Utilization of Target Ranges to Treat Patients With Parkinson's Disease by Objective Measurement Using the Personal KinetiGraph® (PKG®) Compared to Standard of Care Assessment (TARGET-PD)- A Randomized Controlled Trial
Phase: NA
Conditions: Parkinson Disease
Sponsor: Global Kinetics Corporation

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 1 of 31 
Confidential 
 
 
Title:   Utilization of Target Ranges to Treat Patients with 
Parkinson’s Disease by Objective Measurement Using the 
Personal KinetiGraph® (PKG®) compared to Standard of Care 
Assessment (TARGET-PD)- A Randomized Controlled Trial 
 
 
Sponsor:  
 
 
 
Global Kinetics Pty Ltd (GKC) 
 
National Principal investigator:  
Raja Mehanna, MD 
University of Texas Health Science Center at Houston-
McGovern medical school 
6410 Fannin St., Houston, TX 77030, USA 
 
Date of protocol:  
 
 
June 06, 2019 
 
Protocol number: 
 
 
Study 003 
 
Version of protocol:   
 
Version 1.0 
 
Planned Study Dates:  
 
July 2019 to Dec 2023 
 
Data Coordinating Center:   
genae Americas, Inc.     
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 2 of 31 
Confidential 
Table of Contents 
PROTOCOL SIGNATURE PAGE ....................................................................................................................... 4 
SUMMARY OF CHANGES ............................................................................................................................... 5 
Protocol Summary ........................................................................................................................................ 6 
1.0 Introduction ........................................................................................................................................ 10 
2.0 PKG System ......................................................................................................................................... 12 
2.1 
Clinical Interpretation ................................................................................................................. 13 
2.2 
PKG and PKG Report ................................................................................................................... 14 
2.3 
Regulatory Status in the United States ....................................................................................... 15 
3.0 Subject Population .............................................................................................................................. 15 
3.1 
Inclusion Criteria ......................................................................................................................... 15 
3.2 
Exclusion Criteria ......................................................................................................................... 15 
4.0 Methods .............................................................................................................................................. 16 
4.1 
Study Design Overview ............................................................................................................... 16 
4.2 
General Methods ........................................................................................................................ 16 
4.3 
Screening Visit ............................................................................................................................. 18 
4.4 
Baseline Visit ............................................................................................................................... 19 
4.5 
Interim Follow-Up Visits .............................................................................................................. 20 
4.6 
4-Month Follow-Up Visit ............................................................................................................. 21 
4.7 
Annual Follow-Up Visits .............................................................................................................. 22 
5.0 Endpoints ............................................................................................................................................ 23 
5.1 
Primary Endpoint ........................................................................................................................ 23 
5.2 
Secondary Endpoints .................................................................................................................. 23 
5.3 
Ancillary Endpoints ..................................................................................................................... 24 
6.0 Statistical Methods ............................................................................................................................. 24 
6.1 
Hypothesis ................................................................................................................................... 24 
6.2 
Total Sample Size ........................................................................................................................ 25 
6.3 
Statistical Analysis ....................................................................................................................... 25 
6.4 
Analysis Plan Overview ............................................................................................................... 25 
7.0 Investigator Qualifications .................................................................................................................. 26 
8.0 Risk/Benefit Analysis ........................................................................................................................... 26 
9.0 Study Monitoring and Oversight ......................................................................................................... 27 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 3 of 31 
Confidential 
10.0 Abbreviations and Definitions............................................................................................................. 28 
11.0 References .......................................................................................................................................... 30 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 4 of 31 
Confidential 
PROTOCOL SIGNATURE PAGE 
 
Title:   Utilization of Target Ranges to Treat Patients with Parkinson’s Disease by Objective 
Measurement Using the Personal KinetiGraph® (PKG®) compared to Standard of Care 
Assessment (TARGET-PD)- A Randomized Controlled Trial 
 
I have reviewed this protocol and agree to adhere to the requirements and responsibilities listed 
herein.  I am trained to the contents of this protocol, treating Parkinson’s Disease, and the specific 
use of the devices listed in this protocol.  I will ensure that the study is conducted in compliance 
with the protocol, Good Clinical Practices, Declaration of Helsinki, and all applicable regulatory 
requirements.  
 
 
 
 
_______________________________  
 
_____________________ 
Site Principal Investigator Signature  
 
Date (DD/MMM/YYY) 
 
 
 
_______________________________ 
 
Site Principal Investigator Printed Name 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 5 of 31 
Confidential 
 
SUMMARY OF CHANGES 
Revision 
Level 
Description of Changes 
Date 
1.0 
Initial Release 
June 11, 2019 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 6 of 31 
Confidential 
Protocol Summary 
Device 
Personal KinetiGraph® (PKG®) System 
Control  
Clinic Standard of Care 
Study Objective 
This is a randomized controlled trial (RCT) to evaluate treating uncontrolled 
patients with Parkinson’s Disease (PwP) to a target range established by a 
published expert opinion manuscript. The study aims to evaluate clinical patient 
outcomes, quality of life measures and health care utilization of those patients 
specifically treated to a target range when using the PKG data in the clinical 
management of Parkinson’s disease (PD) in routine clinical care (treatment 
group) compared to those managed with medical history and clinical evaluation 
alone (control group) performed by a neurologist experienced in PD 
management.  Both groups will be recommended to undergo medication changes 
until they reach a “controlled state” that is determined by either the clinician 
using standard of care (SOC) (PKG- Group) or using PKG based targets and SOC 
assessments (PKG+ Group).  For subjects in the treatment arm (PKG+ Group) the 
references will be according to the following table using PKG scores*:  
 
Target Range 
Bradykinesia 
Score (BKS) 
Median BKS 23-25 and/or FDS > 7.5 
Dyskinesia 
Score (DKS) 
Median DKS 7-9 and FDS < 13 
 
The main objective of this study is to evaluate whether PwP who are managed 
with the aid of objective measurement and use of target ranges have improved 
PD symptoms and outcomes as compared to individuals treated using only 
standard of care (medical history, neurological examination).   
Study Design 
Prospective, multi-center, single-blind randomized (1:1) controlled, longitudinal 
follow-up study (1, 2, 3 years)  
Number of 
Subjects 
Up to 350 randomized subjects total (approximately 175 in each arm) 
Number of Sites 
Up to 40 Centers in the U.S. comprised of Movement Disorder Specialists (MDS) 
and General Neurologists (GN) experienced in PD management. 
Primary 
Endpoint 
 The change in MDS-UPDRS Total score at 4 months from baseline defined as 
sections I, II, III and IV in PwP. The endpoint will be compared between those who 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 7 of 31 
Confidential 
are treated with standard of care and PKG data (PKG+ Group) and those who are 
treated per standard of care alone (PKG- Group). 
Subjects will be assessed in the ON state.  
Secondary 
Endpoints 
Secondary endpoints will include measurements as indicated below: 
• Percent “responders” for MDS-UPDRS Total score (based on a minimum 
clinically important change of >4 points)**  
• 
Change in motor endpoints at 4 months, 1, 2, 3, years including: 
o MDS-UPDRS Part III;  
o PKG Bradykinesia score (BKS),  
o PKG Dyskinesia score (DKS) and measurement of OFF time  
• Change in PDQ-39 from baseline to 4 months, 1, 2, 3 years 
• Change in MDS-UPDRS Total score from baseline to 1, 2, 3 years 
• Change in MDS-UPDRS Parts I from baseline to 4 months, 1, 2, 3, years 
• Change in MDS-UPDRS Parts II from baseline to 4 months, 1, 2, 3, years  
• Change in MDS-UPDRS Part IV from baseline to 4 months, 1, 2, 3, years 
• Change in PKG Scores including BKS, DKS, PTT, FDS and PTI from baseline to 4 
months, 1, 2, 3 years  
• Change in Levodopa Equivalent Dose (LED) from baseline to each interim visit 
and 4 months, 1, 2, 3 years  
• PKG Patient Survey at 4 months, 1, 2, 3, years 
 
Subjects will be assessed in the ON state as applicable. 
Ancillary Endpoints 
Ancillary endpoints will include measurements as indicated below:  
• Rate of protocol defined adverse events affecting health care utilization 
including: hospitalizations, emergency department, urgent care or 
unanticipated clinic visits from baseline to 4 months, 1, 2, 3 years follow-up 
• Rate of protocol defined adverse events and potential contraindications for 
increasing dopaminergic therapy including: falls, orthostatic hypotension, 
bothersome hallucinations, delirium, and impairment that prohibits 
interaction with the PKG watch from baseline to 4 months, 1, 2, 3 years 
follow up 
• Rate of enrolled subjects in PKG+ Group who are unable to be brought into 
Target Range throughout follow-up period 
Study Population 
Patients with Parkinson’s Disease  
Inclusion Criteria 
 Study subjects must fulfill the following criteria: 
• Able and willing to sign a written informed consent for study participation 
• Presumed to have Levodopa responsive idiopathic Parkinson’s Disease 
• Age inclusive at the time of consent per PKG Indications for Use (46-83 years 
old)  

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 8 of 31 
Confidential 
• Has not been previously managed with the PKG 
Exclusion Criteria 
Subject with any of the following clinical criteria should be excluded: 
• Contraindication to increasing levodopa (e.g. orthostatic hypotension, 
hallucinations/psychosis or any other medical condition in the last year that 
would preclude increasing levodopa or other appropriate Parkinson’s Disease
medications) 
• MoCA score <23 at screening visit 
• Diagnosis of Essential Tremor 
• Wheelchair bound or bedridden  
• Currently utilizing or planning in the next 6 months advanced PD therapies 
(DBS, infusion, etc.)  
• In the investigator’s or sponsor’s opinion, subject has any unstable or 
clinically significant condition that would impair the participant’s ability to 
comply with study requirements or interfere with interpretation of the study 
endpoints (e.g., subject unable to complete PKG watch wear instructions per 
Patient Instruction Manual) 
 
Subjects will be assessed in the ON state where applicable. 
Statistical Methods 
The primary endpoint of change in total MDS-UPDRS will be compared 
between the treatment group (PKG+ Group) and the control group (PKG- 
Group) based on a two-sample t-test. In the event normality assumptions are 
violated, a non-parametric analog will be used. A difference between groups 
of 5 points is assumed for the change in total MDS-UPDRS as well as a 
standard deviation of 13 based on historical data.  With these assumptions, a 
sample size of 280 evaluable subjects will provide approximately 83% power 
for the statistical hypothesis test for the primary endpoint. To account for 
attrition of up to 20%, a total enrollment of 350 subjects is planned.  
 
The primary analysis will be based on the intent-to-treat (ITT) population 
defined as all randomized subjects analyzed according to the treatment 
group assigned.  Except where otherwise specified, the following general 
principles apply to the planned statistical analyses. All statistical analyses will 
be conducted using SAS version 9.4 or later (SAS Institute Inc., Cary, NC) or 
other widely-accepted statistical or graphical software as required. 
Continuous variables will be summarized with mean, standard deviation, 
median, max, min, and number of evaluable observations.  Categorical 
variables will be summarized with frequency and percentages.  Confidence 
intervals may be presented where appropriate using the t-distribution for 
continuous variables and Clopper-Pearson Exact method for categorical 
variables. Unless otherwise specified, statistical analyses will be performed 
using a one-sided 0.025 alpha level.     

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 9 of 31 
Confidential 
Study Visits 
• Screening 
• Baseline (28 days +/- 7 days) 
• Interim Visits (within approximately 21-35 days of previous visit)– 
investigators will be recommended to change medications until the patient 
is within the defined target range (PKG+ Group) or per investigator SOC 
assessments (PKG- Group); up to 3 interim visits allowed 
• 4 months follow-up (120 days +/- 30 days) 
• 1 year follow-up (12 months +/- 2 months) 
• 2 year follow-up (24 months +/- 2 months) 
• 3 year follow-up (36 months +/- 2 months) 
* Pahwa R, Isaacson SH, Torres-Russotto D, Nahab F, Lynch PM, Kotschet KE. Role of the Personal KinetiGraph in the routine 
clinical assessment of Parkinson's disease: recommendations from an expert panel. Expert Rev Neurother. 2018 Jul 26; 1-12. 
** Shulman LM, Gruber-Baldini AL, Anderson KE, et al. The Clinically Important Difference on the Unified Parkinson’s Disease 
Rating Scale. Arch Neurol 2010: 67(1):64-70. 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 10 of 31 
Confidential 
1.0 Introduction 
Importance of motor management in Parkinson’s Disease 
Parkinson’s disease is a progressive disease of the nervous system marked by tremor, muscular 
rigidity, and slow, imprecise movement, chiefly affecting middle-aged and elderly people. These 
symptoms are associated with degeneration of the basal ganglia in the brain and a deficiency of 
the neurotransmitter dopamine. Parkinsonism refers to the collective clinical symptoms of 
bradykinesia, rigidity, resting tremor, and postural and gait impairments.  Accumulation of 
alpha-synuclein in the brain is a typical neuropathological hallmark of Parkinson’s disease 
occurring early in the course of the disease and may predate the appearance of clinical features 
of the disease.  Manifestations in the autonomic system controlling certain functions like heart 
rate, digestion, etc. may also precede motor deficits of the disease. Disease progression has 
been shown to be attributed to alpha-synuclein spreading from diseased to healthy cells. 1 
Individuals with Parkinson’s may exhibit diverse symptoms including behavioral, autonomic, 
somatic, and cognitive deficits however motor impairment, specifically bradykinesia or slowed 
movement, is required for diagnosis.   
Motor symptoms are secondary to the continued loss of dopaminergic neurons in the par 
compacta of the substantia nigra.2 Upon treatment with dopaminergic therapies, individuals 
may develop iatrogenic motor complications that may be controlled through adjustment of 
medications.  Approximately 40% of patients develop fluctuations and dyskinesia within 4-6 
years of treatment and 70% after long-term treatment (>9 years). Patients with fluctuations 
tend to have greater disease severity and disability, and those that fail to derive adequate 
benefit from medications report poorer quality of life.3,4 Signs and symptoms of fluctuations 
vary, and it is thought that they may be under-recognized by clinicians as direct observation is 
often impractical and patient symptom recall can be incomplete and unreliable.5   
 
Other symptoms may impact PD patients through the disease progression.  Tremor is present in 
about 60-70% of subjects with the typical resting tremor being helpful in differentiating PD 
from other forms of parkinsonism. Additionally, approximately 90% of patients with PD will 
develop at least one nonmotor symptom, and nonmotor symptoms can be the presenting 
feature in PD.2 
 
Justification for use of objective targets in the management of Parkinson’s disease 
Treating Parkinson’s disease is challenging because of fluctuations in symptoms from day to day 
and throughout the course of a day. Other symptoms can also impact the variability of PD on an 
ongoing basis.  Currently, in routine practice, most clinicians rely on clinical evaluation, a 
patient’s self-reporting of symptoms and response to medication, to guide therapy. Clinical 
evaluations may be in the form of an unstructured interview or semi-structured questionnaires, 
that vary from provider to provider in terms of content, depth, and scope, or formal clinical 
assessment tools such as the Unified Parkinson’s Disease Rating System (UPDRS). Some 
clinicians employ the use of subject symptom diaries. There are well-known limitations with 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 11 of 31 
Confidential 
these assessment methods including: no assessment during activities of daily living, poor 
visibility of compliance with medications, inadequate recall and/or reporting of symptoms, no 
or poor data quality control and inter-rater variability.6 
Wearable technologies have been developed in response to the lack of objective measurement 
tools for movement disorders symptoms and are being used in the clinical care of Parkinson’s 
patients.7,8  Recent studies have suggested that the use of wearable sensors can inform 
medication choices in a clinical trial setting and correlate with relevant clinical assessment 
scales.9   
A recent study by Farzanehfar, et al.10 demonstrated that the use of objective targets and 
measurement with the PKG® system significantly improved clinical care and quality of life for 
people with PD. For the first time, this study provided clinicians with objective and continuous 
information to help calibrate their treatment recommendations in a timely method. The study 
included 103 PD patients from the Northern part of Tasmania, Australia, with low levels of access 
to specialist care. 
Key findings of this study included: 
• Most people with PD (78%) were living with excessive symptoms that were out of target, 
including high levels of bradykinesia (slowness and freezing), dyskinesia (involuntary 
movements) and tremor (constant shaking). 
• With the use of objective measurements and targets reported with the PKG® system, 
management was improved in more than half (58%) of the 77 participants who completed 
the study. 
• Most significantly, PKG monitoring and use of targets led to changes in oral medication, 
which improved quality of life and clinical outcomes of 43% of patients who completed 
the study (33 patients): 
o 10-point improvement in quality of life as assessed by the PD Questionnaire (PDQ-
39) (p<0.08). 
o 8-point improvement in clinical symptoms as measured by Total UPDRS clinical 
scale (p<0.0009). 
 
Additionally, in 2018, two panels of movement disorder specialists published expert opinion 
manuscripts that serve as a basis for objective measurement to be incorporated into clinical 
practice guidelines.  Both expert groups developed treatment targets for the management of 
bradykinesia, dyskinesia and motor fluctuations.11,12 These therapeutic targets will be evaluated 
in this study. 
 
Personal KinetiGraph (PKG®) Movement Recording System  

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 12 of 31 
Confidential 
The Personal KinetiGraph (PKG®) Movement Recording System was developed by neurologists 
at the Melbourne-based Florey Institute of Neuroscience and Mental Health. The product is 
manufactured and marketed by GKC. 
 
The Personal KinetiGraph (PKG®) Movement Recording System consists of the following: 
• A wrist-worn data logger (PKG Watch) designed to acquire data on the kinematics of 
movement disorder symptoms over a 6-10 day period. 
• An application to configure the data logger and transfer the acquired data at the end of 
a recording. 
• A series of algorithms that analyze the uploaded data, producing a PDF that is delivered 
to the clinician.  The PDF contains objective data distinguishing the movement patterns 
consistent with tremor, bradykinesia, dyskinesia and immobility. 
• Supporting device accessories. 
 
2.0 PKG System 
PKG Watch 
The PKG Watch is a wrist worn medical device that looks like a wristwatch. It is worn on the 
wrist of the most severely affected side and contains a rechargeable battery, a triaxial 
accelerometer, memory, an optional vibration and indicator light-based reminder to the subject 
when PD medications are due and a means for recording when Parkinson’s disease (PD) 
medications were taken, as well as a capacitive sensor to detect removal from the wrist.  
 
Subjects wear the device for 6-10 consecutive days. During this wear time the PKG Watch 
automatically collects data on the type of movement experienced by the patient 24 hours per 
day, can remind the patient to register when they have taken their PD medication as prescribed 
by their clinician, and the patient can indicate when he/she has taken each prescribed dose of 
PD medication. 
 
At the end of the recording period, data are downloaded and analyzed using a proprietary 
algorithm to translate raw movement data collected by the PKG Watch into a multi-page, 
printable output of the patient's movement over the wear period. This output is called a “PKG.” 
The maximum acceleration in each 2-minute epoch is identified and the mean spectral power 
surrounding this peak is calculated. Algorithms produce Bradykinesia Scores (BKS) and 
Dyskinesia Scores (DKS) every two minutes. The PKG includes: 
• a scaled record of a dyskinesia score (DKS) representative of dyskinesia plotted against 
time of day for individual days over the full recording period (Figure 2).  
• a scaled record of a bradykinesia score (BKS) representative of bradykinesia plotted 
against time of day for individual days over the full recording period (Figure 2).  
• a record of periods of immobility, which may be indicative of periods of daytime sleep 
and somnolence, plotted against time of day.  

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 13 of 31 
Confidential 
• a record of periods when the patient was not wearing the PKG Watch or when it was 
‘off-wrist’.  
• a record of the patient’s self-reported compliance with their prescribed program of 
Parkinson’s disease medication.  
• a record of periods of tremor for each day and a tremor summary. 
 
Figure 1: PKG Main Plot 
2.1 Clinical Interpretation 
Bradykinesia Scores (BKS) and Dyskinesia Scores (DKS) are continuous variables. In the case of 
the BKS, the scores can range from movements that are made with normal acceleration to 
those that have very low or no acceleration. There is a correlation between the median BKS and 
DKS between 0900-1800 hour and clinical rating scales.12 
A very high bradykinesia score represents compete immobility of the logger for that 2-minute 
period.13 These periods of immobility had a 85.2% concordance with the detection of sleep by 
ambulatory daytime polysomnography, (p < 0.0001 Chi Squared)13.  High Epworth Sleepiness 
Scores (ESS) were associated with a high proportion of time immobile (PTI) throughout the day 
(p > 0.01 Mann-Whitney). The median PTI between 0900 -1800 hours in 30 age matched 
control subjects was 2%, representing 10 min.  PD patients had higher PTI (median 4.8%) than 
controls (p < 0.0001, Mann-Whitney).  PD subjects with a PTI above the 75th percentile (5% or 
27 min) of controls had more bradykinesia, less dyskinesia and higher PDQ-39 scores than those 
with PTI below this level. There was no relationship between PTI and dose or type of PD 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 14 of 31 
Confidential 
medications.  However, in 53% of subjects, PTI increased in the 30-60 min after levodopa 
confirming that in some subject’s levodopa results in increased sleepiness.14 
The PKG Watch can deliver a reminder to take PD medication by delivering a vibratory cue to 
the wrist.  Consumption of medications is acknowledged by the subject.  Some patients 
performed this acknowledgement repeatedly and unconsciously and this behavior is a risk 
marker for Impulse Control Disorder.15   A Response Ratio (RR) represents the number of 
acknowledgements/ number of doses and is expressed as a percentage.  In ~75% of people with 
PD who had high Impulsive-Compulsive Behavior (ICB) Scores, the RR was tightly correlated 
with ratings of Impulsive-Compulsive Behaviors (r2=0.79).  These patients had dyskinesia, 
particularly when making extraneous responses.  In the other 25% who had high Impulsive-
Compulsive Behavior Scores according to rating scales, the RR was low and these subjects had 
higher Apathy scores and low levels of dyskinesia.  It was concluded that the elevated Response 
Ratio is a specific measure of a type of Impulse Control behavior where increased incentive 
salience is attributed to cues by the presence of high striatal dopamine levels, manifest by high 
levels of dyskinesia and that there is a second form of ICBs which occur in the absence of 
dyskinesia, has normal Response Ratios and higher Apathy scores and may represent prefrontal 
pathology.15 
A Fluctuation Dyskinesia Score (FDS) was produced from the PKG data by summing the 
interquartile range of bradykinesia scores and dyskinesia scores and expressing it as an 
algorithm.16   This FDS can distinguish between fluctuating and non-fluctuating patients with 
high sensitivity and selectivity and was significantly lower following activation of deep brain 
stimulators. The FDS following deep brain stimulation lay in a band just above the score 
separating fluctuators from non-fluctuators, suggesting a range representing adequate motor 
control. When compared with control subjects the FDS of newly diagnosed patients show a loss 
of fluctuation with onset of PD.  The FDS was calculated in subjects whose duration of disease 
was known and this showed that newly diagnosed patients soon develop higher scores which 
either fall under or within the range representing adequate motor control or instead go on to 
develop more severe fluctuations.  It was concluded that the FDS promises to be a useful tool 
for identifying patients whose fluctuations are progressing and may require therapeutic 
changes.16 
 
2.2 PKG and PKG Report 
The investigator will be provided a summary report of the PKG that includes key findings by an 
independent neurologist, registered nurse and/or neuro diagnostic technologist trained 
specifically in interpreting the PKG for the PKG+ Group only. It is intended that the investigator 
then reviews and assesses the PKG information and additionally reviews findings with the 
patient, concluding the likely impact of the disease on the movement of the patient. This PKG 
and PKG report may lead the clinician to prescribe a change in medication amount/frequency or 
recommend a new therapy until the patient becomes controlled. 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 15 of 31 
Confidential 
2.3 Regulatory Status in the United States 
The PKG Movement Recording System was first FDA cleared on August 22, 2014 (K140086) and 
is intended to quantify kinematics of movement disorder symptoms in conditions such as 
Parkinson’s disease, including tremor, bradykinesia and dyskinesia. Generation 2 PKG system 
510(k) clearance was issued on September 20, 2016 (K161717) for Model: GKC-2000 (Gen 2) in 
which internal hardware to the logger was modified.  Future generations of the PKG Movement 
Recording System will be cleared by the FDA through the regulatory approval process prior to 
being utilized in this clinical study. All commercially available versions of the PKG System and 
associated product instructions for use may be used in this study. The study is a post-market 
study and the system will be used within its FDA-cleared indication for use.  
 
 
3.0 Subject Population 
Approximately 350 subjects with Parkinson’s Disease will be consented to provide 280 subjects 
followed through the initial 4-month follow-up period, which includes up to 20% attrition 
during this phase.  
 
Subject selection criteria will include patients with PD who meet the following criteria.  Subjects 
will be assessed in the ON state where applicable. 
 
3.1 Inclusion Criteria 
Study subjects must fulfill the following criteria: 
• Able and willing to sign a written informed consent for study participation 
• Presumed levodopa responsive idiopathic Parkinson’s Disease 
• Age inclusive at the time of consent per PKG Indications for Use (46-83 years old)  
• Has not been previously managed with the PKG 
 
3.2 Exclusion Criteria 
Subject with any of the following clinical criteria should be excluded: 
• Contraindication to increasing levodopa (e.g. orthostatic hypotension, 
hallucinations/psychosis or any other medical condition in the last year that would 
preclude increasing levodopa or other appropriate Parkinson’s Disease medications) 
• MoCA score <23 at screening visit 
• Diagnosis of Essential Tremor 
• Wheelchair bound or bedridden  
• Currently utilizing or planning in the next 6 months advanced PD therapies (DBS, 
infusion, etc.)  
• In the investigator’s or sponsor’s opinion, subject has any unstable or clinically 
significant condition that would impair the participant’s ability to comply with study 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 16 of 31 
Confidential 
requirements or interfere with interpretation of the study endpoints (e.g., subject 
unable to complete PKG watch wear instructions per Patient Instruction Manual) 
 
Subjects will be assessed in the ON state where applicable. 
4.0 Methods 
4.1 Study Design Overview 
The TARGET-PD RCT investigates the use of the PKG and standard of care in treating towards a 
target range compared to standard of care alone in the treatment of patients with uncontrolled 
Parkinson’s disease. This is a prospective, multi-center, single-blind, randomized controlled 
study.  
 
Each subject will be followed for 4 months after the baseline visit. All subjects in either group 
will have interim visits until they are considered to be controlled by the clinician per SOC (PKG- 
Group) or in the PKG based target range (i.e., controlled per expert review paper guidance in 
Pahwa et al., 2018)11 for the PKG+ Group.  Interim visits may be conducted via telephone or in-
office.   
 
4.2 General Methods 
Protocol-Required Data Collection 
Protocol-required data collection at a given visit interval may be completed on one or multiple 
visit dates, if preferred by the institution as long as the testing is performed in compliance with 
protocol requirements and occurs within the corresponding visit window. 
 
Data will be collected on study-specific case report forms (CRFs). 
 
In the event inaccurate and/or incomplete PKG data collection occurs (e.g., subject wore PKG 
successfully but for less than the required duration, subject PKG Watch wrist band was not 
sufficiently secured creating PKG artifacts precluding interpretation, subject performed 
activities, such as the use of power tools, for a sufficient duration that interfered with PKG data 
collection, data collection completed when subject was OFF), data collection may be repeated 
one time. A note will be made in the case report form (CRF) that documents the reason for the 
repeated data collection and the initial and final test results will be recorded in the medical 
record. Only the final results will be recorded on the CRF. 
 
Parkinson’s Disease Medication Use  
All subjects in the study will be asked to continue taking Parkinson’s disease medication(s) as 
prescribed by their Parkinson’s clinician throughout the duration of this study. Any 
modifications to medicines made during this study will be based on the clinician’s judgment. 
Changes to medications will be recommended until the patient is considered to be controlled 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 17 of 31 
Confidential 
unless contraindications are identified by the investigator. All PD medications and subsequent 
changes will be recorded in the medication log CRF.  In addition, non-PD prescription 
medications of anti-depressants, anti-psychotics and blood pressure lowering agents will be 
tracked in the other medication log CRF. 
 
Timing of Clinical Visits  
Subjects will be asked to plan administration of Parkinson’s medications to coincide with the 
time of each study-required clinic visit to ensure that in-clinic study evaluations occur when the 
subject is “ON” or believes they are achieving benefit from prescribed medications to 
standardize data collection for each patient and within the overall study cohort.  
 
PKG Watch Administration 
Study staff will be trained on the deployment and use of the PKG Watch to answer any patient 
questions and on the GKC ordering portal.  The PKG Watch request will be entered into the GKC 
clinical portal.  GKC will receive the order for the PKG Watch and send the PKG Watch to the 
patient for wear prior to the next study visit. The patient will return the PKG Watch to GKC and 
GKC will then upload the PKG including a summary of key findings for the study staff to 
download.   
 
For both PKG+ Group and PKG- Group subjects, the PKG Watch will be programmed per 
standard commercial practices with the PD medication alert feature enabled (see Technical 
Instructions Manual). Subjects will be instructed to provide acknowledgement of PD 
medications taken by swiping the PKG Watch as described in the Patient Instruction Manual.  
The Patient Instruction Manual instructs patients to take PD medications as prescribed by their 
doctor. 
 
The study staff will provide each subject with training on the use of the PKG Watch, a copy of 
the Patient Instruction Manual and complete the patient demonstration. Study staff will place 
the PKG Watch order in the Portal to allow GKC to deliver the PKG Watch to the subject. Once 
the subject has completed 6 full days of wear, the subject will return the PKG Watch to GKC. 
GKC will then download data from the PKG Watch per the instructions for use prior to the 
baseline visit. If, for any reason, the subject is unable to provide at least 6 full days of PKG data, 
the subject may have another PKG Watch programmed and dispensed for an additional wear 
period.  
 
If at any time during the study, the subject is unable to successfully wear the PKG Watch or 
comply with study requirements, the subject may be exited from the study per Principal 
Investigator discretion. 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 18 of 31 
Confidential 
 
Figure 2. Study Flow Chart  
4.3 Screening Visit 
 
Subjects that have not been treated previously with the PKG (i.e. PKG naïve) will be identified 
from routine clinical care, offered study participation, and provided a study informed consent 
document. Study goals and expectations will be discussed with subjects and all subject 
questions will be answered by a study Investigator and/or delegated designee. Subjects willing 
to participate will provide written informed consent.  
 
Subject selection criteria will be documented. A Montreal Cognitive Assessment (MoCA) will be 
performed as part of selection criteria at the screening visit to exclude patients with dementia 
who are unlikely to be able to use the PKG independently. Only versions 7 or 8 of the MoCA will 
be used. Version and subform will be recorded in the screening visit CRF. Subjects who do not 
meet the study selection criteria will be documented as a screen failure on Subject Enrollment 
Logs in the Site Regulatory Binder and in the Electronic Data Capture system (EDC), as required 
Eligible subjects will be assigned a Subject ID number and randomized using the EDC system in a 
1:1 ratio to the PKG- Group (standard of care clinical assessments without use of PKG data) or 
the PKG+ Group (standard of care clinical assessments plus use of PKG data). Medical history 
and demographics will be collected on all patients after randomized into the study. The point of 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 19 of 31 
Confidential 
enrollment into this study is when all selection criteria are met, an informed consent form is 
completed, and the randomization assignment has been completed.  
 
A PKG Watch will be ordered through the GKC Portal and dispensed to the all subjects as 
previously described. 
 
Screening and enrollment activities may be done remotely by phone or secure video 
conferencing (per existing site practices), as part of a routine clinic visit, as per local clinic 
and/or IRB requirements. 
 
4.4 Baseline Visit 
At 28 days +/- 7 days (21-35 days) after the screening visit, subjects will return to the clinic for 
the Baseline Visit. For the PKG+ Group, the site staff will ensure the PKG Report is available 
prior to the Baseline Visit. A subject unable to wear a PKG Watch for at least 6 full days may be 
exited from the study (complete Study Completion Form) if they are unable to complete a 
repeat wear of the PKG Watch. 
 
Subjects in both groups will undergo the routine clinical evaluation per standard of care. For all 
subjects, a medical history update, medication history, and an “ON” state neurological 
assessment will be completed. Protocol defined adverse events including falls, orthostatic 
hypotension, bothersome hallucinations, delirium, impairment that prohibits interaction with 
the PKG watch will be recorded. All subjects will also complete the PDQ-39 questionnaire and 
MDS-UPDRS.  If the MDS-UPDRS is not considered part of the routine clinic visit, the MDS-
UPDRS will be conducted for all visits by an independent certified rater.  
 
For subjects in the PKG- Group (SOC control group), protocol required data collection will occur 
at the baseline visit. A Subject “ON” State Assessment will be completed and changes in 
medical history and medications will be recorded.  The study investigator will complete the 
Clinician Assessment CRF to denote patient-reported symptoms, treatable findings, and clinical 
management planning based on his/her routine clinical assessment procedures. The study 
investigator will be blinded to the PKG information.  In this group, the investigator will use 
clinical history and examination to determine if the subject is “controlled” or “uncontrolled” 
based on standard of care.  
 
For subjects in the PKG+ Group, the study investigator will review and report on the PKG prior 
to the visit and use the information to guide the discussion with the subject during the clinical 
assessment. Subjects will remain blinded to their treatment group so direct reference to the 
PKG is to be avoided. The PKG will be used to determine if the subject is “controlled” or 
“uncontrolled” using the consensus-derived target ranges.12 PKG results will be recorded in the 
PKG Reporting CRF. The study investigator will complete the Clinician Assessment CRF to 
denote patient-reported symptoms, treatable findings, and clinical management planning 
based on his/her routine clinical assessment procedures along with the PKG information.  

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 20 of 31 
Confidential 
 
Target Range 
Bradykinesia 
Score (BKS) 
Median BKS 23-25 and/or FDS > 7.5 
Dyskinesia 
Score (DKS) 
Median DKS 7-9 and FDS < 13 
 
4.5 Interim Follow-Up Visits  
Interim follow-ups will be completed for subjects who are not considered to be controlled.  For 
PKG- group subjects, controlled means per clinician standard of care assessment and for PKG+ 
group subjects, this is per the Acceptable Target Range12:  
 
Target Range 
Bradykinesia 
Score (BKS) 
Median BKS 23-25 and/or FDS > 7.5 
Dyskinesia 
Score (DKS) 
Median DKS 7-9 and FDS < 13 
 
Interim visits can be completed in-clinic or remotely via telephone per institutional 
requirements. This timeframe may vary depending on a variety of factors such as physician care 
practices, amount of total medication change needed, subject medication regimen compliance 
and subject tolerance to medication changes. 
 
Approximately 28 days prior to each planned subject follow-up visit, a PKG Watch will be 
ordered through the GKC Portal and dispensed to each subject as previously described and PKG 
report obtained prior to the visit of PKG+ group subjects for investigator review.  
 
For subjects in the PKG+ Group, the site staff will ensure the PKG is available prior to the 
Interim Follow-up Visit. Protocol required data collection will occur at each follow-up interim 
visit. A Subject “ON” State Assessment will be completed and changes in medical history and 
medications will be recorded. Any protocol defined AEs that have occurred will be captured on 
the AE Reporting CRF (see Section 8). The study investigator will review the PKG provided by 
GKC prior to the visit and use the information to guide the discussion with the subject during 
the clinical assessment. PKG results will be recorded in the PKG Reporting CRF. The study 
investigator will complete the Clinician Assessment CRF to denote patient-reported symptoms, 
treatable findings, and clinical management planning based on his/her routine clinical 
assessment procedures along with the PKG information.  
 
For subjects in the PKG- Group, protocol required data collection will occur at each follow-up 
interim visit. A Subject “ON” State Assessment will be completed and changes in medical 
history and medications will be recorded.  The study investigator will complete the Clinician 
Assessment CRF to denote patient-reported symptoms, treatable findings, and clinical 
management planning based on his/her routine clinical assessment procedures. The study 
investigator will be blinded to the PKG information during interim visits.    

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 21 of 31 
Confidential 
 
These steps will be repeated for each interim follow-up until the study subject is determined to 
be controlled or a maximum of the 4-month follow-up visit.   
 
Up to 4 medication changes including at the Baseline visit and up to 3 interim visits will be 
allowed to get each subject into a “controlled” state.  Interim follow-up visits end when PD 
symptoms have become optimized (considered controlled on oral therapies) per standard of 
care assessments for PKG- group subjects and per the Acceptable Target Range as published in 
Pahwa et al., 2018 and no further treatment changes are indicated as assessed by the study 
investigator and the subject will proceed to the next required study visit at 4-months Follow-
Up. 
 
4.6 4-Month Follow-Up Visit 
All subjects will complete a follow-up visit approximately 4-months +/- 30 days (90-150 days) 
from the Baseline Visit.  
 
Approximately 28 days prior to each planned subject follow-up, a PKG Watch will be ordered 
through the GKC Portal and dispensed to each subject as previously described. The site staff will 
ensure the PKG is available prior to the visit for the PKG+ Group.  
 
Subjects in both groups will undergo the routine clinical work-up per standard of care. Protocol 
required data collection will occur at the visit. A Subject “ON” State Assessment will be 
completed and changes in medical history and medications will be recorded.  Any protocol 
defined AEs that have occurred will be captured on the AE Reporting CRF (see Section 8). 
Subject surveys will be administered and include the PKG Patient Survey, PDQ-39, MDS-UPDRS, 
and MoCA.  Medication changes (PD and other) will be updated in the corresponding 
medication log in the CRF. 
 
For subjects in the PKG- Group (control group), the study investigator will complete the 
Clinician Assessment CRF to denote patient-reported symptoms, treatable findings, and clinical 
management planning based on his/her routine clinical assessment procedures. The study 
investigator will be blinded to the PKG information.  In this group, the investigator will use 
clinical history and examination to determine if the subject is “controlled” or “uncontrolled.”  
 
For the PKG+ Group, the site staff will ensure the PKG Report is available prior to the 4-Month 
Follow-Up Visit. A subject unable to wear a PKG Watch for at least 6 full days may be exited 
from the study (complete Study Completion Form) if they are unable to complete a repeat wear 
of the PKG Watch. The study investigator will review and report on the PKG prior to the visit 
and use the information to guide the discussion with the subject during the clinical assessment. 
The PKG will be used to determine if the subject is “controlled” or “uncontrolled.”12 PKG results 
will be recorded in the PKG Reporting CRF. The study investigator will complete the Clinician 
Assessment CRF to denote patient-reported symptoms, treatable findings, and clinical 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 22 of 31 
Confidential 
management planning based on his/her routine clinical assessment procedures along with the 
PKG information.  
 
 
Target Range 
Bradykinesia 
Score (BKS) 
Median BKS 23-25 and/or FDS > 7.5 
Dyskinesia 
Score (DKS) 
Median DKS 7-9 and FDS < 13 
 
4.7 Annual Follow-Up Visits 
All subjects will undergo annual follow-up clinic visits at 12 months (+/- 2 months), 24 months 
(+/- 2 months) and 36 months (+/- 2 months) following the Baseline Visit.   
 
Approximately 28 days prior to each planned subject follow-up, a PKG Watch will be ordered 
through the GKC Portal and dispensed to each subject as previously described. The site staff will 
ensure the PKG is available prior to the Annual Follow-up Visit. Protocol required data 
collection will occur at each follow-up. A Subject “ON” State Assessment will be completed and 
changes in medical history and medications will be recorded. Any protocol defined AEs that 
have occurred will be captured on the AE Reporting CRF (see Section 8). All subjects will 
complete a PKG Patient Survey, PDQ-39, MDS-UPDRS and MoCA.  
 
For subjects in the PKG+ Group, the study investigator will review the PKG prior to the visit and 
use the information to guide the discussion with the subject during the clinical assessment. 
Treatment decisions based on the PKG results will be recorded in the PKG Reporting CRF. The 
study investigator will complete the Clinician Assessment CRF to denote patient-reported 
symptoms, treatable findings, and clinical management planning based on his/her routine 
clinical assessment procedures along with the PKG information. 
 
If a subject requires medication changes in between annual follow-up visits, interim visits will 
be conducted per clinic standard of care. If medication changes are made, these will be 
documented in the Medication log and on the Clinician Assessment CRF. 
Table 1. Schedule of Events  
Study Activity 
Screening 
Baseline 
(28 days; 
+/- 7 days) 
Interims 
(Up to 3 
visits) 
Follow-Up 
(4 month +/- 
30 days) 
Annual follow-
ups (1, 2, 3 year 
+/-2 months) 
Visit Type 
In-clinic or 
phone per 
standard of 
care 
In-clinic 
21-35 days 
In-clinic or 
phone per 
standard of 
care 
In-clinic 
90-150 days 
In-clinic 
Medical History 
X 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 23 of 31 
Confidential 
ICF 
X 
 
Subject Selection Criteria 
X 
 
 
 
 
Randomization 
X 
 
 
 
 
Clinical Management 
Plans 
 
X 
X 
X 
X 
PD and Other Medications 
X 
X 
X 
X 
X 
AE collection (protocol 
defined only) 
 
X 
X 
X 
X 
PKG Scores  
(provided for PKG + 
Group) 
X 
X 
X 
X 
MDS-UPDRS I, II, III, IV and 
Total Score 
 
X 
 
X 
X 
MoCA 
X 
X 
X 
PDQ-39 
X 
X 
X 
PKG Patient Survey 
 
 
 
X 
X 
 
5.0 Endpoints 
5.1 Primary Endpoint 
The change in MDS-UPDRS Total score at 4 months from baseline defined as sections I, II, III and 
IV in PwP. The endpoint will be compared between those who are treated with standard of care 
and PKG data (PKG+ Group) and those who are treated per standard of care alone (PKG- 
Group). 
 
Subjects will be assessed in the ON state. 
 
5.2 Secondary Endpoints 
Secondary endpoints will include measurements as indicated below: 
• Percent “responders” for MDS-UPDRS Total score (based on a minimum clinically 
important change of >4 points)17 
• Change in motor endpoints at 4 months, 1, 2, 3, years including: 
o MDS-UPDRS Part III;  
o PKG Bradykinesia score (BKS),  

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 24 of 31 
Confidential 
o PKG Dyskinesia score (DKS) and measurement of OFF time 
• Change in PDQ-39 from baseline to 4 months, 1, 2, 3 years 
• Change in MDS-UPDRS Total score from baseline to 1, 2, 3 years 
• Change in MDS-UPDRS Part I from baseline to 4 months, 1, 2, 3, years 
• Change in MDS-UPDRS Part II from baseline to 4 months, 1, 2, 3, years 
• Change in MDS-UPDRS Part IV from baseline to 4 months, 1, 2, 3, years 
• Change in PKG Scores including BKS, DKS, PTT, FDS and PTI from baseline to 4 months, 1, 
2, 3 years  
• Change in LED from baseline to each interim visit and 4 months, 1, 2, 3 years  
• PKG Patient Survey at 4 months, 1, 2, 3, years 
 
Subjects will be assessed in the ON state as applicable. 
5.3 Ancillary Endpoints 
Ancillary endpoints will include measurements as indicated below:  
• Rate of protocol defined adverse events affecting health care utilization including: 
hospitalizations, emergency department, urgent care or unanticipated clinic visits from 
baseline to 4 months, 1, 2, 3 years follow-up 
• Rate of protocol defined adverse events and potential contraindications for increasing 
dopaminergic therapy including: falls, orthostatic hypotension, bothersome 
hallucinations, delirium, and impairment that prohibits interaction with the PKG watch 
from baseline to 4 months, 1, 2 3 years follow up 
• Rate of enrolled subjects in PKG + group who are unable to be brought into Target 
Range through follow-up visits 
 
6.0 Statistical Methods 
6.1 Hypothesis 
The primary endpoint of change in total MDS-UPDRS will be compared between the treatment 
group (PKG+ Group) and the control group (PKG- Group) based on a two-sample t-test. In the 
event normality assumptions are violated, a non-parametric analog will be used. A difference 
between groups of 5 points is assumed for the change in total MDS-UPDRS as well as a standard 
deviation of 13 based on historical data.  With these assumptions, a sample size of 280 evaluable 
subjects will provide approximately 83% power for the statistical hypothesis test for the primary 
endpoint. To account for attrition of up to 20%, a total enrollment of 350 subjects is planned.  
 
The difference in the primary endpoint between randomized groups will be compared with a 
two-sample t-test of means at the 1-sided alpha of 0.025 (equivalent to a two-sided 0.05 alpha 
level). In the event normality assumptions are violated, a non-parametric analog will be used. 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 25 of 31 
Confidential 
6.2 Total Sample Size 
Approximately 350 subjects will be consented to provide an estimated 280 subjects followed 
through the 4-Month follow-up period (assuming 20% attrition).  
 
Initial sample size has been generated on currently available information and may be revised 
mid-study as new information external to the trial becomes available. As noted by FDA 
guidance (https://www.fda.gov/downloads/drugs/guidances/ucm201790.pdf), this approach 
does not raise issues of bias or concern if the interim comparative trial data is blinded and the 
sole source of changes to the sample size is external information. The independent Clinical Trial 
Steering Committee will be responsible for reviewing the data, recommending a go-forward 
decision and ensuring minimization of bias.  
 
6.3 Statistical Analysis 
Analysis Populations 
The primary analysis will be based on the intent-to-treat (ITT) population defined as all 
randomized subjects analyzed according to the treatment group assigned.  
In addition, analyses based on the per-protocol (PP) population and the modified intent-to-
treat (mITT) population will be performed for the primary and secondary endpoints. The PP 
population is defined as all subjects who are randomized and adhere to the study protocol 
requirements, including: meeting all of the subject selection criteria, completion of the PKG 
Watch wear period, inability for investigator to further make treatment changes due to known 
contraindication, completion of subject surveys and completion of follow-up visits. The mITT 
population is defined as all study subjects who are randomized, meet all subject selection 
criteria throughout the study, and complete the 3-year final study visit. 
 
6.4 Analysis Plan Overview 
Interim analyses will be performed after approximately 100 and 200 subjects have been 
randomized and followed through the 4-month follow-up period. 
 
The primary endpoint will be compared between those who are treated with standard of care 
and access to the PKG (PKG+ Group) and those who are treated per standard of care alone 
(PKG- Group) via a two-sample t-test. Except where otherwise specified, the following general 
principles apply to the planned statistical analyses. All statistical analysis will be conducted 
using SAS version 9.4 or later (SAS Institute Inc., Cary, NC) or other widely-accepted statistical 
or graphical software as required. Continuous variables will be summarized with mean, 
standard deviation, median, max, min, and number of evaluable observations.  Categorical 
variables will be summarized with frequency and percentages.  Confidence intervals may be 
presented where appropriate using the t-distribution for continuous variables and Clopper -

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 26 of 31 
Confidential 
Pearson Exact method for categorical variables. Unless otherwise specified, statistical analyses 
will be performed using a one-sided 0.025 alpha level. 
 
Additional analyses will be conducted to adjust for key baseline characteristics associated with 
either outcome or group assignment. A subset analysis related to falls per the ancillary 
endpoint will be performed at selected sites.  These analyses will be performed using linear 
regression with primary predictor of group assignment and outcome of change in Total MDS-
UPDRS. and further detailed in the study Statistical Analysis Plan.  
 
 
7.0 Investigator Qualifications 
Movement Disorder Specialists and General Neurologists who treat PD participating in this 
study will be using the PKG in routine clinical care and have completed PKG product training 
provided by GKC and be trained on the use of target ranges prior to participating in this study. 
 
 
8.0 Risk/Benefit Analysis 
All aspects of clinical management will be made at the clinician’s discretion and with the 
patient’s safety in mind.  This study represents a minimal risk as both groups are undergoing 
clinician-guided medication management.  Furthermore, the PKG Movement Recording System 
within this study fulfills the following general criteria: 
• Not intended as an implant or presents a potential for serious risk to the health, safety, 
or welfare of a subject;  
• Not purported or represented to be for use in supporting or sustaining human life and 
presents a potential for serious risk to the health, safety, or welfare of a subject, or 
• Not for a use of substantial importance in diagnosing, curing, mitigating, or treating 
disease, or otherwise preventing impairment of human health and presents a potential 
for serious risk to the health, safety, or welfare of a subject. 
 
In the case of the PKG+ group, additional objective measures will also be used to help guide the 
clinician.  The results of this study are expected to yield generalizable knowledge about the 
utility of using objective measures in the management of PD.   
In this post-market clinical study, study sites and participants will use commercially available 
system components according to existing product labeling. The study includes non-invasive 
clinical assessments and patient surveys routinely used to characterize Parkinson’s disease 
symptoms. The study includes study-specific clinician and patient surveys as well.    
Adverse events and risks associated with this study are similar to those normally associated 
with standard clinical care of patients with Parkinson’s disease; thus, additional adverse events 
are not anticipated.  

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 27 of 31 
Confidential 
However, only the list below of protocol defined adverse events will be collected starting at 
point of enrollment and analyzed for the ancillary endpoints: 
• falls 
• orthostatic hypotension 
• bothersome hallucinations  
• delirium  
• impairment that prohibits interaction with the PKG watch 
• hospitalizations 
• emergency department visits  
• urgent care visits 
• unanticipated clinic visits 
 
An independent review of protocol collected adverse and serious adverse events will be 
performed and assessed related to protocol, study eligibility and outcomes. Events will be 
reported to IRBs and regulatory authorities as applicable. 
Current product safety information, including contraindications, warnings, and precautions, are 
located in the Patient Instructions Manual, Technical Instructions Manual, and Clinical 
Interpretation Guide. Any complaints regarding any component of the PKG Movement 
Recording System will be reported to GKC and processed per GKC’s standard post-market 
surveillance processes and any adverse events associated with the use of the PKG Movement 
Recording System will be summarized in the final report for this study. 
 
 
9.0 Study Monitoring and Oversight 
Trained personnel appointed by GKC will conduct monitoring activities to ensure that the study 
is conducted in accordance with this study protocol, applicable regulatory requirements and 
clinical guidelines. Monitoring activities will include a combination of ongoing remote data 
review, risk-based monitoring and on-site source document verification. No formal Data Safety 
and Monitoring Committee will be established for this study as this is a minimal safety risk 
study.  However, as previously outlined, the Clinical Trial Steering Committee will periodically 
review study parameters including interim analyses. 
Each center will obtain Institutional Review Board (IRB) approval of this study protocol and 
informed consent prior to commencement of subject enrollment and remain under the 
administration of an IRB throughout the duration of the study. 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 28 of 31 
Confidential 
10.0 Abbreviations and Definitions 
AE 
Adverse Event – Any untoward medical occurrence in a participant, which does not 
necessarily have a causal relationship with the trial intervention. 
BKS 
Bradykinesia Score – A score produced by PKG algorithms indicating symptoms of 
bradykinesia  
DKS 
Dyskinesia Score – A score produced by PKG algorithms indicating symptoms of 
dyskinesia.   
FDS 
Fluctuation Dyskinesia Score – A score produced by PKG algorithms indicating levels of 
fluctuation shown but interquartile ranges.  
IQR 
Interquartile Range - A measure of statistical dispersion, being equal to the difference 
between 75th and 25th percentiles. 
LED 
Levodopa Equivalent Dose – The comparison of levodopa with other medication 
regimes. 
MoCA 
Montreal Cognitive Assessment – A rapid screening instrument for mild cognitive 
dysfunction. 
PD 
Parkinson’s Disease – A progressive disease of the nervous system marked by tremor, 
muscular rigidity, and slow, imprecise movement, chiefly affecting middle-aged and 
elderly people. It is associated with degeneration of the basal ganglia of the brain and a 
deficiency of the neurotransmitter dopamine. 
PDQ-39 
Parkinson’s Disease Questionnaire – A 39 self-report questionnaire that assesses 
Parkinson’s disease-specific health related quality over the previous month. 
PKG 
Personal KinetiGraph - The output (including graphs, values, and curation) generated 
from the data captured on the PKG watch  
PTI 
Percent Time Immobile – Overall percentage of time the PKG detects that the patient is 
motionless. 
PTT 
Percent Time Tremor – Overall percentage of time the PKG detects that the patient 
experiences tremors. 
PwP 
People with Parkinson’s Disease 
Target Ranges Defined using Pahwa R, Isaacson SH, Torres-Russotto D, Nahab FB, Lynch PM, Kotschet 
KE. Role of the Personal KinetiGraph in the routine clinical assessment of Parkinson’s 
disease: Recommendations from an expert panel. Expert Review of Neurotherapeutics. 
2018. DOI: 10.1080/14737175.2018.1503948. 
 
Target Range 
Bradykinesia 
Score (BKS) 
Median BKS 23-25 and/or FDS > 7.5 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 29 of 31 
Confidential 
Dyskinesia 
Score (DKS) 
Median DKS 7-9 and FDS < 13 
 
UPDRS-MDS 
Unified Parkinson’s Disease Rating Scale, MDS version – A revision of the universally 
accepted UPDRS. (Goetz CG et al. Movement Disorder Society-Sponsored Revision of the 
Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Scale Presentation and Clinimetric 
Testing Results. Movement Disorders. Vol. 23, No. 15, 2008, pp. 2129-2170.) 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 30 of 31 
Confidential 
11.0 References 
 
1. Longhena, F., Faustini G., Missale C., Pizzi M., Spano PF., Bellucci A., Contribution of α-
Synuclein Spreading to Parkinson’s Disease Synaptopathy. Neural Plasticity, vol. 2017, 
article ID 5012129. http://dx.doi.org/10.1155/2017/5012129.  
2. Hess, CW., Okun, MS. Diagnosing Parkinson Disease. American Academy of Neurology 
Continuum Journal. 2016; 22(4):1047-1063.  
3. Ahlskog JE, Muenter MD. Frequency of Levodopa-Related Dyskinesias and Motor 
Fluctuations as Estimated from the Cumulative Literature. Mov Disord. 2001;16(3):448-58. 
PubMed PMID: 11391738.  
4. Schrag A, Quinn N. Dyskinesias and Motor Fluctuations in Parkinson's Disease. A 
Community-Based Study. Brain. 2000 Nov;123 (Pt 11):2297-305. PubMed PMID: 11050029. 
5. Stacy M, Bowron A, Guttman M, Hauser R, Hughes K, Larsen JP, et al. Identification of Motor 
and Non-motor Wearing-off in Parkinson's Disease: Comparison of a Patient Questionnaire 
Versus a Clinician Assessment. Mov Disord. 2005;20:726–733. doi: 10.1002/mds.20383. 
PubMed PMID: 15719426. 
6. Bergquist F, Horne M. Can Objective Measurements Improve Treatment Outcomes in 
Parkinson's Disease? European Neurological Review. 2014;9(1):27-30. 
7. Sánchez-Ferro, A, Maetzler, W. Advances in sensor and wearable technologies for 
Parkinson's disease. Mov Disord. 2016;31(9):1257. 
8. Maetzler W, Klucken J, Horne M. A clinical view on the development of technology-based 
tools in managing Parkinson's disease. Mov Disord. 2016;31(9):1263-1271. 
9. Horne M, Kotschet K, McGregor S. The clinical validation of objective measurement of 
movement in Parkinson’s Disease. CNS. 2016;2(1):16-23. 
10. Parisa Farzanehfar, Holly Woodrow, Michelle Braybrook, Sarah McGregor, Andrew Evans, 
Frank Nicklason, and Malcolm Horne (2018). Objective measurement in routine care of 
people with Parkinson’s disease improves outcomes. NPJ Parkinsons Disease. Doi: 
10.1038/s41531-018-0046-4. 
11. Odin P, Chaudhuri R, Volkmann J, Antonini A, Storch A, Dietrichs E, et al. Viewpoint and 
practical recommendations from a movement disorder specialist panel on objective 
measurement in the clinical management of Parkinson’s disease. npj Parkinson's Disease. 
2018. 4:14. DOI:10.1038/s41531-018-0051-7. 
12. Pahwa R, Isaacson SH, Torres-Russotto D, Nahab FB, Lynch PM, Kotschet KE. Role of the 
Personal KinetiGraph in the routine clinical assessment of Parkinson’s disease: 
Recommendations from an expert panel. Expert Review of Neurotherapeutics. 2018. DOI: 
10.1080/14737175.2018.1503948. 
13. Griffiths R, Kotschet K, Arfon S, et al. Automated assessment of bradykinesia and dyskinesia 
in Parkinson's disease. J Parkinsons Dis. 2012;2(1):47-55. 

 
 
 
 
 
 
 
 
 
 
 
 
 
TARGET-PD 
TARGET-PD V1 06Jun2019 
Page 31 of 31 
Confidential 
14. Kotschet K., Johnson W, McGregor S, et al. Daytime sleep in Parkinson's disease measured 
by episodes of immobility. Parkinsonism Relat Disord. 2014;20(6):578-83. 
15. Evans A, Kettlewell J, McGregor S, et al. A conditioned response as a measure of impulsive-
compulsive behaviours in Parkinson's disease. PLoS One. 2014;9(2):e89319. 
16. Horne M, McGregor S, Bergquist F. An objective Fluctuation Score for Parkinson's Disease. 
PLoS One. 2015;10(4):e0124522. 
17. Shulman LM, Gruber-Baldini AL, Anderson KE, et al. The Clinically Important Difference on 
the Unified Parkinson’s Disease Rating Scale. Arch Neurol 2010: 67(1):64-70.