not walking

number of steps per hour while wearing device

Change from Baseline to Visit 2 (Week 12) in the 39-Item Parkinson’s Disease 
Questionnaire (PDQ-39) scores.

Change from Baseline to Visit 2 (Week 12) in subject engagement questionnaire scores.
Has been changed to:
Other efficacy varibles are:

Change from Baseline to Visit 2 in the motor scores derived from the Kinesia-360 wearable 
technology by time (weekly/monthly) for the Experimental Group in:

average daily tremor score

average daily slowness score

average daily dyskinesia score

percent wear-time tremor detected

percent wear-time dyskinesia detected

percent wear-time user not moving

percent wear-time user was walking score

percent wear-time user active but not walking

number of steps per hour while wearing device

Number of days on Kinesia-360 device

Change from Baseline to Visit 2 (Week 12) in the 39-Item Parkinson’s Disease 
Questionnaire (PDQ-39) scores.

Change from Baseline to Visit 2 (Week 12) in subject engagement questionnaire scores.
Changes in section 3.1
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 32 of 39
The visit dates and phone contact dates will be presented in a listing. This includes the scheduled 
phone contacts in the Experimental Group and the unscheduled phone contacts in both groups. 
As scheduled phone contacts in the Experimental Group were consistently reported on both the 
form for scheduled contacts as well as on the unscheduled telephone log, duplicate phone 
contacts will be removed at the SDTM level. It will be considered at the SDTM level that the 
scheduled phone contacts do not appear twice, unless two or more phone contacts were 
documented as conducted on the same day.
Changes in section 3.2
Following subsection 3.2.4 was added at the end of section 3.2:
3.2.4 Rescreening
Rescreening was not foreseen in the clinical study protocol. However one subject was 
rescreened. In this case, the initial screening is documented with a different subject number than 
the second screening and following visits of this same subject. The fact that a rescreened subject 
has 2 different subject numbers is not accounted for in the analysis, which means that the subject 
will be counted twice in the tables based on the Enrolled Set. This was decided to be acceptable 
due to the exploratory nature of this study, and will not impact the efficacy and safety analysis.
Changes in section 3.5.2
The SS will consist of all subjects who received at least 1 dose of Neupro. The SS will be used 
for the analysis of all demographic, disposition, and safety data.
Has been changed to:
The SS will consist of all subjects who received at least 1 dose of Neupro. A subject who 
received Neupro after screen failing is not considered as treated within the study and 
therefore not included in the SS. The SS will be used for the analysis of all demographic, 
disposition, and safety data.
Changes in section 3.9
Not applicable.
Has been changed to:
Additional Kinesia-ONE scores which were not prespecified in the clinical study protocol 
are provided by the vendor. These will be analyzed in the same way as the prespecified 
variables.
Changes in section 5.1
The following listings will be provided: study eligibility criteria text, subjects who did not meet 
study eligibility criteria, subject disposition, subject analysis sets, study discontinuation and visit 
dates.
Has been changed to:
The following listings will be provided: study eligibility criteria text, subjects who did not meet 
study eligibility criteria, subject disposition, subject analysis sets, Neupro discontinuation and 
visit dates.
Changes in section 6.1
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 33 of 39
The calculation of age is based on the date of informed consent and the date of birth. If the date 
of birth is incomplete, it will be completed with January as imputed month if month is missing 
and it will be completed with 1 as imputed day of birth if day is missing. Age is calculated as 
follows: Age (years) = ([Date of Informed Consent] – [Imputed Date of Birth]) / 365.25. It will 
be summarized as a continuous variable and as a categorical variable based on the categories: 
<65 years, ≥65 years, and also based on the categories: <75 years, ≥75 years.
Has been changed to:
The calculation of age is based on the date of informed consent and the date of birth. If the date 
of birth is incomplete, it will be completed with January as imputed month if month is missing 
and it will be completed with 1 as imputed day of birth if day is missing. Age is calculated as 
follows: Age (years) = ([Date of Informed Consent] – [Imputed Date of Birth]) / 365.25. It will 
be summarized as a continuous variable and as a categorical variable based on the categories: 
<65 years, 65-<85 years, ≥85 years, also based on the categories: <65 years, ≥65 years, and also 
based on the categories: <75 years, ≥75 years.
Changes in section 6.4
Prior and concomitant medications will be summarized separately for the SS. The number and 
percentage of subjects who used prior and concomitant medications, respectively, will be 
presented according to the anatomical main group (level  1), the pharmacological subgroup (level 
2), and the preferred term.
Has been changed to:
Prior and concomitant medications will be summarized separately for the SS. The number and 
percentage of subjects who used prior and concomitant medications, respectively, will be 
presented according to the anatomical main group (level 1), the pharmacological subgroup 
(level 3), and the preferred term.
Changes in section 8.1.1.2
The Kinesia-ONE data includes the following variables collected at Baseline and at Visit 2:

finger tapping speed score

rest tremor score

averaged finger tapping speed and resting tremor scores

postural tremor score

finger tapping amplitude score

hand grasp speed score

hand grasp amplitude score

rapid alternating movement speed score

rapid alternating amplitude score

dyskinesia score
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 34 of 39
These scores are all calculated as an average from triplicate repeated assessments at a 
measurement point. 
Has been changed to:
The Kinesia-ONE data includes the following variables collected at Baseline and at Visit 2:

finger tapping speed score

rest tremor score

averaged finger tapping speed and resting tremor scores

postural tremor score

finger tapping amplitude score

hand grasp speed score

hand grasp amplitude score

rapid alternating movement speed score

rapid alternating amplitude score

dyskinesia score

kinetic tremor score

rapid alternating movement rhythm score

hand movements rhythm score

finger tapping rhythm score 
These scores are all calculated as an average from triplicate repeated assessments at a 
measurement point. 
In addition, a composite Kinesia-ONE score will be calculated as the average of following 
scores: 

finger tapping speed score

rest tremor score

postural tremor score

kinetic tremor score

finger tapping amplitude score

finger tapping rhythm score

hand grasp speed score

hand grasp amplitude score

hand grasp rhythm score

rapid alternating movement speed score
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 35 of 39

rapid alternating amplitude score

rapid alternating rhythm score
The composite score will only be calculated if at least 50% of the scores are available.
Changes in section 8.1.2
The Neupro dose per 24h at Visit 2 will be summarized by group, as well as the Neupro starting 
dose per 24h. Both assessments of Neupro dose will be related in a shift table by group.
The number of Neupro dose changes after first administration until Visit 2 will be summarized 
by group.
The comparison of the rate of discontinuation of treatment with Neupro during the course of the 
study for the control group and the experimental group will be performed using logistic 
regression with factors for treatment and center.
Has been changed to:
The Neupro dose per 24h at Visit 2 will be summarized by group, as well as the Neupro starting 
dose per 24h. Both assessments of Neupro dose will be related in a shift table by group. In 
addition, Neupro dose and Neupro dose change will be tabulated as continuous variable.
The number of Neupro dose changes after first administration until Visit 2 will be summarized 
by group.
The comparison of the rate of discontinuation of treatment with Neupro during the course of the 
study for the control group and the experimental group will be performed using logistic 
regression with factors for treatment and center.
Changes in section 8.2.1
Kinesia-360-based efficacy data will be presented descriptively for the Experimental Group. Due 
to repeated measurements (during titration weekly and during maintenance), comparisons will be 
performed by time point and also by dose, if applicable (dependent on number of subjects in 
respective dose groups). Optional time points might also be subject to analysis (dependent on 
number of subjects at respective time points or windows for time points).
Change from Baseline to Week 2, Week 3, Week 4, Week 7/8, and Week 11 in the motor scores 
derived from the Kinesia-360 wearable technology by Neupro dose level (mg/24h) for the 
Experimental Group will be summarized for following scores:

average daily tremor score

average daily slowness score

average daily dyskinesia score

percent wear-time tremor detected

percent wear-time dyskinesia detected

percent wear-time user not moving

percent wear-time user was walking score
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 36 of 39

percent wear-time user active but not walking

number of steps per hour while wearing device
The scores will be averaged from 2 consecutive days of wearing in the respective assessment 
week. Assessments on study day 8 to 14 are eligible for Week 2 scores, assessments on study 
day 15 to 21 are eligible for Week 3 scores, assessments on study day 22 to 28 are eligible for 
Week 4 scores, assessments on study day 43 to 56 are eligible for Week 7/8 scores, and 
assessments on study day 71 to 77 are eligible for Week 11 assessments. The Week 7/8 is an 
artificially added Week, which considers the data collected on voluntary basis during that time 
interval, and therefore might have sparse data. If more than 2 consecutive assessments are 
available for Week 7/8, the latest 2 consecutive values will be considered. The same applies for 
the assessments in Week 2, Week 3, Week 4, and Week 11: If more than 2 consecutive 
assessments are available per week, the latest 2 consecutive values will be considered.
Has been changed to:
Kinesia-360-based efficacy data will be presented descriptively for the Experimental Group. Due 
to repeated measurements (during titration weekly and during maintenance), comparisons will be 
performed by time point and also by dose, if applicable (dependent on number of subjects in 
respective dose groups). Optional time points might also be subject to analysis (dependent on 
number of subjects at respective time points or windows for time points).
Change from Baseline to Week 2, Week 3, Week 4, Week 7/8, and Week 11 in the motor scores 
derived from the Kinesia-360 wearable technology by Neupro dose level (mg/24h) for the 
Experimental Group will be summarized for following scores:

average daily tremor score

average daily slowness score

average daily dyskinesia score

percent wear-time tremor detected

percent wear-time dyskinesia detected

percent wear-time user not moving

percent wear-time user was walking score

percent wear-time user active but not walking

number of steps per hour while wearing device
The average daily scores of tremor, slowness and dyskinesia will be derived from the 2-
minutes interval data. Only those 2-minutes interval data records, when the device was not 
paused, will be considered. For each day, starting at 0:00 until 23:58, the available non-
paused 2-minutes interval scores of tremor (and similarly for slowness and dyskinesia) will 
be selected and the arithmetic mean of these will be calculated which results in the average 
daily scores. 
The percent wear-times and number of steps per hour will be derived from the daily 
Kinesia-360 data. Multiple records per day will be averaged and weighted by wear-time.
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 37 of 39
These daily scores will be used to derive the scores per visit week. The daily scores will be 
averaged from 2 consecutive days of wearing in the respective assessment week. Assessments on 
study day 8 to 14 are eligible for Week 2 scores, assessments on study day 15 to 21 are eligible 
for Week 3 scores, assessments on study day 22 to 28 are eligible for Week 4 scores, 
assessments on study day 43 to 56 are eligible for Week 7/8 scores, and assessments on study 
day 71 to 77 are eligible for Week 11 assessments. The Week 7/8 is an artificially added Week, 
which considers the data collected on voluntary basis during that time interval, and therefore 
might have sparse data. If more than 2 consecutive assessments are available for Week 7/8, the 
latest 2 consecutive values will be considered. The same applies for the assessments in Week 2, 
Week 3, Week 4, and Week 11: If more than 2 consecutive assessments are available per week, 
the latest 2 consecutive values will be considered.
In addition, the maximum relative day of Kinesia-360 usage will be listed, and the number 
of days the subject used the Kinesia-360 device will be calculated by subject and 
summarized.
Changes in section 8.2.2
The Parkinson’s Disease Questionnaire (PDQ-39; Jenkinson, 1997) is a simple questionnaire that 
assesses health related quality of life in individuals with PD. The answer categories are coded as 
follows: 0=never, 1=occasionally, 2=sometimes, 3=often, 4=always or cannot do at all. It 
provides scores in 8 scales: mobility (questions 1-10), activities of daily living (questions 11-16), 
emotions (questions 17-22), stigma (questions 23-26), social support (questions 27-29), 
cognition (questions 30-33), communication (questions 24-36), and bodily discomfort (questions 
37-39). It is designed for self-completion by subjects and should take only a few minutes for the 
subject to complete. 
For each of the 8 domains a score will be calculated: The coded answer categories of the 
corresponding domain questions will be added. This domain raw value will be multiplied with 
100 and divided by the maximum domain raw value (e.g. 4*10=40 for the 10 questions of 
mobility domain). This transformation gives domain scores between 0 and 100. 
Domain scores will only be calculated if at least 50% of items on the scale have been answered. 
If this is the case, the missing items, if any, will be replaced with the overall mean of the item, 
and the corresponding domain score will be calculated based on the replaced questions. 
Has been changed to:
The Parkinson’s Disease Questionnaire (PDQ-39; Jenkinson, 1997) is a simple questionnaire that 
assesses health related quality of life in individuals with PD. The answer categories are coded as 
follows: 0=never, 1=occasionally, 2=sometimes, 3=often, 4=always or cannot do at all. It 
provides scores in 8 scales: mobility (questions 1-10), activities of daily living (questions 11-16), 
emotions (questions 17-22), stigma (questions 23-26), social support (questions 27-29), 
cognition (questions 30-33), communication (questions 34-36), and bodily discomfort (questions 
37-39). It is designed for self-completion by subjects and should take only a few minutes for the 
subject to complete. 
For each of the 8 domains a score will be calculated: The coded answer categories of the 
corresponding domain questions will be added. This domain raw value will be multiplied with 
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UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 38 of 39
100 and divided by the maximum domain raw value (e.g. 4*10=40 for the 10 questions of 
mobility domain). This transformation gives domain scores between 0 and 100. 
Domain scores will only be calculated if at least 50% of items on the scale have been answered. 
If this is the case, the missing items, if any, will be replaced with the overall mean of the item, 
and the corresponding domain score will be calculated based on the replaced questions. 
The social support domain consists of questions 27, 28, and 29. If respondents indicate that 
they do not have a spouse or partner on question 28 then social support will be calculated 
as follows: social support = (sum of questions 27 + 29) / (4 * 2) * 100.
13.2
AMENDMENT 2
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations 
at
ti
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ted 
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thereof. 


UCB
31 Jan 2018
Statistical Analysis Plan
Rotigotine transdermal system
PD0049
Confidential
Page 39 of 39
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.