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: PHASE4
Conditions: Parkinson´s Disease
Sponsor: UCB Biopharma S.P.R.L.

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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UCB
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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UCB
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)
REDACTED COPY 
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v

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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16 Dec 2016
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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UCB
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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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 
X
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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
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E Group: Subject wears Kinesia-360 wrist and ankle 
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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
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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.
Experimental Group, home:

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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UCB
16 Dec 2016
Clinical Study Protocol
Rotigotine transdermal system
PD0049
Confidential
Page 31 of 38
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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UCB
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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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 

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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