Adaptive DBS Algorithm for Personalized Therapy in Parkinson's Disease (ADAPT-PD)
Phase: NA
Conditions: Parkinson Disease
Sponsor: MedtronicNeuro

Clinical Investigational Plan Cover Page 
CIP Cover page 
Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease 
(ADAPT-PD) Trial 
Clinicaltrials.gov ID:  NCT04547712 
Document Date: 11 September 2023 
 
 
 

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Clinical Investigation Plan 
Clinical Investigation Plan/Study Title  Adaptive DBS Algorithm for Personalized Therapy 
in Parkinson’s Disease (ADAPT-PD) Trial 
Clinical Investigation Plan Identifier MDT19001 
CA - CIV-20-07-034284 
EUDAMED identifier will be provided under a 
separate cover when available 
Study Product Name Percept™ PC with Adaptive DBS (aDBS™) 
Sponsor/Local Sponsor Medtronic  
Medtronic Neuromodulation  
7000 Central Ave. NE  
Minneapolis, MN 55432 USA 
 
Medtronic International Trading Sàrl  
 
Route du Molliau 31 
1131 Tolochenaz, Switzerland 
 
EU Legal Representative 
Medtronic Bakken Research Center 
Endepolsdomein 5 
6229 GW Maastricht The Netherlands 
 
Medtronic Canada ULC 
99 Hereford Street 
Brampton, Ontario L6Y 0R3 Canada 
+1-905-460-3800 
Document Version  5.0 
Version Date 11 September 2023 
Lead Principal Investigator Helen Bronte-Stewart MD MSE, FAAN, FANA 
John E. Cahill Family Professor, 
Director, Stanford Movement Disorders Center 
(SMDC) 
Director, Human Motor Control and 
Neuromodulation Lab (HCMNL) 
Department of Neurology and Neurological 
Sciences, 
Stanford University School of Medicine 
Center for Academic Medicine 

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453 Quarry Road, mail code 5235 Stanford CA 
94304 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of 
Medtronic. Any distribution, copying, or disclosure without the prior written authorization of 
Medtronic is strictly prohibited. Persons to whom the information is disclosed must know that it is 
confidential and that it may not be further disclosed by them. 
 
 

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Table of Contents  
 
Table of Contents ...................................................................................................................... 3 
1. 
Glossary ......................................................................................................................... 10 
2. 
Synopsis ......................................................................................................................... 17 
3. 
Introduction .................................................................................................................. 26 
3.1. Background ........................................................................................................................... 26 
3.2. Purpose ................................................................................................................................. 28 
4. 
Objectives and Endpoints .............................................................................................. 28 
4.1. Objectives ............................................................................................................................. 28 
4.1.1. 
Primary Objective .................................................................................................................. 28 
4.1.2. 
Secondary Objective.............................................................................................................. 28 
4.1.3. 
Safety Assessments ............................................................................................................... 28 
4.1.4. 
Additional Objectives ............................................................................................................ 28 
4.2. Endpoints .............................................................................................................................. 30 
4.2.1. 
Primary Endpoint .................................................................................................................. 30 
4.2.2. 
Secondary Endpoint .............................................................................................................. 30 
5. 
Study Design .................................................................................................................. 30 
5.1. Duration ................................................................................................................................ 31 
5.2. Rationale ............................................................................................................................... 32 
6. 
Product Description ....................................................................................................... 33 
6.1. General ................................................................................................................................. 33 
6.1.1. 
Medtronic Commercially Available DBS System Components.............................................. 36 
6.1.2. 
Medtronic Investigational DBS System Components............................................................ 38 
6.2. Manufacturer ......................................................................................................................... 41 
6.3. Packaging .............................................................................................................................. 42 
6.4. Intended Population ............................................................................................................... 43 
6.5. Equipment ............................................................................................................................. 43 
6.6. Product Use ........................................................................................................................... 44 

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6.7. Product Training Requirements ............................................................................................... 44 
6.8. Product Receipt and Tracking ................................................................................................. 44 
6.9. Product Storage ..................................................................................................................... 44 
6.10. 
Product Return ............................................................................................................. 45 
6.11. 
Product Accountability ................................................................................................... 45 
7. 
Study Site Requirements ............................................................................................... 46 
7.1. Investigator/Investigation Site Selection .................................................................................. 46 
7.2. Study Site Activation .............................................................................................................. 46 
7.3. Role of the Sponsor Representatives ....................................................................................... 47 
8. 
Selection of Subjects ..................................................................................................... 48 
8.1. Study Population .................................................................................................................... 48 
8.2. Subject Enrollment ................................................................................................................. 48 
8.3. Inclusion Criteria .................................................................................................................... 49 
General (Primary Cohort): ................................................................................................................... 49 
General (Directional Stimulation Cohort): .......................................................................................... 49 
LFP Screening: ..................................................................................................................................... 49 
8.4. Exclusion Criteria ................................................................................................................... 50 
General (Primary Cohort): ................................................................................................................... 50 
General (Directional Stimulation Cohort): .......................................................................................... 50 
9. 
Study Procedures........................................................................................................... 50 
9.1. Schedule of Events ................................................................................................................. 52 
9.2. Data Collection ...................................................................................................................... 53 
9.3. Scheduled Follow-up Visit Windows ......................................................................................... 56 
9.4. Subject Screening .................................................................................................................. 56 
9.5. Prior and Concomitant Medications ......................................................................................... 57 
9.6. Subject Consent ..................................................................................................................... 57 
9.7. Enrollment and Screening Phase ............................................................................................. 60 
9.7.1. 
Enrollment ............................................................................................................................. 60 
9.8. cDBS Baseline Phase .............................................................................................................. 61 
9.8.1. 
LFP Screening Visit ................................................................................................................ 61 

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9.8.2. 
cDBS Baseline Period ............................................................................................................. 63 
9.8.3. 
cDBS Baseline Visit ................................................................................................................ 63 
9.9. aDBS Setup and Adjustment Phase ......................................................................................... 64 
9.9.1. 
aDBS Setup Visit .................................................................................................................... 64 
9.9.2. 
aDBS Adjustment Period (optional) ...................................................................................... 66 
9.9.3. 
Randomization ...................................................................................................................... 67 
9.10. 
aDBS Evaluation Phase .................................................................................................. 68 
9.10.1. 
Evaluation Visit 1 ............................................................................................................... 68 
9.10.2. 
Evaluation Visit 2 ............................................................................................................... 69 
9.11. 
Long-term Follow-up Phase ........................................................................................... 70 
9.11.1. 
Visit 3 ................................................................................................................................. 71 
9.11.2. 
Visit 4 ................................................................................................................................. 72 
9.11.3. 
Visit 5 ................................................................................................................................. 72 
9.11.4. 
Visit 6 ................................................................................................................................. 72 
9.12. 
Extended Access Phase ................................................................................................. 73 
9.12.1. 
Extended Access Visits ....................................................................................................... 73 
9.13. 
Unscheduled Visit .......................................................................................................... 73 
9.14. 
System Modification ...................................................................................................... 74 
9.15. 
Assessment of Efficacy and Device Performance ............................................................. 74 
9.15.1. 
Parkinson’s Disease (PD) Home Diary ............................................................................... 74 
9.15.2. 
Total Electrical Energy Delivered (TEED) ........................................................................... 75 
9.15.3. 
Wearable Data ................................................................................................................... 75 
9.15.4. 
European Quality of Life – 5 Dimensions (EQ-5D-5L) ........................................................ 75 
9.15.5. 
Parkinson’s Disease Questionnaire (PDQ-39) .................................................................... 76 
9.15.6. 
Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) ... 76 
9.15.7. 
Parkinson’s Disease Sleep Scale 2 (PDSS-2) ....................................................................... 77 
9.15.8. 
Voice Handicap Index (VHI) ............................................................................................... 77 
9.15.9. 
Patient Preference ............................................................................................................. 78 
9.15.10. 
Patient Satisfaction ............................................................................................................ 78 

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9.15.11. 
aDBS Global Impression of Change ................................................................................... 78 
9.16. 
Assessment of Safety .................................................................................................... 78 
9.17. 
Recording Data ............................................................................................................. 79 
9.18. 
Deviation Handling ........................................................................................................ 80 
9.19. 
Subject Exit, Withdrawal or Discontinuation .................................................................... 81 
9.19.1. 
Study Exit ........................................................................................................................... 81 
9.19.2. 
Study Completed ............................................................................................................... 82 
9.19.3. 
Lost to Follow-up ............................................................................................................... 82 
9.19.4. 
Subject Chooses to Exit (i.e. Revokes Consent) ................................................................. 82 
9.19.5. 
Investigator Withdraws Subject ........................................................................................ 83 
9.19.6. 
Conditional Disengagement .............................................................................................. 83 
10. 
Risks and Benefits ......................................................................................................... 83 
10.1. 
Potential Risks .............................................................................................................. 83 
10.1.1. 
Pregnancy .......................................................................................................................... 84 
10.1.2. 
Potential aDBS risks ........................................................................................................... 84 
10.1.3. 
Potential Study Procedures Risks ...................................................................................... 84 
10.1.4. 
Potential Study Procedure Inconveniences ....................................................................... 84 
10.2. 
Risk Minimization .......................................................................................................... 85 
10.3. 
Potential Benefits .......................................................................................................... 86 
10.4. 
Risk-Benefit Rationale ................................................................................................... 86 
10.5. 
Risk Determination ........................................................................................................ 86 
11. 
Adverse Events and Device Deficiencies ....................................................................... 87 
11.1. 
Adverse Events ............................................................................................................. 87 
11.2. 
Device Deficiency .......................................................................................................... 87 
11.3. 
Processing Updates and Resolution ................................................................................ 87 
11.4. 
Definitions/Classifications .............................................................................................. 88 
11.5. 
Reporting of Adverse Events .......................................................................................... 93 
11.5.1. 
Adverse Event and Device Deficiency Classification.......................................................... 93 
11.5.2. 
Adverse Event and Device Deficiency Reporting Requirements ....................................... 94 
11.6. 
Subject Death ............................................................................................................... 97 

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11.7. 
Product Complaint Reporting ......................................................................................... 98 
12. 
Data Review Committees .............................................................................................. 99 
12.1. 
Data Monitoring Committee ........................................................................................... 99 
12.2. 
Clinical Events Committee ............................................................................................ 100 
13. 
Statistical Design and Methods ................................................................................... 100 
13.1. 
General Aspects of Analysis ......................................................................................... 100 
13.2. 
General Statistical Considerations ................................................................................. 101 
13.2.1. 
Analysis sets ..................................................................................................................... 101 
13.2.2. 
Factors That May Compromise the Outcome or Interpretation of the Results .............. 102 
13.2.3. 
Familywise error rate and hypothesis testing ................................................................. 102 
13.2.4. 
Sample size rationale ....................................................................................................... 102 
13.2.5. 
Handling of missing data ................................................................................................. 103 
13.2.6. 
Interim sample size adjustment ...................................................................................... 104 
13.2.7. 
Reports ............................................................................................................................ 104 
13.2.8. 
Demographics and baseline variables ............................................................................. 104 
13.2.9. 
Pooling of aDBS mode ..................................................................................................... 104 
13.2.10. 
Center pooling ................................................................................................................. 105 
13.3. 
Analysis Execution ...................................................................................................... 105 
13.4. 
Primary Objective ........................................................................................................ 106 
13.4.1. 
Hypothesis ....................................................................................................................... 106 
13.4.2. 
Endpoint definition .......................................................................................................... 106 
13.4.3. 
Sample size justification .................................................................................................. 107 
13.4.4. 
Analysis methods ............................................................................................................. 107 
13.4.5. 
Handling of missing data ................................................................................................. 108 
13.4.6. 
Supporting analyses ......................................................................................................... 109 
13.5. 
Secondary Objective ................................................................................................... 110 
13.5.1. 
Secondary Objective ........................................................................................................ 110 
13.5.2. 
Hypothesis ....................................................................................................................... 110 
13.5.3. 
Endpoint definition .......................................................................................................... 110 

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13.5.4. 
Sample Size justification .................................................................................................. 111 
13.5.5. 
Analysis methods ............................................................................................................. 111 
13.5.6. 
Handling of missing data ................................................................................................. 111 
13.5.7. 
Supporting analyses ......................................................................................................... 112 
13.6. 
Safety Assessment ...................................................................................................... 112 
13.7. 
Additional Objectives ................................................................................................... 113 
13.8. 
Minimization of Bias .................................................................................................... 113 
14. 
Ethics ........................................................................................................................... 113 
14.1. 
Statement(s) of Compliance......................................................................................... 114 
15. 
Study Administration ................................................................................................... 115 
15.1. 
Monitoring .................................................................................................................. 115 
15.1.1. 
Monitoring Visits ............................................................................................................. 116 
15.2. 
Data Management ....................................................................................................... 116 
15.3. 
Direct Access to Source Data/Documents ..................................................................... 117 
15.4. 
Confidentiality ............................................................................................................. 117 
15.5. 
Liability/Insurance Information .................................................................................... 118 
15.5.1. 
Insurance (Canada) .......................................................................................................... 118 
15.5.2. 
Insurance (Europe) .......................................................................................................... 118 
15.6. 
CIP Amendments ........................................................................................................ 118 
15.7. 
Record Retention ........................................................................................................ 119 
15.7.1. 
Investigator Records ........................................................................................................ 119 
15.7.2. 
Sponsor Records .............................................................................................................. 120 
15.8. 
Reporting Requirements .............................................................................................. 121 
15.8.1. 
Investigator Reports ........................................................................................................ 121 
15.8.2. 
Sponsor Reports .............................................................................................................. 124 
15.9. 
Publication and Use of Information .............................................................................. 128 
15.9.1. 
Publication Committee .................................................................................................... 128 
15.9.2. 
Management of Primary, Secondary, and Ancillary Publications ................................... 128 
15.9.3. 
Criteria for Determining Authorship................................................................................ 129 
15.9.4. 
Transparency ................................................................................................................... 129 

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15.10. 
Suspension or Early Termination .................................................................................. 130 
15.10.1. 
Planned Study Closure ..................................................................................................... 130 
15.10.2. 
Early Termination or Suspension ..................................................................................... 130 
15.10.2.1. 
Study-wide termination or suspension ........................................................................ 130 
15.10.2.2. 
Investigator/study site termination or suspension ..................................................... 130 
15.10.3. 
Procedures for Termination or Suspension ..................................................................... 131 
15.10.3.1. 
Medtronic-initiated and regulatory authority initiated ............................................... 131 
15.10.3.2. 
Investigator-initiated ................................................................................................... 131 
15.10.3.3. 
Ethics Committee-initiated .......................................................................................... 132 
16. 
References ................................................................................................................... 133 
17. 
Version History ............................................................................................................ 138 
Appendix A - aDBS Global Impression of Change Score (GIC) ............................................. 152 
 
 
 

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1. Glossary 
Term/Acronym 
Definition 
µV/√Hz 
Micro-volts per root-hertz (amplitude spectral 
density)  
Acute stimulation-induced effects 
Transient effects that occur during implantable 
neurostimulator programming sessions or while 
running adaptive Deep Brain Stimulation that 
resolve with, or without, stimulation adjustments 
prior to the subject leaving a clinic visit and do 
not require further follow-up or medical care 
outside of the visit. 
aDBS 
Adaptive Deep Brain Stimulation (aDBS). This is 
the general concept under study whereby 
stimulation amplitude is automatically adjusted 
in real-time in response to LFP signal of interest 
aDBS Mode 
An aDBS Mode is an amplitude increment / 
decrement stimulation algorithm. 
The two aDBS modes being evaluated in this 
study are Dual and Single Threshold Modes 
aDBS Setup 
The initial process of setting up a subject to an 
aDBS mode.  
ADE 
Adverse Device Effect 
AE 
Adverse Event 
ASADE 
Anticipated Serious Adverse Device Effect 
Algorithm 
A defined process or set of rules to be followed 
for decision-making, (i.e., to increase or decrease 
stimulation amplitude). 
Alpha - Beta  
Synchronized local field potential neural 
oscillatory activity within the 8-30 Hertz 
frequency range. This is the signal of interest for 
this study.  
App 
Application 
BDI-II 
Beck Depression Inventory©- II 
Best condition 
The time period when PD subjects are receiving 
relief from their Parkinson’s disease symptoms, 
also known as “on” time or “on” period 

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Term/Acronym 
Definition 
BKS 
Bradykinesia Score (from wearable) 
BrainSense™ Technology 
The family of features in the Percept PC system 
that make use of the system capability to capture 
and display local field potential (LFP) signals.  
CA 
Competent Authority 
cDBS 
Continuous Deep Brain Stimulation (cDBS) is the 
commercially available Deep Brain Stimulation 
Therapy. 
CDU Application 
Clinical Data Upload web-based application 
CEC 
Clinical Events Committee 
CE Mark 
A certification mark that indicates conformity 
with health, safety, and environmental protection 
standards for products sold within the European 
Economic Area (EEA). 
CFR 
Code of Federal Regulations (US) 
CIP 
Clinical Investigation Plan 
clDBS   
Closed Loop Deep Brain Stimulation 
CPA 
Clinician Programmer Application 
CRF 
Case Report Form 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CSV 
Comma Separated Values, a data file format 
CTA 
Clinical Trial Agreement 
CTM 
Clinician Telemetry Module 
CV 
Curriculum Vitae 
DBS 
Deep Brain Stimulation 
DD 
Device Deficiency 
Directional Stimulation 
3387 and 3389 leads are not capable of delivering 
directional stimulation  

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Term/Acronym 
Definition 
For SenSight leads, the same amplitude is not 
used on all three electrodes at the same 
electrode level (e.g. 1a-1c, 2a-2c) 
Directional Stimulation Cohort 
Cohort comprised of study subjects with the 
SenSight™ system programed to directional 
stimulation 
DKS 
Dyskinesia Score (from wearable) 
DMC 
Data Monitoring Committee 
DoH 
Declaration of Helsinki 
DTL 
Delegated Task List 
Dual Monopolar 
A Deep Brain Stimulation configuration where 
two contacts of one (or more) electrodes are 
programmed as a cathode (-) and the implantable 
neurostimulator (case) is programmed as the 
anode (+). 
eCRF 
Electronic Case Report Form 
EC 
Ethics Committee  
ECT 
Electroconvulsive Therapy 
EEA 
European Economic Area 
EQ-5D-5L 
Five-dimensional five-level generic measure 
designed to measure, compare and value health 
status across disease areas; developed by the 
EuroQol Group. 
Event markers 
Used to capture and record patient triggered 
events and provide additional information for 
analysis around patients outside the clinic.  
EU 
European Union 
EU MDR 
European Union Medical Device Regulation 
FAL 
Foreseeable Adverse Events Listing 
FD 
Financial Disclosure 

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Term/Acronym 
Definition 
FDA 
US Food and Drug Administration  
FDAAA 
Food and Drug Administration Amendments Act 
FDS 
Fluctuation and Dyskinesia Score (from wearable) 
FW 
Firmware 
GCP 
Good Clinical Practice 
GIC 
Global Impression of Change 
GKC 
Global Kinetics Corporation 
GPi 
Globus Pallidus Internus 
HIPAA 
Health Insurance Portability and Accountability 
Act  
Hz 
Hertz  
IB 
Investigator's Brochure 
IC 
Informed Consent  
IDE 
Investigational Device Exemption 
INS 
Implantable Neurostimulator 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
ITA 
Investigational Testing Authorization 
JSON 
JavaScript Object Notation, a data file format  
LFP 
Local Field Potential 
MAR 
Missing at Random 
MCIC 
Minimal Clinically Important Change 
MDS-UPDRS  
Movement Disorder Society-Sponsored Revision 
of the Unified Parkinson’s Disease Rating Scale – 
The assessment has 4 parts, I-IV 

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Term/Acronym 
Definition 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple Imputation 
Monopolar 
A Deep Brain Stimulation configuration where 
one contact of one or more electrodes is 
programmed as a cathode (-) and the implantable 
neurostimulator (case) is programmed as the 
anode (+). 
NPU 
Neuro Programmer Upload. The NPU database 
will store clinician programmer JSON session 
reports from the neurostimulator interrogations. 
OC 
Oracle Clinical 
PHI 
Protected Health Information 
PD 
Parkinson’s Disease  
PDQ-39 
The 39-item Parkinson’s Disease Questionnaire 
PDQ-39 SI  
PDQ-39 summary index 
PDSS-2 
Parkinson’s Disease Sleep Scale 2 
PKG® 
Personal KinetiGraph®(US), Parkinson’s 
Kinetigraph (EU) 
PMA 
Premarket Approval 
PPA 
Patient Programmer Application 
Primary Cohort 
Cohort comprised of study subjects implanted 
with legacy lead models 3387 or 3389, or with 
the SenSight™ Directional Lead programmed to 
ring mode stimulation 
PRO 
Patient Reported Outcome 
PTM 
Patient Telemetry Module 
PW 
Pulse Width 
RA 
Regulatory Authority 
RDC 
Remote Data Capture 

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Term/Acronym 
Definition 
RF 
Radio Frequency 
Ring Mode 
For 3387 and 3389 leads, stimulation is always 
delivered in Ring Mode 
For SenSight leads, all segmented electrodes at 
the same electrode level (e.g. 1a-1c, 2a-2c) are 
activated at the same amplitude   
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event  
SAP 
Statistical Analysis Plan 
SOI 
Signal of interest, also referred to as a biomarker 
in literature. The signal of interest for this study is 
Alpha - Beta local field potential. 
Stable (cDBS Programming) 
The current cDBS settings are deemed by the 
physician to be acceptable and not likely to 
require substantial changes in the near term. 
STN 
Subthalamic Nucleus 
SW 
Software 
TEED 
Total Electrical Energy Delivered  
TMS 
Transcranial Magnetic Stimulation 
Troublesome dyskinesia 
Dyskinesia which interferes with function or 
causes meaningful discomfort. 
TÜV 
TÜV SÜD is the EU Notified Body 
UADE 
Unanticipated Adverse Device Effect 
UAE 
Unavoidable Adverse Event 
USADE 
Unanticipated Serious Adverse Device Effect 
VHI 
Voice Handicap Index 
WHODrug 
World Health Organization Drug  
Worst condition 
The time period when PD subjects are not 
receiving relief from their Parkinson’s disease 

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Term/Acronym 
Definition 
symptoms, also known as “off” time or “off” 
period. 
Percept™ PC Neurostimulator, BrainSense™ Technology, SenSight™ and aDBS™ Therapy are registered 
trademarks of Medtronic.  
 

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2. Synopsis 
Title 
Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s 
Disease (ADAPT-PD) Trial 
Clinical Study Type 
Pivotal Trial  
Product Name 
Percept™ PC Neurostimulator and aDBS™ Therapy 
Sponsor  
Medtronic  
Local Sponsor 
Medtronic Neuromodulation, USA 
Medtronic International Trading Sàrl, Switzerland 
EU Legal Representative: Medtronic Bakken Research Center B.V., The 
Netherlands   
Medtronic Canada ULC, Canada 
Indication under 
investigation  
Parkinson’s disease (PD) – Deep Brain Stimulation (DBS) implant to 
subthalamic nucleus (STN) or Globus Pallidus (GPi) target sites 
Investigation Purpose 
The purpose of the study is to demonstrate the safety and 
effectiveness of adaptive DBS (aDBS) for Parkinson’s disease. 
Product Status 
Investigational aDBS firmware will be enabled on an already 
implanted, commercially available Model B35200 Percept PC 
implantable neurostimulator (INS). An investigational version of the 
DBS Clinician Programmer will enable the aDBS functionality on the 
INS. An investigational version of the DBS Patient Programmer will be 
available to study subjects.  
Primary Objective(s) 
To demonstrate that the proportion of aDBS subjects with “On” time 
without troublesome dyskinesia during the Evaluation Phase exceeds 
a performance goal of 50%. 
Secondary Objective 
To demonstrate decreased stimulation energy use during the aDBS 
Evaluation Phase as compared with continuous DBS (cDBS). 
Safety Assessments 
To characterize: 
• 
Stimulation-related adverse events during the aDBS 
Evaluation and the cDBS Baseline Phases. 
• 
Serious adverse events, adverse events and device 
deficiencies throughout the study. 
Additional Objectives 
To characterize aDBS during the Evaluation Phase as compared to 
cDBS (Primary Cohort): 
• 
Voice Handicap Index (VHI): “best” and “worst” conditions 
• 
Movement Disorder Society Unified Parkinson’s Disease 
Rating Scale (MDS-UPDRS) Part III subscore (On stim/On med) 
of tremor, rigidity, and bradykinesia questions where a side 
can be determined: 3.3 b, c, d, e (rigidity), 3.4 a, b (finger 
taps/bradykinesia), 3.15 a, b (postural tremor of hands), 3.16 
a, b (kinetic tremor of hands), and 3.17 a, b, c, d (rest tremor 
amplitude) 

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• 
MDS-UPDRS III (On stim/On med) 
• 
MDS-UPDRS II: “best” and “worst” conditions 
• 
MDS-UPDRS III speech question (On stim/On med) q 3.1  
• 
MDS-UPDRS IV 
• 
EQ-5D-5L 
• 
PDSS-2 
• 
Data collected from wearable (for example: % of wear time 
tremor was detected, Dyskinesia Score [DKS], Bradykinesia 
Score [BKS], Fluctuation and Dyskinesia Score [FDS]) 
• 
Parkinson’s Disease Questionnaire (PDQ)-39 Summary Index 
(SI) and subscores: mobility, activities of daily living, 
emotional well-being, stigma, social support, cognition, 
communication, bodily discomfort 
• 
PDQ-39 speech questions 34 and 35 
• 
% of subjects with at least 25% increase in projected battery 
longevity as compared with cDBS 
• 
Parkinson’s Disease Home Diary: “On” time without 
troublesome dyskinesia, “On” time without dyskinesia, “On” 
time with non-troublesome dyskinesia, “On” time with 
troublesome dyskinesia, “Off” time, and Asleep time. 
• 
Patient preference of aDBS vs cDBS (as assessed by a 
Medtronic-developed patient preference questionnaire) 
• 
Patient satisfaction with aDBS (as assessed by a Medtronic-
developed patient satisfaction questionnaire) 
• 
Device data from JSON file, including BrainSense data 
Subgroup analyses (from the entire study population):  
• 
For those with dyskinesia at least 25% of time: Wearable data 
• 
For those with speech side effects: VHI 
• 
For those with mixed programming (aDBS and cDBS): MDS-
UPDRS III by side 
• 
For those who use event markers in long-term follow-up: 
characterize subject population and satisfaction with use of 
event markers 
• 
For those who finished the aDBS Evaluation Phase: one aDBS 
mode will be selected per subject based on subject 
preference or programming availability at the end of the aDBS 
Evaluation Phase. The aDBS Evaluation Phase results may be 
characterized based on the selected mode. 
Primary Endpoint 
Proportion of aDBS subjects with “On” time without troublesome 
dyskinesia exceeding the threshold.  The threshold will be determined 
using the following: on a per-patient basis, the hours of “On” time 

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without troublesome dyskinesia for aDBS is no worse than 1 standard 
deviation less than cDBS. The standard deviation is calculated from 
the difference between aDBS and cDBS in the Full Analysis Set (FAS). 
Secondary Endpoint 
Decreased total electrical energy delivered (TEED) during the 
respective aDBS Evaluation Period as compared with cDBS during the 
cDBS Baseline Phase. 
Safety Analyses 
• 
Stimulation-related adverse events during the cDBS baseline 
and aDBS evaluation phases for all subjects, with tabulations 
individualized by aDBS mode and by target site and combined 
after statistical comparisons for poolability. 
• 
Serious adverse events, adverse events and device 
deficiencies throughout the study for all subjects. 
Study Design 
Prospective, single-blind, randomized crossover, multi-center study of 
aDBS in subjects with Parkinson’s disease. 
The study is expected to be conducted at approximately 12 centers 
located in the US, Europe and Canada. It is estimated that 
approximately 70-100 subjects implanted with a commercially 
available Medtronic DBS system with Percept PC INS will be enrolled 
to obtain 40 subjects for whom at least 1 aDBS mode is acceptable 
and who enter the aDBS evaluation phase. Accounting for a 10% 
dropout during the aDBS Evaluation Phase, a minimum of 36 subjects 
(at least 8 per brain target) will complete the aDBS Evaluation phase.  
In addition, approximately 15 subjects implanted with a commercially 
available Medtronic DBS system with Percept PC INS and SenSight 
system will be enrolled in the Directional Stimulation Cohort to obtain 
9 subjects for whom at least 1 aDBS mode is acceptable and who 
enter the aDBS Evaluation Phase. Accounting for dropout during the 
aDBS Evaluation Phase, a minimum of 8 subjects will complete the 
aDBS Evaluation Phase.   
Study visits and/or phases include:  
• 
Enrollment Visit: Consent, Screening 
• 
cDBS Baseline Phase: Local Field Potential (LFP) Screening and 
Baseline cDBS visits   
• 
aDBS Setup and Adjustment Phase: aDBS Setup visit and 
additional optional visits during an aDBS Adjustment period 
• 
aDBS Evaluation Phase: One-month treatment periods in each 
acceptable aDBS mode with aDBS evaluation visits at the end of 
each period.  Randomized crossover to the two investigational 
treatments in subjects for whom both aDBS modes were 
acceptable and a single treatment period in those subjects for 
whom only one aDBS mode was acceptable.   

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• 
Long-Term Follow Up Phase: Four visits in preferred aDBS mode 
for approximately 10 months 
• 
Extended Access Phase: Additional visits in the preferred aDBS 
mode every 6 months through commercial approval of aDBS 
Randomization 
Randomization to a crossover sequence of aDBS single threshold and 
aDBS dual threshold modes 
Sample Size 
Primary Cohort 
It is estimated that approximately 70-100 subjects implanted with a 
commercially available Medtronic DBS system with Percept PC INS 
will be enrolled in the study to obtain 40 subjects for whom at least 1 
aDBS mode is acceptable and who enter the aDBS evaluation phase. It 
is expected that approximately 50% of enrolled subjects will be exited 
from the study at LFP Screening due to insufficient Alpha - Beta band 
amplitude and/or artifact. Accounting for a 10% dropout during the 
aDBS Evaluation Phase, a minimum of 36 subjects (at least 8 per brain 
target) are expected to complete the aDBS Evaluation phase.  
Because the device implant will occur outside of the study and the 
study requires participants to be stable on cDBS, the standard 
deviation of the change from cDBS to aDBS in “On” time without 
troublesome dyskinesia will be used to establish a threshold for 
assessing the performance goal. The threshold will be set as 1 
standard deviation. If the difference between aDBS and cDBS (aDBS-
cDBS) for a subject is at least -1 standard deviation, the threshold will 
be met for the subject. Using this threshold, the proportion of 
subjects who exceed the threshold will be computed. 
The sample size was estimated using a binomial distribution for a one-
sided test for a proportion to compare to a performance goal of 50%. 
Assuming the alternative hypothesis of 85% of subjects exceeding the 
threshold described above, a minimum of 36 subjects achieves at 
least 90% power to reject a performance goal of 50%. Sample size was 
computed in PASS 11. 
For the safety analysis, a minimum of 30 subjects followed for 
approximately 30 days with aDBS out-of-clinic in the subjects’ real-
world environments provides greater than 95% probability that all 
stimulation-related adverse events with a true adverse event rate of 
at least 10% would be reported at least once. 
Directional Stimulation Cohort 
In addition, approximately 15 subjects implanted with a commercially 
available Medtronic DBS system with Percept PC INS and SenSight 

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system will be enrolled in the Directional Stimulation Cohort to obtain 
9 subjects for whom at least 1 aDBS mode is acceptable and who 
enter the aDBS Evaluation Phase. Accounting for dropout during the 
aDBS Evaluation Phase, a minimum of 8 subjects will complete the 
aDBS Evaluation Phase.  
Inclusion/Exclusion Criteria 
There are two sets of criteria for study participation prior to the 
investigational use of aDBS. 
1. Subjects must meet all general inclusion/exclusion criteria (as 
assessed at the Enrollment Visit) 
2. Subjects must meet the LFP screening inclusion criterion (as 
assessed at the LFP Screening Visit) 
General  
Inclusion Criteria 
Primary Cohort: 
1. Subject has idiopathic Parkinson’s disease 
2. Subject is implanted with Percept PC (Model B35200) and 
Medtronic DBS leads (Model 3387, 3389, B33005 or B33015) 
and extensions (Model 37085, 37086 or B34000) bilaterally in 
the same target (physician confirmed), STN or GPi  
3. In the opinion of the investigator, the subject responds to DBS 
Therapy.  
4. Based on the opinion of the investigator, the subject’s cDBS 
parameters and PD medications are stable and expected to 
remain stable from enrollment through the end of the aDBS 
Evaluation phase 
5. Subject is configured to ring mode monopolar or dual 
monopolar stimulation using contacts 1 and/or 2 (9 and/or 
10) on at least one side.  
6. Subject is willing and able to attend all study-required visits 
and complete the study procedures (e.g. 1-month recall 
questionnaires, MDS-UPDRS III) 
7. Subject has the ability to understand and provide written 
informed consent for participation in the study prior to the 
study-related procedures being conducted 
8. Subject is a male or non-pregnant female. If female of child-
bearing potential, and if sexually active, must be using, or 
agree to use, a medically-acceptable method of birth control 
as confirmed by the investigator 
9. For subjects with the SenSight system: Subject is configured 
to the following stimulation rates: 55, 85, 110, 125, 145, 164 
or 180 Hz (as required for sensing/aDBS) 
 

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Directional Stimulation Cohort: 
Subjects must meet the same inclusion criteria as the primary cohort 
except for revised #2 and #5. 
 
Revised Inclusion Criteria: 
2. Subject is implanted with Percept PC (Model B35200) and 
Medtronic DBS leads (Model B33005 or B33015) and 
extensions (Model B34000) bilaterally in the same target 
(physician confirmed), STN or GPi  
5. Subject is configured to directional monopolar or dual 
monopolar stimulation using contacts 1 and/or 2 (9 and/or 
10)  
Exclusion Criteria (All Cohorts) 
1. Subject and/or caregiver is unable to utilize the patient 
programmer  
2. Subject has more than one lead in each hemisphere of the 
brain 
3. Subject has cortical leads or additional unapproved hardware 
implanted in the brain 
4. Subject has more than one INS 
5. At enrollment, the subject’s INS has a predicted battery life of 
<1 year 
6. Subject has Beck Depression Inventory II (BDI-II) > 25 
7. Subject requires diathermy, transcranial magnetic stimulation 
(TMS), or electroconvulsive therapy (ECT)  
8. Subject has a metallic implant in the head, (eg, aneurysm clip, 
cochlear implant) 
9. Subject has, or plans to obtain, an implanted electrical 
stimulation medical device anywhere in the body (eg, cardiac 
pacemaker, defibrillator, spinal cord stimulator) 
10. Subject has, or plans to obtain, an implanted medication 
pump for the treatment of Parkinson’s disease (eg, DUOPATM 
infusion pump) and/or portable infusion pump 
11. Based on the opinion of the investigator, the subject has an 
abnormal neurological examination that would preclude them 
from study participation  
12. Subject is breast feeding  
13. Subject is under the age of 18 years 
14. Subject is currently enrolled in or plans to enroll in any 
concurrent drug and/or device study that may confound the 

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results of this study as determined by the Medtronic study 
team  
15. Subject is unable to use or tolerate wearable  
16. Subjects with signal artifact on all 6 aDBS sense pathways (3 
each on both DBS leads) which preclude the clinician from 
setting thresholds 
LFP Screening 
Inclusion Criteria (All Cohorts) 
1. Subject has Alpha - Beta band (8-30 Hz) amplitude ≥ 1.2 µVp 
detected on either left and/or right DBS leads on sensing 
channels 0-2, 0-3, or 1-3; 8-10, 8-11, or 9-11 
Study Procedures and 
Assessments 
Subjects will be considered enrolled at the time they sign the 
informed consent form. 
Scheduled visits will include the following:  
Enrollment, LFP Screening, cDBS Baseline, aDBS Setup, 
Randomization, aDBS Evaluation Visit 1, aDBS Evaluation Visit 2, Long-
term follow-up Visit 3, Long-term follow-up Visit 4, Long-term follow-
up Visit 5, and Long-term follow-up Visit 6. 
Subjects participating in the extended access phase prior to 
commercial approval of aDBS, will have visits every 6 months.  
The following assessments / data will be collected during the study: 
• 
Concomitant medications 
• 
PDQ-39 
• 
EQ-5D-5L 
• 
MDS-UPRDS Parts I-IV 
• 
Parkinson’s Disease Home Diary  
• 
VHI 
• 
PDSS-2 
• 
aDBS Global Impression of Change score 
• 
Patient preference questionnaire 
• 
Patient satisfaction questionnaire 
• 
Wearable data 
• 
Programming session data, including BrainSense data 
• 
Event markers (optional) 
• 
Adverse Events and Device Deficiencies 
 Statistics 
Primary and secondary objectives will be analyzed using the FAS. The 
FAS includes all Primary Cohort subjects, using the intention-to-treat 
(ITT) principle, who initiate the aDBS Evaluation Phase using the 
randomized treatment assignment for each subject that was 
randomized and the programmable treatment assignment for those 
subjects that may only be configured to one aDBS mode (dual or 

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single threshold). Safety analyses will be evaluated using the As-
Treated (AT) Analysis Set. AT includes all Primary Cohort subjects who 
are treated with continuous Deep Brain Stimulation (cDBS) and/or 
adaptive Deep Brain Stimulation (aDBS) during the cDBS Baseline 
Evaluation Phase and/or the aDBS Evaluation Phase, and Long-term 
Follow-up Phase and uses the observed treatment used for each 
subject in each phase. 
The Parkinson’s Disease Home Diary from the two weeks prior to the 
Baseline visit (cDBS) and the aDBS Evaluation visits (aDBS) will be used 
to evaluate the primary objective. The observed proportion will be 
computed for each aDBS mode separately and compared to the 
performance goal using a binomial exact test.   
The secondary objective will evaluate the decrease in Total Electrical 
Energy Delivered (TEED) for each aDBS mode compared to cDBS using 
data from the 14-days prior to the Baseline visit (cDBS) or the 
respective aDBS Evaluation Visit (aDBS).  
Supporting analyses for the objectives in the Primary Cohort include: 
verifying the lack of a period or carryover effect, verifying poolability 
by assessing target site effects (STN/GPi) and center effects. In 
addition, summarized results from the Directional Stimulation Cohort 
will be provided as supporting analyses to the primary, secondary, 
and safety Primary Cohort results. Sensitivity analyses will be 
performed.  
The additional objectives will be evaluated from the Primary Cohort 
to compare each outcome for each aDBS mode during the aDBS 
Evaluation Phase compared to cDBS during the cDBS Baseline Phase.  
The familywise error rate will be controlled using one-sided tests with 
an overall alpha-level of 0.025 approach to multiple testing. Each 
primary hypothesis (one for each aDBS mode) will be assigned a 
Bonferroni corrected alpha (0.0125) for the respective primary 
hypothesis (see Section 13.4.1). The primary hypothesis will serve as a 
gatekeeper for the secondary hypothesis within each mode. 
Sample size in the Primary Cohort may be increased to a maximum of 
55 subjects for whom at least 1 aDBS mode is acceptable and who 
enter the aDBS evaluation phase to obtain at least 8 subjects per 
aDBS mode and 8 subjects per target site (STN/GPi). 

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All attempts will be made to minimize missing data. If 5% of the data 
or fewer are missing for the analysis, no imputation will be used. 
Otherwise, if missing data are observed, multiple imputation will be 
used with the primary and secondary objectives. If an aDBS mode is 
not programmable to a patient, summary statistics will be computed 
to summarize the percent who were not programmed to a mode and 
no imputation will occur for that outcome for that aDBS mode.  The 
Complete Case Analysis Set and the As-Treated Analysis Set will be 
used for sensitivity analysis to the primary and secondary objective 
analyses. 

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3. Introduction  
3.1. Background  
Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease associated with both motor 
and non-motor symptoms.  It affects 2-3 percent of people aged 65 or older but can begin as early as the 
third or fourth decade.1  PD is caused by a loss of dopamine-producing cells in the substantia nigra and is 
associated with pathological beta (approximately 13-35 Hz) bursts and excessive synchronization within 
the cortico-basal ganglia network of the brain.1,2,3  This disruption in brain activity is associated with the 
characteristic motor symptoms of the disease:  resting tremor, rigidity, bradykinesia, and postural 
instability.4-5, 6,7 
In the initial stages of PD, motor symptoms are often well controlled using dopaminergic drugs.  
However, chronic use of these levodopa medications over a 5-10 year period is associated with 
symptom fluctuations, dyskinesia and other motor complications in up to 80% of PD patients.4  These 
complications may be equal to or worse in severity than the motor impairment caused by the disease 
itself.8  Deep Brain Stimulation (DBS) Therapy may be used to treat some of the motor complications of 
PD that are not adequately controlled with medication. DBS is a surgical intervention that involves the 
placement of electrodes in targeted areas of the brain. These electrodes are arranged on a lead and are 
connected to an implanted neurostimulator that delivers mild electrical pulses to targeted brain areas. 
Once patients are implanted with the DBS device, clinicians may adjust the electrical stimulation 
parameters to obtain maximal symptom relief and minimize stimulation-induced adverse effects. 
The use of DBS in the subthalamic nucleus (STN) and globus pallidus interna (GPi) has been shown to 
improve symptoms of PD.4,9,10,11,12,13,14,15,16,17 Several multicenter, randomized controlled trials 
conducted in the United States, Europe, and in several other geographies worldwide provide evidence of 
its effectiveness.18,19,20,21,22,23,24 Deep Brain Stimulation Therapy is currently delivered in a continuous 
fashion (cDBS) where stimulation settings are constant over time and do not adjust to fluctuations in 
symptoms typically experienced by Parkinson’s disease patients during medication On and Off states.  
During On-medication states the addition of stimulation is thought to contribute to dyskinesias and 
other side effects experienced by the patient.25 To make DBS more responsive to an individual patient’s 
clinical state, investigators have explored the use of adaptive DBS (aDBS) therapy.   
aDBS Therapy, also known as closed-loop DBS (clDBS), adjusts stimulation in a variable fashion. It relies 
on a biomarker, or signal of interest (SOI), to adjust stimulation.  The SOI must correlate to a patient’s 
clinical state (i.e. severity of disease symptoms), dynamically reflect changes in disease symptoms, be 
persistent over time, be discernible from background artifacts and be measurable with minimal 
additional intervention.26,27,28,29  Perhaps the most studied SOIs within this context are local field 

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potentials (LFPs), which represent the transient oscillatory activity of various neuronal populations in 
the brain. 
During the last decade, researchers have worked to characterize LFP signals in the brain.  LFPs represent 
the summed pre- and post-synaptic neuronal activity in the area of the brain where the LFPs are being 
recorded.  Researchers have shown the presence of excessive LFP beta oscillations in the range of 
approximately 13-35 Hz and over-synchronization in the cortico-basal ganglia network in the brains of 
PD patients.4,30,31,32,33  In a review of 20 publications between 2001 and 2011, researchers reported 
measurable beta peaks in the Off-medication state in a mean of 95% of PD patients/nuclei.29 These beta 
LFP signals are persistent over time,34,35,36,37,38,39  can be measured using the currently approved 
Medtronic DBS leads,34,35,36,38,40 can correlate with severity of bradykinesia and rigidity in PD patients and 
are attenuated by both levodopa (i.e., in the ON-medication state) and DBS stimulation.7,28,31,32,41,42,43 
The degree to which these LFP signals are attenuated correlates with the degree of improvement in 
symptoms of bradykinesia and rigidity.7,28,31,32,42,43,44   
In recent years, research has been conducted to test the feasibility of using aDBS Therapy where the 
stimulation adjusts automatically based on LFPs in the basal ganglia. Based on evidence that beta LFPs 
decrease in response to increasing stimulation, two slightly different aDBS control mechanisms have 
been utilized in these studies. The first is a scalar approach (i.e., dual threshold aDBS mode) whereby 
stimulation amplitude is incrementally adjusted between upper and lower, clinician-defined therapeutic 
limits to maintain beta LFP within a defined range.45,46,47 The second is a binary approach (i.e., single 
threshold aDBS mode), whereby stimulation switches on when the beta LFP exceeds a preset threshold 
and switches off when the LFP falls below the preset threshold. 25,48,49,50  Clinical studies using both single 
and dual threshold aDBS control mechanisms support the technical feasibility of using beta LFP signals 
as a signal of interest for aDBS.45,46,47,48,49,50,51,52,53,54 
Evidence from single center feasibility studies has demonstrated that aDBS is at least as efficacious as 
cDBS based on UPDRS III motor scores and could potentially be up to 27% more effective.47,48,49 aDBS 
may also reduce stimulation-induced adverse effects such as dyskinesia and speech impairment. In 
multiple studies, PD patients receiving aDBS showed less dyskinetic effects compared to cDBS, 
potentially by reducing the sum effect of stimulation and medication.25,52,54 Regarding speech, one study 
of 10 subjects showed a clinically meaningful improvement in speech intelligibility with aDBS over 
cDBS.50  Overall aDBS was well tolerated in freely moving PD subjects both On and Off medications for 
up to 8 hours.47,49,52,53,55  In addition, multiple studies showed a significant reduction in the power usage 
with aDBS compared to cDBS, averaging about 50% of the power demand of standard cDBS Therapy.45-
49,52,54 

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Although the subjects and conditions of the individual studies assessing aDBS vary, these studies have 
consistently shown the feasibility of using aDBS controlled by STN beta LFP feedback and its potential to 
effectively reduce PD symptoms while reducing side effects and increasing battery longevity. 
3.2. Purpose 
The purpose of the study is to demonstrate the safety and effectiveness of adaptive DBS (aDBS) for 
Parkinson’s disease.  
4. Objectives and Endpoints 
4.1. Objectives 
4.1.1. 
Primary Objective 
To demonstrate that the proportion of aDBS subjects with “On” time without troublesome dyskinesia 
during the Evaluation Phase exceeds a performance goal of 50%. 
4.1.2. 
Secondary Objective 
To demonstrate decreased stimulation energy use during the aDBS Evaluation Phase as compared with 
cDBS. 
4.1.3. 
Safety Assessments 
To characterize: 
• 
Stimulation-related adverse events (AEs) during the aDBS evaluation and the cDBS baseline 
phases. 
• 
Serious adverse events (SAEs), adverse events and device deficiencies throughout the study. 
4.1.4. 
Additional Objectives 
To characterize aDBS as compared to cDBS (Primary Cohort): 
• 
Voice Handicap Index (VHI): “best” and “worst” conditions 
• 
MDS-UPDRS III subscore (On stim/On med) of tremor, rigidity, and bradykinesia questions where 
a side can be determined: 3.3 b, c, d, e (rigidity), 3.4 a, b (finger taps/bradykinesia), 3.15 a, b 
(postural tremor of hands), 3.16 a, b (kinetic tremor of hands), and 3.17 a, b, c, d (rest tremor 
amplitude) 

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• 
MDS-UPDRS III (On stim/On med) 
• 
MDS-UPDRS II: “best” and “worst” conditions 
• 
MDS-UPDRS III speech question (On stim/On med) q 3.1  
• 
MDS-UPDRS IV 
• 
EQ-5D-5L 
• 
PDSS-2 
• 
Data collected from wearable (for example: % of wear time tremor was detected, Dyskinesia 
Score [DKS], Bradykinesia Score [BKS], Fluctuation and Dyskinesia Score [FDS]) 
• 
PDQ-39 Summary Index (SI) and subscores: mobility, activities of daily living, emotional well-
being, stigma, social support, cognition, communication, bodily discomfort 
• 
PDQ-39 speech questions 34 and 35 
• 
% of subjects with at least 25% increase in projected battery longevity as compared with cDBS 
• 
Parkinson’s Disease Home Diary: “On” time without troublesome dyskinesia, “On” time without 
dyskinesia, “On” time with non-troublesome dyskinesia, “On” time with troublesome dyskinesia, 
“Off” time, and Asleep time. 
• 
Patient preference of aDBS vs cDBS (as assessed by a Medtronic-developed patient preference 
questionnaire) 
• 
Patient satisfaction with aDBS (as assessed by a Medtronic-developed patient satisfaction 
questionnaire) 
• 
Device data from JSON file including BrainSense data  
Subgroup analyses (from the entire study population):  
• 
For those with dyskinesias: at least 25% of time: Wearable data 
• 
For those with speech side effects: VHI 
• 
For those with mixed programming (one hemisphere with aDBS and one with cDBS): MDS-
UPDRS III by side 
• 
For those who use event markers in long-term follow-up: characterize subject population and 
satisfaction with use of event markers  
• 
For those who finished the aDBS Evaluation Phase: one aDBS mode will be selected per subject 
based on subject preference or programming availability at the end of the aDBS Evaluation 
Phase. The aDBS Evaluation Phase results may be characterized based on the selected mode. 
 

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4.2. Endpoints 
4.2.1. 
Primary Endpoint 
Proportion of aDBS subjects with “On” time without troublesome dyskinesia exceeding the threshold.  
The threshold will be determined using the following: on a per-patient basis, the hours of “On” time 
without troublesome dyskinesia for aDBS is no worse than 1 standard deviation less than cDBS. The 
standard deviation is calculated from the difference between aDBS and cDBS in the Full Analysis Set 
(FAS). 
A performance goal of 50% was chosen for this study in order to demonstrate that at least 50% of the 
subjects are able to achieve the threshold with 95% confidence, demonstrating some level of efficacy. 
The endpoint of the Parkinson’s Disease (PD) Home Diary was chosen to determine the threshold of 
success as it is a measure of the subject response to DBS therapy over time, because the aDBS algorithm 
will adapt the therapy over time, and because the PD Home Diary has been used as an endpoint in 
previous DBS trials.  A unit of one standard deviation was chosen as it is an acceptable amount of 
statistical variability in the PD Home Diary endpoint given the fluctuating nature of Parkinson’s disease 
and the percentiles of a normal distribution. 
4.2.2. 
Secondary Endpoint 
Decreased total electrical energy delivered (TEED) for each aDBS mode during the respective aDBS 
Evaluation Period as compared with cDBS during the cDBS Baseline Phase. 
5. Study Design  
The ADAPT-PD trial is a prospective, multicenter, single-blind, randomized crossover clinical 
investigation and is designed to demonstrate the safety and effectiveness of adaptive DBS for 
Parkinson’s disease. It is composed of a primary trial cohort (Primary cohort) with subjects programmed 
in ring mode and a cohort of subjects implanted with the SenSight system and programmed to 
directional stimulation (Directional Stimulation Cohort). For subjects with the 3387 and 3389 DBS leads, 
stimulation is always delivered in Ring mode. In subjects with the SenSight lead, ring mode is when all 
segmented electrodes at the same electrode level (e.g. 1a-1c, 2a-2c) are activated at the same 
amplitude. Directional stimulation, which can only be programmed in subjects with SenSight leads, is 
when the same amplitude is not used on all three electrodes at the same electrode level (e.g. 1a-1c, 2a-
2c). 
The study is expected to be conducted at approximately 12 centers located in the US, Europe and 
Canada. It is estimated that approximately 70-100 subjects implanted with a commercially available 

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Medtronic DBS system with Percept PC INS will be enrolled in the Primary Cohort to obtain 40 subjects 
for whom at least 1 aDBS mode is acceptable and who enter the aDBS Evaluation Phase. Accounting for 
a 10% dropout during the aDBS Evaluation Phase, a minimum of 36 subjects (at least 8 per brain target) 
will complete the aDBS Evaluation Phase. In addition, approximately 15 subjects implanted with a 
commercially available Medtronic DBS system with Percept PC INS and SenSight system will be enrolled 
in the Directional Stimulation Cohort to obtain 9 subjects for whom at least 1 aDBS mode is acceptable 
and who enter the aDBS Evaluation Phase and a minimum of 8 subjects who complete the aDBS 
Evaluation Phase.  
There is no minimum number of subjects required to be enrolled at a center. For the Primary Cohort, 
each study center will stop enrollment after they have identified a maximum of 8 subjects for whom at 
least 1 aDBS mode is acceptable and who enter the aDBS Evaluation Phase (~25% of the total planned 
number of subjects). For the Directional Stimulation Cohort, each study center will stop enrollment after 
they have identified a maximum of 5 subjects for whom at least 1 aDBS mode is acceptable and who 
enter the aDBS Evaluation Phase. The actual number of subjects at a study center may be slightly larger 
due to the number of subjects that are enrolled prior to cessation of enrollment. This restriction is 
intended to reduce the possibility that the results from one study center will be overly influential in the 
overall study results.  
The study consists of four phases following enrollment: 
• 
cDBS Baseline Phase (approximately 1 month): LFP Screening, Baseline cDBS and Off stimulation 
Assessments  
• 
aDBS Setup and Adjustment Phase (up to 2 months): aDBS Setup visit and additional optional 
visits during an aDBS Adjustment period 
• 
aDBS Evaluation Phase (approximately 2 months): One-month treatment periods in each 
acceptable aDBS mode with aDBS evaluation visits at the end of each period.  Randomized 
crossover to the two investigational treatments in subjects for whom both aDBS modes were 
acceptable and a single treatment period in those subjects for whom only one aDBS mode was 
acceptable.   
• 
Long-Term Follow Up Phase (approximately 10 months): Four scheduled visits in the preferred 
aDBS mode 
Subject participation in an Extended Access Phase is optional and includes additional visits in the 
preferred aDBS mode every 6 months through commercial approval of aDBS. 
The design of the Directional Stimulation Cohort is the same as the main ADAPT-PD trial. Subjects 
enrolled in the Directional Stimulation Cohort will follow the same visit schedule. 
5.1. Duration 

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The study duration is expected to be approximately 5 years. It is estimated that approximately 16 
months will be needed to enroll 70-100 subjects in order to obtain 40 subjects for whom at least 1 aDBS 
mode is acceptable and who will enter the aDBS Evaluation Phase of the Primary cohort and to enroll 
approximately 15 subjects in order to obtain 9 subjects for whom at least 1 aDBS mode is acceptable 
and a minimum of 8 who complete the aDBS Evaluations Phase in the Directional Stimulation Cohort. 
Study participation for subjects who are enrolled, but do not meet the LFP screening criteria is 
estimated to be approximately 1 month. Subjects who do not meet the LFP screening criteria will be 
exited at the beginning of the cDBS Baseline phase. 
Subjects who meet the LFP screening criteria will be followed for approximately an additional 4 months 
in the cDBS Baseline and aDBS Setup and Adjustment phases. Subjects who cannot be set up or 
acceptably configured on at least one aDBS mode will be exited prior to randomization. 
Subjects who meet the LFP screening criteria and can be acceptably configured on at least one aDBS 
mode will enter the aDBS Evaluation Phase. If both aDBS modes were acceptable subjects will be 
randomized and followed for approximately 2 months. If only one aDBS mode was acceptable, they will 
complete a single one-month period in the aDBS Evaluation phase. This will be followed by 
approximately 10 months in the Long-term Follow-up phase for a total of approximately 1 year in aDBS.  
Subjects will be allowed extended access to aDBS through commercial approval of aDBS in the 
geography in which the subject is enrolled. The subject will continue the study in their preferred aDBS 
mode until aDBS is commercially approved or closure of the study, whichever comes sooner.  
The study may also be stopped on recommendation of the DMC. See Section 12.1. 
5.2. Rationale  
The ADAPT-PD study will utilize the commercially approved Model B35200 Percept PC INS that has 
investigational aDBS functionality enabled.  This aDBS functionality was developed using the clinical 
knowledge gained in numerous investigator-sponsored, single-center, feasibility studies and investigator 
experience with the Medtronic Activa PC+S INS, a first generation aDBS device.  The aDBS control 
algorithm will rely on STN and GPi Alpha- - Beta band (approximately 8-30 Hz) activity as the signal of 
interest.  The feasibility of using Alpha - Beta LFP has been demonstrated by multiple centers and across 
multiple research groups.25,45,46,47,48,49,50,51,52,53,54,55 The ADAPT-PD Study will assess both dual and  single 
threshold aDBS modes (algorithms).  Evidence generated by the Bronte-Stewart/Stanford group using a 
dual threshold algorithm and the Brown/Oxford group using a single threshold algorithm has 
demonstrated that aDBS is feasible. In addition, both dual and single threshold aDBS were well 
tolerated, were as effective or more effective than cDBS, may reduce DBS induced side effects and were 
associated with a significant reduction in DBS power usage compared to cDBS.25,45,46,47,48,49,50  Based on 

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this evidence, this protocol will use a larger sample size across multiple centers under controlled 
conditions to further evaluate these results to support the use of aDBS as an additional programming 
tool to further personalize the already established and effective cDBS therapy. 
6. Product Description 
6.1. General 
Medtronic DBS Therapy uses implantable, programmable neurostimulators, leads and extensions to 
deliver electrical stimulation to the STN or GPi to manage some of the symptoms of PD.  
The Percept PC system includes the Percept PC INS and external components that use telemetry to 
communicate with the INS for programming stimulation parameters. Table 1 provides a listing of the 
Percept PC system components which will be used in the ADAPT-PD Trial. Figure 1 illustrates the full 
Percept PC system. The commercially available components are described below in Section6.1.1.  
The devices that are considered investigational for the ADAPT-PD system include the Model B35200 
Percept PC INS when aDBS firmware is enabled, the Model A610 Clinician Programmer Application 
Version 3.0 with aDBS software enabled and the Model A620 Version 2.0 Patient Programmer 
Application (PPA) with aDBS functionality. These components are described in Section 6.1.2. The devices 
will become investigational in the ADAPT-PD Trial when the aDBS firmware or software feature flags are 
enabled or when aDBS screens are displayed on the programmers. There is no physical difference 
between the commercially available components of the Percept PC system and the investigational 
components. Parts of the clinician programmer system and patient programmer system to be used in 
the ADAPT-PD Trial are completely unchanged from the commercially available versions but are 
packaged and used with devices that will be considered investigational once aDBS is enabled and will 
therefore also be considered investigational. 
The combination of approved labeling, investigational labeling and the Clinical Investigation Plan 
contains adequate information for the purposes of the investigation.  The investigational labeling will be 
provided to investigational sites, IRBs/ECs and Regulatory Authorities (as applicable) in the Investigator’s 
Brochure (IB). Investigational labeling for the Patient Programmer System will be provided to patients 
after aDBS is set up.   
 
 

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Table 1: Medtronic DBS System Components 
 
Component 
Model 
Implantable 
Neurostimulator 
Model B35200 Percept PC INS with aDBS firmware (FW) 
enabled* 
• 
Product Firmware Version 7.5 
• 
Device Firmware Version 7.5 
• 
Core Firmware Version 7.5 
External 
Clinician Programmer 
System Components 
• 
Model 8880T2 Version 1.107 Clinician Telemetry 
Module** 
• 
Model CT900 Clinician Programmer Tablet** 
o Model A610 Clinician Programmer Application 
Version 3.0 with aDBS software enabled** 
o Model A901 Version 1.0 Communication 
Manager** 
o Model A902 Version 1.0 Patient Data 
Services** 
Patient Programmer 
System Components 
TH91 Package Kit 
1. Model TM91 Version 2.1 Patient Telemetry 
Module**  
2. Model HH90 Patient Programmer Phone** 
3. Model A620 Version 2.0 Patient Programmer 
Application (PPA) with aDBS functionality* 
*Components are physically the same as the commercially available product with investigational firmware or 
software feature flags enabled or investigational screens displayed. The software/firmware versions are the same 
as the commercially available product. 
**Components are not modified from the commercially available version but will be considered investigational as 
they are packaged together with the Patient and Clinician Programmer Applications as a system.  
 
The commercially approved (FDA approved, CE marked, and Health Canada licensed) devices will be 
used within the scope of their approved labeling for which FDA approval, CE mark, or Health Canada 
approval has been obtained. 

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Figure 1: Percept PC System 

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6.1.1. 
Medtronic Commercially Available DBS System Components 
Model B35200 Percept PC INS  
The model B35200 Percept PC Neurostimulator with BrainSense™ (Product Firmware Version 7.5, Device 
Firmware Version 7.5, Core Firmware Version 7.5) is commercially available for DBS Therapy and is part 
of an active implantable device system for deep brain stimulation and sensing. The DBS system delivers 
electrical stimulation to targeted regions of the brain, defined by anatomy and/or physiology, to 
suppress the symptoms associated with a neurologic disorder treatable by brain stimulation. The 
neurostimulator is a multiprogrammable device that delivers stimulation through 1 or 2 leads. The 
stimulation settings are stored in programs. Programmable parameters include amplitude, pulse width, 
rate, and cycling. Percept PC is able to deliver cDBS and also has the capability to sense and record 
bioelectric data through the DBS leads implanted in the brain. 
Percept PC has embedded firmware which adjusts the stimulation output of the device to conform to 
clinician programmed parameters. The firmware stores data pertinent to device operation and sends 
the data via radio frequency (RF) telemetry when requested by one of the programmers (clinician 
programmer or patient programmer). The firmware limits stimulation outputs to within clinician-defined 
ranges and modes.  
The commercially available Model B35200 Percept PC INS will be implanted prior to subject enrollment 
in the study. The commercially available Model B35200 Percept PC INS contains the aDBS FW, but the 
FW is not active.  
DBS Leads (Includes models 3387, 3389, B33005 and B33015)  
The Models 3387 and 3389 DBS Leads are composed of a polyurethane protective sheath with four 
platinum/iridium electrodes located at the distal end, which are used to deliver the electrical stimulation 
to the target site.   
The Model 3387 DBS Lead features wide (1.5 mm) spacing between each of the four electrodes at the 
distal end. The Model 3389 DBS Lead features narrow (0.5 mm) spacing between each of the four 
electrodes at the distal end.  
The Models B33005 and B33015 SenSight Leads are composed of a polyurethane protective sheath with 
eight platinum/iridium electrodes located at the distal end (in a 1-3-3-1 configuration with the second 
and the third electrodes separated into three separate electrodes spaced 120° from the center of each 
segment), which are used to deliver the electrical stimulation to the target site.  

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The Model B33015 SenSight Lead features wide (1.5 mm) spacing between each of the four electrode 
levels at the distal end. The Model B33005 SenSight Lead features narrow (0.5 mm) spacing between 
each of the four electrode levels at the distal end.  
DBS Extension Kits (Includes models 37085, 37086, or B34000 in 40, 60, 95 cm lengths) 
The Model 37085 and 37086 Extensions connect the neurostimulator to the lead, providing an electrical 
path that allows stimulation to be delivered to the target site.  The Model 37085 and 37086 DBS 
Extensions are identical.  The only difference is the Model 37085 DBS Extension Kit contains a tunneling 
tool and the Model 37086 DBS Extension Kit does not. 
The Model B34000 SenSight Extension connects the neurostimulator to the lead, providing an electrical 
path that allows stimulation to be delivered to the target site. 
Clinician Programmer System Components (Model A610 Clinician Programmer Application, Model 
CT900 Clinician Programmer Tablet, Model 8880T2 Clinician Telemetry Module, Model A901 
Communication Manager and Model A902 Patient Data Services) 
The Medtronic Model A610 DBS Version 3.0 () Clinician Programmer Application (CPA) is intended for 
use by clinicians in the programming of Medtronic neurostimulators (external and implantable) for deep 
brain stimulation (DBS).   
The Model CT900 clinician programmer tablet, with Android®-based operating system, is intended for 
use by clinicians to use in conjunction with the CPA to program Medtronic neurostimulators. 
The Model 8880T2 Communicator is intended for use by clinicians to use in conjunction with the 
clinician tablet and CPA for communication with Medtronic Neuromodulation therapy devices. 
The Model A901 Version 1.0 Communication Manager Application is intended to manage the telemetry 
communications for the clinician tablet.  
The Model A902 Version 1.0 Patient Data Service Application is intended for use by clinicians to access 
reports for all patients whose Medtronic devices have been programmed using the CPA on the clinician 
tablet. The Patient Data Service app can also be used to access reports for all patients whose Medtronic 
devices have been programmed using any clinician programmer application on the same clinician tablet. 
The Patient Data Service app can be used to adjust (or disable) the auto-delete feature, which 
automatically deletes patient data (after it has been compiled into reports) after a designated amount of 
time. 
Patient Programmer System Components (TH91 package kit includes: Model A620 Patient 
Programmer Application, Model HH90 Patient Programmer Phone, Model TM91 PTM) 

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The Model HH90 Patient Programmer Handset has a screen like a smartphone and contains the Model 
A620 patient programming application. 
The Model TM91 PTM allows the A620 Patient Programmer Application on the HH90 Patient 
Programmer Phone to connect with the subject’s neurostimulator. 
6.1.2. 
Medtronic Investigational DBS System Components 
aDBS Feature 
The intended purpose of the aDBS feature is to automatically adjust stimulation amplitude, within 
clinician-defined limits, based on changes in a patient’s brain state measured using Alpha - Beta LFPs as 
a signal of interest.  Under the assumption that correlations exist between brain state and clinical 
symptoms and side effects, the goal is to maintain the brain state such that certain clinical symptoms 
and side effects can be managed. The aDBS feature is investigational for this study and is enabled using 
a Clinician Programmer System with investigational aDBS software enabled. The ADAPT-PD Trial will 
study two aDBS modes, Dual and Single Threshold modes. Additional modes will be available on the 
clinician programmer as part of the aDBS feature but will not be used in the ADAPT-PD Trial. 
aDBS Dual Threshold Mode 
Dual threshold mode includes both an upper and lower control threshold on the LFP SOI and aDBS 
makes changes to the stimulation amplitude to attempt to maintain the LFP SOI between the two 
thresholds.  In this scheme, when the LFP SOI is “high”, then stimulation is increased, whereas when the 
LFP SOI is “low” stimulation is decreased to control the LFP SOI.  When the patient tailored LFP Alpha - 
Beta power SOI remains between the upper and lower thresholds, stimulation amplitude is held 
constant. When the Alpha - Beta power SOI exceeds the upper threshold, stimulation increments. When 
the Alpha - Beta power SOI dips below the lower threshold, stimulation decrements. This aDBS mode is 
shown in Figure 2.   

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Figure 2: Dual Threshold aDBS Mode 
 
aDBS Single Threshold Mode 
Single threshold mode includes a single control threshold on the LFP SOI and aDBS makes changes to the 
stimulation amplitude based on the measured LFP and whether it is above or below the threshold.  In 
this scheme, when the LFP SOI is above the threshold, then stimulation is incremented and when the 
LFP SOI is below the threshold, the stimulation is decremented.  This mode has shorter default 
stimulation ramp up and ramp down durations than dual mode.  This aDBS mode is illustrated in Figure 
3. 
Figure 3: Single Threshold aDBS Mode 
 
Investigational Model B35200 Percept PC INS with aDBS Firmware Enabled 

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Although no physical changes are made to the Model B35200 Percept PC INS, it becomes investigational 
at the aDBS Setup visit when the investigational aDBS FW is enabled by software on an investigational 
version of the Clinician Programmer System. When the firmware is enabled, the device has the ability to 
adapt stimulation based on the sensed bioelectric data from the DBS leads implanted in the brain. 
The estimated number of times the investigational aDBS firmware will be enabled on the commercially 
available Model B35200 Percept PC is 70. Once for each patient that enters the aDBS Setup and 
Adjustment phase.   
Investigational Clinician Programmer System Components (Model 8880T2 Clinician Telemetry Module; 
Model CT900 Clinician Programmer Tablet, with Model A610 Clinician Programmer Application, Model 
A901 Communication Manager and Model A902 Patient Data Services installed) 
The Medtronic Model A610 DBS Version 3.0  Clinician Programmer Application (CPA) utilized for the 
study will have investigational aDBS software enabled by Medtronic. The investigational aDBS feature 
allows the physician to program aDBS on the Percept PC INS, including selecting an LFP signal of interest 
(Alpha -Beta for this study), programming electrode configuration, capturing LFP thresholds, setting 
upper and lower stimulation limits, transition durations and suspend amplitude. The software version 
number (3.0) is the same for the commercial and investigational versions. A feature identifier will 
indicate if the aDBS feature is enabled or disabled (i.e. whether it can configure/modify aDBS).  
The Model 8880T2 Communicator; the Model CT900 clinician programmer tablet, with Android®-based 
operating system with the Model A901 Version 1.0 Communication Manager Application and the Model 
A902 Version 1.0 Patient Data Service Application installed are unchanged from the commercially 
available versions.  
Although only the CPA will be modified from the commercially available version by displaying 
investigational screens which allow programming of aDBS, all components will be considered 
investigational as they are packaged together as a system.  
The estimated number of Investigational Clinician Programmer Systems to be used in the study is 24 
clinician systems, two for each participating center. These systems will be provided to the participating 
centers exclusively for use in this study. 
Investigational Patient Programmer System Components (TH91 package kit includes: Model TM91 
PTM and Model HH90 Patient Programmer Phone with Model A620 Patient Programmer Application 
installed) 
The patient programmer system components utilized in the study will be investigational marked 
versions of the commercially available product. When the patient programmer system is paired with a 

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Percept PC with investigational aDBS enabled, the Model A620 Version 2.0 Patient Programmer 
Application will display investigational screens which are not seen in the commercially available product. 
These screens allow the subject to pause and resume Adaptive Therapy. The software version number 
(2.0) is the same for the commercial and investigational versions. A feature identifier will indicate if the 
aDBS feature is enabled or disabled (i.e. whether it can configure/modify aDBS). 
The Model HH90 Patient Programmer Handset and the Model TM91 PTM are unchanged from the 
commercially available versions. Although only the Patient Programmer Application will be modified 
from the commercially available version by displaying investigational screens, all three components will 
be considered investigational as they are packaged together as a system.  
The estimated number of Investigational Patient Programmer Systems to be used in the study is 70 
patient systems, one for each patient that enters the aDBS Setup and Adjustment phase. These systems 
will be provided to the participating centers for distribution to patients exclusively for use in this study. 
6.2. Manufacturer 
Medtronic, Inc., 710 Medtronic Parkway, Minneapolis, MN 55432, USA, is the legal manufacturer of the 
Percept PC System for the ADAPT-PD Trial. Detailed manufacturing information for the investigational 
products used in this study is listed in Table 2 below.  
Table 2: Manufacturing Information for Investigational Products 
Facility 
Responsibility 
Medtronic Puerto Rico Operations Co., Juncos 
Road 31, Km. 24, Hm 4 
Ceiba Norte Industrial Park 
Juncos, Puerto Rico 00777 
Establishment Registration: #3004209178 
Manufacturer for: 
• 
Model B35200 Percept PC INS 
Medtronic Rice Creek Facility 
Medtronic Neuromodulation 
7000 Central Ave NE 
Minneapolis, MN 55432 
Establishment Registration #2182207 
Product specification developer for: 
• 
Model A610 Clinician Programmer 
Application  
• 
Model 8880T2 Communicator 
• 
Model A620 Patient Programmer 
Application  
• 
Model TM91 Communicator 
Application of investigational labeling for: 
• 
Study Patient Programmer System 
• 
Study Clinician Programmer System 

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Plexus Manufacturing Sdn. Bhd. 
Bayan Lepas Free Industrial Zone, Phase II 
Bayan Lepas, Penang, Malaysia 11900 
Establishment Registration #3004593495 
Contract Manufacturer for: 
• 
Model 8880T2 Communicator 
Jabil Circuit (Shanghai), LTD. 
600 Tian Lin Road 
Shanghai, China 200233 
Establishment Registration #3005210579 
Contract Manufacturer for: 
• 
Printing the labeling for A620 PPA 
• 
Placing A620 PPA labeling inside the 
TM91 box 
• 
Manufacture the TM91 Communicator 
product 
Medtronic Sofamor Danek USA, Inc 
Memphis Manufacturing 
438 Swinnea Road 
Memphis, TN 38118 
Establishment Registration #3003120897 
Kit Assembler for: 
• 
Placing the TM91 box and the HH90 
Handset box into the TH91 box 
• 
Print the TH91 label and place on the box 
6.3. Packaging 
The following investigational components (physical components of the Clinician Programmer System 
and Patient Programmer System) and their immediate package will be affixed with a sticker which 
contains a statement according to local requirements: 
• 
Clinician Programmer System 
o Model CT900 Clinician Programmer Tablet 
o Model 8880T2 Communicator (also referred to as the Clinician Telemetry Module 
(CTM)) 
• 
Patient Programmer System 
o Model HH90 Patient Programmer Handset 
o Model TM91 Communicator (also referred to as the Patient Telemetry Module (PTM)) 
o Model TH91 Package Kit that contains the above parts 
The Percept PC Model B35200 Neurostimulator will not be physically labeled as an investigational device 
as the device will have been implanted as part of a commercially available DBS System. 
In the US, the Medtronic investigational DBS System components listed above or their immediate 
package will be labeled with the following information according to 21CFR§812.5: 
• 
Name and place of business of the manufacturer, packer or distributor 
• 
The quantity of the contents, if appropriate 
• 
The statement “CAUTION – Investigational device. Limited by Federal (or United States) law to 
investigational use” 
• 
A description of all relevant contraindications, hazards, adverse effects, interfering substances 
or devices, warnings, and precautions will be provided in labeling under a separate cover. 

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In the EU and the UK, labeling for the investigational devices listed above will follow the applicable 
ISO14155:2020 and EU MDR 2017/745 requirements. This shall include a statement indicating the 
device is “exclusively for clinical investigation,” and follow applicable local labeling language 
requirements in accordance with national regulations. 
In Canada, following Medical Devices Regulations / SOR98-282, the Medtronic investigational devices 
listed above will be labeled with the following information: 
• 
The name of the manufacturer 
• 
The name of the device 
• 
The statements “Investigational Device” and “Instrument de recherche”, or any other 
statement, in English and French, that conveys that meaning 
• 
The statements “To Be Used by Qualified Investigators Only” and “Réservé uniquement à l’usage 
de chercheurs compétents”, or any other statement, in English and French, that conveys that 
meaning 
Labeling for the investigational devices will be provided under a separate cover and will also be labeled 
with a statement according to local requirements.  
Products used in this study that are commercially available are packaged and labeled accordingly 
consistent with local regulations.  Labeling and patient material are provided in local language for CE 
marked devices. 
6.4. Intended Population 
The intended study population is subjects with idiopathic Parkinson’s disease implanted with a 
Medtronic DBS system, including bilateral leads targeted to the internal globus pallidus (GPi) or the 
subthalamic nucleus (STN), extensions and a single Percept PC implantable neurostimulator. 
6.5. Equipment 
The Global Kinetics Corporation (GKC) PKG® or Personal KinetiGraph®(US) /Parkinson’s Kinetigraph (EU) 
system will be used to provide a continuous, objective monitoring of key movement symptoms of 
Parkinson’s disease, including bradykinesia, dyskinesia and tremor. The PKG system consists of a wrist-
worn movement recording device known as the PKG Watch, proprietary algorithms and a data-driven 
report known as the PKG. GKC will provide a processed data file to Medtronic for analysis. GKC will be 
responsible for maintenance and calibration of the PKG Watch.  
In Canada, the PKG system is considered investigational and will be used in the study under an 
Investigational Testing Authorization (ITA). Investigational product requirements in Sections 6.8-6.11 
also apply to the PKG system. 

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6.6. Product Use 
Commercially available products for the study will be used consistently with the Medtronic DBS Therapy 
for PD indication and the associated product labeling.  
The Medtronic investigational product will be described in the Investigator’s Brochure (IB), provided 
under separate cover. The investigator agrees not to use the investigational devices on any person 
except subjects enrolled in this study.  
6.7. Product Training Requirements 
Selected investigators will have experience with commercially available Medtronic DBS Therapy 
products. Investigators and delegated site staff will receive training on the use of the investigational 
products prior to enrollment of the site’s first subject. 
6.8. Product Receipt and Tracking 
In order to allow shipment of non-implantable investigational product (Clinician Programmer System 
and Patient Programmer System) to a study center and for a study center to enable aDBS FW on a 
commercially available Percept PC INS, Medtronic must declare in writing that the study center is 
activated and ready to enroll subjects. The investigational product must only be used for the purpose of 
the ADAPT-PD Trial and in compliance to the clinical investigation plan.  
Upon receipt of non-implantable investigational product (Clinician and Patient Programmer Systems), 
the principal investigator or designated individual, will visually inspect and notify Medtronic of any 
noted issues or discrepancies.  
The investigational products listed in Table 1 above will be tracked using a product accountability log, 
with the exception of the TH91 package kit (box). Refer to Section 6.11: Product Accountability. Detailed 
instructions on the maintenance of records related to investigational product receipt and tracking will 
be provided under a separate cover. 
6.9. Product Storage 
Investigational products must be stored in a secured and locked location accessible only to those 
delegated individuals who are authorized by the principal investigator to access them. It is the 
responsibility of the investigator to correctly handle, store, and track the investigational products 
maintained at the study center.   

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6.10. Product Return 
Medtronic investigational products must be returned to Medtronic when they are no longer in use, 
regardless of the reason for explant or removal from use. The PKG System must be returned to GKC at 
the end of the study. 
Prior to the explant of the Percept PC neurostimulator, a device interrogation should be completed, if 
possible, and the device data submitted. The aDBS feature should be disabled prior to explant. Once 
disabled the device is no longer investigational.  
Medtronic also requests the return of explanted devices from non-clinical sources such as funeral homes 
and will assume responsibility for storage and disposal of the product once received, if possible. 
For explanted devices, Return Product kits or envelopes are available to send neurostimulators to 
Medtronic. These kits are sized to accommodate the devices from a single subject and are designed to 
meet postal regulations for mailing biohazardous materials.  
Commercially available DBS System components will be returned, when possible, to Medtronic for 
analysis if opened and not successfully implanted or upon explant or when no longer in use, regardless 
of the reason for explant or removal from use.  
At the end of the study, all unused investigational products provided for the study will be returned to 
Medtronic.  
6.11. Product Accountability  
The study center is responsible for maintaining tracking of the investigational devices listed in Table 1. 
Medtronic will provide an electronic accountability log. Non-implantable investigational product 
accountability begins at the point of distribution from Medtronic. Accountability for the investigational 
Percept PC INS begins at the time aDBS FW is enabled on the INS and ends when aDBS FW is turned off 
at subject withdrawal.  
Each product will be identified using serial, lot, or part number and installed software/firmware 
version(s). A product accountability log must be updated at each investigational center when non-
implantable investigational components are received, opened but not used, distributed to a subject, 
explanted, disposed of, or returned to Medtronic or when aDBS FW is enabled or turned off on the 
Percept PC INS. Products that are unused, expired or malfunctioning will also be tracked. A Medtronic 
monitor, or trained Medtronic staff, will review the product accountability log during monitoring or 
study visits. The product accountability log will indicate dates and the quantity and description, including 
serial, lot, or part number, installed software/firmware version(s) and expiration date (if applicable for 
non-implantable products), subject ID (if applicable), reason(s) for and method of destruction/disposal 

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for explanted components not returned to Medtronic (if applicable), and name of the person 
responsible for return or destruction/disposal (if applicable) of all investigational DBS System 
components on hand at any time during the study. 
Medtronic will perform periodic reconciliation of the investigational product to ensure traceability. 
7. Study Site Requirements 
7.1. Investigator/Investigation Site Selection 
All investigators managing the subject’s Parkinson’s disease must be qualified practitioners and 
experienced in the diagnosis and treatment of subjects with PD. All investigators must be experienced 
and trained in the use of DBS.   
The role of the principal investigator is to implement and manage the day-to-day conduct of the clinical 
investigation as well as ensure data integrity and the rights, safety and well-being of the subjects 
involved in the clinical investigation. 
The principal investigator shall: 
• 
Be qualified by education, training, and experience to assume responsibility for the proper 
conduct of the clinical investigation 
• 
Be experienced in the field of application and training in the use of Deep Brain Stimulation 
• 
Disclose potential conflicts of interest, including financial, that interfere with the conduct of the 
clinical investigation or interpretation of results 
• 
Be able to demonstrate that the proposed investigational study site: 
o Has the required number of eligible subjects needed within the recruitment period 
o Has one or more qualified investigators, a qualified investigational study site team and 
adequate facilities for the foreseen duration of the clinical investigation 
Study site personnel training will be completed and documented prior to participation in this study. 
7.2. Study Site Activation  
During the activation process (prior to subject enrollment), Medtronic will train study site personnel on 
the clinical investigation plan, on relevant standards and regulations (as required), informed consent, 
and on data collection and reporting tools. If new members join the study site team, they will receive 
training on the applicable study requirements relevant to their role before contributing to the study.  
Prior to performing study related activities, all regulatory requirements shall be fulfilled, including, but 
not limited to the following:  

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• 
IRB/EC approval (and voting list, as required by local law) of the current version of the CIP and 
Informed Consent (IC) 
• 
Regulatory Approval (RA) or notification (as required per local law)  
• 
Fully executed Clinical Trial Agreement (CTA)  
• 
Financial disclosure (if applicable)  
• 
Current Curriculum Vitae (CV) of investigators and key members of the investigation study site 
team  
• 
Documentation of delegated tasks  
• 
Documentation of study training  
Additional requirements imposed by local regulations, the IRB/EC and RA shall be followed, if 
appropriate.  
In addition, all participating study site staff must be trained on the current version of the CIP as well as 
on the applicable study requirements (depending on their role) and must be delegated by the principal 
investigator to perform study related activities.  
Medtronic will provide each study site with documentation of study site/investigator readiness; this 
letter must be received prior to performing study related activities. 
7.3. Role of the Sponsor Representatives 
Sponsor representatives who are qualified and designated on the sponsor technical support list may 
participate in the conduct of the study under the direct supervision of the investigator as described 
below. The investigator or authorized study center personnel designated on the delegation of authority 
form (eg, programmer, neurologist) must be present to collect data, record the study activities, and to 
be responsive to the subject’s needs during an activity performed by a Medtronic representative. 
In addition to performing monitoring and auditing activities, Medtronic personnel may: 
• 
Provide technical support during study visits under the supervision of a study investigator. This 
support may include technical assistance for products, systems, and programming, and the 
training of study center personnel on the use of Medtronic equipment or CIP-related procedures 
and other study activities 
• 
Take responsibility for product transfer, but will not have direct access to the locked device 
storage area 
• 
Clarify and troubleshoot device behavior, operation, or diagnostic output as requested by the 
investigator or other health care professional  
• 
Privately discuss any issues with programming or subject compliance with the Principal 
Investigator or site personnel 
• 
Observe study-related procedures to provide information relevant to study-required data 
collection 
• 
Review collected data and study documentation for completeness and accuracy 

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• 
Perform device interrogation while under the direction of the investigator or study center 
personnel with delegated responsibility for device programming  
• 
Facilitate device data transfer to Medtronic 
Medtronic personnel may not: 
• 
Practice medicine provide medical diagnoses or make decisions related to subject 
treatment/care 
• 
Assist the subject by direct physical contact except as required by the specific protocol-related 
task to be conducted 
• 
Discuss a subject’s condition or medical treatment with the subject or a member of the subject’s 
family 
• 
Provide the subject with any form/questionnaires related to the product(s) used in this study 
• 
Create source documentation on data collection and reporting tools (unless tools are explicitly 
created to be completed by sponsor staff and the sponsor staff is on the Technical Support List)  
8. Selection of Subjects 
8.1. Study Population 
The intended Primary Cohort study population is subjects 18 years of age or older with idiopathic 
Parkinson’s disease implanted with a full Medtronic DBS system, including bilateral leads targeted to the 
internal globus pallidus (GPi) or the subthalamic nucleus (STN), extensions and a single Percept PC 
implantable neurostimulator. The subject and/or caregiver must be able to utilize the patient 
programmer. In addition, subjects must be responsive to DBS Therapy, and have a Alpha - Beta band (8-
30 Hz) amplitude ≥1.2 µVp detected on left and/or right DBS leads on sensing channels 0-2, 0-3, or 1-3; 
8-10, 8-11, or 9-11. 
The Directional Stimulation Cohort population is the same with the exception that subjects must be 
implanted with the SenSight system and using directional stimulation.  
8.2. Subject Enrollment 
Subjects are enrolled into the study at the time they sign and date a study-specific subject Informed 
Consent (IC). The date the subject signed the IC must be documented in the subject’s medical records. 
There are two sets of criteria for study participation prior to the investigational use of aDBS. 
• 
Subjects must meet all general inclusion/exclusion criteria (as assessed at the Enrollment Visit) 
• 
Subjects must meet the LFP screening inclusion criterion (as assessed at the LFP Screening Visit) 

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8.3. Inclusion Criteria 
To be eligible to participate in the study, a subject must meet all the following inclusion criteria:  
General (Primary Cohort): 
1. Subject has idiopathic Parkinson’s disease 
2. Subject is implanted with Percept PC (Model B35200) and Medtronic DBS leads (Model 3387, 
3389, B33005 or B33015) and extensions (Model 37085, 37086 or B34000) bilaterally in the 
same target (physician confirmed), STN or GPi  
3. In the opinion of the investigator, the subject responds to DBS Therapy.  
4. Based on the opinion of the investigator, the subject’s cDBS parameters and PD medications are 
stable and expected to remain stable from enrollment through the end of the aDBS Evaluation 
phase 
5. Subject is configured to ring mode monopolar or dual monopolar stimulation using contacts 1 
and/or 2 (9 and/or 10) on at least one side.  
6. Subject is willing and able to attend all study-required visits and complete the study procedures 
(e.g. 1-month recall questionnaires, MDS-UPDRS III) 
7. Subject has the ability to understand and provide written informed consent for participation in 
the study prior to the study-related procedures being conducted 
8. Subject is a male or non-pregnant female. If female of child-bearing potential, and if sexually 
active, must be using, or agree to use, a medically acceptable method of birth control as 
confirmed by the investigator 
9. For subjects with the SenSight system: Subject is configured to the following stimulation rates: 
55, 85, 110, 125, 145, 164 or 180 Hz (as required for sensing/aDBS) 
General (Directional Stimulation Cohort): 
Subjects must meet the same inclusion criteria as the primary cohort except for revised #2 and #5. 
Revised inclusion criteria: 
2. Subject is implanted with Percept PC (Model B35200) and Medtronic DBS leads (Model B33005 
or B33015) and extensions (Model B34000) bilaterally in the same target (physician confirmed), 
STN or GPi  
5. Subject is configured to directional monopolar or dual monopolar stimulation using contacts 1 
and/or 2 (9 and/or 10)  
LFP Screening: 
1. Subject has Alpha - Beta band (8-30 Hz) amplitude ≥ 1.2 µVp detected on either left and/or right 
DBS leads on sensing channels 0-2, 0-3, or 1-3; 8-10, 8-11, or 9-11 

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8.4. Exclusion Criteria 
A potential subject who meets any of the following criteria will be excluded from participating in the 
study: 
General (Primary Cohort):  
1. Subject and/or caregiver is unable to utilize the patient programmer  
2. Subject has more than one lead in each hemisphere of the brain 
3. Subject has cortical leads or additional unapproved hardware implanted in the brain 
4. Subject has more than one INS 
5. At enrollment, the subject’s INS has a predicted battery life of <1 year 
6. Subject has Beck Depression Inventory II (BDI-II) > 25 
7. Subject requires diathermy, transcranial magnetic stimulation (TMS), or electroconvulsive 
therapy (ECT)  
8. Subject has a metallic implant in the head, (eg, aneurysm clip, cochlear implant) 
9. Subject has, or plans to obtain, an implanted electrical stimulation medical device anywhere in 
the body (eg, cardiac pacemaker, defibrillator, spinal cord stimulator) 
10. Subject has, or plans to obtain, an implanted medication pump for the treatment of Parkinson’s 
disease (eg, DUOPATM infusion pump) and/or portable infusion pump 
11. Based on the opinion of the investigator, the subject has an abnormal neurological examination 
that would preclude them from study participation  
12. Subject is breast feeding  
13. Subject is under the age of 18 years 
14. Subject is currently enrolled in or plans to enroll in any concurrent drug and/or device study that 
may confound the results of this study as determined by the Medtronic study team 
15. Subject is unable to use or tolerate wearable  
16. Subjects with signal artifact on all 6 aDBS sense pathways (3 each on both DBS leads) which 
preclude the clinician from setting thresholds 
General (Directional Stimulation Cohort):  
General exclusion criteria for the Directional Stimulation Cohort are the same as for the Primary Cohort. 
9. Study Procedures  
The study schedule, procedures, and methods of assessment are defined in detail to enable compliance 
with the required activities, and to ensure that the resulting data meet the criteria for evaluability Figure 
4. Case report forms (CRFs) will be provided for use in collecting data for all subjects; the pertinent CRFs 
along with the applicable source documentation will be completed for each subject at the time of each 

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study visit. Subjects enrolled in the Directional Stimulation Cohort will follow the same study schedule, 
procedures and methods of assessment. 
The start of the study is defined as the date the first subject signs the informed consent. The completion 
of the study is defined as the completion of the last required follow-up visit by the last subject. 

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9.1. Schedule of Events 
Figure 4: Study Schematic 
       

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9.2. Data Collection 
Data collection requirements are summarized in Table 3 below. 
Table 3: Study Procedures and Data Collection by Visit 
PHASE NAME 
 
cDBS Baseline 
Phase 
aDBS Setup and Adjustment 
Phase 
aDBS Evaluation 
Phase 
Long-term Follow-up Phase 
Extended 
Access Phase 
 
 
VISIT NAME 
Enrollment 
LFP 
Scree
ning 
cDBS 
Basel
ine 
aDBS 
Setup 
Randomization 
Visit 1 
Visit 2* 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Extended 
Access Visits 
Subject 
Withdrawal / 
Discontinuation 
Unsched. 
Visit 
System 
Mod. 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical & surgical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PD history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C-SSRS (screening) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BDI-II 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Device information 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Signal Test 
X 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
PD medication at 
visit 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
PD medication 
prior to visit 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
PDQ-39 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
EQ-5D-5L 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
MDS-UPDRS IA 
 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
 
MDS-UPDRS 
Patient 
Questionnaire 
(Part IB & II) Worst 
condition 
 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
 

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PHASE NAME 
 
cDBS Baseline 
Phase 
aDBS Setup and Adjustment 
Phase 
aDBS Evaluation 
Phase 
Long-term Follow-up Phase 
Extended 
Access Phase 
 
 
VISIT NAME 
Enrollment 
LFP 
Scree
ning 
cDBS 
Basel
ine 
aDBS 
Setup 
Randomization 
Visit 1 
Visit 2* 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Extended 
Access Visits 
Subject 
Withdrawal / 
Discontinuation 
Unsched. 
Visit 
System 
Mod. 
MDS-UPDRS 
Patient 
Questionnaire 
(Part IB & II) Best 
condition 
 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
MDS-UPDRS III 
On stim (cDBS) / 
On med 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
MDS-UPDRS III 
Off stim (cDBS) / 
Off med 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
MDS-UPDRS III 
On stim (aDBS) / 
On med  
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
MDS-UPDRS IV 
 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
 
PD Home Diary 
 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
 
C-SSRS (follow-up) 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
VHI  
Worst condition 
 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
 
VHI  
Best condition 
 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
 
PDSS-2 
 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
 
BrainSense setup 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
aDBS 
programming 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X** 
 
Physician 
programming 
survey 
 
 
 
X** 
 
 
 
 
 
 
 
 
 
X** 
 
Patient preference 
questionnaire 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 

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PHASE NAME 
 
cDBS Baseline 
Phase 
aDBS Setup and Adjustment 
Phase 
aDBS Evaluation 
Phase 
Long-term Follow-up Phase 
Extended 
Access Phase 
 
 
VISIT NAME 
Enrollment 
LFP 
Scree
ning 
cDBS 
Basel
ine 
aDBS 
Setup 
Randomization 
Visit 1 
Visit 2* 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Extended 
Access Visits 
Subject 
Withdrawal / 
Discontinuation 
Unsched. 
Visit 
System 
Mod. 
Patient 
satisfaction 
questionnaire 
 
 
 
 
 
 
 
 
 
 
X 
 
X*** 
 
 
GIC 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Preferred aDBS 
mode 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Wearable data 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
Event Markers 
with LFP capture** 
 
 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
 
Programming 
session upload via 
CDU 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X**** 
AEs 
As they occur 
Device deficiencies 
As they occur 
Protocol 
Deviations 
As they occur 
Reason for exit 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
* If two aDBS modes are set up 
** Optional 
*** If early discontinuation following aDBS Evaluation Phase 
**** If INS is modified 
 

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9.3. Scheduled Follow-up Visit Windows 
Data analyses include follow-up visits, regardless of whether the visit occurs within the window. 
Therefore, a late visit is preferred over a missed visit but must be accompanied by a deviation report. 
Follow-up visit windows are listed in Table 4. Should a subject miss a visit or the visit falls outside the 
pre-specified window, a study deviation must be reported and the original follow-up schedule 
maintained for subsequent visits.  
Table 4: Visit Windows 
Visit 
Visit ranges 
LFP Screening 
1-45 days after enrollment 
cDBS Baseline  
30-45 days after LFP Screening 
aDBS Setup 
1-45 days after Baseline 
aDBS Adjustment 
0-60 days after aDBS setup complete 
Randomization / Day 0 
No greater than 60 days after aDBS setup 
complete 
aDBS Evaluation Visit 1 
30-45 days after Day 0 
aDBS Evaluation Visit 2* 
30-45 days after Evaluation visit 1 
Visit 3 
45-60 days after Evaluation Visit 2 (or Evaluation 
Visit 1 if the subject is only configured to one 
aDBS mode) 
Visit 4 
45-60 days after Visit 3 
Visit 5 
90 +/- 14 days after Visit 4 
Visit 6 
90 +/- 14 days after Visit 5 
Extended Access Visits 
Every 180 +/- 60 days beginning after Visit 6 and 
every 6 months thereafter following the 
previous extended access visit 
 
* If two aDBS modes are set up 
9.4. Subject Screening  
Subjects may be recruited through the investigator’s practice, referring physicians, and/or the use of 
recruitment tools approved by the reviewing IRB/EC. Potential subjects may be identified through a 
study center database query (e.g. chart reviews) or as new or existing patients attend clinic visits. 
The investigator, or authorized center personnel, will screen potential subjects by reviewing the study’s 
inclusion/exclusion criteria. A screening log will be provided for use in tracking potential subjects. All 
subjects that are considered for the study must be included on the study screening log. The reason for 

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non-eligibility, as determined by the Investigator must also be recorded on the study pre-screening log. 
The screening log serves as a method for Medtronic to assess selection bias in the trial.  
If a subject fails the inclusion/exclusion criteria, and is discontinued from the study, and it is the 
investigator’s medical judgment that re-screening may be appropriate at a later date during the study, 
the investigator may contact the Medtronic study team to request approval to re-screen the subject 
prior to proceeding. Approval will be provided in writing by Medtronic for subjects who are permitted to 
repeat the screening process. 
9.5. Prior and Concomitant Medications 
All concomitant medications, except for over-the-counter medications and herbal supplements, will be 
collected for this study. All Parkinson’s disease medications will be collected for this study. Subjects’ 
Parkinson’s disease medication must be stable at the time of enrollment in the trial through the end of 
the aDBS Evaluation Phase. During this time, the investigator should make only clinically necessary 
changes to PD medication.  
There are no medication restrictions in the study unless they are investigational and may confound the 
study results, in which case, prior approval would be needed from Medtronic. 
Parkinson’s disease medications will be held prior to the LFP Screening and aDBS Setup visits. See Table 
5: PD Medication Off/On Definitions. 
9.6. Subject Consent 
Informed consent is defined as a legally effective documented confirmation of a subject’s voluntary 
agreement to participate in a particular study after information has been given and explained to the 
subject on all aspects of the study that are relevant to the subject’s decision to participate. This process 
includes obtaining an IC form and an Authorization to Use and Disclose Personal Health 
Information/Research Authorization/other privacy language as required by law that has been approved 
by the study site’s IRB/EC and signed and dated by the subject. A subject may only consent after 
information has been given and explained to the subject on all aspects of the clinical investigation that 
are relevant to the subject’s decision to participate.  
Prior to enrolling subjects, the site IC and the Authorization to Use and Disclose Personal Health 
Information/Research Authorization/other privacy language as required by law must be approved by the 
IRB/EC.  The document(s) must be controlled (i.e. versioned and/or dated) to ensure it is clear which 
version(s) were approved by the IRB/EC.  Any adaptation of the sample IC must be reviewed and 

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approved by Medtronic and the IRB/EC reviewing the application prior to enrolling subjects or if the IC is 
updated at any time during the study.  
The investigator must notify the subject of any significant new findings about the study that become 
available during the course of the study which are pertinent to the safety and well-being of the subject, 
as this could impact a subject’s willingness to participate in the study. If relevant, consent may be 
requested from subjects to confirm their continued participation. 
Templates for the study-specific subject IC and Authorization to Use and Disclose Personal Health 
Information/Research Authorization/other privacy language for this study are provided by Medtronic 
under a separate cover.  
Prior to initiation of any study-specific procedures, IC must be obtained from the subject. Likewise, 
privacy or health information protection regulation may require subjects to sign additional forms to 
authorize study sites to submit subject information to the study sponsor. The IC process must be 
conducted by the principal investigator or an authorized designee, and the IC Form and Authorization to 
Use and Disclose Personal Health Information/Research Authorization/other privacy language as 
required by law must be given to the subject in a language he/she is able to read and understand. The 
process of IC must be conducted without using coercion or undue improper influence on or inducement 
of the subject to participate by the investigator or other study site personnel. The IC process shall not 
waive or appear to waive subject’s legal right. The language used shall be as non-technical as possible 
and must be understandable to the subject and the impartial witness, where applicable.  
The subject must have ample time and opportunity to read and understand the IC form, to inquire about 
details of the study, and to decide whether or not to participate in the study. All questions about the 
study should be answered to the satisfaction of the subject. 
When the subject decides to participate in the study, the IC must be signed and personally dated by the 
subject and investigator or authorized designee, as required by the IC, and ensured by the principal 
investigator or his/her authorized designee.  
A copy of the IC and the Authorization to Use and Disclose Personal Health Information/Research 
Authorization/other privacy language, signed and dated as required by law, must be provided to the 
subject.  
If the IC is obtained the same day the subject begins participating in study-related procedures, it must 
be documented in the subject’s case history that consent was obtained prior to participation in any 

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study-related procedures. It is best practice for the IC process to be documented in the subject’s case 
history, regardless of circumstance. 
In the event the subject or legally designated representative cannot read, the IC process shall be 
obtained through a supervised oral process. An independent and impartial witness must be present 
during this process. The IC and any other information must be read aloud to the prospective subject or 
his/her legally designated representative. Whenever possible, either the subject or his/her legally 
designated representative shall sign and personally date the informed consent form. The witness signs 
and personally dates the IC attesting that the information was accurately explained and that informed 
consent was freely given. 
The original signed IC must be filed in the hospital/clinical chart and/or with the subject’s study 
documents.  
The IC and Authorization to Use and Disclose Personal Health Information/Research Authorization/other 
privacy language as required by law must be available for monitoring and auditing. Any Medtronic Field 
personnel who support the study procedures must be able to review the subject’s signed and dated IC 
and verify its completeness prior to proceeding with the aDBS setup. In the event the Medtronic Field 
personnel identify IC as being incomplete, the aDBS setup will not be allowed to occur until the consent 
of the subject can be adequately and appropriately obtained.  
Consistent with the DoH, vulnerable adults (i.e. those subjects mentally incapable of giving consent) are 
excluded from this protocol.  Any subjects with mental incompetence (e.g. Alzheimer’s, dementia, 
psychiatric disorders, developmental disorders) should be assessed for vulnerable status. This protocol 
defines vulnerable adult as those subjects mentally incapable of giving consent, in the Investigator’s 
opinion.  The Investigator should consider the definition of vulnerable adult per ISO 14155, which 
defines vulnerable adults as: “individuals who are unable to fully understand all aspects of the 
investigation that are relevant to the decision to participate, or who could be manipulated or unduly 
influenced as a result of a compromised position, expectation of benefits or fear of a retaliatory 
response.” For example, this could include Individuals with loss of autonomy due to immaturity or 
through mental disability, persons in nursing homes, children, impoverished persons, subjects in 
emergency situations, ethnic minority groups, homeless persons, nomads, refugees, and those 
incapable of giving IC. Other vulnerable subjects could include, for example, members of a group with a 
hierarchical structure such as university students, subordinate hospital and laboratory personnel, 
employees of the sponsor, members of the armed forces, and persons kept in detention. 

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In some countries, patients must specifically opt-in for data use for other purposes than the study 
objectives. In those countries, patients will have the option to indicate that in the consent (e.g., via a 
checkbox or via a separate signature). 
9.7. Enrollment and Screening Phase 
This phase begins at consent and includes an Enrollment visit and an LFP Screening visit.  
9.7.1. 
Enrollment 
Subjects who have a complete Medtronic DBS system, including Percept PC, leads and extensions and 
whose cDBS parameters and PD medications are stable may be approached to participate in the study. 
From enrollment to the end of the aDBS Evaluation Period, the investigator should make only clinically 
necessary changes to cDBS settings. 
A subject is considered enrolled when the consent process has been fully executed. The date the subject 
signed the IC and Data Protection Authorization, as required by law, must be documented in the 
subject’s medical records. A log of all subjects enrolled in the study will be maintained. Once consent is 
obtained, report adverse events/deaths, study deviations and subject exits as they occur.  
The study-specific IC will be signed and dated prior to completion of any study-related procedures. 
Enrolled subjects who do not meet all inclusion criteria or who meet any exclusion criteria will be 
discontinued from the study. No further study-related procedures will be completed, and subjects will 
be followed according to the center’s standard procedures. 
The subject will arrive for the visit with PD medications and cDBS according to the center’s standard 
procedures. After consent, the clinician will perform a Signal Test, using a commercially available 
Clinician Programmer System, to ensure the subject has adequate signal quality. The clinician should 
ensure the subject movement is minimized during this test. 
If signal artifact is detected on all six aDBS sense pathways (3 each on both DBS leads), the Signal Test 
may be repeated. If signal artifact is persistent on all six aDBS sense pathways, the clinician should 
determine whether this precludes them from setting thresholds. If not, the subject can continue in the 
study. If the subject will not continue, device identification information will be collected, the 
programming session, with BrainSense data included in the JSON session data report, will be uploaded 
to Medtronic via CDU, and an AE and device deficiency assessment will be performed. The subject will 
then be discontinued from the study, and no further study-related procedures will be completed.  
Following the Signal Test, data will be collected and assessments administered. The following data will 
be collected at enrollment: 
• 
Demographics 
• 
Medical & surgical history 

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• 
PD history 
• 
Concomitant medications 
• 
Columbia Suicide Severity Rating Scale (C-SSRS) (screening) 
• 
Beck Depression Inventory II (BDI-II) 
• 
Pregnancy test (for female subjects of child-bearing potential) 
• 
Device identification information, including historical DBS implant information 
• 
Programming session upload to Medtronic via CDU, with BrainSense data included in the JSON 
session data report  
• 
AE and device deficiency assessment 
The clinician will ensure the INS device time matches that of the clinician programmer tablet (network 
enabled). If the INS time does not match the network time, the INS time will be updated.  
The subject will be instructed on the use of the PD Home Diary. For at least 3 consecutive days in the 14 
days prior to the cDBS Baseline and aDBS Evaluation visits, the subject will record, in 30-minute 
intervals, whether they were Asleep, “Off,” “On” without dyskinesia, “On” with non-troublesome 
dyskinesia, or “On” with troublesome dyskinesia. The subject will also be instructed on the use of the 
PKG Watch.  
The subject will leave the visit on their current cDBS settings (including BrainSense settings). 
9.8. cDBS Baseline Phase 
This phase begins when the enrollment visit is complete and includes an LFP screening visit, cDBS 
Baseline period and cDBS Baseline visit.  
9.8.1. 
LFP Screening Visit 
1-45 days after Enrollment 
The subject will arrive for the visit off PD medication and on cDBS. Confirm the subject’s PD medication 
was appropriately withheld as specified in Table 5. If the subject’s PD medications were not 
appropriately withheld, consider rescheduling the study visit. 
Table 5: PD Medication Off/On Definitions 
Term 
Definition  
Off PD Medication 
Subject stops taking PD medication(s) for the following time periods 
prior to a study visit: 
• 
72 hours extended-release forms of dopamine agonists 
• 
24 hours regular form of dopamine agonists, controlled release 
forms of carbidopa/levodopa  

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• 
12 hours regular carbidopa/levodopa, entacapone, rasagiline, 
selegiline, amantadine 
On PD Medication  
Optimal motor response to PD medication (“best” On). The clinical 
symptoms should be stable for at least 10 minutes and both, patient 
and investigator should agree that the best On of the patient has been 
reached.  
Current PD 
Medication(s) 
Medication the subject is taking for treatment of PD on the day prior to 
initiating the hold requirements for the Off medication state 
Data will be collected, including the following: 
• 
MDS-UPDRS III (Off stim/Off med)  
• 
BrainSense setup and Signal test 
• 
Concomitant medications 
• 
Time of last dose of PD medications taken prior to the visit 
• 
Programming session upload to Medtronic via CDU, with BrainSense data included in the JSON 
session data report  
• 
Adverse Event and device deficiency assessment 
At the start of the visit, the clinician will turn off the subject’s cDBS for approximately 15 minutes. 
Following this DBS washout, the trained rater will conduct the MDS-UPDRS III Off med/Off stim 
assessment.  
Next, the clinician should follow the BrainSense setup workflow and perform a Signal Test, using the 
commercially available Clinician Programmer System, to assess LFP the screening inclusion criterion. The 
subject must have Alpha - Beta band amplitude ≥ 1.2 µVp detected on at least one (left or right) DBS 
lead on sensing channels 0-2, 0-3, or 1-3; 8-10, 8-11, or 9-11.  
If the subject does not meet all of the LFP screening inclusion criteria and/or meets the LFP screening 
exclusion criterion, they will be exited from the study following the process in Section 9.19, including a 
programming session upload to Medtronic via CDU.  No further study-related procedures will be 
completed, and subjects will be followed according to the center’s standard procedures. 
At the end of the visit, the programming session, with BrainSense data included in the JSON session data 
report, will be uploaded to Medtronic via CDU. The subject may resume taking their normal PD 
medication. 
The subject will be reminded of the use of the PD Home Diary and the use of the PKG Watch.  
The subject will leave the visit on their current cDBS settings with BrainSense set to Passive Sensing Only 
in all groups where BrainSense setup was utilized. 

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9.8.2. 
cDBS Baseline Period  
The subject will remain on cDBS with BrainSense set to Passive Sensing Only for the duration of the 
period.  
Prior to the scheduled cDBS Baseline visit, the PKG Watch will be given to the subject or mailed to the 
subject’s home. Upon receipt, the subject will put on and activate the PKG Watch. The PKG Watch will 
be worn on the most affected side for at least 6 consecutive days in the 14 days prior to the scheduled 
cDBS Baseline visit. After the recording, the subject will return the PKG Watch in the pre-paid mailer or 
bring it to the site for return at the visit.  
The PD Home Diary will also be provided to the subject in advance of the visit and will be completed for 
at least 3 consecutive days in the 14 days prior to the scheduled cDBS Baseline visit. If possible, the PD 
Home Diary will be completed at the same time as the PKG Watch is worn. 
Some assessments may be completed prior to each scheduled visit. See Section 9.15 for detailed 
information about the administration of each assessment. 
Subjects should be contacted prior to the cDBS Baseline Visit to remind them to complete the required 
between-visit activities (PKG Watch, PD Home Diary and assessments (if applicable)). 
9.8.3. 
cDBS Baseline Visit 
30-45 days after LFP screening 
Baseline data will be collected, including the following: 
• 
PDQ-39 
• 
EQ-5D-5L 
• 
VHI (worst condition) 
• 
VHI (best condition) 
• 
Parkinson’s Disease Sleep Scale (PDSS-2) 
• 
MDS-UPDRS I (Part A) – trained rater 
• 
MDS-UPDRS Patient Questionnaire (Part IB and II) (best condition) 
• 
MDS-UPDRS Patient Questionnaire (Part IB and II) (worst condition) 
• 
MDS-UPDRS III (On stim (cDBS)/On med) – trained rater 
• 
MDS-UPDRS IV – trained rater 
• 
Collect PD Home Diary and review for completeness 
• 
Concomitant medications 
• 
Collect PKG Watch or confirm it was returned  
• 
AE and device deficiency assessment 
• 
Programming session upload to Medtronic via CDU, with BrainSense data included in the JSON 
session data report  

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Following cDBS baseline data collection, the programming session, with BrainSense data included in the 
JSON session data report, will be uploaded to Medtronic via CDU. 
9.9. aDBS Setup and Adjustment Phase 
This phase consists of an aDBS Setup Visit and an optional aDBS Adjustment period and ends with 
randomization. Subjects will be blinded to the aDBS mode during the aDBS Setup and Adjustment Phase. 
If the blind is broken, document the reasons for unblinding in the subject’s source documentation and 
report as a deviation. 
9.9.1. 
aDBS Setup Visit 
1-45 days after cDBS Baseline visit 
The aDBS Setup visit may be conducted in one day or may occur over two days, with the final day being 
no more than 45 days following the cDBS Baseline visit.  The aDBS Setup visit should be conducted on 
sequential days, but when non-sequential days are scheduled there must be no more than 14 days 
between the visit days.  
The subject will arrive for the visit off PD medication and on cDBS. Confirm the subject’s PD medication 
was appropriately withheld as specified in Table 5. If the subject’s PD medications were not 
appropriately withheld, consider rescheduling the study visit. 
Data will be collected, including the following: 
• 
Concomitant medications 
• 
Time of last dose of PD medications taken prior to the visit 
• 
PD medication dose given at the visit (if applicable) 
• 
Adverse Event and device deficiency assessment 
The clinician should follow the BrainSense setup workflow using the investigational Clinician 
Programmer System. The subject must have Alpha - Beta band amplitude ≥ 1.2 µVp detected on at least 
one (left or right) DBS lead on sensing channels 0-2, 0-3, or 1-3; 8-10, 8-11, or 9-11.  
Utilizing Signal Test, if the subject no longer meets the LFP screening inclusion criterion, it is allowable to 
re-assess LFP inclusion criterion, at the investigator’s discretion, at the start of the first day of aDBS 
Setup Visit.  If the subject does not meet the inclusion criterion, they will be exited from the study 
following the process in Section 9.19, including uploading the programming session, with BrainSense 
data included in the JSON session data report, to Medtronic via CDU.  No further study-related 
procedures will be completed, and subjects will be followed according to the center’s standard 
procedures. 
The clinician will set up both aDBS Dual and Single Threshold Modes while the subject is Off PD 
medication. As part of the Off PD medication aDBS setup, the clinician configures the stimulation 

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amplitude which is automatically adjusted based on the changes to sensed brain signals. Streaming 
transition schemes and wrist flexion tasks may be utilized as assessments for each mode. Following the 
Off PD medication aDBS setup, the clinician will assess the programmed aDBS settings (both Dual and 
Single Threshold Modes) while the subject is On PD medication.  
In cases where only one hemisphere has LFP Alpha - Beta signal which meets the inclusion criterion, the 
following configurations will be used to set up aDBS.  
Dual Threshold (DT) Mode: 
If only one hemisphere has LFP Alpha - Beta signal >=1.2μVp when setting up the Dual Threshold mode, 
the clinician should configure adaptive therapy in both hemispheres, using sensing from the hemisphere 
with LFP Alpha - Beta signal >=1.2μVp. 
For example, when utilizing BrainSense Setup, if the Left hemisphere has LFP Alpha - Beta signal 
>=1.2μVp, and the Right hemisphere does not, then proceed with the following: 
• 
Set up Dual Threshold mode in the Left hemisphere with the sensing electrode configuration 
that has met the LFP Alpha - Beta signal inclusion criterion (Preferably the active cDBS card).  
• 
In the Right hemisphere, at Signal Test, select Left STN/GPi as the sensing configuration. 
• 
Note: the stimulation electrode(s) or cathode(s) in the Right hemisphere is not constrained to a 
sensing configuration.  
Single Threshold (ST) Mode: 
If only one hemisphere has LFP Alpha - Beta signal >=1.2μVp when setting up Single Threshold mode, 
the clinician should configure adaptive therapy in only that hemisphere with LFP Alpha - Beta signal 
>=1.2μVp. 
• 
cDBS should be setup in the hemisphere with LFP Alpha - Beta signal <1.2uVp (set to Passive 
Sensing, if possible).  
• 
Note: that the stimulation electrode(s) or cathode(s) in the hemisphere set to cDBS is not 
constrained to a sensing configuration. 
If one aDBS mode cannot be set up, the subject should continue with the study using only the mode that 
can be set up and the subject will not be randomized. 
If neither aDBS mode can be set up, the subject will be exited from the study following the process in 
Section 9.19, including uploading the programming session, with BrainSense data included in the JSON 
session data report, to Medtronic via CDU. No further study-related procedures will be completed, and 
subjects will be followed according to the center’s standard procedures. 
Following each aDBS setup visit day, the programming sessions, with BrainSense data included in the 
JSON session data report, will be uploaded to Medtronic via CDU.  
Once aDBS is set up, and prior to the subject leaving the study center On aDBS, the subject’s 
commercially available Patient Programmer System will be replaced with an investigational-marked 
Patient Programmer System, and the subject will be given the investigational patient labeling. The 

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clinician or appropriately delegated study personnel will assist the subject to pair the investigational 
Patient Programmer System with the INS.  
Subjects will be instructed on how to pause aDBS any time they feel like the therapy is not working for 
them by selecting Pause Adaptive Therapy. This Pause Adaptive Therapy (amplitude last delivered in 
that group prior to starting aDBS therapy (i.e. the suspend amplitude)) is defined by the clinician as part 
of the aDBS setup process, following the streaming transition schemes testing and prior to starting 
adaptive therapy. Subjects will notify the investigator when they pause aDBS to assess the scenario and 
need for any adjustments.  
If the visit occurs over 2 days, the clinician may program the subject to one aDBS mode between visit 
day 1 and visit day 2.  
At the end of the aDBS Setup Visit, the subject may resume taking their normal PD medication. The 
physician may also be surveyed to understand rationale for programming settings. The investigator may 
determine that additional aDBS programming adjustments are needed for one or both of the aDBS 
modes, or the subject may proceed directly to randomization, or. If additional adjustment is planned for 
only one aDBS mode, the investigator will send the subject home in that mode for as much time as 
needed within the aDBS Adjustment Period. If additional adjustment is planned for both aDBS modes, 
the investigator will send the subject home in one of the aDBS modes to start the aDBS Adjustment 
Period. The investigator and subject will determine how and when to adjust the other aDBS mode within 
the aDBS Adjustment Period (if applicable). Event markers may be set up to further capture information 
about the patient’s out of clinic experience with aDBS.  
Every attempt will be made to blind the subject to the aDBS mode being adjusted. The clinician should 
set on the investigational Clinician Programmer the group names of the aDBS modes being adjusted in a 
manner which will not unblind the subject. For example, “aDBS 1” and “aDBS 2” or “aDBS” and “Do not 
use.” These group names will be displayed on the investigational Patient Programmer.  
9.9.2. 
aDBS Adjustment Period (optional) 
0-60 days after aDBS setup complete 
Additional visits for the clinician to adjust settings for one or both aDBS modes may be conducted as 
needed for up to 60 days following the final aDBS setup visit to ensure the aDBS mode(s) will be 
acceptable to the subject. These visits will be completed either at the study center, by telephone or 
telehealth/video consult. The subject will remain blinded to the programmed aDBS mode. Any aDBS 
adjustment visit will be recorded as an unscheduled visit (see Section9.13). The physician may also be 
surveyed to understand rationale for programming settings. 
If programming sessions or device interrogations occur, these sessions with BrainSense data included in 
the JSON session data report, will be uploaded to Medtronic via CDU. 

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9.9.3. 
Randomization 
Day 0 (no greater than 60 days after aDBS setup complete) 
Randomization may occur at the aDBS setup visit, at an unscheduled visit during the aDBS Adjustment 
Period, or as a standalone visit. All subjects for whom aDBS was set up will complete this visit. 
The investigator will assess each aDBS mode that was set up utilizing the aDBS Global Impression of 
Change (GIC) provided in Appendix A - aDBS Global Impression of Change Score (GIC). Efficacy and side 
effects are assessed on a scale from 1 to 21.  The lower the score the better the efficacy and the less 
side effects.  A score of 8 or less indicates the aDBS mode is acceptable. The investigator will also ensure 
that the subject is comfortable remaining in the aDBS mode(s) for the duration of the trial. 
If only one aDBS mode was set up for a subject, they will not be randomized, but the physician should 
still complete the aDBS GIC and data collection for the visit. 
Data will be collected, including the following: 
• 
Concomitant medications 
• 
GIC value for each aDBS mode that was set up 
• 
Adverse Event and device deficiency assessment 
For subjects in whom both aDBS modes are acceptable as compared to cDBS (using the aDBS GIC), 
unblinded site personnel will obtain the randomization assignment via Remote Data Capture (RDC). The 
randomization assignment can be obtained upon completion of the aDBS GIC and randomization CRFs. 
Randomization will occur to one of two possible treatment sequences if both aDBS modes are 
acceptable as compared to cDBS (using the aDBS GIC) (dual threshold mode followed by single threshold 
mode or vice versa) and will be stratified by target site location (STN/GPi). The two sequences will be 
randomly permuted in blocks of two and four. If an aDBS mode is unacceptable as compared to cDBS 
(using the aDBS GIC), that subject will be assigned the mode which was acceptable. The randomization 
schedule will be prepared by Medtronic and it will be maintained at Medtronic. Subjects will continue to 
be blinded to the aDBS mode during the aDBS Evaluation Phase. If the blind is broken, document the 
reasons for unblinding in the subject’s source documentation and report as a deviation. 
Following randomization, the clinician will program one group to the randomized aDBS mode. 
Subjects for whom one aDBS mode is unacceptable as compared to cDBS (using the aDBS GIC) or for 
whom only one mode could be acceptably configured will not be randomized and will complete one 
aDBS evaluation visit in the aDBS mode that was acceptable to the subject. 
In order to blind the subject to the aDBS mode assigned, the clinician will set the group name of the 
aDBS mode being evaluated during each period to “aDBS,” and the group name of the mode not being 
evaluated to “Do not use” on the Clinician Programmer. These group names will be displayed on the 
Patient Programmer.  

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If neither aDBS mode is acceptable to the subject, the subject will be exited from the study following the 
process in Section 9.19. No further study-related procedures will be completed, and the subject will be 
followed according to the center’s standard procedures. 
If randomization is conducted as a separate visit, the programming session, with BrainSense data 
included in the JSON session data report, will be uploaded to Medtronic via CDU. 
The subject will be instructed on the use of the PKG Watch and PD Home Diary in the aDBS Evaluation 
Phase. 
9.10. aDBS Evaluation Phase 
This phase consists of up to two treatment periods; one per acceptable aDBS mode.  After each 
treatment period, there is an aDBS evaluation visit. The subject’s PD medications will remain stable from 
enrollment through the end of the aDBS Evaluation Phase, unless changes are clinically necessary. 
During the aDBS Evaluation Phase, the subject may return to the study center for further aDBS 
adjustment in each randomized aDBS mode. All adjustments must be completed at least 14 days prior to 
the evaluation visit for that mode. Any adjustments will be recorded as unscheduled visits. Any 
adjustments during the 14 days prior to the evaluation visit will be considered a protocol deviation. 
Prior to each scheduled aDBS Evaluation visit, the PKG Watch will be given to the subject or mailed to 
the subject’s home. Upon receipt, the subject will put on and activate the PKG Watch. The PKG Watch 
will be worn on the most affected side for at least 6 consecutive days. After the recording, the subject 
will return the PKG Watch in the pre-paid mailer or bring it to the site for return at the visit. The subject 
will also be provided with the PD Home Diary in advance of the visit and will complete it for at least 3 
consecutive days in the 14 days prior to each scheduled aDBS Evaluation Visit. If possible, the PD Home 
Diary will be completed at the same time as the PKG Watch is worn. 
Some assessments may be completed prior to each scheduled visit. See Section 9.15 for detailed 
information about the administration of each assessment. 
Subjects should be contacted prior to each aDBS Evaluation Visit to remind them to complete the 
required between-visit activities (PKG Watch, PD Home Diary and assessments (if applicable)). 
9.10.1. 
Evaluation Visit 1 
30-45 days after randomization 
The subject will arrive for the visit on their normal PD medications and on aDBS.  
The clinician will confirm the subject is in the assigned mode for the visit. If the subject is not in aDBS, 
the clinician will program the subject to the assigned aDBS mode and all On stim assessments will be 

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performed in the assigned mode. If the subject completed the evaluation period in the incorrect aDBS 
mode, all On stim assessments will be performed in the incorrect aDBS mode. 
The following data will be collected: 
• 
PDQ-39 
• 
EQ-5D-5L 
• 
C-SSRS 
• 
MDS-UPDRS I (Part A) – trained rater 
• 
MDS-UPDRS Patient Questionnaire (Part IB and II) (best condition) 
• 
MDS-UPDRS Patient Questionnaire (Part IB and II) (worst condition) 
• 
MDS-UPDRS III (On stim (aDBS)/On med) – trained rater 
• 
MDS-UPDRS IV – trained rater 
• 
VHI (worst condition) 
• 
VHI (best condition) 
• 
PDSS-2  
• 
Patient preference questionnaire 
• 
Collect PD Home Diary and review for completeness 
• 
Concomitant medications 
• 
Collect PKG Watch or confirm it was returned via mail 
• 
Adverse Event and device deficiency assessment 
At the end of the visit, the programming session, with BrainSense data included in the JSON session data 
report, will be uploaded to Medtronic via CDU. 
Next, the clinician will program the subject to the other assigned aDBS mode and label that group 
“aDBS.” The group for the aDBS mode the subject just completed evaluation of will be re-labeled “Do 
not use” on the Patient Programmer. 
The subject should be reminded that they will receive the PKG Watch prior to the aDBS Evaluation Visit 
2 and will put on and activate the PKG Watch upon receipt. The subject will wear the PKG Watch for at 
least 6 consecutive days in the 14 days prior to the scheduled aDBS Evaluation Visit 2.  After the 
recording, the subject will return the PKG Watch in the pre-paid mailer or bring it to the site for return at 
the visit. The subject will also be reminded that they will be provided with the PD Home Diary in advance 
of the visit and will complete it for at least 3 consecutive days in the 14 days prior to the next aDBS 
Evaluation Visit. 
If only one aDBS mode is being evaluated, the subject will continue into the Long-term Follow-up phase 
and skip aDBS Evaluation Visit 2. 
9.10.2. 
Evaluation Visit 2 
If two aDBS modes are being assessed 
30-45 days after Evaluation visit 1 

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The subject will arrive for the visit on their normal PD medications and on aDBS.  
The clinician will confirm the subject is in the assigned mode for this visit. If the subject is not in aDBS, 
the clinician will program the subject to the assigned aDBS mode and all On stim assessments will be 
performed in the assigned mode. If the subject completed the evaluation period in the incorrect aDBS 
mode, all On stim assessments will be performed in the incorrect aDBS mode. 
The following data will be collected: 
• 
PDQ-39 
• 
EQ-5D-5L 
• 
C-SSRS 
• 
MDS-UPDRS I (Part A) – trained rater 
• 
MDS-UPDRS Patient Questionnaire (Part IB and II) (best condition) 
• 
MDS-UPDRS Patient Questionnaire (Part IB and II) (worst condition) 
• 
MDS-UPDRS III (On stim (aDBS)/On med) – trained rater 
• 
MDS-UPDRS IV – trained rater 
• 
VHI (worst condition) 
• 
VHI (best condition) 
• 
PDSS-2  
• 
Patient preference questionnaire 
• 
Collect PD Home Diary and review for completeness 
• 
Concomitant medications 
• 
Patient and physician preferred aDBS mode and reason for selecting preferred mode (at end of 
visit) 
• 
Collect PKG Watch or confirm it was returned via mail 
• 
Adverse Event and device deficiency assessment 
At the end of the visit, the programming session, with BrainSense data included in the JSON session data 
report, will be uploaded to Medtronic via CDU. 
Following the final aDBS visit, the clinician will program the subject to the chosen DBS mode (clinician & 
patient preference) for the long-term follow-up phase and record the reason for selecting that mode. 
If the chosen DBS mode is cDBS, the subject will be exited from the study following the process in 
Section 9.19. No further study-related procedures will be completed, and the subject will be followed 
according to the center’s standard procedures. 
The subject should be reminded that they will receive the PKG Watch prior to the next visit and will put 
on and activate the PKG Watch upon receipt. The subject will wear the PKG Watch on the most affected 
side for at least 6 consecutive days in the 14 days prior to the scheduled visit.   
9.11. Long-term Follow-up Phase 

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Once subjects complete the aDBS Evaluation Phase (one or two evaluation visits), they enter a Long-
term Follow-up Phase. During this Phase, the investigator may choose to switch aDBS modes as needed, 
so long as the subject received both modes during the aDBS Evaluation Phase. Any changes to the aDBS 
mode must be done at a study visit, either scheduled or unscheduled.  
Prior to each scheduled long-term follow-up visit (visit #3 through #6 inclusive), the PKG Watch will be 
given to the subject or mailed to the subject’s home. Upon receipt, the subject will put on and activate 
the PKG Watch. The PKG Watch will be worn on the most affected side for at least 6 consecutive days in 
the 14 days prior to each visit. After the recording, the subject will return the PKG Watch in the pre-paid 
mailer or bring it to the site for return at the visit. 
The PDQ-39 and EQ-5D-5L may be completed prior to each scheduled visit. See Section 9.15 for detailed 
information about the administration of each assessment. 
In the Long-term Follow-up Phase, subjects may choose to participate in optional data collection of 
Events with LFP capture (snapshots). The clinician may set up a maximum of 4 event types, selected 
from the following options: dyskinesia, tremor, rigidity, freezing, sleep disturbance, took PD medication. 
Study personnel will instruct the subject on how to record each event type utilizing the Patient 
Programmer System.  
9.11.1. 
Visit 3 
45-60 days after Evaluation Visit 2 (or Evaluation Visit 1 if the subject is only configured to one aDBS 
mode) 
The subject will arrive for the visit on their preferred aDBS mode.  
Data collection: 
• 
Concomitant medications 
• 
PDQ-39  
• 
EQ-5D-5L 
• 
Collect PKG Watch or confirm it was returned via mail 
• 
Programming session upload to Medtronic via CDU, with BrainSense data included in the JSON 
session data report  
• 
Adverse Event and device deficiency assessment 
The subject should be reminded that they will receive the PKG Watch prior to the next visit and will put 
on and activate the PKG Watch upon receipt. The subject will wear the PKG Watch on the most affected 
side for at least 6 consecutive days in the 14 days prior to the scheduled visit. The subject will return the 
PKG Watch in the pre-paid mailer or bring it to the site for return at Visit 4. 

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9.11.2. 
Visit 4 
45-60 days after Visit 3 
The subject will arrive for the visit on their preferred aDBS mode. 
Data collection: 
• 
Concomitant medications 
• 
PDQ-39 
• 
EQ-5D-5L 
• 
Collect PKG Watch or confirm it was returned via mail 
• 
Programming session upload to Medtronic, with BrainSense data included in the JSON session 
data report  
• 
Adverse Event and device deficiency assessment 
The subject should be reminded that they will receive the PKG Watch prior to the next visit and will put 
on and activate the device upon receipt. The subject will wear the PKG Watch on the most affected side 
for at least 6 consecutive days in the 14 days prior to the scheduled visit. The subject will return the PKG 
Watch in the pre-paid mailer or bring it to the site for return at Visit 5. 
9.11.3. 
Visit 5 
90 +/- 14 days after Visit 4 
The subject will arrive for the visit on their preferred aDBS mode.  
Data collection: 
• 
Concomitant medications 
• 
PDQ-39 
• 
EQ-5D-5L 
• 
Collect PKG Watch or confirm it was returned via mail 
• 
Programming session upload to Medtronic via CDU, with BrainSense data included in the JSON 
session data report  
• 
Adverse Event and device deficiency assessment 
The subject should be reminded that they will receive the PKG Watch prior to the next visit and will put 
on and activate the device upon receipt. The subject will wear the PKG Watch on the most affected side 
for at least 6 consecutive days in the 14 days prior to the scheduled visit. The subject will return the PKG 
Watch in the pre-paid mailer or bring it to the site for return at Visit 6. 
9.11.4. 
Visit 6 
90 +/- 14 days after Visit 5 
Data collection: 
• 
Concomitant medications 

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• 
PDQ-39 
• 
EQ-5D-5L 
• 
Patient satisfaction questionnaire 
• 
Collect PKG Watch or confirm it was returned via mail 
• 
Programming session upload to Medtronic via CDU, with BrainSense data included in the JSON 
session data report  
• 
Adverse Event and device deficiency assessment 
At the completion of this visit, if aDBS is not commercially approved, the subject may choose to continue 
participation in the study as described in Section 9.12. If the subject chooses to exit the study after this 
visit and before aDBS is commercially approved, aDBS will be turned off as directed in Section 9.19. 
9.12. Extended Access Phase 
Following the final long-term follow-up visit (Visit 6), subjects will be allowed extended access to aDBS 
through aDBS is commercially approved in the geography in which the subject is enrolled. The subject 
will continue the study in aDBS and return for a visit every 6 months or until aDBS is commercially 
approved or closure of the study, whichever comes sooner.  
9.12.1. 
Extended Access Visits 
Every 180 +/- 60 days beginning after Visit 6 and every 6 months thereafter following the previous 
extended access visit 
Data collection: 
• 
Concomitant medications 
• 
PDQ-39 
• 
EQ-5D-5L 
• 
Programming session upload to Medtronic, with BrainSense data included in the JSON session 
data report  
• 
Adverse Event and device deficiency assessment 
9.13. Unscheduled Visit 
Any time the subject has a visit (in person, by telephone and/or telehealth/video consult) for aDBS 
programming adjustment/optimization (including resuming aDBS if it was unintentionally turned off) or 
for an Adverse Event, the following data will be collected: 
• 
Reason for the visit 
• 
Concomitant medications 
• 
Programming session upload to Medtronic via CDU, with BrainSense data included in the JSON 
session data report (if applicable) 
• 
Adverse Event and device deficiency assessment 

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9.14. System Modification 
System modifications made to the DBS System will be completed according to the center’s standard 
procedures. If the system modification occurs prior to randomization, the subject should be exited, prior 
to receiving the system modification if possible, and considered for re-enrollment as applicable. If the 
system modification occurs after randomization, the investigator should assess if the subject should be 
exited from the study or proceed to the long term follow up phase on aDBS. The subject will not 
complete or repeat the aDBS evaluation period(s). If the subject proceeds to the long term follow up 
phase, aDBS will be programmed after (s)he is healed and stable on cDBS.  aDBS can be programmed by 
either performing the full aDBS setup or by using the subject’s prior aDBS parameters and assessing for 
acceptability.  Any visits for aDBS setup due to a system modification will be recorded as unscheduled 
visits. Once aDBS is set up, the subject will enter the long-term follow-up. If aDBS cannot be acceptably 
set up, the subject will be exited from the study following the process in Section 9.19. 
Data collection: 
• 
Device information (if applicable) 
• 
Concomitant medications 
• 
Programming session upload to Medtronic via CDU, with BrainSense data included in the JSON 
session data report (if INS is being modified) 
• 
Adverse Event and Device deficiency assessment 
9.15. Assessment of Efficacy and Device Performance 
9.15.1. 
Parkinson’s Disease (PD) Home Diary 
The Parkinson’s Disease Home Diary (Copyright © The University of South Florida, 2000.  All rights 
reserved) is a standard home diary to assess functional status in patients with PD. In 30-minute intervals, 
patients record whether they were in the “On” condition, with or without dyskinesia, “Off” condition, or 
asleep.a In the On condition with dyskinesia, patients record whether they were On with troublesome or 
non-troublesome dyskinesia. For the purposes of the PD home diary, at least 3 consecutive days means 
at least 3 consecutive 24-hour periods. 
 
 
 
a Hauser, et al. “A home diary to assess functional status in patients with Parkinson's disease with motor 
fluctuations and dyskinesia.” Clinical Neuropharmacology. 2000 Mar-Apr;23(2):75-81. 

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9.15.2. 
Total Electrical Energy Delivered (TEED) 
TEED is defined as the total energy delivered by an electrical system through the DBS leads over an 
arbitrary period of time. TEED is determined by the stimulation parameters (e.g., pulse width, 
frequency, amplitude) and the measured impedance.  
The calculation of TEED when using constant voltage is:  
TEED = (Voltage2 * Frequency * Pulse width) / Impedanceb  
The calculation of TEED when using constant current is: 
TEED = Current2 * Frequency * Pulse width * Impedance 
9.15.3. 
Wearable Data 
Wearable data will be collected via the PKG Watch as a continuous measure of bradykinesia score (BKS), 
dyskinesia score (DKS) and the % of wear time with Tremor. A Fluctuation and Dyskinesia score (FDS) will 
also be derived from the wearable data. 
9.15.4. 
European Quality of Life – 5 Dimensions (EQ-5D-5L) 
The European Quality of Life – 5 Dimensions, version 5L (EQ-5D-5L), is a standardized measure of health 
status developed by the EuroQol Group and a widely used validated tool to determine health-related 
quality of life.c The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels of severity: no 
problems, slight problems, moderate problems, severe problems, extreme problems. The subject will be 
asked to indicate his/her health state by selecting the most appropriate statement in each of the 5 
dimensions. This decision results in a 1-digit number expressing the level selected for that dimension. 
The digits for 5 dimensions can be combined into a 5-digit number describing the respondent’s health 
state. It should be noted that the numerals 1-5 have no arithmetic properties and should not be used as 
a cardinal score. In a second step, the responses to the five EQ-5D dimensions (i.e. an EQ-5D health state 
or profile) will be converted into a single number called an index value using the United Kingdom value 
 
 
 
b Koss AM, et al. “Calculating Total Electrical Energy Delivered by Deep Brain Stimulation Systems.” Annals of 
Neurology. Vol 58. No 1. July 2005. P. 168-169. 
c The EuroQol Research Foundation. "EQ-5D-5L User Guide: Basic information on how to use the EQ-5D-5L 
instrument." https://euroqol.org/wp-content/uploads/2016/09/EQ-5D-5L_UserGuide_2015.pdf 

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set. The index value reflects how good or bad the health state is according to the preferences of the 
general population of a country/region.  
This assessment may be completed either in person, or over the telephone a maximum of 7 days prior 
to the study visit. 
9.15.5. 
Parkinson’s Disease Questionnaire (PDQ-39) 
The Parkinson’s Disease Questionnaire is a self-completion Patient Reported Outcome (PRO) designed to 
address aspects of functioning and well-being for those affected by Parkinson’s disease.d There are 39 
questions in the long form Parkinson’s Disease Questionnaire, with 8 discrete scales: 
• 
mobility (10 items) 
• 
activities of daily living (6 items) 
• 
emotional well-being (6 items) 
• 
stigma (4 items) 
• 
social support (3 items) 
• 
cognitions (4 items) 
• 
communication (3 items) 
• 
bodily discomfort (3 items) 
Patients are asked to think about their health and general well-being and to consider how often in the 
last month they have experienced certain events (e.g. difficulty walking 100 yards). Patients are asked to 
indicate the frequency of each event by selecting one of 5 options (Likert Scale): 
never/occasionally/sometimes/often/always or cannot do at all. 
This assessment may be completed either in person, or a copy may be sent to the subject to be 
completed a maximum of 7 days prior to the study visit. 
9.15.6. 
Movement Disorders Society Unified Parkinson’s Disease Rating 
Scale (MDS-UPDRS) 
The MDS-UPDRS is a MDS-sponsored revision of the UPDRS clinical rating scale for Parkinson’s disease. It 
has been the most widely used scale to assess impairment and disability in PD. The MDS-UPDRS is a 
comprehensive 50 question assessment of both motor and non-motor PD symptoms. The assessment 
has four parts: Part I (non-motor experiences of daily living), Part II (motor experiences of daily living), 
 
 
 
d Oxford University Innovation. “Parkinson’s Disease Questionnaire (PDQ-39 and PDQ-8).” 
https://innovation.ox.ac.uk/outcome-measures/parkinsons-disease-questionnaire-pdq-39-pdq-8/  

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Part III (motor examination) and Part IV (motor complications).e Parts 1A, III and IV are assessed by the 
trained rater and Parts IB and III are a self-administered patient questionnaire that is completed with or 
without the aid of the caregiver. 
Each question is scored from 0 to 4 reflecting the subject’s usual level of function; Normal, Slight, Mild, 
Moderate and Severe. Each part (I-IV) can be reported as sub-scores, or all parts can be reported as an 
overall score. 
This assessment must be completed in person whenever possible. In the event the assessment cannot 
be completed in person, Parts IA, IB, II and IV may be administered via telephone/telehealth a maximum 
of 7 days prior to the study visit, and a protocol deviation recorded.  
9.15.7. 
Parkinson’s Disease Sleep Scale 2 (PDSS-2) 
The PDSS-2 assesses a wide spectrum of disease-specific sleep problems and is administered as a patient 
self-rating scale. 
The PDSS-2 consists of 15 questions about various sleep and nocturnal disturbances which are to be 
rated by the patients using one of five categories, from 0 (never) to 4 (very frequent). PDSS-2 total score 
ranges from 0 (no disturbance) to 60 (maximum nocturnal disturbance).f 
This assessment must be completed in person whenever possible. In the event the assessment cannot 
be completed in person, the assessment may be administered via telephone a maximum of 7 days prior 
to the study visit, and a protocol deviation recorded.  
9.15.8. 
Voice Handicap Index (VHI) 
The VHI has been designed to evaluate the quality-of-life specific to dysphonia. It was developed and 
validated with patients with a wide range of disorders, including neurological disorders and quantifies 
the patients’ perceptions of the handicap they experience in everyday life due to speech disorders. 
The 30-item self-administered questionnaire consists of a 10-item functional subscale, a 10-item 
emotional subscale, and a 10-item physical subscale. Patients are asked to read each item and circle one 
of five response comprising an equal-appearing five-point scale. The scale has the words “never” and 
“always” anchoring each end and the words “almost never”, “sometimes”, and “almost always” 
 
 
 
e Movement Disorder Society. “MDS-UPDRS.” https://www.movementdisorders.org/MDS-Files1/PDFs/Rating-
Scales/MDS-UPDRS_English_FINAL_Updated_June2019.pdf  
f Trenkwalder C, et al. “Parkinson’s Disease Sleep Scale – Validation of the Revised Version PDSS-2.” Movement 
Disorders. Vol. 26. No. 4. March 2011. P. 644-652. 

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appearing in between. An “always” response was scored 4 points, a “never” response was scored 0 
points, and the remaining options were scored between 1 and 3 points.  g 
This assessment may be completed either in person, or a copy may be sent to the subject to be 
completed a maximum of 7 days prior to the study visit. 
9.15.9. 
Patient Preference 
Patient preference for aDBS vs. cDBS and Single vs. Dual Threshold aDBS modes (if both were evaluated) 
will be assessed by a Medtronic-developed questionnaire. 
This assessment may be completed either in person, or a copy may be sent to the subject to be 
completed a maximum of 7 days prior to the study visit. 
9.15.10. Patient Satisfaction 
Patient satisfaction with aDBS as assessed by a Medtronic-developed questionnaire. 
This assessment may be completed either in person, or a copy may be sent to the subject to be 
completed a maximum of 7 days prior to the study visit. 
9.15.11. aDBS Global Impression of Change  
Acceptability of each aDBS mode is be assessed by a Medtronic-developed aDBS Global Impression of 
Change. Efficacy and side effects are assessed on a scale from 1 to 21.  Lower scores represent better 
efficacy and fewer side effects.  A score of 8 or less indicates the aDBS mode is acceptable. 
9.16. Assessment of Safety 
Subjects will be assessed for all potential Adverse Events and device deficiencies, as applicable, at each 
study visit from the time the study informed consent form is signed until discontinuation from the study. 
Safety data collected for this study will include all device deficiencies, and all reportable AEs. Refer to 
Section 11: Adverse Events and Device Deficiencies. 
 
 
 
g Jacobson B, et al. “The Voice Handicap Index (VHI): Development and Validation.” American Journal of Speech-
Language Pathology. Vol 6. No 3. August 1997. P. 66-70. 

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9.17. Recording Data 
The investigator must ensure accuracy, completeness and timeliness of the data reported in the case 
report forms (CRFs) and in all other required reports. Source documentation is defined as the first time 
data appear, and may include original documents, data, and records (e.g., hospital records, clinical and 
office charts, procedure reports, laboratory notes, memoranda, subjects’ diaries or evaluation 
checklists, pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, 
microfilm or magnetic media, X-rays, subject files, device data and records kept at the pharmacy, at the 
laboratories and at medico-technical departments involved in the study). 
In general, eCRFs (or paper copies) may not serve as source documents. Subject questionnaires (e.g. PD 
Home Diary, MDS-UPDRS, VHI, PDQ-39, PDSS-2) and physician assessments (e.g. C-SSRS, GIC, MDS-
UPDRS) may be collected on paper forms provided by the sponsor to be entered into the RDC system by 
the center personnel. If used, the paper forms of the questionnaires will be retained at the center as 
original source documentation. Source documentation for data elements not routinely captured in 
medical records may vary from study site to study site; the study site may use source document 
worksheets if identified as source documents. Data reported on the CRFs, which are derived from source 
documents, must be consistent with the source documents and discrepancies need to be justified with 
documented rationale, and approved by the principal investigator or delegate. The investigator must 
ensure the availability of source documents from which the information on the eCRFs was derived. 
Where printouts of electronic medical records are provided as source documents, or where copies of 
source documents are retained as source documents, those should be certified. Certification must 
contain (1) the signature of the individual making the copy, (2) the date the copy was made and (3) a 
statement attesting to the accuracy and completeness of the copy.  
The source documents must be made available for monitoring or auditing by Medtronic’s representative 
or representatives of the competent authorities and other applicable regulatory agencies. 
The study will use the Oracle Clinical (OC) RDC system which allows the study centers to enter study 
data into the sponsor’s database over a secured internet connection. The system controls user access, 
ensures data integrity, and maintains an audit trail on entries, changes or corrections in CRFs. The 
principal investigator will ensure that only appropriately delegated study personnel are given access to 
the RDC system; user IDs and passwords may not be shared. 
Programming session files, with BrainSense data included in the JSON session data report, will be 
collected for the study and uploaded via CDU to the NPU (Neuro Programmer Upload) server and study 
database.  

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9.18. Deviation Handling 
A study deviation is an event within a study that did not occur according to the clinical investigation 
plan, CTA, investigator agreement, IRB/EC policies or applicable standards, laws and regulations.  
The investigator may not deviate from the CIP unless the deviation is necessary in an emergency 
situation to protect the rights, safety and wellbeing of the subject. or due to an unforeseen 
circumstance that is beyond the investigator’s control (eg, subject failure to attend a scheduled follow-
up visit, inadvertent errors, equipment failure). All deviations must be documented in the study 
database whether an inadvertent occurrence or taken to protect the subject in an emergency. Multiple 
deviations of the same type at the same visit may be reported on one case report form. 
In the event the deviation involves a failure to obtain a subject’s consent, or is made to protect the life 
or physical well-being of a subject in an emergency, the deviation must be reported to the IRB/EC as well 
as Medtronic within five (5) working days. Reporting of all other study deviations should comply with 
IRB/EC policies and/or local laws and must be reported to Medtronic as soon as possible upon the study 
site becoming aware of the deviation. Reporting of deviations must comply with IRB/EC policies, local 
laws, and/or RA requirements. Refer to Section 15.8.1 for geography-specific deviation reporting 
requirements and timeframes for reporting to Medtronic and/or RAs.    
Deviations include, but are not limited to, the following: 
• 
Failure to obtain subject informed consent prior to beginning study activities 
• 
Subject does not meet general inclusion/exclusion criteria after the enrollment visit  
• 
Failure to report AEs or Device Deficiencies per Table 9: Safety Reporting Requirements  
• 
Failure to collect CIP-required assessments 
• 
Subject missed visit or visit outside of window 
• 
Subject unblinding 
• 
Programming adjustments during the 14 days prior to each aDBS Evaluation Visit 
• 
For subjects with the SenSight system enrolled in the Primary Cohort: change of programming 
from ring mode to directional stimulation before the end of the aDBS Evaluation Phase 
• 
For subjects enrolled in the Directional Stimulation Cohort: change of programming from 
directional stimulation to ring mode before the end of the aDBS Evaluation Phase 
Deviations will be reviewed by Medtronic on an ongoing basis. Medtronic will assess the significance of 
all deviations for the study and evaluate the need for any corrective and/or preventative actions (e.g. 
amend the CIP, conduct additional training, terminate the study). Repetitive or serious investigator 
compliance issues may suggest a need to implement a corrective action plan with the investigator and 
study center. If needed, subject enrollment may be suspended until the compliance issues are resolved. 
If compliance issues are left unresolved, the investigator’s participation in the study may be terminated.  
Medtronic will provide study site-specific reports to investigators summarizing information on 
deviations that occurred at the investigational study site on a periodic basis. 

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During the aDBS Evaluation Phase, every effort should be made to keep the subjects in the study, with 
applicable protocol deviations reported as necessary. 
9.19. Subject Exit, Withdrawal or Discontinuation  
Subjects will discontinue the study following completion of all study visits.  
Prior to early discontinuation, or after the completion of the final study visit if aDBS is not commercially 
available, subjects will return to the study center to have aDBS turned off and be programmed back to 
standard cDBS Therapy. This is done by interrogating the subject’s INS with a commercially available 
Clinician Programmer System. The subject will return the investigational Patient Programmer System to 
the study center and the investigator will re-pair the subject’s INS with a commercially available Patient 
Programmer System. A final device interrogation will be obtained to confirm that aDBS has been turned 
off. The programming session, with BrainSense data included in the JSON session data report, will be 
uploaded to Medtronic via CDU. BrainSense and passive sensing functionality will be on or off at the 
discretion of the clinician. Once aDBS is no longer active, the subject’s INS is no longer considered 
Investigational, and subjects will be discontinued and followed according to the study center’s standard 
procedures.  
If a subject discontinues from the study prior to normal completion, the eCRFs for visits that have 
occurred up to the point of withdrawal as well as the study exit eCRF must be completed. 
After study discontinuation, the updates for ongoing, and for any new events (eg, AEs or device 
deficiencies), will be reported through Neuromodulation Customer Quality as required by regulation. 
9.19.1. 
Study Exit 
A study exit eCRF is required for all subjects. Subjects are urged to remain in the study as long as 
possible but may be exited from the study for any of the following situations: 
• 
Study completed (visit #6) 
• 
Subject lost to follow-up 
• 
Subject death 
• 
Subject’s DBS Therapy System permanently explanted (i.e., neurostimulator, lead, extension) 
• 
Subject did not meet inclusion/exclusion criteria (prior to randomization) 
• 
Subject did not provide consent or data use protection authorization 
• 
Subject chooses to withdraw (e.g., consent withdrawal, relocation to another geographic 
location)  
• 
Investigator deems withdrawal necessary (e.g., medically justified, inclusion/exclusion criteria 
not met, failure of subject to maintain adequate study compliance)  
• 
Neither aDBS mode is acceptable 

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The Investigator will attempt to collect the following information prior to the subject’s early 
discontinuation from the study: 
• 
Adverse event and device deficiency assessment  
• 
Programming session report, with BrainSense data included in the JSON session data report 
upload to Medtronic via CDU (after aDBS has been turned off) 
• 
A brief description of why the subject discontinued (if applicable) 
• 
Patient satisfaction questionnaire (if early discontinued after the aDBS Evaluation Phase) 
9.19.2. 
Study Completed 
At the completion of Visit 6, subjects may exit from the study. Both the CRFs for Visit 6 and a Study Exit 
CRF need to be completed. If aDBS is not commercially approved at the time the subject completes all 
study visits, the subject may choose to continue participation in the study until aDBS is commercially 
approved or closure of the study, whichever comes sooner.  
9.19.3. 
Lost to Follow-up  
A subject is considered to be lost to follow-up if at least two attempts to contact the subject are 
unsuccessful. The method of attempt (e.g., one letter and one phone record, or two letters) must be 
documented in the subject’s medical record. In addition, regulation set forth by the governing IRB/EC 
must be followed. 
When subjects are lost to follow-up the investigator will make efforts to confirm the vital status of the 
subject, as described in the informed consent. 
9.19.4. 
Subject Chooses to Exit (i.e. Revokes Consent) 
A subject can withdraw from the study at any time. If the subject wishes to exit from the study (i.e., the 
subject revokes consent), the study site is required to document the reason for exit on the Exit CRF. In 
addition, study sites shall follow the regulations set forth by the governing IRB/EC. Permission may be 
requested to follow up with the subject outside of the study due to withdrawal based on problems 
related to the investigational feature safety or performance.  
If possible, the following data should be collected prior to subject withdrawal: 
• 
Adverse event and device deficiency assessment  
• 
Final device interrogation and data upload via CDU (after aDBS has been turned off)  
o Export JSON Session Data  
• 
A brief description of why the subject discontinued (if applicable) 

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9.19.5. 
Investigator Withdraws Subject 
No subjects should be withdrawn by investigators unless compelling medical justification is present. It is 
recommended investigators discuss any withdrawals with the study team prior to withdrawing subjects. 
If the subject was randomized, it is preferred to keep the subject in the study and perform study 
procedures/collect data to the extent possible. If an investigator withdrawal is necessary, the following 
data should be collected prior to subject withdrawal if possible: 
• 
Adverse event and device deficiency assessment  
• 
Final programming session upload to Medtronic via CDU, with BrainSense data included in the 
JSON session data report (after aDBS has been turned off)  
• 
A brief description of why the subject was withdrawn by the investigator  
9.19.6. 
Conditional Disengagement 
After a subject is enrolled/randomized every effort should be made to keep the subject in the study. 
However, it is recognized that there are circumstances where limited data may be collected, or study 
exit will need to occur. In these cases we will consider either modified data collection requirements 
where subjects may conditionally disengage in study procedures but data from the subject can still be 
collected because the subject has not revoked consent, or exit when study participation is completely 
ended. In randomized subjects, modified data collection is always preferred over exit. 
Subjects may be conditionally disengaged from study procedures for any of the following reasons: 
• 
Subject chooses to disengage (e.g., follow-up schedule cannot be adhered to, study 
burden too large, relocation to another geographic location but telephone follow-up still 
acceptable)  
• 
Investigator deems conditional disengagement necessary (e.g. medically justified)  
If the subject wishes to disengage from the study, or the investigator deems it necessary, the study site 
is required to document the reason. Prior approval from the study team is required and a Limited Data 
Collection CRF needs to be completed. Data collection requirements no longer apply, but study sites are 
encouraged to collect as much data as possible on the regular CRFs. 
10. Risks and Benefits 
10.1. Potential Risks 
Deep Brain Stimulation Therapy is a reversible procedure (,i.e., the system can be turned off or removed 
in most cases) with stimulation parameters that are adjustable to minimize or reverse complications and 
maximize therapeutic effects. Deep Brain Stimulation Therapy has CE Mark, Health Canada and FDA 
approval, and is commercially available in the European Union, Canada and the United States. The risks 
associated with the Medtronic DBS Therapy are included in commercially available product information. 

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The risks, precautions, warnings, cautions, and contraindications associated with the Medtronic DBS 
Therapy and each system component are included in the product labeling.  These risks may be 
temporary or permanent and must be continuously monitored, assessed and documented by the 
investigator. 
Medtronic follows rigorous Quality Assurance and Control procedures throughout the life of a product, 
from the business analysis phase through development, market release, and post-market surveillance. 
The risk management process for the aDBS feature is being performed in accordance with ISO 14971 
and will ensure that the level of risk is acceptable prior to starting the study.  
10.1.1. 
Pregnancy 
The safety of neurostimulation systems is unknown for pregnancy, unborn fetus, or delivery. Because 
the risks to the subject and/or unborn child while receiving neurostimulation are unknown, female 
subjects of childbearing potential must have a negative pregnancy test at enrollment and agree to not 
become pregnant during the study by using a medically acceptable method of birth control. Should a 
pregnancy occur during the study, the subjects are instructed to notify their physician immediately and 
the investigator will notify Medtronic in a timely manner. Careful considerations of the risks and benefits 
of continuation in the study will be weighed by the subject and their physician. 
10.1.2. 
Potential aDBS risks 
The primary function of the aDBS is to adjust stimulation amplitude within clinician-defined stimulation 
limits. The risks of adaptive DBS are no different than the risks of commercially available cDBS risks, 
which are not increased due to participation in the study.  
10.1.3. 
Potential Study Procedures Risks 
The clinical investigation has been designed to involve as little pain, discomfort, fear and any other 
foreseeable risk as possible for the subjects, and both the risk threshold and the degree of distress are 
specifically defined in the clinical investigation plan. Potential risks related to study procedures include: 
• 
Subjects may experience skin irritation from the PKG watch. Should irritation occur, the subject 
should remove the watch 
• 
There may be risks or side effects which are unknown at this time. 
10.1.4. 
Potential Study Procedure Inconveniences 
• 
The patient assessments subjects are required to complete for the study may be burdensome. 
• 
The patient assessments that are required for the study may request information of a personal 
nature 

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10.2. Risk Minimization 
The potential risks associated with the aDBS feature were identified and have been successfully 
mitigated as far as possible (Table 6). Any potential risks associated with this study are further 
minimized by selecting qualified investigators and training study personnel on the CIP. Medtronic has 
also attempted to minimize risk to subjects implementing a DMC to review safety issues as part of the 
study. 
Risks will be minimized by careful assessment of each subject prior to, during, and after enabling aDBS. 
In addition, investigators will be actively involved in the follow-up of the subjects with aDBS enabled on 
their Percept PC device. 
Medtronic has further minimized the possibility of risks by: performing required laboratory and pre-
clinical testing prior to the ADAPT-PD study, implementing design assurance and quality control 
measures into production processes, providing guidelines for subject selection and evaluation, and 
providing adequate instructions and labeling. 
 
 

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Table 6: Potential Risks and Risk Minimization 
Potential Risk 
Risk Minimization 
Non-optimum stimulation, due to noise to LFP 
• 
System requirements ensures that patient 
has the capability to switch from aDBS to 
cDBS, if needed.   
• 
Product requirements and software 
requirements ensure that aDBS works 
reliably as designed. 
10.3. Potential Benefits 
Some subjects may experience benefits from aDBS, such as: Parkinson’s disease symptom management, 
improvement of movement symptoms, improved quality of life and/or energy savings of their device. 
The information gained from this study might benefit other patients in the future. 
10.4. Risk-Benefit Rationale 
The benefit of the study lies in the knowledge to be gained from the results and the potential to improve 
future DBS therapies. All the potential risks have been controlled to a level as far as possible. Based on 
the risk acceptance criteria for the ADAPT-PD Trial laid out in the Study Risk Management Plan, the 
study-specific residual risk is determined to be acceptable given the expected benefits.  
10.5. Risk Determination 
The Percept PC INS used in the ADAPT-PD Trial meets the definition for a significant risk device in 
21CFR§812.3(m), because it is an implanted device and presents a potential for serious risk to the 
health, safety, or welfare of a subject.   
The Percept PC INS used in the ADAPT-PD Trial is currently classified as AIMD in accordance with 
90/385/EEC and in the future will be classified as Class III in accordance Annex VIII, Rule 8 of EU 
Regulation 2017/745. The Percept PC INS is considered an investigational device in the ADAPT-PD Trial 
once aDBS is enabled. 
As per Schedule 1 of the Canadian Medical Device Regulations (SOR-98-282), the Percept PC INS used in 
the ADAPT-PD Trial is classified as a Class IV Medical Device according to Rule 1(2): A surgically invasive 
device that is intended to diagnose, monitor, control or correct a defect of the central cardiovascular 
system or the central nervous system or of a fetus in utero is classified as Class IV. 

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As per Schedule 1 of the Canadian Medical Device Regulations (SOR-98-282), the PKG Watch used in the 
ADAPT-PD Trial is classified as a Class II Medical Device according to Rule 10(1), which states: Subject to 
subrule (2), an active diagnostic device, including any dedicated software, that supplies energy for the 
purpose of imaging or monitoring physiological processes is classified as Class II.  
11. Adverse Events and Device Deficiencies 
11.1. Adverse Events 
AE definitions are provided in Table 7. All AE information will be collected throughout the study 
duration, starting at the time of signing the IC.  
Reporting of these events to Medtronic will occur on an AE eCRF. Each event must be reported 
separately. Documented pre-existing conditions are not considered AEs unless the nature or severity of 
the condition has worsened.  
In all geographies, UAE, listed in Table 7, need not be reported unless the adverse event worsens or is 
present outside the stated timeframe post-system modification. 
For AEs that require immediate reporting (see Table 9), initial reporting may be done by phone, email, or 
on the CRF completing as much information as possible. The completed AE CRF must be submitted to 
Medtronic as soon as possible.   
Any medication/treatment associated with the treatment of an AE must be reported.  
All non-subject AEs will be collected throughout the study duration 
Subject deaths are also required to be reported. Refer to Section 11.6 for Subject Death collection and 
reporting requirements. 
11.2. Device Deficiency 
The Device Deficiency (DD) definition is provided in Table 7. All DD information will be collected 
throughout the study and reported to Medtronic on the DD eCRF. Note that DD that result in an AE to 
the subject should be captured as an AE only. 
DD that did not lead to an AE but could have led to a SADE (i.e., if suitable action had not been taken, if 
intervention had not been made, or if the circumstances had been less fortunate) require reporting 
according to the timeframes listed in Table 9. 
11.3. Processing Updates and Resolution 

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For any changes in status of a previously reported AE or DD (i.e. change in actions taken, change in 
outcome, change in relatedness), information needs to be updated on, or added to the original AE or DD 
eCRF. All AEs must be followed until the AE has been resolved, is unresolved with no further actions 
planned, the subject dies or exits the study, or until study closure, whichever occurs first.  
At the time of study exit, all collected AEs that are unresolved must be reviewed and an update to the 
original AE must be reported. 
After study discontinuation, subjects will be followed according to the study center’s standard 
procedures and updates for AEs that are ongoing, and any new events (eg, AEs or device deficiencies) 
will be reported through Neuromodulation Customer Quality as required by regulation. 
11.4. Definitions/Classifications 
This study will be following ISO14155:2020 and will collect all Adverse Events and Device Deficiencies 
from the time of enrollment through study exit/discontinuation.  It is the responsibility of the 
Investigator to identify the occurrence of all adverse events and device deficiencies and to ensure the 
required information is accurately documented in the medical records and reported to Medtronic.  
Where the definition indicates “device”, it refers to any device used in the study. This might be the 
device under investigation, or any market released component of the system, and includes but is not 
restricted to the components listed in Table 1: Medtronic DBS System Components and the PKG Watch. 
Table 7: Adverse Event and Device Deficiency Definitions 
General 
Adverse Event (AE) 
Untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in 
subjects, users or other persons, whether or not related to the 
investigational medical device and whether anticipated or unanticipated. 
Note 1: This definition includes events related to the investigational 
medical device or the comparator. 
Note 2: This definition includes events related to the procedures 
involved. 
Note 3: For users or other persons, this definition is restricted to events 
related to the use of investigational medical devices or comparators.    
(ISO 14155:2020, 3.2) 
Adverse Device Effect 
(ADE) 
AE related to the use of an investigational medical device. 
Note 1: This definition includes AEs resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, 
or operation, or any malfunction of the investigational medical device. 
Note 2: This definition includes any event resulting from use error or 
from intentional misuse of the investigational medical device. 

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NOTE 3: this includes ‘comparator’ if the comparator is a medical device 
(ISO 14155:2020, 3.1) 
Device Deficiency  
Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, usability, safety or performance.  
Note 1: DD include malfunctions, use errors and inadequacy in the 
information supplied by the manufacturer including labeling.  
Note 2: This definition includes device deficiencies related to the 
investigational medical device or the comparator. (ISO 14155:2020, 3.19) 
Relatedness 
Relationship of Adverse 
Events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The relationship of an adverse event will be classified as device-related, 
therapy/stimulation-related, procedure-related, related to the disease 
under study, and/or related to an underlying condition or disease 
based on the following definitions: 
• 
Device Related: An adverse event that results from the presence or 
performance (intended or otherwise) of the DBS system or any of 
the DBS system components 
• 
Procedure Related: An adverse event that occurs due to any 
procedure related to the surgical modification, or explant of the 
DBS system or any of the DBS system components. 
• 
Therapy/Stimulation Related: An adverse event related to therapy 
delivery by the DBS system (i.e. stimulation).  Normally therapy-
related events resolve when the device is turned off or 
reprogrammed. 
• 
Related to the disease under study:  An adverse event that is 
caused by Parkinson’s disease 
• 
 
Each of the relatedness classifications will be assessed for causality using 
five different levels of causality based on the following definitions: 
• 
Not Related: relationship to the device, comparator or procedures 
can be excluded when: 
o the event has no temporal relationship with the use of the 
investigational device or the procedures related to application 
of the investigational device; 
o the serious event does not follow a known response pattern to 
the medical device (if the response pattern is previously known) 
and is biologically implausible; 
o the discontinuation of medical device application or the 
reduction of the level of activation/exposure - when clinically 
feasible – and reintroduction of its use (or increase of the level 

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of activation/exposure), do not impact on the serious adverse 
event; 
o the event involves a body-site or an organ not expected to be 
affected by the device or procedure; 
o the serious event can be attributed to another cause (e.g. an 
underlying or concurrent illness/ clinical condition, an effect of 
another device, drug, treatment or other risk factors); 
o the event does not depend on a false result given by the 
investigational device used for diagnosis, when applicable; 
In order to establish the non-relatedness, not all the criteria listed 
above might be met at the same time, depending on the type of 
device/procedures and the serious adverse event 
• 
Unlikely: the relationship with the use of the device seems not 
relevant and/or the event can be reasonably explained by another 
cause, but additional information may be obtained. 
• 
Possible: the relationship with the use of the investigational device 
or comparator is weak but cannot be ruled out completely. 
Alternative causes are also possible (e.g. an underlying or 
concurrent illness/ clinical condition or/and an effect of another 
device, drug or treatment). Cases were relatedness cannot be 
assessed or no information has been obtained should also be 
classified as possible. 
• 
Probable: the relationship with the use of the investigational 
device or comparator seems relevant and/or the event cannot 
reasonably be explained by another cause 
• 
Causal relationship: the serious adverse event is associated with 
the investigational device, comparator or with procedures beyond 
reasonable doubt when: 
o the event is a known side effect of the product category the 
device belongs to or of similar devices and procedures; 
o the event has a temporal relationship with investigational 
device use/application or procedures;  
o the event involves a body-site or organ that 
 
the investigational device or procedures are applied to; 
 
the investigational device or procedures have an effect on; 
o the serious adverse event follows a known response pattern to 
the medical device (if the response pattern is previously 
known); 
o the discontinuation of medical device application (or reduction 
of the level of activation/exposure) and reintroduction of its use 
(or increase of the level of activation/exposure), impact on the 
serious adverse event (when clinically feasible); 

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o other possible causes (e.g. an underlying or concurrent illness/ 
clinical condition or/and an effect of another device, drug or 
treatment) have been adequately ruled out; 
o harm to the subject is due to error in use; 
o the event depends on a false result given by the investigational 
device used for diagnosis, when applicable; 
In order to establish the relatedness, not all the criteria listed 
above might be met at the same time, depending on the type of 
device/ procedures and the serious adverse event. 
Events are considered “related” to the investigational medical device if 
their relationship to the device, procedure, or therapy is classified as 
“possible”, “probable”, or “causal”. 
Seriousness 
Serious Adverse Event 
(SAE) 
 
 
AE that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users or other 
persons as defined by one or more of the following:  
1) A life-threatening illness or injury, or 
2) A permanent impairment of a body structure or a body 
function, including chronic diseases, or 
3) In-patient or prolonged hospitalization, or 
4) Medical or surgical intervention to prevent life-threatening 
illness or injury, or permanent impairment to a body structure 
or a body function, 
c) foetal distress, foetal death, a congenital abnormality, or birth 
defect including physical or mental impairment. 
Note 1:  Planned hospitalization for pre-existing condition, or a 
procedure required by the CIP, without serious deterioration in health, is 
not considered a SAE. 
(ISO 14155:2020, 3.45) 
Serious Adverse Device 
Effect (SADE) 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
(ISO 14155:2020, 3.44)  
Unanticipated Adverse 
Device Effect (UADE) 
 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or 
welfare of subjects. 
(US 21 CFR§812.3(s)) 

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The following are not considered an AE for the study. 
• 
Pregnancy  
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
 
Serious adverse device effect which by its nature, incidence, severity or 
outcome has not been identified in the current  risk assessment. 
Note 1: Anticipated serious adverse device effect (ASADE) is an effect 
which by nature, incidence, severity or outcome has been identified in 
the risk assessment. 
(ISO14155:2020 3.51) 
Serious Health Threat 
Signal from any adverse event or device deficiency that indicates an 
imminent risk of death or a serious deterioration in the health in 
subjects, users or other persons, and that requires prompt remedial 
action for other subjects, users or other persons 
NOTE 1: This would include events that are of significant and unexpected 
nature such that they become alarming as a potential serious health 
hazard or possibility of multiple deaths occurring at short intervals.  
(ISO 14155:2020, 3.46) 
Unavoidable Adverse 
Event (UAE) 
An AE inherent to a surgical procedure that is expected to occur in all 
subjects for a projected duration according to the Investigator’s opinion, 
including, but not limited to:  
Event Description 
Timeframe 
(hours) from 
the Surgical 
Procedure 
Anesthesia related nausea / vomiting  
24 
Low-grade fever (<100°F or 37.8°C) 
48 
Pocket site / Incisional pain 
72 
Mild to moderate bruising / ecchymosis 
168 
Sleep problems (insomnia) 
72 
Back pain related to laying on table 
72 
Shoulder pain/discomfort/stiffness 
related to shoulder immobilization 
during procedure 
72 

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• 
Documented pre-existing conditions unless the intensity, duration, or frequency of the condition 
is worsened from the time of enrollment 
• 
Programming adjustment (optimizations) or therapy suspension (could be an action taken as a 
result of an AE) 
• 
Transient (acute) stimulation-induced effects that occur during programming sessions or while 
running aDBS that resolve with or without programming adjustments prior to the subject leaving 
a study follow-up visit and do not require further follow-up or medical care outside of the visit 
• 
Neurostimulator replacement for battery depletion as disclosed in the product labeling 
(documented as a system modification)  
• 
Worsening quality-of-life patient-reported outcome scores (e.g. EQ-5D-5L, PDQ-39, PDSS-2, VHI, 
MDS-UPDRS Part IB & II) 
• 
Expected side-effects of Parkinson’s disease medication 
11.5. Reporting of Adverse Events 
All reportable AEs and device deficiencies must be recorded in the subject’s medical record, the study 
CRF, and promptly reported to Medtronic or its designee. Investigators are required to keep records on 
all relevant observations.  
Reportable adverse events and device deficiencies will include the following information, at a minimum: 
• 
Date of event 
• 
Diagnosis and description of the event 
• 
Assessment of the seriousness and relationship to the product(s) under investigation, therapy, 
and procedure (AE only) 
• 
Model and identifier (serial, lot number) for the involved device (if applicable) 
• 
Treatment (AE only) 
• 
Outcome and date of resolution (AE only) 
It is the responsibility of the investigator to identify the occurrence of reportable AEs and DDs and to 
ensure the required information is accurately documented on the CRF. 
For emergency reporting of SAEs and SADEs, the following Medtronic contact information may be used: 
Phone: +1 763.514.4000 
Email : rs.ADAPT-PDTrial@medtronic.com  
Address: 7000 Central Avenue NE, RCE375 | Minneapolis, MN 55432  |  USA 
11.5.1. 
Adverse Event and Device Deficiency Classification 
All AE and DD will be reviewed by a Medtronic representative. AEs will be classified according to the 
definitions provided.  
Upon receipt of AE/DD at Medtronic, a Medtronic representative will review the AE/DD for 
completeness and accuracy and when necessary, will request clarification and/or additional information 

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from the Investigator. Medtronic will utilize MedDRA for Regulatory Activities, to assign a MedDRA term 
for each AE/DD based on the information provided by the investigator. Copies of de-identified source 
documentation regarding an adverse event or device deficiency (eg, clinician notes or summaries) will 
be provided to Medtronic upon request.   
Regulatory reporting of AEs and DDs will be completed according to local regulatory requirements. Refer 
to Table 9 for a list of required investigator and Medtronic reporting requirements and timeframes. It is 
the responsibility of both to abide by any additional AE reporting requirements stipulated by the IRB/EC 
responsible for oversight of the study. 
For emergency contact regarding a UADE, USADE, SAE and/or SADE, contact a study representative 
immediately (refer to the study contact list provided in the study site’s study documents 
binder/investigator site file or refer to the Sponsor contact information provided on the title page). 
AEs will be classified according to the standard definitions as outlined below in Table 8: 
Table 8: Event Classification Responsibilities 
*Adverse events that are classified as having a relationship of possible, probable or causal to the investigational device, procedure or 
therapy/stimulation are considered to be related to the investigational medical device and are classified as ADEs.  
In addition, all ADEs and deaths will be reviewed and adjudicated (seriousness, relationship/causality) by 
an independent Clinical Events Committee. Refer to Section 12.2. 
11.5.2. 
Adverse Event and Device Deficiency Reporting Requirements 
Regulatory reporting of AEs and DDs will be recorded and reported according to local requirements. It is 
the responsibility of the Investigator and the sponsor to abide by the AE reporting requirements 
stipulated by local law and the study site’s IRB/EC. Refer to Table 9: Safety Reporting Requirements for 
more details related to reporting timelines.  
What is Classified 
Who Classifies 
Classifications 
Relatedness* 
• Investigator 
• Sponsor 
• Relationship to the: 
o Procedure 
o Device 
o Therapy/Stimulation 
o Disease under study 
USADE/UADE potential 
Sponsor 
USADE/UADE 
Seriousness 
Investigator 
SAE, DD with SADE potential 
Sponsor 
SAE, DD with SADE potential 
Diagnosis 
Investigator 
Based on presenting signs and symptoms and 
other supporting data 
Sponsor 
MedDRA term assigned based on the data 
provided by investigator 

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Table 9: Safety Reporting Requirements 
SAE 
Investigator shall submit to: 
Medtronic Europe: To the sponsor in acceptable timely conditions, but not later 
than within 3 calendar days after investigational site study personnel’s 
awareness of the event or of new information in relation with an already 
reported event. 
All other geographies: Report to the sponsor, without unjustified delay, 
all serious adverse events 
IRB/EC All geographies: Submit to IRB/EC as per local requirement.  
Regulatory Authority All geographies: As per local requirement. 
Sponsor shall submit to: 
IRB/EC All geographies: Submit to IRB/EC as per local requirement.  
Regulatory Authority All geographies: Reporting timeframe as per local requirement. 
SADE 
Investigator shall submit to: 
Medtronic Canada: SADEs on the patient, the user or any other person must be 
reported to the regulator and to the Sponsor within 72 hours after it 
comes to the attention of the qualified investigator. 
Europe: To the sponsor in acceptable timely conditions, but not later 
than within 3 calendar days after investigational site study personnel’s 
awareness of the event or of new information in relation with an already 
reported event 
US: Report to the sponsor, without unjustified delay, all serious adverse 
device events 
IRB/EC All geographies: Submit to IRB/EC as per local requirement.  
Regulatory Authority Canada: SADEs on the patient, the user or any other person must be 
reported to the regulator and to the Sponsor within 72 hours after it 
comes to the attention of the qualified investigator. 
All other geographies: As per local requirement. 
Sponsor shall submit to: 
IRB/EC All geographies: Submit to IRB/EC as per local requirement.  
Regulatory Authority All geographies: Reporting timeframe as per local requirement. 
UADE 
Investigator shall submit to: 
Medtronic US: As soon as possible, but in no event later than 10 working days after 
the investigator first learns of the effect. 
IRB/EC US: As soon as possible, but in no event later than 10 working days after 
the investigator first learns of the effect. 
Regulatory Authority US: As per local requirement. 
Sponsor shall submit to: 
IRB/EC US: Submit to IRB/EC as per local requirement.  

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Regulatory Authority US: Reporting timeframe as per local requirement. 
USADE 
Investigator shall submit to: 
Medtronic Canada:  USADEs on the patient, the user or any other person must be 
reported within 72 hours after it comes to the attention of the qualified 
investigator. 
Europe:  To the sponsor in acceptable timely conditions, but not later 
than within 3 calendar days after investigational site study personnel’s 
awareness of the event or of new information in relation with an already 
reported event. 
IRB/EC Canada:  Submit to IRB/EC as per local requirement.   
Europe: Submit to IRB/EC as per local requirement. 
Regulatory Authority Canada:  USADEs on the patient, the user or any other person must be 
reported within 72 hours after it comes to the attention of the qualified 
investigator. 
All other geographies: As per local requirement. 
Sponsor shall submit to: 
IRB/EC All geographies: Submit to IRB/EC as per local requirement.  
Regulatory Authority All geographies: Reporting timeframe as per local requirement. 
Deaths 
Investigator shall submit to: 
Medtronic All geographies: Without unjustified delay after learning of a subject’s 
death, regardless of whether the death is related to the device system or 
therapy. 
IRB/EC Canada: All subject deaths must be reported the EC as soon as possible, 
but no more than 72 hours of learning of a subject’s death, regardless of 
whether or not the death is related to the device system or therapy. 
All other geographies: Submit to IRB/EC as per local requirement. 
Regulatory Authority All geographies: As per local requirement. 
Sponsor shall submit to: 
IRB/EC All geographies: Submit to IRB/EC as per local requirement.  
Regulatory Authority All geographies: Reporting timeframe as per local requirement. 
All other AEs 
Investigator shall submit to: 
Medtronic 
All geographies: Submit in a timely manner after the Investigator 
first learns of the event 
IRB/EC 
All geographies: Submit to IRB/EC as per local requirement. 
Regulatory Authority 
All geographies: As per local requirement. 
Sponsor shall submit to: 
IRB/EC 
All geographies: Submit to IRB/EC as per local requirement.  
Regulatory Authority 
All geographies: Reporting timeframe as per local requirement. 

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IRB/EC and Competent Authority (CA) reporting must be completed in accordance with the local 
reporting policies of the governing IRB/EC and CA.  
11.6. Subject Death 
The investigator must notify Medtronic and the governing IRB/EC (as required) without unjustified delay 
after learning of a subject’s death, regardless of whether the death is related to the device system or 
therapy. The Investigator should also attempt to determine, as conclusively as possible, whether such 
deaths are related to the device, procedure or therapy.  
Investigational DDs with SADE potential 
Investigator shall submit to: 
Medtronic 
Canada: DDs that have resulted in any of the consequences 
characteristic of an SAE on the patient, the user or any other person or 
could do so were it to reoccur must be reported to the regulator and the 
Sponsor within 72 hours after it comes to the attention of the qualified 
investigator. 
Europe: To the sponsor in acceptable timely conditions, but not later 
than within 3 calendar days after investigational site study personnel’s 
awareness of the event or of new information in relation with an already 
reported deficiency. 
US: Reporting timeframe as per local requirement 
IRB/EC 
All geographies: Submit to IRB/EC as per local requirement. 
Regulatory Authority 
Canada:  DDs that have resulted in any of the consequences 
characteristic of an SAE on the patient, the user or any other person or 
could do so were it to reoccur must be reported to the regulator and the 
Sponsor within 72 hours after it comes to the attention of the qualified 
investigator. 
All other geographies: As per local requirement. 
Sponsor shall submit to: 
IRB/EC 
All geographies: Submit to IRB/EC as per local requirement.  
Regulatory Authority 
All geographies: Reporting timeframe as per local requirement. 
All other Device Deficiencies 
Investigator shall submit to: 
Medtronic All geographies:  Submit in a timely manner after the Investigator first 
learns of the device deficiency 
IRB/EC All geographies: Reporting timeframe as per local IRB/EC requirement. 
Sponsor shall submit to: 
IRB/EC 
All geographies: Submit to IRB/EC as per local requirement.  
Regulatory Authority 
All geographies: Reporting timeframe as per local requirement. 

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Any subject death will be reported on the Adverse Event and Study Exit eCRF accordingly. For the 
Adverse Event eCRF, the death should not be reported as a diagnosis of the event, rather as an outcome 
of the event which led to death. 
If an autopsy is conducted, a copy of the de-identified report will be provided to Medtronic. Medtronic 
requests that all device system components that were being used at the time of the death be returned 
to Medtronic for analysis per Section 6.10, Product Return.  
A copy of the death certificate, if available and allowed by state/local law, should be sent to the 
Medtronic clinical study team. When a death occurs in a hospital, a copy of the death summary report 
and all relevant hospital records, if available should be sent to the Medtronic clinical study team. When 
the death occurs at a remote study site, it is the investigative study site’s responsibility to attempt 
retrieval of information about the death. If a death certificate or summary report are unavailable, and 
investigator summary of the death is acceptable. Additionally, device disposition information should be 
updated.  
In summary, the following data will be collected: 
• 
Date of death 
• 
Detailed description of death 
• 
Cause of death  
• 
Relatedness to system and procedure 
• 
Device interrogation information/reports (if available) 
• 
Device disposition information 
• 
Death summary/hospital records (if available and allowed by state/local law) 
• 
Autopsy report (if available and allowed by state/local law) 
• 
Death certificate (if available and allowed by state/local law) 
11.7. Product Complaint Reporting 
Product complaint reporting and vigilance reporting are applicable and AEs related to any market-
released device during the study must be reported. The reporting of product complaints is not part of 
the study and should be done in addition to the AE reporting requirements.  Refer to local regulations 
for reporting requirements.  
Product Complaint: Any written, electronic or oral communication that alleges deficiencies related to 
the identity, quality, durability, reliability, safety, effectiveness or performance of a medical device that 
has been placed on the market. 
It is the responsibility of the investigator to report all product complaint(s) associated with a medical 
device distributed by Medtronic, regardless of whether they are related to intended use, misuse or 
abuse of the product. Reporting must be done immediately and via the regular channels for market-

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released products. The reporting of product complaints by the clinical team must be done according to 
the local Standard Operating Procedures. Medtronic will notify the RAs (e.g. CA) as applicable for the 
following incidents immediately upon learning of them and is not limited to AEs and DDs only: 
• 
Any malfunction or deterioration in the characteristics and/or performance of a device, 
as well as any inadequacy in the labeling or instructions for use which led or might have 
led to the death or serious deterioration in the state of health of a patient, user, or 
other person. 
• 
Any technical or medical reason resulting in withdrawal of a device from the market by 
the manufacturer. 
• 
Any serious deterioration in the state of health, including: 
 
Life-threatening illness or injury 
 
Permanent impairment of a body function or permanent damage to a body 
structure 
 
A condition necessitating medical or surgical intervention to prevent permanent 
impairment of a body function or permanent damage to a body structure 
12. Data Review Committees 
12.1. Data Monitoring Committee 
The main objective of the ADAPT-PD Trial Data Monitoring Committee (DMC) is to advise Medtronic 
regarding the continued safety of study subjects and those yet to be recruited to the study; and to 
ensure the validity and scientific merit of the study. 
The DMC will be external to Medtronic and independent of the study investigators. The physician 
members will have specialties appropriate to the therapeutic area and all members will meet 
requirements established in the DMC charter. 
The DMC will be responsible for: 
• 
Assessing the progress of the ADAPT-PD trial, including the accumulation of safety data  
• 
Evaluating study conduct (eg, data quality) for the impact on validity and scientific merit of the 
ADAPT-PD Trial 
• 
Considering factors external to the study when relevant information becomes available, such as 
scientific or therapeutic developments that may have an impact on the safety of the participants 
or the ethics of the study 
• 
Recommending to the sponsor whether to continue, modify, or stop the study 
Medtronic personnel (eg, statistician, Medtronic study management team) may facilitate the DMC 
meetings, provide study progress updates and answer questions. Medtronic personnel will not be voting 
members.  

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The DMC Charter will define the DMC processes for member selection, meeting frequency, roles and 
responsibilities, procedures, and record keeping. The DMC may call additional meetings whenever there 
are concerns regarding any aspect of the study. 
12.2. Clinical Events Committee 
This study will utilize a Clinical Events Committee (CEC) to review and adjudicate all reportable 
stimulation/therapy, procedure and device related (S)AEs and deaths for seriousness and relationship to 
the procedure, device, and therapy/stimulation using the definitions provided in Section 11.4.  The CEC 
Charter will define the CEC processes for member selection, meeting frequency, roles and 
responsibilities, procedures, and record keeping. 
Prior to making a final adjudication decision, the CEC may request clarification and/or additional 
information from the principal investigator who reported the event. If the conclusion of the review 
differs from the principal investigator’s assessment, both opinions will be reported back to the 
investigator and noted in the final study report. Incidence rates will be tabulated using the final CEC 
determination. 
13. Statistical Design and Methods 
13.1. General Aspects of Analysis 
The ADAPT-PD Trial will be considered successful when the primary objective of the study is met for one 
or both aDBS algorithms independently or the algorithms combined.  
The main analysis of the study objectives will use the Full Analysis Set (FAS) which includes all Primary 
Cohort subjects, using the intention-to-treat (ITT) principle, who initiate the aDBS Evaluation Phase using 
the randomized treatment assignment for each subject that was randomized and the programmable 
treatment assignment for those subjects that may only be configured to one aDBS mode (dual or single 
threshold).  
The main analysis will include data from all contributing geographies and centers. A poolability analysis 
for a center effect will be performed as described in Section 13.2.10.  
The subjects’ baseline status will be summarized with standard descriptive summary statistics, including 
counts and percentages for categorical variables, and mean, standard deviation for continuous 
variables. Safety data will be summarized as specified in Section 13.6.  
Subject disposition will be illustrated in a CONSORT diagram and attrition will be identified and 
summarized. 

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The handling of missing data for the primary and secondary objective is described generally in Section 
13.2.5 and also with each objective. Subgroup analyses are described in Section 4.1.4 
13.2. General Statistical Considerations 
Data analysis will be performed by Medtronic-employed statisticians or designees. A validated statistical 
software package will be used to analyze the study results. 
Additional details of the analyses outlined in this section will be described in a separate Statistical 
Analysis Plan prior to the data freeze for the Primary Analysis Report. Any deviations from this section 
and/or the Statistical Analysis Plan will be described and justified in the Primary Analysis Report, as 
appropriate or in an amended CIP, if applicable. 
13.2.1. 
Analysis sets 
All-Consented (AC): includes all subjects who properly signed the study-specific informed consent (IC). 
This patient set will be used to summarize patient disposition. 
Full Analysis Set (FAS): includes all Primary Cohort subjects, using the intention-to-treat (ITT) principle, 
who initiate the aDBS Evaluation Phase using the randomized treatment assignment for each subject 
that was randomized and the programmable treatment assignment for those subjects that may only be 
configured to one aDBS mode (dual or single threshold). 
As-Treated (AT): includes all Primary Cohort subjects who are treated with continuous Deep Brain 
Stimulation (cDBS) and/or adaptive Deep Brain Stimulation (aDBS) during the cDBS Baseline Evaluation 
Phase and/or the aDBS Evaluation Phase, and Long-term Follow-up Phase and uses the observed 
treatment used for each subject in each phase. 
All-Randomized (AR): includes all Primary Cohort subjects who were randomized in the aDBS Evaluation 
Phase, excludes those that were not configured to both modes. 
Complete-Case (CC): FAS without imputation that includes all Primary Cohort subjects who have 
available measures for the respective analysis and are analyzed in their randomization group for those 
randomized or the programmable treatment for those configured to one aDBS mode. 
Directional Stimulation As-Treated (DSAT): includes all Directional Stimulation Cohort subjects who have 
SenSight leads in a directional stimulation configuration who are treated with continuous Deep Brain 
Stimulation (cDBS) and/or adaptive Deep Brain Stimulation (aDBS) during the cDBS Baseline Evaluation 
Phase and/or the aDBS Evaluation Phase, and Long-term Follow-up Phase and uses the observed 
treatment used for each subject in each phase. 
Directional Stimulation Complete-Case (DSCC): includes all Directional Stimulation Cohort subjects who 
completed the aDBS Evaluation Phase. 

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13.2.2. 
Factors That May Compromise the Outcome or Interpretation of the 
Results 
Missing PD Home Diary Data 
PD Home Diary non-compliance or incorrect completion are most concerning in the assessment of the 
primary effectiveness objective. PD Home Diaries will be collected, regardless of completeness or 
accuracy of completion. PD Home Diaries and other efficacy data collected while the subject is in the 
wrong treatment assignment or stimulation is inactive will be included in analyses, following Section 
13.4.5. 
PD Home Diary compliance will be continuously monitored throughout the duration of the study to 
ensure that compliance is maintained.  
13.2.3. 
Familywise error rate and hypothesis testing 
The familywise error rate will be controlled using one-sided tests with an overall alpha-level of 0.025. 
Each primary hypothesis (one for each aDBS mode) will be assigned a Bonferroni corrected alpha 
(0.0125) for the respective primary hypothesis (0.025/2, see Section 13.4.1). The primary hypothesis will 
serve as a gatekeeper for the secondary hypothesis within each mode. 
13.2.4. 
Sample size rationale 
Since the device implant will occur outside of the study and the study requires participants to be stable 
on cDBS prior to enrollment, the standard deviation of the change from cDBS to aDBS in “On” time 
without troublesome dyskinesia will be used to establish a threshold for assessing the performance goal. 
The threshold will be set as 1 standard deviation. If the difference between aDBS and cDBS (aDBS-cDBS) 
for a subject is at least -1 standard deviation, the threshold will be met for the subject. Using this 
threshold, the proportion of subjects who exceed the threshold will be computed. 
The sample size was estimated using a binomial distribution for a one-sided exact test (alpha=0.0125) 
for a proportion (PASS 2011 module Tests for One Proportion [Differences]) to compare to a 
performance goal of 50%. Assuming the alternative hypothesis of 85% of subjects exceeding the 
threshold, a minimum of 36 subjects achieves at least 90% power to reject a performance goal of 50%. 
Simulations have shown that this sample size is sufficient to cover possible deviations from normality 
such as a uniform distribution. The threshold criterion will remain the same as the standard deviation is 
robust to moderate departures from normality. 
Sample size in the Primary Cohort may be increased to a maximum of 55 subjects for whom at least 1 
aDBS mode is acceptable and who enter the aDBS Evaluation Phase to obtain at least 8 subjects per 

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aDBS mode and 8 subjects per target site (STN/GPi). Criteria for increasing sample size is described in 
Section 13.2.6.  
For the safety analyses, a minimum of 30 subjects followed for approximately 30 days with aDBS out-of-
clinic in the subjects’ real-world environments provides at least 95% probability that all events with a 
true event rate of at least 10% would be reported at least once. 
It is estimated that approximately 70-100 subjects implanted with a commercially available Medtronic 
DBS system with Percept PC INS will be enrolled in the study to obtain 40 subjects for whom at least 1 
aDBS mode is acceptable and who enter the aDBS Evaluation Phase. Accounting for a 10% dropout 
during the aDBS Evaluation Phase, a minimum of 36 subjects (at least 8 per brain target site (STN/GPi) 
and 8 per aDBS mode) will complete the aDBS Evaluation phase. 
In addition, approximately 15 subjects implanted with a commercially available Medtronic DBS system 
with Percept PC INS and SenSight system will be enrolled in the Directional Stimulation Cohort to obtain 
9 subjects for whom at least 1 aDBS mode is acceptable and who enter the aDBS Evaluation Phase. 
Accounting for dropout during the aDBS Evaluation Phase, a minimum of 8 subjects will complete the 
aDBS Evaluation Phase.  
13.2.5. 
Handling of missing data 
All attempts will be made to minimize missing data. If 5% of the data or fewer are missing for the 
analysis, no imputation will be used.h Otherwise, if missing data are observed, multiple imputation will 
be used for the analysis of the primary and secondary objectives, as described in the objective sections 
below. If an aDBS mode is not programmable to a subject no imputation will occur for those subjects for 
that aDBS mode. 
Appropriate standard errors will be computed to account for the multiple imputations.i,j A Complete-
Case Analysis Set and As-Treated Analysis Set will be used for sensitivity analyses of the primary and 
secondary objective analyses.  
 
 
 
h Buhi, E, Goodson, P, Neilands T. Out of Sight, Not Out of Mind: Strategies for Handling Missing Data. Am J Health 
Behav. 2008 Jan-Feb;32(1):83-92, doi: 10.5555/ajhb.2008.32.1.83. 
i Rubin, D. B. (1976). “Inference and Missing Data.” Biometrika 63:581–592. 
j Rubin, D. B. (1987). Multiple Imputation for Nonresponse in Surveys. New York: John Wiley & Sons. 

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13.2.6. 
Interim sample size adjustment 
Sample size for the Primary Cohort may be increased to a maximum of 55 subjects based on 
acceptability of the aDBS modes during the aDBS Setup Phase and to ensure a minimum number of 
subjects in each target site (STN/GPi) as described in 13.2.9.  
13.2.7. 
Reports 
Annual reports of study progress and safety data will be provided. After all aDBS treated subjects in the 
Primary Cohort have reached the end of their aDBS Evaluation Phase (randomized or programmable 
mode) a Pre-Market Approval (PMA) supplement will be submitted to request FDA approval of aDBS; a 
Technical Document will be submitted to request TUV approval of aDBS. These requests will include 
available data through the final aDBS Evaluation Phase visit and any available safety data for those 
subjects in the long-term follow-up phase. A final study report, which will include data covering all 
phases of subject follow-up, will be prepared after all subjects have completed the study. 
13.2.8. 
Demographics and baseline variables 
Demographics and baseline characteristics will be summarized for the AC, FAS, and DSCC analysis sets.  
13.2.9. 
Pooling of aDBS mode 
Most planned analyses for the Primary Cohort are to be done separately for each mode. Summary 
statistics will be computed to summarize the percentage who were programmed to each mode and 
subject characteristics of each subgroup. If fewer than 24 subjects are programmed to one of the aDBS 
modes because aDBS is unacceptable as compared to cDBS (using the aDBS GIC), the evaluation of aDBS 
effectiveness will use data from the first period of the aDBS Evaluation Phase from all subjects. If the 
modes are considered poolable, the modes would be combined and the alpha level of the test would be 
alpha=0.025 (one-sided). To test for a treatment difference in the first period by aDBS mode group, 
subjects will be categorized based on the modes they are programmable to: aDBS – Dual Threshold only; 
aDBS – Single Threshold only; and aDBS – both modes. The Freeman and Halton’s extension of Fisher’s 
exact test will be computed testing for differences between aDBS modes in the proportion of subjects 
exceeding threshold for the primary outcome using data only from the first period. The same 
categorization of mode will be used and tested using F-tests using linear regression models for the 
secondary outcome measure. P-values >0.1 for the tests of association with aDBS mode group will be 
deemed as supporting the assumption of no aDBS mode group effect and the data will be considered 
poolable across aDBS mode groups. If the aDBS mode group factor approaches statistical significance 

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(defined as ≤0.1),k the data will not be considered poolable. A minimum of 8 subjects per aDBS mode 
will be required for the pooled analysis using the first period outcome data. 
If data are pooled, missing data observed in the cDBS Baseline Phase and aDBS Evaluation Period 1 will 
be imputed as described in 13.2.5.  
13.2.10. Center pooling 
All investigators in the proposed study will conduct the study according to a common protocol and 
utilize the same CRFs to collect study data. Throughout the trial, efforts will be made to ensure 
consistency among investigative sites in selection of patients and conduct of the study procedures.  In 
addition, site study personnel training will be conducted prior to initiation of the study at each site and 
periodic monitoring will be conducted by Medtronic to ensure compliance with protocol requirements. 
Data will be pooled across centers for all analyses. Each study center will stop enrollment in the Primary 
Cohort after they have identified a maximum of 8 subjects for whom at least 1 aDBS mode is acceptable 
and who enter the aDBS Evaluation Phase (~25% of the total planned number of subjects). For the 
Directional Stimulation Cohort, each study center will stop enrollment after they have identified a 
maximum of 5 subjects for whom at least 1 aDBS mode is acceptable and who enter the aDBS Evaluation 
Phase. The actual number of subjects at a study center may be slightly larger due to the number of 
subjects that are enrolled prior to cessation of enrollment. This restriction is intended to reduce the 
possibility that the results from one study center will be overly influential in the overall study results.  
Tests for a treatment difference in the Primary Cohort among centers are described in the supporting 
analyses of the objective sections below. When testing for differences between centers, centers with 5 
or more FAS subjects will each be tested as separate centers. Those with less than 5 FAS subjects will be 
combined into a “pooled” pseudo-center to minimize the impact of small samples on the analysis. If the 
pseudo-center contains more than 50% of the subjects, the centers will be combined into more than 
one pseudo-center. If more than one pseudo-center is needed, the centers will be randomly ordered 
and divided as near the midpoint as possible. If ambiguity between assigning a center to the first or 
second pseudo-center exits, the center will be assigned to the first pseudo-center. 
13.3. Analysis Execution 
A formal analysis for the ADAPT-PD Trial will occur when all active subjects in the Primary Cohort have 
completed the Evaluation Phase of the study. Analysis will include both the primary and secondary 
 
 
 
k Fleiss JL. The statistical basis of meta-analysis. Stat Methods Med Res. 1993; 2(2):121-45. 

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objectives. Additional objectives will be addressed based on available data. A final report will be 
prepared once all data collection has ended and all subjects have completed the Long-Term Follow-up 
Phase or have been exited. The inferential analysis for the primary and secondary objectives will not be 
updated for the final report. Additional objectives will be addressed based on complete data. 
13.4. Primary Objective 
To demonstrate that the proportion of aDBS subjects with “On” time without troublesome dyskinesia 
during the Evaluation Phase exceeds a performance goal of 50%. 
13.4.1. 
Hypothesis 
Two hypotheses are being tested for the primary objective in order to compare each aDBS mode relative 
to cDBS at baseline, separately. The alternative hypotheses are: 
• 
H11: The proportion of subjects with “On” time without troublesome dyskinesia during aDBS 
dual threshold mode Evaluation Period exceeding threshold > 50% 
• 
H21: The proportion of subjects with “On” time without troublesome dyskinesia during aDBS 
single threshold mode Evaluation Period exceeding threshold > 50% 
13.4.2. 
Endpoint definition 
The primary endpoint is the proportion of aDBS subjects with “On” time without troublesome dyskinesia 
that exceed threshold. This endpoint will combine the diary categories of “On” time without dyskinesia 
and “On” time with non-troublesome dyskinesia. Since the device implant will occur outside of the study 
and the study requires participants to be stable on cDBS, the within-subject standard deviation of the 
change between cDBS and DBS in “On” time without troublesome dyskinesia will be used to establish a 
threshold for assessing the performance goal. The threshold will be set as 1 standard deviation. If the 
difference between aDBS and cDBS (aDBS-cDBS) for a subject is at least -1 standard deviation, the 
threshold will be met for the subject. Using this threshold, the proportion of subjects who exceed the 
threshold will be computed. The primary endpoint proportion of subjects above threshold will be 
compared to a performance goal of 50% using a binomial exact test. The lower bound of the 97.5% 
confidence limit will also be presented. Data will be imputed as described in 13.2.5 prior to computing 
the mean “On” time without troublesome dyskinesia for all periods when using the FAS. 
Rationale for endpoint 
Continuous Deep Brain Stimulation (cDBS) is a proven FDA-approved therapy in the treatment of 
Parkinson’s disease symptoms. This study aims to show that aDBS is a viable optional feature that can 
provide similar benefit and safety to cDBS for some subjects. The primary endpoint for this study 
compares aDBS to cDBS directly for each subject to ensure some level of consistent comparability 

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between cDBS and aDBS. The endpoint of PD Home Diary was chosen to determine the threshold of 
success as it is a measure of the subject response to DBS therapy over time, the aDBS algorithm will 
adapt the therapy over time, and the PD Home Diary has been used as an endpoint in previous DBS 
trials.  
Rationale for 1 standard deviation threshold 
A unit of one standard deviation was chosen as it is an acceptable amount of statistical variability in the 
PD Home Diary endpoint given the fluctuating nature of Parkinson’s disease and the percentiles of a 
normal distribution. 
Rationale for 50% performance goal 
A performance goal of 50% was chosen for this study in order to demonstrate that at least 50% of the 
subjects are able to achieve the threshold with 95% confidence demonstrating some level of efficacy.   
13.4.3. 
Sample size justification 
The sample size justification for the primary objective is provided in Section 13.2.4. 
13.4.4. 
Analysis methods 
The primary analysis will use the FAS as described in Section 13.2.1 The PD Home Diary will be collected 
for at least 3 consecutive days (24 hour “periods”) prior to each visit to evaluate the primary objective. 
Complete diary periods collected anytime during the cDBS Baseline period will be used for analysis as 
subjects should be on stable cDBS stimulation from enrollment through the end of this period. In the 
aDBS Evaluation Phase, diary periods will be defined starting with the first completed diary record which 
is no more than 14 days prior to the visit. If diary is collected more than 14 days prior to the visit, the 
diary may be used for analysis if there is no change in aDBS stimulation settings. Complete diary periods 
are defined as any diary period where at least 21 hoursl (defined as 42 30-minute records) of diary were 
completed during the 24-hour period, and only complete periods will be used for analysis. If the diary is 
collected for more than 3 complete periods, up to 7 which are closest to the visit will be used for the 
 
 
 
l Neurostimulation for Parkinson's disease with early motor complications. Schuepbach WM, Rau J, Knudsen K, 
Volkmann J, Krack P, Timmermann L, Hälbig TD, Hesekamp H, Navarro SM, Meier N, Falk D, Mehdorn M, Paschen 
S, Maarouf M, Barbe MT, Fink GR, Kupsch A, Gruber D, Schneider GH, Seigneuret E, Kistner A, Chaynes P, Ory-
Magne F, Brefel Courbon C, Vesper J, Schnitzler A, Wojtecki L, Houeto JL, Bataille B, Maltête D, Damier P, Raoul S, 
Sixel-Doering F, Hellwig D, Gharabaghi A, Krüger R, Pinsker MO, Amtage F, Régis JM, Witjas T, Thobois S, Mertens 
P, Kloss M, Hartmann A, Oertel WH, Post B, Speelman H, Agid Y, Schade-Brittinger C, Deuschl G; EARLYSTIM Study 
Group. N Engl J Med. 2013 Feb 14;368(7):610-22. doi: 10.1056/NEJMoa1205158. 

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analysis, while if a subject has zero complete periods, their diary will be considered missing. Diaries with 
at least 1 complete period available will be used for analysis. Data from non-contiguous complete 
periods may be used in the analysis. 
The change in daily “On” time without troublesome dyskinesia from cDBS to aDBS will be computed for 
each subject. The overall standard deviation of the change will be computed for the FAS. The threshold 
will be set as 1 standard deviation. If the difference between aDBS and cDBS (aDBS-cDBS) for each 
subject is at least -1 standard deviation, the threshold will be met for the subject. Using this threshold, 
the proportion of subjects who exceed the threshold will be computed. The proportion with “On” time 
without troublesome dyskinesia during the respective aDBS Evaluation Period that exceed the threshold 
will be compared to the performance goal of 50% for each aDBS mode separately using a binomial exact 
test. The objective will be considered passed if the p-value is less than 0.0125. The lower bound of the 
97.5% confidence interval will also be presented.  
13.4.5. 
Handling of missing data 
All attempts will be made to minimize missing data. If 5% of the data or fewer are missing (as defined in 
Section 13.4.4) for the analysis, no imputation will be used and the data will be analyzed as specified in 
the previous section. Otherwise, if missing data are observed, multiple imputation will be used for the 
analysis of the key primary objective.  
Prior to the MI, the distribution of the continuous variables will be assessed for normality (using the 
Shapiro-Wilk test) to determine whether regression (P≥0.05) or predictive mean matching (P<0.05) 
multiple imputation will be used for each variable. First, multiple imputation will be applied to impute 
missing values in continuous hours of “On” time without troublesome dyskinesia for each mode 
separately (aDBS single threshold, aDBS dual threshold). Variables for target site (STN or GPi) and cDBS 
hours of “On” time without troublesome dyskinesia will be considered for the model. The fully 
conditional specification (FCS) method within SAS (version 9.4 or higher) with 5 repetitions and 100 
burn-in iterations will be used for imputation. No limits will be defined for imputed values. Following 
imputation, the “On” time without troublesome dyskinesia will be assessed against the “On” time 
threshold, and the estimate for the proportion of subjects meeting threshold will be determined for 
each imputation and combined using MI analysis methods. The lower bound of the 97.5% confidence 
limit will be determined from the MI Clopper-Pearson mean success approachm.  In addition, the 
 
 
 
m Mandan, Arpita (2018). Two Applications of Summary Statistics: Integrating Information Across Genes and 
Confidence Intervals With Missing Data. Master's thesis, Duke University. Retrieved 
from https://hdl.handle.net/10161/17533 

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objective will be tested by comparing the lower bound to 50% for each imputation, and the overall p-
value will be computed as the median of the p-values from the multiply imputed datasets.n 
13.4.6. 
Supporting analyses 
Supporting analyses for the primary objective in the Primary Cohort include verifying the lack of a period 
or carryover effect (randomized subjects only), a target site effect (STN/GPi), a lead type effect (legacy 
Models 3387 and 3389 compared to SenSight Models B33005 and B33015), or a center effect. 
Summarized results from the Directional Stimulation Cohort will be provided as supporting analyses to 
the Primary Cohort results. In addition, sensitivity analyses will be conducted using the CC and the AT 
Analysis Set. 
An analogy of Prescott’s testo will be computed to test for a period or carryover effect and p-values >0.1 
will be deemed as supporting the assumption of no period or carryover effect in the proportion of 
subjects exceeding threshold for the primary outcome using data from both periods. If the assumption 
of no period or carryover effect is accepted, target site (STN/GPi), lead type, and center pooling 
assessments will be made using data from all subjects treated with aDBS in the aDBS evaluation phase. If 
a period effect exists, only data from the first period will be used for the analysis. 
To test for a treatment difference by target site (STN/GPi), lead type, and center within each mode, 
Fisher’s exact test and Freeman and Halton’s extension of Fisher’s exact test, respectively, will be 
computed testing for differences between target sites, lead type, or centers in the proportion of 
subjects exceeding threshold for the primary outcome using data from both periods. P-values >0.1 will 
be deemed as supporting the assumption of no target site effect, lead type effect, or center effect, 
respectively, and the data will be considered poolable across the respective variable. If the p-value 
approaches statistical significance (defined as ≤0.1),k the proportion exceeding threshold and the lower 
bound of the 97.5% confidence interval will also be estimated at each target site, lead type, or center, as 
applicable (eg, if the target sites (STN/GPi) do not allow for pooling the analysis will be conducted by 
target site for that mode.) 
If center(s) causing the significance are identified, variables relating to patient characteristics and other 
factors will be analyzed to try to identify why this center is showing a different treatment effect.  
 
 
 
n Ekhout, I., van de Wiel, M.A., and Heymans, M.W. (2017), Methods for significance testing of categorical 
covariates in logistic regression models after multiple imputation: power and applicability analysis. BMC Med. Res. 
Methodol.17: 129. doi: 10.1186/s12874-017-0404-7 
o Nagelkerke, N.J.D., Hart, A.A.M. and Oosting, J. (1986), The Two Period Binary Response Cross‐Over Trial. Biom. 
J., 28: 863-869. doi:10.1002/bimj.4710280715 

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As part of the additional objectives, “On” time without troublesome dyskinesia will be summarized as 
absolute change from cDBS Baseline Phase to the Evaluation Phase.  
13.5. Secondary Objective 
13.5.1. 
Secondary Objective 
To demonstrate decreased stimulation energy use during the aDBS Evaluation Phase as compared with 
cDBS. 
13.5.2. 
Hypothesis 
Two secondary hypotheses are being tested using independent gatekeeper procedures to control the 
alpha-level as described in Section 13.4.1. The two secondary alternative hypotheses comparing aDBS 
(Evaluation Phase) to cDBS (Baseline Phase) separately, are: 
• 
H12: Mean Difference between aDBS dual threshold (Evaluation Phase) minus cDBS (Baseline 
Phase) for TEED < 0 
• 
H22: Mean Difference between aDBS single threshold (Evaluation Phase) minus cDBS (Baseline 
Phase) for TEED < 0 
13.5.3. 
Endpoint definition 
The secondary endpoint is to decrease energy use as measured by TEED during the aDBS Evaluation 
Phase as compared with TEED during the cDBS Baseline Phase. The Total TEED will be calculated as a 
sum of the energy use in the left and right leads.  There will be one value per patient for each mode 
evaluated (eg, cDBS, aDBS Dual Threshold, aDBS Single Threshold). 
The reduction in TEED will be calculated as: 
TEED ΔaDBS dual threshold mode = TEEDaDBS dual threshold mode – TEEDcDBS 
and 
TEED ΔaDBS single threshold mode = TEEDaDBS single threshold mode – TEEDcDBS 
Computing TEED in cDBS 
To compute TEED using the formula in Section 9.15.2 in the cDBS mode, the current drain, pulse-width, 
frequency, and impedance will be determined from the JSON session data at the cDBS Baseline visit.  
Computing TEED in aDBS 
To compute TEED using the formula in Section 9.15.2 in an aDBS mode, the average current drain from 
the JSON session data will be computed using the average stimulation currents from the timeline 
feature. This will be computed as the average of the currents from the timeline feature using the epochs 

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that align with the analysis set (e.g., As-Treated analysis set uses the actual aDBS mode as reported from 
the device). Included days should be in the 14 days prior to the visit. The pulse-width, frequency, and 
impedance will be determined from the JSON session data at the aDBS Evaluation visit.  
Impedance  
Leads programmed with monopolar settings will use the electrode unipolar impedance between the 
case and the active electrode. If 2 cathodes are used (dual monopolar settings), TEED will be calculated 
for each contact separately, and total TEED will be determined for the lead as the sum of the two TEED. 
Leads programmed to bipolar will use the impedance between the active electrodes. In case electrode 
impedance was not collected at cDBS Baseline or aDBS Evaluation Phase, impedance from aDBS Setup 
would be used. 
13.5.4. 
Sample Size justification 
The sample size was estimated using a one-sided test (alpha=0.0125) for one mean (PASS 2011 module 
Tests for One Mean) to compare the difference in aDBS TEED to cDBS TEED of 22 and a standard 
deviation of 35, a minimum of 36 subjects achieves at least 90% power. 
Based on the registry data and the bench testing, a conservative estimate based on the first quartile of 
TEED data for initial devices in the registry, TEED is expected to decrease 35 and 22 units for aDBS single 
threshold mode and aDBS dual threshold mode, respectively. A SD of 36 results in a medium to large 
effect size of 0.629. 
13.5.5. 
Analysis methods 
The secondary analysis will use the FAS Analysis Set as described in Section 13.2.1. Change in TEED will 
be used to evaluate the secondary objective. A paired t-test will be used to compare the difference in 
TEED for each aDBS mode (Evaluation Phase) to cDBS (Baseline Phase), separately. Normality of the 
outcome will be assessed with the Shapiro-Wilk test. If large violations to the normality assumption are 
observed (p<0.05), the primary analysis will use a Wilcoxon signed-rank test to assess statistical 
significance. 
13.5.6. 
Handling of missing data 
All attempts will be made to minimize missing data. If 5% of the data or fewer are missing for the 
analysis, no imputation will be used and the data will be analyzed as specified in the previous section. 
Otherwise, if missing data are observed, multiple imputation will be used for the analysis of the 
secondary objective.  
Prior to the MI, the distribution of the continuous variables will be assessed for normality (using the 
Shapiro-Wilk test) to determine whether regression (P≥0.05) or predictive mean matching (P<0.05) 

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multiple imputation will be used for each variable. First, multiple imputation will be applied to impute 
missing values in TEED for each mode separately (aDBS single threshold, aDBS dual threshold). Variables 
for target site (STN or GPi) and cDBS TEED will be included in the model. The fully conditional 
specification (FCS) method within SAS (version 9.4 or higher) with 5 repetitions and 100 burn-in 
iterations will be used for imputation. No limits will be defined for imputed values. Following 
imputation, the mean and standard error of the change in TEED will be determined for each imputation 
and combined using MI analysis and tested with a t-statistic comparing the value to no change. 
13.5.7. 
Supporting analyses 
Supporting analyses for the secondary objective in the Primary Cohort include verifying the lack of a 
period or carryover effect (randomized subjects only), tests for poolability by target site (STN/GPi), tests 
for poolability by lead type (legacy Models 3387 and 3389 compared to SenSight Models B33005 and 
B33015), and tests for poolability by center. The test for a carryover effect will use a two-sample t-test, 
all other supporting analysis tests will use linear regression models. In addition, results from the 
Directional Stimulation Cohort will be described as a supportive analysis. The test of no period or 
carryover effect will be computed first, and if the assumption of no period or carryover effect is 
accepted, data from both periods from all subjects treated with aDBS in the aDBS Evaluation Phase will 
be used for the models to assess poolability by target site, lead type, and center. The models will use the 
change between aDBS and cDBS and include an intercept and a covariate for the respective parameter. 
P-values >0.1 for the terms testing the effect of the respective parameters will be deemed as supporting 
the assumption of no period or carryover effect, target site effect, lead type effect, or center effect, 
respectively, and the data will be considered poolable across the respective variable. Normality of the 
outcome will be assessed with the Shapiro-Wilk test. If large violations to the normality assumption are 
observed (p<0.05), the secondary endpoint may be transformed (e.g., log-transformation) or apply non-
parametric method for the supporting analyses. 
In addition, sensitivity analyses will be conducted using the CC and AT Analysis Sets without imputation.  
13.6. Safety Assessment 
The safety assessment is to characterize: 
• 
Stimulation-related adverse events during the aDBS evaluation and the cDBS baseline phases. 
• 
Serious adverse events, adverse events, and device deficiencies throughout the study. 
Stimulation-related adverse events will be summarized during the cDBS Baseline and aDBS Evaluation 
Phases for all subjects, with tabulations individualized by aDBS mode in the Primary Cohort, by target 
site in the Primary Cohort, by lead type in the Primary Cohort, and the Directional Stimulation Cohort 
(DSAT analysis set). Summarized results from the Directional Stimulation Cohort will be provided as 
supporting analyses to the Primary Cohort results. In the Primary Cohort, if statistical comparisons of 

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poolability across mode, lead type, and target site are accepted, overall tabulations will be provided as 
appropriate. To test for a difference in safety by target site (STN/GPi) and lead type, Fisher’s exact test 
will be computed testing for differences between target sites and lead types in the proportion of 
subjects with a stimulation-related adverse event during the aDBS evaluation phase using data from 
both periods. A repeated measures logistic regression model will be used to test for a difference 
between aDBS modes in the proportion of subjects with stimulation-related adverse events.  P-values 
>0.1 will be deemed as supporting the assumption of no target site, lead type, or mode effect, 
respectively, and the data will be considered poolable across the respective variable. If the p-value 
approaches statistical significance (defined as ≤0.1),k safety summaries will not be provided as a 
combined summary for that variable.   
Serious adverse events, adverse events, and device deficiencies that occur from the time of enrollment 
through study exit/discontinuation will be summarized for all enrolled subjects. The denominator will 
include the appropriate number of subjects for each respective phase and period. Events will be 
summarized by number of events, number of subjects who experienced the event, and percentage of 
subjects who experienced the event.  
13.7. Additional Objectives 
To characterize each aDBS mode as compared to cDBS, the additional objectives described in Section 
4.1.4 will be evaluated for the FAS separately for each aDBS mode. In addition, the subgroup analyses as 
described in Section 4.1.4 will be performed for the FAS and DSAT. 
Summary statistics will be presented for continuous measures (N, means, medians, standard deviations, 
minimums and maximums) and categorical measures (N, percentage, frequency distributions) with 95% 
confidence intervals as appropriate.  No adjustment will be made for multiple testing of the additional 
study objectives. 
13.8. Minimization of Bias 
Selection of subjects, treatment of subjects, and evaluation of study data are potential sources of bias. 
Methods incorporated in the study design to minimize potential bias include (but are not limited to):  
• 
Single-blind of subjects during the Evaluation Phase 
• 
Randomized crossover to evaluate the dual threshold and single threshold modes  
In summary, potential sources of bias that may be encountered in this study have been considered and 
minimized by careful study design. 
14. Ethics 

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14.1. Statement(s) of Compliance  
This study will be conducted in compliance with international ethical and scientific quality standards, 
known as GCP. GCP includes review and approval by an independent EC before initiating a study, 
continuing review of an ongoing study by an EC, and obtaining and documenting the freely given 
informed consent of a subject before initiating the study. 
The ADAPT-PD Trial was designed to reflect the Good Clinical Practice (GCP) principles outlined in ISO 
14155:2020 and other international clinical requirements outlined below. These include the protection 
of the rights, safety and well-being of human subjects, controls to ensure the scientific conduct and 
credibility of the clinical investigation and the definition of responsibilities of the sponsor and 
investigators. In accordance with ISO 14155:2020, the sponsor shall avoid improper influence on, or 
inducement of, the subject, monitor, any investigator(s) or other parties participating in, or contributing 
to, the clinical investigation. All investigators shall avoid improper influence on or inducement of the 
subject, sponsor, monitor, other investigator(s) or other parties participating in or contributing to the 
clinical investigation. AE and DD handling in the ADAPT-PD Trial is ISO 14155:2020 compliant for all 
participating geographies.  
The principles of the DoH have been implemented through the IC process, EC approval, study training, 
clinical trial registration, pre-clinical testing, risk-benefit assessment and publication policy.  
Ultimately, all study sites in all geographies will follow and comply with: 
• 
Principles of DoH 
• 
ISO 14155:2020 
• 
21 CFR Part 11 (Electronic Records, Electronic Signatures) 
• 
21 CFR Part 54 (Financial Disclosure by Clinical Investigators) 
• 
The CTA 
• 
The procedures described within this CIP 
• 
Local IRB/EC Requirements 
• 
Local regulatory authority requirements 
In addition to the regulatory requirements outlined above, the study will be conducted according to 
federal, national and local laws, regulations, standards, and requirements of the countries/geographies 
where the study is being conducted. These include but are not limited to:  
• 
In the United States, the study will be conducted under an FDA IDE in compliance with 
21 CFR Parts: 
 
50: Protection of Human Subjects 
 
54: Financial Disclosure by Clinical Investigators 
 
56: IRBs 
 
812: IDEs 
• 
In Canada, SOR/98-282, section 59-88 will be followed and Mandatory Problem 
Reporting 59(1), 59(2), 60 (1)). 

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• 
In Europe the study will be conducted in compliance with the AIMDD 90/385/EEC and  
EU MDR 2017/745, and DoH version 2013.  
The study will be publicly registered prior to the first enrollment in accordance with the 2007 FDAAA 
and DoH on http://clinicaltrials.gov (PL 110-85, section 810(a)). In addition, the study may be registered 
in local regulatory databases where required by local law.  
Study investigators will be required to sign and date an investigator agreement or CIP signature page 
stating their intent to adhere to applicable regulations. 
Approval of the CIP and CIP amendments is required from the following groups prior to any study 
procedures at a study site: 
• 
Medtronic 
• 
Principal Investigators (where required by local law/regulations) 
• 
Geography-specific regulatory authorities (if regulatory approval is required) 
• 
An independent medical EC or IRB. 
Similarly, approval of subsequent revisions to the CIP is required at each study site from the above-
mentioned groups prior to implementation of the revised CIP at the study site. 
Medtronic contracts with participating institutions/investigators through a Clinical Trial Agreement that 
defines the scope and responsibilities and associated compensation related to carrying out the 
obligations under a clinical study sponsored by Medtronic.  
15. Study Administration 
15.1. Monitoring  
It is the responsibility of Medtronic to ensure proper monitoring of this study.  Trained Medtronic 
personnel or delegates appointed by Medtronic may perform study monitoring at the study site in order 
to ensure that the study is conducted in accordance with the CIP, the CTA, and the applicable regulatory 
and local requirements. Medtronic, or delegates, must therefore be allowed direct access to the 
subjects’ case histories (all clinic and hospital records, and other source data/documentation) upon 
request as per the IC, Research Authorization (where applicable) and CTA.  The principal investigator 
should also be available during monitoring visits.   
Contact information for the study monitoring: 
Medtronic Clinical & Regulatory Solutions 
8200 Coral Sea Street, N.E., MVS33 
Mounds View, MN 55112 

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15.1.1. 
Monitoring Visits 
Frequency of monitoring visits may be based upon subject enrollment, study compliance, number of 
adverse events, number of deviations, observations from previous monitoring visits and any suspected 
inconsistency in data that requires investigation. Regulatory documents will be reviewed at each study 
site. Monitoring for the study including site initiation visits, interim monitoring visits, and closeout visits, 
will be done in accordance to the study-specific monitoring plan. 
Monitoring visits may be conducted periodically to assess study site progress, the investigator’s 
adherence to the CIP, regulatory compliance including but not limited to IRB/EC approval and review of 
the study, maintenance of records and reports, and review of source documents against subject CRFs in 
accordance to the study-specific monitoring plan. Monitors review study site regulatory and study 
compliance by identifying observations of non-compliance and communicating those observations along 
with recommendations for preventative/corrective actions to study site personnel.  Monitors may work 
with study personnel to determine appropriate corrective action recommendations and to identify 
trends within the study or at a particular study site. 
15.2. Data Management 
Medtronic personnel will perform routine edit and consistency checks for items such as missing data or 
inconsistent data. Identified data inconsistencies will be resolved by use of data discrepancies; 
investigators and center personnel will review data discrepancies and respond to the discrepancies in a 
timely manner. The resolved discrepancy will become a part of the CRF record for the subject. 
The Oracle Clinical Remote Data Capture (RDC) system is a fully validated system and 21CFR§11 
compliant. The RDC system controls user access, ensures data integrity, and maintains an audit trail of 
entries, and changes, and corrections in the CRFs. User access will be granted to each individual based 
on his or her delegation of authority for the study and completion of the required training. 
CRF data will be stored in a secure, password-protected database which will be backed up nightly.  Data 
will be reviewed using programmed and manual data checks.  Data queries will be made available to 
study sites for resolution.  Study management reports may be generated to monitor data quality and 
study progress.  At the end of the study, the data will be frozen and will be retained by Medtronic in 
accordance with applicable local regulations. 
The Principal Investigator, or designated representative, is responsible for the accuracy, completeness 
and timeliness of the data submitted and must review all data for accuracy and provide his/her approval 
of the CRF and sign each form with an electronic signature. If a person only authorized to complete CRFs 
makes changes to an already signed CRF, the system will require the principal investigator, or authorized 
delegate, to re-sign the CRF. 

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All records and other information about subjects participating in this study will be treated as 
confidential. Data will be transferred and processed by Medtronic or a third party designated by 
Medtronic in a key coded form.     
Procedures in the CIP require source documentation. Source documentation will be maintained at the 
study site. Source documents, which may include worksheets, subject medical records, programmer 
printouts, and interrogation files, must be created and maintained by the investigational study site 
team.  
The investigator will clearly mark clinical records to indicate that the subject is enrolled in this clinical 
investigation.  
The data reported on the CRFs shall be derived from source documents and be consistent with these 
source documents, and any discrepancies shall be explained in writing.  
Device data, including BrainSense data, will be uploaded to secure servers.  Upon receipt, device data 
will be maintained in the NPU database and retrieved for analysis and reporting. 
GKC will store information collected by the wearables and provide this data to Medtronic for use in 
analysis.   
15.3. Direct Access to Source Data/Documents  
Medtronic or third-party auditors representing Medtronic may perform clinical center audits to verify 
the performance of the monitoring process and study conduct, and to ensure compliance with 
applicable regulations. IRBs/ECs, representatives for regulatory bodies such as the FDA, CA and Notified 
Body may also perform center inspections related to this clinical study. The investigator and/or 
institution shall permit Medtronic, IRBs/ECs and RAs direct access to source data and documents during 
monitoring, audits and regulatory inspections. 
15.4. Confidentiality 
Subject confidentiality is assured through use of subject identification numbers, and the de-identifying 
of photocopies or records obtained by the Sponsor. In addition to the review of records at the center, 
release of de-identified records to Medtronic may be necessary, such as in the evaluation of adverse 
events. The investigational center personnel must de-identify and label source documentation with the 
subject’s study-specific identification number prior to submission to Medtronic. 
Data relating to the study might be made available to third parties (for example in case of an audit 
performed by RA), provided the data are treated as confidential and that the subject’s privacy is 
guaranteed. No identifiable subject information will be published. 

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Health Insurance Portability and Accountability Act (HIPAA) language will be required to be included at 
every center in the United States. HIPAA language may be included within the IC according to the 
center’s policy. 
15.5. Liability/Insurance Information 
The compensation and covered liability associated with this study conduct will be documented in a 
separate financial agreement signed by Medtronic, the Principal Investigator, and/or the management 
of study site/institution. Medtronic maintains appropriate clinical study liability insurance coverage as 
required under applicable laws and regulations and will comply with applicable local law and custom 
concerning specific insurance coverage. If required, a Clinical Trial insurance statement/certificate will 
be provided to the IRB/EC. 
15.5.1. 
Insurance (Canada) 
Medtronic of Canada Ltd. is a wholly owned subsidiary of Medtronic, which as the parent company of 
such entity maintains appropriate general liability insurance coverage as required under applicable laws 
and regulations and will comply with applicable local law and custom concerning specific insurance 
coverage. If required, a General Liability insurance statement/certificate will be provided to the EC. 
15.5.2. 
Insurance (Europe) 
Medtronic Bakken Research Site B.V. is a wholly owned subsidiary of Medtronic, which as the parent 
company of such entity maintains appropriate clinical study liability insurance coverage as required 
under applicable laws and regulations and will comply with applicable local law and custom concerning 
specific insurance coverage. If required, a Clinical Trial insurance statement/certificate will be provided 
to the EC. 
15.6. CIP Amendments 
Clinical investigation plan amendments may be initiated by Medtronic to address changes to the scope 
or conduct of the study. Protocol amendments will be submitted to the appropriate regulatory 
authorities for their approval, if required, and to the IRBs/ECs. Prior to a study center’s implementation 
of a CIP amendment and/or associated changes to the IC, approval must be obtained, in writing, by the 
reviewing IRB/EC and Medtronic except: 
• 
When necessary to eliminate an immediate/or apparent immediate hazard to participating 
subjects 
• 
When the change involves purely administrative or logistical aspects of the study  

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15.7. Record Retention 
The principal investigator is responsible for ensuring that all essential study documentation is retained 
and accessible for a minimum of 2 years after the date the investigation is completed or terminated or 
the records are no longer required to support a marketing application (or longer in compliance to local 
requirements). The retention period may be longer if required by Medtronic or local or global regulatory 
requirements. Medtronic will not store any personal data longer than necessary and always in line with 
the required storage periods defined by the applicable laws.  
The principal investigator will ensure that essential study documents are not destroyed until written 
permission has been obtained from Medtronic. The investigator should take measures to prevent 
accidental or premature destruction of documents. Medtronic will be notified in writing prior to the 
transfer of study documentation. 
Medtronic will retain the study records according to Medtronic corporate policy and record retention 
schedule. 
15.7.1. 
Investigator Records 
At a minimum, the investigator is responsible for the preparation, review, and retention of the records 
listed below. The below records pertaining to the study, with the exception of case history records and 
case report forms, should be kept in the Investigator Site File (i.e., the study binder provided to the 
investigator) or Subject Study Binder. CRFs must be maintained and signed electronically within the 
electronic data capture system during the study. The following records are subject to inspection and 
must be retained for a period of two years (or longer as local law or hospital administration requires) 
after product approval or the date on which the investigation is terminated or the date that the records 
are no longer required for purposes of supporting a pre-market approval application. 
• 
Correspondence with another investigator, an IRB/EC, the sponsor, a monitor or regulatory body 
(eg, FDA, CA, Notified Body) including required reports  
• 
Device receipt/use/disposition records (i.e., product accountability) 
• 
Records of each subject’s case history and exposure to the device. Case histories include the 
CRFs and supporting data (source documentation), such as: 
o Signed and dated IC (In U.S. and Canada, signed by subject. In Europe, Middle East, 
Africa, signed by subject and investigator) 
o Observations of AEs/ADEs/DDs 
o Medical records, including, for example, progress notes of the physicians, the subject’s 
hospital and clinic chart(s) and the nurse’s notes 
• 
Subject Screening log and Enrollment log  
• 
Signed and dated CTA 
• 
Signed investigator agreement 

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• 
Current Curriculum vitae of principal investigators and key members of investigation study site 
team  
• 
Documentation of delegated tasks 
• 
IRB/EC approval documentation. Written information that the investigator or other study staff, 
when member of the IRB/EC, did not participate in the approval process. Approval 
documentation must include the IRBs/ECs composition, where required per local law.  
• 
RA notification, correspondence and approval, where required per local law.  
• 
All approved versions of the CIP, IC and IB/Report of Prior Investigations 
• 
Signed financial disclosure forms for all investigators 
• 
Study personnel training records 
• 
Insurance certificates (Europe and Canada only) 
• 
Final Study Report including the statistical analysis 
A list of the study sponsor staff, and a list of the investigator names, emergency contact details, 
addresses and professional positions of the principal clinical investigators will be kept separately from 
the CIP. The sponsor will maintain updated lists. 
15.7.2. 
Sponsor Records 
Medtronic shall maintain the following accurate, complete, and current records:  
• 
All correspondence which pertains to the investigation  
• 
Investigational device traceability record containing Model and serial numbers of devices, 
shipping date and name and address of person that received shipped device, location (if 
different than person shipped to), transfer and receipt by Medtronic dates.  
• 
Sample of label attached to investigational device  
• 
Signed Investigator Trial Agreements, FD (if applicable) and current CV of principal investigator 
and key members of the investigation study site team (as required by local law), delegated task 
list  
• 
All approved IC templates, and other information provided to the subjects and advertisements, 
including translations  
• 
Randomization records  
• 
Copies of all IRB/EC approval letters and relevant IRB/EC correspondence and IRB/EC voting 
list/roster/letter of assurance  
• 
Names of the institutions in which the study will be conducted  
• 
RA correspondence, notification and approval as required by national legislation  
• 
Insurance certificates (Europe, Canada)  
• 
Names/contact addresses of monitors  
• 
Monitoring visit reports  
• 
Statistical analyses and underlying supporting data  
• 
Final report of the study  
• 
The CIP, IB and study related reports, and revisions  
• 
Study training records for study site personnel and Medtronic personnel involved in the study  

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• 
Any other records that local regulatory agencies require to be maintained.  
Medtronic records and reports will be maintained in a password-protected document management 
system, and paper documents (where applicable) will be stored in stored in secured file cabinets at 
Medtronic during the course of this study.  
After closure of the study Medtronic will archive records and reports in accordance with the required 
storage periods defined by the applicable laws. 
15.8. Reporting Requirements 
15.8.1. 
Investigator Reports 
The investigator is responsible for the preparation (review and signature) and submission to the sponsor 
of all case report forms, adverse events and adverse device effects (reported per the country-specific 
collection requirements), device deficiencies, deaths, and any deviations from the clinical investigation 
plan.  If any action is taken by an IRB/EC with respect to this study, copies of all pertinent 
documentation must be forwarded to Medtronic in a timely manner. Reports are subject to inspection 
and to the retention requirements as described above for investigator records.  
Safety reporting requirements are listed in Table 9. The investigator shall prepare and submit in a 
complete, accurate and timely manner the applicable reports listed in this section (Table 10, Table 11 
and Table 12).

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Table 10: Investigator reports applicable for all geographies per Medtronic requirements 
Report  
Submit to 
Description/Constraints 
Withdrawal of IRB/EC 
approval 
Sponsor and Relevant 
Authorities 
The investigator must report a withdrawal of approval by the reviewing IRB/EC of the 
investigator’s part of the investigation within 5 working days. 
Study Deviations  
Sponsor and IRB/EC  
Any deviation from the clinical investigational plan shall be recorded together with the 
explanation of the deviation. 
Notice of deviations from the CIP to protect the life or physical well-being of a subject in 
an emergency shall be given as soon as possible, but no later than 5 working days after the 
emergency occurred.  Except in such emergency, prior approval is required for changes in 
the plan or deviations.  
IRBs/ECs will be notified only if required by local laws or by the IRB/EC. 
Final Report 
IRBs/ECs and Relevant 
Authorities 
This report must be submitted within 3 months of study completion or termination. 

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Table 11: Additional Investigator reports applicable to the United States per FDA regulations 
Report  
Submit to 
Description/Constraints 
Withdrawal of IRB/EC 
approval (either 
suspension or termination) 
Sponsor 
The investigator must report a withdrawal of approval by the reviewing IRB/EC of the 
investigator’s part of the investigation within 5 working days.  (21 CFR 812.150(a)(2)) 
Progress report  
Sponsor and IRB/EC 
The investigator must submit this report to the sponsor and IRB/EC at regular intervals, 
but in no event less than yearly intervals. (21 CFR 812.150 (a)(3)).   
Study deviations  
Sponsor and IRB/EC 
Notice of deviations from the CIP to protect the life or physical wellbeing of a subject in an 
emergency shall be given as soon as possible, but no later than 5 working days after the 
emergency occurred.  Except in such emergency, prior approval is required for changes in 
the plan or deviations.  If the deviation may affect the scientific soundness of the plan or 
the rights, safety and welfare of the subjects, the deviation must be approved by 
Medtronic, the IRB/EC, and the FDA/applicable RA.  If the deviation does not affect these 
issues then only Medtronic must approve it.  (21 CFR 812.150(a)(4)) 
Failure to obtain IC prior to 
investigational device use Sponsor and IRBs/ECs 
If an investigator uses a device without obtaining IC, the investigator shall report such use 
within 5 working days after device use.  (21 CFR 812.150(a)(5)) 
Final report 
Sponsor, IRBs/ECs and 
Relevant Authorities 
This report must be submitted within 3 months of study completion or termination of the 
investigation or completion or termination of the investigator’s part of the investigation.  
(21 CFR 812.150(a)(6)) 
Other 
IRB/EC and FDA 
An investigator shall, upon request by a reviewing IRB/EC, FDA or any other RA, provide 
accurate, complete, and current information about any aspect of the investigation. (21 CFR 
812.150(a)(7)) 
 
 
 

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Table 12: Investigator reports applicable to Europe, Middle East and Africa per ISO 14155 
Report  
Submit to 
Description/Constraints 
Withdrawal of IRB/EC 
approval 
Sponsor 
Report if required by local law. 
Progress Report  
Sponsor IRB/EC 
Provide if required by local law or IRB/EC.  
Study Deviations  
Sponsor, Competent 
Authority and IRB/EC 
Any deviation from the CIP shall be recorded together with an explanation for the 
deviation.  Deviations shall be reported to the sponsor who is responsible for analyzing 
them and assessing their significance.   
Note: When required, ECs, CAs or the appropriate RAs should be informed by sponsor. 
(ISO 14155:2020) 
Failure to obtain IC 
Sponsor and IRBs/ECs 
IC shall be obtained in writing and documented before a subject is enrolled into the clinical 
investigation.  (ISO 14155:2020) 
15.8.2. 
Sponsor Reports 
Medtronic shall prepare and submit the following complete, accurate, and timely reports listed in the tables below (by geography).  In addition to 
the reports listed below, Medtronic shall, upon request of the reviewing IRB/EC, RA or FDA, provide accurate, complete and current information 
about any aspect of the investigation.  
Table 13: Sponsor reports for Canada 
Report  
Submit to 
Description/Constraints 
Premature termination or 
suspension of the clinical 
investigation 
Investigators, IRB/EC, 
Relevant regulatory 
authorities, and  
Head of the Institution 
Provide prompt notification of termination or suspension and reason(s).  

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Report  
Submit to 
Description/Constraints 
Recall and device 
disposition 
Investigators, Head of 
Institution, IRB/EC, relevant 
authorities, and Health 
Canada 
Notification within 30 working days and will include the reasons for any request that an 
investigator return, repair, or otherwise dispose of any devices.   
Study deviation  
Investigators 
Ensure that all deviations from the CIP are reviewed with the appropriate clinical 
investigator(s), are reported on the CRFs and the final report of the clinical investigation.  
Study center specific study deviations will be submitted to investigators periodically.   
Table 14: Sponsor reports for Europe, Middle East and Africa 
Report  
Submit to 
Description/Constraints 
Normal closure of the 
clinical investigation 
Investigators, IRB/EC, and 
Relevant regulatory 
authorities (if applicable) 
Provide prompt notification of national/global study closure. 
Premature termination or 
suspension of the clinical 
investigation 
Investigators, IRB/EC, 
Relevant regulatory 
authorities and Head of the 
Institution 
Provide prompt notification of termination or suspension and reason(s). (ISO 14155:2020) 
Withdrawal of IRB/EC 
approval 
Investigators, Head of 
Institution, and relevant 
regulatory authorities 
Investigators, IRBs/ECs will be notified only if required by local laws or by the IRB/EC. 
Withdrawal of CA approval Investigators, Head of 
Institution, IRB/EC 
Investigators, IRBs/ECs will be notified only if required by local laws or by the IRB/EC. 

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Report  
Submit to 
Description/Constraints 
Progress Reports 
IRB/EC and Regulatory 
authorities 
This will be submitted to the IRB/EC only if required by the IRB/EC and regulatory 
authorities). 
Final report 
Investigators, IRB/EC, and 
RAs if required 
• 
The investigator shall have the opportunity to review and comment on the final 
report.  
• 
If a clinical investigator does not agree with the final report, his/her comments 
shall be communicated to the other investigator(s).   
• 
The coordinating investigator shall sign the report. If no coordinating investigator 
is appointed, then the signature of the principal Investigator in each study center 
should be obtained.    (ISO 14155:2020) 
Study deviation  
Investigators and 
Regulatory authorities  
Ensure that all deviations from the CIP are reviewed with the appropriate clinical 
investigator(s), are reported on the CRFs and the final report of the clinical investigation.  
(ISO 14155:2020) 
Study center specific study deviations will be submitted to investigators periodically.   
Table 15: Sponsor reports for the United States 
Report  
Submit to 
Description/Constraints 
Withdrawal of IRB/EC 
approval 
Investigators, IRB/EC, and 
FDA 
Notification within five working days of receipt of notice.  (21 CFR 812.150(b)(2))   
Withdrawal of FDA 
approval 
Investigators and 
IRB/EC 
Notification within five working days of receipt of notice.  (21 CFR 812.150(b)(3)) 
Investigator List 
FDA 
Submit at 6-month intervals, a current list of the names and addresses of all investigators 
participating in the investigation.  (21 CFR 812.150(b)(4)) 
Progress Reports 
IRB/EC and  
FDA 
Progress reports will be submitted at least annually.  (21 CFR 812.150(b)(5), 812.36(f)   

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Report  
Submit to 
Description/Constraints 
Recall and device 
disposition 
Investigators, Head of 
Institution, IRB/EC, relevant 
authorities, and FDA 
Notification within 30 working days and will include the reasons for any request that an 
investigator return, repair, or otherwise dispose of any devices.  (21 CFR 812.150(b)(6)) 
Final report 
Investigators, IRB/EC, RAs 
upon request, and FDA 
Medtronic will notify FDA within 30 working days of the completion or termination of the 
investigation.  A final report will be submitted to the FDA, investigators, and IRBs/ECs 
within six months after completion or termination of this clinical study.  (21 CFR 
812.150(b)(7)) 
Failure to obtain informed 
consent  
FDA 
Investigator’s report will be submitted to FDA within five working days of notification.  (21 
CFR 812.150(b)(8)) 
Study deviation  
Investigators 
Ensure that all deviations from the CIP are reviewed with the appropriate clinical 
investigator(s), are reported on the CRFs and the final report of the clinical investigation.  
Study center specific study deviations will be submitted to investigators periodically.   
Other 
IRB/EC, FDA 
Accurate, complete, and current information about any aspect of the investigation. (21 
CFR 812.150(b)(10)) 
Premature termination or 
suspension of clinical study 
IRB/EC, Investigators, and 
RAs, where applicable 
Medtronic will provide prompt notification of termination or suspension and reason(s) to 
investigator and where required to IRB/EC and RAs. 

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15.9. Publication and Use of Information 
Publications from the ADAPT-PD Trial will be handled according to Standard Operating Procedures and 
as indicated in the CTA. 
15.9.1. 
Publication Committee 
Medtronic may form the ADAPT-PD Trial Publication Committee from study investigators. Medtronic 
personnel may serve as members of the committee. This committee will manage study publications with 
the goal of publishing findings from the data. The Publication Committee will develop the final 
Publication Plan as a separate document.  
The Publication Committee’s role is to: 1) develop the final Publication Plan under separate cover, 2) 
execute the Publication Plan, 3) oversee the publication of primary, secondary and ancillary study 
results, 4) review and prioritize publication proposals, 5) provide input on publication content, and 6) 
determine authorship. In addition, the committee will apply and reinforce the authorship guidelines set 
forth in the Publication Plan.  
Membership in the Publication Committee does not guarantee authorship. The committee will meet as 
needed. 
15.9.2. 
Management of Primary, Secondary, and Ancillary Publications 
The Publication Committee reviews, prioritizes, and manages all publications including primary, 
secondary and ancillary publications.  Primary and secondary publications are those that address 
analyses of any or all primary objectives or secondary objectives, respectively, as specified in the CIP.  
An ancillary publication is any publication that does not address the study objectives identified in the 
CIP.  They include publications proposed and developed by other Medtronic departments or entities, 
clinicians participating in this study, and clinicians not participating in this study.  The committee will 
work with Medtronic to ensure that requests do not present conflicts with other proposals, are not 
duplicative, and to determine which ancillary publication proposals, if any, will be supported.   
The committee may decide that no publications, including abstracts, will be published prior to the end of 
the study or with individual study site data.  Requests for publications on study objectives utilizing 
subset data (e.g., regional) will be evaluated for scientific validity and the ability of Medtronic to provide 
resources.   

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15.9.3. 
Criteria for Determining Authorship 
Publications will adhere to authorship criteria defined by the International Committee of Medical 
Journal Editors (ICMJE, Uniform requirements for manuscripts submitted to biomedical journals, 
www.icmje.org).  Individual authorship criteria defined by the target journal or conference will be 
followed when it differs from ICMJE criteria. 
Authors, including Medtronic personnel, must at a minimum meet all of the conditions below: 
• 
Substantial contributions to conception and design of the work, or the acquisition, 
analysis, or interpretation of data for the work; AND 
• 
Drafting the work or revising it critically for important intellectual content; AND 
• 
Final approval of the version to be published; AND 
• 
Agreement to be accountable for all aspects of the work in ensuring that questions 
related to the accuracy or integrity of any part of the work are appropriately 
investigated and resolved.  
Decisions regarding authorship and contributor-ship will be made by the committee. The selected 
authors will be responsible for drafting the publication. All selected authors must fulfill the authorship 
conditions stated above to be listed as authors, and all contributors who fulfill the conditions must be 
listed as authors. 
All investigators not listed as co-authors will be acknowledged as the “Medtronic ADAPT-PD Study 
Investigators” and will be individually listed according to the guidelines of the applicable scientific 
journal when possible and affiliation. Any other contributors will be acknowledged by name with their 
specific contribution indicated. 
15.9.4. 
Transparency 
Transparency of clinical study results will be maintained by the following means: 
• 
A final report, describing the results of all objectives and analysis, will be distributed to all 
investigators, ECs and CAs of participating countries when required by local law 
• 
Registering and posting the study results on ClinicalTrials.gov based on the posting rules 
stipulated  
• 
Submitting for publication the primary study results after the study ends  
• 
Disclosing conflicts of interest (e.g., financial) of the co-authors of publications according to the 
policies set forth by the corresponding journals and conferences  
• 
Making an individual study sites study data accessible to the corresponding investigator after 
the completion of the study, if requested 

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15.10. 
Suspension or Early Termination 
Medtronic reserves the right to suspend or terminate the study at any time. Reasons for study 
suspension or termination may include, but are not limited to: 
• 
Insufficient enrollment to complete the study within the expected timeframe 
• 
Identification of unacceptable safety profile (suspicion of an unacceptable risk will result in a 
suspension, confirmation of an unacceptable risk will result in termination) 
• 
Product performance/product supply issues  
15.10.1. Planned Study Closure 
Study Closure is a process initiated by distribution of a study closure letter. Study closure is defined as 
closure of a study that occurs when Medtronic and/or regulatory requirements have been satisfied per 
the CIP and/or by a decision by Medtronic or RA, whichever occurs first. The study closure process is 
complete upon distribution of the Final Report or after final payments, whichever occurs last. Ongoing 
IRB/EC oversight is required until the overall study closure process is complete. Refer to Section 9.19 for 
additional information regarding study exit procedures. 
15.10.2. Early Termination or Suspension 
Early Termination is the closure of a study that occurs prior to meeting defined endpoints. This is 
possible for the whole study or a single study site. Suspension is a temporary postponement of study 
activities related to enrollment and distribution of the product. This is possible for the whole study or a 
single study site.  
15.10.2.1. 
Study-wide termination or suspension  
Possible reasons for considering study-wide suspension or termination of the study include but are not 
limited to:  
• 
AEs associated with the system or product under investigation which might endanger the safety 
or welfare of the subject  
• 
Observed/suspected performance different from the product’s design intent  
• 
Decision by Medtronic or RA (where the study is operating under RA)  
• 
Recommendation of early termination by the DMC  
15.10.2.2. 
Investigator/study site termination or suspension 
Possible reasons for investigator or study site termination or suspension include but are not limited to:  
• 
IRB/EC approval lapse/expiration 
• 
Persistent noncompliance with the clinical investigation plan 
• 
Lack of enrollment 

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• 
Noncompliance to regulations and the terms of the CTA (e.g. failure to submit data in a timely 
manner, failure to follow up on data queries and monitoring observations in a timely manner, 
etc.) 
• 
Loss of appropriately trained study center personnel 
• 
Insufficient or lack of investigator oversight 
• 
IRB/EC suspension of the study site 
• 
Fraud or fraudulent misconduct is discovered (as defined by local law and regulations) 
• 
Investigator request (e.g. no longer able to support the study)  
15.10.3. Procedures for Termination or Suspension 
In cases of study suspension/termination, standard medical care will continue to be provided to subjects 
enrolled in the study and IRB/EC/CA requirements will be followed. Subjects will be notified by the 
investigator of suspension/termination due to unacceptable risk or of termination due to any other 
cause.  
If applicable, an attempt will be made to transfer active subjects to another study center prior to 
termination whenever possible.  
Individual study centers may be closed by Medtronic if all subjects have completed the study or no 
active subjects are actively being followed. 
15.10.3.1. 
Medtronic-initiated and regulatory authority initiated 
• 
Medtronic will promptly inform the clinical investigators of the termination or suspension and 
the reasons and inform the RAs where required 
• 
In the case of study termination or suspension for reasons other than a temporary IRB/EC 
approval lapse, the IRB/EC will be promptly informed as required per local regulation 
• 
In the case of study termination, the investigator must inform the subjects and may inform the 
personal physician of the subjects to ensure appropriate care and follow-up is provided 
• 
In the case of a study suspension, subject enrollment must stop until the suspension is lifted by 
Medtronic 
• 
In the case of a study suspension, enrolled subjects should continue to be followed out of 
consideration of their safety, rights and welfare 
15.10.3.2. 
Investigator-initiated 
• 
The investigator will inform Medtronic and provide a detailed written explanation of the 
termination or suspension 
• 
The investigator will promptly inform the institution (where required per regulatory 
requirements)  

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• 
The investigator will promptly inform the IRB/EC 
• 
The investigator will promptly inform the regulatory authorities 
• 
The investigator will promptly inform the subjects and/or the personal physician of the subjects 
to ensure appropriate care and follow-up is provided 
• 
In the case of a study suspension, subjects enrolled should continue to be followed out of 
consideration of their safety, rights and welfare 
15.10.3.3. 
Ethics Committee-initiated 
• 
The investigator will inform Medtronic and provide a detailed written explanation of the 
termination or suspension within 5 business days 
• 
Subject enrollment must stop until the suspension is lifted 
• 
Subjects already enrolled should continue to be followed in accordance with EC policy or its 
determination that an overriding safety concern or ethical issue is involved 
• 
The investigator will inform his/her institution (where required per local requirements)  
• 
The investigator will promptly inform the subjects and/or the personal physician of the subjects 
with the rationale for the study termination or suspension 
• 
The investigator will promptly inform the RAs 
 

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16. References 
 
 
 
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16 Rodriguez-Oroz MC, Obeso JA, Lang AE, Houeto J-L, Pollak P, Rehncrona S, Kulisevsky J, et al. Bilateral deep brain 
stimulation in parkinson’s disease: a multicenter study with 4 years follow-up. Brain. 2005;128:2240–2249. 
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Contarino MF, Mink MS, Bour LJ, van den Munckhof P, Schmand BA, de Haan RJ, Schuurman PR, de Bie RM. 
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(NSTAPS study): a randomised controlled trial. Lancet Neurol. 2013;12:37– 44. 
21 Okun MS, Fernandez HH, Wu SS, Kirsch-Darrow L, Bowers D, Bova F, Suelter M, Jacobson CE 4th, Wang X, 
Gordon CW Jr, Zeilman P, Romrell J, Martin P, Ward H, Rodriguez RL, Foote KD. Cognition and mood in 
parkinson’s disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE 
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22 Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, et al. Neurostimulation for parkinson’s 
disease with early motor complications. N. Engl. J. Med. 2013;368:610–622. 
23 Weaver FM, Follett K, Stern M, Hut K, Harris C, Marks WJ Jr, Rothlind J, Sagher O,Reda D, Moy CS, et al. Bilateral 
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24 Weaver FM, Follett KA, Stern M, Luo P, Harris CL, Hur K, et al. Randomized trial of deep brain stimulation for 
parkinson disease: thirty-six-month outcomes. Neurology. 2012;79:55–65. 
25 Tinkhauser G, Pogosyan A, Tan H, Herz DM, Kühn A.A, Brown P. Beta burst dynamics in Parkinson's disease off 
and on dopaminergic medication. Brain (2017) 140:11 (2968-2981). Date of Publication: 1 Nov 2017. 
26 Bouthour W. Mégevand P. Donoghue J. Lüscher C. Birbaumer N. Krack P. Biomarkers for closed-loop deep brain 
stimulation in parkinson disease and beyond. Nature Reviews Neurology. 2019;Published online at 
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27 Hoang KB, Cassar IR, Grill WM, Turner DA.  Biomarkers and stimulation algorithms for adaptive brain stimulation. 
Frontiers in Neuroscience. 2017;11:564. 
28Kuhn AA, Tsui A, Aziz T, Ray N, Brüke C, Kupsch A, Schneider G-H, Brown P. Pathological synchronization in the 
subthalamic nucleus of patients with parkinson’s disease relates to both bradykinesia and rigidity. Exp Neurol 
2009;215:380–387. 
29 Little S, Brown P. What brain signals are suitable for feedback control of deep brain stimulation in parkinson’s 
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30 Brown P, and Williams D. Basal ganglia local field potential activity: character and functional significance in the 
human. Clin Neurophysiol. 2005;116(11):2510-913. 
31 Chen CC, Hsu YT, Chan HL, et al. Complexity of subthalamic 13-35 Hz oscillatory activity directly correlates with 
clinical impairment in patients with Parkinson’s disease. Exp Neurol 2010; 224:234–240. 
32 Pogosyan A, Yoshida F, Chen CC, Martinez-Torres I, Foltynie T, Limousin P, Zrinzo L, Hariz MI, Brown P. 
Parkinsonian impairment correlates with spatially extensive subthalamic oscillatory synchronization. 
Neuroscience. 2010;171:245–257. 
33 Thompson JA, Lanctin D, Ince NF, Abosch A. Clinical implications of local field potentials for understanding and 
treating movement disorders. Stereotactic and Functional Neurosurgery. 2014;92(4):251-263. 
34 Abosch A, Lanctin D, Onaran I, Eberly L, Spaniol M, Ince NF. Long-term recordings of local field potentials from 
implanted deep brain stimulation electrodes. Neurosurgery. 2012;71(4):804-814. 
35 Giannicola G, Rosa M, Servello D, Menghetti C, Carrabba G, Pacchetti C, Zangaglia R, Cogiamanian F, Scelzo E, 
Marceglia S, Rossi L, Priori A. Subthalamic local field potentials after seven-year deep brain stimulation in 
parkinson's disease. Experimental Neurology. 2012;237(2):312-317. 
36 Quinn EJ, Blumenfeld Z, Velisar A, Koop MM, Shreve LA, Trager MH, Hill BC, Kilbane C, Henderson JM, Brontë-
Stewart H. Beta oscillations in freely moving parkinson's subjects are attenuated during deep brain stimulation. 
Mov Disord. 2015;30(13):1750-1758. 
37 Beudel M, Brown P. Adaptive deep brain stimulation in parkinson's disease. Parkinsonism and Related Disorders. 
2016;22(1):S123-S126. 
38 Neumann WJ, Staub-Bartelt F, Horn A, Schanda J, Schneider GH, Brown P, Kühn AA. Long term correlation of 
subthalamic beta band activity with motor impairment in patients with parkinson's disease. Clinical 
Neurophysiology. 2017;128(11):2286-2291. 
39 Swann NC, de Hemptinne C, Miocinovic S, et al. Chronic multisite brain recordings from a totally implantable 
bidirectional neural interface: experience in 5 patients with parkinson's disease. J Neurosurg. 2018;128(2):605-
616. 
40 Trager MH, Koop MM, Velisar A, Blumenfeld Z, Nikolau JS, Quinn EJ, Martin T, Bronte-Stewart H. Subthalamic 
beta oscillations are attenuated after withdrawal of chronic high frequency neurostimulation in parkinson's 
disease.  Neurobiol Dis. 2016;96:22-30. 
41 Eusebio A, Thevathasan W, Doyle Gaynor L, Pogosyan A, Bye E, Foltynie T, Zrinzo L, Ashkan K, Aziz T, Brown P. 
Deep brain stimulation can suppress pathological synchronisation in parkinsonian patients. J Neurol Neurosurg 
Psychiatry. 2011;82(5):569-573. 
42 Kuhn AA, Kupsch A, Schneider G-H, Brown P. Reduction in subthalamic 8-35 Hz oscillatory activity correlates with 
clinical improvement in parkinson’s disease. Eur J Neurosci 2006;23:1956–1960. 
43 Ray NJ, Jenkinson N, Wang S, Holland P, Brittain JS, Joint C, Stein JF, Aziz T. Local field potential beta activity in 
the subthalamic nucleus of patients with parkinson’s disease is associated with improvements in bradykinesia 
after dopamine and deep brain stimulation. Exp Neurol. 2008;213:108–113. 
 
 
 

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44 Kuhn AA, Kempf F, Brucke C, et al. High-frequency stimulation of the subthalamic nucleus suppresses oscillatory 
beta activity in patients with Parkinson’s disease in parallel with improvement in motor performance. J Neurosci 
2008;28:6165–6173. 
45 Malekmohammadi M, Herron J, Velisar A, Blumenfeld Z, Trager MH, Chizeck HJ, Brontë-Stewart, H. Kinematic 
adaptive deep brain stimulation for resting tremor in parkinson's disease. Mov Disord. 2016;31(3):426-428. 
46 Afzal M.F. Velisar A. Anidi C. Neuville R. Prabhakar V. Bronte-Stewart H. Subthalamic Neural Closed-loop Deep 
Brain Stimulation for Bradykinesia in Parkinson's Disease. Brain Stimulation. 2019;12(4):e152-e154. 
47 Velisar A, Syrkin-Nikolau J, Blumenfeld Z, Trager MH, Afzal MF, Prabhakar V, Bronte-Stewart H.  Dual threshold 
neural closed loop DBS in PD patients. Brain Stimulation, https://doi.org/10.1016/j.brs. 2019.02.020 
48 Little S, Pogosyan A, Neal S, Zavala B, Zrinzo L, Hariz M, Foltynie T, Limousin P, Ashkan K, FitzGerald J, Green AL, 
Aziz TZ, Brown P. Adaptive deep brain stimulation in advanced parkinson disease. Ann Neurol. 2013;74(3):449-
57. 
49 Little S, Beudel M, Zrinzo L, Foltynie T, Limousin P, Hariz M, Neal S, Cheeran B, Cagnan H, Gratwicke J, Aziz TZ, 
Pogosyan A, Brown P. Bilateral adaptive deep brain stimulation is effective in parkinson's disease.  J Neurol 
Neurosurg Psychiatry. 2016;87(7):717-721. 
50 Little S, Tripoliti E, Beudel M, Pogosyan A, Cagnan H, Herz D, Bestmann S, Aziz T, Cheeran B, Zrinzo L, Hariz M, 
Hyam J, Limousin P, Foltynie T, Brown P. Adaptive deep brain stimulation for parkinson's disease demonstrates 
reduced speech side effects compared to conventional stimulation in the acute setting. J Neurol Neurosurg 
Psychiatry. 2016;87(12):1388-1389. 
51 Arlotti M, Rossi L, Rosa M, Marceglia S, Priori A. An external portable device for adaptive deep brain stimulation 
(aDBS) clinical research in advanced parkinson's disease. Med Eng Phys. 2016;38(5):498-505. 
52 Arlotti M, Marceglia S, Foffani G, Volkmann J, Lozano A.M, Moro E, Cogiamanian F, Prenassi M, Bocci T, Cortese 
F, Rampini P, Barbieri S, Priori A. Eight-hours adaptive deep brain stimulation in patients with parkinson disease. 
Neurology. 2018;90(11):e971-e976. 
53 Arlotti M, Palmisano C, Minafra B, Todisco M, Pacchetti C, Canessa A, Pozzi NG, Cilia R, Prenassi M, Marceglia S, 
Priori A, Rampini P, Barieri S, Servello D, Volkmann J, Pezzoli G, Isaias IU. Monitoring subthalamic oscillations for 
24 hours in a freely moving parkinson’s disease patient.  Movement Disorders. 2019;34(5):757-759. 
54 Rosa M, Arlotti M, Marceglia S, Cogiamanian F, Ardolino G, Fonzo AD, Lopiano L, Scelzo E, Merola A, Locatelli M, 
Rampini PM, Priori A. Adaptive deep brain stimulation controls levodopa-induced side effects in parkinsonian 
patients. Mov Disord. 2017;32(4):628-629. 
55 Piña-Fuentes D, Little S, Oterdoom M, Neal S, Pogosyan A, Tijssen MAJ, van Laar T, Brown P, van Dijk JMC, 
Beudel M. Adaptive DBS in a parkinson's patient with chronically implanted DBS: a proof of principle.  Mov 
Disord. 2017;32(8):1253-1254. 

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Appendix A - aDBS Global Impression of Change Score (GIC) 

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17. Version History 
Version 
Summary of Changes 
Justification of changes 
Potential impact of 
the change on 
performance, 
effectiveness, or 
safety or other 
endpoints 
Identification of 
the affected 
study 
documents 
Author(s)/Title 
1.0 
Not Applicable, New Document 
Not Applicable, New Document 
Not Applicable, 
New Document 
Not Applicable, 
New Document 
 
 
 
2.0 
4. Updated visit schedule 
to move LFP screening 
earlier in the study as a 
standalone visit 
5. Corrected motor diary to 
PD Home Diary and 
updated patient diary 
categories  
6. Removed risks of 
commercially available 
DBS and included 
reference to labeling  
7. Added sections: 
• 
7: Study Site 
requirements 
1. CIP V1.0 not approved by 
regulators or distributed for use; 
internal version only 
2. Updated to new Medtronic 
template CIP 
3. Additional revisions made to 
improve execution of CIP 
procedures 
 
Not Applicable 
1. IC  
2. CRFs 
 
 
 

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effectiveness, or 
safety or other 
endpoints 
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study 
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Author(s)/Title 
• 
9.19.6 Conditional 
disengagement 
• 
10.2 Risk Minimization 
• 
11.3 Processing Updates 
and Resolution 
• 
11.5.1 AE and DD 
Classification 
• 
AE and DD Reporting 
requirements 
• 
11.7 Product Complaint 
Reporting 
• 
13.1 General Aspects of 
Analysis 
• 
13.8 Minimization of 
Bias 
• 
15.1.1 Monitoring Visits 
• 
Clerical updates 
3.0 
1. Clerical updates 
throughout 
2. Removed Prof Andrea 
Kühn as lead PI 
3. Updated the following 
sections to add 
1. None 
2. No longer participating 
3. New study subject cohort 
4. New SW version available 
5. Clarification 
6. TH91 is a box, not a medical device 
None 
• 
IC 
• 
CRFs 
• 
IB 
 
 
 
 
 

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performance, 
effectiveness, or 
safety or other 
endpoints 
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study 
documents 
Author(s)/Title 
Directional Stimulation 
Cohort 
• 
2 Synopsis 
• 
3 Purpose 
• 
4 Objectives and 
Endpoints 
• 
5 Study Design 
• 
6 Product Description 
• 
8 Selection of Subjects 
• 
9 Study Procedures 
• 
10 Risks and Benefits 
• 
13 Statistical Design and 
Methods 
4. Section 6.1: updated 
software versions for 
Model A610 
5. Section 6.5: Equipment. 
Clarified that PKG watch 
will be used under an ITA 
in Canada 
6. Section 6.8: Clarified 
that TH91 package kit 
will not be tracked 
7. Technical requirement for SenSight 
8. Detected artifact may not preclude 
programming of aDBS 
9. COVID-19 restrictions 
10. Expansion of the visit window from 
3 days to 1 day after the previous 
visit does not change the 
expectation for the subject to be 
fully withdrawn from PD 
medication. The increased window 
allows for subjects who do not take 
controlled release carbidopa/ 
levodopa or dopamine agonists to 
be seen earlier as they will have 
fully withdrawn from medication 
(per Table 5) in 12 hours. 
11. Clarification 
12. Clarification 
13. Clarification to improve execution 
of CIP procedures 
14. Added more detail to improve 
execution of CIP procedures 
15. Clarification 

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effectiveness, or 
safety or other 
endpoints 
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7. Section 8.3: Added 
inclusion #9 
8. Section 8.4: Updated 
exclusion #16 
9. Updated Section 9 Study 
Procedures to allow 
administration of 
assessments outside of 
the visit when necessary. 
Section 9.15 provides 
guidance on which 
assessments may be 
done remotely and in 
what time frame. 
10. Section 9.3: updated 
visit windows for LFP 
screening and aDBS 
setup visits from 3-45 
days to 1-45 days 
11. Moved blinding language 
earlier in Section 9.9 and 
clarified that unblinding 
at any time during aDBS 
16. Updated per final published 
ISO14155:2020; Germany no longer 
participating 
17. Updated per Medtronic procedure 
18. No longer following MEDDEV 

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endpoints 
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setup and adjustment is 
a deviation 
12. Re-ordered Section 9.9.1 
for better flow 
13. Added clarification to 
Section 9.9.1 that if the 
visit occurs over 2 days, 
the clinician may 
program the subject to 
one aDBS mode 
between visit day 1 and 
visit day 2 and may have 
more freedom for 
naming aDBS modes.   
14. Section 9.15 added aDBS 
Global Impression of 
Change description 
15. Section 10.5, added 
information about PKG 
watch classification in 
Canada  
16. Section 11.4, table 7 
updated AE definition 

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performance, 
effectiveness, or 
safety or other 
endpoints 
Identification of 
the affected 
study 
documents 
Author(s)/Title 
Note 3; removed 
Germany SAE definition 
17. Section 11.4, table 7 
updated causality 
definitions 
18. Section 11.7 removed 
MEDDEV definitions 
4.0 
1. Glossary: Added 
definitions for 
directional stimulation, 
Primary Cohort and ring 
mode; updated SADE 
definition 
2. Section 5: defined 
primary cohort, ring 
mode and directional 
stimulation 
3. Section 7.1: Clarified 
that all investigators 
must be trained and 
experienced in DBS and 
management of PD 
4. Section 7.2: removed “as 
required” from CV 
1. Clarification/correction 
2. More clearly defined the 
cohorts and which 
programming configurations 
fall within each 
3. Clarification 
4. Required per ISO14155 
5. Reminder per GDP 
6. More clearly defined the 
cohorts and which 
programming configurations 
fall within each 
7. Real-world experience shows 
non-cardiac artifact may vary 
over time and based upon 
patient state and LFP signal 
may be affected by factors 
None 
1-5, 7-28: None 
6: CRFs 
 
 

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5. Section 8.2: added note 
that the date of IC 
signature must be 
documented in the 
subject’s medical 
records. 
6. Section 8.3: Updated 
general inclusion 
criterion #5 for both 
Primary and Directional 
Stimulation Cohort 
7. Section 9.4: removed 
prohibition for re-
screening due to signal 
artifact and inadequate 
LFP signal 
8. Section 9.7.1: clarified 
signal artifact 
requirement and actions 
to be taken 
9. Section 9.9.1: Clarified 
re-testing procedure for 
LFP inclusion criterion 
other than medication (e.g. 
movement) 
8. Clarification 
9. Clarification 
10. Clarification  
11. Clarification 
12. In current practice, clinicians 
can adjust therapy parameters 
as the subject’s disease state 
dictates. Investigators have 
always been allowed to make 
changes in programming 
outside of the study Enrollment 
to aDBS Evaluation Phase 
(allowed only when clinically 
necessary). This update clarifies 
that a change in aDBS mode is 
considered a change in 
programming. The investigator 
may only change modes if 
subject received both in the 
aDBS Evaluation Phase. 
13. Same as #11 

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effectiveness, or 
safety or other 
endpoints 
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study 
documents 
Author(s)/Title 
10. Section 9.9.1: Re-worded 
instructions for Dual and 
single threshold setup 
when only one 
hemisphere has signal 
meeting the LFP 
screening inclusion 
criterion 
11. Section 9.9.1: re-ordered 
end of visit instruction 
12. Section 9.11: Added 
allowance that 
investigator may choose 
to switch aDBS modes as 
needed in the Long-term 
Follow-up phase. 
13. Section 9.12: clarified 
that the subject will 
continue into the 
Extended Access Phase 
in aDBS, not necessarily 
the preferred mode. 
14. Sections 9.19 & 11.3: 
updated RTG to 
14. Update in Medtronic business 
name 
15. Clarification 
16. Correction, this is not collected 
17. Correction. Data will continue 
to be retained in accordance 
with applicable local 
regulations. 
18. Clarification 
19. Correction: records will 
continue to be retained in line 
with applicable laws 
20. Reformatting and clarification 
21. Additional administrative 
information 
22. Administrative change 

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effectiveness, or 
safety or other 
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documents 
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Neuromodulation and 
removed RTG from 
Glossary 
15. Section 11.4: Added 
clarification as to what 
“device” means in the 
context of AE definitions 
16. Section 11.5.1, Table 8: 
Removed “An underlying 
condition or disease” 
from relatedness 
classification 
17.  Section 15.2: removed 
“indefinitely” from data 
retention description 
18. Section 15.4: Clarified 
third party data access 
19. Section 15.7: Updated 
record retention 
information 
20. Section 15.9: moved to 
new Section 15.9.4 
Transparency 

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effectiveness, or 
safety or other 
endpoints 
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study 
documents 
Author(s)/Title 
21. New Sections 15.9.2 & 
15.9.3: added 
information regarding 
publication and 
authorship 
22. Moved content from 
Section 15.10.2.2 to 
15.10.3 
5.0 
1. Updated the CIP Template vE 
and v5.0. 
2. Added Competent Authority 
Number 
3. Updated Glossary of terms – 
Alpha – Beta, Globus Pallidus 
Internus, Multiple Imputations 
4. Definition updated Beta to 
Alpha - Beta throughout 
document 
5. Added sub-group analysis of 
selected mode 
1.Updated template and version. 
2.Update only - Added Competent 
Authority number 
3. Updated and added missing terms 
 
 
4. Updating name of frequency range 
to accurately describe frequency 
ranges in accordance with current 
literature and align with EEG 
1-15: No impact 
1 – 5: CIP 
6 (duration) – 
CIP, ICF 
7-11, 13-20: CIP 
12 (addition of 
Impartial 
Witness) – CIP, 
ICF 
 
 

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effectiveness, or 
safety or other 
endpoints 
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study 
documents 
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6. Section 5.1 – updated study 
duration from 2.5 to 5 years 
7. Removed reference to A610 
Clinician Programmer 
Application v2.0 throughout 
documents 
8. Section 6.1.2.1 Investigational 
DBS system– updated number of 
patient programmers from 40-70  
9. Section 6.10 Product Return–
aDBS feature should be disabled 
Standardized terminology16,17. 
Frequency updated to 8-30 Hz 
5.Updated to include sub-group 
analysis in long-term and extended 
phase 
6.Updated timeline to accommodate 
regulatory review and study closure 
7.All sites now on A610 v3.0 
8.Updated to account for DS cohort 
and number of subjects enrolled 
 
 
 
16 Kane N, Acharya J, Benickzy S, et al. A revised glossary of terms most commonly used by clinical electroencephalographers and updated proposal 
for the report format of the EEG findings. Revision 2017. Clin Neurophysiol Pr. 2017;2:170-185. doi:10.1016/j.cnp.2017.07.002 
17 Kane N, Acharya J, Beniczky S, et al. Corrigendum to “A revised glossary of terms most commonly used by clinical electroencephalographers and 
updated proposal for the report format of the EEG findings. Revision 2017” [Clin. Neurophysiol. Practice 2 (2017) 170–185]. Clin Neurophysiol Pr. 
2019;4:133. doi:10.1016/j.cnp.2019.06.001 
 

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prior to explant and is then no 
longer considered investigational 
10. Section 9.3 Scheduled f/u 
windows, Table 4, and Section 
9.12.1 Extended Access visits - 
follow-up windows clarified that 
Extended Access continues until 
commercialization, study exit 
and/or closure  
11. Section 9.5 Prior and 
Concomitant Medications– add 
clarification of no medication 
restrictions 
12. Section 9.6 Subject Consent– 
added impartial witness 
statement to CIP and ICF 
13. Section 9.13 unscheduled 
visits - Programming 
adjustments/optimizations are 
not reportable events 
9.Clarification 
10.Clarification 
11. Template update 
12. Update – with the progression of 
PD addition of a witness to facilitate 
obtaining informed consent for 
subjects with visual difficulties 
 
 
 
 
 
 
 
 
13. Clarification – programming 
adjustments/optimizations not 

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14. Section 9.18 Deviation 
Handling - Changes after the 
aDBS Evaluation Phase would 
not be considered a deviation.  
15. Section 19.1 Study Exit and 
9.19.2 Study Completed - Study 
Completion definition clarified 
16. Section 11.4, Table 7, Table 8 
Definitions/Classifications – 
Table 7 - removed definition of 
underlying condition. Table 8 - 
removed redundant definition 
17. Section 13.4.4 – Clarified 
diary period analysis 
18. Section 13.5.3 – Endpoint 
Definition and Section 13.5.7 
Supporting analyses - TEED 
calculation with missing 
impedance and test for 
carryover effect 
triggered by a change in clinical 
symptoms are not reportable events. 
14.Clarification – changes made after 
the aDBS Evaluation phase does not 
affect the analysis and therefore would 
not be considered a deviation. 
15.Clarification – subjects may exit at 
visit #6 or continue until 
commercialization.  
16. Update – redundant definitions. 
UADE/USADE already listed in table 
17. Clarification - In order to reasonably 
and accurately accommodate more 
actual diary data used in the analysis.  
This was allowed as the programmed 
parameters were still relevant to the 
analysis at the time of data collection.  
18. Clarification - In order to obtain an 
impedance for the TEED calculation and 
considering that impedance would be 
generally stable over the trial period, 

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19. Section 15.3 – updated name 
of MDT monitoring group 
20. Section 17 deleted – 
duplicate section 
impedance values were used from the 
aDBS Setup visit or the closest visit to 
that time. 
19. Updated – Name updated 
20 Duplicate section to Appendix A 

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Appendix A - aDBS Global Impression of Change Score (GIC) 
This scale is used to help assess for acceptability of an aDBS mode vs. cDBS for an individual subject. A 
lower number is better in terms of acceptability (ie, greater efficacy with minimal side effects).  
• 
“Acceptable”: A selection appearing in the white (unshaded) boxes means the mode has been 
deemed “acceptable” and is available for selection for that subject in the aDBS Evaluation 
Phase.  The subject may be programmed with this mode.   
• 
“Unacceptable”:  A selection appearing in the grey shading means the mode has been deemed 
“unacceptable” and is eliminated for selection in the aDBS Evaluation Phase.  The subject will 
not be programmed with that mode.   
To decide if a mode is acceptable to a subject, the following table will be used: 
 
Side effects 
Efficacy 
None 
Does not 
significantly 
interfere with 
patient’s 
functioning 
Significantly 
interferes with 
patient’s 
functioning 
Side effects 
experienced 
outweigh 
efficacy 
Vast 
improvement 
01 
02 
Fail:10 
Fail:11 
Decided 
improvement 
03 
04 
Fail:12 
Fail:13 
Slight 
improvement 
05 
06 
Fail:14 
Fail:15 
Unchanged 
07 
08 
Fail:16 
Fail:17 
Worse 
Fail:18 
Fail:19 
Fail:20 
Fail:21