Efficacy and Safety of the Omnipod 5 System Compared to Pump Therapy in the Treatment of Type 1 Diabetes: a Randomized, Parallel-group Clinical Trial
Phase: NA
Conditions: Type 1 Diabetes
Sponsor: Insulet Corporation

 
 
 
 
 
 OP5-003 Protocol V1.1 
Confidential 
Page | 1 
 
 
 
 
Efficacy and safety of the Omnipod 5 System compared to pump therapy in 
the treatment of type 1 diabetes: a randomized, parallel-group clinical trial 
 
 
 
 
Version 1.1 
November 14, 2022 
 
 
 
Insulet Corporation 
100 Nagog Park 
Acton, MA 01720 
 
 
 
 
 
 
Confidentiality Statement: 
The information in this document contains trade secrets and commercial information that are privileged or 
confidential and may not be disclosed unless such disclosure is required by applicable law or regulations. In 
any event, persons to whom the information is disclosed must be informed that the information is privileged 
or confidential and may not be further disclosed by them. These restrictions on the disclosure shall apply 
equally to all future information supplied to you, which is indicated as privileged or confidential. 
 
 

 
 
 
 
 
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Protocol Approval 
 
Efficacy and safety of the Omnipod 5 System compared to pump therapy in 
the treatment of type 1 diabetes: a randomized, parallel-group clinical trial 
 
Version 1.1 
November 14, 2022 
 
 
 
______________________________________ 
Trang Ly MBBS FRACP PhD - SVP, Clinical and  
Medical Director, Insulet Corporation 
 
 
 
 
 __________________ 
        Date 
 
 
______________________________________ 
Bonnie Dumais, RN – Senior Director, Clinical Affairs, 
Insulet Corporation 
 
 
__________________ 
        Date 
         
 
 
 
______________________________________ 
Julie Perkins - Senior Director, Quality and Regulatory, 
Insulet Corporation 
 
 
 
 
 __________________ 
        Date 
 
 
DocuSign Envelope ID: EEBDF251-820B-42CB-A2CA-4ECCD638558B
12/7/2022
12/9/2022
12/12/2022

 
 
 
 
 
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Investigator Statement 
 
Efficacy and safety of the Omnipod 5 System compared to pump therapy in 
the treatment of type 1 diabetes: a randomized, parallel-group clinical trial 
November 14, 2022 
Version 1.1 
I agree to conduct the above referenced clinical study protocol in accordance with the 
design and specific provisions as designated in this protocol, the signed agreement with 
the Sponsor, all applicable regulatory requirements such as the Food and Drug 
Administration (FDA), Good Clinical Practice (GCP) and Declaration of Helsinki, and any 
conditions of approval imposed by an Institutional Review Board (IRB) or Ethics 
Committee (EC). Modifications to the study protocol are acceptable only in the form of a 
protocol amendment, except when necessary to protect the safety, rights, or welfare of 
participants. I agree to await Institutional Review Board (IRB) /Ethics Committees (EC) 
and Insulet approval for the protocol, informed consent and documentation to be 
presented to participants before initiating the study in accordance with ICH (International 
Conference on Harmonization)-GCP, obtain informed consent from participants prior to 
their enrollment into the study, to collect and record data as required by this protocol and 
case report forms, to report non serious and serious adverse events that may occur for 
any participant participating in this study under my care, to report product complaints for 
any of the devices utilized in this protocol, and to maintain study related documentation 
(regulatory documentation) for the period of time required. I agree to supervise all 
utilization of investigational study devices and to ensure their usage is only in connection 
with the Study. I agree to provide a Financial Disclosure Statement to Sponsor and will 
also notify Sponsor if my disclosed financial information changes during the Study and 
up to one year following the closure of the Study. I have read and understand the 
contents of this protocol. I agree to follow and abide by the requirements set forth in this 
document. 
I understand the information in this document contains trade secrets and commercial 
information that are privileged or confidential and may not be disclosed unless such 
disclosure is required by applicable law or regulations. In any event, persons whom the 
information is disclosed must be informed that the information is privileged or 
confidential and may not be further disclosed by them. These restrictions on disclosure 
will apply equally to all future information supplied to me, which is indicated as privileged 
or confidential. 
___________________________________  
Clinical Site Investigator Name (print) 
 
___________________________________  
 
__________________ 
Clinical Site Investigator Signature 
 
 
 
 
Date 

 
 
 
 
 
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Principal Contacts 
 
Sponsor Contacts:  Trang Ly, MBBS FRACP PhD 
SVP, Clinical and Medical Director 
Insulet Corporation 
100 Nagog Park 
Acton, MA 01720 
Office: 978-600-7628 
E-mail: tly@insulet.com 
 
Bonnie Dumais, RN 
Senior Director, Clinical Affairs 
Insulet Corporation 
100 Nagog Park 
Acton, MA 01720 
Office: 978-932-2869 
E-mail: bdumais@insulet.com 
 
Julie Perkins 
Senior Director, Quality and Regulatory 
Insulet Corporation 
100 Nagog Park 
Acton, MA 01720 
Office: 978-600-7951 
E-mail: jperkins@insulet.com  
 
Protocol Chairs: 
 
Ruth S. Weinstock, MD, PhD 
 
 
 
 
Distinguished Service Professor 
 
  
 
Chief, Endocrinology, Diabetes and Metabolism,  
Department of Medicine 
 
 
 
 
State University of New York, Upstate Medical University  
 
 
 
 
750 East Adams Street (CWB 353) 
 
 
 
 
Syracuse, NY  13210 
 
 
 
 
Office: 315-464-5740 
E-mail: weinstor@upstate.edu 
 
 
 
Professor Eric Renard, MD, PhD, FRCPEdin 
Head of the Department of Endocrinology, Diabetes, Nutrition 
Head of the Clinical Investigation Centre CIC INSERM1411 
Lapeyronie Montpellier University Hospital 
University of Montpellier  
Montpellier, France 
Phone: +33 467 338 382 
 
 
 
 
 
 
Email:  e-renard@chu-montpellier.fr 
 
 
 

 
 
 
 
 
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TABLE OF CONTENTS 
1 
INTRODUCTION .....................................................................................................15 
2 
OMNIPOD 5 SYSTEM OVERVIEW .........................................................................16 
3 
DEVICE DESCRIPTION OF THE OMNIPOD 5 SYSTEM .......................................16 
3.1 Indications for Use (EU) ..............................................................................................18 
3.2 Indication for Use (US) ................................................................................................18 
4 
DATA PORTAL .......................................................................................................19 
5 
STUDY SUMMARY .................................................................................................19 
5.1 Study Purpose ............................................................................................................19 
5.2 Study Design ..............................................................................................................19 
6 
OBJECTIVES AND ENDPOINTS ............................................................................24 
6.1 Primary Objective........................................................................................................24 
6.1.1 Primary Endpoints ...............................................................................................24 
6.2 Secondary Objective ...................................................................................................24 
6.2.1 Secondary Endpoints ...........................................................................................24 
6.3 Exploratory Endpoints .................................................................................................24 
6.4 Patient Reported Outcomes ........................................................................................25 
7 
SCREENING AND ELIGIBILITY ..............................................................................25 
7.1 Visit 1 (Up to 30 days prior to Study Day 1) ................................................................26 
7.1.1 Informed Consent ................................................................................................26 
7.1.2 Confirm Eligibility .................................................................................................26 
7.1.3 Lab and Clinical Screening Assessments ............................................................27 
7.2 Visit 2 (14-days prior to Study Day 1) ..........................................................................28 
7.2.1 Assessment of CGM Usage and Data Criteria .....................................................29 
7.3 CGM Usage ................................................................................................................29 
7.3.1 CGM Initiation ......................................................................................................30 
7.4 Visit 3 (Study Day 1) ...................................................................................................30 
7.4.1 Randomization .....................................................................................................31 
7.5 Visits 4 and 5 ..............................................................................................................31 
7.6 Visits 6 and 7 ..............................................................................................................32 
7.7 Visit 8 ..........................................................................................................................32 
7.8 Unscheduled Visits .....................................................................................................32 
7.9 Early Withdrawal .........................................................................................................33 
7.10 
Lost to Follow-up .................................................................................................33 
8 
SPONSOR REPRESENTATIVES ...........................................................................34 

 
 
 
 
 
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9 
SAFETY ..................................................................................................................34 
9.1 Types of Known Risks and Benefits ............................................................................34 
9.2 Hypoglycemia/Hyperglycemia .....................................................................................35 
9.3 Adverse Events ...........................................................................................................35 
9.4 Reportable Adverse Events ........................................................................................37 
9.5 Hypoglycemic Events ..................................................................................................37 
9.6 Hyperglycemic/Ketotic Events .....................................................................................38 
9.7 Relationship of Adverse Event to Devices or Study Procedures..................................38 
9.8 Severity (Intensity) of Adverse Events.........................................................................39 
9.9 Outcome of Adverse Events .......................................................................................39 
9.10 
Reportable Device Issues ....................................................................................40 
9.11 
Timing of Event Reporting....................................................................................40 
9.12 
Safety Oversight ..................................................................................................41 
10 
STOPPING CRITERIA ............................................................................................41 
10.1 
Participant Discontinuation of Study Participation ................................................41 
10.2 
Criteria for Suspending or Stopping Overall Study ...............................................42 
10.3 
Safety Signal Detection ........................................................................................42 
11 
STATISTICAL CONSIDERATIONS .........................................................................43 
11.1 
Primary Endpoint and Hypotheses .......................................................................43 
11.2 
Secondary Endpoints and Hypotheses ................................................................43 
11.3 
Exploratory Endpoints ..........................................................................................46 
11.4 
Patient-Reported Outcomes .................................................................................46 
11.5 
Sample Size ........................................................................................................47 
11.6 
Analysis Sets .......................................................................................................47 
11.6.1 
ITT (Intention to Treat) Analysis Set ..............................................................47 
11.6.2 
mITT (modified Intention to Treat) Analysis Set ............................................47 
11.7 
PP (Per-Protocol) Analysis Set ............................................................................47 
11.8 
Analysis of Primary and Secondary Endpoints .....................................................48 
12 
PERCENTAGE OF TIME ENDPOINTS ...................................................................49 
12.1 
Subgroup Analyses ..............................................................................................49 
12.2 
Additional Data Analyses .....................................................................................49 
12.3 
Safety Analyses ...................................................................................................49 
12.3.1 
Evaluation of Adverse Events .......................................................................49 
12.3.2 
Evaluation of Device Deficiencies .................................................................50 
12.4 
Baseline Characteristics ......................................................................................50 

 
 
 
 
 
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12.5 
General Statistical Methods .................................................................................50 
12.6 
Missing Data ........................................................................................................50 
12.7 
Statistical Software ..............................................................................................51 
13 
DATA HANDLING AND QUALITY ASSURANCE ....................................................51 
13.1 
Electronic Case Report Forms (eCRFs) ...............................................................51 
13.2 
Electronic Device Outputs ....................................................................................52 
13.2.1 
Omnipod 5 System Data ...............................................................................52 
13.2.2 
CGM Data .....................................................................................................52 
13.2.3 
BG/Ketone Meter Data ..................................................................................52 
13.2.4 
Participant Identifiers ....................................................................................52 
13.2.5 
Monitoring Responsibilities ...........................................................................52 
13.2.6 
Inspection of Records ...................................................................................52 
13.2.7 
Study Record Retention ................................................................................53 
13.2.8 
Device Accountability ....................................................................................53 
14 
STUDY ETHICS AND CONDUCT ...........................................................................53 
14.1 
Role of the Sponsor .............................................................................................53 
14.2 
Ethical Conduct of the Study ................................................................................53 
14.3 
International Review Board (IRB) and Ethics Committees (EC) ...........................53 
14.4 
Informed Consent ................................................................................................54 
14.5 
Confidentiality ......................................................................................................54 
14.6 
Modification of the Protocol ..................................................................................55 
14.7 
Protocol Deviations ..............................................................................................55 
14.8 
Study Reporting Requirements ............................................................................55 
14.9 
Selection of Investigators .....................................................................................56 
14.9.1 
Financial Disclosure ......................................................................................56 
14.9.2 
Investigator Documentation ..........................................................................56 
14.10 
Clinical Site Training ............................................................................................56 
14.11 
Device Use ..........................................................................................................57 
14.12 
Device Returns ....................................................................................................57 
14.13 
Policy for Publication and Presentation of Data ....................................................57 
14.14 
Sponsor or Regulatory Agency Termination of the Study .....................................57 
15 
REFERENCES ........................................................................................................59 
 
 

 
 
 
 
 
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Protocol Summary 
Protocol title 
Efficacy and safety of the Omnipod 5 System compared to pump 
therapy in the treatment of type 1 diabetes: a randomized, parallel-
group clinical trial 
Protocol ID 
OP5-003 
Purpose 
To demonstrate the efficacy and safety of the Omnipod 5 System 
compared to pump and continuous glucose monitor (CGM) therapy in 
adults with type 1 diabetes currently using pump therapy 
Study Devices 
The devices used in the Intervention group include: 
• 
Omnipod 5 System, comprised of the following components: 
o Omnipod 5 Pod 
o Omnipod 5 App (on the Insulet-provided Controller) 
• 
Dexcom G6 Continuous Glucose Monitor 
 
The devices used in the Control group include: 
• 
Participant’s own insulin pump 
• 
Dexcom G6 Continuous Glucose Monitor  
Primary 
objective 
To demonstrate superior efficacy of the Omnipod 5 System compared to 
pump and CGM therapy in adults with type 1 diabetes   
Secondary 
objective 
To demonstrate additional measures of efficacy and safety of the 
Omnipod 5 System compared to pump and CGM therapy in adults with 
type 1 diabetes   
Study Design 
Adults with type 1 diabetes currently on pump therapy with an A1C 
between 7-11%, inclusive, will be recruited for the study. At least 80% of 
participants must have an A1C ≥ 8%. At least 50% of participants must 
be using Omnipod for pump therapy at the time of enrollment. 
 
Following a two-week standard therapy period where CGM data will be 
collected, participants will be randomized (2:1 ratio) to either: 
 
• 
Intervention Group – Omnipod 5 System with Dexcom G6 CGM or 
• 
Control Group – Participant’s current insulin pump with Dexcom G6 
CGM 
 
Both groups will participate for 13-weeks after completion of standard 
therapy.   
 
All participants will be required to use the study provided Dexcom G6 
sensor for the duration of the study. 
Primary 
Endpoint 
The primary endpoint is per-participant percentage of time in range (TIR) 
70-180 mg/dL as measured by study CGM and comparing the 
Intervention group to the Control group during the 13-week randomized 
period  
Secondary 
Endpoints 
The following secondary per-participant endpoints will be evaluated and 
compared in the Intervention group vs. Control group at the end of the 
13-week randomized period:  

 
 
 
 
 
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Secondary Endpoints: 
• 
Percentage of time <54 mg/dL (non-inferiority) 
• 
Percentage of time >180 mg/dL  
• 
Mean glucose  
• 
Change from baseline in A1C  
• 
Percentage of time < 70 mg/dL 
• 
Change from baseline in Type 1-Diabetes Distress Scale (T1-DDS) 
total score  
• 
Change from baseline in Hypoglycemia Confidence Scale (HCS) 
total score  
• 
Change from baseline in Diabetes Quality of Life-brief (DQOL-brief) 
total score  
Exploratory 
Endpoints 
The following exploratory endpoints will be evaluated and compared in 
the Intervention group vs. Control group at the end of the 13-week 
randomized period: 
 
• 
Proportion of participants with A1C <7%  
• 
Proportion of participants with A1C <8%  
• 
Proportion of participants with ≥1% improvement in A1C from 
baseline  
• 
Proportion of participants with ≥10 percentage point relative 
improvement in A1C from baseline  
• 
Proportion of participants with either ≥1% improvement in A1C from 
baseline OR ≥10 percentage point relative improvement in A1C 
from baseline 
• 
Change from baseline in Body Mass Index (BMI) 
• 
Change from baseline in total daily insulin (TDI) (units/kg)  
• 
Additional CGM-derived endpoints, such as coefficient of variation, 
time above range >250 mg/dL, percentage of time < 54 mg/dL 
(superiority), TIR during daytime and nighttime hours 
• 
Number of episodes of severe hypoglycemia 
• 
Number of episodes of DKA 
 
Patient-Reported Outcomes: 
The following questionnaires will be used to evaluate general and 
disease-specific quality of life, and device usability. Results will be 
assessed at 13 weeks compared to baseline (Intervention and Control 
group) 
• 
Clarke Hypoglycemia Awareness 
• 
EQ-5D-3L 
• 
Type 1 Diabetes Distress Scale (T1-DDS) 
• 
Diabetes Quality of Life-brief (DQOL-brief) 
• 
DAWN Impact of Diabetes Profile (DIDP) 
• 
Hypoglycemia Confidence Scale (HCS) 
• 
Pittsburgh Sleep Quality Index (PSQI) 
• 
System Usability Scale (SUS) 
• 
Insulin Dosing Systems: Perceptions, Ideas, Reflections, and 
Expectations (INSPIRE) 
 

 
 
 
 
 
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Eligibility 
Criteria 
Inclusion Criteria: 
Participants must meet all the following criteria to be included in the 
study: 
1. Age at time of consent 18-70 years of age 
2. Diagnosed with type 1 diabetes for at least 1 year. Diagnosis is 
based on investigator’s clinical judgment. 
3. On pump therapy for ≥ 3 months prior to screening and familiar with 
pump therapy concepts such as basal and bolus insulin delivery, 
and carbohydrate counting. Participants using automated insulin 
delivery (AID) devices, including devices with predictive low glucose 
suspend (PLGS), in the 3 months prior to screening, will be 
excluded from participating. 
4. A1C 7.0-11.0% by point-of-care taken at screening visit 
5. Willing to use and obtain U-100 insulin: (either insulin aspart 
(Novolog, NovoRapid), or insulin lispro (Humalog, Admelog)), as the 
primary insulin treatment    
6. Must have a smartphone that supports the Dexcom app download 
and participants must be willing to use the app throughout the study 
7. Investigator has confidence that the participant can safely operate 
all study devices and can adhere to the protocol 
8. Willing to wear the system continuously throughout the study 
9. Willing and able to sign the Informed Consent Form (ICF) 
 
Exclusion Criteria: 
Participants who meet any of the following criteria will be excluded from 
the study: 
1. Any medical condition, such as untreated malignancy, unstable 
cardiac disease, unstable or end-stage renal failure, eating 
disorders, or other conditions which in the opinion of the 
investigator, would put the participant at an unacceptable safety risk 
2. History of severe hypoglycemia in the past 6 months 
3. History of diabetic ketoacidosis (DKA) in the past 6 months, 
unrelated to an intercurrent illness or infusion set failure 
4. Blood disorder or dyscrasia within 3 months prior to screening, 
including use of hydroxyurea, which in the investigator’s opinion 
could interfere with determination of HbA1C. 
5. Currently on systemic steroids or intends to receive systemic steroid 
treatment during study participation, including stable treatment for 
adrenal insufficiency. Inhaled, ophthalmic, topical, joint injection, 
and other locally applied steroids are allowed. 
6. Unable to tolerate adhesive tape or has any unresolved skin 
condition in the area of sensor or pump placement 
7. Use of non-insulin anti-hyperglycemic medication other than 
metformin, in the 12 weeks prior to the Baseline Visit. Participants 
taking metformin should remain on a steady dose during study 
participation. 
8. Pregnant or lactating, or is a woman of childbearing potential and 
not on acceptable form of birth control (acceptable forms of 
contraception include abstinence, barrier methods such as 
condoms, hormonal contraceptives, intrauterine device, surgical 

 
 
 
 
 
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sterilization such as tubal ligation or hysterectomy, or vasectomized 
partner) 
9. Participation in another clinical study using an investigational drug 
or device within 30-days or 5 half-lives (whichever is longer) prior to 
screening, or intends to participate in any other study during this 
study period  
10. Unable to follow clinical protocol for the duration of the study or is 
otherwise deemed unacceptable to participate in the study per the 
investigator’s clinical judgment 
11. Participant is an employee of Insulet, an Investigator or 
Investigator’s study team, or immediate family member of any of the 
aforementioned 
Sample Size 
A total of up to 200 participants at up to 15 clinical sites across the 
United States (US) and France will be enrolled in the study, to obtain a 
minimum of 170 randomized participants.  
Study Arms 
Parallel-group 13-week randomized trial: 
• 
Intervention Group: Omnipod 5 System with Dexcom G6 CGM 
• 
Control Group: Participant’s current insulin pump with Dexcom G6 
CGM 
Study Duration 
The study is expected to be completed within 12-months which includes 
clinical site initiation to completion and all data entry and monitoring 
procedures.  Each participant is expected to participate for approximately 
15 weeks.    
Device 
Indication 
Europe (EU)  
and  
United States 
(US) 
Europe: 
The Omnipod 5® Automated Insulin Delivery System (Omnipod 5 
System) is a single hormone insulin delivery system intended to deliver 
U-100 insulin subcutaneously for the management of type 1 diabetes in 
persons aged 2 and older requiring insulin. 
 
The Omnipod 5 System is intended to operate as an automated insulin 
delivery system when used with compatible CGM. 
 
When in Automated Mode, the Omnipod 5 System is designed to assist 
people with type 1 diabetes in achieving glycemic targets set by their 
healthcare providers. It is intended to modulate (increase, decrease or 
pause) insulin delivery to operate within predefined threshold values 
using current and predicted CGM values to maintain blood glucose at 
variable target glucose levels, thereby reducing glucose variability. This 
reduction in variability is intended to lead to a reduction in the frequency, 
severity, and duration of both hyperglycemia and hypoglycemia. 
 
The Omnipod 5 System can also operate in a manual mode that delivers 
insulin at set or manually adjusted rates. 
 
The Omnipod 5 System is intended for single patient use.  
The Omnipod 5 System is indicated for use with Novolog/NovoRapid, 
Humalog and Admelog U-100 insulin. 
 
 
United States: 

 
 
 
 
 
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The Omnipod 5 Automated Insulin Delivery System in the US consists of 
3 regulated devices.  The indications for use for the 3 devices are as 
follows: 
 
The Omnipod 5 ACE (alternate controller enabled) Pump (Pod) is 
intended for the subcutaneous delivery of insulin, at set and variable 
rates, for the management of diabetes mellitus in persons requiring 
insulin. The Omnipod 5 ACE Pump is able to reliably and securely 
communicate with compatible, digitally connected devices, including 
automated insulin dosing software, to receive, execute, and confirm 
commands from these devices. The Omnipod 5 ACE Pump is intended 
for single patient, home use and requires a prescription. 
 
SmartAdjust™ technology is intended for use with compatible integrated 
continuous glucose monitors (iCGM) and ACE pumps to automatically 
increase, decrease, and pause delivery of insulin based on current and 
predicted glucose values. SmartAdjust technology is intended for the 
management of type 1 diabetes mellitus in persons 6 years of age and 
older. SmartAdjust technology is intended for single patient use and 
requires a prescription. 
 
The Omnipod 5 SmartBolus Calculator is software intended for the 
management of diabetes in persons aged 6 and older requiring rapid-
acting U-100 insulin. The Omnipod 5 SmartBolus Calculator calculates a 
suggested bolus dose based on user-entered carbohydrates, most 
recent sensor glucose value (or blood glucose reading if using 
fingerstick), rate of change of the sensor glucose (if applicable), insulin 
on board (IOB), and programmable correction factor, insulin to 
carbohydrate ratio, and target glucose value. The Omnipod 5 
SmartBolus Calculator is intended for single patient, home use and 
requires a prescription. 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
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Glossary of Acronyms  
ACE 
Alternate Controller Enabled 
ADA 
American Diabetes Association 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AID 
Automated Insulin Delivery 
ASADE 
Anticipated Serious Adverse Device Effect 
AWS 
Amazon Web Services  
BG 
Blood Glucose 
BMI 
Body Mass Index 
CE 
Conformite Europeenne 
CFR 
Code of Federal Regulations 
CGM 
Continuous Glucose Monitoring 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CV 
Curricula Vitae 
DCCT 
Diabetes Control and Complications Trial 
DD 
Device Deficiency 
DIDP 
Dawn2 Impact of Diabetes Profile 
DKA 
Diabetic Ketoacidosis 
dL 
Deciliter 
DQOL 
Diabetes Quality of Life 
eCRF 
Electronic Case Report Form 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
EU 
European Union  
EW 
Early Withdrawal 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HCS 
Hypoglycemia Confidence Scale 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ID 
Identification 
IFU 
Instructions For Use 
INSPIRE 
Insulin Dosing Systems:  Perceptions, Ideas, 
Reflections, and Expectations 
IOB 
Insulin On Board 

 
 
 
 
 
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IRB 
Institutional Review Board 
ITT 
Intention to Treat 
MDD 
Medical Device Directive  
mg 
Milligram 
mITT 
Modified Intention to Treat 
mmol 
Millimole 
MPC 
Model Predictive Control 
PI 
Principal Investigator 
PLGS 
Predictive Low Glucose Suspend 
POC 
Point of Care 
PP 
Per Protocol 
PSQI 
Pittsburgh Sleep Quality Index 
QC 
Quality Control 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SMP 
Safety Management Plan 
SUS 
System Usability Scale 
TIR 
Time In Range 
T1D 
Type 1 Diabetes 
T1DDS 
Type 1 Diabetes Distress Scale 
TSH 
Thyroid Stimulating Hormone 
TDI 
Total Daily Insulin 
USADE 
Unanticipated Serious Adverse Device Effect 
US 
United States 
UV 
Unscheduled Visit 

 
 
 
 
 
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1 
INTRODUCTION 
Diabetes is a disorder affecting the homeostatic regulation of blood glucose, with 
potential to cause short-term sequelae of critical hyperglycemia as well as long-term 
effects of microvascular complications including blindness, kidney disease, and 
amputation1 Multiple studies have shown that the risk for long-term complications of 
diabetes can be reduced by maximizing the time in euglycemia.2-4 Strict avoidance of 
hyperglycemia must be balanced with risk for hypoglycemia, a distinctive cause of 
morbidity and mortality.5 Furthermore, fear of hypoglycemia is an important barrier to 
improved glucose control.6  
The American Diabetes Association (ADA) recommends that adults with type 1 diabetes 
(T1D) should aim for target A1C levels of less than 7.0% as a goal for glucose control, 
with the caveat that targets should be individualized and may be higher or lower 
depending on additional factors.7 The widespread use of continuous glucose monitoring 
(CGM) has brought additional granularity to clinical decision-making, and glycemic 
targets have expanded to include measures like time in range (TIR), defined as percent 
of CGM readings within the range of 70-180 mg/dL, with TIR of 70% aligning with an 
A1C of about 7%.7  
As technology for glucose monitoring has evolved, so has insulin delivery. Connected 
insulin pumps, including those which suspend insulin delivery during low glucose and 
with automated insulin delivery algorithms, have become available and improve both TIR 
and A1C.8-12  
The Omnipod® 5 Automated Insulin Delivery System (Omnipod 5 System) has a novel 
algorithm with customizable glucose targets and unique configuration utilizing a tubeless 
insulin pump (Pod), which is a small (3.9 x 5.2 x 1.45 cm) adhesive patch pump worn on 
the body. The cannula is automatically deployed directly under the Pod, creating an 
infusion site without external tubing. The Pod is waterproof (IP28) and is worn 
continuously for up to 72 hours. All user interactions are conducted wirelessly through a 
mobile app on a smartphone. The algorithm itself is located on the Pod, and the glucose 
sensor communicates directly with the Pod through Bluetooth® wireless technology. 
Therefore, the system can continuously provide automated insulin delivery (AID) via the 
wearable on-body components alone (Pod and sensor), without the smartphone 
controller needing to be nearby.  
Omnipod 5 was developed through several feasibility studies.13-16 Subsequently, it was 
evaluated in a prospective, multi-center, single-arm safety study and shown to be safe 
and effective in the glycemic management of children, adolescents, and adults ages 2 to 
70 years with type 1 diabetes, with minimal episodes of severe hypoglycemia and 
diabetic ketoacidosis, in addition to significant improvements in glycemic outcomes, 
including decreased A1C and increased time in range, 70-180 mg/dL.8,16,17 Among 128 
adolescents and adults (14 to 70 years), A1C decreased by 0.38% from 7.16 ± 0.86% at 
baseline to 6.78 ± 0.68% after 13 weeks of automated mode use. Time in range 
increased by 9.3% from 64.7 ± 16.6% during a 2-week standard therapy phase where 
participants used their usual insulin therapy, to 73.9 ± 11.0% with Omnipod 5.8 

 
 
 
 
 
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Still, there is little data available allowing a direct comparison of outcomes with the 
Omnipod 5 system compared to conventional therapy with a CGM and insulin pump 
without automated features. Data from a study pause during the aforementioned single-
arm trial allowed a post-hoc comparison of outcomes with Omnipod 5 with and without 
the algorithm enabled. During the study, use of the automated insulin delivery function 
was paused for a mean of 106 days. During the pause, participants could continue 
study system use without activation of automated delivery where the device functioned 
as a stand-alone insulin pump (manual mode, 77% of participants), or they could use 
another insulin regimen (23%). For adolescents and adults who used Omnipod 5 in 
manual mode during the pause (n=83), TIR was 62.7% during the standard therapy 
phase, rising to 74.4% during the first automated phase (mean duration 44 days). TIR 
then decreased to 65.5% with manual mode use during the pause, and then increased 
again to 73.6% during the second automated phase (mean duration 49 days). This 
post-hoc crossover comparison provides initial evidence of the additional glycemic 
benefit achieved by the Omnipod 5 algorithm compared with the same combination of 
devices used with manual delivery, where the additional benefit from the algorithm is 
expected to be about 8-12%.18 
While these results are encouraging, robust comparative efficacy data in a randomized 
controlled environment is needed for the Omnipod 5 system, as compared to insulin 
pump with CGM to support changes in standards of care for people with diabetes. As 
such, this clinical trial aims to determine efficacy and safety of Omnipod 5 in patients 
with glucose targets above the recommended treatment range. 
2 
OMNIPOD 5 SYSTEM OVERVIEW 
This study will demonstrate the efficacy and safety of the Omnipod 5 System compared 
to pump and continuous glucose monitor (CGM) therapy in adults with type 1 diabetes 
currently using pump therapy.  
The Omnipod 5 System is developed and manufactured by Insulet Corporation. 
The Omnipod 5 Automated Insulin Delivery System used during the study is the system 
FDA cleared in K203768, K203772, and K203774 and will be used in accordance with its 
intended use.  The Omnipod 5 System was under review for CE mark under the Medical 
Device Regulation (MDR) in the European Union (EU) at the time of its submission to 
ANSM/CPP.  It has since received CE mark on 16 September 2022 under the reference 
MDR 744313 R000 (Notified body BSI) and will be used in accordance with its proposed 
intended use. 
3 
DEVICE DESCRIPTION OF THE OMNIPOD 5 SYSTEM 
The Omnipod 5 System is comprised of two components: 
• 
Omnipod 5 Pod (insulin infusion pump with SmartAdjust technology).  
• 
Omnipod 5 App (installed on the Insulet-provided Controller)  
The Dexcom G6 CGM (sold separate and manufactured by Dexcom) is required for use 
with Omnipod 5 for automated insulin delivery. 

 
 
 
 
 
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The Omnipod 5 Pod interacts with the Omnipod 5 App and a CGM via secure Bluetooth 
technology.  With SmartAdjust technology, the system receives glucose values and 
trend data from the CGM, automatically calculates insulin dose, and sends delivery 
commands to the Pod for delivery of insulin. Insulin is delivered through a soft cannula 
that is automatically inserted by the Pod into the subcutaneous tissue.  
The system can work in Automated Mode and Manual Mode. In Automated Mode 
(SmartAdjust technology activated), the system calculates insulin micro-boluses every 
five minutes based upon the predicted glucose over a 60-minute prediction horizon. The 
Omnipod 5 Algorithm adjusts its insulin delivery based on several factors including a 
user-set glycemic target (110-150 mg/dL) and the user’s Total Daily Insulin (TDI). In 
Manual Mode, the system operates by delivering insulin at programmed basal rates like 
a standard insulin pump.  
The Omnipod 5 App contains a SmartBolus Calculator that is used to deliver meal bolus 
doses of insulin based on entered carbohydrates as well as sensor and trend data. The 
SmartBolus Calculator works in both Automated and Manual Modes.  
The Omnipod 5 System (with SmartAdjust technology activated) can automatically 
adjust delivery of insulin based on CGM values and can pause delivery of insulin when 
the glucose sensor value falls below or is predicted to fall below predefined threshold 
values. The Omnipod 5 System is currently interoperable with the Dexcom G6 CGM. 
 
 
Figure 1:  System components of the Omnipod 5 System 
Controller 
Dexcom G6® app 

 
 
 
 
 
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Figure 2:Omnipod 5 Pod 
The Omnipod 5 Controller used in this study has an English language user interface. 
Participants will be provided with the French translated User Guide. 
3.1 
Indications for Use (EU) 
Due to regional regulatory requirements, the indications for use are different for the US 
and the EU.   
The Omnipod 5 System is a single hormone insulin delivery system intended to deliver 
U-100 insulin subcutaneously for the management of type 1 diabetes in persons aged 6 
and older requiring insulin. 
The Omnipod 5 System is intended to operate as an automated insulin delivery system 
when used with compatible CGMs. 
When in Automated Mode, the Omnipod 5 System is designed to assist people with type 
1 diabetes in achieving glycemic targets set by their healthcare providers. It is intended 
to modulate (increase, decrease or pause insulin delivery to operate within predefined 
threshold values using current and predicted CGM values to maintain blood glucose at 
variable target glucose levels, thereby reducing glucose variability. This reduction in 
variability is intended to lead to a reduction in the frequency, severity, and duration of 
both hyperglycemia and hypoglycemia. 
The Omnipod 5 System can also operate in a Manual Mode that delivers insulin at set or 
manually adjusted rates. 
The Omnipod 5 System is intended for single patient use. The Omnipod 5 System is 
indicated for use with Novolog/NovoRapid, Humalog and Admelog U-100 insulin. 
3.2 
Indication for Use (US) 
The Omnipod 5 System in the US consists of 3 regulated devices.  The indications for 
use for the 3 devices are as follows: 

 
 
 
 
 
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The Omnipod 5 ACE Pump (Pod) is intended for the subcutaneous delivery of insulin, at 
set and variable rates, for the management of diabetes mellitus in persons requiring 
insulin. The Omnipod 5 ACE Pump is able to reliably and securely communicate with 
compatible, digitally connected devices, including automated insulin dosing software, to 
receive, execute, and confirm commands from these devices. The Omnipod 5 ACE 
Pump is intended for single patient, home use and requires a prescription. 
SmartAdjust™ technology is intended for use with compatible integrated continuous 
glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically 
increase, decrease, and pause delivery of insulin based on current and predicted 
glucose values. SmartAdjust technology is intended for the management of type 1 
diabetes mellitus in persons 6 years of age and older. SmartAdjust technology is 
intended for single patient use and requires a prescription. 
The Omnipod 5 SmartBolus Calculator is software intended for the management of 
diabetes in persons aged 6 and older requiring rapid-acting U-100 insulin. The Omnipod 
5 SmartBolus Calculator calculates a suggested bolus dose based on user-entered 
carbohydrates, most recent sensor glucose value (or blood glucose reading if using 
fingerstick), rate of change of the sensor glucose (if applicable), insulin on board (IOB), 
and programmable correction factor, insulin to carbohydrate ratio, and target glucose 
value. The Omnipod 5 SmartBolus Calculator is intended for single patient, home use 
and requires a prescription. 
4 
DATA PORTAL 
Data are securely uploaded from the Omnipod 5 Controller to the Insulet Cloud by both 
cellular connection and Wi-Fi.  Data are then copied from the Insulet Cloud to the Data 
Portal, which is an application for data analytics and monitoring. The Data Portal 
currently runs on an Amazon Web Services (AWS) infrastructure. The Data Portal will 
provide insights including but not limited to time in range, time at each target blood 
glucose (BG), Automated/Manual Mode comparisons, and time spent in each mode. 
Investigators will have access to all uploaded deidentified Omnipod 5 data and be able 
to view historical trends.  The Data Portal will function as the data analytics and 
monitoring system for this study for those participants randomized to Omnipod 5. 
5 
STUDY SUMMARY 
5.1 
Study Purpose 
The purpose of this study is to demonstrate the efficacy and safety of the Omnipod 5 
System compared to pump and CGM therapy in adults with type 1 diabetes currently 
using pump therapy.     
5.2 
Study Design 
Adults with type 1 diabetes currently on pump therapy with an A1C between 7-11%, 
inclusive, will be recruited for the study.  At least 80% of participants must have an A1C 
≥ 8%.  At least 50% of participants must be using Omnipod for pump therapy at the time 

 
 
 
 
 
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of enrollment. 
 
Following a two-week standard therapy period where CGM data will be collected, 
participants will be randomized in a 2 (Intervention group):1 (Control group) ratio as 
follows: 
 
• 
Intervention Group - Omnipod 5 System with Dexcom G6 CGM or  
• 
Control Group – Participant’s current insulin pump with Dexcom G6 CGM 
 
Both groups will participate in a randomized period for 13-weeks after completion of 
standard therapy.   
 
A total of up to 200 participants at up to 15 clinical sites in the US and France will be 
enrolled in the study, to obtain a minimum of 170 randomized participants.  

 
 
 
 
 
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Table 1:Schedule of Assessments  
  
Screening 
Standard 
Therapy  
(14-days)  
13 Week Follow Up 
  
Visit Number 
1a 
2a 
3 
4h 
5 
6 
7 
8 
UVf 
 EWe 
Study Day/Visit Window 
Up to 30-
days prior to 
Study Day 1 
14-days prior 
to Study Day 
1  
1 
2 
+1d 
14 
±3d 
30 
±3d 
60 
±3d 
90 
±3d 
N/A 
  
Telephone (T) or Office (O) Visit 
O 
O 
O 
T/Od 
T/Od 
T/Od 
T/Od 
O 
T/Od 
O 
Screening/Randomization 
Informed Consent 
X 
  
  
  
  
  
  
  
  
  
Confirm eligibility 
X 
  
  
  
  
  
  
  
  
  
Randomization 
  
  
X 
  
  
  
  
  
  
  
Laboratory Assessments 
A1C (Central Lab) 
X 
  
  
  
  
  
  
X 
  
X 
A1C (Point of Care (POC) for eligibility) 
X 
  
  
  
  
  
  
  
  
  
TSH, Serum Creatinine, Lipid Panelb 
X 
  
  
  
  
  
  
  
  
  
Pregnancy Test (urine dipstick)j 
X 
  
X 
  
  
  
  
  
  
  
Clinical Assessments 
Medical History  
X 
  
  
  
  
  
  
  
  
  
Demographics  
X 
  
  
  
  
  
  
  
  
  
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
  
X 
Height 
X 
  
  
  
  
  
  
  
  
  
Weight 
X 
  
  
  
  
  
  
X 
  
X 
Vital signsc  
X 
  
X 
X 
X 
X 
X 
X 
  
X 
Electrocardiogram  
X 
  
  
  
  
  
  
  
  
  
Adverse events 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Insulin Delivery (Control arm only after visit 
3)k 
  
  
X 
  
  
X 
X 
X 
  
X 

 
 
 
 
 
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Questionnaires (See Table 2) 
Study Devices 
Study device training (BG/ketone meter, and 
CGM) 
  
X 
  
  
  
  
  
  
  
  
Dispense/Return QC Tested BG/ketone 
meter, and CGM 
  
Xh 
  
  
  
  
  
Xi 
  
Xi 
Study CGM sensor placement (Enrollment) 
  
X 
  
  
  
  
  
  
  
  
Start/Stop CGM data collection 
  
X 
  
  
  
  
  
X 
  
X 
Assess CGM usage to ensure data criteria 
has been metg 
  
Xg 
X 
  
  
  
  
  
  
  
Training on Glucagon administration and 
information on treatment of 
hypo/hyperglycemia 
  
 X 
  
  
  
  
  
  
  
Omnipod 5 training 
(Intervention arm only) 
  
  
X 
  
  
  
  
  
  
  
Dispense/Return Omnipod 5 System 
(Intervention arm only) 
  
  
X 
  
  
  
  
X 
  
X 
Data Portal initiation/discontinuation 
(Intervention arm only) 
  
  
X 
  
  
  
  
X 
  
X 
Complaints/device deficiencies 
  
  
X 
X 
X 
X 
X 
X 
X 
X 
BG/ketone meter data reviewd  
  
  
  
X 
X 
X 
X 
X 
  
X 
Pump and CGM data review 
  
  
  
X 
X 
X 
X 
X 
X 
X 
 
aScreening and Standard Therapy visits may be completed on the same day 
bTSH, Serum Creatinine and Lipid Panel (includes total cholesterol, HDL, LDL, triglycerides) laboratory assessments within the past 60 
days may be used for screening 
cVital signs include body temperature, respirations, pulse, and blood pressure should be performed at all in person visits 
dVisits identified as "T/O" can either be conducted in person at the clinical site or over the telephone.  Visits identified as "O" can only 
be conducted in person at the clinical site.  Vital signs are not required at any visit conducted via telephone, however, BG/Ketone 
meter data review should still occur 
eEarly withdrawal visit will only be conducted for participants who complete visit 3 and discontinue prior to visit 8    

 
 
 
 
 
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fUnscheduled visits will serve as extra study visits, if needed 
g Participants meeting the CGM usage and data criteria with their own Dexcom G6 will be eligible to immediately commence the study 
at Visit 3 (in which case, visit 1, visit 2, and visit 3 may occur on the same day). CGM data for EU subjects during Standard Therapy will 
be collected prospectively, and thus EU Subjects will need to participate in the full 14-day Standard Therapy phase.   
h BG/ketone meter must pass at least one level of quality control testing prior to dispensing 
I Undispensed BG/ketone meters do not need to be returned to sponsor 
j Pregnancy tests are only required at both visit 1 and visit 3 if these visits do not occur on the same day 
k Insulin delivery data will be collected and documented on a case report form for the control arm, the intervention arm data will automatically be collected by 
Insulet cloud  
Abbreviations:  S=Screening; EW=Early Withdrawal; QC=Quality Control Testing;  UV=Unscheduled Visit 
 
Table 2:Patient Reported Outcomes (Questionnaires) 
Visit 
Adult 
(ages 18-70) 
Visit 2 
Standard Therapy 
Clarke  
EQ-5D-3L 
T1DDS 
DQOL-brief 
DIDP 
HCS 
PSQI 
SUS 
INSPIRE-Adult 
  
Visit 8 
(End of Study) or 
Early Withdrawal 
Clarke  
EQ-5D-3L 
T1DDS 
DQOL-brief 
DIDP 
HCS 
PSQI 
SUS 
INSPIRE-Adult 
  

 
 
 
 
 
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6 
OBJECTIVES AND ENDPOINTS 
6.1 
Primary Objective 
To demonstrate superior efficacy of the Omnipod 5 System compared to pump and 
CGM therapy in adults with type 1 diabetes.   
6.1.1 Primary Endpoint 
The primary endpoint is per-participant percentage of time in range (TIR) 70-180 
mg/dL as measured by study CGM and comparing the Intervention group to the 
Control group during the 13 week randomized period.   
6.2 
Secondary Objective 
To demonstrate additional measures of efficacy and safety of the Omnipod 5 System 
compared to pump and CGM therapy in adults with type 1 diabetes.   
6.2.1 Secondary Endpoints 
The following secondary per-participant endpoints will be evaluated and 
compared in the Intervention group vs. Control group at the end of the 13-
weekrandomized period:  
• 
Percentage of time <54 mg/dL (non-inferiority) 
• 
Percentage of time >180 mg/dL  
• 
Mean glucose  
• 
Change from baseline in A1C 
• 
Percentage of time < 70 mg/dL 
• 
Change from baseline in T1-DDS total score  
• 
Change from baseline in HCS total score  
• 
Change from baseline in DQOL-brief total score  
6.3 
Exploratory Endpoints 
The following exploratory endpoints will be evaluated and compared in the Intervention 
group vs. Control group at the end of the 13-week randomized period: 
• 
Proportion of participants with A1C <7%  
• 
Proportion of participants with A1C <8%  
• 
Proportion of participants with ≥1% improvement in A1C from baseline  
• 
Proportion of participants with ≥10 relative percentage point improvement in 
A1C from baseline  
• 
Proportion of participants with either ≥1% improvement in A1C from baseline 
OR ≥10 relative percentage point improvement in A1C from baseline 
• 
Change from baseline in Body Mass Index (BMI) 
• 
Change from baseline in total daily insulin (TDI) (units/kg)  
• 
Additional CGM-derived endpoints, such as coefficient of variation, time 
above range >250 mg/dL, percentage of time < 54 mg/dL (superiority), TIR 
during daytime and nighttime hours 
• 
Number of episodes of severe hypoglycemia 
• 
Number of episodes of DKA 
 

 
 
 
 
 
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6.4 
Patient Reported Outcomes 
Questionnaires will be used to evaluate general and disease-specific quality of life, and 
device usability. Results will be assessed at 13 weeks compared to baseline 
(Intervention and Control group) 
• 
Clarke Hypoglycemia Awareness 
• 
EQ-5D-3L – Used to measure quality of life 
• 
T1-DDS1 – Used to measure four critical dimensions of distress 
• 
DQOL-brief2 – Used to assess the relative burden of an intensive diabetes 
treatment regimen 
• 
DIDP – Used to assess the perceived impact of diabetes in physical health, 
finances, relationships with family/friends, leisure activities, work/studies and 
emotional well-being  
• 
HCS3 – Used to measure hypoglycemia unawareness, hypoglycemia 
frequency, severity, and impact 
• 
PSQI – Used to measure sleep disturbance and usual sleep habits 
• 
SUS – Used to measure usability of a system 
• 
INSPIRE – Used to evaluate the impact of AID systems on the psychosocial 
functioning and quality of life 
7 
SCREENING AND ELIGIBILITY 
A total of up to 200 participants aged 18-70 years with type 1 diabetes currently on pump 
therapy with an A1C between 7-11%, inclusive, will be recruited for the study.  A 
screening visit will be scheduled for the potential participant for the clinical site to assess 
eligibility.  Participants who appear to meet the eligibility criteria will review and sign an 
informed consent form (ICF). Once the informed consent form has been signed and 
eligibility assessments have been completed and confirmed, study participants will be 
eligible to enroll in the study.  Enrollment will occur when the participant begins wearing 
the Dexcom G6 CGM dispensed for the study.  All study participants will receive 
Dexcom G6 CGM device training prior to enrollment.  Commencement of the standard 
therapy period will follow placement of the Dexcom G6 CGM.   
Participants who do not meet the eligibility criteria will not continue in the study and will 
be considered screen failures. 
Laboratory results within the last 60 days, except for A1C, may also be used if available.  
At the conclusion of the standard therapy period, participants will be randomized and 
assigned to either the Intervention group or the Control group using 2:1 randomization.  
Twice as many participants are expected to be randomized to the Intervention group 
versus the Control group.  
After completing the 14-day standard therapy period, participants randomized to the 
Intervention arm will be trained on the Omnipod 5 system, and all participants will 
transition to the 13-week period of the study.  Participants randomized to the control arm 
 
1 Change from baseline in T1-DDS total score at 13 weeks is a secondary endpoint. 
2 Change from baseline in DQOL-brief total score at 13 weeks 
3 Change from baseline in HCS total score at 13 weeks is a secondary endpoint. 

 
 
 
 
 
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will continue their usual pump therapy for the 13-week period of the study while using 
the study CGM. 
7.1 
Visit 1 (Up to 30 days prior to Study Day 1) 
Visit 1 will be conducted in person at the clinical study site. This visit will assess 
eligibility and will include: 
• 
Signing of informed consent 
• 
Review of inclusion/exclusion criteria and confirmation of eligibility 
• 
Assessments performed following Table 1:Schedule of Assessments  
 
7.1.1 Informed Consent 
Participants who appear to meet the eligibility criteria will be asked to review and 
sign an ICF approved by each respective Institutional Review Board (IRB) or 
Ethics Committee (EC) for participation in the study before any procedure or 
collection of any data that are not part of usual care.  
Participants will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR part 50, local regulations, ICH guidelines, Health 
Insurance Portability and Accountability Act (HIPAA) requirements, where 
applicable, and the IRB/IEC or study center. 
After informed consent is obtained, a participant identification number will be 
issued to uniquely identify each participant. The unique identifier will be used to 
identify the participant throughout the study and will be used for all source 
documents and electronic Case Report Forms (eCRFs). 
7.1.2 Confirm Eligibility 
7.1.2.1 Inclusion Criteria 
Participants must meet all the following criteria to be enrolled in the study: 
1. Age at time of consent 18-70 years of age 
2. Diagnosed with type 1 diabetes for at least 1 year. Diagnosis is based on 
investigator’s clinical judgment. 
3. On pump therapy for at least ≥ 3 months prior to screening and familiar with 
pump therapy concepts such as basal and bolus insulin delivery, and 
carbohydrate counting. Participants using automated insulin delivery (AID) 
devices, including devices with predictive low glucose suspend (PLGS), in the 
3 months prior to screening, will be excluded from participating. 
4. A1C 7.0-11.0% by point-of-care taken at screening visit 
5. Willing to use and obtain U-100 insulin: (either insulin aspart (Novolog, 
NovoRapid), or insulin lispro (Humalog, Admelog)), as the primary insulin 
treatment    
6. Must have a smartphone that supports the Dexcom app download and 
participants must be willing to use the app throughout the study 
7. Investigator has confidence that the participant can safely operate all study 
devices and can adhere to the protocol 
8. Willing to wear the system continuously throughout the study 
9. Willing and able to sign the Informed Consent Form (ICF) 
 

 
 
 
 
 
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7.1.2.2 Exclusion Criteria 
Participants who meet any of the following criteria will be excluded from the 
study: 
1. 
Any medical condition, such as untreated malignancy, unstable cardiac 
disease, unstable or end-stage renal failure, eating disorders, or other 
conditions which in the opinion of the investigator, would put the participant 
at an unacceptable safety risk 
2. 
History of severe hypoglycemia in the past 6 months 
3. 
History of diabetic ketoacidosis (DKA) in the past 6 months, unrelated to an 
intercurrent illness or infusion set failure 
4. 
Blood disorder or dyscrasia within 3 months prior to screening, including use 
of hydroxyurea, which in the investigator’s opinion could interfere with 
determination of HbA1C  
5. 
Currently on systemic steroids or intends to receive systemic steroid 
treatment in the next 6 months, including stable treatment for adrenal 
insufficiency. Inhaled, ophthalmic, topical, joint injection, and other locally 
applied steroids are allowed.  
6. 
Unable to tolerate adhesive tape or has any unresolved skin condition in the 
area of sensor or pump placement 
7. 
Use of non-insulin anti-hyperglycemic medication other than metformin, in 
the 12 weeks prior to the Baseline Visit. Participants taking metformin should 
remain on a steady dose during study participation. 
8. 
Pregnant or lactating, or is a woman of childbearing potential and not on 
acceptable form of birth control (acceptable forms of contraception include 
abstinence, barrier methods such as condoms, hormonal contraceptives, 
intrauterine device, surgical sterilization such as tubal ligation or 
hysterectomy, or vasectomized partner) 
9. 
Participation in another clinical study using an investigational drug or device 
within 30-days or 5 half-lives (whichever is longer) prior to screening, or 
intends to participate in any other study during this study period  
10. Unable to follow clinical protocol for the duration of the study or is otherwise 
deemed unacceptable to participate in the study per the investigator’s 
clinical judgment 
11. Participant is an employee of Insulet, an Investigator or Investigator’s study 
team, or immediate family member of any of the aforementioned 
 
7.1.3 Lab and Clinical Screening Assessments 
Participants who have signed the informed consent and appear to meet the 
eligibility criteria will continue to the screening assessments which will be 
performed at the clinical study site.   
Assessments may be completed up to 30-days prior to enrollment. Participants 
are considered enrolled upon placement of the first study CGM.  Assessments 
include the following: 
• A1C (Central Lab) 
• A1C (Point of Care for eligibility) 

 
 
 
 
 
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• TSH, Serum Creatinine, Lipid Panel (includes total cholesterol, HDL, 
LDL, triglycerides, assessments within the past 60 days may be used 
for screening) 
• Pregnancy test (urine dipstick) for women of childbearing potential 
• Medical history (including prior and current medical conditions and 
surgical history) 
• Demographics (age, gender, race (US only), ethnicity (US only)) 
• Review of concomitant medications 
• Height & weight 
• Vital signs (body temperature, respirations, pulse, and blood pressure) 
• Electrocardiogram 
 
Clinical sites will send a blood specimen for A1C to a central laboratory.  A point 
of care (POC) A1C will be used to determine eligibility.   
7.2 
Visit 2 (14-days prior to Study Day 1) 
Visit 2 will be conducted in person at the clinical study site and may be combined with 
Visit 1 if all eligibility criteria are met and laboratory assessments are determined to meet 
study criteria.  All scheduled assessments will be performed according to Table 
1:Schedule of Assessments and Table 2:Patient Reported Outcomes 
(Questionnaires).This visit will include: 
• 
Review of concomitant medications 
• 
Assessment of AEs 
• 
Questionnaires (Table 2:Patient Reported Outcomes (Questionnaires)) 
• 
Study device training per manufacturer’s instructions (CGM and BG/ketone 
meter) 
• 
Dispense BG/ketone meter, and CGM: 
o BG/ketone meter 
o Contour® Next One blood glucose meter (US sites only) 
o Contour® Next One blood glucose meter test strips (US sites only) 
o Precision Xtra blood ketone meter (US sites only) 
o Precision Xtra blood ketone meter test strips (US sites only) 
o FreeStyle Optium Neo blood glucose and ketone meter (EU sites only) 
o FreeStyle Optium Neo blood glucose and ketone strips (EU sites only) 
o Lancets 
o Dexcom G6 CGM (sensor and transmitter) 
o CGM Data Collection Device (EU sites only) 
• 
QC testing of BG/ketone meter 
o Must pass at least one level of quality control testing prior to dispensing 
• 
Study CGM sensor placement (Enrollment)  
o Assess CGM usage and data criteria are met for participants currently 
using Dexcom G6 (US sites only).  
o Sensor placement location will be reinforced as well as the importance 
of using approved locations 
o Ensure all participants understand how to troubleshoot sensor errors 
and avoid over-calibration of sensors 
• 
Start CGM data collection  

 
 
 
 
 
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• 
Training on glucagon administration and information on treatment of 
hypo/hyperglycemia   
7.2.1 Assessment of CGM Usage and Data Criteria  
7.2.1.1 Current Dexcom G6 Users (US Sites Only) 
Current Dexcom G6 users may be exempt from the standard therapy 14-day 
period if the following criteria are met: 
• Willing to provide 14-days of CGM data from the past 30-days 
• Meet the success criteria of 80% CGM use during any consecutive 
14-days in the past 30-days 
• Must have ≥ 2,016 CGM values during the 14-days 
 
The site staff will review the device use and data criteria to see if they have met 
the exemption criteria.  If exemption criteria are not met, participants may choose 
to continue to collect data until they meet the criteria or will be required to 
participate in the entire 14-day standard therapy period consistent with the 
requirements for non-G6 users. 
If participants meet the criteria, they will be immediately eligible to proceed with 
Visit 3, in which case Visit 1, Visit 2, and Visit 3 may occur on the same day, 
commencing the 13-week study. 
7.2.1.2 Non-G6 Users (US Sites Only) 
All non-G6 users will be required to participate in the entire standard therapy 14-
day period.  At the commencement of standard therapy, participants will be 
dispensed an unblinded Dexcom G6 CGM and will be instructed on how to 
download the Dexcom app on their personal cellular devices.  The site staff will 
link the participant’s Dexcom app with the data collection portal.  Participants will 
commence the 14-day period data collection period. 
7.2.1.3 CGM Data Criteria (EU Sites Only) 
All subjects in the EU will be required to participate in the entire standard therapy 
14-day period. At the commencement of standard therapy, participants will be 
dispensed a Dexcom G6 CGM and a CGM data collection device. The site staff 
will link the CGM data collection device with the data portal.  Participants will 
commence the 14-day data collection period. 
 
7.3 
CGM Usage 
During the standard therapy 14-day period, participants will be asked to do the 
following: 
• Manage their diabetes at home per their usual routine 
• Administer meal boluses per their usual dosing routine 
• Change their sensor if a sensor fails, or as needed 
• Calibrate their CGM, if required, per the manufacturer’s instructions   
• Monitor their capillary blood glucose (BG) as needed 
 

 
 
 
 
 
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At the conclusion of the 14-day standard therapy period, the data criteria will be 
reviewed to see if they have met the device use and data criteria.  If criteria are 
not met, participants may choose to continue to collect data until they meet the 
criteria.  Extending standard therapy past 14-days will not constitute a protocol 
deviation unless standard therapy extends past 30-days. If participants extend 
beyond the 14-days, the most recent 14-days of data meeting the criteria defined 
for CGM use and data criteria will be used in the endpoint analysis. 
7.3.1 CGM Initiation 
Participants will be provided with the Dexcom G6 CGM and instructed to use the 
devices throughout the study.  Dexcom G6 CGM training will be provided to all 
participants.  Current CGM users will be instructed to remove their personal CGM 
and place the study Dexcom G6 CGM.  Participants will be instructed to only use 
the study provided Dexcom G6 CGM device for the duration of the study. 
Participants will be provided with contact information for the clinical study site 
and advised to contact the site for any health or device related issues. 
7.4 
Visit 3 (Study Day 1) 
Visit 3 will mark the start of the 13-week study and will commence upon the conclusion 
of the standard therapy 14-day period and after all assessments are performed 
according to Table 1:Schedule of Assessments  
Visit 3 will be conducted in person at the clinical study site. All scheduled assessments 
will be performed according to Table 1:Schedule of Assessments This visit will include: 
• 
Randomization 
• 
Pregnancy test (urine dipstick) for women of childbearing potential (required 
only if Visit 1 and Visit 3 do not occur on the same day) 
• 
Review of concomitant medications 
• 
Vital signs 
• 
Assessment of AEs 
• 
Insulin delivery metrics (e.g., TDI, average basal and bolus insulin dose, and 
time on device over the past 30 days)  
• 
Assess CGM usage and data criteria has been met (at least 80% CGM use 
(11.2-days) during any consecutive 14-days in the past 30-days and ≥ 2,016 
CGM values during the 14-days) 
• 
All participants are required to have access to glucagon and receive training 
on how to deliver the medication 
• 
Omnipod 5 System device training conducted by trained clinical site staff 
(Intervention arm only) 
• 
Dispense Omnipod 5 System (Intervention group only) 
• 
Data Portal initiation (Intervention group only) 
• 
Dispense Dexcom CGM and confirm data transmission for those in control 
arm (Control group only) 
• 
Complaints/device deficiencies since last visit 
 

 
 
 
 
 
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7.4.1 Randomization 
Participants who meet all eligibility criteria, have completed all screening 
assessments, and have met the CGM device usage and data criteria will be 
randomized 2:1 using a computer-generated randomization scheme stratified by 
site, A1C (7% to <8% vs. ≥8% to 11%), and Omnipod use (user vs. non-user).  A 
permuted-block randomization scheme will be implemented to balance group 
assignments.  Randomization will be assigned via study database access during 
Visit 3 to the two study groups (Intervention Group:  Omnipod 5 System with 
Dexcom G6 CGM or Control Group:  Participant’s current pump with Dexcom G6 
CGM).  
 
During the 13-week study period, all participants will be asked to do the following: 
• 
Follow insulin therapy per recommendations from the clinical study staff 
• 
Follow their pre-exercise management such as insulin reduction for meal 
boluses, consumption of snacks, or adjusting their insulin delivery settings 
• 
Treat themselves per their usual routine if they become hypoglycemic or 
hyperglycemic or have symptoms of either at any time during the study 
• 
Consume meals and snacks of their own choosing. Participants will be 
encouraged to estimate the grams of carbohydrates for each meal or snack 
per their usual routine. The estimate should be entered into the meal bolus 
calculator. 
• 
Give meal boluses per their usual dosing routine 
• 
Change their CGM per manufacturer’s instructions or sooner if necessary 
• 
Change the Pod at least once every 72 hours (Intervention group only) 
• 
Change pump infusion site as recommended by manufacturer 
In the event of unexplained hyperglycemia, where the CGM is >300mg/dL for 1 hour or 
>250 mg/dL for 2 hours, blood glucose (measured with BG meter) and ketones should 
be checked. If BG is ≥300 mg/dL and ketones are >1.0 mmol/L, an occlusion or 
dislodged cannula should be suspected. The Pod or infusion set should be removed, 
and the participant will be instructed to replace the Pod or infusion set at a different 
location on the body. Participants should contact the clinical site for further instructions 
to determine whether an additional injection of insulin is required. This prolonged 
hyperglycemic event, defined as meter BG ≥300 mg/dL and ketones >1.0 mmol/L, will be 
recorded as an adverse event.  
7.5 
Visits 4 and 5 
Visit 4 and 5 will be conducted either over the telephone or in person at the clinical 
study site on study days 2 (+1d) and 14 (±3d) respectively. All scheduled assessments 
will be performed according to Table 1:Schedule of Assessments These visits will 
include: 
• 
Review of concomitant medications 
• 
Vital signs (for in person visits) 
• 
Assessment of AEs 
• 
Complaints/device deficiencies since last visit 
• 
BG/ketone meter data review by clinician  

 
 
 
 
 
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• 
Pump and CGM data review by clinician 
 
7.6 
Visits 6 and 7 
Visit 6 and 7 will be conducted either over the telephone or in person at the clinical 
study site on study day 30 (±3d) and 60 (±3d). All scheduled assessments will be 
performed according to Table 1:Schedule of Assessments This visit will include: 
• 
Review of concomitant medications 
• 
Vital signs (for in person visits) 
• 
Assessment of AEs 
• 
Complaints/device deficiencies since last visit 
• 
BG/ketone meter data review by clinician  
• 
Insulin delivery metrics (e.g., TDI, average basal and bolus insulin dose, and 
time on device over the past 30 days) (Control group only) 
• 
Pump and CGM data review by clinician  
 
7.7 
Visit 8 
Visit 8 will be conducted in person at the clinical study site on study day 90(±3d). All 
scheduled assessments will be performed according to Table 1:Schedule of 
Assessments  This visit will include: 
• 
A1C (central laboratory) 
• 
Review of concomitant medications 
• 
Weight 
• 
Vital signs 
• 
Assessment of AEs 
• 
Insulin delivery metrics (e.g., TDI, average basal and bolus insulin dose, and 
time on device over the past 30 days) (Control group only) 
• 
Completion of questionnaires (Table 2:Patient Reported Outcomes 
(Questionnaires)) 
• 
Return BG meter, Ketone meter, and study CGM, if unused 
• 
Stop CGM data collection  
• 
Return Omnipod 5 System (Intervention group only) 
• 
Data Portal (Intervention group only) discontinuation 
• 
Complaints/device deficiencies since last visit 
• 
BG/ketone meter data review by clinician 
• 
Pump and CGM Data review by clinician 
 
7.8 
Unscheduled Visits  
Aside from scheduled visits, participants may require an unscheduled visit either by 
telephone or in person at the clinical study site. All assessments will be performed 
according to Table 1:Schedule of Assessments . This visit will include, at a minimum: 
• 
Assessment of AEs  
• 
Complaints/device deficiencies since last visit 
• 
Pump and CGM data review by clinician 

 
 
 
 
 
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Additional assessments, including review of BG/ketone meter data, may be warranted at 
the discretion of the investigator. 
Unscheduled visits should be documented when there is meaningful contact with the 
subject, such as when updating device settings, subject retraining, or any in-person 
contact.  Basic or minor contacts to discuss subject visit scheduling, device questions, 
subject reminders, requests for or providing additional supplies, or follow up activities 
related to another scheduled visit should not be documented as an Unscheduled Visit. 
Instructions will be given to participants on how to contact clinical study staff 24 hours 
per day to report any study related problems. Participants will be encouraged to call the 
clinical study site at any time with any concerns.  
7.9 
Early Withdrawal 
Any participant may withdraw from the study at any time for any reason. Upon 
withdrawal, assessments will be performed following Table 1:Schedule of Assessments  
and Table 2:Patient Reported Outcomes (Questionnaires). The investigator may also 
terminate a participant’s participation in the study if it is in the best interest of the 
participant or if the Sponsor or local regulatory agency terminates the study. 
The Early Withdrawal visit will include: 
• 
A1C (central laboratory) 
• 
Review of concomitant medications 
• 
Weight 
• 
Vital signs 
• 
Assessment of AEs 
• 
Insulin delivery metrics (e.g., TDI, average basal and bolus insulin dose, and 
time on device) (Control group only) 
• 
Completion of questionnaires (Table 2:Patient Reported Outcomes 
(Questionnaires) 
• 
Return BG meter, Ketone meter, and study CGM, if unused 
• 
Return Omnipod 5 System (Intervention group only) 
• 
Stop CGM data collection   
• 
Data Portal discontinuation (Intervention group only) 
• 
Complaints/device deficiencies such as occlusion alarms and system hazard 
alarms since last visit 
• 
BG/ketone meter data review by clinician 
• 
Pump and CGM data review by clinician 
The reason for withdrawal will be recorded, and their participation in the study will end. 
In the event of a participant’s death during the study, the participant’s participation will be 
considered terminated, and the date of death will be used as the date of study exit. 
7.10 Lost to Follow-up 
Every effort will be made to contact a participant in the event of a missed scheduled visit. 
A participant will be considered lost to follow-up if they are inaccessible by two or more 

 
 
 
 
 
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different methods of contact and fail to show up for two scheduled visits. The site will 
document each attempt made to contact the participant and specify the reason for early 
withdrawal as lost to follow-up.      
8 
SPONSOR REPRESENTATIVES 
One or more representatives of the Sponsor may be present at the clinical study site 
during study visits under supervision of study site personnel. 
9 
SAFETY 
9.1 
Types of Known Risks and Benefits 
There are known risks and benefits. Most of the risks are not unique to the study and are 
typical for patients using insulin pumps, CGM, and BG meters. For the Control group, 
the applicable Instructions for use (IFU) should be referenced for any additional potential 
risks. 
The known risks are as follows: 
• Hypoglycemia and/or hyperglycemia as a result of change in diet, 
activity, diabetes management or insulin regimen during the study. 
• Hypoglycemia and/or hyperglycemia as a result of over or under delivery 
of insulin due to a device defect, failure or malfunction of any of the 
system components. 
• Hypoglycemia, hyperglycemia, diabetic ketoacidosis, seizure, coma or 
death related to insulin administration, pump use or misuse, or Omnipod 
5 System use or misuse. 
• Use of the Pod – because the Pod uses only rapid-acting insulin, users 
are at increased risk for developing hyperglycemia if insulin delivery is 
interrupted. If it is untreated, prolonged hyperglycemia can lead to 
diabetic ketoacidosis (DKA). DKA can cause symptoms such as 
breathing difficulties, shock, coma, or death. Further, occlusions can 
interrupt insulin delivery and lead to hyperglycemia or DKA. Other 
potential risks associated with using the Pod are: 
• Anaphylaxis (allergic shock) 
• Bruising at the Pod site 
• Bleeding at the Pod site 
• Erythema (redness at the Pod site) 
• Excoriation (raw skin at Pod site) 
• Pruritus (itching) 
• Induration (hardening of the skin at the Pod site) 
• Infection (can include heat, redness, swelling, pain, and drainage) 
• Inflammation (redness, swelling) 
• Skin reaction to adhesive at the Pod site 
• Papule (small, solid raised area on the skin similar to a pimple) 
• Pain or discomfort 
• Ulceration (skin sores) 
• Vesicles (blisters) 
• 
Use of the CGM – risk of bruising, infection, pain and/or bleeding at the site of 
insertion, and skin site reaction to adhesive 

 
 
 
 
 
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• 
Use of the Controller – risk of overheating of the Omnipod 5 Controller 
charging port and cable, including the cable melting, deforming, or 
discoloring. The excess heat may cause minor burns if those areas of the 
controller are touched or could lead to fire. 
• 
On rare occasions, the CGM sensor may break and leave a small portion of 
the sensor under the skin that may cause redness, swelling, or pain at the 
insertion site, and may require surgical removal. 
• 
Blood sampling with fingerstick – minor discomfort and risk of infection at site 
of fingerstick 
There may be no direct benefits to participating in this study however knowledge will be 
gained that may benefit others. In addition, participants may experience improvements in 
glycemic control. 
9.2 
Hypoglycemia/Hyperglycemia 
Participants will be asked to treat per their usual routine if they suspect either 
hypoglycemia or hyperglycemia, either by confirmation of hypoglycemia with a 
fingerstick BG, symptoms, or perceived risk.  
Participants will be encouraged to manage their hyperglycemia per their usual routine. 
This includes checking for ketones and administering a correction bolus if needed.   
In the event of unexplained hyperglycemia, where the CGM is >300mg/dL for 1 hour or 
>250 mg/dL for 2 hours, blood glucose (measured with BG meter) and ketones should 
be checked. If BG is ≥300 mg/dL and ketones are >1.0 mmol/L, an occlusion or 
dislodged cannula should be suspected. The Pod or infusion set should be removed, 
and the participant will be instructed to replace the Pod or infusion set at a different 
location on the body. Participants should contact the clinical site for further instructions 
to determine whether an additional injection of insulin is required. This prolonged 
hyperglycemic event, defined as meter BG ≥300 mg/dL and ketones >1.0 mmol/L, will be 
recorded as an adverse event.  
9.3 
Adverse Events 
Adverse Event (AE): is defined as any untoward medical occurrence, unintended 
disease or injury, or any untoward clinical signs (including an abnormal laboratory 
finding) in participants, users or other persons, whether or not related to the 
investigational medical device. 
NOTE 1: This includes events related to the investigational medical device or the 
comparator.22 
NOTE 2: This definition includes events related to the procedures involved (any 
procedure in the clinical investigation plan).22 
Serious Adverse Event (SAE): Any untoward medical occurrence that: 
• 
Led to death 
• 
Led to serious deterioration in the health of the participant, that either resulted 
in: 

 
 
 
 
 
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• 
a life-threatening illness or injury, or 
• 
a permanent impairment of a body structure or a body function, or 
• 
hospitalization, or prolonged existing hospitalization, or 
• 
medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function. 
• 
Led to fetal distress, fetal death, or a congenital abnormality or birth defect. 
 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by 
the clinical investigational plan, without serious deterioration in health, is not considered 
a serious adverse event.22 
Unanticipated Serious Adverse Device Effect (USADE): 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 participants. 22 
Adverse Device Effect (ADE): An adverse device effect (ADE) is an adverse event 
related to the use of an investigational medical device.22 
NOTE 1: This definition includes any adverse event resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or operation, or 
any malfunction of the investigational medical device. 22 
NOTE 2: This definition includes any event resulting from user error or from intentional 
misuse of the investigational medical device. 22 
An event that occurs solely due to participant (i.e., user) error in which the device 
functions properly generally will not be considered an ADE unless it is determined that 
the instructions on the screen of the device or user manual (or similar training materials) 
may have contributed to the event (note: the event may still meet criteria for reporting as 
an adverse event). 
Serious Adverse Device Effect (SADE): A serious adverse device effect is defined as 
an adverse device effect that has resulted in any of the consequences characteristic of a 
serious adverse event. 22 
Anticipated Serious Adverse Device Effect (ASADE): anticipated serious adverse 
device effect (ASADE) is an effect which by its nature, incidence, severity or outcome 
has been identified in the risk assessment.  
Device Deficiency (DD): A device deficiency is defined as a device related complaint or 
malfunction or any inadequacy of a device with respect to its identity, quality, durability, 
reliability, safety or performance and includes misuse or use errors and inadequate 
labeling. A device deficiency is something that happens to a device or is related to 
device performance, whereas an adverse event happens to a participant. A device 
deficiency may occur independently from an AE, or along with an AE. An AE may occur 
without a device deficiency or there may be an AE related to a device deficiency. 
For any event where there is suspicion that the Omnipod 5 study device is involved, the 
Sponsor will request that the investigator return the device component for evaluation. 

 
 
 
 
 
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All device deficiencies will be reported to the Sponsor within 3 business days of 
knowledge of the deficiency and documented on an appropriate eCRF. Once entered, 
notifications will be sent automatically to Sponsor.  Alternate reporting methods will be 
provided to site for notifying Sponsor if database entry is inaccessible.  All device 
components associated with a reported device deficiency (Controller, Pod, and CGM) 
should be retained at the clinical site and returned to the Sponsor or CGM manufacturer 
for investigation and analysis. 
9.4 
Reportable Adverse Events 
Adverse events will be assessed on an ongoing basis throughout the study. Adverse 
event reporting will begin at the start time of the standard therapy (i.e., insertion of the 
CGM sensor) and continue until the participant’s participation has ended. All adverse 
events must be followed until resolution, or until the AE has stabilized, or until the study 
has been completed. 
Pre-existing medical conditions or symptoms observed prior to the start time of the 
standard therapy phase will not be recorded as an AE and should be collected in the 
participant’s medical history. In the event there is a change (i.e., worsening) in the pre-
existing medical condition or symptoms after enrollment meeting the criteria of a 
reportable adverse event, then an AE must be reported. 
For this protocol, a reportable adverse event includes any untoward medical occurrence 
that meets one of the following criteria: 
1. An SAE 
2. An ADE unless excluded from reporting in Hypoglycemic Events and 
Hyperglycemic/Ketotic Events sections below 
3. An AE not related to a study device issue which leads to temporary or 
permanent discontinuation of the study devices or the participant’s own insulin 
pump, or creates a clinically significant impact on a participant’s glucose control 
4. An AE that affects the participant’s ability to complete any study procedures 
5. An AE for which a visit is made to a hospital emergency department   
6. Hypoglycemic Events as defined below 
7. Hyperglycemia/Ketotic Events as defined 
9.5 
Hypoglycemic Events 
Hypoglycemia is only reportable as an adverse event when one of the following criteria 
is met:   
• 
Severe Hypoglycemia: The event required assistance of another person due 
to altered consciousness, and required another person to actively administer 
carbohydrate, glucagon, or other resuscitative actions21. This means that the 
participant was impaired cognitively to the point that he/she was unable to 
treat himself/herself, was unable to verbalize his/her needs, was incoherent, 
disoriented, and/or combative, or experienced seizure or loss of 
consciousness. These episodes may be associated with sufficient 
neuroglycopenia to induce seizure or loss of consciousness.  If plasma 

 
 
 
 
 
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glucose measurements are not available during such an event, neurological 
recovery attributable to the restoration of plasma glucose to normal is 
considered sufficient evidence that the event was induced by a low plasma 
glucose concentration. 
• 
Hypoglycemia resulting in an SAE that may not otherwise meet the definition 
of Severe Hypoglycemia defined above. 
When a hypoglycemic event meets the above reporting requirements, an Adverse Event 
Form should be completed. A severe hypoglycemia event should be considered a 
serious adverse event and follow the SAE reporting requirements. 
9.6 
Hyperglycemic/Ketotic Events 
Hyperglycemia is only reportable as an adverse event when any of the following criteria 
is met:   
• The event involved DKA, as defined by the Diabetes Control and 
Complications Trial (DCCT)20 , i.e. if all of the following are present: 
• Symptoms such as polyuria, polydipsia, nausea, or vomiting; 
• Serum ketones >1.5 mmol/L or large/moderate urine ketones; 
• Either arterial blood pH <7.30 or venous pH <7.24 or serum 
bicarbonate <15; and 
• Treatment provided in a health care facility 
• 
Evaluation or treatment was obtained at a health care provider facility for an 
acute event involving hyperglycemia or ketosis, or the participant contacted 
the site and received guidance on how to manage the hyperglycemia/ketosis 
• 
Prolonged hyperglycemia: defined as meter BG ≥300 mg/dL for over 1 hour 
and ketones >1.0 mmol/L 
• 
Hyperglycemia resulting in an SAE that may not otherwise meet the above 
criteria 
When a hyperglycemia/ketotic event meets the above reporting requirements, Adverse 
Event Form should be completed.  
Events meeting DKA criteria should be considered a serious adverse event and follow 
the SAE reporting requirements. Hyperglycemia events not meeting criteria for DKA 
generally will not be considered as serious adverse events unless one of the SAE 
criteria above is met 
9.7 
Relationship of Adverse Event to Devices or Study Procedures 
The investigator will be responsible for deciding on the causal relationship of the AE. 
Specifically, the investigator will report whether the AE was related to study procedures 
and/or related to the devices (participant’s own insulin pump, study CGM and Omnipod 
5). 
To ensure consistency of adverse event causality assessments, investigators should 
apply the following general guidelines when determining whether an adverse event is 
related. 
The causal relationship to the study procedures and the devices for each adverse event 
will be rated as follows:  

 
 
 
 
 
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• Unrelated: The event is not related to the procedures or the investigational 
device.  
• Possibly Related: The temporal sequence is such that the relationship is not 
unlikely or there is no contradicting evidence that can reasonably explain the 
participant’s condition. There is a possibility of any relation between the 
event and the procedures or the devices.  
• Related: The temporal sequence is relevant, or the event abates upon 
completion of the procedure/ use of devices, or the event cannot be 
reasonably explained by the participant’s condition or comorbidities. The 
event is related or most likely associated with the procedures or the devices. 
 
9.8 
Severity (Intensity) of Adverse Events 
The severity (intensity) of an adverse event will be rated on a three-point scale: (1) mild, 
(2) moderate, or (3) severe. A severity assessment is a clinical determination of the 
intensity of an event. Thus, a severe adverse event is not necessarily serious. For 
example, itching for several days may be rated as severe, but may not be clinically 
serious. 
• 
Mild: Usually transient, requires no special treatment, and does not interfere 
with the participant’s daily activities. 
• 
Moderate: Usually causes a low level of inconvenience, discomfort or 
concern to the participant and may interfere with daily activities but is 
usually ameliorated by simple therapeutic measures and participant is able 
to continue in study. 
• 
Severe: Interrupts a participant’s usual daily activities, causes severe 
discomfort, may cause discontinuation of study device, and generally 
requires systemic drug therapy or other treatment. 
 
9.9 
Outcome of Adverse Events 
The outcome of each reportable adverse event will be classified by the investigator as 
follows: 
• Recovered/Resolved – The participant recovered from the AE/SAE without 
sequelae. Record the AE/SAE stop date. 
• Recovered/Resolved with Sequelae – The event persisted and had 
stabilized without further anticipated change in the event status. Record the 
AE/SAE stop date. 
• Fatal – A fatal outcome is defined as the SAE that resulted in death. Only 
the event that was the cause of death should be reported as fatal.  
AEs/SAEs that were ongoing at the time of death; however, were not the 
cause of death, will be recorded as “resolved” at the time of death. 
• Not Recovered/Not Resolved (Ongoing) – An ongoing AE/SAE is defined as 
the event was ongoing with an undetermined outcome. 
• An ongoing outcome will require follow-up by the site in order to 
determine the final outcome of the AE/SAE or until participant 
completes the study. 
• The outcome of an ongoing event at the time of death that was not 
the cause of death, will be updated and recorded as “resolved” with 
the date of death recorded as the stop date. 

 
 
 
 
 
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• Unknown – An unknown outcome is defined as an inability to access the 
participant or the participant’s records to determine the outcome (for 
example, a participant that was lost to follow-up). 
 
If any USADEs are ongoing when a participant completes the study (or withdraws), the 
participant will continue to be followed until the event resolves or has no prospect of 
improvement or change, even after the participant has completed all applicable study 
visits/contacts, unless that participant has withdrawn their consent. For all other 
reportable adverse events, data collection will end at the time the participant completes 
the study. Note: Participants should continue to receive appropriate medical care for an 
adverse event after their participation in the study ends.  
9.10 Reportable Device Issues 
Device deficiencies will be reported except in the following circumstances. These 
occurrences are expected and will not be reported on a Device Deficiency Form: 
• 
CGM sensor, Pod or infusion set lasting fewer days than expected per 
manufacturer 
• 
CGM tape, Pod or infusion set adherence issues 
• 
Battery lifespan deficiency of the Controller due to inadequate charging or 
extensive wireless communication 
• 
Intermittent device communication issues not requiring replacement  
• 
Device issues, including alerts and alarms, clearly addressed in the user 
guide that do not require additional troubleshooting 
 
9.11 Timing of Event Reporting 
SAEs possibly related or related to a study device or study procedures and UADEs must 
be reported to the Sponsor/CRO within 2 business days of the site becoming aware of 
the event. This can occur via phone or email to the CRA/site monitor or Study Physician, 
or by completion of the AE eCRF. If the form is not initially completed, it should be 
completed as soon as possible after there is sufficient information to evaluate the event. 
All other reportable AEs should be submitted by completion of the AE eCRF within 5 
business days of the site becoming aware of the event.  
Each principal investigator is responsible for reporting adverse events required by this 
protocol and abiding by any other reporting requirements specific to his/her Institutional 
Review Board or Ethics Committee.  
Upon receipt of a USADE report, the Sponsor will investigate the UADE and if indicated, 
report the results of the investigation to all participating investigators, overseeing IRBs or 
ECs, and Regulatory Authorities within 7 calendar days of the Sponsor becoming aware 
of the USADE. Copies of the associated reports and correspondence with the 
investigators, regulatory authorities, and Sponsor must be retained with study records. 
The Medical Monitor will determine if the USADE presents an unreasonable risk to 
participants as described in the safety management plan (SMP) and in accordance with 
local regulations.  
Device deficiencies will be handled by the Sponsor or designee. 

 
 
 
 
 
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If the participant is hospitalized because of or during the course of an SAE, then a copy 
of the hospital discharge summary should be requested for inclusion with the SAE 
documentation. In case of death, the investigator must make every effort to obtain a 
copy of the death certificate to submit to the Sponsor. When submitting copies of 
documentation, all participant identifying information must be redacted and only the 
unique participant number will be used to label the forms for identification purposes. All 
relevant documents in the local language should be summarized in English on the Case 
Report Form. 
For any event where there is suspicion that the Omnipod 5 device is involved, the 
investigator will return the device for evaluation when possible. 
9.12 Safety Oversight 
The Medical Monitor will review all adverse events and adverse device events that are 
reported during the study. SAEs will typically be reviewed within 24-hours of reporting. 
Upon receipt of the SAE Report Form, the Medical Monitor will determine whether the 
event is unanticipated based on the investigator brochure (IB). 
A listing of all AEs will be reviewed periodically by the Medical Monitor as part of routine 
safety signal detection. 
10 
STOPPING CRITERIA 
10.1 Participant Discontinuation of Study Participation 
In the case of a USADE for Intervention group participants, the Medical Monitor will 
determine if the use of the investigational device will be suspended while the problem is 
diagnosed. The use of the investigational device may continue if the Medical Monitor 
believes the event is explainable, unlikely to reoccur and that it is safe for the participant 
to continue using the device. Alternatively, the Medical Monitor may request the study 
participant, or all study participants, to stop using the investigational device or to only 
use in Manual Mode. Should Intervention group study participants be required to stop 
using the study device or to only use in Manual Mode due an USADE, use of the study 
device or Automated Mode will not be restarted until approval is received from the 
regulatory authorities. 
Use of the investigational device by a participant will be discontinued if any of the 
following occur:  
• 
The investigator, sponsor, or Medical Monitor believes it is unsafe for the 
participant to continue in the study for any reason. This could be due to the 
development of a new medical condition or worsening of an existing 
condition; or participant behavior contrary to the indications for use of the 
device that imposes on the participant’s safety. 
• 
The participant requests that the treatment be stopped 
• 
Participant pregnancy 
• 
Two distinct episodes of DKA as defined above 
• 
Two distinct severe hypoglycemia events as defined above 
• 
One episode of DKA and one severe hypoglycemia event as defined above 

 
 
 
 
 
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An additional requirement for continued study device use following a single DKA or 
severe hypoglycemia event will be that (1) the site investigator believes that the event is 
explainable, unlikely to recur, and that it is safe for the participant to continue to use the 
system and (2) the Medical Monitor concurs. If the Medical Monitor determines that the 
occurrence of the event indicates that it is not safe for the participant to continue to use 
the system, use will be discontinued, and the participant will be withdrawn from the 
study. 
10.2 Criteria for Suspending or Stopping Overall Study 
Error! Reference source not found.For unanticipated adverse device effects 
(USADEs), the Study Physician, together with the Medical Monitor per the Safety 
Management Plan (SMP), will determine whether the study should proceed or not based 
upon risk of additional serious adverse events and the underlying root cause analysis of 
the USADE. 
Study activities could be similarly suspended if the manufacturer of any component of 
the investigational study device requires stoppage of device use for safety reasons (e.g., 
product recall).  
The affected study activities may resume if the underlying problem can be corrected by a 
protocol or system modification that will not invalidate the results obtained prior to 
suspension.  
The Study Physician and Medical Monitor may recommend suspension of study 
activities or stoppage of the study if deemed necessary based on the totality of safety 
data available. 
10.3 Safety Signal Detection 
Selected data from this study will be reviewed periodically to detect as early as possible 
any safety concern(s) related to the device so that Investigators, clinical study 
participants, regulatory authorities, and IRBs/IECs will be informed appropriately and as 
early as possible. 
The Medical Monitor will conduct adjudication of any events of DKA or severe 
hypoglycemia or any additional events as requested by the Sponsor. The specified 
events will be adjudicated to determine: 
• 
event relatedness to the study procedures and/or the devices (participant’s 
own insulin pump, study CGM and Omnipod 5) 
• 
whether an adverse event is unanticipated 
The adjudication decision of the Medical Monitor will be used for the final classification of 
events, including relatedness to the study procedures and/or the devices, for the 
determination of safety endpoints and for all regulatory reports, product labeling, and 
publications or presentations. 
Detailed roles and responsibilities of the Study Physician and Medical Monitor are 
described in the SMP.  

 
 
 
 
 
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11 
STATISTICAL CONSIDERATIONS 
11.1 Primary Endpoint and Hypotheses 
The primary endpoint is per-participant percentage of time in range (TIR) 70-180 mg/dL 
as measured by study CGM and comparing the Intervention group to the Control group 
during the 13-week randomized period. The null hypothesis is that the mean percentage 
of TIR 70-180 mg/dL in the Intervention group is equal to the mean percentage of TIR 
70-180 mg/dL in the Control group during the 13 weeks. The alternative hypothesis is 
that the mean percentage of TIR 70-180 mg/dL in the Intervention group is not equal to 
the mean percentage of TIR 70-180 mg/dL in the Control group during the 13 weeks. 
Formally, the null and alternative hypotheses for the primary efficacy endpoint are: 
H0: µI - µC = 0 
HA: µI - µC ≠ 0 
Where µI and µC are the population means of per-participant percentage of TIR 70-180 
mg/dL as measured by the study CGM during the 13 weeks in the Intervention and 
Control groups, respectively. 
The primary endpoint will be analyzed with a linear mixed effects model with TIR 70-180 
mg/dL during the 13-weeks as the outcome. The full model specification will be 
described in the SAP. 
11.2 Secondary Endpoints and Hypotheses 
The following secondary per-participant endpoints will be evaluated and compared in the 
Intervention group vs. Control group at the end of the 13-week randomized period:  
• 
Percentage of time <54 mg/dL (non-inferiority) 
• 
Percentage of time >180 mg/dL  
• 
Mean glucose  
• 
Change from baseline in A1C  
• 
Percentage of time < 70 mg/dL 
• 
Change from baseline in Type 1-Diabetes Distress Scale (T1-DDS) total 
score at 13 weeks 
• 
Change from baseline in Hypoglycemia Confidence Scale (HCS) total score 
at 13 weeks 
• 
Change from baseline in Diabetes Quality of Life-brief (DQOL-brief) total 
score at 13 weeks 
 
Secondary Endpoints will be tested in a hierarchical fashion. 
The null and alternative hypotheses for the secondary endpoints are as follows: 
Percentage of time < 54 mg/dL (non-inferiority): 
H0: µI - µC  ≥ 1% 
HA: µI - µC < 1% 
Where µI and µC are the population means of percentage of time < 54 mg/dL during the 
13 weeks in the Intervention and Control groups, respectively. The non-inferiority margin 
is 1%. If the upper bound of the two-sided 95% confidence interval for the difference (µI 

 
 
 
 
 
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minus µC) is <1%, non-inferiority will be established. If the upper bound of the two-sided 
95% confidence interval for the difference (µI minus µC) is <0%, superiority of the 
Intervention group compared to the Control group will be established. 
 
Percentage of time >180 mg/dL: 
H0: µI - µC  = 0 
HA: µI - µC ≠ 0 
 
Where µI and µC are the population means of percentage of time >180 mg/dL during the 
13 weeks in the Intervention and Control groups, respectively. 
 
Mean glucose: 
H0: µI - µC  = 0 
HA: µI - µC ≠ 0 
 
Where µI and µC are the population means of mean glucose during the 13 weeks in the 
Intervention and Control groups, respectively. 
 
Change from baseline in A1C: 
H0: µI - µC = 0 
HA: µI - µC ≠ 0 
 
Where µI and µC are the population means of change from baseline in A1C after 13 
weeks in the Intervention and Control groups, respectively. 
 
Percentage of time < 70 mg/dL: 
H0: µI - µC = 0 
HA: µI - µC ≠ 0 
 
Where µI and µC are the population means of percentage of time < 70 mg/dL during the 
13 weeks in the Intervention and Control groups, respectively. 
 
Change from baseline in Type 1-Diabetes Distress Scale (T1-DDS) total score at 13 
weeks:  
H0: µI - µC =0 
HA: µI - µC ≠ 0 

 
 
 
 
 
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Where µI and µC are the population means of change from baseline in T1-DDS total 
score after 13 weeks in the Intervention and Control groups, respectively. 
If change from baseline in T1-DDS total score after 13 weeks is found to be statistically 
significantly different in the Intervention group compared to the Control group, the 
proportion of subjects in each treatment group achieving an improvement of ≥≥2 0.19 
points (MCID) in the T1-DDS total score after 13 weeks will also be compared. Those 
hypotheses are stated as:  
H0: πI - πC = 0  
HA: πI - πC ≠ 0  
  
Where πI and πC are the proportion of subjects achieving an improvement of 0.19 ≥2 
points (MCID) in the T1-DDS total score after 13 weeks in the Intervention and Control 
groups, respectively.  
 
Change from baseline in Hypoglycemia Confidence Scale (HCS) total score at 13 
weeks: 
H0: µI - µC = 0 
HA: µI - µC ≠ 0 
 
Where µI and µC are the population means of change from baseline in HCS total score 
after 13 weeks in the Intervention and Control groups, respectively. 
If change from baseline in HCS total score after 13 weeks is found to be statistically 
significantly different in the Intervention group compared to the Control group, the 
proportion of subjects in each treatment group achieving a score of ≥3 points in the HCS 
total score after 13 weeks will also be compared. Those hypotheses are stated as:  
H0: πI - πC = 0  
HA: πI - πC ≠ 0  
  
Where πI and πC are the proportion of subjects achieving a score of ≥3 points in the HCS 
total score after 13 weeks in the Intervention and Control groups, respectively.  
 
 
Change from baseline in Diabetes Quality of Life-brief (DQOL-brief) total score at 13 
weeks: 
H0: µI - µC = 0 
HA: µI - µC ≠0 
 
Where µI and µC are the population means of change from baseline in DQOL-brief total 
score after 13 weeks in the Intervention and Control groups, respectively. 

 
 
 
 
 
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If change from baseline in DQOL-brief total score after 13 weeks is found to be 
statistically significantly different in the Intervention group compared to the Control 
group, the proportion of subjects in each treatment group achieving a clinically 
meaningful improvement in the DQOL-brief total score after 13 weeks will also be 
compared. Those hypotheses are stated as:  
H0: πI - πC = 0  
HA: πI - πC ≠ 0  
  
Where πI and πC are the proportion of subjects achieving a clinically meaningful 
improvement (defined as ≥0.5*standard deviation of change from baseline in DQOL-
brief total score at 13 weeks) in the DQOL-brief total score after 13 weeks in the 
Intervention and Control groups, respectively.  
 
Secondary endpoints will be analyzed using linear mixed effect models. The full model 
specifications will be described in the SAP. 
 
11.3 Exploratory Endpoints 
The following additional endpoints will be evaluated and compared in the Intervention 
group vs. Control group at the end of the 13-week randomized period: 
• 
Proportion of participants with A1C <7%  
• 
Proportion of participants with A1C <8%  
• 
Proportion of participants with ≥1% improvement in A1C from baseline  
• 
Proportion of participants with ≥10 relative percentage point improvement in 
A1C from baseline  
• 
Proportion of participants with either ≥1% improvement in A1C from baseline 
OR ≥10 relative percentage point improvement in A1C from baseline 
• 
Change from baseline in Body Mass Index (BMI) 
• 
Change from baseline in total daily insulin (TDI) (units/kg)  
• 
Additional CGM-derived endpoints, such as coefficient of variation, time 
above range >250 mg/dL, percentage of time < 54 mg/dL (superiority), TIR 
during daytime and nighttime hours 
• 
Number of episodes of severe hypoglycemia 
• 
Number of episodes of DKA 
 
11.4 Patient-Reported Outcomes 
The following questionnaires will be used to evaluate general and disease-specific 
quality of life, and device usability. Results will be assessed at 13 weeks compared to 
baseline (Intervention and Control group). 
• 
Clarke hypoglycemia awareness questionnaire - Used to assess impaired 
awareness of hypoglycemia 
• 
EQ-5D-3L – Used to measure quality of life 
• 
T1-DDS1 – Used to measure four critical dimensions of distress 
• 
DQOL-brief2 – Used to assess the relative burden of an intensive diabetes 
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• 
DIDP – Used to assess the perceived impact of diabetes in physical health, 
finances, relationships with family/friends, leisure activities, work/studies and 
emotional well-being  
• 
HCS3 –Used to measure hypoglycemia unawareness, hypoglycemia 
frequency, severity, and impact 
• 
PSQI – Used to measure sleep disturbance and usual sleep habits 
• 
SUS – Used to measure usability of a system 
• 
INSPIRE – Used to evaluate the impact of AID systems on the psychosocial 
functioning and quality of life 
Any endpoint that is not listed as a Primary, Secondary, or Exploratory endpoint will be 
treated as exploratory. 
11.5 Sample Size 
The study is powered at 90% to detect a between-group difference of 10% in TIR 70-180 
mg/dL and assuming a standard deviation of 16.5% in each group.  Under these 
assumptions and with 2:1 Intervention:Control randomization, a total sample size of 131 
participants is required (87 Intervention, 44 Control). To allow for pre-randomization 
attrition of up to 15%, and post-randomization attrition of up to 22.9%,a total sample size 
of up to 200 will be enrolled to obtain 170 randomized participants with 131 participants 
completing the 13 weeks. The anticipated difference in TIR 70-180 mg/dL was projected 
from the OP5 pivotal study. PASS 2022 was used for sample size calculations. 
11.6 Analysis Sets 
The following analysis sets are planned for the study: 
11.6.1 ITT (Intention to Treat) Analysis Set 
The ITT analysis set includes all participants that are enrolled in the study. All 
safety analyses will be based on the ITT analysis set. 
11.6.2 mITT (modified Intention to Treat) Analysis Set 
The modified Intention to Treat (mITT) analysis set is a subset of the ITT analysis 
set. The mITT analysis set will consist of all participants who have been 
randomized. The mITT analysis set will be used as the primary analysis for the 
primary and secondary endpoints and for other clinical outcome data. 
11.7 PP (Per-Protocol) Analysis Set 
The Per-Protocol (PP) analysis set is a subset of the mITT analysis set. Participants will 
be included in the PP analysis set if they have a minimum of 80% system use as 
measured by the study CGM (control group) or Omnipod 5 (intervention group) during 
the 13-week randomized period over a minimum duration of 10 weeks and have 
completed the study without major protocol deviations. The PP analysis set will be used 
as supportive analysis for the endpoints. The following will be considered major protocol 
deviations: 
• 
Major inclusion/exclusion criterion deviation 

 
 
 
 
 
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• 
Significant protocol non-compliance that may confound the study objective 
data (e.g., use of prohibited medications, not using control group pump for 
prolonged period) 
The list of participants excluded from the PP analysis set will be determined prior to 
analysis while blinded to treatment group. If the PP analysis set does not differ from the 
mITT analysis set, separate analyses will not be presented. 
11.8 Analysis of Primary and Secondary Endpoints 
The primary endpoint will be tested for statistical significance in the mITT analysis set at 
a two-sided significance level of.5%. Hypothesis testing for the secondary endpoints will 
commence if and only if the primary endpoint is found to be statistically significant (i.e. 
two-sided p-value ≤ 0.05). Strict control of Type I error will be maintained with a 
hierarchical testing procedure, with secondary endpoints tested in the following order: 
• 
Percentage of time <54 mg/dL (non-inferiority) 
 
If the upper bound of the two-sided 95% confidence interval for the 
difference (µI minus µC) is <1%, non-inferiority will be established. If the 
upper bound of the two-sided 95% confidence interval for the difference 
(µI minus µC) is <0%, superiority of the Intervention group compared to the 
Control group will be established.  
• 
Percentage of time >180 mg/dL  
• 
Mean glucose  
• 
Change from baseline in A1C  
• 
Percentage of time < 70 mg/dL 
• 
Change from baseline in Type 1-Diabetes Distress Scale (T1-DDS) total 
score at 13 weeks 
 
If change from baseline in T1-DDS total score at 13 weeks is found to be 
statistically significantly different in the Intervention group compared to 
the Control group, the proportion of subjects in each treatment group 
achieving an improvement of ≥0.19 points (MCID) in the T1-DDS total 
score at 13 weeks will also be compared.  
• 
Change from baseline in Hypoglycemia Confidence Scale (HCS) total score 
at 13 weeks 
 
If change from baseline in HCS total score at 13 weeks is found to be 
statistically significantly different in the Intervention group compared to 
the Control group, the proportion of subjects in each treatment group 
achieving a score of ≥3 points in the HCS total score at 13 weeks will also 
be compared.  
• 
Change from baseline in Diabetes Quality of Life-brief (DQOL-brief) total 
score at 13 week  
 
If change from baseline in DQOL-brief total score at 13 weeks is found to 
be statistically significantly different in the Intervention group compared to 
the Control group, the proportion of subjects in each treatment group 
achieving a clinically meaningful improvement (defined as ≥0.5*standard 
deviation of change from baseline in DQOL-brief total score at 13 weeks) 
in the DQOL-brief total score at 13 weeks will also be compared.  
Each endpoint with a two-sided p-value of ≤0.05 (equivalent to one-sided p-value ≤ 
0.025) is considered to be met until a secondary endpoint with a two-sided p-value of 

 
 
 
 
 
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>0.05 (equivalent to one-sided p-value > 0.025) is encountered. That secondary 
endpoint, and all subsequent secondary endpoints, are considered to not be met 
irrespective of their observed p-values.   
There will be no formal hypothesis testing for the exploratory endpoints.  
The primary, secondary, and additional endpoints will be summarized for the mITT and 
PP analysis sets. If the PP analysis set does not differ from the mITT analysis set, 
separate analyses will not be presented.  
12 
PERCENTAGE OF TIME ENDPOINTS 
The primary endpoint and the secondary endpoints that summarize time in specific 
glycemic ranges will be calculated from device data outputs as follows: 
100 × # 𝑜𝑜𝑜𝑜 𝐶𝐶𝐶𝐶𝐶𝐶 𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟 𝑖𝑖𝑖𝑖 𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟 
# 𝑜𝑜𝑜𝑜 𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒 𝐶𝐶𝐶𝐶𝐶𝐶 𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟= % 𝑜𝑜𝑜𝑜 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡 
12.1 Subgroup Analyses 
Summary statistics will be stratified by time points of interest (e.g., day vs. night, overall). 
Any additional subgroup analyses will be detailed in the SAP. 
12.2 Additional Data Analyses 
CGM and Omnipod 5 device data will be made available to Sponsor representatives for 
periodic reviews. Reviews of the controller data will be conducted to identify any 
anomalies and to confirm the algorithm appears to be functioning as expected. These 
reviews, including any findings, will be documented. Unless potential safety concerns 
are identified, the results of such reviews will not be shared with study sites or 
participants and thus, will not impact study endpoints. Should a potential safety concern 
be identified, sites may be notified as appropriate to ensure participant safety and 
measures may be taken to address the issue such as, but not limited to, changes to the 
protocol and/or device. Any resulting device deficiencies will be reported, if applicable. A 
brief summary of the controller data reviews will be included in the final clinical study 
report. 
12.3 Safety Analyses 
12.3.1 Evaluation of Adverse Events 
All adverse events reported over the course of the study will be summarized and 
tabulated by study phase (standard therapy or 13-week follow-up), event 
category, seriousness, severity, and relationship to the study procedure and the 
devices. For the purposes of summarization, an event will be considered 
“Related” if the relationship was deemed as “Possibly Related” or “Related”. In 
cases where the same event is reported more than once per participant, the 
event will only be counted once in the incidence table(s).  
Adverse events leading to death or to discontinuation from the study will be listed 
separately. A listing of all adverse events will be provided.  

 
 
 
 
 
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12.3.2 Evaluation of Device Deficiencies 
Device deficiencies will be tabulated and listed in a manner similar to the 
methods described for adverse events. Any device deficiency leading to 
an AE or to study termination will be listed separately. 
12.3.3 Episodes of Severe Hypoglycemia and DKA 
The number of severe hypoglycemia and DKA adverse events, and the number 
and percent of subjects with at least one event in each group will be summarized. 
Statistical testing will be performed for the rate of SH (and DKA) if there are ≥5 
events (of SH or DKA, respectively) combined across both treatment groups. The 
rates will be calculated as the number of events per 100 person years.   
 
12.4 Baseline Characteristics 
The distribution of each baseline characteristic or demographic parameter of interest 
(such as age, gender, medical history, etc.) will be presented. Data on all enrolled 
participants will be presented. Continuous variables will be summarized using count, 
mean, median, standard deviation, and range. Categorical variables will be summarized 
using counts and percentages. 
12.5 General Statistical Methods 
Standard statistical methods will be employed to analyze all data. Data collected in this 
study will be presented using summary tables and participant data listings. Unless 
otherwise noted, all p-values will be considered significant at a two-sided significance 
level of 5%. Continuous variables will be summarized using descriptive statistics, 
including count, mean, median, standard deviation (SD), minimum and maximum. 
Where appropriate, 95% two-sided confidence intervals for the means or medians will be 
presented. If the observed data are found not to follow a normal distribution, appropriate 
non-parametric methods may be employed. Categorical variables will be summarized by 
frequencies and percentages. Unless explicitly stated otherwise, percentages will utilize 
a denominator corresponding to the number of unique participants. 
12.6 Missing Data 
All practical monitoring and follow-up steps will be taken to ensure complete and 
accurate data collection.   
Due to the nature of the data and study design, it is anticipated that all randomized 
subjects will contribute some CGM data post-randomization. Hence, it is possible that 
there will be no need for imputation of missing values for the CGM endpoints. A subject 
will be included in analysis of CGM endpoints in the mITT analysis set only if the subject 
provides at least seven days’ worth of sensor readings during the course of 13 weeks. 
This is equivalent to 2016 readings, assuming CGM readings are taken at approximately 
every five minutes for a total of 288 readings per day. No additional imputations for 
missing data are planned for the primary endpoint, and secondary endpoints involving 
CGM data.  Missing records (i.e. gaps in data) will not be imputed for either the 
intervention or control group. 
CGM values for other reasons will not be imputed.   

 
 
 
 
 
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It is likely that at least some subjects do not contribute data for the A1C and patient-
reported outcome endpoints (e.g., due to early withdrawal).  
For the main analysis of A1C and patient-reported outcomes, missing values for the 
subjects in the mITT analysis set will be imputed using the subject’s last known 
A1C/ePRO value if collected within the analysis window (such as during Early Withdrawal 
visit). The analysis windows are assigned as follows:  
• 
A1C à 13±2 weeks from start of the 13-week randomized period  
• 
PROs à 13±5 weeks from start of the 13-week randomized period   
Questionnaire scoring will follow the scoring guidelines; PRO scores either at baseline or 
at 13 weeks that are missing for other reasons (e.g., due to unanswered questions) will not 
be imputed. No imputation for missing data will be included in the analyses based on Per 
Protocol analysis set. Additional sensitivity analyses will be detailed in the SAP. 
 
12.7 Statistical Software 
The statistical software package SAS® 9.4 or later will be used for all the data 
derivations, summarization, data listings and statistical analyses. Additional software 
such as Splus or R may be used for graphics or validation as appropriate. 
Additional details regarding statistical analyses will be provided in the SAP which will be 
prepared prior to data analysis. If discrepancies exist between the protocol and the SAP, 
the SAP will prevail. Any deviations from the finalized SAP will be described in the final 
study report. 
13 
DATA HANDLING AND QUALITY ASSURANCE 
Data in this study will be collected on Electronic Case Report Forms as well as via 
electronic device outputs. 
13.1 Electronic Case Report Forms (eCRFs) 
Study data are collected through a combination of participant electronic CRFs (eCRFs) 
and electronic device data files.  eCRF Data will be recorded in a 21 CFR Part 11 
compliant database that will reside on a central server accessible via the Internet. 
Electronic data files contain the primary source data for study devices.  When data are 
directly collected in the eCRFs, this will be considered source data.  When data is not 
directly collected in the eCRFs, electronic or paper documents containing source data 
that is transcribed into the eCRF are the source. 
The investigator is responsible for the accuracy and completeness of data reported on 
the eCRFs. Each set of participant eCRFs must be reviewed and signed by the 
investigator in the Electronic Data Capture (EDC) system. The investigator also agrees 
to maintain accurate source documentation supporting the data. When pertinent 
supportive information is available for data entered directly into the eCRFs, this 
supporting documentation will also be maintained. Source documents may include chart 
notes, laboratory reports, images, study specific source worksheets, eCRFs, device data 
files, etc. 

 
 
 
 
 
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13.2 Electronic Device Outputs 
13.2.1 Omnipod 5 System Data 
For the Intervention group, the study will collect insulin delivery data from the 
Omnipod 5 System. All insulin delivery and CGM data from the Omnipod 5 
System will be stored on the device and exported to the Insulet Cloud. Data will 
be saved in a compatible format that will be extractable for statistical analysis 
purposes.   
13.2.2 CGM Data 
The study will collect CGM data from the CGM device for all participants. All 
CGM data will be stored and exported to the Cloud. CGM data will be saved in a 
compatible format that will be extractable for statistical analysis purposes. 
13.2.3 BG/Ketone Meter Data 
This study will also utilize measurements from a BG and ketone meter. BG or 
Ketone meter data, in any format, may be uploaded to the database if requested.  
13.2.4 Participant Identifiers 
All data used in the analysis and reporting of the study will be without identifiable 
reference to the participant. Only the unique participant number will be used to 
identify participant data submitted to the Sponsor, and only the investigating 
clinical site will be able to link the unique participant ID to the participant’s name. 
13.2.5 Monitoring Responsibilities 
This study will be monitored for compliance with the protocol and applicable 
regulatory requirements. A study specific monitoring plan will specify the 
minimum frequency, scope, and general conduct of monitoring visits as well as 
identify any relevant study-specific monitoring responsibilities. 
Monitors for this study will be qualified by education, experience and training. 
The monitor will report to the Sponsor any non-compliance with the protocol, 
applicable regulations, or any conditions imposed by the IRB or local regulatory 
authority. If compliance cannot be secured, device shipments to the Investigator 
may be discontinued and the Investigator’s participation in the study terminated. 
Investigators and clinical site coordinators are expected to make source files and 
other records and reports available to the monitors as required. 
13.2.6 Inspection of Records 
The Sponsor or its designee may perform quality assurance site and study file 
audits. Investigators and institutions involved in the study will permit trial-related 
monitoring, audits, IRB/EC review, and regulatory inspection by providing direct 
access to all study records. In the event of an audit or inspection, the investigator 
agrees to allow the Sponsor, representatives of the Sponsor, or regulatory 
authorities access to all study records. 

 
 
 
 
 
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The investigator should promptly notify the Sponsor of any study inspections 
scheduled by the regulatory authorities and promptly forward copies of any audit 
reports received to the Sponsor. 
13.2.7 Study Record Retention 
Records and reports will be archived according to local regulations and in 
accordance with maximum period of time permitted by institution or for a 
minimum of two years after the later of either the completion/termination of the 
study or the date of market approval for the indication being studied. They may 
be discarded only upon approval from the Sponsor. The Principal Investigator 
must contact the Sponsor before destroying any records and reports pertaining to 
the study to ensure that they no longer need to be retained. In addition, the 
Sponsor must be contacted if the investigator plans to leave the investigational 
site to ensure that arrangements for a new investigator or records transfer are 
made prior to investigator departure. 
13.2.8 Device Accountability 
Investigators will be responsible for device accountability, reconciliation, and 
records maintenance throughout the course of the investigation. Accountability 
records will include receipt, use and final disposition of study supplied devices.  
Study devices must be stored according to the conditions set forth for the device 
on the label in a controlled, locked area. All device shipment records (packing lists, 
etc.) must be maintained at the clinical site.  
The study monitor will verify accountability of the study devices during routine 
monitoring visits to the clinical site. 
14 
STUDY ETHICS AND CONDUCT 
14.1 Role of the Sponsor 
As the Sponsor of this clinical study, Insulet has the overall responsibility for the conduct 
of the study, including assurance that the study meets the requirements of the 
appropriate regulatory bodies. In this study, the Sponsor will have certain direct 
responsibilities and may delegate certain study tasks to the Contract Research 
Organization (CRO). 
14.2 Ethical Conduct of the Study 
The investigation will be conducted according to the ethical principles that have their 
origin in the Declaration of Helsinki and are consistent with GCP and the applicable 
regulatory requirements with the rights, safety, and well-being of the trial participant the 
most important consideration. The investigator will conduct all aspects of this study in 
accordance with all state, and local laws or regulations. 
14.3 International Review Board (IRB) and Ethics Committees (EC) 
Regulations require that approval/favorable opinion be obtained from an IRB/EC for 
protocol, informed consent and any written information to be provided to the participants 
prior to participation of participants in research studies. Prior to participant enrollment, 
IRB/EC approval letter must be submitted to the Sponsor.  Documentation of all IRB/EC 

 
 
 
 
 
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approvals will be maintained by the clinical site and will be available for review by the 
Sponsor or its designee. 
All IRB/EC approvals should be signed by the IRB/EC chairperson or designee and must 
identify the IRB/EC by name and address, the clinical protocol by title and/or protocol 
number, and the date approval was granted. 
The Investigator is responsible for submitting and obtaining initial and continuing review 
of the trial at intervals not exceeding 1 year or as otherwise directed by the IRB/EC. The 
investigator must supply the Sponsor, or its designee written documentation of continued 
review of the study. 
14.4 Informed Consent 
A written informed consent in compliance with applicable regulations must be obtained 
from each participant prior to participating in the study or performing any unusual or non-
routine procedure that involves risk to the participant. An informed consent form (ICF) 
template will be provided by the Sponsor or designee to investigative clinical sites. If any 
institution-specific modifications to study-related procedures are proposed or made by 
the clinical site, the consent must be reviewed by the Sponsor prior to IRB/EC 
submission. Once reviewed, the consent will be submitted by the investigator to their 
IRB/EC for review and approval prior to the start of the study. 
Before recruitment and enrollment, each prospective participant will be given a full 
explanation of the study and be given ample time to read the approved ICF and ask 
questions. Once the investigator or designee is assured that the participant understands 
the implications of participating in the study, the participant will be asked to give consent 
to participate in the study by signing the ICF.     
The investigator or designee shall provide a copy of the signed ICF to the participant. 
The original form shall be maintained in the participant binder at the clinical site. 
14.5 Confidentiality 
All information and data sent to the Sponsor concerning study participants or their 
participation in this trial will be considered confidential. Only authorized personnel will have 
access to these confidential files. All records will be kept in secure storage areas and on 
password-protected computers.  
This includes, but is not limited to the following: 
• 
Participants will be identified on all eCRFs by a unique participant ID 
• 
eCRFs are confidential documents and will only be available to the Sponsor 
(including delegates, such as CRAs), Medical Monitor, CRO, the investigator 
and study staff, and if requested, to the IRB/EC or regulatory authorities. The 
investigator will maintain, as part of the investigation file, a list identifying all 
participants entered into the study. 
All laboratory specimens, evaluation forms, reports, and other records will be identified in 
a manner designed to maintain participant confidentiality. Clinical information will not be 
released without the written permission of the participant, except as necessary for 
monitoring and auditing by the Sponsor, its designee, the regulatory authorities, or the 
IRB/EC. 

 
 
 
 
 
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The investigator and all clinical site staff involved in this study may not disclose (or use 
for any purpose other than performance of the study), any data, record, or other 
unpublished confidential information disclosed to those individuals for the purpose of the 
study. Prior written agreement from the Sponsor or its designee must be obtained for the 
disclosure of any said confidential information to other parties. 
14.6 Modification of the Protocol 
Any changes in this research activity, except those necessary to remove an apparent 
immediate hazard to the participant, must be reviewed and approved by the Sponsor. 
The protocol amendment(s) must be signed by the investigator and approved by the 
IRB/EC before implementation. The protocol amendment(s) will be filed with the 
appropriate regulatory agency(s) having jurisdiction over the conduct of the study and 
may require approval prior to implementation. 
Substantial changes will require approval from the Sponsor and IRB/EC prior to 
implementation. 
14.7 Protocol Deviations 
The investigator will not deviate from the protocol except in medical emergencies or in 
unforeseen, isolated instances where minor changes are made that will not increase the 
participant’s risk or affect the validity of the trial. In medical emergencies, prior approval 
for protocol deviations will not be required, but the Sponsor must be notified within 2 
working days of the incident. Periodic monitoring of protocol compliance will be 
performed for each clinical site. The Sponsor has the right to suspend enrollment at 
clinical sites deemed to have excessive protocol compliance issues. 
All deviations related to study inclusion or exclusion criteria, conduct of the study, 
participant management or participant assessment must be appropriately documented 
and reported. Other protocol deviations to be considered include non-adherence to the 
protocol that results in a significant additional risk to the participant.  
The investigator must document and explain any protocol deviation in the participant’s 
source documentation. The IRB/EC should be notified of all protocol deviations in a 
timely manner. Protocol deviations should be reported to the IRB/EC periodically, 
according to their requirements. Deviations will also be reviewed by the monitor during 
clinical site visits and those observations may be discussed with the investigator. 
The Sponsor will evaluate circumstances where the investigator deviates from the study 
protocol and will retain the right to remove either the investigator or the investigational 
clinical site from the study. 
14.8 Study Reporting Requirements 
By participating in this study, the investigator agrees to submit SAE reports according to 
the timeline and method outlined in this protocol. In addition, the investigator agrees to 
submit annual reports to his/her IRB/EC as appropriate. 
Upon completion or termination of the study, the principal investigator (PI) must submit a 
final written report to the Sponsor and IRB/EC. The report must be submitted within 3 
months (90 days) of completion or termination of the trial. 

 
 
 
 
 
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The Sponsor will submit all reports required by the appropriate regulatory authorities, 
including unanticipated adverse device effects, SAE, withdrawal of IRB/EC approval, list 
of current investigators, annual progress reports, recall information, final reports and 
protocol deviations. 
14.9 Selection of Investigators 
The Sponsor will select qualified investigators, ship devices only to participating 
investigators, obtain a signed Investigator’s Agreement and provide all investigators with 
the information and training necessary to conduct the study. 
14.9.1 Financial Disclosure 
Investigators and sub-investigators are required to provide financial disclosure 
information to allow the Sponsor to submit the complete and accurate 
certification or disclosure statements required under 21 CFR 54. In addition, the 
investigator must notify the Sponsor promptly of any relevant changes that occur 
during the course of the study, at the completion of the study, and 1 year 
following the completion of the study. 
14.9.2 Investigator Documentation 
Prior to beginning the study, the investigator will be asked to provide the 
following essential documents, including but not limited to: 
• 
An investigator-signed Investigator Agreement page of the 
protocol  
• 
An investigator-signed Investigator Agreement page of the 
Investigator Brochure 
• 
An IRB/EC approved informed consent, samples of clinical site 
advertisements for recruitment for this study, and any other written 
information regarding this study that is to be provided to the 
participant 
• 
IRB/EC approval of the investigator, protocol, and 
acknowledgement of the user guide 
• 
Curricula vitae (CV) for the PI and each investigator participating 
in the study. Current licensure must be noted on the CV or a copy 
of the license provided. CVs must be signed and dated by the 
investigators within 1 year of study start-up, indicating that they 
are accurate and current. 
• 
Financial disclosure information (as stated above) and a 
commitment to promptly update this information if any relevant 
changes occur 
• 
Investigator Agreement Form signed agreement to conduct the 
study in accordance with the relevant, current Protocol, and 
applicable regulatory authority and IRB/EC regulations 
• 
Laboratory certifications and normal ranges for any local 
laboratories used by the clinical site. 
 
14.10 Clinical Site Training 
The training of appropriate clinical site personnel will be the responsibility of the Sponsor 
or its designee. To ensure proper device usage, uniform data collection, and protocol 

 
 
 
 
 
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compliance, the Sponsor or designee will present formal training sessions to relevant 
clinical study site personnel. Clinical study personnel trained by the Sponsor may also 
train additional clinical study personnel at their site. The Sponsor reserves the right to 
enforce retraining for clinical sites who have demonstrated study or procedure 
compliance issues. Protocol-specific training will occur for all research personnel and 
key ancillary staff who will be involved in participant care. 
14.11 Device Use 
The Omnipod 5 System consists of the following primary components: The Pod (insulin 
infusion pump with SmartAdjust technology), Omnipod 5 App(installed on the Insulet-
provided Controller), and the Dexcom G6 CGM (sold separate and manufactured by 
Dexcom). 
The Pod and Controller are intended for single use only.  The Controller will be returned 
to the Sponsor after completion of the study. 
The Dexcom G6 CGM sensor (the component of the system that enters the skin) and 
the Dexcom G6 CGM transmitter (the component of the system that attaches to the 
sensor to transmit the signal) will all be single use only in this study.  
New blood glucose meters, ketone meters, CGM sensors, and transmitters will be 
dispensed to each participant. Any unused blood glucose meters, ketone meters, CGM 
sensors, and transmitters will be returned to Insulet. 
14.12 Device Returns 
Any unused or damaged investigational devices or investigational devices related to a 
suspected deficiency or adverse event must be returned to the study Sponsor. To initiate 
the return, the clinical site will contact the Sponsor representative and provide the 
following information: 
• 
Part number/Lot number 
• 
Quantities 
• 
Tracking number 
 
14.13 Policy for Publication and Presentation of Data 
All data and results and all intellectual property rights in the data and results derived 
from the study will be the property of the study Sponsor, Insulet.  
14.14 Sponsor or Regulatory Agency Termination of the Study 
Although the Sponsor intends to complete the study, the Sponsor reserves the right to 
stop the study at any time for clinical or administrative reasons, or if required by the local 
regulatory authority, with suitable written notice to the investigators and regulatory 
authorities as appropriate. 
Similarly, investigators may withdraw from the study by providing written notification to 
the Sponsor within 30 days of intent to withdraw. However, the Sponsor and 
investigators will be bound by their obligation to complete the follow-up of participants 
already enrolled in the trial. Participants must be followed according to the clinical 
protocol and information obtained during participant follow-up shall be reported on the 
eCRF. 

 
 
 
 
 
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15 
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