Evaluating the Safety and Effectiveness of the Omnipod Horizon™ Automated Glucose Control System in Children With Type 1 Diabetes Aged 2.0-5.9 Years: Preschool Cohort
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Sponsor: Insulet Corporation

 
 
Omnipod 
Horizon™ Preschool Protocol V3.1 
Confidential 
Page | 1 
 
 
Evaluating the Safety and Effectiveness of the Omnipod 
Horizon™ Automated Glucose Control System in Children with 
Type 1 Diabetes Aged 2.0-5.9 Years: Preschool Cohort 
 
 
IDE G190270 
Version 3.1 
October 14, 2021 
 
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 
 
Evaluating the Safety and Effectiveness of the Omnipod 
Horizon™ Automated Glucose Control System in Children with 
Type 1 Diabetes Aged 2.0-5.9 Years: Preschool Cohort 
 
IDE G190270 
Version 3.1 
October 14, 2021 
 
 
 
______________________________________ 
Trang Ly MBBS FRACP PhD - SVP, Clinical and  
Medical Director, Insulet Corporation 
 
 
 
 
 
        _____________________ 
        Date 
 
 
______________________________________ 
Bonnie Dumais, RN – Senior Director of Clinical Affairs, 
Insulet Corporation 
 
 
 
        _____________________ 
        Date 
 
 
 
______________________________________ 
Julie Perkins - Senior Director, Quality and Regulatory,  
Insulet Corporation 
 
 
 
 
        _____________________ 
        Date 
 
 

 
 
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INVESTIGATOR STATEMENT 
 
Evaluating the Safety and Effectiveness of the Omnipod 
Horizon™ Automated Glucose Control System in Children with 
Type 1 Diabetes Aged 2.0-5.9 Years: Preschool Cohort 
IDE G190270 
Version 3.1 
October 14, 2021 
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, applicable FDA regulations, and any conditions of approval imposed by an 
Institutional Review Board (IRB) or Food and Drug Administration (FDA). 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 subjects. I agree to await 
Institutional Review Board (IRB) and Insulet approval for the protocol, informed consent 
and documentation to be presented to subjects before initiating the study pursuant to 21 
CFR Part 56, to obtain informed consent from subjects prior to their enrollment into the 
study pursuant to 21 CFR Part 50, to collect and record data as required by this 
protocol and case report forms, to report non serious and serious adverse events as 
required per protocol that may occur for any subject 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 the Sponsor and will also notify the 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 
 
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: 
 
Bruce Buckingham, MD 
 
 
 
 
Professor, Pediatrics 
Division of Endocrinology and Diabetes 
 
Stanford School of Medicine 
 
 
 
 
780 Welch Road 
Palo Alto, CA 94305 
 
E-mail: bbendo@stanford.edu 
 
Sue Brown, MD 
Associate Professor of Medicine 
Division of Endocrinology 
University of Virginia 
Centers for Diabetes Technology 
560 Ray C. Hunt Drive, 3rd Floor 
Charlottesville, VA  22908 
Email: sab2f@virginia.edu 
 
 
 
 
 

 
 
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TABLE OF CONTENTS 
TITLE PAGE ......................................................…........................................................................1 
PROTOCOL APPROVAL ............................................................................................................... 2 
INVESTIGATOR STATEMENT ...................................................................................................... 3 
PRINCIPAL CONTACTS ................................................................................................................ 4 
TABLE OF CONTENTS ................................................................................................................. 5 
PROTOCOL SUMMARY ................................................................................................................ 8 
GLOSSARY OF ACRONYMS ...................................................................................................... 12 
1 
INTRODUCTION ................................................................................................................. 14 
2 
OMNIPOD HORIZON™ SYSTEM STUDY DEVICE OVERVIEW ...................................... 15 
2.1 
Device Description of the Omnipod Horizon™ System ................................. 15 
3 
HORIZON™ DATA PORTAL ............................................................................................... 19 
4 
RESULTS FROM FEASIBILITY STUDIES .......................................................................... 19 
5 
STUDY SUMMARY ............................................................................................................. 19 
5.1 
Study Purpose .............................................................................................. 19 
5.2 
Study Design ................................................................................................ 19 
6 
OBJECTIVES AND ENDPOINTS ........................................................................................ 28 
6.1 
Primary Safety Objective .............................................................................. 28 
6.1.1 
Primary Safety Endpoints .......................................................................... 28 
6.2 
Primary Effectiveness Objective.................................................................... 28 
6.2.1 
Primary Effectiveness Endpoints ............................................................... 28 
6.3 
Secondary Objective ..................................................................................... 28 
6.3.1 
Secondary Endpoints ................................................................................ 28 
6.4 
Exploratory Endpoints ................................................................................... 29 
6.5 
Patient Reported Outcomes .......................................................................... 30 
7 
SCREENING AND ELIGIBILITY .......................................................................................... 30 
7.1 
Visit 1 ............................................................................................................ 31 
8 
STANDARD THERAPY - PHASE 1 ..................................................................................... 34 
8.1 
Visit 2 ............................................................................................................ 35 
8.2 
Visit 3 ............................................................................................................ 36 
9 
HYBRID CLOSED-LOOP - PHASE 2 .................................................................................. 37 
9.1 
Challenge Visits ............................................................................................ 38 
9.2 
Visit 4 ............................................................................................................ 39 
9.3 
Visit 5 ............................................................................................................ 40 
9.4 
Visit 6 ............................................................................................................ 40 
9.5 
Visit 7 ............................................................................................................ 41 
9.6 
Visit 8 ............................................................................................................ 41 
9.7 
Visit 9 ............................................................................................................ 41 
9.8 
Visits 10, 11 and 12 ...................................................................................... 41 
9.9 
Visit 13 (End of Phase 2) .............................................................................. 42 
9.10 
Unscheduled Visits (Phase 2) ....................................................................... 43 

 
 
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9.11 
Early Withdrawal (Phase 2) ........................................................................... 43 
10 
HYBRID CLOSED-LOOP – PHASE 3 ................................................................................. 44 
10.1 
Visit 14 .......................................................................................................... 45 
10.2 
Visit 15 .......................................................................................................... 45 
10.3 
Visit 16 .......................................................................................................... 45 
10.4 
Visits 17 and 18 ............................................................................................ 46 
10.5 
Visit 19 .......................................................................................................... 46 
10.6 
Visit 20 .......................................................................................................... 46 
10.7 
Visit 21 .......................................................................................................... 47 
10.8 
Visit 22 .......................................................................................................... 47 
10.9 
Visits 23 ........................................................................................................ 47 
10.10 
Extension Through Commercialization Visits ............................................ 48 
10.11 
Unscheduled Visits (Phase 3) ................................................................... 48 
10.12 
Early Withdrawal (Phase 3) ....................................................................... 48 
10.13 
Lost to Follow-up ....................................................................................... 49 
11 
SPONSOR REPRESENTATIVES ....................................................................................... 49 
12 
SAFETY ............................................................................................................................... 49 
12.1 
Types of Known Risks and Benefits .............................................................. 49 
12.2 
Hypoglycemia/Hyperglycemia ....................................................................... 50 
12.3 
Adverse Events ............................................................................................. 51 
12.3.1 
Definitions ............................................................................................. 51 
12.3.2 
Reportable Adverse Events ................................................................... 52 
12.3.3 
Hypoglycemic Events ............................................................................ 53 
12.3.4 
Hyperglycemic/Ketotic Events ............................................................... 54 
12.3.5 
Relationship of Adverse Event to Investigational Device ....................... 54 
12.3.6 
Severity (Intensity) of Adverse Events ................................................... 55 
12.3.7 
Outcome of Adverse Events .................................................................. 55 
12.4 
Reportable Device Issues ............................................................................. 56 
12.5 
Timing of Event Reporting............................................................................. 56 
12.6 
Safety Oversight ........................................................................................... 57 
12.7 
Stopping Criteria ........................................................................................... 58 
12.7.1 
Participant Discontinuation of Study Participation .................................. 58 
12.7.2 
Criteria for Suspending or Stopping Overall Study ................................ 58 
12.8 
Data Safety Monitoring Board (DSMB).......................................................... 59 
12.9 
Medical Monitor ............................................................................................ 60 
13 
STATISTICAL CONSIDERATIONS ..................................................................................... 60 
13.1 
Objectives and Endpoints ............................................................................. 60 
13.1.1 
Primary Safety Objective ....................................................................... 60 
13.1.2 
Primary Effectiveness Objective ............................................................ 61 
13.1.3 
Secondary Objective ............................................................................. 62 
13.1.4 
Secondary Endpoints ............................................................................ 62 
13.2 
Sample Size ................................................................................................. 64 
13.2.1 
Primary Endpoint of A1C at End of Phase 2 (~13 Weeks) Compared to 
Baseline 64 
13.2.2 
Primary Endpoint of Percentage of Time in Range 70-180 mg/dL During 
Phase 2 Compared to Phase 1 ............................................................................. 65 
13.3 
Analysis Sets ................................................................................................ 65 
13.3.1 
ITT (Intention to Treat) Analysis Set ...................................................... 65 

 
 
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13.3.2 
mITT (modified Intention to Treat) Analysis Set ..................................... 65 
13.3.3 
PP (Per-Protocol) Analysis Set .............................................................. 66 
13.4 
Analysis of Primary and Secondary Endpoints .............................................. 66 
13.4.1 
Time in Range Endpoints ...................................................................... 66 
13.5 
Additional Data Analyses .............................................................................. 67 
13.6 
Safety Analyses ............................................................................................ 67 
13.6.1 
Evaluation of Adverse Events ................................................................ 67 
13.6.2 
Evaluation of Device Deficiencies ......................................................... 67 
13.7 
Baseline Characteristics ............................................................................... 67 
13.8 
General Statistical Methods .......................................................................... 67 
13.9 
Missing Data ................................................................................................. 68 
13.10 
Statistical Software ................................................................................... 68 
14 
DATA HANDLING AND QUALITY ASSURANCE ............................................................... 68 
14.1 
Electronic Case Report Forms (eCRFs) ........................................................ 68 
14.2 
Electronic Device Outputs ............................................................................. 69 
14.2.1 
PDM Data ............................................................................................. 69 
14.2.2 
CGM Data ............................................................................................. 69 
14.2.3 
BG and Ketone Meter Data ................................................................... 69 
14.3 
Subject Identifiers ......................................................................................... 69 
14.4 
Monitoring Responsibilities ........................................................................... 69 
14.5 
Inspection of Records ................................................................................... 69 
14.6 
Study Record Retention ................................................................................ 70 
14.7 
Device Accountability .................................................................................... 70 
15 
STUDY ETHICS AND CONDUCT ....................................................................................... 70 
15.1 
Role of the Sponsor ...................................................................................... 70 
15.2 
Ethical Conduct of the Study ......................................................................... 70 
15.3 
Institutional Review Board (IRB) ................................................................... 71 
15.4 
Informed Consent ......................................................................................... 71 
15.5 
Confidentiality ............................................................................................... 71 
15.6 
Modification of the Protocol ........................................................................... 72 
15.7 
Protocol Deviations ....................................................................................... 72 
15.8 
Study Reporting Requirements ..................................................................... 73 
15.9 
Selection of Investigators .............................................................................. 73 
15.9.1 
Financial Disclosure .............................................................................. 73 
15.9.2 
Investigator Documentation ................................................................... 73 
15.10 
Clinical Site Training ................................................................................. 74 
15.11 
Device Use ............................................................................................... 74 
15.12 
Device Returns ......................................................................................... 74 
15.13 
Policy for Publication and Presentation of Data ......................................... 75 
15.14 
Sponsor or Regulatory Agency Termination of the Study .......................... 75 
REFERENCES ............................................................................................................................. 76 
APPENDIX A ................................................................................................................................ 79 
 
 

 
 
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PROTOCOL SUMMARY 
Protocol title 
Evaluating the safety and effectiveness of the Omnipod Horizon™ Automated 
Glucose Control System in children with type 1 diabetes aged 2.0-5.9 years: 
preschool cohort 
Protocol ID 
G190270 
Purpose 
To evaluate the safety and effectiveness of the Omnipod Horizon™ Automated 
Glucose Control System in preschool children with type 1 diabetes.  
Design 
This study is a single-arm, multi-center, prospective clinical study  
Enrollment 
A total of up to 80 children, aged 2-5.9 years, will be enrolled in the study in 
order to obtain a minimum of 60 evaluable subjects.   
 
The study will consist of three phases;  
 
1) 14-day standard therapy outpatient phase (Phase 1) 
2) 13-week outpatient hybrid closed-loop phase (Phase 2) 
3) Hybrid closed-loop extension phase until the Omnipod 5 System 
(also known as Omnipod Horizon™ Automated Glucose Control 
System) is commercially available (Phase 3) 
 
Subjects will be enrolled across 6-12 clinical study sites.  
 
Indication 
The Omnipod Horizon™ Automated Glucose Control System is a single 
hormone insulin delivery system intended for the management of diabetes in 
persons requiring insulin. Continuous subcutaneous insulin infusion may be 
delivered by user-defined settings (manual mode) or automatically adjusted in 
response to feedback from a continuous glucose monitor (CGM).  
 
The Omnipod Horizon™ System can automatically increase insulin delivery 
based on CGM sensor glucose values and can decrease or suspend delivery of 
insulin when the glucose value falls below or is predicted to fall below 
predefined threshold values. The Omnipod HORIZON™ System is 
interoperable with compatible iCGMs and ACE pumps. 
 
The Omnipod Horizon™ System is designed to assist patients with diabetes in 
achieving glycemic targets set by their health care providers.  
Study duration 
The study is expected to be completed within 36-months which includes clinical 
site initiation to completion of Phase 3 and all data entry and monitoring 
procedures. The sponsor intends to submit results from Phase 2 for marketing 
clearance after data collection for Phase 2 is complete. The results from Phase 
3 will be submitted separately.   
Investigational 
devices 
The Omnipod Horizon™ Automated Glucose Control System is comprised of 
the following components: 
• 
Omnipod Horizon™ tubeless, insulin delivery alternate controller enabled 
(ACE) pump (Pod) with the Horizon™ algorithm 
• 
Omnipod Horizon™ Personal Diabetes Manager (PDM) which is a 
Samsung J3 locked down Android device that operates the Omnipod 
Horizon™ App.  

 
 
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• 
Dexcom G6 - Continuous Glucose Monitoring (CGM) system  
Non-
investigational, 
commercially 
available devices 
• 
Contour® Next One blood glucose meter (Ascensia Diabetes Care, 5 Wood 
Hollow Road, Parsippany, NJ 07054 USA) 
• 
Precision Xtra ketone meter (Abbott Diabetes Care Inc., 1360 South Loop 
Road, Alameda, CA 94502 USA) 
Primary safety 
objective 
To evaluate the safety of the Omnipod Horizon™ Automated Glucose Control 
System in preschool children with type 1 diabetes.  
Primary safety 
endpoints 
The primary safety objective will be evaluated by summarizing the following 
events during Phase 2, and separately during Phase 3:  
 
• 
Incidence rate of severe hypoglycemia (events per person months) 
• 
Incidence rate of diabetic ketoacidosis (DKA) (events per person months) 
Primary 
effectiveness 
objective 
To evaluate the effectiveness of the Omnipod Horizon™ Automated Glucose 
Control System. 
Primary 
effectiveness 
endpoints 
• 
A1C at the end of Phase 2 compared to baseline A1C 
• 
A1C at Visit 16, 19, 21, and 23 compared to baseline 
• 
Percentage of time in range (70-180 mg/dL) during Phase 2, and 
separately during Phase 3  of the hybrid closed-loop phase compared 
to Phase 1 (standard therapy) 
Secondary 
objective 
To evaluate additional glycemic measures of effectiveness of the Omnipod 
Horizon™ Automated Glucose Control System. 
Secondary 
endpoints 
The secondary objective will be evaluated using the following per subject 
endpoints with prespecified hypotheses: 
 
• 
Glucose metrics from system CGM during the hybrid closed-loop phase 
for Phase 2 will be compared to Phase 1 overall: 
• 
% of time > 180 mg/dL 
• 
% of time < 70 mg/dL 
 
Additional per subject secondary endpoints without prespecified hypotheses 
used to evaluate the secondary objective include: 
 
• 
A1C: 
• 
A1C at the end of Phase 2 (Visit 13), at 6 months (Visit 16) and 
at the end of Phase 3 (Visit 23; approximately 15 months) 
• 
Change from baseline in A1C at the end of Phase 2 (Visit 13), 
at 6 months (Visit 16) and at the end of Phase 3 (Visit 23; 
approximately 15 months) 
• 
Proportion of subjects demonstrating an improvement from 
baseline in A1C at the end of Phase 2 (Visit 13), at 6 months 
(Visit 16) and at the end of Phase 3 (Visit 23; approximately 15 
months) 
 
• 
Glucose metrics from system CGM during the hybrid closed-loop phase 
during Phase 2, and separately during Phase 3 will be compared to 
Phase 1 during the day, overnight, and overall: 
• 
Mean glucose 

 
 
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• 
% of time in range 70-180 mg/dL 
• 
% of time in range 70-140 mg/dL 
• 
% of time > 180 mg/dL 
• 
% of time ≥ 250 mg/dL 
• 
% of time ≥ 300 mg/dL 
• 
% of time < 70 mg/dL 
• 
% of time < 54 mg/dL 
• 
Standard deviation 
• 
Coefficient of variation 
 
• 
Percentage of time in hybrid closed-loop as proportion of overall device 
usage time during Phase 2, and separately during Phase 3 
• 
Glucose management indicator (GMI) based on overall mean glucose 
during Phase 2, and separately during Phase 3 will be compared to 
Phase 1 
• 
Insulin requirements during Phase 2, and separately during Phase 3 
will be compared to Phase 1: 
 
• 
Total daily insulin (TDI) (units, units/kg) 
• 
Total daily basal insulin (units, units/kg) 
• 
Total daily bolus insulin (units, units/kg) 
 
• 
Change from baseline in BMI (kg/m2) at end of Phase 2, and at the end 
of Phase 3  
 
Patient Reported 
Outcomes 
Various caregiver-completed questionnaires will be used to evaluate general 
and disease-specific quality of life, and device usability. 
Eligibility criteria 
Inclusion Criteria 
Subjects must meet all of the following criteria to be included in the study: 
1. Age at time of consent 2.0-5.9 years 
2. Living with parent/legal guardian 
3. Diagnosed with type 1 diabetes. Diagnosis is based on investigator’s clinical 
judgment 
4. Deemed appropriate for pump therapy per investigator’s assessment taking 
into account previous history of severe hypoglycemic and hyperglycemic 
events, and other comorbidities 
5. Investigator has confidence that the subject and/or 
parent/guardian/caregiver can successfully operate all study devices and is 
capable of adhering to the protocol 
6. Willing to use only the following types of insulin during the study: Humalog, 
Novolog, Admelog or Apidra during the study  
7. Willing to wear the system continuously throughout the study 
8. Willing to participate in challenges for 2 consecutive days, consisting of 
a minimum of 3 hours of activity per day and dietary challenge by 
reducing the number of carbohydrates entered for a given meal by 50% 
9. A1C <10% at screening visit 
10. Subject and/or parent/guardian must be willing to use the Dexcom App on 
the Omnipod Horizon™ PDM as the sole source of Dexcom data (with the 
exception of the Dexcom Follow App) during the hybrid closed-loop phase 
11. Subject and/or parent/guardian is able to read and speak English 
fluently  
12. Has a parent/legal guardian willing and able to sign the ICF.  
 

 
 
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Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from the study: 
1. A medical condition, which in the opinion of the investigator, would put the 
subject at an unacceptable safety risk 
2. History of severe hypoglycemia in the past 6 months 
3. History of DKA in the past 6 months, unrelated to an intercurrent illness, 
infusion set failure or initial diagnosis 
4. Diagnosed with sickle cell disease 
5. Diagnosed with hemophilia or any other bleeding disorders 
6. Plans to receive blood transfusion over the course of the study 
7. Clinical evidence of acute or chronic kidney disease (e.g. estimated GFR < 
45) or currently on hemodialysis 
8. History of adrenal insufficiency 
9. Has taken oral or injectable steroids within the past 8-weeks or plans to 
take oral or injectable steroids during the course of the study 
10. Unable to tolerate adhesive tape or has any unresolved skin condition in the 
area of sensor or pump placement 
11. Plans to use insulin other than U-100 insulin intended for use in the study 
device during the course of the study 
12. Use of non-insulin anti-diabetic medication other than metformin (e.g. GLP1 
agonist, SGLT2 inhibitor, DPP-4 inhibitor, pramlintide) 
13. Thyroid Stimulating Hormone (TSH) is outside of normal range with 
clinical signs of hypothyroidism or hyperthyroidism 
14. Currently participating or plans to participate in another clinical study using 
an investigational drug or device other than the Omnipod Horizon™ 
Automated Glucose Control System during this study period  
15. 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 
Study schedule 
overview 
The study schedule consists of the following three phases: 
 
1) 14-day outpatient standard therapy phase (Phase 1) 
2) 13-week outpatient hybrid closed-loop phase (Phase 2) 
3) Hybrid closed-loop extension phase until the Omnipod 5 System is 
commercially available (Phase 3) 
 
Following subject screening, system training and enrollment, subjects will 
commence the outpatient standard therapy phase of the study.  
 
Current Dexcom G6 CGM users may provide data from a 14-day period within 
the last 30 days. The CGM data meeting the minimum criteria must be the most 
recent data from the last 30-days. For non-G6 users, subjects will wear a study 
CGM, in blinded mode, to record glucose measurements over 14-days while 
subjects manage their diabetes at home per their usual routine and remaining 
on their current MDI or pump therapy, and sensor, if applicable, for 14-days.  
 
After completion of the standard therapy phase, subjects and/or 
parents/guardians will be trained on the system and transition to the hybrid 
closed-loop phase initiating treatment with the Omnipod Horizon™ System. A 
subset of subjects (N=40) will participate in activity and dietary challenges over 
the course of 2 consecutive days during Phase 2. Subjects who complete 
Phase 2 can commence their participation in the extension phase (Phase 3). 
 
 

 
 
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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 
AWS 
Amazon Web Services  
BG 
Blood Glucose 
BLE 
Bluetooth Low Energy 
CFR 
Code of Federal Regulations 
CGM 
Continuous Glucose Monitoring 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CV 
Curricula Vitae 
DD 
Device Deficiency 
DKA 
Diabetic Ketoacidosis 
DSMB 
Data Safety Monitoring Board 
DTSQ 
Diabetes Treatment Satisfaction Questionnaire 
dL 
Deciliter 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EGV 
Estimated Glucose Value 
FDA 
Food and Drug Administration 
GMI 
Glucose Management Indicator 
HABS 
Hypoglycemic Attitudes and Behavior Scale 
HCL 
Hybrid Closed Loop 
HDP 
Horizon Data Portal 
HF 
Human Factors 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
iCGM 
Interoperable Continuous Glucose Monitoring 
IDSS 
Insulin Delivery Satisfaction Survey 
IOB 
Insulin on Board 
IRB 
Institutional Review Board 
ITT 
Intention to Treat 
MD 
Doctor of Medicine 
MDI 
Multiple Daily Injections 
mg 
Milligram 
mITT 
Modified Intention to Treat 
mmol 
Millimole 
MPC 
Model Predictive Control 
NGSP 
National Glycohemoglobin Standardization Program 

 
 
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PAID 
Problem Areas In Diabetes 
PDM 
Personal Diabetes Manager 
PHI 
Protected Health Information 
POC 
Point of Care 
pMPC 
Personalized Model Predictive Control 
PP 
Per Protocol 
PSQI 
Pittsburgh Sleep Quality Index 
PTOF 
Pump Therapy Order Form 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SMP 
Safety Management Plan 
SUS 
System Usability Scale 
T1DDS 
Type 1 Diabetes Distress Scale 
TSH 
Thyroid Stimulating Hormone 
TDI 
Total Daily Insulin 
UADE 
Unanticipated Adverse Device Effect 

 
 
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1 
INTRODUCTION 
Diabetes is a disorder affecting the normal homeostatic regulation of blood glucose. In 
type 1 diabetes, insulin insufficiency occurs due to autoimmune destruction of the beta 
cells in the pancreas resulting in persistently elevated glucose. The long-term effects of 
elevated blood glucose or hyperglycemia may result in a range of microvascular 
complications including retinopathy, nephropathy, and neuropathy. Diabetes is the 
leading cause of blindness, kidney disease, and amputation in the United States.1 
The risk for long-term complications of diabetes can be reduced, however, by 
minimizing patient exposure to hyperglycemia and maximizing the time in euglycemia. 
The landmark Diabetes Control and Complications Trial published in 1993 found that 
maintenance of near normal glucose levels reduced the risk of long-term microvascular 
complications. In 2005, the publication of the Epidemiology of Diabetes Interventions 
and Complications study found that despite the multifactorial etiology of heart disease, 
intensive insulin therapy in patients with type 1 diabetes was shown to reduce the 
incidence of nonfatal myocardial infarction, stroke, and death from cardiovascular 
disease.2 
Unfortunately, efforts to minimize hyperglycemia and maximize euglycemia are 
invariably accompanied by episodes of hypoglycemia. Indeed, the justifiable fear of 
hypoglycemia is often described as the single most significant barrier to improved 
glucose control in patients with diabetes.3 A paper by Weinstock et. al. reported on data 
collected by the T1D Exchange and found an annual incidence of 11.8% of one or more 
severe hypoglycemic events defined as a seizure or loss of consciousness. The annual 
incidence of severe hypoglycemic events increased to 18.6% in patients with diabetes 
duration greater than 40 years.4 
Two other recent papers have highlighted the effect of acute and chronic complications 
on the longevity of patients with diabetes. Livingstone et. al. found premature death in a 
Scottish registry of patients with diabetes of 11 years in males and 13 years in females.5 
Lind et. al. found a twofold increase in mortality in a Swedish registry compared with 
age-matched non-diabetic cohorts even in patients with recommended levels of 
glycemic control (A1C < 7.0%).6 The most recent treatment guidelines from the 
American Diabetes Association now recommend that adults with type 1 diabetes should 
aim for target A1C levels of 7.0% and that children and adolescents should aim for 
target A1C levels of 7.5%.7 These recommendations are equivalent to a mean blood 
glucose of 154 mg/dL in adults and 169 mg/dL in children and adolescents compared 
with mean blood glucose in patients without diabetes of 100 mg/dL or less.8 
The last 20 years have seen a number of significant improvements in diabetes care, 
most notably the advent of faster analog insulins, the widespread use of insulin pumps 
and the introduction of continuous glucose monitoring systems. Despite these 
advances, diabetes data registries continue to show that the majority of patients are 
unable to meet recommended glycemic targets with available medication and 
technology. In the 2012 report from the T1D Exchange Registry, Beck et. al. found the 
average A1C across all ages greater than 8.0% or, equivalently, greater than 183 
mg/dL and only 30% of patients met the ADA target A1C of 7.0% (adults) and 7.5% 
(children).9 A more recent paper from the T1D Exchange Registry by Foster et. al. 
comparing the 2016-2018 cohort with 2010-2012 cohort indicated that among the 9,657 

 
 
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participants that had data in both cohorts and at least 3 years of diabetes duration in 
2010-2012, mean HbA1c was higher in the 2016-2018 cohort. The increase in HbA1c 
over time was predominately seen in adolescents and young adults. The American 
Diabetes Association (ADA) HbA1c target as of 2018 of < 7.5% for children and 
adolescents was achieved by only a small percentage of youth < 18 years of age (17%); 
only 21% of adults achieved the ADA treatment goal of < 7.0%.10 
The current dilemma of persistent poor diabetes outcomes despite significant 
improvements in diabetes technology such as modern blood glucose meters, insulin 
pumps and continuous glucose monitoring systems is summarized in the FDA 
Guidance Document on Artificial Pancreas Device Systems: “Even with the aid of these 
devices, maintaining blood glucose concentrations within a suggested optimal range is 
a daily struggle for people living with diabetes mellitus and the risk of hypoglycemia 
associated with attempts at improved glycemic control remains an ever-present 
danger”.11 
Insulet has developed the Omnipod Horizon™ Automated Glucose Control System 
(hereafter named Omnipod Horizon™ System or Omnipod Horizon™) which is similar 
in function to the systems described in the FDA guidance document dated November 9, 
2012. The system provides automated glucose control at all times, but for optimum 
performance, requires user input for meal boluses. The commercial system will consist 
of an Omnipod® tubeless, insulin delivery ACE pump, a Personal Diabetes Manager 
(PDM), and the Dexcom G6 CGM. The control algorithm will reside on the Pod.  
 
2 
OMNIPOD HORIZON™ SYSTEM STUDY DEVICE OVERVIEW 
This study will evaluate the safety and effectiveness of the Omnipod Horizon™ System. 
The Omnipod Horizon™ System is a hybrid closed-loop automated insulin delivery 
(AID) system developed by Insulet. 
2.1 Device Description of the Omnipod Horizon™ System 
The Omnipod Horizon™ System intended for commercialization is composed of three 
primary components as shown in Figure 1: 
 
• 
Omnipod Horizon™ Controller – Horizon App (PDM) and Algorithm 
• 
Omnipod Horizon™ ACE Pump – Pod  
• 
iCGM – Dexcom G6 
The Omnipod Horizon™ System will provide automated insulin delivery when 
connected to CGM. The system is expected to reduce hypoglycemia without incurring 
an unacceptable increase in hyperglycemia and mean glucose. The system is also 
expected to reduce the extent and magnitude of hyperglycemia associated with meals. 
Optimal post-prandial control requires the user to deliver meal boluses as in current 
open-loop therapy, but the normal operation of the control algorithm will be expected to 
compensate for mismatched meal boluses and prevent prolonged hyperglycemia. The 
system uses a control-to-target strategy that attempts to achieve and maintain a set 
target glucose level. 

 
 
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Figure 1:  System components of the Omnipod Horizon™ System  
2.1.1. Omnipod Horizon™ Controller (App and Algorithm) 
 
The Omnipod Horizon™ Controller is composed of two parts: the Horizon application 
(“app”) and the model predictive control (MPC) algorithm on the Pod. The MPC 
algorithm provides insulin micro-boluses once every 5 minutes based upon the 
predicted glucose over a 60-minute prediction horizon. Optimal post-prandial control will 
require the user to give meal boluses in the same manner as current pump therapy, but 
normal operation of the MPC algorithm will compensate for missed meal boluses and 
mitigate prolonged hyperglycemia. The MPC algorithm uses a control-to-target strategy 
that attempts to achieve and maintain a set target glucose value, thereby reducing the 
duration of prolonged hyperglycemia and hypoglycemia. The MPC algorithm resides on 
the Pod (Pump) component of the Omnipod Horizon™ System (similar to the DASH 
ACE pump cleared in K191679), as described further below). 
 
The Omnipod Horizon™ app will be the primary user interface and will be used to start 
and stop a Pod, program basal and bolus calculator settings for Manual Mode as well 
as program settings specific for Automated Mode (hybrid closed-loop).  
 
 
Manual Mode 
 
In Manual Mode, the Horizon™ System will function equivalently to the Omnipod® 
DASH System, which was first cleared under K180045, most recently under K191679. 
This includes delivering insulin at programmed basal rates and bolus amounts with the 
option to set temporary basal profiles. The Omnipod Horizon™ Controller will also have 
the ability to function as a sensor augmented pump in Manual Mode, using sensor 
glucose data provided by the iCGM to populate the bolus calculator. 
 
 
 

 
 
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Automated Mode 
 
In Automated Mode, the system will support the use of multiple target glucose values, 
currently intended to be 110-150 mg/dL at commercialization, in 10 mg/dL increments. 
The experience for the user will reflect current setup flows whereby the health care 
provider assists the user to program basal rates, glucose targets and bolus calculator 
settings. These in turn will inform the MPC algorithm for insulin dosing parameters. The 
insulin dosing parameters will be adapted over time based on the total daily insulin 
(TDI) delivered during each Pod use. A temporary hypoglycemia protection mode (Hypo 
Protect) may be implemented by the user for various time durations during Automated 
Mode. With Hypo Protect, the algorithm reduces insulin delivery and is intended for use 
over temporary durations when insulin sensitivity is expected to be higher, such as 
during exercise. 
 
The Omnipod Horizon™ System will include two apps on a locked-down smartphone 
(the Samsung J3), referred to as Personal Diabetes Manager (PDM): the Horizon App 
and the Dexcom App. The Horizon App, which will have a similar interface to the 
cleared Omnipod® DASH System (K191679), will allow the use of large text, graphics, 
and on-screen instructions to prompt the user through set-up processes. It will also be 
used to program the user’s custom basal insulin delivery profile, check the Pod status, 
initiate bolus doses of insulin, make changes to a patient’s insulin delivery profile, 
handle system alerts and alarms, and enter Automated Mode.  
 
The Dexcom App interface is identical to the current app of the interoperable Dexcom 
G6 Continuous Glucose Monitoring System (K191450) and will provide CGM data, 
alerts, and alarms to the user.  
 
The Horizon App and Dexcom App will not directly communicate with one another. 
Instead, the iCGM transmitter will communicate EGV (estimated glucose values) 
directly to the Pod. The Dexcom transmitter number must be entered into the Horizon 
App, and this information is sent to the Pod to allow transmission of EGV. The Pod will 
pair directly to the transmitter to receive EGV for the algorithm and also sends the EGV 
back to the Horizon App as shown in Figure 1. 
 
The Omnipod Horizon™ Controller provides the ability to calculate a suggested bolus 
dose through the use of the bolus calculator. The bolus calculator will have the option 
for user selected population of the EGV, which is communicated to the app via the Pod. 
This suggested bolus calculation feature is provided as a convenience to the user to aid 
in determining the suggested bolus dose based on ingested carbohydrates, most recent 
sensor glucose reading (or blood glucose reading if using fingerstick), programmable 
correction factor, insulin to carbohydrate ratio, target glucose value and insulin on board 
(IOB). IOB is calculated by the algorithm taking into account any manual bolus and 
insulin delivered by the algorithm. 
 
As with the cleared Omnipod® DASH System, Insulet will utilize a proprietary encrypted 
security stack embedded within the Bluetooth Low Energy (BLE) communication 
between the Horizon app and Pod. The communication to the iCGM will use Dexcom’s 
communication protocol. The proprietary security stack increases the resilience of the 
device and improves the ability of the system to be protected in the event of future 
identification of vulnerabilities in standard communication protocols. 
 

 
 
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2.1.2. Omnipod Horizon™ ACE Pump 
The Pod component of the Omnipod Horizon™ System is similar to the Omnipod® 
DASH ACE Pump cleared under K191679. Compared to the DASH ACE Pump 
(K191679), the Horizon™ ACE Pump (Pod) has additional software to optimize 
communication to accept inputs from the iCGM (initially the Dexcom G6) and the 
Horizon™ Controller. The insulin delivery mechanism and the patient and fluid 
contacting components are identical to the DASH Pod. 
 
The Pod is a lightweight, self-adhesive device that the user fills with U-100 rapid-acting 
insulin and wears directly on their body. The Pod delivers insulin into the user’s body 
through a small flexible tube, called a cannula, based on the commands from the 
compatible controller. In the Omnipod Horizon™ System, the Pod will house the MPC 
algorithm and communicate directly with the iCGM and the Horizon App. The algorithm 
commands the Pod’s insulin delivery in the form of micro-boluses based on predicted 
glucose values. As with the cleared Omnipod® DASH System, the Pod of the Omnipod 
Horizon™ System will come pre-packaged in a sterile container with a fill needle and a 
fill syringe. Figure 2 below is a representation of the Pod.  
 
 
Figure 2:  The Pod of the Omnipod Horizon™ ACE pump 
 
 
2.1.3. iCGM 
The third component of the Omnipod Horizon™ System is the iCGM. The Omnipod 
Horizon™ System will be interoperable with a compatible iCGM, currently the Dexcom 
G6 Continuous Glucose Monitoring System (K191450). The Omnipod Horizon™ Pod 
will communicate with the Dexcom G6 via Bluetooth Low Energy (BLE). Glucose values 
from the Dexcom transmitter will be sent to the MPC algorithm residing on the Pod and 
used in insulin dosing adjustments. The glucose values from the Dexcom transmitter 
will be sent independently to the Dexcom App on the controller.  

 
 
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3 
HORIZON™ DATA PORTAL 
Data are securely uploaded from the PDM to Insulet Cloud by cellular connection. Data 
are then transferred from Insulet Cloud to the Horizon Data Portal (HDP), which is a 
platform for data review and management. The HDP runs on an Amazon-based web 
server. The HDP will provide insights including but not limited to: time in range, time at 
each target BG, automated/manual mode comparisons, and time spent in each mode. 
 
Investigators will have access to all uploaded data and be able to view historical trends.  
The HDP will function as the data management review platform for this study.  
 
 
4 
RESULTS FROM FEASIBILITY STUDIES 
The Omnipod Horizon™ System has been tested in 194 subjects across IDE G160169, 
G170012 and G170143 yielding approximately 13,000 subject hours of hybrid closed-
loop control. The study results were presented in part at ATTD 2017 and 2018, and 
ADA 2017, 2018 and 2019, and have also been published in Diabetes Technology and 
Therapeutics 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 29.   
5 
STUDY SUMMARY 
5.1 Study Purpose 
The purpose of this study is to assess the safety and effectiveness of the 
Omnipod Horizon™ System in preschool children with type 1 diabetes.     
5.2 Study Design 
This is a single-arm, multi-center, prospective clinical study. A total of up to 80 
children aged 2.0-5.9 years with type 1 diabetes will be enrolled in the study in 
order to obtain a minimum of 60 evaluable subjects. Subjects will be considered 
evaluable if they have at least 8-weeks of data during Phase 2. 
Subjects will be enrolled across 6-12 clinical study sites. The study schedule 
consists of the following three phases: 
1) 14-day outpatient standard therapy phase (Phase 1) 
2) 13-week outpatient hybrid closed-loop phase (Phase 2) 
3) Hybrid closed-loop extension phase until the Omnipod 5 System is 
commercially available (Phase 3) 
 
 
 

 
 
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Figure 2:  Study Schedule Timeline 
 
14-Days 
Standard 
Therapy 
                   13-Weeks                                         Extension 
             Hybrid Closed-loop 
 
 
 
Following subject screening, consenting, system training and enrollment, subjects will 
commence the standard therapy phase of the study.  
Current Dexcom G6 CGM users may provide data from a 14-day period within the last 
30-days. The CGM data meeting the minimum criteria must be the most recent data 
from the last 30-days. For non-G6 users, subjects will wear a study CGM, in blinded 
mode, to record glucose measurements over 14-days while subjects manage their 
diabetes at home per their usual routine while wearing a study CGM while remaining on 
their current MDI or pump therapy, and sensor, if applicable, for 14-days.   
After completion of Phase 1 (the standard therapy phase), subjects and/or 
parents/guardians/caregivers will be trained on the system and transition to Phase 2 
(the hybrid closed-loop phase) initiating treatment with the Omnipod Horizon™ System.  
A subset of subjects (N=40) will participate in activity for a minimum of 3 hours and 
dietary challenges over the course of 2 consecutive days during Phase 2. Phase 2 will 
be followed by the extension phase (Phase 3).   
Table 1 and Table 3 outline the schedule of assessments for each phase of the study. 
Figure 3:  Study Schedule Timeline 
Phase 1 
Phase 2
Phase 3 

 
 
 
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Table 1:  Schedule of Assessments for Phase 1 and Phase 2 
Assessment Schedule 
Screening 
ST1 
ST2 
Hybrid Closed-Loop (HCL) 
EWa 
  
Phase 1 
Phase 2 
  
Visit Number 
1b 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
UVc 
  
Study Day/Visit Windowd 
-30 to -14d  
HCL start 
-14d to 
HCL start 
-1d to HCL 
start 
1 
2 
±1d 
3 
±1d 
10 
±3d 
24 
±3d 
38 
±3d 
52 
±3d 
66 
±3d 
80 
±3d 
94 
±3d 
N/A 
  
Telephone (T) or Office 
(O) Visit 
O 
O 
O 
O 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
O 
Laboratory Assessments 
A1C 
X (POC & 
Blood 
Draw) 
  
  
  
  
  
  
  
  
  
  
  
X 
(Blood 
Draw) 
  
X 
(Bloo
d 
Draw) 
Clinical Assessments 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Xn 
 
 
Medical History 
(including demographics) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm Eligibility 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medications 
X 
Xg 
 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Average total daily 
insulin (~ 7 days) 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Average total basal 
insulin (~ 7 days) 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Average total bolus 
insulin (~ 7 days) 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Pump settings/MDI 
dosing 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Weight 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Vital signs 
X 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
X 
Adverse events 
 
X 
X 
X 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 

 
 
 
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Assessment Schedule 
Screening 
ST1 
ST2 
Hybrid Closed-Loop (HCL) 
EWa 
  
Phase 1 
Phase 2 
  
Visit Number 
1b 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
UVc 
  
Study Day/Visit Windowd 
-30 to -14d  
HCL start 
-14d to 
HCL start 
-1d to HCL 
start 
1 
2 
±1d 
3 
±1d 
10 
±3d 
24 
±3d 
38 
±3d 
52 
±3d 
66 
±3d 
80 
±3d 
94 
±3d 
N/A 
  
Telephone (T) or Office 
(O) Visit 
O 
O 
O 
O 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
O 
Questionnaires 
See Table 2 for specific 
questionnaires 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Study Devices 
Training on Glucagon 
administration and 
information on 
treatment of 
hypo/hyperglycemia 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Horizon Data Portal 
initiation/discontinuation 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
X 
Study device training 
 
Xh 
 
Xi 
 
 
 
 
 
 
 
 
 
 
 
Dispense/Return 
BG/Ketone meter, and 
CGM 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
QC testing of BG/Ketone 
meter by site 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CGM sensor placement 
(as needed throughout) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assess CGM usage and 
ensure data criteria has 
been met 
 
Xj 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of activity 
and routine carb 
consumption 
 
X 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 

 
 
 
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Assessment Schedule 
Screening 
ST1 
ST2 
Hybrid Closed-Loop (HCL) 
EWa 
  
Phase 1 
Phase 2 
  
Visit Number 
1b 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
UVc 
  
Study Day/Visit Windowd 
-30 to -14d  
HCL start 
-14d to 
HCL start 
-1d to HCL 
start 
1 
2 
±1d 
3 
±1d 
10 
±3d 
24 
±3d 
38 
±3d 
52 
±3d 
66 
±3d 
80 
±3d 
94 
±3d 
N/A 
  
Telephone (T) or Office 
(O) Visit 
O 
O 
O 
O 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
T/Oe 
O 
Dispense/Return Horizon 
Systemk 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
X 
Complaints/device 
deficiencies 
 
 
 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
Device uploads 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Data review 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Challenges 
Day 1 
 
 
 
X (any day during Phase 2) 
 
Day 2 
 
 
 
X (consecutive day after Day 1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Abbreviations:  S=Screening; ST1=Standard Therapy Day One; HCL=Hybrid Closed-loop; EW=Early Withdrawal; QC=Quality Control Testing;  UV=Unscheduled Visit 
aEarly withdrawal visit will only be conducted for any subjects that started but did not complete the full study to include standard therapy and the hybrid closed-loop 
phase.   
bAll Screening and all ST1  assessments do not need to occur on the same day as long as the assessments occur within 30 days prior to the start of Phase 2/HCL Start/Study 
Day 1. 
cUnscheduled visits will serve as extra study visits, if needed. 
dIn the event of overlapping visit windows, no Phase 2 visits are to occur on the same date.  
eVisits 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, device uploads/data review from the BG and Ketone meter are not required at any visit conducted via telephone. 
fLab values obtained within six months prior to the screening visit may be used. 
gDocumentation only applicable if there are changes from previous assessment 
hStudy device training for the CGM, blood glucose and ketone meters 
iStudy device training for the Omnipod Horizon™ System 
jSubjects deemed exempt from wearing the study CGM for 14-days will be eligible to immediately commence the hybrid closed-loop phase at Visit 4 and may skip Visit 3 
(Visit 1, Visit 2 and/or Visit 4 may all occur on the same day). For all subjects, any assessment required at more than one visit will only need to be completed once if the 
visits are done on the same day.  
kDevices will be returned to the site at the end of the subject’s participation if the subject is not participating in the extension phase. 

 
 
 
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Table 2:  Questionnaires 
Visit    
Caregiver of Subject* 
 
Screening (Visit 1) 
Clarke Questionnaire 
Visit 2 
WHO-5 
DTSQs Parent 
P-PAID-Child 
Hypoglycemia Confidence Scale 
PSQI 
IDSS (T1) 
SUS 
End of Phase 2 (~13 weeks) or 
Early Withdrawal 
WHO-5 
DTSQc Parent 
P-PAID-Child 
Hypoglycemia Confidence Scale 
PSQI 
IDSS (T1) 
SUS 
INSPIRE-Parent 
Clarke Questionnaire 
Human Factors 
*Parents/guardians completing questionnaires must be the parent/guardian that provided consent for study participation, or 
subsequently signed a consent form. It is preferable that the parent/guardian completing a questionnaire at Screening (Visit 1) and 
Visit 2 is the same parent/guardian completing questionnaires at the End of Phase 2 (~13 weeks) or at the time of withdrawal from 
the study.  No questionnaires will be completed during or at the conclusion of Phase 3. 
 

 
 
 
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Table 3:  Schedule of Assessments for Phase 3  
Assessment Schedule 
Hybrid Closed-Loop (HCL) 
  
Phase 3 
  
Visit Number 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 or 
Study 
Exit 
Extension Through 
Commercializationp 
UV 
EW 
Study Day/Visit Window 
120 
150 
180 
210 
240 
270 
315 
360 
405 
450 
+ 45d ± 5d  
-  
-  
± 5d 
± 5d 
± 5d 
± 5d 
± 5d 
± 5d 
± 5d 
± 5d 
± 5d 
± 5d 
(or sooner if Study 
Exit) 
Telephone (T) or Office 
(O) Visit 
T/Ol 
T/Ol 
T/Ol 
T/Ol 
T/Ol 
T/Ol 
T/Ol 
T/Ol 
T/Ol 
T/Ol 
T/Ol 
T/Ol  
O  
Laboratory Assessments 
A1C 
  
  
X 
  
  
X 
  
X 
  
X 
  
  
X 
Clinical Assessments 
Informed Consent 
  
  
  
  
  
Xn 
  
  
  
 Xn 
  
  
  
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
  
  
  
  
  
  
  
  
  
X 
  
  
X 
Weight 
  
  
  
  
  
  
  
  
  
X 
  
  
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Devices 
Return Horizon System 
  
  
  
  
  
  
  
  
  
X 
X 
  
X 
Complaints/Device 
Deficiencies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Device Uploads 
(BG/Ketone Meter) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
X 

 
 
 
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Data Reviewm 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
lDevice uploads from the BG and Ketone meter are not required at any visit conducted via telephone. 
mData review for Horizon Automated Mode occur at all visits. Data review for BG/Ketone Meters to occur during onsite visits only.   
nSubjects extending their participation into the extension phase are to be consented for both the first 6-month and the second 6-month extension, as well as 
the extension through commercial availability.  Consent for each interval must occur on or any time before commencing that study interval (e.g. consent for 
first 6-months of Phase 3 must occur on or before Visit 13, consent for second 6-months of Phase 3 must occur on or before Visit 19, consent for visits beyond 
Visit 23 until commercial availability must occur on or before Visit 23). 
ODevices will be returned to the site at the end of the subject’s participation if the subject is not participating in the extension phase. 
p Extension Through Commercialization (ETC) visits begin with Visit 24 and each additional visit will be numbered in consecutive order ending with the Study 
Exit visit. 
 
 
 
 

 
 
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6 
OBJECTIVES AND ENDPOINTS 
6.1 Primary Safety Objective 
The primary safety objective of this study is to evaluate the safety of the Omnipod 
Horizon™ System in preschool children with type 1 diabetes. 
6.1.1 Primary Safety Endpoints 
The primary safety objective will be evaluated by summarizing the following 
events during Phase 2, and separately during Phase 3 
 
• 
Incidence rate of severe hypoglycemia (events per person months) 
• 
Incidence rate of diabetic ketoacidosis (DKA) (events per person months) 
 
6.2 Primary Effectiveness Objective 
The primary effectiveness objective of this study is to evaluate the effectiveness of 
the Omnipod Horizon™ System. 
 
6.2.1 Primary Effectiveness Endpoints 
There are two primary effectiveness endpoints.  
 
• 
A1C at the end of Phase 2 compared to baseline A1C 
• 
A1C at Visit 16, 19, 21, and 23 compared to baseline 
• 
Percentage of time in range (70-180 mg/dL) during Phase 2, and 
separately during Phase 3  of the hybrid closed-loop phase compared to 
Phase 1 (standard therapy) 
6.3 Secondary Objective 
The secondary objective of this study is to evaluate additional glycemic measures 
of effectiveness of the Omnipod Horizon™ System.  
6.3.1 Secondary Endpoints 
The secondary objective will be evaluated using the following per subject 
endpoints with prespecified hypotheses:   
• 
Glucose metrics from system CGM during the hybrid closed-loop phase for 
Phase 2 will be compared to Phase 1 overall: 
• 
% of time > 180 mg/dL 
• 
% of time < 70 mg/dL 
 
Additional per subject secondary endpoints without prespecified hypotheses 
used to evaluate the secondary objective include:  
  
• 
A1C: 
• 
A1C at the end of Phase 2 (Visit 13), at 6 months (Visit 16), and at the 
end of Phase 3 (Visit 23; approximately 15 months) 

 
 
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• 
Change from baseline in A1C at the end of Phase 2 (Visit 13), at 6 
months (Visit 16), and at the end of Phase 3 (Visit 23; approximately 15 
months) 
• 
Proportion of subjects demonstrating an improvement from baseline in 
A1C at the end of Phase 2 (Visit 13), at 6 months (Visit 16), and at the 
end of Phase 3 (Visit 23; approximately 15 months) 
 
• 
Glucose metrics from system CGM during the hybrid closed-loop phase 
during Phase 2, and separately during Phase 3 will be compared to Phase 1 
during the day, overnight, and overall: 
 
• 
Mean glucose 
• 
% of time in range 70-180 mg/dL 
• 
% of time in range 70-140 mg/dL 
• 
% of time > 180 mg/dL 
• 
% of time ≥ 250 mg/dL 
• 
% of time ≥ 300 mg/dL 
• 
% of time < 70 mg/dL 
• 
% of time < 54 mg/dL 
• 
Standard deviation 
• 
Coefficient of variation  
 
• 
Percentage of time in hybrid closed-loop as proportion of overall device 
usage time during Phase 2, and separately during Phase 3 
• 
Glucose management indicator (GMI) based on overall mean glucose during 
Phase 2 and, separately during Phase 3 will be compared to Phase 1 
• 
Insulin requirements during Phase 2 and, separately during Phase 3 will be 
compared to Phase 1: 
 
• 
Total daily insulin (TDI) (units, units/kg) 
• 
Total daily basal insulin (units, units/kg) 
• 
Total daily bolus insulin (units, units/kg) 
 
• 
Change from baseline in BMI (kg/m2) at end of Phase 2, and at the end of 
Phase 3 
 
6.4 Exploratory Endpoints 
Analysis of the following exploratory endpoints will be considered. The analyses 
may be used for internal research purposes and/or scientific presentations and/or 
manuscripts and may not all be provided in a regulatory submission:   
• 
Number of hypoglycemic and hyperglycemic events as measured by the 
system CGM during the hybrid closed-loop phase will be compared to Phase 
1 
• 
Glucose metrics from the system CGM during Phase 2 stratified by device 
mode 
• 
Change from baseline in A1C and BMI at the last follow-up visit given at 
least 8-weeks of participation in Phase 2 

 
 
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• 
Change from baseline in A1C at end of Phase 2, stratified by baseline A1C 
(e.g. A1C ≥7.5%, ≥9.0%) 
• 
Proportion of subjects with A1C <7.0% at baseline and end of Phase 2; 
similar analyses using A1C cutoffs of <7.5%, <8.0% and <9.0% 
• 
Proportion of subjects with change from baseline in A1C at end of Phase 2 
of >0.5% and >1.0% 
• 
Proportion of subjects who either had an improvement from baseline of 
>1.0% in A1C or A1C <7.0% at end of Phase 2 
• 
Percentage of time the CGM was used during Phase 2 
• 
Number of meal and correction boluses 
• 
Compare glycemic outcomes (e.g., time in range <70 mg/dL, time in range 
>180 mg/dL) by bolus frequency per day  
• 
Compare glycemic outcomes (e.g., time in range <70 mg/dL, time in range 
>180 mg/dL) by use of CGM informed bolus calculator (i.e., days with CGM 
informed bolus calculator used at least once and days without CGM 
informed bolus calculator use)   
• 
Glycemic outcomes and other measures based on evaluable subjects (i.e., 
those subjects with at least 8-weeks of data during Phase 2) 
 
6.5 Patient Reported Outcomes 
Various caregiver-completed questionnaires will be used to evaluate general and 
disease-specific quality of life, and device usability. These include, but are not 
limited to:   
• 
WHO-5 
• 
DTSQ Parent 
• 
P-PAID-Child 
• 
Hypoglycemia Confidence Scale 
• 
PSQI 
• 
IDSS (T1) 
• 
SUS 
• 
INSPIRE-Parent 
• 
Human Factors Questionnaire 
• 
Clarke Questionnaire 
 
7 
SCREENING AND ELIGIBILITY 
Potential subjects for this study will include individuals who have been diagnosed with 
type 1 diabetes are appropriate for pump therapy per investigator’s assessment. 
Potential subjects will be selected at each clinical study site and screened accordingly. 
Clinical study sites will be advised to: 
 
• 
Recruit subjects using insulin aspart, lispro, and glulisine also known as 
Humalog, Novolog, Admelog, or Apidra 
 
Every effort will be made to establish eligibility of the patient prior to enrollment. Only 
patients who appear to meet all eligibility criteria will be enrolled in the study. Subject 
eligibility will be confirmed by study staff during a screening visit at the clinical site. 

 
 
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Blood draws will be collected as required to demonstrate study eligibility as noted 
below. Laboratory results within the last 6 months of the screening visit, with the 
exception of A1C, may also be used if available. 
 
7.1 Visit 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/assent 
• 
Review of inclusion/exclusion criteria 
• 
Screening assessments performed following Table 1:  Schedule of 
Assessments for Phase 1 and Phase 2 
 
Informed Consent 
Subjects who appear to meet the eligibility criteria will be required to have their 
parent/caregiver sign an Informed Consent Form (ICF) approved by the respective 
Institutional Review Board (IRB) before participating in the study. Failure to 
provide informed consent will render the subject ineligible for the study. 
Subjects must also have a HIPAA (Health Insurance Portability and Accountability 
Act) release of protected health information (PHI) signed by their parent/caregiver. 
The release may be a stand-alone document or part of the informed consent. 
After informed consent is obtained, a subject identification number will be issued 
to uniquely identify each subject. The unique identifier will be used to identify the 
subject throughout the study and will be used for all source documents and 
electronic Case Report Forms (eCRFs). 
Inclusion Criteria 
Subjects must meet all of the following criteria in order to be enrolled in the study: 
1. Age at time of consent 2.0-5.9 years 
2. Living with parent/legal guardian 
3. Diagnosed with type 1 diabetes. Diagnosis is based on investigator’s 
clinical judgment 
4. Deemed appropriate for pump therapy per investigator’s assessment 
taking into account previous history of severe hypoglycemic and 
hyperglycemic events, and other comorbidities 
5. Investigator has confidence that the subject and/or 
parent/guardian/caregiver can successfully operate all study devices and is 
capable of adhering to the protocol 
6. Willing to use only the following types of insulin during the study: Humalog, 
Novolog, Admelog or Apidra during the study  
7. Willing to wear the system continuously throughout the study 
8. Willing to participate in challenges for 2 consecutive days, consisting of 
a minimum of 3 hours of activity per day and dietary challenge by 
reducing the number of carbohydrates entered for a given meal by 
50% 

 
 
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9. A1C <10% at screening visit 
10. Subject and/or parent/guardian must be willing to use the Dexcom App on 
the Omnipod Horizon™ PDM as the sole source of Dexcom data (with the 
exception of the Dexcom Follow App) during the hybrid closed-loop phase 
11. Subject and/or parent/guardian is able to read and speak English 
fluently 
12. Has a parent/legal guardian willing and able to sign the ICF.   
 
Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from the study: 
1. A medical condition, which in the opinion of the investigator, would put the 
subject at an unacceptable safety risk 
2. History of severe hypoglycemia in the past 6 months 
3. History of DKA in the past 6 months, unrelated to an intercurrent illness, 
infusion set failure or initial diagnosis 
4. Diagnosed with sickle cell disease 
5. Diagnosed with hemophilia or any other bleeding disorders 
6. Plans to receive blood transfusion over the course of the study 
7. Clinical evidence of acute or chronic kidney disease (e.g. estimated GFR < 
45) or currently on hemodialysis 
8. History of adrenal insufficiency 
9. Has taken oral or injectable steroids within the past 8-weeks or plans to 
take oral or injectable steroids during the course of the study 
10. Unable to tolerate adhesive tape or has any unresolved skin condition in 
the area of sensor or pump placement 
11. Plans to use insulin other than U-100 insulin intended for use in the study 
device during the course of the study 
12. Use of non-insulin anti-diabetic medication other than metformin (e.g. 
GLP1 agonist, SGLT2 inhibitor, DPP-4 inhibitor, pramlintide) 
13. Thyroid Stimulating Hormone (TSH) is outside of normal range with 
clinical signs of hypothyroidism or hyperthyroidism 
14. Currently participating or plans to participate in another clinical study using 
an investigational drug or device other than the Omnipod Horizon™ 
Automated Glucose Control System during this study period  
15. 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  
 
Screening Assessments 
 
Subjects who appear to meet the eligibility criteria and whose parent/guardian has 
signed the informed consent will continue to the screening assessments which will 
be performed at the clinical study site.   
Screening assessments must be completed within 30-days prior to the start date 
of the hybrid closed-loop phase unless otherwise stated (assessments do not 
need to be completed on the same day) and include the following: 

 
 
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• 
Medical history (including prior and current medical conditions and surgical 
history) 
• 
Demographics (age, gender, race) 
• 
A1C* 
• 
Review of concomitant medications 
• 
Height 
• 
Weight 
• 
Assessment of vital signs 
• 
Questionnaire (Table 2:  Questionnaires) 
o Clarke Questionnaire 
▪ 
Used to assess impaired awareness of hypoglycemia 
• 
For Dexcom G6 users, assessment of whether subjects have met the 
CGM usage and data criteria to participate in an abbreviated standard 
therapy phase (Visit 2 only) per Table 1:  Schedule of Assessments 
o At least 80% CGM use (11.2-days) during any consecutive 14-days in 
the past 30-days and 
o ≥ 2,016 CGM values during the 14-days 
 
*Clinical sites will send the blood specimens for A1C to a NGSP (National 
Glycohemoglobin Standardization Program) certified central laboratory.  A point of 
care (POC) A1C may be used to determine eligibility.   
Subjects that meet the CGM usage and data criteria at Visit 1 may combine Visit 
1, Visit 2, and/or Visit 4 into the same visit if all screening assessments are 
completed and eligibility is confirmed.  Visit 3 will not be applicable for these 
subjects.   
 
MDI subjects that meet the CGM usage and data criteria at Visit 1 may combine 
Visit 1 and Visit 2.  At Visit 2 MDI subjects will be given an MDI Subject Diary to 
record their daily insulin doses for at least 7-days prior to the start of the hybrid 
closed-loop phase.   Visit 3 will not be applicable for these subjects.   
 
The Clarke Questionnaire will be administered during the screening visit.   
Enrollment 
 
Subjects who meet all eligibility criteria and have completed all screening 
assessments will continue to enrollment. A subject is enrolled in the study upon 
placement of the first study CGM. Subjects that do not meet the eligibility criteria 
will not continue in the study and will be considered screen failures.  
 
If for any reason a subject is no longer eligible for the study after the standard 
therapy phase has commenced but prior to the commencement of the hybrid 
closed-loop phase, the subject will not continue in study. No additional study 
assessments will be required. The reason for study exit will be clearly 
documented. 
 
 

 
 
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8 
STANDARD THERAPY - PHASE 1 
The standard therapy phase will commence after all standard therapy assessments are 
completed per Visit 2 – see Table 1:  Schedule of Assessments for Phase 1 and Phase 
2.  
 
During the standard therapy phase, subjects and/or parents/guardians will be asked to 
perform 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) per usual routine 
• 
Give meal boluses. The timing of the bolus delivery will be per each subject’s 
typical dosing routine. 
 
Extending standard therapy past 14-days will not constitute a protocol deviation unless 
standard therapy extends past 30-days. If subjects extend beyond the 14-days, the 
most recent 14-days of data will be used in the endpoint analysis if the data meets the 
criteria defined for CGM use and data availability. 
 
The standard therapy phase will be customized depending on the following subject 
profile: 
 
• 
Current Dexcom G6 users 
• 
Non-G6 users 
• 
Pump Naïve users 
 
Current Dexcom G6 Users 
 
Current Dexcom G6 users will be required to participate in the assessments required as 
part of standard therapy (ST1/Visit 2) but may be exempt from wearing the study CGM 
for 14-days 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 
 
If exemption criteria are not met, subjects and/or parents/guardians 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 phase consistent with the requirements for non-G6 
users. 
 
Subjects deemed exempt from wearing the study CGM for 14-days will be immediately 
eligible to commence the hybrid closed-loop phase starting at Visit 4.   
 
Non-G6 Users 

 
 
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All non-G6 users will be required to participate in the entire 14-day standard therapy 
phase.  At the commencement of the standard therapy phase, subjects will be 
dispensed a CGM receiver that will be blinded and all user settable CGM alerts will be 
turned off.  The device will record continuous glucose information over the 14-day 
period. 
Pump Naïve Users 
Subjects who are naïve to pump therapy will have the opportunity to participate in a 
saline trial during the standard therapy phase.  A saline trial consists of wearing a 
cleared Omnipod® DASH System with the Pod filled with saline to simulate pump 
therapy. This would enable subjects and/or parents/guardians to familiarize themselves 
with the basic concepts of basal and bolus insulin delivery as well as provide the 
experience of wearing an on-body device prior to their participation in the hybrid closed-
loop phase, if they choose to do so.  This is optional and not required. If a pump naïve 
subject is also a current G6 user that meets the criteria as stated above, the subject will 
complete the saline trial prior to enrollment in the study.  
8.1 Visit 2 
Visit 2 represents the commencement of the standard therapy phase.  All 
scheduled assessments will be performed according to Table 1:  Schedule of 
Assessments for Phase 1 and Phase 2.  This visit will include: 
 
• 
Review of concomitant medications 
• 
Average total daily insulin (approximately over the past 7 days) 
• 
Average total daily basal insulin (approximately over the past 7 days) 
• 
Average total daily bolus insulin (approximately over the past 7 days) 
• 
Review of pump settings/MDI dosing 
• 
Assessment of AEs 
• 
Completion of questionnaires (see Table 2:  Questionnaires): 
• 
WHO-5 
o Used to measure current mental well-being 
• 
DTSQs Parent 
o Used to measure satisfaction with diabetes treatment regimens 
• 
P-PAID-Child 
o Measures diabetes-related burden 
• 
Hypoglycemia Confidence Scale 
o Used to measure hypoglycemia unawareness, hypoglycemia 
frequency, severity and impact 
• 
PSQI 
o Used to measure sleep disturbance and usual sleep habits 
• 
IDSS (T1) 
o Used to measure patient satisfaction with their devices and impact 
on quality of life 
• 
SUS 
o Used to measure usability of a system 
• 
Training on Glucagon administration and information on treatment of 
hypo/hyperglycemia   

 
 
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• 
All subjects and/or parents/guardians are required to have access to 
glucagon and receive training on how to deliver the medication 
• 
Study device training per manufacturer’s instructions (CGM, BG, and 
ketone meters) 
• 
Dispensing of CGM (blinded for non-G6 users), BG, and ketone meter 
• 
QC testing of BG and ketone meter 
• 
Must pass as least one level of quality control testing prior to 
dispensing. QC testing can be done at any time prior to dispensing to 
the subject. 
• 
CGM sensor placement (Enrollment)   
• 
Approved anatomical locations for CGM sensor placement will be 
reinforced as well as the importance of using approved location 
• 
Assessment of activity and routine carb consumption 
  
During this visit, subjects and/or parents/guardians will be dispensed the following 
supplies: 
• 
Dexcom transmitter 
• 
Dexcom receiver 
• 
Dexcom sensors 
• 
Contour® Next One blood glucose meter 
• 
Contour® Next One blood glucose meter test strips 
• 
Lancets 
• 
Precision Xtra blood ketone meter 
• 
Precision Xtra blood ketone meter test strips 
 
Subjects and/or parents/guardians will be provided, by the site, information regarding 
treatment of hypoglycemia and hyperglycemia including sick day management and 
emergency management of severe hypoglycemia and diabetic ketoacidosis. Subjects 
and/or parents/guardians will be given contact information for study personnel and 
product support. 
If a subject is on MDI, the investigator will advise the subject and/or parent/guardian on 
the treatment regimen to reduce insulin depending on the insulin action profile of 
injected doses prior to the commencement of the hybrid closed-loop phase. MDI 
subjects will be required to keep a MDI Subject Diary to record daily doses of insulin 
during the standard therapy phase.  
8.2 Visit 3 
Visit 3 will be conducted in person at the clinical study site up to one (1) day prior 
to the start of the hybrid closed-loop phase. Visit 3 and Visit 4 may be combined 
and conducted on the same day.  All scheduled assessments will be performed 
according to Table 1:  Schedule of Assessments for Phase 1 and Phase 2.  This 
visit will include: 
 
• 
Assessment of AEs 
• 
Assessment of whether subjects have met the CGM usage and data 
criteria 

 
 
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Prior to the commencement of the hybrid closed-loop phase, subjects must meet 
the following criteria: 
 
o At least 80% CGM use (11.2 days) during any consecutive 14-days in the 
past 30-days and 
o ≥ 2,016 CGM values during the 14-days 
If the CGM criteria is not met, the standard therapy phase may be extended up to 
30-days, per investigator discretion, or the subject may be withdrawn from the 
study.   
At the conclusion of the standard therapy phase, if the investigator determines that 
there have been no safety concerns, the subject will continue to the hybrid closed-loop 
phase. If the investigator determines that it is unsafe for the subject to continue into the 
hybrid closed-loop phase, the subject will not be allowed to continue in the second 
phase of the study, and the reason for study exit will be documented.  
9 
HYBRID CLOSED-LOOP - PHASE 2 
The hybrid closed-loop phase will commence at Visit 4 upon the conclusion of the 
standard therapy phase and after all assessments are performed according to the Table 
1:  Schedule of Assessments for Phase 1 and Phase 2.  
During the hybrid-closed loop phase, subjects and/or parents/guardians will be asked to 
do the following: 
 
• 
Manage their diabetes while in Automated Mode 
• 
Adjust pump and CGM parameters to optimize their insulin therapy in 
collaboration with the 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. Subjects and/or 
parents/guardians 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. 
• 
Administer 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 
• 
Complete questionnaires (Table 2:  Questionnaires) 
Subjects will have scheduled follow-up visits according to Table 1:  Schedule of 
Assessments for Phase 1 and Phase 2 and complete questionnaires according to Table 
2:  Questionnaires. Visits will be conducted either in person at the clinical study site or 
over the telephone or videoconference.  Subjects and/or parents/guardians may also 
choose to use email or text as a substitute for their scheduled telephone visit. In the 
event of overlapping visit windows, no visits occurring during Phase 2 are to occur on 
the same date.   

 
 
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The duration of the hybrid closed-loop phase for Phase 2 will last ~13-weeks. 
9.1 Challenge Visits 
A subset of subjects (N=40) will take part in activity and dietary challenges. 
Subjects will participate in challenges during any consecutive 2 days during Phase 
2.  Subjects should be in Automated Mode during this time. Subjects should 
engage in a minimum of 3 hours of activity per day. Activity in this age group could 
include examples such as playing, walking, hiking, running, gymnastics, kicking a 
ball, throwing a ball, or riding a bike or trike. Meal challenge will include under-
bolusing for one meal per challenge day by reducing the number of carbohydrates 
for a given meal by 50%. 
Subjects will be allocated to challenges based on investigator discretion until a 
subset of 40 subjects are reached.  
Table 4:  Challenges 
Challenges 
Day 1 
Day 2 
Meal: 
50% reduction in carb entry into the 
bolus calculator for a given meal 
X 
X 
Activity examples: 
Playing, walking, hiking, running, 
gymnastics, kicking a ball, throwing 
a ball, riding a bike or trike  
X 
X 
Challenges will be conducted in an environment of the caregiver’s choosing and 
will not require a visit to the clinical study site. On the day of challenges, 
caregivers will be instructed to contact the clinical site on the agreed upon day to 
confirm the time of the activity and dietary challenges planned.  At the conclusion 
of the activity, caregivers will contact the clinical site to provide the time the activity 
ended and provide a description of the activity and dietary challenges. 
 
During the challenge visits, caregivers will be encouraged to:  
• 
Follow their pre-exercise management such as insulin reduction for meal 
boluses, consumption of snacks, or adjust their insulin delivery settings.  
• 
Treat themselves per their usual routine if they become hypoglycemic or 
hyperglycemic at any time during the exercise challenge.  
• 
Obtain a fingerstick blood glucose value using the study dispensed BG 
meter if CGM is < 70 mg/dL or > 300 mg/dL.  
During the challenges, clinical site staff will monitor the Horizon Data 
Portal. Subjects may participate in exercise if their CGM value is ≥70 mg/dL with 
the corresponding CGM trend either steady or increasing. Subjects will be 
discharged (meaning the site no longer has to actively monitor the HDP) from 

 
 
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each day of challenges when they meet the CGM criteria between 70-300 mg/dL 
on two consecutive checks for the last 30-minutes of their participation given that 
the CGM trend is not rapidly increasing or decreasing at these timepoints. 
 
Investigator/site staff will conduct a telephone visit with the subject and caregiver 
within a few hours of the completion of each day of challenges to ensure the 
subject is safe. 
Measuring Activity Levels and Carbohydrate intake 
At Visit 2, Visit 9, Visit 11, and Visit 13, site staff will interview all subject 
caregivers to record the approximate amount of daily activity as well as daily 
carbohydrate intake with the addition of these questions: 
1. Over the last week, how many hours on average does your child exercise 
per day?  This may include activities such as playing, walking, hiking, 
running, gymnastics, kicking a ball, throwing a ball, riding a bike or trike. 
2. Over the last week, what is the average daily carbohydrate consumption 
for your child? 
9.2 Visit 4 
Visit 4 represents the commencement of Phase 2 (hybrid closed-loop phase) and 
will be conducted in person at the clinical site on Study Day 1.  All scheduled 
assessments will be performed according to Table 1:  Schedule of Assessments 
for Phase 1 and Phase 2.  This visit will include: 
• 
Review of concomitant medications 
• 
Average total daily insulin (approximately over the past 7 days) 
• 
Average total daily basal insulin (approximately over the past 7 days) 
• 
Average total daily bolus insulin (approximately over the past 7 days) 
• 
Pump settings/MDI dosing 
• 
Assessment of AEs 
• 
Initiation of Horizon Data Portal monitoring 
• 
Omnipod Horizon™ System device training conducted by trained clinical 
site staff 
o Subjects and/or parents/guardians will be trained on operating 
Omnipod Horizon™ in both Manual and Automated Modes.  
o This will include first time device set-up with entry of basal profile, bolus 
calculator settings with insulin:carbohydrate ratio, target glucose and 
correction factor.  
o The Pod will be filled with the subject’s own U-100 rapid-acting insulin 
and placed on body. Subjects will also be trained on use of Dexcom G6 
CGM, regardless of previous experience, setting up low (recommended 
to be 70 mg/dL or higher) and high glucose alerts (recommended to be 
300 mg/dL or lower) and entering transmitter serial number into the 
Horizon App.  
o Subjects and/or parents/guardians may choose their desired target BG 
ranging between 110-150 mg/dL in increments of 10mg/dL, although 
the default and recommended setpoint is 120 mg/dL.  

 
 
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o In addition, Omnipod Horizon™ has a novel bolus calculator feature 
that incorporates both the CGM value and trend into the suggested 
bolus amount. In general, if the CGM values are trending up or down, 
the calculator will add or subtract insulin from the suggested bolus 
amount to help keep BGs within target range. 
• 
Dispense Omnipod Horizon™ System 
• 
Complaints/device deficiencies for CGM, BG and ketone meter 
• 
Device uploads for CGM (via IQVIA), BG and ketone meter (not applicable 
if combining with Visit 2) 
• 
Data review by clinician 
• 
Removal of the subject’s personal insulin pump (if applicable) 
o Investigators will use the Insulet-provided Patient Therapy Order Form 
(PTOF) as a guide to transition subjects from MDI to pump therapy 
(Appendix A) 
If a subject is a current Dexcom G6 User and Visit 2 and Visit 4 occur on the same 
day, average total daily insulin and pump settings/MDI dosing only needs to be 
collected once.  
At the conclusion of the training and completion of assessments, each subject’s 
treatment will be initiated marking their commencement of the hybrid closed-loop 
phase. 
 
9.3 Visit 5  
Visit 5 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 2 ± 1 day.  This visit will include: 
• 
Review of concomitant medications 
• 
Assessment of AEs since last visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted in person at 
the clinical study site) 
• 
Data review of Automated Mode use by clinician 
 
9.4 Visit 6 
Visit 6 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 3 ± 1 day, respectively. This visit will include: 
• 
Review of concomitant medications 
• 
Assessment of AEs since last visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted in person at 
the clinical study site) 
• 
Data review of Automated Mode use by clinician 
 

 
 
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9.5 Visit 7 
Visit 7 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 10 ± 3-days. This visit will include: 
 
• 
Review of concomitant medications 
• 
Assessment of vital signs (if visit is conducted in person at the clinical 
study site) 
• 
Assessment of AEs since last visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted in person at 
the clinical study site) 
• 
Data review of Automated Mode use by clinician 
 
9.6 Visit 8 
Visit 8 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 24 ± 3-days. This visit will include: 
• 
Review of concomitant medications 
• 
Assessment of AEs since last visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted in person at 
the clinical study site) 
• 
Data review of Automated Mode use by clinician 
 
9.7 Visit 9 
Visit 9 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 38 ± 3-days. This visit will include: 
• 
Review of concomitant medications 
• 
Assessment of vital signs 
• 
Assessment of AEs since last visit (if visit is conducted in person at the 
clinical site) 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted in person at 
the clinical site) 
• 
Data review of Automated Mode use by clinician 
• 
Assessment of activity and routine carb consumption 
 
9.8 Visits 10, 11 and 12 
Visits 10, 11 and 12 will be conducted either over the telephone or in person at 
the clinical study site on Study Day 52 ± 3-days, 66 ± 3-days, and 80 ± 3-days. 
These visits will include: 
• 
Review of concomitant medications 

 
 
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• 
Assessment of AEs since last visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted in person at 
the clinical study site) 
• 
Data review of Automated Mode use by clinician 
• 
Assessment of activity and routine carb consumption (Visit 11 only) 
 
9.9 Visit 13 (End of Phase 2) 
Visit 13 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 94 ± 3 days.  This visit will include: 
• 
A1C (blood draw sent to NGSP laboratory) 
• 
Review of concomitant medications 
• 
Height (if visit is conducted in person at the clinical site) 
• 
Weight (if visit is conducted in person at the clinical site) 
• 
Assessment of vital signs (if visit is conducted in person at the clinical site) 
• 
Assessment of AEs since last visit 
• 
Completion of questionnaires (See Table 2:  Questionnaires for specific 
requirements by age group): 
• 
WHO-5 
• 
DTSQc Parent 
• 
P-PAID-Child 
• 
Hypoglycemia Confidence Scale 
• 
PSQI 
• 
IDSS (T1) 
• 
SUS 
• 
INSPIRE-Parent 
▪ 
Used to measure a caregiver’s experience of the support they 
receive 
• 
Clarke Questionnaire 
• 
Human Factors (HF) Questionnaire 
▪ 
Measures trust in the Horizon System 
• 
Discontinuation of Horizon Data Portal monitoring if not continuing into 
Phase 3 
• 
Return study devices if not continuing into Phase 3 (Omnipod Horizon™ 
System, CGM, BG and ketone meters) if not participating in the extension 
phase 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter 
• 
Data review of Automated Mode use by clinician  
• 
Assessment of activity and routine carb consumption  
 
This visit will mark the discontinuation of Phase 2 and mark the end of the study 
for subjects not continuing to Phase 3.        

 
 
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9.10 Unscheduled Visits (Phase 2) 
Aside from scheduled visits, subjects may require an unscheduled visit either by 
telephone (inclusive of email or text options) or in person at the clinical study site. 
All scheduled assessments will be performed according to Table 1:  Schedule of 
Assessments for Phase 1 and Phase 2. This visit will include: 
 
• 
Review of concomitant medications 
• 
Assessment of AEs since last visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (recommendation only if visit is 
conducted at the clinical site) 
• 
Data review of Automated Mode use by clinician 
 
Additional assessments may be warranted at the discretion of the investigator. 
 
Instructions will be given to subjects and/or parents/guardians on how to contact clinical 
study staff 24 hours per day to report any study related problems. Subjects and/or 
parents/guardians will be encouraged to call the clinical study site at any time with any 
concerns.  
 
 
9.11 Early Withdrawal (Phase 2) 
Any subject may withdraw early from the study at any time for any reason. Upon 
withdrawal, subjects will be asked to complete the assessments according to 
Table 1:  Schedule of Assessments for Phase 1 and Phase 2. The investigator 
may also terminate a subject’s participation in the study if it is in the best interest 
of the subject or if the Sponsor or local regulatory agency (e.g., FDA) terminates 
the study. 
 
The Early Withdrawal visit will include: 
 
• 
A1C (blood draw sent to NGSP laboratory) 
• 
Review of concomitant medications 
• 
Height 
• 
Weight 
• 
Assessment of vital signs 
• 
Assessment of AEs since last visit 
• 
Completion of questionnaires (see Table 2:  Questionnaires for specific 
requirements by age group): 
• 
WHO-5 
• 
DTSQc Parent 
• 
P-PAID-Child 
• 
Hypoglycemia Confidence Scale 
• 
PSQI 
• 
IDSS (T1) 
• 
SUS 
• 
INSPIRE-Parent 

 
 
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▪ 
Used to measure a caregiver’s experience of the support they 
receive 
• 
Clarke Questionnaire 
• 
Human Factors (HF) Questionnaire 
▪ 
Measures trust in the Horizon System 
• 
Discontinuation of Horizon Data Portal monitoring 
• 
Return all study devices  
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter 
• 
Data review by clinician  
• 
Assessment of activity and routine carb consumption  
The reason for withdrawal will be recorded, and their participation in the study will 
end. 
In the event of a subject’s death during the study, the subject’s participation will be 
considered terminated and the date of death will be used as the date of study exit. 
10 HYBRID CLOSED-LOOP – PHASE 3 
The hybrid closed-loop Phase 3 extension will commence at Visit 13 upon conclusion 
of hybrid closed-loop Phase 2 and after all assessments are performed according to  
Table 1:  Schedule of Assessments for Phase 1 and Phase 2. Phase 3 assessments 
are to be performed according to Table 3:  Schedule of Assessments for Phase 3 
For subjects that do not extend their participation into the extension phase, the reason 
for study exit at Visit 13 will be documented. This will not be considered an early 
withdrawal from the study. 
Subjects extending their participation into the extension phase are to be consented for 
both the first 6-month extension and the second 6-month extension, as well as the 
extension through commercial availability.  Consent for each interval must occur on or 
any time before commencing that study interval (e.g. consent for first 6-months of 
Phase 3 must occur on or before Visit 13, consent for second 6-months of Phase 3 
must occur on or before Visit 19, consent for the extension through commercial 
availability must occur on or before Visit 23).  
During the hybrid-closed loop extension phase, subjects will continue to perform the 
following: 
 
• 
Adjust pump and CGM parameters to optimize their insulin therapy in 
collaboration with the 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. Subjects 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. 

 
 
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• 
Administer 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 
Subjects will have scheduled follow-up visits. Visits will be conducted either in person at 
the clinical study site or over the telephone.  Subjects may also choose to use email or 
text as a substitute for their scheduled telephone visit.  
The duration of the hybrid closed-loop extension phase will last approximately 12-
months. 
Subjects will be encouraged to call the clinical study site at any time with any concerns.  
 
10.1 Visit 14 
Visit 14 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 120 ± 5 days.  This visit will include: 
• 
Review of concomitant medications 
• 
Assessment of adverse events since previous visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted at the clinical 
site) 
• 
Data review of Automated Mode use by clinician 
 
10.2 Visit 15 
Visit 15 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 150 ± 5 days.  This visit will include: 
• 
Review of concomitant medications 
• 
Assessment of AEs since last visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted at the clinical 
site) 
• 
Data review of Automated Mode use by clinician 
 
10.3 Visit 16 
Visit 16 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 180 ± 5 days.  This visit will include: 
• 
A1C (blood sample sent to NGSP laboratory) 
• 
Review of concomitant medications 
• 
Assessment of AEs since last visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 

 
 
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• 
Device uploads for BG and ketone meter (if visit is conducted at the clinical 
site) 
• 
Data review of Automated Mode use by clinician 
 
10.4 Visits 17 and 18 
Visits 17 and 18 will be conducted either over the telephone or in person at the 
clinical study site on Study Day 210 ± 5 days and Study Day 240 ± 5 days, 
respectively.  These visits will include: 
• 
Review of concomitant medications 
• 
Assessment of AEs since last visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted at the clinical 
site) 
• 
Data review of Automated Mode use by clinician 
 
10.5 Visit 19  
Visit 19 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 270 ± 5 days.  This visit will include: 
• 
A1C (blood sample sent to NGSP laboratory) 
• 
Informed Consent (consent for second 6-month interval of Phase 3 may 
occur on or any time before this visit) 
• 
Review of concomitant medications 
• 
Assessment of AEs since last visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted at the clinical 
site) 
• 
Data review of Automated Mode use by clinician 
 
10.6 Visit 20 
Visit 20 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 315 ± 5 days.  This visit will include: 
• 
Review of concomitant medications 
• 
Assessment of AEs since previous visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted at the clinical 
site) 
• 
Data review of Automated Mode use by clinician 
 

 
 
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10.7 Visit 21 
Visit 21 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 360 ±5 days.  This visit will include: 
• 
A1C (blood sample sent to NGSP laboratory) 
• 
Review of concomitant medications 
• 
Assessment of AEs since previous visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted at the clinical 
site) 
• 
Data review of Automated Mode use by clinician 
 
10.8 Visit 22 
Visit 22 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 405 ± 5 days.  This visit will include: 
 
• 
Review of concomitant medications 
• 
Assessment of AEs since previous visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter (if visit is conducted at the clinical 
site) 
• 
Data review of Automated Mode use by clinician 
 
10.9 Visits 23 
Visits 23 will be conducted either over the telephone or in person at the clinical 
study site on Study Day 450 ± 5 days. This visit will include: 
• 
A1C (blood sample sent to NGSP laboratory) 
• 
Informed Consent (consent for extension in study through commercial 
availability of the Omnipod 5 System may occur on or any time before this 
visit) 
• 
Review of concomitant medications 
• 
Height 
• 
Weight 
• 
Assessment of AEs since previous visit  
• 
Return study devices (Omnipod Horizon™ System, CGM, BG and ketone 
meters) if this visit marks the Study Exit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter  
• 
Data review of Automated Mode use by clinician 
 
Subjects continuing in the study after Visit 23 will continue in the study through 
commercialization.  Subjects will complete their final study visit at their next study visit 

 
 
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once commercially available.  Therefore, subjects may complete the study at different 
visits depending on the timing of their visit in relation to commercialization.   
 
10.10 Extension Through Commercialization Visits 
These visits will be conducted either over the telephone or in person (in person 
for final study visit) at the clinical study site + 45 days from the last visit with a 
visit window of ± 5 days. The final study visit after commercialization may occur 
sooner than 45 days from the prior visit. These visits will include: 
• 
Review of concomitant medications 
• 
Assessment of AEs since previous visit  
• 
Return study devices (Omnipod Horizon™ System, CGM, BG and ketone 
meters) (if this visit marks the Study Exit) 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter  
• 
Data review of Automated Mode use by clinician 
      
 
10.11 Unscheduled Visits (Phase 3) 
Aside from scheduled visits, subjects may require an unscheduled visit either by 
telephone or in person at the clinical study site. All scheduled assessments will be 
performed according to Table 3:  Schedule of Assessments for Phase 3. This visit 
will include, at a minimum: 
 
• 
Review of concomitant medications 
• 
Assessment of AEs since last visit 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Data review of Automated Mode use by clinician 
 
Additional assessments may be warranted at the discretion of the investigator. 
 
 
10.12 Early Withdrawal (Phase 3) 
Any subject may withdraw early from the study at any time for any reason. Upon 
withdrawal, assessments will be performed following Table 3:  Schedule of 
Assessments for Phase 3. The investigator may also terminate a subject’s 
participation in the study if it is in the best interest of the subject or if the Sponsor 
or local regulatory agency (e.g., FDA) terminates the study. 
 
The Early Withdrawal visit will include: 
 
• 
A1C (blood sample sent to NGSP laboratory) 
• 
Review of concomitant medications 
• 
Height 
• 
Weight 

 
 
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• 
Assessment of AEs since last visit 
• 
Return study devices (Omnipod Horizon™ System, CGM, BG and ketone 
meters) 
• 
Complaints/device deficiencies such as occlusion alarms and system 
hazard alarms since last visit 
• 
Device uploads for BG and ketone meter 
• 
Data review by clinician 
 
The reason for withdrawal will be recorded, and their participation in the study will 
end. 
In the event of a subject’s death during the study, the subject’s participation will be 
considered terminated, and the date of death will be used as the date of study exit. 
 
10.13 Lost to Follow-up 
Every effort will be made to contact the subject and/or parent/guardian in the 
event of a missed scheduled visit. A subject will be considered lost to follow-up if 
they are inaccessible by two or more different methods of contact and fail to show 
up for two scheduled visits. The site will document each attempt made to contact 
the subject and specify the reason for early withdrawal as lost to follow-up.      
 
11 SPONSOR REPRESENTATIVES 
One or more representatives of the Sponsor may be present at the hybrid closed-loop 
clinical study site visits under supervision of the investigator. 
 
12 SAFETY 
12.1 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. 
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 Horizon™ System 
use or misuse. 

 
 
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• 
Use of the Pod (Omnipod® tubeless, insulin delivery pump) - 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 quickly 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: 
o Anaphylaxis (allergic shock) 
o Bruising at the Pod site 
o Bleeding at the Pod site 
o Erythema (redness at the Pod site) 
o Excoriation (raw skin at Pod site) 
o Pruritus (itching) 
o Induration (hardening of the skin at the Pod site) 
o Infection (can include heat, redness, swelling, pain, and drainage) 
o Inflammation (redness, swelling) 
o Skin reaction to adhesive at the Pod site 
o Papule (small, solid raised area on the skin similar to a pimple) 
o Pain or discomfort 
o Ulceration (skin sores) 
o 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 
• 
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 are several potential benefits from this study. The Omnipod Horizon™ 
System is designed to provide automated glucose control. The system is expected 
to reduce hypoglycemia without incurring an unacceptable increase in 
hyperglycemia and mean glucose. The system is also expected to reduce the 
extent and magnitude of hyperglycemia associated with meals. The Omnipod 
Horizon™ System uses a control-to-target strategy that attempts to achieve and 
maintain a set target glucose level. 
 
12.2 Hypoglycemia/Hyperglycemia 
Subjects and/or parents/guardians 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.  
Subjects and/or parents/guardians will be encouraged to manage their 
hyperglycemia per their usual routine. This includes checking for ketones using 
the study-approved ketone meter and administering a correction bolus if needed.   

 
 
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In the event of unexplained hyperglycemia, where the CGM is >300mg/dL for 1h 
or >250 mg/dL for 2h, 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 should be 
removed, and the subject and/or parent/guardian will be instructed to replace the 
Pod. Subjects and/or parent/guardian 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 and cause may be attributed to 
suspected occlusion if the cannula is in situ or dislodged cannula if it has been 
pulled out. Pods will be requested to be returned to Insulet for analysis.  An 
Adverse Event form will be completed per the Reportable Adverse Events section 
below. 
12.3 Adverse Events 
12.3.1 Definitions 
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 subjects, 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.28 
NOTE 2: This definition includes events related to the procedures involved (any 
procedure in the clinical investigation plan).28 
Serious Adverse Event (SAE): Any untoward medical occurrence that: 
o Led to death 
o Led to serious deterioration in the health of the subject, that either 
resulted in: 
▪ 
a life-threatening illness or injury, or 
▪ 
a permanent impairment of a body structure or a body function, or 
▪ 
in-patient or prolonged hospitalization, or 
▪ 
medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function. 
o 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.28 
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated 
with, a device, if that effect, problem, or death was not previously identified in 
nature, severity, or degree of incidence in the investigational plan or application 
(including a supplementary plan or application), or any other unanticipated serious 

 
 
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problem associated with a device that relates to the rights, safety, or welfare of 
participants.28 
Adverse Device Effect (ADE): An adverse device effect (ADE) is an adverse 
event related to the use of an investigational medical device. 28  
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.28 
NOTE 2: This definition includes any event resulting from user error or from 
intentional misuse of the investigational medical device.28 
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. 28 
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. 
Note: for reporting purposes, sites will not be asked to distinguish between device 
complaints and malfunctions.  
For any event where there is suspicion that the study device is involved, the 
Sponsor will request that the investigator return the device for evaluation. 
All device complaints or malfunctions involving any investigational component of 
the Omnipod Horizon™ System used in the study will be reported to the Sponsor 
within 5 business days of knowledge of the deficiency and documented on an 
appropriate eCRF. All study product associated with a reported device deficiency 
(PDM, Pod, and CGM) should be retained at the clinical site and returned to the 
Sponsor or CGM manufacturer for investigation and analysis. 
12.3.2  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 phase 
(i.e., insertion of the CGM sensor) and continue through the hybrid closed-loop 
Phase 2 and 3 until the subject’s participation has ended. All reported adverse 

 
 
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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 subject’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 occurring in association with a study procedure 
4. An AE not related to a study device issue which leads to temporary or 
permanent discontinuation of the study device 
5. An AE that affects the participant’s ability to complete any study 
procedures 
6. An AE for which a visit is made to a hospital emergency department   
7. Hypoglycemic Events as defined below 
8. Hyperglycemia/Ketotic Events as defined 
Skin reactions from sensor or pod placement are only reportable if severe and/or 
required treatment. 
For the purpose of this protocol, mild symptoms of hypoglycemia and 
hyperglycemia (i.e., clinically non-significant) or blood glucose values out of the 
normal range (whether or not they resulted in delayed meals or correction 
boluses) will not be reported as AEs unless determined to meet the reportable 
criteria in the Hypoglycemic Events and Hyperglycemic/Ketotic Events sections 
below. 
All reportable AEs—whether volunteered by the participant, discovered by study 
personnel during questioning, or detected through physical examination, 
laboratory test, or other means—will be reported on an AE eCRF.  
 
12.3.3 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 actions25. 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 

 
 
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loss of consciousness. These episodes may be associated with sufficient 
neuroglycopenia to induce seizure or loss of consciousness.  If plasma 
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. 
 
12.3.4 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)24 and described below 
• 
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 and ketones 
>1.0 mmol/L 
• 
Hyperglycemia resulting in an SAE that may not otherwise meet the above 
criteria 
 
Hyperglycemic events are classified as DKA24 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 
 
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. 
 
12.3.5 Relationship of Adverse Event to Investigational Device 
The investigator will be responsible for making a determination 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 investigational device. 

 
 
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To ensure consistency of adverse event causality assessments, investigators 
should apply the following general guideline when determining whether an 
adverse event is related. 
The causal relationship to the study procedures and the investigational device for 
each adverse event will be rated as follows:  
• 
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 subject’s condition. There is a possibility of any relation 
between the event and the procedures or the investigational device.  
• 
Related: The temporal sequence is relevant or the event abates upon 
completion of the procedure/ investigational device, or the event cannot be 
reasonably explained by the subject’s condition or comorbidities. The 
event is related or most likely associated with the procedures or the 
investigational device. 
 
12.3.6 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. 
 
12.3.7 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.  

 
 
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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. 
• 
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 UADEs are ongoing when a participant completes the study (or withdraws), 
the subject 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 subject 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.  
12.4 Reportable Device Issues 
Device complaints and device malfunctions will be reported except in the following 
circumstances. These occurrences are expected and will not be reported on a 
Device Deficiency Form: 
• 
CGM sensor, transmitter or Pod lasting fewer days than expected per 
manufacturer 
• 
CGM tape or Pod adherence issues 
• 
Battery lifespan deficiency due to inadequate charging or extensive wireless 
communication 
• 
Intermittent device component disconnections/communication failures not 
requiring system replacement or workaround/resolution not specified in user 
guide/manual. 
• 
Device issues clearly addressed in the user guide manual that do not require 
additional troubleshooting 
 
12.5 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, or by completion 
of the AE eCRF. If the form is not initially completed, it should be competed 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.  

 
 
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Upon receipt of a UADE report, the Sponsor will investigate the UADE and if 
indicated, report the results of the investigation to all participating investigators, 
overseeing IRBs, and the FDA within 10 business days of the Sponsor becoming 
aware of the UADE per 21CFR 812.46(b). Copies of the associated reports and 
correspondence with the investigators, regulatory authorities, and Sponsor must 
be retained with study records. 
The Medical Monitor must notify the DSMB of any UADEs and determine if the 
UADE presents an unreasonable risk to participants. If so, the Sponsor must 
ensure that all investigations, or parts of investigations presenting that risk, are 
terminated as soon as possible but no later than 5 working days after the Medical 
Monitor makes this determination and no later than 15 working days after first 
notice of the UADE. 
Device deficiencies will be handled by the Sponsor or designee as described 
below. In the case of a Dexcom CGM transmitter or sensor device malfunction, 
information will be forwarded to Dexcom by the site personnel, to be handled by 
Dexcom’s complaint management system. 
If the subject is hospitalized because of or during the course of an SAE, then a 
copy of the hospital discharge summary must 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 subject identifying information must be redacted and 
only the unique subject number will be used to label the forms for identification 
purposes. 
For any event where there is suspicion that the study device is involved, the 
investigator will return the device for evaluation when possible. 
 
12.6 Safety Oversight 
The study Medical Monitor will review all reportable adverse events and adverse 
device events that are reported during the study.  SAEs will typically be reviewed 
within 24-hours of reporting.  Other AEs will typically be reviewed approximately 
weekly.  
A Data and Safety Monitoring Board (DSMB) will be informed of all cases of 
severe hypoglycemia and diabetic ketoacidosis irrespective of device relationship, 
all UADEs during the study and will review compiled safety data at periodic 
intervals. The DSMB also will be informed of any SADEs and ADEs not meeting 
criteria for a UADE if the Medical Monitor requests the DSMB review. The DSMB 
can request modifications to the study protocol or suspension or outright stoppage 
of the study if deemed necessary based on the totality of safety data available. 
Details regarding DSMB review will be documented in a separate DSMB Charter. 
 
A safety review including 4 weeks of Phase 2 data following study 
recommencement from the Omnipod Horizon™ Pivotal Study will be conducted by 
the DSMB prior to enrollment of subjects into this study. At minimum, this will 
include a review of 20 pivotal subjects, with at least 3 (three) of those subjects 
aged 6.0-7.9 years. 
 

 
 
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12.7 Stopping Criteria 
12.7.1 Participant Discontinuation of Study Participation 
In the case of a UADE, the Medical Monitor will determine if the use of the study 
device will be suspended while the problem is diagnosed. The use of the study 
device may continue if the Medical Monitor believes the event is explainable, 
unlikely to reoccur and that it is safe for the subject to continue using the device. 
Alternately, the Medical Monitor may request the study subject, or all study 
subjects, to stop using the study device or to only use in Manual Mode. Should all 
study subjects be required to stop using the study device or to only use in Manual 
Mode due an UADE, use of the study device or Automated Mode will not be 
restarted until approval is received from the IRB, DSMB and FDA. 
Use of the study device by a participant will be discontinued if any of the following 
occur:  
• 
The investigator believes it is unsafe for the participant to continue on the 
intervention. 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 
• 
One distinct episode of DKA as defined above 
• 
One distinct severe hypoglycemia events as defined above 
 
12.7.2 Criteria for Suspending or Stopping Overall Study 
Stopping criteria for  Phase 2 will be determined by an independent DSMB, who 
will assess the specific event rates for DKA and severe hypoglycemia from the 
study at specific timepoints relative to published rates from large, population-
based datasets.  Stopping rules may be modified for the Phase 3 extension. 
 
In consideration of adverse events rates occurring in this proposed study, the 
rates will be assessed relative to published rates from Foster et. al.10 and Miller et. 
al.26 to determine whether severe hypoglycemia or diabetic ketoacidosis are within 
expected rates during this study. Table 5:  T1D Exchange Rates of Severe 
Hypoglycemia and Diabetic Ketoacidosis10,26 provides a summary of these 
published rates. 
 
Table 5:  T1D Exchange Rates of Severe Hypoglycemia and Diabetic 
Ketoacidosis10,26 
Adverse Event 
Frequency of subjects to experience ≥ 1 
event extrapolated from T1DX registry 
2016-2018, 2013-2014 
Severe hypoglycemia (loss of consciousness or 
seizure) 
4-5% < 18 years  
7% ≥ 18 years 

 
 
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Diabetic ketoacidosis (overnight hospitalization) 
3-4% < 18 years   
2-3% ≥ 18 years  
 
For unanticipated adverse device effects (UADEs), the DSMB 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 UADE.   
 
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 Medical Monitor will review all adverse events that are reported during 
the study, and the DSMB will review all cases of severe hypoglycemia, DKA and 
UADEs as well as compiled safety data at periodic intervals. The Medical Monitor 
and/or DSMB may recommend suspension of study activities or stoppage of the 
study to the Sponsor if deemed necessary based on the totality of safety data 
available. 
 
12.8 Data Safety Monitoring Board (DSMB) 
The DSMB will be established prior to the first enrollment and consist, at a 
minimum, of two physicians and one statistician independent from the Sponsor 
and study. The physicians will have relevant therapeutic and medical expertise. 
The DSMB will determine the stopping criteria for Phase 2 of the study and review 
Severe Hypoglycemia and DKA as well as compiled safety data at periodic 
intervals to determine if the stopping rules apply. Stopping rules may be modified 
for the Phase 3 extension. 
 
Compiled safety data may include listings of protocol deviations, device 
deficiencies, subject terminations, and subject withdrawals related to device or 
procedure safety. In addition, the DSMB members will be notified upon the 
occurrence of any UADEs to determine whether the study should proceed or not 
based upon risk and may request an ad hoc meeting to discuss. The DSMB will 
meet approximately every 6 months after the start of enrollment. The DSMB will 
also be requested to indicate whether or not they would like to conduct a review 
meeting after the notification of any events of Severe Hypoglycemia or Diabetic 
Ketoacidosis. If the DSMB requests a review meeting, one will be scheduled as 
soon as possible. Additional reviews may be conducted at any time based on the 
request of the DSMB, Sponsor or Medical Monitor. At the conclusion of each 
meeting, the DSMB will make a recommendation to the Sponsor concerning the 
continuation, modification, and/or termination, of the study and/or a statement 
regarding their overall assessment of device safety and continuation of the pivotal 
study. The final decision regarding the continuation, modification or termination of 
the study will reside with the Sponsor. Responsibilities, qualifications, membership 
and committee procedures, including the final stopping rules, will be outlined in the 
DSMB Charter. 

 
 
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12.9 Medical Monitor 
An independent Medical Monitor will be responsible for individual and timely 
review of adverse events as defined below. The Medical Monitor will be a 
physician with relevant therapeutic and medical expertise that is not participating 
as an Investigator in the study and does not have a financial, scientific, or other 
conflict of interest with the clinical study. 
 
Specific responsibilities of the Medical Monitor include:  
 
• 
Review of all adverse events reported during the study 
• 
Review all serious study procedure-related and/or investigational device-
related adverse events to determine if the adverse event warrants 
consideration as a UADE and facilitate the reporting of UADEs if applicable  
• 
Adjudicate the following(a) all SAEs; (b) any events of Diabetic Ketoacidosis 
or Severe Hypoglycemia; (c) all AEs reported by the site as related or 
possibly related to the investigational device; and/or (d) any additional 
events as requested by the Sponsor.  
• 
The specified events will be adjudicated to determine: 
o event relatedness to the study procedures and/or the 
investigational device 
o event categorization and assess seriousness and severity 
o whether an adverse event is anticipated or 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 
investigational device, for the determination of safety endpoints and for all 
regulatory reports, product labeling, and publications or presentations. 
 
The Medical Monitor’s roles and responsibilities are described in the Safety 
Management Plan (SMP).  
 
13 STATISTICAL CONSIDERATIONS 
13.1 Objectives and Endpoints 
13.1.1 Primary Safety Objective 
The primary safety objective of the study is to evaluate the safety of the Omnipod 
Horizon™ System in preschool patients with type 1 diabetes. 
13.1.1.1 Primary Safety Endpoints 
The primary safety objective will be evaluated by summarizing the following 
events during Phase 2, and separately during Phase 3:  
 
• 
Incidence rate of severe hypoglycemia (events per person months) 
• 
Incidence rate of diabetic ketoacidosis (DKA) (events per person months) 
 

 
 
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13.1.2 Primary Effectiveness Objective 
The primary effectiveness objective of this study is to evaluate the effectiveness of 
the Omnipod Horizon™ System 
 
13.1.2.1 Primary Effectiveness Endpoints 
There are two primary effectiveness endpoints.  
 
• 
A1C at the end of Phase 2 compared to baseline A1C  
• 
A1C at Visit 16, 19, 21, and 23 compared to baseline 
• 
Percentage of time in range (70-180 mg/dL) during Phase 2, and 
separately during Phase 3 of the hybrid closed-loop phase compared to 
Phase 1 (standard therapy) 
 
A1C-Phase 2 
 
The end of Phase 2 (~13 weeks) A1C will be compared to baseline A1C as 
measured by the core laboratory by calculating the change from baseline in A1C 
at Visit 13 (~13 weeks) for each subject. The change in A1C is calculated as A1C 
at Visit 13 minus baseline A1C (where negative change indicates decrease or 
improvement in A1C). The null hypothesis associated with this endpoint states 
that the mean change in A1C is greater than or equal to zero. Rejection of the null 
hypothesis indicates that the observed data support the alternative hypothesis that 
the mean change in A1C is less than zero. 
 
The hypotheses associated with the first primary endpoint are defined as: 
H0: µ ≥ 0 
H1: µ < 0 
where µ is the mean of the per subject differences in A1C from baseline to Visit 
13.  
 
A1C – Phase 3 
 
A1C at Visit 16 (~6 months total HCL participation) will be compared to baseline 
A1C as measured by the core laboratory by calculating the change from baseline 
in A1C at follow-up visit for each subject.  
 
The change in A1C is calculated as A1C at follow-up minus baseline A1C.  There 
are no hypotheses associated with this endpoint.   
 
 
Percentage of Time in Range 70-180 mg/dL -Phase 2 
 
The percentage of time in range 70-180 mg/dL during Phase 2 of the hybrid 
closed-loop phase will be compared to Phase 1 (standard therapy) by calculating 
the change between the time in range percentages between Phase 2 of hybrid 
closed-loop and Phase 1 (standard therapy) for each subject. The change in 
percentage of time in range 70-180 mg/dL is calculated as the percentage of time 
in range during Phase 2 minus the percentage of time in range during Phase 1  
(where positive change indicates increased time in range). The null hypothesis 

 
 
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associated with this endpoint states that the mean change in percentage of time in 
range 70-180 mg/dL is less than or equal to zero. Rejection of the null hypothesis 
indicates that the observed data support the alternative hypothesis that the mean 
change in percentage of time in range 70-180 mg/dL is greater than zero. 
 
The hypotheses associated with this primary endpoint are defined as: 
H0: µ ≤ 0 
H1: µ > 0 
where µ is the mean of the per subject differences in percentage of time in range 
70-180 mg/dL during Phase 2 compared to Phase 1. 
 
Percentage of Time in Range 70-180 mg/dL – Phase 3 
 
The percentage of time in range 70-180 mg/dL during Phase 3 of the hybrid 
closed-loop phase will be compared to standard therapy by calculating the change 
between the time in range percentages between Phase 3 of hybrid closed-loop 
and Phase 1 (standard therapy) for each subject. The change in percentage of 
time in range 70-180 mg/dL is calculated as the percentage of time in range 
during Phase 3 minus the percentage of time in range during Phase 1. There are 
no hypotheses associated with this endpoint.   
 
13.1.3 
Secondary Objective 
The secondary objective of the study is to evaluate additional glycemic measures 
of effectiveness of the Omnipod Horizon™ System. 
13.1.4 
Secondary Endpoints 
The secondary objective will be evaluated using the following per subject 
endpoints with prespecified hypotheses: 
Glucose metrics from system CGM during the hybrid closed-loop phase for Phase 
2 will be compared to Phase 1 overall: 
• 
% of time > 180 mg/dL 
• 
% of time < 70 mg/dL 
 
Additional per subject secondary endpoints without prespecified hypotheses used 
to evaluate the secondary objective include:   
• 
A1C: 
• 
A1C at the end of Phase 2 (Visit 13), at 6 months (Visit 16), and at the 
end of Phase 3 (Visit 23; approximately 15 months) 
• 
Change from baseline in A1C at the end of Phase 2 (Visit 13), at 6 
months (Visit 16), and at the end of Phase 3 (Visit 23; approximately 15 
months) 
• 
Proportion of subjects demonstrating an improvement from baseline in 
A1C at the end of Phase 2 (Visit 13), at 6 months (Visit 16), and at the 
end of Phase 3 (visit 23; approximately 15 months) 
 

 
 
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• 
Glucose metrics from system CGM during the hybrid closed-loop phase 
during Phase 2, and separately during Phase 3 will be compared to Phase 
1 during the day, overnight, and overall: 
 
• 
Mean glucose 
• 
% of time in range 70-180 mg/dL 
• 
% of time in range 70-140 mg/dL 
• 
% of time > 180 mg/dL 
• 
% of time ≥ 250 mg/dL 
• 
% of time ≥ 300 mg/dL 
• 
% of time < 70 mg/dL 
• 
% of time < 54 mg/dL 
• 
Standard deviation 
• 
Coefficient of variation 
 
• 
Percentage of time in hybrid closed-loop as proportion of overall device 
usage time during Phase 2, and separately during Phase 3 
• 
Glucose management indicator (GMI) based on overall mean glucose during 
Phase 2, and separately during Phase 3 will be compared to Phase 1 
• 
Insulin requirements during Phase 2, and separately during Phase 3 will be 
compared to Phase 1 during the day, overnight, and overall: 
 
• 
Total daily insulin (TDI) (units, units/kg) 
• 
Total daily basal insulin (units, units/kg) 
• 
Total daily bolus insulin (units, units/kg) 
 
• 
Change from baseline in BMI (kg/m2) at end of Phase 2, and at end of Phase 
3 
 
Percentage of Time in Range >180 mg/dL 
 
The percentage of time in range >180 mg/dL during Phase 2 will be compared to 
Phase 1 by calculating the change between the time in range percentages 
between Phase 2 and Phase 1 for each subject. The change in percentage of time 
in range >180 mg/dL is calculated as the percentage of time in range during 
Phase 2 minus the percentage of time in range during Phase 1. The null 
hypothesis associated with this endpoint states that the mean change in 
percentage of time in range >180 mg/dL is greater than or equal to zero. Rejection 
of the null hypothesis indicates that the observed data support the alternative 
hypothesis that the mean change in percentage of time in range >180 mg/dL is 
less than zero. 
 
The hypotheses associated with this secondary effectiveness endpoint are defined 
as: 
H0: µ ≥ 0 
H1: µ < 0 
where µ is the mean of the per subject differences in percentage of time in range 
>180 mg/dL during Phase 2 compared to Phase 1. 
 
Percentage of Time in Range <70 mg/dL 

 
 
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The percentage of time in range <70 mg/dL during Phase 2 will be compared to 
Phase 1 by calculating the change between the time in range percentages 
between the Phase 2 and Phase 1 for each subject. The change in percentage of 
time in range <70 mg/dL is calculated as the percentage of time in range during 
Phase 2 minus the percentage of time in range during Phase 1. The null 
hypothesis associated with this endpoint states that the mean change in 
percentage of time in range <70 mg/dL is greater than or equal to zero. Rejection 
of the null hypothesis indicates that the observed data support the alternative 
hypothesis that the mean change in percentage of time in range <70 mg/dL is less 
than zero. 
 
The hypotheses associated with this secondary effectiveness endpoint are defined 
as: 
H0: µ ≥ 0 
H1: µ < 0 
where µ is the mean of the per subject differences in percentage of time in range 
<70 mg/dL during Phase 2 compared to Phase 1. 
 
13.2 Sample Size 
This is a single-arm, multi-center, prospective study. The sample size and study 
duration were determined to allow for adequate safety profile of the investigational 
device. The study will be claimed successful if rates of Severe Hypoglycemia and 
DKA during Phase 2 are considered acceptable compared to published rates. 
In addition, a statistically powered sample size was determined for the two Phase 
2 primary effectiveness endpoints. Since each of the Phase 2 primary 
effectiveness endpoints will be evaluated separately, the significance level will be 
adjusted so that the overall type I error can be maintained at one-sided 2.5% and 
each endpoint will be tested at one-sided 1.25%. 
13.2.1 
Primary Endpoint of A1C at End of Phase 2 (~13 Weeks) Compared 
to Baseline 
The sample size estimation is based on the following assumptions: 
• 
Mean difference between paired observations of A1C at the end of 
Phase 2 compared to baseline -0.5% 
• 
Standard deviation of the difference between paired observations of A1C 
at the end of Phase 2 compared to baseline is 0.8% 
• 
Power of 90% and one-sided significance level of 1.25% 
The estimates for the mean difference and standard deviation of the difference 
between the paired observations were obtained from previous Omnipod studies, 
where subjects experienced a mean change in A1C of 0.38% over 3 months 
(standard pump therapy only), from 8.1 to 7.7%, n=85 (data on file). Based on the 
above assumptions, 35 subjects are required to provide evaluable data. 

 
 
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13.2.2 
Primary Endpoint of Percentage of Time in Range 70-180 mg/dL 
During Phase 2 Compared to Phase 1 
The sample size estimation is based on the following assumptions: 
• 
Mean difference between paired observations of percentage of time in 
range 70-180 mg/dL during Phase 2 of hybrid closed-loop phase 
compared Phase 1 is 10% 
• 
Standard deviation of the difference between paired observations of 
percentage of time in range 70-180 mg/dL during Phase 2 of hybrid 
closed-loop phase compared to Phase 1 is 10%% 
• 
Power of 90% and one-sided significance level of 1.25% 
The estimates for the mean difference and standard deviation of the difference 
between the paired observations were obtained from recent Omnipod study, 
G170143, where twelve (12) subjects aged 3.4-5.9 years experienced a mean 
change in percentage of time in range 70-180 mg/dL of 13.2 ± 10.2%. Based on 
the above assumptions, 11 subjects are required to provide evaluable data.  
To gather adequate safety and effectiveness data on the performance of the 
Omnipod Horizon™ System, a total of up to 80 subjects will be enrolled in the 
study in order to obtain a minimum of 60 evaluable subjects.  
Subjects will be enrolled across 6-12 clinical study sites. No single site should 
enroll more than 24 subjects.  
13.3 Analysis Sets 
The following analysis sets are planned for the study and will apply to the 
endpoints through the end of Phase 2.  There are no prespecified analysis sets for 
Phase 3; all available data will be used to summarize Phase 3 endpoints. 
13.3.1 
ITT (Intention to Treat) Analysis Set 
The ITT analysis set includes all subjects that are enrolled in the study. All safety 
analyses (other than primary analysis of primary safety endpoints) will be based 
on the ITT analysis set. 
13.3.2 
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 subjects who have entered the hybrid 
closed-loop phase of the study successfully. The mITT analysis set will be used as 
the primary analysis for the primary and secondary endpoints and other clinical 
outcome data. 

 
 
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13.3.3 
PP (Per-Protocol) Analysis Set 
The Per-Protocol (PP) analysis set is a subset of the mITT analysis set. Subjects 
will be included in the PP analysis set if they have a minimum of 80% system use 
during the hybrid closed-loop phase inclusive of Manual and hybrid closed-loop 
(Automated) modes 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 
• 
Significant protocol non-compliance that may confound the study objective 
data (e.g., use of prohibited medications) 
The list of subjects excluded from the PP analysis set will be determined prior to 
analysis. If the PP analysis set does not differ from the mITT analysis set, 
separate analyses will not be presented. 
13.4 Analysis of Primary and Secondary Endpoints 
Both Phase 2 primary effectiveness endpoints will be tested independently of each 
other for statistical significance using a paired t-test at a one-sided significance 
level of 1.25%.  
If at least one of the Phase 2  primary effectiveness endpoints are found to be 
significant, the testing for Phase 2  secondary endpoints can commence. The 
details on how the family-wise error rate will be maintained at the 2.5% 
significance level (one-sided) will be provided in the Statistical Analysis Plan 
(SAP). In addition, the Phase 2  primary effectiveness endpoints may also be 
tested for significance within a smaller cohort of subjects. The details of subgroup 
analyses and testing will also be detailed in the SAP. 
There are no hypotheses associated with the other Phase 2 secondary endpoints 
or any of the Phase 3 endpoints. Summary statistics will be presented by age 
cohort for all endpoints, stratified by time points of interest (e.g., day vs. night, 
overall). The Phase 2  primary and secondary endpoints will be summarized for 
modified Intention to Treat (mITT) and Per Protocol (PP) analysis sets. If the PP 
analysis set does not differ from the mITT analysis set, separate analyses will not 
be presented. The data may be stratified by phase of the study, where the data 
collected in the standard therapy phase of the study will be compared to the data 
collected in the hybrid closed-loop phase of the study.  
13.4.1 Time in Range Endpoints 
The primary effectiveness endpoint and the secondary endpoints that summarize 
time in specific glycemic ranges will be calculated from device data outputs as 
follows: 
100 × # 𝑜𝑓 𝐶𝐺𝑀 𝑟𝑒𝑐𝑜𝑟𝑑𝑠 𝑖𝑛 𝑟𝑎𝑛𝑔𝑒 
# 𝑜𝑓 𝑒𝑣𝑎𝑙𝑢𝑎𝑏𝑙𝑒 𝐶𝐺𝑀 𝑟𝑒𝑐𝑜𝑟𝑑𝑠= 𝑇𝐼𝑅% 

 
 
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13.5 Additional Data Analyses 
Following the upload of controller data into the database, the 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 subjects and thus, will 
not impact study outcomes. Should a potential safety concern be identified, sites 
may be notified as appropriate to ensure subject 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. 
 
13.6 Safety Analyses 
13.6.1 
Evaluation of Adverse Events  
All adverse events reported over the course of the study will be summarized and 
tabulated by study phase, event category, seriousness, severity, and relationship 
to the study procedure and the investigational device. 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 subject, 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. 
13.6.2 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. 
13.7 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 subjects 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. 
13.8 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 subject 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), 

 
 
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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 subjects. 
13.9 Missing Data 
All practical monitoring and follow-up steps will be taken to ensure complete and 
accurate data collection. All analyses will be based on available data only; no 
imputation for missing data is planned. 
13.10 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 Statistical 
Analysis Plan (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. 
14 DATA HANDLING AND QUALITY ASSURANCE 
Data in this study will be collected on Electronic Case Report Forms as well as via 
electronic device outputs. 
 
14.1 Electronic Case Report Forms (eCRFs) 
Study data are collected through a combination of subject 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 subject eCRFs must be reviewed and signed 
by the investigator in the 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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14.2 Electronic Device Outputs 
14.2.1 
PDM Data 
This study will utilize insulin delivery data from the PDM device. All insulin delivery 
data and all CGM readings from the hybrid closed-loop phase will be stored on the 
PDM and exported to Insulet Cloud. Data will be saved in a compatible format that 
will be extractable for statistical analysis purposes. Data from the hybrid closed-
loop phase will be uploaded to the database and used for analysis.  
14.2.2 
CGM Data 
This study will utilize CGM measurements from the CGM device. CGM data will be 
saved in a compatible format that will be extractable for statistical analysis 
purposes. CGM data from the standard therapy phase will be uploaded to the 
database and used for comparative analysis.  
14.2.3 
BG and Ketone Meter Data 
This study will also utilize measurements from a BG and ketone meter. BG and 
Ketone meter data, in any format, will be uploaded to the database.  
14.3 Subject Identifiers 
All data used in the analysis and reporting of the study will be without identifiable 
reference to the subject. Only the unique subject number will be used to identify 
subject data submitted to the Sponsor, and only the investigating clinical site will 
be able to link the unique subject ID to the subject’s name. 
14.4 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. 
14.5 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 review, and regulatory inspection by providing direct 
access to all study records. In the event of an audit or inspection, the investigator 

 
 
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agrees to allow the Sponsor, representatives of the Sponsor, the FDA, or other 
regulatory authorities access to all study records. 
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. 
14.6 Study Record Retention 
Records and reports must remain on file at the investigational site 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. 
14.7 Device Accountability 
Investigators will be responsible for investigational device accountability, 
reconciliation and records maintenance throughout the course of the investigation. 
Accountability records will include receipt, use and final disposition of 
investigational product.  
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. 
15 STUDY ETHICS AND CONDUCT 
15.1 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). 
15.2 Ethical Conduct of the Study 
The investigation will be conducted according to the applicable FDA regulations 
(21CFR 812, 56, 54, 50). The investigator will conduct all aspects of this study in 
accordance with all state, and local laws or regulations. 

 
 
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15.3 Institutional Review Board (IRB) 
Federal regulations (21 CFR 812) require that approval be obtained from an IRB 
prior to participation of subjects in research studies. Prior to subject enrollment, a 
signed copy of the IRB approval letter must be submitted to the Sponsor. In 
addition, the protocol, informed consent, advertisements to be used for subject 
recruitment, and any other written information regarding this study to be provided 
to the subject must be approved by the IRB. Documentation of all IRB approvals 
will be maintained by the clinical site and will be available for review by the 
Sponsor or its designee. 
All IRB approvals should be signed by the IRB chairperson or designee and must 
identify the IRB 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. The investigator must supply the Sponsor, or its designee written 
documentation of continued review of the study. 
15.4 Informed Consent 
A written informed consent in compliance with 21 CFR 50 shall be obtained from 
each subject or their parent or caregiver prior to the subject participating in the 
study or performing any unusual or non-routine procedure that involves risk to the 
subject. 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 submission. Once reviewed, the 
consent will be submitted by the investigator to their IRB for review and approval 
prior to the start of the study. 
Before recruitment and enrollment, each prospective subject and/or 
parent/guardian will be given a full explanation of the study and be allowed to read 
the approved ICF. Once the investigator or designee is assured that the subject 
and/or parent/guardian understands the implications of participating in the study, 
the subject and/or parent/guardian 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 subject 
and/or parent/guardian. The original form shall be maintained in the subject binder 
at the clinical site. 
15.5 Confidentiality 
All information and data sent to the Sponsor concerning study subjects 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: 

 
 
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• 
Subjects will be identified on all eCRFs by a unique subject ID 
• 
eCRFs are confidential documents and will only be available to the Sponsor 
(including delegates, such as CRAs), DSMB, Medical Monitor, CRO, the 
investigator and study staff, and if requested, to the IRB or regulatory 
authorities. The investigator will maintain, as part of the investigation file, a 
list identifying all subjects entered into the study. 
All laboratory specimens, evaluation forms, reports, and other records will be 
identified in a manner designed to maintain subject confidentiality. Clinical 
information will not be released without the written permission of the subject 
and/or parent/guardian, except as necessary for monitoring and auditing by the 
Sponsor, its designee, the FDA, or the IRB. 
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. 
15.6 Modification of the Protocol 
Any changes in this research activity, except those necessary to remove an 
apparent immediate hazard to the subject, must be reviewed and approved by the 
Sponsor. The protocol amendment(s) must be signed by the investigator and 
approved by the IRB before implementation. The protocol amendment(s) will be 
filed with the appropriate regulatory agency(s) having jurisdiction over the conduct 
of the study. 
Substantial changes will require approval from the Sponsor, FDA, and IRB prior to 
implementation. 
15.7 Protocol Deviations 
The investigator will not deviate from the protocol without prior written approval 
from the Sponsor except in medical emergencies or inadvertent instances that will 
not increase the subject’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, 
subject management or subject 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 subject, or non-
adherence to FDA regulations.  

 
 
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The investigator must document and explain any protocol deviation in the 
subject’s source documentation. The IRB should be notified of all protocol 
deviations in a timely manner. Protocol deviations should be reported to the IRB 
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. 
15.8 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 as appropriate. 
Upon completion or termination of the study, the principal investigator (PI) must 
submit a final written report to the Sponsor and IRB. The report must be submitted 
within 3 months (90 days) of completion or termination of the trial. 
The Sponsor will submit all reports required by the appropriate regulatory 
authorities, including unanticipated adverse device effects, withdrawal of IRB 
approval, list of current investigators, annual progress reports, recall information, 
final reports and protocol deviations. 
15.9 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. 
15.9.1 
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. 
15.9.2 
Investigator Documentation 
Prior to beginning the study, the investigator will be asked to comply with 21 CFR 
812 by providing the following essential documents, including but not limited to: 
• 
An investigator-signed Investigator Agreement page of the protocol  
• 
An IRB 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 subject and/or parent/guardian 

 
 
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• 
IRB 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 
• 
Laboratory certifications and normal ranges for any local laboratories used 
by the clinical site. 
15.10 Clinical Site Training 
The training of appropriate clinical site personnel will be the responsibility of the 
Sponsor or its designee. Sites will not be required to be retrained on the study 
devices since the sites have previously been trained during the execution of the 
Omnipod Horizon™ Pivotal Study (G190270). To ensure proper device usage, 
uniform data collection, and protocol 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 subject care. 
15.11 Device Use 
The Omnipod Horizon™ System consists of the following primary components: 
an Omnipod Horizon™ Pod, Omnipod Horizon™ Controller, and the iCGM. 
The Pod and PDM are intended for single use only.  The PDMs 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), the Dexcom G6 CGM transmitter (the component of the system that 
attaches to the sensor to transmit the signal), and the Dexcom G6 CGM receiver 
will all be single use only in this study. The Dexcom G6 receiver will be returned 
to the Sponsor after completion of the study. 
Study blood glucose meters and ketone meters will not be cleaned or reused by 
subjects. A new meter will be used for each subject. 
15.12 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: 

 
 
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• 
Part number/Lot number 
• 
Quantities 
• 
Tracking number 
15.13 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.  
15.14 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 subjects already enrolled in the trial. Subjects must be followed 
according to the clinical protocol and information obtained during subject follow-
up shall be reported on the eCRF. 
 
 

 
 
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APPENDIX A