Multi-center, Randomized, Parallel, Adaptive, Controlled Trial in Adult and Pediatric Patients With Type 1 Diabetes Using Hybrid Closed Loop System and Control (CSII, MDI and SAP) at Home
Phase: NA
Conditions: Type 1 Diabetes
Sponsor: Medtronic MiniMed, Inc.

 
Study Title 
Multi-center, Randomized, Parallel, Adaptive, 
Controlled Trial in Adult and Pediatric Patients 
with Type 1 Diabetes Using Hybrid Closed Loop 
System and Control (CSII, MDI and SAP) at 
Home  
NCT Number 
NCT02748018 
Document Description 
Clinical Investigation Plan (Version H) 
Document Date 
01-FEB-2024 
 

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Trial in Adult and Pediatric Patients with Type 1 Diabetes 
Using Hybrid Closed Loop System and Control (CSII, MDI 
and SAP) at Home 
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MiniMed® 670G Pump labeled as MiniMed Insulin 
Pump - referred to as MiniMed Pump throughout the 
protocol 
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MiniMed 770G Pump labeled as MiniMed Insulin 
Pump - referred to as MiniMed Pump throughout the 
protocol 
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Guardian® Link (3) Transmitter  
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MiniMed Mobile Application referred to as the Mobile 
App in the protocol  
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CareLink Connect Application  
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Transmitter Charger  
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CONTOUR® NEXT LINK 2.4 by Ascencia Blood Glucose 
Meter  - referred to as the Study Meter throughout 
this protocol) 
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Roche Accu-Chek Guide Link Meter  -referred to as the 
Accu-Chek Guide Link study meter in this protocol 
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Guardian® Sensor (3), referred to as Guardian Sensor 
(3) throughout this protocol 
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One-Press Serter  -referred to as the Serter 
throughout the protocol 
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USA: 
 
Medtronic MiniMed (“Medtronic”) 
18000 Devonshire St 
Northridge, CA 91325
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866.948.6633 
 
Europe: 
  
Medtronic International Trading Sarl. (“Medtronic”)  
Route du Molliau 31 
Case Postale 
1131 Tolochenaz 
Switzerland 
(+41) 21 803 80 84 
Canada: 
Medtronic Canada ULC.  
99 Hereford St. 
Brampton, Ontario, Canada  
L6Y 0R3 
905 460 37211 
 
Australia: 
  
Medtronic Australasia Pty. Ltd 
2 Alma Road 
Macquarie Park, NSW 2113 
Australia 
(+61) 2 9857 9000 
 
New Zealand: 
 
Medtronic New Zealand Limited 
Level 3, Bldg 5, 666 Great South Road 
Penrose, Auckland 1051 
New Zealand 
(+64) 9 9674600
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The information contained in this document is confidential and the proprietary property of Medtronic. Any 
distribution, copying, or disclosure without the prior written authorization of Medtronic is strictly prohibited. 
Persons to whom the information is disclosed must know that it is confidential and that it may not be further 
disclosed by them. 
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H/01-FEB-2024
I have read the protocol, including all appendices, and I agree that it contains all necessary details for me 
and my staff to conduct this study as described. I will conduct this study as outlined herein and will make a 
reasonable effort to complete the study within the time designated. 
I agree to comply with all applicable regulatory guidelines under which the study is being conducted, i.e., 
International Conference on Harmonization Guidelines on Good Clinical Practice (US only), United Stated 
Food and Drug Administration regulations (21 CFR Part 50, 21CFR Part 56, 21 CFR 812, etc.) (US only), United 
Stated Food and Drug Administration regulations (21 CFR Part 54 and part 11) (US and Europe), Health 
Canada Regulations (SOR/98-282 – Canada only), International Organization for Standardization (ISO 
14155:2011 – Europe only). In Australia and New Zealand, the study will be carried out in conformity with 
the ethical principles of the Declaration of Helsinki, the requirements of ISO14155:2011 and with all the 
other local laws and regulations relevant to the use of new and approved medical devices in the country. 
I agree to ensure that the confidential information contained in this document will not be used for any 
purpose other than the evaluation and conduct of the clinical investigation without the prior written consent 
of Medtronic. 
I will provide all study personnel under my supervision copies of the protocol and access to all information 
provided by Medtronic. I will discuss this material with them to ensure that they are fully informed about 
the products and the study. 
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Term 
Definition 
A1C 
Glycosylated hemoglobin 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
ASIC 
Application Specific Integrated Circuit 
BLE 
Bluetooth Low Energy 
BMI 
Body Mass Index 
CEC
Clinical Events Committee
CFR 
Code of Federal Regulations 
CGM 
Continuous Glucose Monitoring 
CGMS
Continuous Glucose Monitoring System
CL 
Closed Loop  
CSII 
Continuous Subcutaneous Insulin Infusion 
CV
Coefficient of Variation
DCCT 
Diabetes Control and Complications Trial 
DKA 
Diabetic Ketoacidosis 
DMC
Data Monitoring Committee
eCRF 
Electronic Case Report Form 
EC 
Ethics Committee 
EIS 
Electrochemical Impedance Spectroscopy 
ER 
Emergency Room 
EU MDR 
European Medical Device Regulation 
FDA 
United States Food and Drug Administration 

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Term 
Definition 
FST
Frequent Sample Testing 
GCRC 
General Clinical Research Center 
hCG
Human chorionic gonadotropin 
HCL 
Hybrid Closed Loop  
HCP 
Health Care Professional 
HFE
Human Factors Engineer
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
Informed Consent Form 
IDE
Investigational Device Exemption
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
IV
Intravenous
JDRF 
Juvenile Diabetes Research Foundation 
LSL 
Low Suspend Limit 
MAGE 
Mean Amplitude of Glycemic Excursions 
MDD 
Medical Device Directive  
MDI 
Multiple Daily Injections 
MedDRA 
Medical Dictionary for Regulatory Activities 
NDC 
National Drug Code 
NGSP 
National Glycohemoglobin Standardization Program 
OC-RDC 
Oracle Clinical Remote Data Capture 
OLS 
Clinical Online Store 

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Term 
Definition 
PC 
Personal Computer 
QC 
Quality Control 
RF
Radio Frequency
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SAP
Sensor Augmented Pump
SG 
Sensor Glucose 
SGV 
Sensor Glucose Value 
SMBG
Self-Monitoring of Blood Glucose
SR 
Significant Risk 
Tel-D  
Telemetry-Diabetes 
TLS
Transport Layer Security
TDD 
Total Daily Dose 
TGA 
Therapeutic Goods Administration 
TS 
Technical Support 
TSH 
Thyroid-stimulating hormone 
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
 
© 2024 Medtronic. All rights reserved. Medtronic, Medtronic logo and Engineering the extraordinary are 
trademarks of Medtronic.  
™*Third party brands are trademarks of their respective owners. All other brands are trademarks of a 
Medtronic company. 
CGMS®, CareLink®, Guardian®, MiniLink®, MiniMed®, Paradigm® and Enlite® are registered or unregistered

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trademarks of Medtronic 
Ascensia, the Ascensia Diabetes Care logo, and Contour are trademarks and/or registered trademarks of 
Ascensia Diabetes Care.  
 
 

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Title 
Multi-center, Randomized, Parallel, Adaptive Controlled Trial in Adult and 
Pediatric Patients with Type 1 Diabetes Using Hybrid Closed Loop System and 
Control (CSII, MDI and SAP) at Home 
Clinical Study Type 
Phase IV; Interventional 
Product Name 
Hybrid Closed Loop System   
Sponsor  
Medtronic MiniMed 
Local Sponsor 
 
Medtronic MiniMed 
18000 Devonshire St 
Northridge, CA 91325, USA 
 
  
Medtronic International Trading Sarl. (“Medtronic”)  
Route du Molliau 31 
Case Postale 
1131 Tolochenaz, Switzerland 
 
Medtronic Canada ULC 
99 Hereford St. 
Brampton, Ontario, Canada L6Y 0R3 
  
Medtronic Australasia Pty. Ltd 
2 Alma Road 
Macquarie Park, NSW 2113 
Australia 
PI
PI
PI

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(+61) 2 9857 9000 
 
 
Medtronic New Zealand Limited 
Level 3, Bldg 5, 666 Great South Road 
Penrose, Auckland 1051 
New Zealand 
(+64) 9 9674600 
Indication under 
investigation  
Type 1 Diabetes 
Investigation Purpose 
The purpose of this study is to evaluate the safety and effectiveness of the 
Hybrid Closed Loop system (HCL) in adult and pediatric patients with type 1 
diabetes in the home setting. A diverse population of patients with type 1 
diabetes will be studied. The study population will have a large range for 
duration of diabetes and glycemic control, as measured by glycosylated 
hemoglobin (A1C). The following cohorts will be enrolled:  
1) Cohort 1: Continuous Subcutaneous Insulin Infusion (CSII) or HCL;  
2) Cohort 2: Multiple Daily Injections (MDI) or HCL and  
3) Cohort 3: Sensor-Augmented Pump therapy (SAP) or HCL. 
Product Status 
Investigational Devices  
 
MiniMed 670G US only – Subjects 2-6 years:  
R MiniMed 670G Pump labeled as MiniMed Insulin Pump (MMT-
1780), referred to as MiniMed Pump throughout the protocol 
R Guardian® Link (3) Transmitter (MMT-7811)
R Guardian® Sensor (3) (MMT-7020), referred to as Guardian Sensor 
(3) throughout this protocol 
R CONTOUR® NEXT LINK 2.4 by Ascencia Blood Glucose Meter (MMT-
1152 or MMT-1352 in US) - referred to as the Study Meter 
PI

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throughout this protocol) 
MiniMed 770G Australia – Subjects 2-6 years: 
R MiniMed 770G Pump labeled as MiniMed Insulin Pump (MMT-1881, 
MMT-1891), referred to as MiniMed Pump throughout the protocol 
R Guardian® Link (3) Transmitter (MMT-7910W5, MMT-7911W) 
R MiniMed Mobile Application (MMT-6103 Android/6104 IOS)- 
referred to as the Mobile App in this protocol, Medical Device Data 
System exempt device 
R CareLink Connect Application (MMT-6113 Android/6114 IOS), 
Medical Device Data System exempt device 
R Roche Accu-Chek Guide Link Meter (Model 08116113186M) -
referred to as the Accu-Chek Guide Link study meter in this protocol 
R Blue adapter (ACC-1003911) 
R Medtronic CareLink® Clinical Software (MMT-7338)– referred to as 
CareLink Clinical Medical Device Data System exempt device 
 
Non-Investigational/Exempt Devices  
MiniMed 670G US - Subjects 7 years and older:  
R MiniMed 670G Pump labeled as MiniMed Insulin Pump (MMT-
1780), referred to as MiniMed Pump throughout the protocol 
R Guardian® Link (3) Transmitter (MMT-7811)
R Transmitter Charger (MMT-7715) 
R CONTOUR® NEXT LINK 2.4 by Ascencia Blood Glucose Meter (MMT-
1152 or MMT-1352 in US) - referred to as the Study Meter 
throughout this protocol) 
R Guardian® Sensor (3) (MMT-7020), referred to as Guardian Sensor 
(3) throughout this protocol 
R Tester (MMT-7736L) 
R Ketone Meter 
R
One-Press Serter (MMT-7512) -referred to as the Serter throughout 

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the protocol 
R Medtronic CareLink® Personal Therapy Management Software for 
Diabetes (MMT-7333) -– referred to as CareLink Personal for Clinical 
Research throughout this protocol; Class 1 exempt device  
 
 MiniMed 670G Europe - Subjects 7 years and older: 
R MiniMed 670G Pump* labeled as MiniMed Insulin Pump (MMT-
1781 or MMT-1782), referred to as MiniMed Pump throughout the 
protocol 
R Guardian® Link (3) Transmitter (MMT-7811)
R Guardian® Sensor 3 (MMT-7020), referred to as Guardian Sensor (3) 
throughout this protocol
R Ketone Meter  
R CONTOUR® NEXT LINK 2.4 by Ascencia Blood Glucose Meter (MMT-
1151 and MMT-1152) - referred to as the Study Meter throughout 
this protocol) 
R Transmitter Charger (MMT-7715) 
R Tester (MMT-7736L)* 
R Medtronic CareLink® Personal Therapy Management Software for 
Diabetes (MMT-7333) -– referred to as CareLink Personal for Clinical 
Research throughout this protocol; CE Marked.  
R One-Press Serter (MMT-7512)-referred to as the Serter throughout 
the protocol 
 
MiniMed 670G Canada - Subjects 7 years and older: 
R MiniMed 670G Pump labeled as MiniMed Insulin Pump (MMT-1781 
(pump) and MMT-1762KCN (kit)) , referred to as MiniMed Pump 
throughout the protocol 
R Guardian® Link (3) Transmitter (MMT-7811) 
R Guardian® Sensor (3) (MMT-7020), referred to as Guardian Sensor 
(3) throughout this protocol 

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R CONTOUR® NEXT LINK 2.4 by Ascencia Blood Glucose Meter (MMT-
1151 and MMT-1152) - referred to as the Study Meter throughout 
this protocol)
R Ketone Meter  
R Medtronic CareLink® Personal Therapy Management Software for 
Diabetes (MMT-7333WW) -– referred to as CareLink Personal for 
Clinical Research throughout this protocol; Medical Device Data 
System exempt device 
R One Press Serter (MMT-7512)- referred to as the Serter throughout 
the protocol 
R Transmitter Charger (MMT-7715) 
R Tester (MMT-7736L) 
 
MiniMed 670G All Geographies: 
R CareLink USB 2.4 GHz (MMT-7306)  
 
MiniMed 770G US Only – Subjects 2 years and older: 
R MiniMed 770G Pump labeled as MiniMed Insulin Pump (MMT-1880, 
referred to as MiniMed Pump throughout the protocol 
R MiniMed Mobile Application (MMT-6103 Android/6104 IOS)- 
referred to as the Mobile App in this protocol, (when available). 
R CareLink Connect Application (MMT-6113 Android/6114 IOS), (when 
available) 
R Roche Accu-Chek Guide Link Meter (Model 08116083022) -referred 
to as the Accu-Chek Guide Link study meter in this protocol 
R Blue adapter (ACC-1003911) 
R Medtronic CareLink® Clinical Software (MMT-7338) – referred to as 
CareLink Clinical; Class 1 exempt device
 
MiniMed 770G Canada - Subjects 2 years and older: 

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R MiniMed 770G Pump labeled as MiniMed Insulin Pump (MMT-1881, 
MMT-1891KCN and MMT-1891CRP (kit)), referred to as MiniMed 
Pump throughout the protocol
R Guardian® Link (3) Transmitter (MMT-7911) 
R MiniMed Mobile Application (MMT-6103 Android/6104 IOS)- 
referred to as the Mobile App in this protocol, Medical Device Data 
System exempt device 
R CareLink Connect Application (MMT-6113 Android/6114 IOS), 
Medical Device Data System exempt device 
R
Roche Accu-Chek Guide Link Meter (Model 08109222001) -referred 
to as the Accu-Chek Guide Link study meter in this protocol 
R
Blue adapter (ACC-1003911)
R Medtronic CareLink® Clinical Software (MMT-7338)– referred to as 
CareLink Clinical Medical Device Data System exempt device 
 
MiniMed 770G Australia – Subjects 7 years and older: 
R MiniMed 770G Pump labeled as MiniMed Insulin Pump (MMT-1881, 
MMT-1891), referred to as MiniMed Pump throughout the protocol 
R Guardian® Link (3) Transmitter (MMT-7910W5, MMT-7911W)
R MiniMed Mobile Application (MMT-6103 Android/6104 IOS)- 
referred to as the Mobile App in this protocol, Medical Device Data 
System exempt device 
R CareLink Connect Application (MMT-6113 Android/6114 IOS), 
Medical Device Data System exempt device 
R Roche Accu-Chek Guide Link Meter (Model 08116113186M) -
referred to as the Accu-Chek Guide Link study meter in this protocol 
R Blue adapter (ACC-1003911) 
R Medtronic CareLink® Clinical Software (MMT-7338)– referred to as 
CareLink Clinical Medical Device Data System exempt device 
 
MiniMed 770G New Zealand– Subjects 2 years and older: 

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R MiniMed 770G Pump labeled as MiniMed Insulin Pump (MMT-1881, 
MMT-1891), referred to as MiniMed Pump throughout the protocol 
R
Guardian® Link (3) Transmitter (MMT-7910W5, MMT-7911W)
R MiniMed Mobile Application (MMT-6103 Android/6104 IOS)- 
referred to as the Mobile App in this protocol, Medical Device Data 
System exempt device 
R CareLink Connect Application (MMT-6113 Android/6114 IOS), 
Medical Device Data System exempt device 
R Roche Accu-Chek Guide Link Meter (Model 08116113186M) -
referred to as the Accu-Chek Guide Link study meter in this protocol
R Blue adapter (ACC-1003911) 
R Medtronic CareLink® Clinical Software (MMT-7338)– referred to as 
CareLink Clinical Medical Device Data System exempt device 
Europe Classification 
of devices by Rules 
according to Medical 
Device Directive 
(MDD)
x
Infusion set: MDD, Annex IX, Rule 8, Class IIb  
x
Insertion devices: MDD, Annex IX, Rule 12, Class I 
x
Reservoirs: MDD, Annex IX, Rule 2, Class IIa  
x
Insulin Pump: MDD, Annex IX, Rule 11, Class IIb 
x
Transmitter: MDD, Annex X, Rule 10, Class IIa 
x
Transmitter Charger: MDD, Annex IX, Rule 1, Class I 
x
Sensor: MDD, Annex IX, Rule 8, Class III 
x
Glucose Meter (Ascencia): In vitro diagnostic device, Annex II of the 
DIRECTIVE 98/79/EC, List B 
x
Blood Glucose and Ketone Monitoring System: In vitro diagnostic device, 
Annex II of the DIRECTIVE 98/79/EC, List B 
Europe Classification 
for Biocompatibility 
according to ISO EN 
10993-1  
Table 1 and 2 (Type of 
Body 
x
Infusion sets, Pump reservoirs: In compliance with ISO10993-1 and USP 
requirements for the use of insulin in the infusion sets. 
x
Insulin Pump: In compliance with ISO10993-1 
x
Transmitter: In compliance with ISO10993-1 
x
Sensor: In compliance with ISO10993-1 

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contact/duration) 
Europe Device 
Nomenclature: GMDN 
(Global Medical 
Device Nomenclature) 
x
Reservoirs: 35838, Ambulatory insulin infusion pump reservoir 
x
Infusion sets: 35833, Infusion Pump Administration Set 
x
Insulin Pump: 35983, Insulin Infusion Pump 
x
Transmitter: 44611, Interstitial-Fluid Glucose Monitoring System 
x
Sensor: 59016 Subcutaneous Glucose Sensor 
x
Transmitter Charger: 44611 Interstitial-Fluid Glucose Monitoring System  
x
Serter: 45449, Injector Reset Device 
x
Blood Glucose Meter: 30854 Glucose Meter Self-Testing 
Primary Objective(s) 
The purpose of this study is to evaluate the safety and effectiveness of the 
Hybrid Closed Loop system (HCL) in adult and pediatric patients with type 1 
diabetes in the home setting.  
Study Design 
This is a 6 month, multi-center, randomized, parallel, adaptive study in type 1 
diabetes with a 6 month continuation period. Up to 1500 subjects will be 
enrolled in order to have 1000 subjects who enter the study period. To date, 
959 subjects have enrolled. Up to 70 investigational Centers in the US, Europe, 
Canada, Australia and New Zealand will be enrolled.  For additional information 
on investigational sites and investigators, refer to information listed on public 
databases (e.g., clinicaltrials.gov). 
The study is anticipated to last no longer than 6.5 years from investigational 
center initiation to completion of all data entry and monitoring procedures. The 
study will target 54 months to complete subject enrollment. Subjects can expect 
to participate for approximately 7-8 months during the run-in period and study 
period, with a 6 month continuation period. 
The study will have three periods per Cohort:  
1. Run-in Period: The run-in period can be up to 60 days.  
The run-in period will also be used for CGM data collection for 
approximately two weeks. Two consecutive 7-day sensors will be worn.  
If a sensor falls out, a replacement sensor should make up the 
difference for a total of 14 days of sensor wear (i.e. Monday Day 1 

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through next Sunday Day 14) 
For example: If a sensor falls out on Day 4, a replacement sensor 
should be inserted.   Once that replacement sensor has been worn 
for 7 days, a new sensor should then be inserted and worn for 3 
days so that a total of 14 days of sensor wear is completed.  
 
All patients will wear blinded CGM.  Subjects will be expected to 
demonstrate sensor wear for approximately 14 days total between the 
two 7-day sensor wears (plus replacement sensor if needed). Subjects 
should be instructed to make 4-6 BG measurements per day. Sponsor 
may request a repeat of blinded CGM. Repeat of blinded CGM may 
occur if the following are not met: 
x
A minimum of 12 days of sensor wear have been self-reported to 
research staff 
x
A minimum of 2 blood glucose checks/day during the blinded CGM 
wear are confirmed on the subject’s study BG meter.  
If these requirements are not met then patient should repeat the entire 
2 week blinded CGM data collection unless sponsor has approved that 
there was adequate data collection.   An additional 21 days may be 
added to the run in visit window schedule if blinded CGM data collection 
needs to be repeated.  Additional visits may also be allowed if needed.  
 
2. Study Period: There will be a 6 month randomized study period with 
two arms: HCL system and Control. CSII and MDI control groups will 
undergo two blinded CGM collections during the study period.  
The first blinded CGM data collection during the study period will occur 
before the month three (see visit schedule) for approximately two 
weeks.  Two consecutive 7-day sensors will be worn.  If a sensor falls 
out, a replacement sensor should make up the difference for a total of 
14 days of sensor wear.  (i.e. Monday Day 1 through next Sunday Day 
14) 
For example: If a sensor falls out on Day 4, a replacement sensor 
should be inserted.   Once that replacement sensor has been worn 
for 7 days, a new sensor should then be inserted and worn for 3 

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days so that a total of 14 days of sensor wear is completed.  
All patients will wear blinded CGM. Subjects will be expected to 
demonstrate sensor wear for approximately 14 days total between the 
two 7-day sensor wears (plus replacement sensor if needed). Subjects 
should be instructed to make 4-6 BG measurements per day. Sponsor 
may request a repeat of blinded CGM. The following should have 
occurred:   
x
A minimum of 12 days of sensor wear have been self-reported to 
research staff 
x
A minimum of 2 blood glucose checks/day during the blinded CGM 
wear are confirmed on the subject’s study BG meter.  
If the above requirements are not met then patient should repeat the 
entire 2 week blinded CGM data collection unless the sponsor approves 
that there was adequate data collection.    Additional visits may also be 
allowed if needed. No changes to the remaining visit schedule are 
needed.   
The second blinded CGM data collection during the study period will 
occur before the month six (see visit schedule) for approximately two 
weeks.  Two consecutive 7-day sensors will be worn.  If a sensor falls 
out, a replacement sensor should make up the difference for a total of 
14 days of sensor wear. (i.e. Monday Day 1 through next Sunday Day 14) 
For example: If a sensor falls out on Day 4, a replacement sensor 
should be inserted.   Once that replacement sensor has been worn 
for 7 days, a new sensor should then be inserted and worn for 3 
days so that a total of 14 days of sensor wear is completed.  
All patients will wear blinded CGM. Subjects will be expected to 
demonstrate sensor wear for approximately 14 days total between the 
two 7-day sensor wears (plus replacement sensor if needed). Subjects 
should be instructed to make 4-6 BG measurements per day.  
 
3. Continuation Period: There will be a 6 month continuation period 
during which time all subjects will use the HCL system.   
 

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Enrollment Cohorts According to Treatment 
At Enrollment, subjects will be identified according to the type of treatment 
regimen they are currently on. Treatment regimen is defined as follows:
x
Cohort 1: CSII – subjects using pump (Medtronic or other pump systems) 
for at least 3 months at time of screening without concurrent use of real 
time CGM in the last 3 months. (Self-report acceptable.) Please note 
that alternatives to SMBG such as Freestyle Libre are not considered 
real time CGM and subjects who are using Freestyle Libre at time of 
Screening will be allowed to enroll in the study. During the study, 
however, subjects will not be allowed to use Freestyle Libre. 
x
Cohort 2: Multiple Daily Injections (MDI) - Subjects using MDI with or 
without concurrent use of CGM for at least 3 months prior to Screening.  
(Self report is acceptable.)  
x
Cohort 3: Sensor Augmented Pump (SAP) – subjects using pump for at 
least 3 months at time of screening with real time CGM use (Medtronic 
or other CGM systems) approximately 20% of the time (Self report 
acceptable). Subjects will use the Medtronic CGM starting at Visit 3, but 
they may use their own CGM until then. Sensor insertion placement will 
be according to User guide. 
Staged enrollment in the post approval study for Subjects 2-6 Years of Age: 
x
Subjects 2-6 years of age will be allowed to enroll in the post approval 
study, once DMC has reviewed data from 10 subjects age 2-4 years who 
have completed participation in the study period of the CEP302 study 
and has given approval to enroll.   
In the US and Canada, subjects 2-80 years of age will be allowed to transition 
from the 670G system to the 770G system.  
The Run-In Period: Following successful screening, all subjects (CSII, MDI or SAP) 
will enter the run-in period and collect blinded CGM data while using their own 
diabetes therapy. Blinded CGM consists of using a Guardian Sensor (3) 
connected to a Guardian Link (3) transmitter. A total period of 2 weeks of CGM 
data will be collected.  
Note: Subjects 2-6 years of age will automatically enter the HCL arm at the end 
of the run-in period 

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Cohort 1: CSII 
The Study Period: After completion of the run-in period, subjects with CSII 
therapy (minimum N= 280) will be randomized and placed into one of 2 
different arms during the study period: 
1. The HCL Arm will use the MiniMed System (i.e., using Auto Mode) for 6 
months during the study period. There will be N=140 for the HCL arm. 
2. The Control Arm will use the MiniMed Pump without CGM 
a. Blinded CGM (Guardian Link (3) Transmitter and Guardian 
Sensor (3)) will only be worn at baseline, 3 months, and 6 
months (two weeks of sensors use). There will be N=140. 
 
Cohort 2: MDI 
The Study Period: After completion of the run-in period, subjects with MDI 
therapy (minimum of N=280) will be randomized and placed into one of 2 
different arms during the study period: 
1. The HCL Arm will use the MiniMed system (i.e., using Auto Mode) for 6 
months during the study period. There will be N=140 for the HCL arm. 
2. The Control Arm will be using their current insulin therapy (MDI).  
The Multiple Daily Injection (MDI) subjects will remain on MDI therapy 
with subjects using their own insulin for 6 months during the study 
period. The Sponsor will not provide insulin. Blinded CGM (Guardian 
Link (3) Transmitter and Guardian Sensor (3)) will only be worn at 
baseline, 3 months and 6 months (two weeks of sensors use). There 
will be N=140. 
MDI subjects who are currently using CGM, i.e. Dexcom or Medtronic 
Guardian Connect or who are currently using a SMBG alternative, i.e. 
Libre, will be allowed to enroll in the study and continue using their 
own device. There will be N=100 
 
Cohort 3: SAP 
The Study Period: After completion of the run-in period, subjects with SAP 

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therapy (minimum N=280) will be randomized and placed into one of 2 different 
arms during the study period.  Sensor insertion placement will be according to 
User guide: 
1. The HCL Arm will use the MiniMed system (i.e., using Auto Mode) for 6 
months during the study period. There will be N=140 for the HCL arm. 
2. The Control Arm will be using SAP therapy using the MiniMed System. 
a. The Sensor Augmented Pump (SAP) subjects will use the 
MiniMed System (SAP without Low Management Suspend on 
Low, Low Management Suspend before low or Auto Mode) with 
Real Time CGM for the 6 month study period. There will be 
N=140.  
 
The Continuation Period: All subjects above will enter the continuation period 
for 6 months using the MiniMed system with Auto Mode on.    


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Figure 1.  Study Design 
Cohort1(CSII)
Run-In Period
Study  Period
Continuation  Period
Screening and 2 weeks of 
blinded CGM
Randomization
Treatment (HCL)
Control (CSII)
Treatment (HCL)
End of Study
Cohort2(MDI)
Run-In Period
Study  Period
Continuation  Period
Screening and 2 weeks of 
blinded CGM
Randomization
Treatment (HCL)
Treatment (HCL)
End of Study
Cohort3(SAP)
Run-In Period
Study  Period
Continuation  Period
Screening and 2 weeks of 
blinded CGM
Randomization
Treatment (HCL)
Control (SAP)
Treatment (HCL)
End of Study
Control (MDI) 
 
Subjects may be re-tested as per sponsor discretion. 
 
Per Cohort (CSII, MDI or SAP ), here are the numbers of subjects expected to 
enroll: 
x
A1C at time of screening:
R N = 70 A1C > 8% for HCL Arm  
R EсϳϬϭчϴйĨŽƌ,>ƌŵ 
R N = 70 A1C > 8% for Control Arm 
R EсϳϬϭчϴйĨŽƌŽŶƚƌŽůƌŵ 

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x
Age at time of screening:  
N=Minimum number of eligible 
subjects for each age group within 
each treatment cohort 
N= Minimum number 
of eligible Subjects for 
each age group and 
cohort  
N= Minimum 
number of 
eligible 
subjects for 
each age 
group for 
study 
Age Group 
Cohor
t 
N 
N 
N 
2-6 years 
CSII  
No Minimum 
No minimum 
N =120 
SAP 
MDI 
7 -13 years 
CSII 
No Minimum  
No minimum 
N=180 
SAP 
MDI 
14-21 
years 
CSII 
SAP 
MDI 
N=45 
N=45 
N=135 
22-64 
years 
CSII 
SAP 
MDI 
N=120 
N=120 
N=360 
65-80 
years 
CSII 
No Minimum  
 No minimum 
N=150 
SAP 
MDI 
 
 

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Randomization 
Table 1. Randomization 
Treatment at 
Baseline 
Randomization Options 
Continuation 
CSII 
CSII 
HCL 
HCL 
MDI 
MDI 
HCL 
HCL 
SAP 
SAP 
HCL 
HCL 
Note: Subjects 2-6 years of age will automatically enter the HCL arm at the end 
of the run-in period 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
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PI
PI

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
  

  

 
 
 
Inclusion/
Exclusion Criteria 
Inclusion Criteria:
Subjects will be considered for enrollment in the study if they meet all of the 
following criteria: 
1. Subject is age 2-80 years at time of screening  
a. US, Canada, Australia and New Zealand: Subjects 2-80 years of age 
will be allowed to enroll in the post approval study.  
b. Europe: Only sƵďũĞĐƚƐшϳǇĞĂƌƐŽĨĂŐĞĂƌĞĂůůŽǁĞĚƚŽĞŶƌŽůůŝŶƚŚĞ
post-market study. 
2. Subjects who are 2-21 years are determined by the investigator to have the 
appropriate, requisite support (family, caregiver or social network) to 
successfully participate in this study 
3. Subject must have a minimum daily insulin requirement (Total Daily Dose) of 
equal to or greater than 8 units/day  
4. Subjects who are determined by the investigator to be psychologically sound 
in order to successfully participate in this study 
5. Subject has been diagnosed with type 1 diabetes for at least three months   
Note: Determination of classification for diabetes will be based on 
American Diabetes Association Clinical Practice Guidelines accounting 
for several patient characteristics such as:  age of onset, patient’s 
weight or BMI, history of diabetic ketoacidosis, history of therapy 
management, if available in the medical records.   
6. Subject must be on one of the following management therapies:  
a. Multiple daily injections defined by use of rapid analogue with meals 
and approved long acting analogue (e.g. detemir or glargine) with or 
without CGM 
b. Insulin pump therapy with or without CGM 
7. ^ƵďũĞĐƚŝƐǁŝůůŝŶŐƚŽƉĞƌĨŽƌŵшϰĨŝŶŐĞƌƐƚŝĐŬďůŽŽĚŐůƵĐŽƐĞŵĞĂƐƵƌĞŵĞŶƚƐ
daily  
PI

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8. Subject is willing to perform required study procedures 
9. Subject is willing to wear the system continuously throughout the study for 
at least 80% of the time. 
10.Subject is willing to upload data at least weekly from the study pump/meter, 
must have Internet access and a computer system that meets the 
requirements for uploading the study pump/meter for data collection 
11.Subject must be willing to use the study glucose meter system (i.e. along 
with study meter strips).     
12.If subject has celiac disease, it has been adequately treated as determined 
by the investigator
13.Subject with the diagnosis of myocardial infarction, unstable angina, 
coronary artery bypass surgery, coronary artery stenting, transient ischemic 
attack, cerebrovascular accident, angina, congestive heart failure, ventricular 
rhythm disturbances or thromboembolic disease, within 1 year of screening, 
will be included in the study with the consent of the Investigator  
14.Subject is willing to take one of the following insulins and can financially 
afford to use either of the 2 insulin preparations throughout the course of 
the study (i.e. co-payments for insulin with insurance or able to pay full 
amount) 
a. Humalog® (insulin lispro injection) 
b. NovoLog® (insulin aspart) 
 
Exclusion Criteria: 
1. Subject participated in any Closed Loop study in the past. 
2. Subject is unable to tolerate tape adhesive in the area of sensor placement  
3. Subject has any unresolved adverse skin condition in the area of sensor 
placement (e.g., psoriasis, rash, Staphylococcus infection) or area of infusion 
set placement 
4. Women of child-bearing potential who have a positive pregnancy test at 
screening or plan to become pregnant during the course of the study  
5. Subject is being treated for hyperthyroidism at time of screening 
6. Subject has an abnormality (out of reference range) in thyroid-stimulating 
hormone (TSH) at time of screening visit. TSH is not required for subjects 2-
13 years of age. 
7. Subject has taken any oral, injectable, or IV glucocorticoids within 8 weeks 
from time of screening visit, or plans to take any oral, injectable, or IV 

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glucocorticoids during the course of the study. 
8. Subject is actively participating in an investigational study (drug or device) 
wherein he/she has received treatment from an investigational study drug 
or investigational study device in the last 2 weeks 
9. Subject is currently abusing illicit drugs or marijuana 
10.Subject is currently abusing prescription drugs   
11.Subject is currently abusing alcohol 
12.Subject is using pramlintide (Symlin), SGLT2 inhibitors, GLP agonists, 
biguanides, DPP-4 inhibitors or sulfonylureas at time of screening 
13.Subject is using hydroxyurea at the time of screening or plans to use it 
during the study.     
14.Subject has a history of visual impairment which would not allow subject to 
participate in the study and perform all study procedures safely, as 
determined by the investigator 
15.Subject has a sickle cell disease, hemoglobinopathy; or has received red 
blood cell transfusion or erythropoietin within 3 months prior to time of 
screening  
16.Subject plans to receive red blood cell transfusion or erythropoietin over the 
course of study participation     
17.Subject diagnosed with current moderate to severe eating disorder such as 
anorexia or bulimia 
18.Subject has been diagnosed with chronic kidney disease requiring dialysis or 
resulting in chronic anemia  
19.Subjects who are currently being actively treated for cancer.   
20.Subject who is designated as a research staff member for this study 
Study Procedures and 
Assessments 
Each subject’s participation will be comprised of the following scheduled visits 
listed below over the course of approximately 8 months during the run-in period 
and study period, and for 6 months during the continuation period.   
x
Telemedicine visits will be allowed to replace office visits if they do not 
involve collection of blood samples and device related procedures that 
require staff assistance 
 
 
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The schedule is planned as follows:  
Screening and Run-In Period 
All subjects will complete screening and the run-in period. This period must be 
completed in 60 days.  
Visit 1: Screening Visit – Consent and Screening 
Patients may re-screen once with Sponsor approval  
Visit 2: Begin Run-in Period 
R Placement of blinded sensor to be worn for 2 Weeks (each sensor 
is worn for 7 days) 
R Study training, including instruction on procedures for wearing 
blinded CGM (i.e., insertion of sensor)  
Visit 3: Begin MiniMed Pump (Except MDI Control) 
R Occurs after 2-week blinded sensor wear, either immediately at 
the end of sensor wear or suggested to be within 14 days.  
R The run-in period may be repeated a second time with Sponsor 
approval  
 
Randomization  
At Visit 3 subjects (CSII, MDI or SAP Cohort) will be randomized into one of 2 
arms: 
x
HCL Arm 
Note: Patients who are on SAP at baseline will start Medtronic CGM at 
this visit.  
x
Control Arm  
Note: Patients in SAP will receive and be trained on Medtronic CGM if 
they are randomized to the Control arm to ensure continuity with use of 
real time CGM.   
Note: Subjects 2-6 years of age will automatically enter the HCL arm at the end 

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of the run-in period
 
To schedule Visit 4:  
x
For subjects who have been on insulin pump therapy prior to screening 
for at least 3 months, Visit 4 should occur 3-30 days after Visit 3  
x
For subjects without pump therapy experience, the following should 
occur: 
x
If randomized to the HCL arm, Visit 4 should occur 14-30 days after Visit 
3 
x
If randomized to the MDI Control arm, Visit 4 should occur 1-7 days after 
Visit 3 
The visit schedules for each of these Arms are as follows: 
HCL Arm: 
Visit 4: Start CGM - Day 0  
Start CGM with Guardian Sensor (3) (Note: SAP subjects  will have 
already started CGM with Guardian Sensor (3) at Visit 3) 
Visit 4A: Follow up Telephone visit - 2-3 days after Visit 4 
Visit 5: Follow up Office Visit - 7-21 days after Visit 4  
Auto Mode is enabled and activated. Investigator sets carbohydrate to 
insulin ratios and active insulin time, and basal rates for open loop 
periods  
Visit 6A: Follow-up Telephone Visit (option of office visit) – 1 Day after 
Visit 5 
Visit 6B: Follow-up Telephone Visit (option of office visit) - 2 Days after 
Visit 5  
Visit 6C: Follow-up Telephone Visit - 5 Days (± 1 day) after Visit 5 
Visit 7A: Follow up Office Visit - 14 Days (± 3 days)  after Visit 5  
Visit 7B: Follow-up Telephone Visit - 21 Days (± 3 days) after Visit 5
Visit 7C: Follow up Office Visit - 30 Days after Visit 5 (± 5 days) 
Visit 7D: Follow-up Telephone Visit - 45 Days (± 7 days) after Visit 5    
Visit 8: Follow up Office Visit - 90 Days after Randomization (± 10 days)  
Visit 9: Follow up Office Visit - 180 Days after Randomization (± 10 days)   

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R End of Study Period and Start of Continuation period  
Control Arm: 
a. CSII Cohort 
Visit 4: Day 0:  
R Review pump settings 
 Visit 5: Follow up Office Visit 7-21 days after Visit 4 
R Insulin Pump adjustments 
Visit 6A: Follow up Telephone Visit - 1 Day after Visit 5   
Visit 6B: Follow up Telephone Visit - 2 Days after Visit 5  
Visit 6C: Follow up Telephone Visit - 14 Days (± 7 days)  after Visit 5 
Visit 6D: Follow up Office Visit - 30 Days after Visit 5 (± 7 days) 
Visit 6E: Follow-up Telephone Visit - 45 Days (± 7 days) after Visit 5    
Visit 7: Follow up Office Visit - 76 days after Randomization (-14 days) 
R Blinded CGM Start 
R 14 days of sensor wear before 90 Day study period visit. 
Transmitter is not connected to study pump 
Visit 8A: Follow up Office Visit – 90 Days after Randomization (+14 days) 
R Blinded CGM Return 
Visit 8B: Follow up Office Visit - 166 days after Randomization (-14 days) 
R Blinded CGM Start 
R 14 days of sensor wear before 180 Day study period visit. 
Transmitter is not connected to study pump 
Visit 9: Follow up Office Visit – 180 Days after Randomization (+14 days) 
R Blinded CGM Return 
R End of Study Period and Start of Continuation period. 
R Start CGM with Guardian Sensor (3) 
 
b. MDI Cohort 
Visit 4: Day 0   
Visit 5: Follow up Office Visit 7-21 days after Visit 4 
Visit 6A: Follow up Telephone Visit - 1 Day after Visit 5   

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Visit 6B: Follow up Telephone Visit - 2 Days after Visit 5
Visit 6C: Follow up Telephone Visit - 14 Days (± 7 days)  after Visit 5 
Visit 6D: Follow up Office Visit - 25 Days after Visit 5 (± 5 days) 
Visit 6E: Follow-up Telephone Visit - 35 Days (+1 days) after Visit 5    
Visit 7: Follow up Office Visit - 76 days after Randomization (-2 days) 
R Blinded CGM Start  
R 14 days of sensor wear before 90 Day study period visit.  
Visit 8A: Follow up Office Visit – 90 Days after Randomization (+14 days) 
R Blinded CGM Return 
Visit 8B: Follow up Office Visit - 166 days after Randomization (-14 days) 
R Blinded CGM Start  
R 14 days of sensor wear before 180 Day study period visit.  
Visit 9: Follow up Office Visit – 180 Days after Randomization (+14 days) 
R Blinded CGM Return 
R End of Study Period and Start of Continuation period. 
R Start study pump  
c. SAP Cohort: 
Visit 4:  Day 0 
Visit 4A: Follow up Telephone visit - 2-3 days after Visit 4 
Visit 5: Follow-up Office Visit - 7-21 days after Visit 4 
R Pump and Sensor adjustments 
Visit 6A: Follow-up Telephone Visit (option of office visit) – 1 Day after 
Visit 5 
Visit 6B: Follow-up Telephone Visit (option of office visit) - 2 Days after 
Visit 5  
Visit 6C: Follow-up Telephone Visit 7 days after Visit 5 (+3 days ) 
Visit 7A: Follow-up Telephone Visit - 14 Days after Visit 5 (± 3 days)   
Visit 7B: Follow-up Telephone Visit - 21 Days after Visit 5 (± 3 days) 
Visit 7C: Follow-up Office Visit - 30 Days after Visit 5 (± 5 days) 
Visit 7D: Follow-up Telephone Visit - 45 Days (± 7 days) after Visit 5  
Visit 8: Follow-up Office Visit - 90 Days after Randomization (± 10 days)  

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Visit 9: Follow-up Office Visit - 180 Days after Randomization (± 10 days)   
R End of Study Period and Start of Continuation period 
R Auto Mode is enabled and activated. 
Continuation Period: 
HCL Arm: 
Visit 10: Follow up Office Visit – 1 to 14 days after Visit 9 
Visit 11: Follow up Office Visit – 15 to 30 days after Visit 9 
Visit 12: Follow up Office Visit - 270 Days after Randomization (+/- 21 
days) 
Visit 13: Follow up Office Visit - 365 Days after Randomization (+/- 21 
days)  
R End of Continuation Period and End of Study 
Control Arm 
 
a. CSII Cohort: 
Visit 10A: Follow up Telephone visit - 2-3 days after sensor start 
Visit 10B: Follow up Office Visit 7-21 days after Visit 9  
R Auto Mode is enabled and activated. 
Visit 10C: Follow up Telephone Visit  (option of office visit) – 1 Day after 
Visit 10B 
Visit 10D: Follow up Telephone Visit  (option of office visit) – 2 Days after 
Visit 10B  
Visit 10E: Follow-up Telephone Visit – 5 Days (± 1 day) after Visit 10B 
Visit 11A: Follow up Office Visit - 14 Days after Visit 10B (±3 days)  
Visit 11B: Follow-up Telephone Visit - 21 Days (±3 days) after Visit 10B   
Visit 11C: Follow up Office Visit - 30 Days after Visit 10B (±5 days) 
Visit 11D: Follow-up Telephone Visit - 45 Days (±7 days) after Visit 10B  
Visit 12: Follow up Office Visit - 270 Days after Randomization (+/- 21 
days)  
Visit 13: Follow up Office Visit - 365 Days after Randomization (+/- 21 
days)  
R End of Continuation Period and End of Study 

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b.
MDI Cohort: 
Visit 9A: Follow up Office Visit – 14-30 days after Visit 9 
R Start CGM with Guardian Sensor (3)  
R This visit should occur between 14 and 30 days after pump 
start.  
Visit 10A: Follow up Telephone visit - 2-3 days after sensor start 
Visit 10B: Follow up Office Visit 7-21 days after Visit 9A  
R Patient has been wearing CGM for at least 4 days before 
enabling Auto Mode 
R Auto Mode is enabled and activated.  
Visit 10C: Follow up Telephone Visit (option of office visit) – 1 Day after 
Visit 10B 
Visit 10D: Follow up Telephone Visit (option of office visit) – 2 Days after 
Visit 10B  
Visit 10E: Follow-up Telephone Visit – 5 Days (± 1 day) after Visit 10B 
Visit 11A: Follow up Office Visit - 14 Days after Visit 10B (±3 days) 
Visit 11B: Follow-up Telephone Visit – 21 Days (± 3 day) after Visit 10B   
Visit 11C: Follow up Office Visit - 30 Days after Visit 10B (± 5 days)  
Visit 11D: Follow-up Telephone Visit – 45 Days (± 7 day) after Visit 10B 
Visit 12: Follow up Office Visit - 270 Days after Randomization (+/- 21 
days)  
Visit 13: Follow up Office Visit - 365 Days after Randomization (+/- 21 
days)  
R End of Continuation Period and End of Study 
 
c. SAP Cohort: 
Visit 10A: Follow up Telephone Visit (option of office visit) – 1 Day after 
Visit 9 
Visit 10B: Follow up Telephone Visit (option of office visit) – 2 Days after 
Visit 9  
Visit 10C: Follow-up Telephone Visit – 5 Days (± 1 day) after Visit 9 

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Visit 11A: Follow up Office Visit - 14 Days after Visit 9 (±3 days)  
Visit 11B:  Follow-up Telephone Visit – 21 Days (± 3 day) after Visit 9 
Visit 11C: Follow up Office Visit - 30 Days after Visit 9 (±5 days)  
Visit 11D: Follow-up Telephone Visit – 45 Days (± 5  day) after Visit 9 
Visit 12: Follow up Office Visit - 270 Days after Randomization (+/- 21 
days)  
Visit 13: Follow up Office Visit - 365 Days after Randomization (+/- 21 
days)  
R End of Continuation Period and End of Study 
 
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In order to achieve safety success, the following study success criteria must be met for 
the HCL Arm by the end of the study: 
 
Table 2. Safety Success Criteria
Adverse Event 
Reference 
Reference 
Rate > 25 
years old
Reference 
Rate 
15-25 years 
old 
Reference 
Rate <15 
years old
Study Success 
Criteria 
 
DKA events 
per 100 
patient years 
STAR 3 
Bergenstal et. al  
SAP arm: 
0.68 
Control 
arm: 0
SAP arm:  
2.7
Control 
arm: 3.6 
SAP arm: 
2.2
Control 
arm: 0
< 4 events 
per 100 
patient 
years with 
HCL arm 
530 G Adult inhome 
study CEP 266 
(MDT on file) 
 1.27 
3.4 
N/A 
530 G Pediatric  
inhome study CEP 287
(MDT on file)
N/A
N/A
0 
Type 1 exchange 
Weinstock et. al
4.8
N/A
N/A
Type 1 exchange 
Cengiz et. al 
N/A 
9.9 
9.9
 
 
Severe 
hypoglycemi
a per 100 
patient years 
STAR 3 
Bergenstal et. al  
 
SAP  arm: 
16.5  
Control 
arm: 20.9 
 
SAP arm:  
5.4 
Control 
arm: 3.9
 
SAP arm:  
10.2 
Control 
arm: 3.6 
< 8 events 
per 100 
patient 
years with 
HCL arm 
530 G Adult inhome 
study CEP 266 
(MDT on file) 
0.85 
0 
N/A 
530 G Pediatric  
inhome study CEP 287
N/A 
N/A 
1.42 

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Type 1 exchange 
Weinstock et. al
11.8     
N/A 
N/A 
Type 1 exchange 
Cengiz et. al 
N/A 
6.2  
6.2  
Descriptive summary (i.e. not statistically powered) for severe hypoglycemia and DKA 
events rates will be performed between the HCL and control arms for each age group (< 
15 years, 15-25 years, and > 25 years), as well as the overall event rates. 
Severe hypoglycemia and DKA event rates were taken from the following
1. Richard Bergenstal et.al: Effectiveness of Sensor-Augmented Insulin-Pump Therapy 
in Type 1Diabetes.New England Journal of Medicine, 2010; 363:311-20 
2. Weinstock et. al: Severe hypoglycemia and diabetic ketoacidosis in adults with type 
1 diabetes: results from the T1D Exchange clinic registry. J Clin Endocrinol Metab. 
2013 Aug;98(8):3411-9. 
3. Cengiz et. al: Severe hypoglycemia and diabetic ketoacidosis among youth with type 
1 diabetes in the T1D Exchange clinic registry. Pediatr Diabetes. 2013 Sep;14(6):447-
54. 
4.
MDT on file: Statistical Analysis Plan (SAP) for CEP304, 056-F286 
 
Safety monitoring/risk analysis details are outlined in Section 14. 
 
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The study will be stopped if DMC determines that there are significant safety 
issues. (See DMC section.) 
Note: If it is decided to withdraw patients from participation in the study or if 
the study is stopped, subjects will be followed-up in accordance with standard 
practice. 
 
6XEMHFW6WRSSLQJ
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1. One episode of DKA or 2 episodes of severe hypoglycemia will result in 
withdrawal of subject from study, regardless of which arm or period 
they are in. 
2. The first episode of Severe Hypoglycemia may lead to withdrawal, if it is 
secondary to subject non-compliance or other individual safety 
concerns:   
R Subject is not using the bolus wizard 
R Subject is not checking blood glucose using finger sticks  
R Subject is non-compliant with sensor wear 
R Subject is not following protocol procedures  
 
Statistics 
Effectiveness endpoints will be evaluated during the 6 month study period by 
individual Cohort (CSII, MDI or SAP), stratified by A1C; 

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Group 1: Baseline A1C > 8%  
x
'ƌŽƵƉϮ͗ĂƐĞůŝŶĞϭчϴй 
The comparison of HCL arm vs. Control arm will be performed.  For SG-based 
comparison between HCL vs Control analyses, two weeks of CGM data collected 
at 3 month visit and 6 month visits will be used.  
 
Primary Effectiveness Endpoints – Co-Primary Endpoints: 
 
x
Group ϭ͗ĂƐĞůŝŶĞϭхϴй͗ŚĂŶŐĞŝŶϭ;ѐϭͿ 
The primary effectiveness endpoint  for the baseline A1C > 8% is the change in 
A1C from baseline to the end of the six-month treatment period, defined as A1C 
measured at the six-month treatment visit minus A1C measured at the 
randomization visit. The goal is to show superiority of the HCL Arm compared to 
the Control Arm in reducing A1C from baseline to end of six-month treatment 
period. 
x
Group 2: ĂƐĞůŝŶĞϭчϴй: Time in Hypoglycemic Range  
 
The primary effectiveness endpoint ĨŽƌƚŚĞďĂƐĞůŝŶĞϭчϴй is the time with 
sensor glucose (SG) below 70 mg/dL (3.9 mmol/L) during the six-month study 
period. The goal is to show superiority of the HCL Arm compared to the Control 
Arm in reducing time in hypoglycemic range. : 
 
Key Secondary Effectiveness Endpoints 
x
Group 1: Baseline A1C > 8%: Time in Hypoglycemic Range 
The key secondary effectiveness endpoint for the baseline A1C > 8% is the time 
with SG below 70mg/dL (3.9 mmol/L) during the six-month study period. The 
goal is to show non-inferiority of the HCL Arm compared to the Control Arm in 
reducing time in hypoglycemic range.  
x
Group 2͗ĂƐĞůŝŶĞϭчϴй͗ŚĂŶŐĞŝŶϭ;ѐϭͿ 
The key secondary effectiveness endpoint ĨŽƌƚŚĞďĂƐĞůŝŶĞϭчϴй is the 
change in A1C from baseline to end of six-month treatment period, defined as 
A1C measured at the six-month treatment visit minus A1C measured at the 
randomization visit. The goal is to show non-inferiority of the HCL Arm compared 
to the Control Arm in reducing A1C from baseline to end of six-month treatment 
period.  

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Other Secondary Effectiveness Endpoints 
 
The other secondary effectiveness endpoints are hierarchically ordered and will 
be evaluated in the fixed sequence from endpoint 1 to 5 during the first 6 
months of study phase. 
x
Group 1 + Group 2: Time in Hypoglycemic Range during Night 
The first secondary effectiveness endpoint is the time with SG below 70 mg/dL 
(3.9mmol/L) during Night. The goal is to show superiority of the HCL Arm 
compared to the Control Arm reducing time in hypoglycemic range during night. 
x
Group 1 + Group 2: Time in Hypoglycemic Range during Day and Night 
The endpoint of time in hypoglycemic range below 70 mg/dL (3.9mmol/L) will be 
evaluated for superiority in the combined Groups. The goal is to show 
superiority of the HCL Arm compared to the Control Arm in reducing time in 
hypoglycemic range. 
x
Group 1 + Group 2: Time in Target Range 70mg/dL (3.9mmol/L) – 180 
mg/dL  (10.0mmol/L) during Night 
The endpoint of time in target range measures the time with SG in target range 
70mg/dL (3.9mmol/L) – 180 mg/dL (10.0mmol/L) during Night. The goal is to 
show superiority of the HCL Arm compared to the Control Arm in improving the 
time in target range  
x
Group 1 + Group 2: Time in Target Range 70mg/dL (3.9mmol/L)– 180 
mg/dL (10.0mmol/L) during Day and Night 
 
The endpoint of time in target range measures the time with SG in target range 
70mg/dL (3.9mmol/L) – 180 mg/dL (10.0mmol/L) during Day and Night. The goal 
is to show superiority of the HCL Arm compared to the Control Arm in improving 
the time in target range  
x
Group 1 + Group 2: Change in A1C 
 
The endpoint of change in A1C will be evaluated for superiority in the combined 
Groups. The goal is to show superiority of the HCL Arm compared to the Control 
Arm in reducing A1C from baseline to end of six-month treatment period.  
 

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Primary Safety Endpoints:  
The primary safety endpoint is the event rate of severe hypoglycemia and DKA 
from both Groups (1 & 2) during the first 6 months of study phase and second 6 
months of continuation phase. The descriptive summary statistics will be 
presented by number of event and event rate (100 patient years) for severe 
hypoglycemia and DKA separately.  
The safety of the study will be evaluated and summarized per arm, including but 
not limited to the following: 
x
Diabetic ketoacidosis (DKA) 
x
Severe hypoglycemia 
x
Severe hyperglycemia  
x
Serious adverse events (SAEs) 
x
Unanticipated adverse device effects (UADEs) 
 
 
  
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Provisional studies employing closed loop technology have shown a reduction in both hypoglycemia and 
hyperglycemia, as well as glycemic variability. Previous studies have evaluated prototype versions of the 
Medtronic closed-loop insulin delivery systems in pediatric patients, as well as adolescents and young adults.  
Researchers at the Yale University School of Medicine studied the performance of both a hybrid closed-loop 
algorithm and a fully closed loop algorithm using the Medtronic MMT-715 insulin pump, the Medtronic Sof-
sensor and MiniLink transmitter and a control algorithm running on a laptop computer [Weinzimer et al, 2008].  
Seventeen subjects between the ages of 13 and 20 years participated in the study with eight subjects 
undergoing testing with a fully closed-loop algorithm, and the remaining nine subjects being evaluated using 
the hybrid closed-loop algorithm.  This study demonstrated that a fully closed loop artificial pancreas using an 
external glucose sensor is feasible and effective in adolescents with type 1 diabetes. 
The Type 1 Diabetes TrialNet Study Groups used this same system to evaluate inpatient hybrid closed-loop 
control (HCL) initiated shortly after the diagnosis of type 1 diabetes [Diabetes Research in Children Network 
Study Group,  2013].  Forty eight subjects between the ages of 7.8 and 37.7 years participated in the intensive 
treatment group and received inpatient HCL followed by outpatient sensor augmented pump therapy.  Forty 
six of the 48 subjects were less than 18 years old.  The study found that inpatient HCL safely initiated soon after 
the diagnosis of type 1 diabetes resulted in the rapid decrease in blood glucose levels within 24 hours of 
initiation and that while using HCL, about 80% of the glucose levels were in the target range of 71mg/dL -180 
mg/dL, with minimal hypoglycemia. 
Medtronic has completed 7 phases in the HCL Feasibility Study (CEP 273) with a total of 71 subjects enrolled. In 
this Feasibility study, the closed loop system was stressed by artificially inducing sensor error as well as 
inducing physiologic stress such as exercise and administration of meals without bolus. The Feasibility study 
provided data which was used to develop the device algorithm that is being tested in this study. 
A pivotal trial with 120 subjects was completed in February 2016.  This was a single arm study evaluating the 
safety of the MiniMed 670G HCL system in subjects 14-75 years of age, for 3 months in the home setting. The 
pediatric pivotal study for the HCL system was conducted as an at-home, multi-center study, which enrolled 
162 participants ages 2-13 years of age. Patients were recruited at 11 centers (10 in the United States, 1 in 
Israel). The study was identical in design to the young adult/adult pivotal study.  
Study results in the pediatric study mirrored data from the pivotal trial of the system in adults and adolescents 
(14 and above), showing patients spent more time in euglycemic range, experienced less glycemic variability, 

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had less exposure to hypoglycemia and hyperglycemia and significantly reduced HbA1c compared to baseline 
data where they used sensor-augmented pumps without SmartGuardTM automation activated. No episodes of 
severe hypoglycemia or diabetic ketoacidosis and no serious device-related adverse events were reported. 
The MiniMed 770G Insulin Pump is equivalent in function to the MiniMed 670G insulin pump, with the 
exception of telemetry. While the MiniMed 670G insulin pump communicates on the basis of Tel-D (telemetry-
diabetes) radio frequency (RF) technology, the MiniMed 770G pump contains BLE (Bluetooth Low Energy) RF 
communication, which allows for connectivity to patients’ smartphones, CGM transmitter and an BLE RF 
enabled blood glucose meter.  For detailed information on the MiniMed 770G pump, see Section 7.5. 
 
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The purpose of this study is to evaluate the safety and effectiveness of the Hybrid Closed Loop system (HCL) in 
adult and pediatric patients with type 1 diabetes in the home setting. A diverse population of patients with 
type 1 diabetes will be studied. The study population will have a large range for duration of diabetes and 
glycemic control, as measured by glycosylated hemoglobin (A1C). The following cohorts will be enrolled: 
1) Cohort 1: Continuous Subcutaneous Insulin Infusion (CSII) or HCL;  
2) Cohort 2: Multiple Daily Injections (MDI) or HCL and  
3) Cohort 3: Sensor-Augmented Pump therapy (SAP) or HCL.  
 
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The purpose of this study is to evaluate the safety and effectiveness of the Hybrid Closed Loop system (HCL) in 
adult and pediatric patients with type 1 diabetes in the home setting.  
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All endpoints are hierarchically ordered and will be evaluated in the fixed sequence from primary endpoints to 

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secondary endpoints. Unless the primary endpoints hypotheses are rejected, secondary endpoints will not be 
tested.   
Effectiveness endpoints will be evaluated during the 6 month study period by individual Cohort (CSII, MDI or 
SAP), stratified by A1C; 
 
x
Group 1: Baseline A1C > 8%  
x
'ƌŽƵƉϮ͗ĂƐĞůŝŶĞϭчϴй 
The comparison of HCL arm vs. Control arm will be performed.  For SG-based comparison between HCL vs 
Control analyses, two weeks of CGM data collected at 3 month visit and 6 month visits will be used.   
 
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The primary effectiveness endpoints consist of one-primary endpoint for each group.
Group 1: Baseline A1C > 8%͗ŚĂŶŐĞŝŶϭ;ѐϭͿ
x
The primary effectiveness endpoints for the baseline A1C > 8% group is change in A1C from baseline to 
end of six-month treatment period, defined as A1C measured at the six-month treatment visit minus 
A1C measured at the randomization visit. The goal is to show superiority of the HCL Arm compared to 
the Control Arm in reducing A1C from baseline to end of six-month treatment period.  
x
The hypothesis is mathematically expressed as: 
,Ϭ͗ђ;,>Ϳшђ;ŽŶƚƌŽůͿ 
Ha: μ(HCL) < μ(Control) 
where μ(HCL) is the mean of change in A1C (%) with the HCL Arm, μ(Control) is the mean of change 
in A1C (%) with the Control Arm. 
 
Group Ϯ͗ĂƐĞůŝŶĞϭчϴй: Time in Hypoglycemic Range  
x
dŚĞƉƌŝŵĂƌǇĞĨĨĞĐƚŝǀĞŶĞƐƐĞŶĚƉŽŝŶƚĨŽƌƚŚĞďĂƐĞůŝŶĞϭчϴйŐƌŽƵƉŝƐƚŚĞƚŝŵĞǁŝƚŚ^'ďĞůŽǁϳϬ
mg/dL (3.9mmol/L) during the six-month study period, defined as percentage of SG below 70 mg/dL 
(3.9mmol/L) out of total number of available SG readings. The goal is to show superiority of the HCL 
Arm compared to the Control Arm in reducing daily time in hypoglycemic range. 
x
The hypothesis is mathematically expressed as: 

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Ha: μ(HCL) < μ(Control) 
 
where μ(HCL) is the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in the HCL Arm, μ(Control) is 
the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in Control Arm 
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Key Secondary Effectiveness Endpoints 
Group 1: Baseline A1C > 8%: Time in Hypoglycemic Range 
x
The key secondary effectiveness endpoint for the baseline A1C > 8% group is the time with SG below 
70 mg/dL (3.9mmol/L) during the six-month study period, defined as percentage of SG below 70 mg/dL 
(3.9mmol/L) out of total number of available SG readings. The goal is to show non-inferiority (with a 
non-inferiority margin of 2%) of the HCL Arm compared to the Control Arm.  
x
The hypothesis of non-inferiority is mathematically expressed as: 
,Ϭ͗ђ;,>Ϳшђ;ŽŶƚƌŽůͿнϮй 
Ha: μ(HCL) < μ(Control) + 2% 
where μ(HCL) is the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in the HCL Arm, 
μ(Control) is the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in the Control Arm  
 
Group Ϯ͗ĂƐĞůŝŶĞϭчϴй͗ŚĂŶŐĞŝŶϭ;ѐϭͿ 
x
The key secondary ĞĨĨĞĐƚŝǀĞŶĞƐƐĞŶĚƉŽŝŶƚĨŽƌƚŚĞďĂƐĞůŝŶĞϭчϴйŐƌŽƵƉŝƐĐŚĂŶŐĞŝŶϭĨƌŽŵ
baseline to end of six-month treatment period, defined as A1C measured at the six-month treatment 
visit minus A1C measured at the randomization visit. The goal is to show non-inferiority (with a non-
inferiority margin of 0.4%) of the HCL Arm compared to the Control Arm in reducing A1C from baseline 
to end of six-month treatment period. 
x
The hypothesis of non-inferiority is mathematically expressed as: 
x
,Ϭ͗ђ;,>Ϳшμ(Control) + 0.4% 
x
Ha: μ(HCL) < μ(Control) + 0.4% 
x
where μ(HCL) is the mean of change in A1C (%) with the HCL Arm, μ(Control) is the mean of change in 
A1C (%) with the Control Arm.  

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Rest of Secondary Effectiveness Endpoints 
1. Group 1 + Group 2: Time in Hypoglycemic Range during Night 
The secondary effectiveness endpoint is the time with SG below 70 mg/dL (3.9mmol/L) during Night. The goal 
is to show superiority of the HCL Arm compared to the Control Arm reducing time in hypoglycemic range 
during night . The hypothesis is mathematically expressed as:
,Ϭ͗ђ;,>Ϳшђ;ŽŶƚƌŽůͿ 
Ha: μ(HCL) < μ(Control) 
where μ(HCL) is the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in the HCL Arm during night, 
μ(Control) is the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in the Control Arm during the 
night. 
2. Group 1 + Group 2: Time in Hypoglycemic Range during Day and Night 
The endpoint of time in hypoglycemic range below 70 mg/dL (3.9mmol/L) will be evaluated for superiority in 
the combined Groups during day and night. The goal is to show superiority of the HCL Arm compared to the 
Control Arm in reducing time in hypoglycemic range. The hypothesis is mathematically expressed as: 
,Ϭ͗ђ;,>Ϳшђ;ŽŶƚƌŽůͿ 
Ha: μ(HCL) < μ(Control) 
where μ(HCL) is the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in the HCL Arm, μ(Control) is 
the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in the Control Arm.   
 
3. Group 1 + Group 2: Time in Target Range 70mg/dL (3.9mmol/L) – 180 mg/dL  (10.0mmol/L) 
during Night 
The endpoint of time in target range measures the time with SG in target range 70mg/dL (3.9mmol/L) – 180 
mg/dL (10.0mmol/L) during Night. The goal is to show superiority of the HCL Arm compared to the Control Arm 
in improving the time in target range. The hypothesis is mathematically expressed as:
H0: μ(HCL) ൑ μ(Control)   
Ha: μ(HCL) > μ(Control) 
where μ(HCL) is the subject mean of time with SG between 70mg/dL (3.9mmol/L) – 180 mg/dL (10.0mmol/L) 
range in the HCL Arm during Night, μ(Control) is the subject mean daily time with SG between 70mg/dL 

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(3.9mmol/L) – 180 mg/dL (10.0mmol/L) range in the Control Arm.
4. Group 1 + Group 2: Time in Target Range 70mg/dL (3.9mmol/L)– 180 mg/dL (10.0mmol/L) 
during Day and Night 
The endpoint of time in target range measures the time with SG in target range 70mg/dL (3.9mmol/L) – 180 
mg/dL (10.0mmol/L) during Day and Night. The goal is to show superiority of the HCL Arm compared to the 
Combined Control group in improving the time in target range. The hypothesis is mathematically expressed as:
H0: μ(HCL) ൑ μ(Controls)   
Ha: μ(HCL) > μ(Controls) 
where μ(HCL) is the subject mean of time with SG between 70mg/dL (3.9mmol/L) – 180 mg/dL (10.0mmol/L) 
range in the HCL Arm during Day and Night, μ(Control) is the subject mean daily time with SG between 
70mg/dL (3.9mmol/L)  – 180 mg/dL (10.0mmol/L) range in the  Control Arm 
5. Group 1 + Group 2: Change in A1C 
The endpoint of change in A1C will be evaluated for superiority in the combined groups. The goal is to show 
superiority of the HCL Arm compared to the Control Arm in reducing A1C from baseline to end of six-month 
treatment period. The hypothesis is mathematically expressed as: 
,Ϭ͗ђ;,>Ϳшђ;ŽŶƚƌŽůͿ 
Ha: μ(HCL) < μ(Control) 
where μ(HCL) is the mean of change in A1C (%) with the HCL Arm, μ(Control) is the mean of change in A1C (%) 
with the Control Arm. 
 
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The primary safety endpoint is the event rate of severe hypoglycemia and DKA from both Groups (1 & 2) during 
the first 6 months of study phase and second 6 months of continuation phase. The descriptive summary 
statistics will be presented by number of event and event rate (100 patient years) for severe hypoglycemia and 
DKA separately. 
The safety of the study will be evaluated and summarized per arm, including but not limited to the following: 
x
Diabetic ketoacidosis (DKA) 
x
Severe hypoglycemia 
x
Severe hyperglycemia  

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Serious adverse events (SAEs) 
x
Unanticipated adverse device effects (UADEs) 
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This is a 6 month, multi-center, randomized, parallel, adaptive study in type 1 diabetes with a 6 month 
continuation period. Up to 1500 subjects will be enrolled in order to have 1000 subjects who enter the study 
period. To date, 959 subjects have enrolled. Up to 70 investigational Centers in the US, Europe, Canada, 
Australia and New Zealand will be enrolled. For additional information on investigational sites and 
investigators, refer to information listed on public databases (e.g., clinicaltrials.gov). 
The study will have three periods per Cohort:  
1. Run-in Period: The run-in period can be up to 60 days.  
The run-in period will also be used for CGM data collection for approximately two weeks. Two consecutive 
7-day sensors will be worn.  If a sensor falls out, a replacement sensor should make up the difference for a 
total of 14 days of sensor wear (i.e. Monday Day 1 through next Sunday Day 14)  
For example: If a sensor falls out on Day 4, a replacement sensor should be inserted.   Once that 
replacement sensor has been worn for 7 days, a new sensor should then be inserted and worn for 
3 days so that a total of 14 days of sensor wear is completed.  
All patients will wear blinded CGM. Subjects will be expected to demonstrate sensor wear for 
approximately 14 days total between the two 7-day sensor wears (plus replacement sensor if needed). 
Subjects should be instructed to make 4-6 BG measurements per day. Sponsor may request a repeat of 
blinded CGM. Repeat of blinded CGM may occur if the following are not met: 
x
A minimum of 12 days of sensor wear have been self-reported to research staff 
x
A minimum of 2 blood glucose checks/day during the blinded CGM wear are confirmed on the 
subject’s study BG meter.  
If these requirements are not met then patient should repeat the entire 2 week blinded CGM data 
collection unless sponsor has approved that there was adequate data collection. An additional 21 days may 
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be added to the run in visit window schedule if blinded CGM data collection needs to be repeated.  
Additional visits may also be allowed if needed.  
 
2. Study Period: There will be a 6 month randomized study period with two arms: HCL system and Control. 
CSII and MDI control groups will undergo two blinded CGM collections during the study period. 
The first blinded CGM data collection during the study period will occur before the month three (see visit 
schedule) for approximately two weeks.  Two consecutive 7-day sensors will be worn.  If a sensor falls out, 
a replacement sensor should make up the difference for a total of 14 days of sensor wear.  (i.e. Monday 
Day 1 through next Sunday Day 14) 
For example: If a sensor falls out on Day 4, a replacement sensor should be inserted.   Once that 
replacement sensor has been worn for 7days, a new sensor should then be inserted and worn for 3 
days so that a total of 14 days of sensor wear is completed.  
All patients will wear blinded CGM. Subjects will be expected to demonstrate sensor wear for 
approximately 14 days total between the two 7-day sensor wears (plus replacement sensor if needed). 
Subjects should be instructed to make 4-6 BG measurements per day. The following should have occurred:   
x
A minimum of 12 days of sensor wear have been self-reported to research staff 
x
A minimum of 2 blood glucose checks/day during the blinded CGM wear are confirmed on the 
subject’s study BG meter.  
If the above requirements are not met then patient should repeat the entire 2 week blinded CGM data 
collection unless the sponsor approves that there was adequate data collection.  Additional visits may also 
be allowed if needed. No changes to the remaining visit schedule are needed.   
The second blinded CGM data collection during the study period will occur before the month six (see visit 
schedule) for approximately two weeks.  Two consecutive 7-day sensors will be worn.  If a sensor falls out, 
a replacement sensor should make up the difference for a total of 14 days of sensor wear. (i.e. Monday Day 
1 through next Sunday Day 14). 
For example: If a sensor falls out on Day 4, a replacement sensor should be inserted.   Once that 
replacement sensor has been worn for 7 days, a new sensor should then be inserted and worn for 
3 days so that a total of 14 days of sensor wear is completed.  
All patients will wear blinded CGM. Subjects will be expected to demonstrate sensor wear for 
approximately 14 days total between the two 7-day sensor wears (plus replacement sensor if needed). 
Subjects should be instructed to make 4-6 BG measurements per day.  

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3.
Continuation Period: There will be a 6 month continuation period during which time all subjects will use 
the HCL system.  
 
Enrollment Cohorts According to Treatment 
At Enrollment, subjects will be identified according to the type of treatment regimen they are currently on. 
Treatment regimen is defined as follows: 
x
Cohort 1: CSII – subjects using pump (Medtronic or other pump systems) for at least 3 months at time 
of screening without concurrent use of real time CGM in the last 3 months. (Self-report acceptable.) 
Please note that alternatives to SMBG such as Freestyle Libre are not considered real time CGM and 
subjects who are using Freestyle Libre at time of Screening will be allowed to enroll in the study.  
During the study, however, subjects will not be allowed to use Freestyle Libre.  
x
Cohort 2: Multiple Daily Injections (MDI) - Subjects using MDI with or without concurrent use of CGM 
for at least 3 months prior to Screening.  (Self report is acceptable.)  
x
Cohort 3: Sensor Augmented Pump (SAP) – subjects using pump for at least 3 months at time of 
screening with real time CGM use (Medtronic or other CGM systems) approximately 20% of the time.  
(Self report acceptable.) Subjects will use the Medtronic CGM starting at Visit 3, but they may use their 
own CGM until then. Sensor insertion placement will be according to User guide. 
Staged enrollment for Subjects 2-6 Years of Age: 
x
Subjects 2-6 years of age will be allowed to enroll in the post approval study, once DMC has reviewed  
data from 10 subjects age 2-4 years who have completed participation in the study period of the 
CEP302 study and has given approval to enroll   
In the US and Canada, subjects 2-80 years of age will be allowed to transition from the 670G system to the 
770G system.  
The Run-In Period: Following successful screening, all subjects (CSII, MDI or SAP) will enter the run-in period 
and collect blinded CGM data while using their own diabetes therapy. Blinded CGM consists of using a 
Guardian Sensor (3) connected to a Guardian Link (3) transmitter.  A total period of 2 weeks of CGM data will 
be collected.   
Cohort 1: CSII 
The Study Period: After completion of the run-in period, subjects with CSII therapy (minimum N= 280) will be 
randomized and placed into one of 2 different arms during the study period: 
1. The HCL Arm will use the MiniMed system (i.e., using Auto Mode) for 6 months during the study 

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period. There will be N=140 for the HCL arm.
2. The Control Arm will use the MiniMed Pump without CGM. 
a) Blinded CGM (Guardian Link (3) Transmitter and Guardian Sensor (3)) will only be worn at baseline, 
3 months, and 6 months (two weeks of sensors use). There will be N=140. 
Cohort 2: MDI 
The Study Period: After completion of the run-in period, subjects with MDI therapy (minimum of N=280) will be 
randomized and placed into one of 2 different arms during the study period: 
1. The HCL Arm will use the MiniMed system (i.e., using Auto Mode) for 6 months during the study 
period. There will be N=140 for the HCL arm. 
2. The Control Arm will be using their current insulin therapy (MDI) 
 
The Multiple Daily Injection (MDI) subjects will remain on MDI therapy with subjects using their own 
insulin for 6 months during the study period. The Sponsor will not provide insulin. Blinded CGM 
(Guardian Link (3) Transmitter and Guardian Sensor (3)) will only be worn at baseline, 3 months, and 6 
months (two weeks of sensors use). There will be N=140. 
MDI subjects who are currently using CGM, i.e. Dexcom or Medtronic Guardian Connect or who are 
currently using a SMBG alternative, i.e. Libre, will be allowed to enroll in the study and continue using 
their own device. There will be N=100 
Cohort 3: SAP 
The Study Period: After completion of the run-in period, subjects with SAP therapy (minimum N= 280) will be 
randomized and placed into one of 2 different arms during the study period. Sensor insertion placement will be 
according to User guide: 
1. The HCL Arm will use the MiniMed system (i.e., using Auto Mode) for 6 months during the study 
period. There will be N=140 for the HCL arm. 
2. The Control Arm will be using SAP therapy using the MiniMed System.  
a) The Sensor Augmented Pump (SAP) subjects will use the MiniMed System (SAP without Low 
Management Suspend on Low, Low Management Suspend before low or Auto Mode) with Real 
Time CGM for the 6 month study period. There will be N=140.  
The Continuation Period: All subjects above will enter the continuation period for 6 months using the MiniMed 
system with Auto Mode on. 

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Figure 2. Study Design
Cohort1(CSII)
Run-In Period
Study  Period
Continuation  Period
Screening and 2 weeks of 
blinded CGM
Randomization
Treatment (HCL)
Control (CSII)
Treatment (HCL)
End of Study
Cohort2(MDI)
Run-In Period
Study  Period
Continuation  Period
Screening and 2 weeks of 
blinded CGM
Randomization
Treatment (HCL)
Treatment (HCL)
End of Study
Cohort3(SAP)
Run-In Period
Study  Period
Continuation  Period
Screening and 2 weeks of 
blinded CGM
Randomization
Treatment (HCL)
Control (SAP)
Treatment (HCL)
End of Study
Control (MDI) 
 
 
Subjects may be re-tested as per sponsor discretion. 
 

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Per Cohort (CSII, MDI, or SAP), here is the numbers of subjects expected to enroll: 
 
x
A1C at time of screening: 
R N = 70 A1C > 8% for HCL Arm  
R N = 70 ϭчϴйĨŽƌ,>Arm 
R N = 70 A1C > 8% for Control Arm 
R N = 70 ϭчϴйĨŽƌŽŶƚƌŽůƌŵ 
 
x
Age at time of screening:  
 
N=Minimum number of eligible subjects for 
each age group within each treatment cohort
N= Minimum number of 
eligible Subjects for each age 
group and cohort  
N=Minimum number of 
eligible subjects for each 
age group for study 
Age Group 
Cohort 
N 
N 
N 
2-6 years 
CSII  
No Minimum 
No minimum 
N= 120 
SAP 
MDI 
7 -13 years 
CSII 
No Minimum 
No minimum 
 
N= 180 
SAP 
MDI 
14-21 years 
CSII 
SAP 
MDI 
N= 45 
N=45 
N=135 
22-64 years
CSII 
SAP
MDI 
N= 120
N=120
N=360
65-80 years 
CSII 
No Minimum 
No minimum 
N=150 
SAP 
MDI 

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Table 3. Randomization 
Treatment at Baseline
Randomization Options
Continuation
CSII 
CSII 
HCL 
HCL 
MDI 
MDI 
HCL 
HCL 
SAP 
SAP 
HCL 
HCL 
Note: Subjects 2-6 years of age will automatically enter the HCL arm at the end of the run-in period 
 
Table 4. Site Enrollment (approximate schedule from Protocol approval) 
Month 
Enrollment 
Timelines
Actual Site Enrollment
(per month) 
Site 
Enrollment 
Timelines
Month 1-48 
April 2017 to March 2021 
37 
Month 49-52 
April 2021 to July 2021 
45 
 
 
Table 5. Subject Enrollment at 2-3 month intervals (approximate schedule from first enrollment) 
Month 
Enrollment 
Timelines 
Actual Month Intervals
Subject 
Enrollment 
Timelines 
Month 1-43 
May 2017 to December 2020 
930 
Month 44 -50 
January 2021 to June 2021 
1080 

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Month 
Enrollment 
Timelines 
Actual Month Intervals
Subject 
Enrollment 
Timelines 
Month 51-56 
July 2021 to December 2021 
1120* 
*1120 subject enrollment to target 1000 subjects who enter the study period 
Table 6. Milestone Table 
Major Milestone 
Estimated time required to achieve milestone 
(approximate schedule from study protocol approval)
Protocol Approval / Device Launch
First site enrolled 
30 days 
First subject enrolled 
70 days 
First subject completed 
15 months 
Last site enrolled 
52 months 
Last subject enrolled
55 months – 57 months (target 54 months) 
Last subject completed 
69 months (or sooner based on last subject enrolled) 
Final report submitted 
75 months 
 
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The study is anticipated to last no longer than 6.5 years from investigational center initiation to completion of 
all data entry and monitoring procedures. The study will target 54 months to complete subject enrollment. 
Subjects can expect to participate for approximately 7-8 months during the run-in period and study period, 
with a 6 month continuation period. 
 

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As remote monitoring may play an important role in the pediatric population, we have added this capability 
with the MiniMed 770G system and are introducing this approved device to enhance subject compliance.  In 
the US and Canada subjects 2-80 years of age will be allowed to transition from the 670G system to the 770G 
system. In Australia, the MiniMed 770G system is investigational for 2-6 years of age. 
 
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None of the devices used in this study contain tissues of animal origin, nor derivatives rendered non-viable. The 
devices do not incorporate, as an integral part, a substance which if used separately, may be considered to be a 
medicinal product as defined in Annex I point 7.4, 1st paragraph of Directive 93/42/EEC. 
The sensor contains human serum albumin. The human serum albumin serves to protect the enzyme in the 
chemistry stack from subsequent processes and layers. Human serum albumin is immobilized via crosslinking 
and is not liable to act on the human body. 
 
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A diverse population of patients with type 1 diabetes will be studied. The study population will have a large 
range for duration of diabetes and glycemic control, as measured by glycosylated hemoglobin (A1C). They will 
be enrolled in the study regardless of their prior diabetes regimen, including using Multiple Daily Injections 
(MDI), Continuous Subcutaneous Insulin Infusion (CSII) or Sensor-Augmented Pump therapy (SAP). 
 

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Table 7. MiniMed 670G System Components* 
Device name 
MDT Model 
number/ part 
number 
US 
Canada 
Europe 
MiniMed 670G Pump (closed loop 
algorithm)  
MMT-1780 
(US) 
 MMT-1781 
(pump) and 
MMT-
1762KCN (kit) 
(Canada) 
MMT-1781 
and MMT-
1782 (Europe) 
Age 7-80: Non-
Investigational 
Age 2-6: 
Investigational  
Licensed (age 
шϳǇĞĂƌƐͿ  
CE marked 
;ĂŐĞшϳǇĞĂƌƐͿ 
Guardian Link (3) Transmitter  
MMT-7811 
Age 7-80: Non-
Investigational 
Age 2-6: 
Investigational  
Licensed (age 
шϳǇĞĂƌƐͿ 
CE marked  
Transmitter Charger
MMT-7715 
Non-
Investigational 
Licensed 
CE marked 
Tester   
MMT-7736L 
Non-
Investigational 
Licensed 
CE marked* 
Guardian Sensor (3)  
MMT-7020 
Age 7-80: Non-
Investigational 
Age 2-6: 
Investigational  
Licensed  
CE marked  
One-Press Serter 
 
MMT-7512 
Non-
Investigational 
Exempt 
CE marked 
CareLink USB 2.4 GHz 
(MMT- 7306)
Non-
Investigational 
Licensed
CE marked
Medtronic CareLink® Personal 
Therapy Management Software  
MMT-7333 
Exempt 
Exempt** 
CE marked 

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Device name
MDT Model 
number/ part 
number 
US
Canada
Europe
Paradigm Reservoir  
MMT-332A 
Cleared 
Licensed  
CE marked 
MiniMed Silhouette Infusion Set  
e.g. MMT-368 
Cleared 
Licensed  
CE marked 
MiniMed Sil Serter  
MMT-385 
Cleared 
Exempt 
CE marked 
MiniMed Quick Set Infusion Set 
e.g. MMT-386
Cleared
Licensed
CE marked
MiniMed Mio Infusion Set
e.g. MMT-923
Cleared
Licensed
CE marked
MiniMed Sure-T Infusion Set 
e.g. MMT-864 
 
Cleared 
 Licensed 
CE marked 
 
MiniMed Quick-Serter  
MMT-305 
Cleared 
Exempt 
CE marked 
Ketone Meter  
 
Cleared 
Licensed 
CE marked 
Contour Next Link 2.4 by Ascencia 
Meter 
MMT-1152 or 
MMT-1352 
(US) 
MMT-1151 
(Canada)  
MMT-1151 
and MMT-
1152 (Europe) 
Age 7-80: Non-
Investigational 
Age 2-6: 
Investigational 
Licensed 
CE marked 
* For detailed information on the characteristics materials, see device instructions for use.
** Determined to be a Medical Device Data System by the Medical Device Directorate and as such not subject 
to the Canadian Medical Device Regulations. 
 
Table 8 MiniMed 770G System Components* 
Device name
MDT Model 
number/part number 
US
Canada
Australia
New Zealand
MiniMed 770G 
Pump (closed 
loop algorithm)  
MMT-1890 (US Kit) 
MMT-1880 (US Pump)
MMT-1881 (Canada 
Pump) 
MMT-1891KCN, MMT-
Age 2-80: Non-
Investigational  
Licensed (age 
2-80 years) 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 

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Device name
MDT Model 
number/part number
US 
Canada 
Australia 
New Zealand
1891CRP (Canada Kit) 
Guardian Link 
(3) Transmitter  
MMT-7911 (US GST5C) 
MMT-7910 (US GST5C 
Kit) 
MMT-7911 (Canada 
Transmitter) 
MMT-7910W4, MMT-
7911WW (Canada Kit) 
Age 2-80: Non-
Investigational 
Licensed (age 
2-80 years) 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
Accu-Chek Guide 
Link Meter Blood 
Glucose 
Monitoring 
System 
08116083022 (US) 
08109222001 (Canada) 
Age 2-80: Non-
Investigational 
Licensed (age 
2-80 years) 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
Transmitter 
Charger 
MMT-7715
Non-
Investigational 
Licensed 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
Tester  
MMT-7736L
Non-
Investigational
Licensed
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
Guardian Sensor 
(3)  
MMT-7020  
Non-
Investigational 
Licensed  
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
One-Press Serter 
MMT-7512
Non-
Investigational  
Exempt 
Age 2-6: 
Investigational
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
Blue adapter  
ACC-1003911 
Not a medical 
device  
N/A 
N/A 
N/A 
Medtronic 
Mobile 
Application
MT-6104 (iOS) 
MMT-6103 (Android)
Class II Exempt  
Exempt** 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational

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Device name
MDT Model 
number/part number
US 
Canada 
Australia 
New Zealand
CareLink 
Connect 
Application 
MMT-6114 (iOS) 
MMT-6113 (Android) 
Class II Exempt  
Exempt** 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
Medtronic 
CareLink® Clinical 
Software 
MMT-7338 
Class I Exempt 
Exempt** 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
Paradigm 
Reservoir  
MMT-332A
Cleared
Licensed 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
MiniMed 
Silhouette 
Infusion Set  
MMT-368 
Cleared 
Licensed 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
MiniMed Sil 
Serter 
MMT-385 
Cleared 
Exempt 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
MiniMed Quick 
Set Infusion Set  
eMMT-386
Cleared
Licensed 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
MiniMed Mio 
Infusion Set 
MMT-923 
Cleared 
Licensed 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
MiniMed Sure-T 
Infusion Set 
MMT-864 
Cleared 
Licensed 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
MiniMed Quick-
Serter  
MMT-305
Cleared
Exempt 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 

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Device name
MDT Model 
number/part number
US 
Canada 
Australia 
New Zealand
Ketone Meter  
HMS – Ketone Meter 
Cleared 
Licensed 
Age 2-6: 
Investigational 
Age 7-80: Non-
Investigational 
Age 2-80: Non-
Investigational 
* For detailed information on the characteristics materials, see device instructions for use. 
** Determined to be a Medical Device Data System by the Medical Device Directorate and as such not subject 
to the Canadian Medical Device Regulations. 
 
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The MiniMed 670G Insulin Pump is capable of continuous insulin delivery, at set and variable rates, for the 
management of diabetes mellitus in persons requiring insulin.  When used with the CGM components 
(Guardian Sensor (3), Guardian Link (3) Transmitter), the pump system is capable of continuous or periodic 
monitoring of glucose levels in the interstitial fluid under the skin and detection of possible low or high blood 
glucose episodes.  The pump also displays continuous glucose values, storing this data so that it can be 
retrospectively analyzed to track patterns and improve diabetes management. These features are similar to the 
commercially available Medtronic sensor-enabled system (e.g. MiniMed 530G System (P120010) in the US, 
MiniMed 640G and Veo System OUS, which has the threshold suspend feature). 
The MiniMed 670G Insulin Pump also includes the closed loop algorithm as part of the SmartGuard™ collection 
of features that may be enabled by the user. SmartGuard is comprised of Manual Mode Low Management, 
which includes the suspend on low feature (suspends insulin delivery when a pre-set low SG threshold is 
reached), the suspend before low feature (enables insulin to suspend 30 minutes before a pre-set low SG 
threshold is reached) and Auto Mode (hybrid closed loop) feature. The Auto Mode and Manual Mode -Low 
Management features will not be active at the same time. 
The pump may also be used as a simple pump without CGM or as a sensor augmented pump without the 
SmartGuard features.   
When Auto Mode is enabled on the MiniMed 670G insulin pump, the sensor glucose (SG) values received from 
the Guardian Link (3) Transmitter by the insulin pump will be used to automatically calculate the insulin 
dose.  It will then deliver insulin to the patient, at five minute intervals, to achieve glycemic control. 
With the HCL system, subjects must still deliver bolus insulin for meals as calculated by the insulin to 
carbohydrate ratio. This ratio is determined by the Health Care Professional (HCP)/patient.  In addition, the 

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setting for active insulin must be programmed.  Basal rates are set for period of open loop therapy.
When Auto Mode is not enabled, the user may enable the Low Management feature. Here, basal rate delivery 
will be suspended either when the SG reached a programmed low threshold (Suspend on Low) or before the 
SGV has reached the programmed low threshold (Suspend before Low).  
 
Figure 3. MiniMed 670G Insulin Pump 
 
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The MiniMed 770G Insulin Pump is equivalent in function to the MiniMed 670G insulin pump, with the 
exception of telemetry. While the MiniMed 670G insulin pump communicates on the basis of Tel-D (telemetry-
diabetes) radio frequency (RF) technology, the MiniMed 770G pump contains BLE (Bluetooth Low Energy) RF 
communication, which allows for connectivity to patients’ smartphones, CGM transmitter and an BLE RF 
enabled blood glucose meter.  
The pump is capable of continuous insulin delivery, at set and variable rates, for the management of diabetes 
mellitus in persons requiring insulin.  When used with the CGM components (Guardian Sensor (3), Guardian 
Link (3) Transmitter), the pump system is capable of continuous or periodic monitoring of glucose levels in the 
interstitial fluid under the skin and detection of possible low or high blood glucose episodes. The pump also 
displays continuous glucose values, storing this data so that it can be retrospectively analyzed to track patterns 
and improve diabetes management. These features are similar to the commercially available Medtronic 
sensor-enabled system (e.g. MiniMed 530G System (P120010) in the US, MiniMed 640G and Veo System OUS, 
which has the threshold suspend feature). 
The MiniMed 770G Insulin Pump also includes the closed loop algorithm as part of the SmartGuard™ 
technology collection of features that may be enabled by the user. SmartGuard is comprised of Manual Mode 

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Low Management, which includes the suspend on low feature (suspends insulin delivery when a pre-set low SG 
threshold is reached), the suspend before low feature (enables insulin to suspend 30 minutes before a pre-set 
low SG threshold is reached) and Auto Mode (hybrid closed loop) feature. The Auto Mode and Manual Mode -
Low Management features will not be active at the same time. 
The pump may also be used as a pump without CGM or as a sensor augmented pump without the SmartGuard 
features.   
When Auto Mode is enabled on the MiniMed 770G insulin pump, the sensor glucose (SG) values received from 
the Guardian Link (3) Transmitter by the insulin pump will be used to automatically calculate the insulin 
dose.  It will then deliver insulin to the patient, at five minute intervals, to achieve glycemic control. 
With this system, users must still deliver bolus insulin for meals as calculated by the insulin to carbohydrate 
ratio. This ratio is determined by the Health Care Professional (HCP)/patient.  In addition, the setting for active 
insulin must be programmed.  Basal rates are set for period of open loop therapy. 
When Auto Mode is not enabled, the user may enable the Low Management feature. Here, basal rate delivery 
will be suspended either when the SG reached a programmed low threshold (Suspend on Low) or before the 
SG has reached the programmed low threshold (Suspend before Low). 

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The Guardian Sensor (3) , referred to as Guardian Sensor (3) in this protocol, is a product that contains a 
microelectrode with a thin coating of glucose oxidase beneath several layers of biocompatible membrane. The 
sensor represents the next generation in the Enlite sensor family with design changes in the engineering 
reports for improved accuracy. It is intended to penetrate the skin at a 90-degree angle and is shorter and 
thinner than the previous generation of MiniMed sensors. An introducer needle penetrates the skin surface 
and provides support for the sensor microelectrode during insertion. The electrode tubing maintains the 
electrode structure by providing support during and after subcutaneous insertion. The sensor continuously 
converts small amounts of glucose from the subject’s interstitial fluid into an electronic signal that is received 
by a transmitter or recorder, the strength of which is proportional to the amount of glucose present in the 
blood. The electrode is composed of embedding, signal-conducting and insulating layers. 

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The One-Press Serter , referred to as the Serter (Figure 4) in this protocol, is an insertion device that is used to 

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ensure correct placement of the Guardian Sensor (3) into the user’s subcutaneous tissue. Insertion is triggered 
when the two spring loaded buttons on the sides of the Serter are pressed simultaneously. The Serter is 
intended as a single patient, non-sterile, multi-use device.   
 
Figure 4. One-Press Serter and Guardian Sensor (3) 
 
 
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The Guardian Link (3) Transmitter has the same housing and sensor interface as the MiniLink transmitter. 
However, the internal electronics and firmware of the Guardian Link (3) Transmitter are new. Like the MiniLink 
transmitter, the Guardian Link (3) Transmitter reads the electronic signal generated by the sensor. In addition, 
the transmitter contains a custom Application Specific Integrated Circuit (ASIC), which enables Electrochemical 
Impedance Spectroscopy (EIS). The EIS measurements are used as diagnostics for the sensor, which are 
incorporated into the sensor calibration logic.  
In addition, the transmitter also contains the sensor calibration algorithm which converts the sensor signal to a 
SGV using calibration blood glucose values from a meter relayed to the transmitter through the pump. The 
transmitter transmits the calculated glucose data to the pump via RF technology.  The new algorithm is 
designed to improve and optimize performance when paired with the Guardian Sensor (3). Some elements of 
the new calibration logic include prompting the user to calibrate when needed, referred to as “Smart Cal,” 
instead of strictly scheduled time-based calibration requirements.  
 
 

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Figure 5.  Transmitter and Transmitter Charger
 
 
 
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The Transmitter Charger is used to recharge the Guardian Link (3) Transmitter as needed. A fully charged 
battery provides up to 7 days of Guardian Link (3) Transmitter use. The system includes a battery charger that 
will recharge the device according to the user guide.  
 
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The Tester operates as a sensor simulator creating signal current at a level that is within the range of an in-vivo 
sensor during normal operation.
 
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A CONTOUR Next Link by Ascencia RF-Enabled Blood Glucose Meter, referred to as the Study Meter 
throughout protocol, will be provided to study participants for use with the MiniMed 670G Insulin Pump. The 
meter measures a subject’s capillary blood glucose level using the CONTOUR NEXT Strips by Ascencia, which is 
then used to calibrate the pump. The MiniMed 670G Insulin Pump uses the calibration point in the real-time 
algorithm which calculates the SGVs that are displayed to the subject.  The result of the finger stick (capillary 
SMBG) reading performed is entered into the MiniMed 670G Insulin Pump and can be stored in its memory as 
a glucose point. The MiniMed 670G Insulin Pump asks the user every time if the user wants to use the linked 
meter BG for calibration. If yes is selected, the glucose value will be stored in memory as a calibration point. 
This meter has a remote bolus feature that will not be operational during the closed loop system.  

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The Accu-Chek  Guide Link Meter Blood Glucose Monitoring System for use with the 770G system is comprised 
of the Accu-Chek Guide Link Meter and Accu-Chek Guide Link test strips. This Blood Glucose Monitoring System 
is intended to quantitatively measure glucose in fresh capillary whole blood from the fingertip, palm, and 
upper arm as an aid in monitoring the effectiveness of glucose control. The Accu-Chek Guide Blood Glucose 
Monitoring System is intended for in vitro diagnostic single-patient use by people with diabetes. Transmission 
of data is via Bluetooth Low Energy. 
 
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Medtronic CareLink® Personal For Clinical Research Therapy Management Software for Diabetes and CareLink® 
Clinical are both internet-based software systems which allow the device data to be viewed and easily 
evaluated by the subject and his/her physician. A PC is used to access the Medtronic CareLink®  system via the 
Internet, which then allows subjects and investigational center staff to upload data from Medtronic MiniMed 
insulin pumps and a range of system-supported, third-party BG meters. CareLink® Personal For Clinical 
Research Therapy Management Software for Diabetes, the clinical support version of Medtronic CareLink® 
Personal software, and the CareLink® Clinical allows retrospective review of device data and was developed for 
use by the investigational center staff and subjects. The CareLink®  Clinical software allows the investigational 
center staff to manage, create, and link the subject’s account. For the purposes of this study, all references to 
CareLink®  Personal For Clinical Research software in this document relate to the clinical support version of 
Medtronic CareLink® Personal Therapy Management Software for Diabetes. The data contained in CareLink® 
Personal For Clinical Research software and CareLink® Clinical software is accessible to users using a standard 
browser, i.e., Microsoft® Internet Explorer, on an Internet enabled PC.  
The CareLink® Personal For Clinical Research software and CareLink® Clinical software use standard Transport 
Layer Security (TLS) technology. TLS transmission protocol invokes encryption on both ends of the 
transmissions and is the standard for all security-based systems. The encryption remains in effect whether the 
data is moving to and from the client and server in the United States, or to and from a client in another country 
to the United States. The data is secure behind a three-tier industry standard architecture, which places the 
database behind three different firewalls, where each firewall separates a tier: 
x
The internet to the web server; 

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x
Web server to the application server; 
x
Application server to the database server. 
The CareLink® Clinical software supports both Bluetooth® Low Energy pumps and non- Bluetooth® Low Energy 
pumps, while the CareLink® Personal For Clinical Research software only support non- Bluetooth® Low Energy 
pumps.
 
&DUH/LQN86%*+]
The CareLink USB is an accessory to the CareLink Personal Therapy Management Software that facilitates 
wireless communication between a personal computer and devices employing the Medtronic proprietary RF 
technology. The device is only intended to transfer data, it does not have any diagnostic or therapeutic 
function/benefit. 
 
%OXH$GDSWHU
The Blue Adapter is an optional accessory with Bluetooth technology that facilitates the communication 
between a personal computer and the insulin pump, via BLE wireless communication protocol. The Blue 
Adapter is an off-the-shelf non-medical device intended to transfer data to CareLink Server. The Blue Adapter 
does not have any computation, diagnostic, monitoring or therapeutic function/benefit. Medtronic will provide 
the Blue Adapter as a convenience to customers as an alternative for patients without mobile devices. 
 
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The MiniMed Mobile Application is an optional accessory to the MiniMed 770G insulin pump and provides a 
secondary display and passive monitoring of pump data for users with compatible electronic devices. The 
Mobile App is available for both iOS and Android platforms. 
 
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The CareLink Connect App is an optional accessory which receives pump data wirelessly from the CareLink 
server. The CareLink Connect App provides a mirroring display of the MiniMed Mobile App screen, for remote 

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monitoring by a care partner (e.g., care giver or health care provider). The CareLink Connect App is not 
designed to monitor the performance of the insulin pump nor for direct monitoring of pump data. As a 
mirroring display, the app can provide notifications to the care partner via the user interface. 
 
.HWRQH0HWHU
The Ketone Meter measures both blood glucose (sugar) and blood ß-Ketone. In this study, the meter will only 
be used to collect ß-Ketone data, which will be collected for reporting and review (see 
Investigator/Coordinator binder for details) and as described in the body of this study protocol. This particular 
meter will be used because it is the only commercially available meter which allows quantification of blood ß-
Ketone levels and is the preferred patient method of testing over urine testing. 
Note: In the event the blood ketone meter is not used to collect ketone values, urine ketones must be 
measured and entered into CareLink instead.  
 
,QIXVLRQVHWV
x
Quick Set Infusion sets 
x
Silhouette Infusion sets 
x
Sure-T Infusion sets 
x
Mio Infusion sets 
 
Note: Medtronic may incorporate additional infusion sets into this clinical study as they become commercially 
available. Instructions for the devices used in this study are provided in their respective manuals. All infusion 
sets provided to subjects must be approved or cleared for use with MiniMed Pump for Humalog and Novolog. 
 
 5HVHUYRLUV
Patients are instructed to change their reservoir every 2 to 3 days. All reservoirs provided to subjects must be 
approved or cleared for use with the MiniMed pump for Humalog and Novolog. 
 

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The following infusion set type has a corresponding serter device.
x
Quick-Serter™ (MMT-305)
x
Sil-Serter™ (MMT-385)
The devices are indicated for single patient multi use, i.e. a patient uses the same serter every 2 to 3 days to 
insert a new infusion set as described in the IFU. All infusion set serter devices provided to subjects must be 
approved or cleared for use with the MiniMed pump for Humalog and Novolog. 
 
,QVXOLQ
Patients will use their own rapid-acting analogue insulin (novolog, humalog) during this study. 
 
6XSSOLHV
Study pump, study meters and sensors are supplied with additional, commercially available materials i.e., 
reservoirs, infusion sets, alcohol wipes, meter supplies, tape, etc. free of charge.  
 
3DFNDJLQJ
In Europe, all devices will be labeled in accordance with local language requirements.
Labeling for the study devices will be provided under separate cover. Investigational devices will be labeled in 
accordance to their regulatory requirements. 
 
3URGXFW7UDLQLQJ5HTXLUHPHQWV
Training of the investigational center staff on the conduct of the study and system being studied will be 
initiated before the protocol is implemented.  All participating physicians and coordinators will be familiarized 
with the system. Specific investigational center staff will be trained on each of the system’s components. 
Training will contain both lecture and hands-on experience.

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Trained product support personnel may be present at the training and study follow-up visits to provide technical 
support.  
Trained personnel may also give technical support via the local support service, e.g. Medtronic 24HR Technical 
Support.  
 
3URGXFW5HFHLSWDQG7UDFNLQJ
Upon receipt of the study devices, investigational center staff take inventory of the shipment, making sure that 
information on the packing slips/invoices matches exactly the contents of the containers, as applicable, 
including: 
x
Ship To
x
Reference Number
x
Device Type
x
Quantity  
x
Quantity per package  
x
Lot number (where applicable) 
x
Serial number (where applicable) 
 
Ensure that devices and supplies received have not reached their expiration date.  
Sign and date the packing slips/invoices, noting any discrepancies, and file in appropriate study binder. 
Notify the study Monitor of any discrepancies. 
Enter the study device information on the appropriate eCRF in the study database. 
 
'HYLFH'LVEXUVHPHQW
Each time a study device is disbursed to a Subject by the Investigator or authorized member of the research 
team, all required eCRF and source documentation will be completed (see 7DEOH for details). Documentation 
may include: 

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x
Date of disbursement  
x
Subject ID 
x
Lot number(s)  
x
Serial Number 
x
Reference Number 
x
Amount dispensed 
 
3URGXFW6WRUDJH
Study devices are to be stored in a secure environment with access limited to authorized research personnel. 
Study devices are to be stored in the proper environmental conditions, as identified in the user guide/labeling
 
3URGXFW5HWXUQ
After use by the subject, the investigational center is expected to accept and retain all devices as described in 
Table and store them in a secure environment. If containers/units/devices are missing, document the 
reasons in the eCRF. If discrepancies between amounts used by subjects and amounts expected to be returned 
exist, document the reasons in the eCRF. 
All devices, as described in Table, will be returned by subjects to the investigational center and then to the 
Sponsor. Serialized devices provided to the investigational center may be returned as subjects complete the 
study, at the end of study or upon sponsor request. The quantity received by the investigational center and the 
quantity returned to sponsor should be equal. The investigational center will provide details of the disposition 
of all unreturned serialized devices (excluding the Study Meter and Ketone Meter) in the eCRF.  
Used glucose sensors are not expected to be returned by subjects to the investigational center and therefore 
are not expected to be returned to the sponsor.  Other unused consumable devices (i.e., infusion sets, alcohol 
wipes, Study Meter supplies, tape, etc.), supplies or materials may be returned to the sponsor or retained by 
investigational center for educational purposes only, or may be disposed of properly by the investigational 
center staff.   
Disposable devices and supplies that have been used by a subject will be disposed of properly by the subject or 
the investigational center staff during the conduct of the study. This would include glucose sensors, meter 

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testing strips and supplies, infusion sets and adhesive tape.  
All study devices that were required to be entered into the study database are required to be accounted for as 
described herein prior to return to sponsor or at the end of the study. 
 
3URGXFW$FFRXQWDELOLW\
Good clinical research practice requires that investigators and research teams ensure accurate accountability 
for any investigational device used in a research trial. It is expected that all investigational devices will be used 
in  
the manner intended during the study, that they will be stored under appropriately controlled conditions with 
controlled access and that they will be used only by (on) subjects who have consented to participate in the 
research study. 
Any investigational device being used in clinical research must be strictly accounted for and will not be shipped 
to any site unless all of the necessary approvals (e.g. Regulatory, IRB/EC) have been received. This includes 
keeping records of: 
1. Center receipt and inventory management 
2. Storage  
3. Subject Disbursement   
4. Return (by Subjects and Center) and/or disposal  
During the conduct of the study the investigational center staff will account for, and document, the following: 
 
Table 9. Device Accountability Requirements (U.S. Sites) 
Device 
Site Receipt 
(packing slip 
and eCRF) 
Disbursement to 
Subject (eCRF) 
Device 
Disposition at 
Conclusion of 
Study 
Record 
Device 
Disposition 
(eCRF) 
MiniMed 670G Insulin Pump 
(MMT-1780)
Yes 
Yes 
Return to Sponsor 
Yes 
MiniMed 770G Insulin Pump 
Yes 
Yes
Return to Sponsor
Yes 

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Device 
Site Receipt 
(packing slip 
and eCRF) 
Disbursement to 
Subject (eCRF) 
Device 
Disposition at 
Conclusion of 
Study 
Record 
Device 
Disposition 
(eCRF) 
(MMT-1880)
CONTOUR® NEXT LINK 2.4 by 
Ascencia Blood Glucose 
Meter(MMT-1152 or MMT-
1352)   
Yes 
Yes 
Dispose or return 
unused to Sponsor Yes 
Accu-Chek Guide Link Meter 
Blood Glucose Monitoring 
System (08116083022) 
Yes 
Yes 
Return to Sponsor 
Yes 
Guardian Sensor (3) (MMT-
7020) – for 670G only 
Yes 
Yes 
Dispose or return 
unused to Sponsor Yes 
Guardian Sensor (3) (MMT-
7020) – for 770G only 
Yes
No
Dispose or return 
unused to Sponsor No
One-Press Serter (MMT-7512) 
No 
No 
Dispose or return 
unused to Sponsor
No 
Guardian Link (3) Transmitter 
(MMT-7811) for 670G only 
Yes 
Yes 
Return to Sponsor 
Yes 
Guardian Link (3) Transmitter 
(MMT-7910) for 770G only 
Yes
Yes
Return to Sponsor
Yes
Tester (MMT-7736L) 
No 
No 
Dispose or return 
unused to Sponsor  No 
Transmitter Charger (MMT-
7715) 
No 
No 
Dispose or return 
unused to Sponsor  No 
CareLink USB 2.4 GHz (MMT-
7306)
No 
No 
Dispose or return 
unused to Sponsor No 
Ketone Meter 
No 
No 
Dispose or return 
unused to Sponsor  No 

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Devices may be combined and distributed in kits. 
 
Table 10. Device Accountability Requirements (European Sites) 
Device 
Site Receipt 
(packing slip 
and eCRF) 
Disbursement to 
Subject (eCRF)
Device Disposition 
at Conclusion of 
Study 
Record Device 
Disposition 
(eCRF) 
MiniMed 670G Insulin Pump  
(Europe MMT-1781, and 
MMT-1782) 
Yes 
Yes 
Return to Sponsor 
Yes 
CONTOUR® NEXT LINK 2.4 by 
Ascencia Blood Glucose 
Meter  
(MMT-1352, Europe: MMT-
1151, MMT-1152)  
Yes 
Yes 
Dispose or return 
unused to Sponsor 
Yes 
Guardian Sensor (3) (MMT-
7020) 
No
No
Dispose or return 
unused to Sponsor 
No
Guardian Link (3) 
Transmitter (MMT-7811)
Yes 
Yes 
Return to Sponsor 
Yes 
Tester (MMT-7736L) 
No 
No 
Dispose or return 
unused to Sponsor 
No 
One-Press Serter  
(MMT-7512) 
No 
No 
Dispose or return 
unused to Sponsor 
No 
Transmitter Charger (MMT-
7715) 
No 
No 
Dispose or return 
unused to Sponsor 
No 
CareLink USB 2.4 GHz 
(MMT-7306) 
No 
No 
Dispose or return 
unused to Sponsor 
No 
Ketone Meter 
No 
No  
Dispose  
No 
Devices may be combined and distributed in kits.  
 

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Table 11. Device Accountability Requirements (Canadian Sites)
Device 
Site Receipt 
(packing slip and 
eCRF) 
Disbursement 
to Subject 
(eCRF) 
Device Disposition 
at Conclusion of 
Study 
Record 
Device 
Disposition 
(eCRF) 
MiniMed 670G Insulin Pump 
(Canada MMT-1781 (pump))  
Yes 
Yes 
Return to Sponsor 
Yes 
MiniMed 770G Insulin Pump 
(Canada MMT-1881) 
Yes 
Yes 
Return to Sponsor 
Yes 
CONTOUR® NEXT LINK 2.4 by 
Ascencia Blood Glucose Meter 
(Canada MMT-1351 or MMT-
1352) 
Yes 
Yes 
Dispose or return 
unused to Sponsor 
Yes 
Accu-Chek Guide Link Meter 
Blood Glucose Monitoring 
System (08109222001) 
Yes 
Yes 
Return to Sponsor 
Yes 
Guardian Sensor (3) (MMT-
7020) – for 670G only 
Yes 
Yes 
Dispose or return 
unused to Sponsor 
Yes 
Guardian Sensor (3) (MMT-
7020) – for 770G only 
Yes 
No 
Dispose or return 
unused to Sponsor 
No 
Guardian Link (3) Transmitter 
(MMT-7811WW), 670G only. 
Yes 
Yes 
Return to Sponsor 
Yes 
Guardian Link (3) Transmitter 
(MMT-7911) 770G only 
Yes
Yes 
Return to Sponsor 
Yes 
Tester 
(MMT-7736L)
No 
No 
Dispose or return 
unused to Sponsor 
No 
One-Press Serter 
(MMT-7512) 
No 
No 
Dispose or return 
unused to Sponsor 
No 
Transmitter Charger  
(MMT-7715) 
No 
No 
Dispose or return 
unused to Sponsor 
No 

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Device 
Site Receipt 
(packing slip and 
eCRF) 
Disbursement 
to Subject 
(eCRF) 
Device Disposition 
at Conclusion of 
Study 
Record 
Device 
Disposition 
(eCRF) 
CareLink USB 2.4 GHz (MMT-
7306) 
No 
No 
Dispose or return 
unused to Sponsor 
No 
Ketone Meter 
No 
No 
Dispose 
No 
Devices may be combined and distributed in kits. 
 
Table 12. Device Accountability Requirements (Australian Sites) 
Device 
Site Receipt 
(packing slip and 
eCRF) 
Disbursement 
to Subject 
(eCRF) 
Device Disposition 
at Conclusion of 
Study 
Record 
Device 
Disposition 
(eCRF) 
MiniMed 770G Insulin Pump 
(MMT-1881, MMT-1891) 
Yes
Yes 
Return to Sponsor 
Yes 
Accu-Chek Guide Link Meter 
Blood Glucose Monitoring 
System (08116113186M) 
Yes
Yes 
Return to Sponsor 
Yes 
Guardian Sensor (3)  
(MMT-7020C5) – for 770G 
only 
Yes 
No 
Dispose or return 
unused to Sponsor 
No 
Guardian Link (3) Transmitter 
(MMT-7910WS, MMT-7911W) 
770G only 
Yes 
Yes 
Return to Sponsor 
Yes 
Tester 
(MMT-7736L) 
No 
No 
Dispose or return 
unused to Sponsor 
No 
One-Press Serter  
(MMT-7512) 
No 
No 
Dispose or return 
unused to Sponsor 
No 

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Device 
Site Receipt 
(packing slip and 
eCRF) 
Disbursement 
to Subject 
(eCRF) 
Device Disposition 
at Conclusion of 
Study 
Record 
Device 
Disposition 
(eCRF) 
Transmitter Charger  
(MMT-7715) 
No 
No 
Dispose or return 
unused to Sponsor 
No 
CareLink USB 2.4 GHz 
(Austalia, New Zealand) 
No 
No 
Dispose or return 
unused to Sponsor 
No 
Ketone Meter 
No 
No
Dispose  
No 
Devices may be combined and distributed in kits. 
 
Table 13. Device Accountability Requirements (New Zealand Sites) 
Device 
Site Receipt 
(packing slip and 
eCRF) 
Disbursement 
to Subject 
(eCRF) 
Device Disposition 
at Conclusion of 
Study 
Record 
Device 
Disposition 
(eCRF) 
MiniMed 770G Insulin Pump 
(MMT-1881, MMT-1891)
Yes 
Yes 
Return to Sponsor 
Yes 
Accu-Chek Guide Link Meter 
Blood Glucose Monitoring 
System (08116113186M) 
Yes 
Yes 
Return to Sponsor 
Yes 
Guardian Sensor (3)  
(MMT-7020C5) – for 770G 
only 
Yes 
No 
Dispose or return 
unused to Sponsor 
No 
Guardian Link (3) Transmitter 
(MMT-7910WS, MMT-7911W) 
770G only 
Yes
Yes 
Return to Sponsor 
Yes 
Tester 
(MMT-7736L) 
No 
No 
Dispose or return 
unused to Sponsor 
No 

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Device 
Site Receipt 
(packing slip and 
eCRF)
Disbursement 
to Subject 
(eCRF)
Device Disposition 
at Conclusion of 
Study
Record 
Device 
Disposition 
(eCRF) 
One-Press Serter  
(MMT-7512) 
No 
No 
Dispose or return 
unused to Sponsor 
No 
Transmitter Charger  
(MMT-7715) 
No 
No 
Dispose or return 
unused to Sponsor 
No 
CareLink USB 2.4 GHz (ACC-
1003911D)
No 
No 
Dispose or return 
unused to Sponsor 
No 
Ketone Meter 
No 
No
Dispose  
No 
Devices may be combined and distributed in kits. 
 
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 6WXG\3RSXODWLRQ
A diverse population of patients with type 1 diabetes will be studied. The study population will have a large 
range for duration of diabetes and glycemic control, as measured by glycosylated hemoglobin (A1C). 
 
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6XEMHFW(QUROOPHQW
Subjects will be considered enrolled in the study upon signing the Informed Consent/Assent form(s). 
 
 ,QFOXVLRQ&ULWHULD
Subjects will be considered for enrollment in the study if they meet all of the following criteria:
1. Subject is age 2-80 years at time of screening 

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a.
US, Canada, Australia and New Zealand: Subjects 2-80 years of age will be allowed to enroll in the 
post approval study.  
b. Europe: Only sƵďũĞĐƚƐшϳǇĞĂƌƐŽĨĂŐĞĂƌĞĂůůŽǁĞĚƚŽĞŶƌŽůůŝŶƚŚĞƉŽƐƚ-market study. 
2. Subjects who are 2-21 years are determined by the investigator to have the appropriate, requisite 
support (family, caregiver or social network) to successfully participate in this study 
3. Subject must have a minimum daily insulin requirement (Total Daily Dose) of equal to or greater than 8 
units/day  
4. Subjects who are determined by the investigator to be psychologically sound in order to successfully 
participate in this study. 
5. Subject has been diagnosed with type 1 diabetes for at least three months  
Note: Determination of classification for diabetes will be based on American Diabetes Association 
Clinical Practice Guidelines accounting for several patient characteristics such as:  age of onset, 
patient’s weight or BMI, history of diabetic ketoacidosis, history of therapy management, if available 
in the medical records.   
6. Subject must be on one of the following management therapies:  
x
Multiple daily injections defined by use of rapid analogue with meals and approved long acting 
analogue (e.g. detemir or glargine) with or without CGM 
x
Insulin pump therapy with or without CGM 
7. ^ƵďũĞĐƚŝƐǁŝůůŝŶŐƚŽƉĞƌĨŽƌŵшϰĨŝŶŐĞƌƐƚŝĐŬďůŽŽĚŐůƵĐŽƐĞŵĞĂƐƵƌĞŵĞŶƚƐĚĂŝůǇ 
8. Subject is willing to perform required study procedures  
9. Subject is willing to wear the system continuously throughout the study for at least 80% of the time 
10.Subject is willing to upload data at least weekly from the study pump/meter, must have Internet access 
and a computer system that meets the requirements for uploading the study pump/meter for data 
collection 
11.Subject must be willing to use the study glucose meter system (i.e. along with study meter strips).    
12.If subject has celiac disease, it has been adequately treated as determined by the investigator 
13.Subject with the diagnosis of myocardial infarction, unstable angina, coronary artery bypass surgery, 
coronary artery stenting, transient ischemic attack, cerebrovascular accident, angina, congestive heart 
failure, ventricular rhythm disturbances or thromboembolic disease, within 1 year of screening, will be 
included in the study with the consent of the Investigator  

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14. Subject is willing to take one of the following insulins and can financially afford to use either of the 2 
insulin preparations throughout the course of the study (i.e. co-payments for insulin with insurance or 
able to pay full amount) 
a. Humalog® (insulin lispro injection) 
b. NovoLog® (insulin aspart) 
 
 ([FOXVLRQ&ULWHULD
1. Subject participated in any Closed Loop study in the past 
2.
Subject is unable to tolerate tape adhesive in the area of sensor placement 
3. Subject has any unresolved adverse skin condition in the area of sensor placement (e.g., psoriasis, rash, 
Staphylococcus infection) or area of infusion set placement 
4. Women of child-bearing potential who have a positive pregnancy test at screening or plan to become 
pregnant during the course of the study  
5. Subject is being treated for hyperthyroidism at time of screening 
6. Subject has an abnormality (out of reference range) in thyroid-stimulating hormone (TSH) at time of 
screening visit. TSH is not required for subjects 2-13 years of age.
7. Subject has taken any oral, injectable, or IV glucocorticoids within 8 weeks from time of screening visit, 
or plans to take any oral, injectable, or IV glucocorticoids during the course of the study. 
8. Subject is actively participating in an investigational study (drug or device) wherein he/she has received 
treatment from an investigational study drug or investigational study device in the last 2 weeks 
9. Subject is currently abusing illicit drugs or marijuana 
10. Subject is currently abusing prescription drugs   
11. Subject is currently abusing alcohol 
12. Subject is using pramlintide (Symlin), SGLT2 inhibitors, GLP agonists, biguanides, DPP-4 inhibitors or 
sulfonylureas at time of screening  
13.   Subject is using hydroxyurea at the time of screening or plans to use it during the study 
14. Subject has a history of visual impairment which would not allow subject to participate in the study 
and perform all study procedures safely, as determined by the investigator 

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15. Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or 
erythropoietin within 3 months prior to time of screening  
16. Subject plans to receive red blood cell transfusion or erythropoietin over the course of study 
participation  
17. Subject diagnosed with current moderate to severe eating disorder such as anorexia or bulimia 
18. Subject has been diagnosed with chronic kidney disease requiring dialysis or resulting in chronic 
anemia  
19. Subjects who are currently being actively treated for cancer. 
20. Subject who is designated as a research staff member for this study 
 
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During the activation process (prior to subject enrollment), Medtronic will train investigational center staff 
using the sponsor training protocol.  If new members join the study investigational center team, they will 
receive training on the applicable study requirements relevant to their role before contributing to the study. 
Prior to performing study-related activities, all training requirements shall be fulfilled. 
 
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Run-In Period Synopsis (Run-in Visits 1-3) 
The purpose of the run-in period is to ensure that study subjects are introduced to study devices and to 
provide blinded CGM data. Subjects will be trained on CGM use and blinded CGM will be used to collect 

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data with each subject’s existing diabetes therapy. There is a window of 60 days from the end of Visit 1 
to the end of Visit 3 during which time subjects should complete run-in. Subjects will be started on the 
study pump at Visit 3.  
x
Devices Worn:   
R Medtronic CGM (blinded) only 
R Depending on age group, sensor is self-inserted by subject or inserted with assistance 
R
Existing Therapy

Study Period Synopsis
Overview:  
 
The study period is  6 months Subjects will be randomized at the start the study period into 2 arms:  
x
HCL Arm: Auto Mode feature on the study pump  turned ON  
x
Control Arm: Continue with own therapy for 6 months  
 
R CSII Cohort: The CSII Cohort will use the MiniMed  Pump without Real Time CGM during 
the 6 month study period. Blinded CGM (Guardian Link (3) Transmitter and Guardian 
Sensor (3)) will only be worn at baseline, 3 months, and 6 months (two weeks of sensors 
use)
R MDI Cohort: The Multiple Daily Injection (MDI) Cohort will remain on MDI therapy with 
subjects using their own insulin for 6 months during the study period. Blinded CGM 
(Guardian Link (3) transmitter and Guardian Sensor (3)) will only be worn at baseline, 3 
months, and 6 months (two weeks of sensors use).  
MDI subjects who are currently using CGM, i.e. Dexcom or Medtronic Guardian Connect 

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or who are currently using a SMBG alternative, i.e. Libre, will be allowed to enroll in the 
study and continue using their own device. There will be N=100 
R SAP Cohort: The Sensor Augmented Pump (SAP) Cohort will use the MiniMed Pump 
(SAP without Low Management Suspend on Low, Low Management Suspend before low 
or Auto Mode) with Real Time CGM for the 6 month study period  
R
Note: Subjects 2-6 years of age will automatically enter the HCL arm at the end of the 
run-in period
 
Study Period Device Procedures for HCL Arm
 
x
Devices Worn:   
R
MiniMed Pump 
R Depending on randomization and age group, sensor is self-inserted by subject or 
inserted with assistance  
x
Calibration Requirements with Study Meter:   
R Approximately 30 minutes to 2 hours after the Guardian Sensor (3) is initialized, the 
Study Pump will alert the user to enter meter BGs to perform initial calibration.    
R After the first calibration, the user must calibrate the Guardian Sensor (3) with the study 
meter within 6 hours of the first calibration.   
R
The user must calibrate with the study meter when prompted by the study pump via the 
Smart Cal feature 
R
The user must calibrate with the study meter every 12 hours after last calibration. 
R Recommend 3-4 calibrations per day with the study meter  
R All BGs used for Auto Mode in the MiniMed Pump system can also be used for sensor 
calibration. However, calibrating during rapid changes (2 or 3 arrows) may temporarily 
decrease sensor accuracy. Best practices should be followed for each BG measurement 

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(e.g. clean hands, accepting the calibration on the pump without delay) 
R Other recommendations: 

Always have clean dry fingers when you check your blood glucose 

Only use your fingertips to obtain blood samples for calibration 
 
x
Auto Mode Settings: 
R The Auto Mode (Closed Loop) target for the closed loop algorithm is set at 120 mg/dL 
(6.7 mmol/L).   
R
The Temp target setting in the pump may be used when subject exercises. Temp Target 
Threshold is set to 150 mg/dL (8.3 mmol/L). 
R Alarms that are fixed into system: 

SG at or below 50 mg/dL (2.8 mmol/L) 

When SG at or above 300 mg/dL (16.7 mmol/L) for one hour  

When SG at or above 250 mg/dL (13.9 mmol/L) for 3 hours  
R High Setup limit (i.e. the setting for a high glucose alert threshold based on sensor 
reading) is recommended to be set at 300 mg/dL (16.6 mmol/L)

Alert setting options may be set per investigator discretion 
R
Low Setup limit (i.e. the setting for a low glucose alert threshold based on sensor 
reading) is recommended to be set at 70 mg/dL (4.0 mmol/L) 

Alert setting options may be set per investigator discretion 

For subjects 2-6 years of age, low limit should be set to 80mg/dL (4.4mmol/L) 
and no lower than 70mg/dL(4.0 mmol/L) 

Subjects will be instructed to follow up with an SMBG confirmatory 
measurement when receiving a low alert  
R
Insulin carbohydrate ratios may be adjusted throughout study.  
R Active insulin time may also be adjusted.   

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x
Manual Mode Settings:  
R High Set up Limit recommend to be set at 300 mg/dL (16.6 mmol/L) 

Alert Setting Options may be set per investigator discretion 
R Low Set up Limit recommend to be set at 70 mg/dL (4.0 mmol/L) 

For subjects 2-6 years of age, low limit should be set 80 mg/dL (4.4 mmol/L) and 
no lower than 70 mg/dL(4.0 mmol/L) 

Subjects will be instructed to follow up with an SMBG confirmatory 
measurement when receiving a low alert  
R
Predictive alerts and rate of change alerts are optional
R SmartGuard Manual Mode Low Management features may be used when Auto Mode is 
OFF  
R Consider setting the glucose target in the bolus wizard calculator to the same target as 
the closed loop algorithm, i.e. 120 mg/dL (6.7mmol/L) or higher, based on investigator 
discretion. 
x
Monitoring Method:   
R Study Meter 



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Continuation Period Synopsis 
Overview:  
The continuation period is 6 months in duration. Subjects will use MiniMed Pump System and continue 
from the end of the study period as follows: 
 
Continuation Period Device Procedures
   
x
Devices Worn:   
R MiniMed  Pump with CGM 
R Sensor is self-inserted by subject or inserted with assistance  
x
Calibration Requirements with Study Meter:   
R Approximately 30 minutes to 2 hours after the Guardian Sensor (3) is initialized, the 
Study Pump will alert the user to enter meter BGs to perform initial calibration.    
R After the first calibration, the user must calibrate the Guardian Sensor (3) with the study 
meter within 6 hours of the first calibration.   
R
The user must calibrate with the study meter when prompted by the study pump via the 
Smart Cal feature 
R The user must calibrate with the study meter every 12 hours after last calibration.  
R Recommend 3-4 calibrations per day with the study meter  
R All BGs used for Auto Mode in the MiniMed Pump system can also be used for sensor 
calibration. However, calibrating during rapid changes (2 or 3 arrows) may temporarily 
decrease sensor accuracy. Best practices should be followed for each BG measurement 
(e.g. clean hands, accepting the calibration on the pump without delay)
R Other recommendations: 

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
Always have clean dry fingers when you check your blood glucose 

Only use your fingertips to obtain blood samples for calibration 
 
x
Auto Mode Settings  
R The Auto Mode (Closed Loop) target for the closed loop algorithm is set at 120 mg/dL 
(~6.7 mmol/L).   
R The Temp target setting in the pump may be used when subject exercises. Temp Target 
Threshold is set to 150 mg/dL (~8.3 mmol/L). 
R
Alarms that are fixed into system:

SG at or below 50 mg/dL (~2.8 mmol/L) 

When SG at or above 300 mg/dL (~16.7 mmol/L) for one hour 

When SG at or above 250 mg/dL (~13.9 mmol/L) for 3 hours  
R High Setup limit (i.e. the setting for a high glucose alert threshold based on sensor 
reading) is recommended to be set at 300 mg/dL (16.6 mmol/L) 

Alert setting options may be set per investigator discretion 
R
Low Setup limit (i.e. the setting for a low glucose alert threshold based on sensor 
reading) is recommended to be set at 70 mg/dL (4.0 mmol/L) 

Alert setting options may be set per investigator discretion

For subjects 2-6 years of age, low limit should be set 80mg/dL (4.4 mmol/L) and 
no lower than 70 mg/dL (4.0 mmol/L) 

Subjects will be instructed to follow up with an SMBG confirmatory 
measurement when receiving a low alert  
R Insulin carbohydrate ratios may be adjusted throughout study.   
R Active insulin time may also be adjusted.   
x
Manual Mode Settings: 

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R
High Set up Limit recommend to be set at 300 mg/dL (16.6mmol/L) 

Alert Setting Options may be set per investigator discretion 
R Low Set up Limit recommend to be set at 70 mg/dL (4.0mmol/L) 

For subjects 2-6 years of age, low limit should be set 80mg/dL (4.4 mmol/L) and 
no lower than 70 mg/dL(4.0mmol/L) 

Subjects will be instructed to follow up with an SMBG confirmatory 
measurement when receiving a low alert  
R
Predictive alerts and rate of change alerts are optional
R SmartGuard Manual Mode Low Management features may be used when Auto Mode is 
OFF  
R Consider setting the glucose target in the bolus wizard calculator to the same target as 
the closed loop algorithm, i.e. 120 mg/dL(6.8mmol/L) or higher, based on investigator 
discretion. 
 
x
Monitoring Method:   
Study Meter
 
 
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Refer to the Appendices (Section 24) for the Cohort Visit Tables. 
 
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Each subject’s participation will be comprised of the following scheduled visits listed below over the course of 
approximately 8 months during the run-in period and study period, and for 6 months during the continuation 
period.  

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Telemedicine visits will be allowed to replace office visits if they do not involve collection of blood test 
samples or device related procedures that require staff assistance
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The schedule is planned as follows: 
 
Screening and Run-In Period 
All subjects will complete screening and the run-in period. This period must be completed in 60 days.   
Visit 1: Screening Visit – Consent and Screening 
x
Patients may re-screened once with Sponsor approval 
Visit 2: Begin Run-in Period 
x
Placement of blinded sensor to be worn for 2 Weeks  (each sensor is worn for 7 days) 
x
Study training, including instruction on procedures for wearing blinded CGM (i.e., insertion of sensor)         
Visit 3: Begin MiniMed  Pump (Except MDI Control) 
x
Occurs after 2 week blinded sensor wear, either immediately at the end of sensor wear or suggested to 
be within 14 days.  
x
The run-in period may be repeated a second time with Sponsor approval  
 
Randomization 
At Visit 3 all subjects (CSII, MDI, or SAP Cohort) will be randomized into one of 2 arms:
HCL Arm 
R Note: Patients who are on SAP at baseline will start Medtronic CGM at this visit .  
Control Arm  
R Note: Patients in SAP will receive and be trained on Medtronic CGM if they are randomized to 

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the Control arm to ensure continuity with use of real time CGM.  
 
In the US and Canada, when available, subjects will have the option to begin with MiniMed 770G system or 
exchange their MiniMed 670G for a MiniMed 770G system. 
 
Note: Subjects 2-6 years of age will automatically enter the HCL arm at the end of the run-in period 
 
To schedule Visit 4:  
R For subjects who have been on insulin pump therapy prior to screening for at least 3 months, Visit 4 
should occur 3-30 days after Visit 3  
R For subjects without pump therapy experience, the following should occur: 
x
If randomized to HCL Arm, Visit 4 should occur 14-30 days after Visit 3  
x
If randomized to MDI Control Arm, Visit 4 should occur 1-7 days after Visit 3 
 
The visit schedules for each of these Arms are as follows: 
 
HCL Arm: 
 
Visit 4: Start CGM - Day 0  
R Start CGM with Guardian Sensor (3) (Note: SAP subjects will have already started CGM with Guardian 
Sensor (3) at Visit 3). 
Visit 4A: Follow up Telephone visit - 2-3 days after Visit 4 
Visit 5: Follow up Office Visit -7-21 days after Visit 4  
R Auto Mode is enabled and activated. Investigator sets carbohydrate to insulin ratios and active insulin 
time, and basal rates for open loop periods  
Visit 6A: Follow-up Telephone Visit (option of office visit) – 1 Day after Visit 5 
Visit 6B: Follow-up Telephone Visit (option of office visit) - 2 Days after Visit 5 

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Visit 6C: Follow-up Telephone Visit - 5 Days (± 1 day) after Visit 5
Visit 7A: Follow up Office Visit - 14 Days (± 3 days) after Visit 5  
Visit 7B: Follow-up Telephone Visit - 21 Days (± 3 days) after Visit 5 
Visit 7C: Follow up Office Visit - 30 Days after Visit 5 (± 5 days)   
Visit 7D: Follow-up Telephone Visit - 45 Days (± 7 days) after Visit 5    
Visit 8: Follow up Office Visit - 90 Days after Randomization (± 10 days)  
Visit 9: Follow up Office Visit - 180 Days after Randomization (± 10 days)   
R End of Study Period and Start of Continuation period  
 
Control Arm:
 
a. CSII Cohort 
Visit 4: Day 0:  
R Review pump settings 
Visit 5: Follow up Office Visit 7-21 days after Visit 4 
R Insulin Pump adjustments 
Visit 6A: Follow up Telephone Visit - 1 Day after Visit 5   
Visit 6B: Follow up Telephone Visit - 2 Days after Visit 5   
Visit 6C: Follow up Telephone Visit - 14 Days (± 7 days)  after Visit 5 
Visit 6D: Follow up Office Visit - 30 Days after Visit 5 (± 7 days) 
Visit 6E: Follow-up Telephone Visit - 45 Days (± 7 days) after Visit 5    
Visit 7: Follow up Office Visit - 76 days after Randomization (-14 days) 
R Blinded CGM Start 
R 14 days of sensor wear before 90 Day study period visit. Transmitter is not connected to study pump 
Visit 8A: Follow up Office Visit – 90 Days after Randomization (+14 days) 
R Blinded CGM Return 

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Visit 8B: Follow up Office Visit - 166 days after Randomization (-14 days)
R Blinded CGM Start 
R 14 days of sensor wear before 180 Day study period visit. Transmitter is not connected to study pump 
Visit 9: Follow up Office Visit – 180 Days after Randomization (+14 days) 
R Blinded CGM Return 
R End of Study Period and Start of Continuation period. 
R Start CGM with Guardian Sensor (3) 
 
b. MDI Cohort 
 
Visit 4: Day 0  
Visit 5: Follow up Office Visit 7-21 days after Visit 4 
Visit 6A: Follow up Telephone Visit - 1 Day after Visit 5   
Visit 6B: Follow up Telephone Visit - 2 Days after Visit 5   
Visit 6C: Follow up Telephone Visit - 14 Days (± 5 days)  after Visit 5 
Visit 6D: Follow up Office Visit - 25 Days after Visit 5 (± 5 days) 
Visit 6E: Follow-up Telephone Visit - 35 Days (+1 day) after Visit 5    
Visit 7: Follow up Office Visit - 76 days after Randomization (-2 days) 
R Blinded CGM Start  
R 14 days of sensor wear before 90 Day study period visit.  
Visit 8A: Follow up Office Visit – 90 Days after Randomization (+14 days) 
R Blinded CGM Return 
Visit 8B: Follow up Office Visit - 166 days after Randomization (-14 days) 
R Blinded CGM Start 
R 14 days of sensor wear before 180 Day study period visit.  
Visit 9: Follow up Office Visit – 180 Days after Randomization (+14 days) 

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R
Blinded CGM Return
R End of Study Period and Start of Continuation period. 
R Start study pump  
 
c. SAP Cohort: 
 
Visit 4: Day 0   
Visit 4A: Follow up Telephone visit - 2-3 days after Visit 4 
Visit 5: Follow-up Office Visit - 7-21 days after Visit 4 
R Pump and Sensor adjustments 
Visit 6A: Follow-up Telephone Visit (option of office visit) – 1 Day after Visit 5 
Visit 6B: Follow-up Telephone Visit (option of office visit) - 2 Days after Visit 5  
Visit 6C: Follow-up Telephone Visit 7 days after Visit 5 (+3 days ) 
Visit 7A: Follow-up Telephone Visit - 14 Days after Visit 5 (± 3 days)   
Visit 7B: Follow-up Telephone Visit - 21 Days after Visit 5 (± 3 days)  
Visit 7C: Follow-up Office Visit - 30 Days after Visit 5 (± 5 days) 
Visit 7D: Follow-up Telephone Visit - 45 Days (± 7 days) after Visit 5 
Visit 8: Follow-up Office Visit - 90 Days after Randomization (± 10 days)  
Visit 9: Follow-up Office Visit - 180 Days after Randomization (± 10 days)   
R End of Study Period and Start of Continuation period 
R Auto Mode is enabled and activated. 
 
Continuation Period: 
HCL Arm: 
Visit 10: Follow up Office Visit – 1 to 14 days after Visit 9 
Visit 11: Follow up Office Visit – 15 to 30 days after Visit 9 

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Visit 12: Follow up Office Visit - 270 Days after Randomization (+/- 21 days)
Visit 13: Follow up Office Visit - 365 Days after Randomization (+/- 21 days)  
R End of Continuation Period and End of Study 
 
Control Arm 
a. CSII Cohort: 
Visit 10A: Follow up Telephone visit - 2-3 days after sensor start 
Visit 10B: Follow up Office Visit 7-21 days after Visit 9  
R Auto Mode is enabled and activated. 
Visit 10C: Follow up Telephone Visit  (option of office visit) – 1 Day after Visit 10B 
Visit 10D: Follow up Telephone Visit  (option of office visit) – 2 Days after Visit 10B  
Visit 10E: Follow-up Telephone Visit – 5 Days (± 1 day) after Visit 10B 
Visit 11A: Follow up Office Visit - 14 Days after Visit 10B (±3 days)   
Visit 11B: Follow-up Telephone Visit - 21 Days (±3 days) after Visit 10B 
Visit 11C: Follow up Office Visit - 30 Days after Visit 10B (±5 days)   
Visit 11D: Follow-up Telephone Visit - 45 Days (±7 days) after Visit 10B  
Visit 12: Follow up Office Visit - 270 Days after Randomization (+/- 21 days)  
Visit 13: Follow up Office Visit - 365 Days after Randomization (+/- 21 days)  
R End of Continuation Period and End of Study 
 
b. MDI Cohort: 
Visit 9A: Follow up Office Visit – 14-30 days after Visit 9 
R Start CGM with Guardian Sensor (3)  
R This visit should occur between 14 and 30 days after pump start. 
Visit 10A: Follow up Telephone visit - 2-3 days after sensor start 
Visit 10B: Follow up Office Visit 7-21 days after Visit 9A  

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Patient has been wearing CGM for at least 4 days before enabling Auto Mode
R Auto Mode is enabled and activated. 
Visit 10C: Follow up Telephone Visit  (option of office visit) – 1 Day after Visit 10B 
Visit 10D: Follow up Telephone Visit  (option of office visit) – 2 Days after Visit 10B  
Visit 10E: Follow-up Telephone Visit – 5 Days (± 1 day) after Visit 10B 
Visit 11A: Follow up Office Visit - 14 Days after Visit 10B (±3 days) 
Visit 11B: Follow-up Telephone Visit – 21 Days (± 3 day) after Visit 10B    
Visit 11C: Follow up Office Visit - 30 Days after Visit 10B (±5 days)   
Visit 11D: Follow-up Telephone Visit – 45 Days (± 7 day) after Visit 10B 
Visit 12: Follow up Office Visit - 270 Days after Randomization (+/- 21 days)  
Visit 13: Follow up Office Visit - 365 Days after Randomization (+/- 21 days)  
R End of Continuation Period and End of Study 
 
c. SAP Cohort: 
Visit 10A: Follow up Telephone Visit  (option of office visit) – 1 Day after Visit 9 
Visit 10B: Follow up Telephone Visit  (option of office visit) – 2 Days after Visit 9  
Visit 10C: Follow-up Telephone Visit – 5 Days (± 1 day) after Visit 9 
Visit 11A: Follow up Office Visit - 14 Days after Visit 9 (±3 days)   
Visit 11B:  Follow-up Telephone Visit – 21 Days (± 3 day) after Visit 9 
Visit 11C: Follow up Office Visit - 30 Days after Visit 9 (±5 days)   
Visit 11D: Follow-up Telephone Visit – 45 Days (± 5  day) after Visit 9 
Visit 12: Follow up Office Visit - 270 Days after Randomization (+/- 21 days)  
Visit 13: Follow up Office Visit - 365 Days after Randomization (+/- 21 days)  
R End of Continuation Period and End of Study 

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For detailed data collection and study procedure requirements, see Appendices. 
 6XEMHFW&RQVHQW
Informed Consent/Assent will be obtained in accordance with the Code of Federal Regulations (CFR) Title 21, 
Part 50 (US only) or ISO14155:2011 (Europe, Australia and New Zealand only) or Tri-Council Policy Statement, 
Article 3.2 (Canada only), and applicable local regulations. The Investigator or designee must obtain written 
informed consent/assent before any clinical study related activity takes place. Prior to entry into the study, the 
California Experimental Subject’s Bill of Rights (if applicable), the IRB/EC and Medtronic-approved Informed 
Consent Form (ICF)/Assent form, and the Health Insurance Portability and Accountability Act (HIPAA) 
Authorization Form (US only) will be given to each subject and legally authorized representative (if applicable). 
The Investigator or designee will fully inform the subject of all aspects of the clinical study that are relevant to 
the subject’s decision to participate in the clinical study (e.g. purpose and duration of the study, requirements 
of the subject during the study, potential risks and possible benefits associated with participation in this study.  
Subjects will be considered enrolled in the study upon signing the Informed Consent/Assent form(s). 
All items addressed in the Informed Consent/Assent Form must be explained. The language used shall be as 
non-technical as possible and must be understandable to the subject or parent/guardian. 
The subject or parent/guardian must have ample time and opportunity to read and understand the Informed 
Consent/Assent Forms, to inquire about details of the clinical study, and to decide whether or not to 
participate in the clinical study. All questions about the clinical study should be answered to the satisfaction of 
the subject. 
Neither the investigator, nor the investigation site staff shall coerce or unduly influence a subject or 
parent/guardian to participate or to continue to participate in the clinical study. The informed consent process 
shall not waive or appear to waive the subject’s rights. 
When the subject decides to participate in the clinical study, the California Experimental Subject’s Bill of Rights 
(if applicable), the HIPAA Form (US only) and the Informed Consent/Assent Form must be signed and 
personally dated by the patient or legally authorized representative. In the Europe, Canada, Australia and New 
Zealand the investigator or authorized designee must also countersign the Informed Consent/Assent Form. The 
consenting process must be documented in each subject’s source files. 
After all persons have signed and dated the Informed Consent/Assent Form, the investigator must provide the 
subject with a fully signed and dated copy. 
Medtronic will inform the investigators whenever information becomes available that may be relevant to the 

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subject’s confirmed participation in the clinical study. The investigator or his/her authorized designee should 
inform the subject or parent/guardian in a timely manner.  
Medtronic will revise the written Informed Consent/Assent Form whenever new information becomes 
available that may be relevant to the subject’s confirmed participation in the clinical study. The revised 
information will be sent to the investigator for approval by the IRB/EC. After approval by the IRB/EC, a copy of 
this information must be provided to the participating subjects, and the informed consent process as described 
above needs to be repeated. 
If the ICF is amended during the course of the study, the IRB/EC will determine: 
x
Whether or not active subjects should be re-consented at their next visit and  
x
Whether or not subjects who have completed the study at the time of the amendment should repeat 
the informed consent process.  
Subjects will be informed that qualified personnel from the investigational center, the sponsor (Medtronic), 
agencies such as the FDA/Health Canada/local regulatory authority in Europe, Australia, and New Zealand 
and/or the IRB/EC may have access to clinic records that reveal their identity.  
The investigational center must report the following violations to their IRB/EC: 
x
Failure to obtain informed consent/assent prior to performing one or more study procedures. 
x
Failure to maintain ICFs on file for all subjects who have provided informed consent.  
x
Use of an ICF that has not received approval from the IRB/EC. 
x
Use of an incorrect version of the ICF.   
 
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At the end of the run-in period, subjects are randomized to either the HCL or the Control arm. Depending on 
the type of therapy subjects are using at the start of the study the randomization will be to participate in the 
Hybrid Closed Loop arm or use their own therapy for the duration of the study period. Randomization is 
generated via the RDC study database. 
Note: Subjects 2-6 years of age  will automatically enter the HCL arm at the end of the run-in period.  
 

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The Medtronic Clinical Research Department, in conjunction with the Regulatory Affairs Department, will 
monitor and manage adverse event reporting for the study and determine whether the event requires 
reporting to regulatory agencies. The sponsor will ensure timely Adverse Event reporting to meet regulatory 
requirements.  
Throughout the course of the study, investigational centers will make all efforts to remain alert to possible 
reportable adverse events or untoward findings. The study personnel will elicit reports of adverse events from 
the subject at each visit (including phone calls) documenting the medical diagnosis, date of event start and end, 
causality (relationship to device or procedure), treatment, resolution and description that includes the details 
of the event.  

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wearing the device and participating in the study. The event should be reviewed to determine if the device or 
study procedure could have possibly caused the event and therefore is related to the study device or 
procedure. It should also be noted that should the control arm utilize a non-Medtronic device, these would not 
be considered device related.   
Causality assessment is the determination of the relationship between an adverse event and the device being 
studied.  It is expected that the investigational center will review all elements surrounding the adverse event to 
properly assess the causality of the event to the study device or to a study procedure.  
This review would include the subjects description of the event, study device uploads and medical records (if 
applicable) from the treating facility. These records will be made available to sponsor.  
Investigators should classify the relationship between the AE and the study device or study procedures using 
one of the five possible causality categories listed below: 
 
x
Not related:  relationship to the device or procedures can be excluded when: 
R the event is not a known side effect of the product category the device belongs to or of similar 
devices and procedures 
R the event has no temporal relationship with the use of the investigational device or the 
procedures; 

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R
the event does not follow a known response pattern to the medical device (if the response 
pattern is previously known) and is biologically implausible; 
R the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or increase of the 
level of activation/exposure), do not impact on the serious event; 
R the event involves a body-site or an organ not expected to be affected by the device or 
procedure; 
R the event can be attributed to another cause (e.g. an underlying or concurrent illness/ clinical 
condition, an effect of another device, drug, treatment or other risk factors); 
R the event does not depend on a false result given by the investigational device used for 
diagnosis, when applicable; 
R harms to the subject are not clearly due to use error; 
R In order to establish the non-relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of device/procedures and the serious event. 
 
x
Unlikely: the relationship with the use of the device seems not relevant and/or the event can be 
reasonably explained by another cause, but a relationship to the device cannot be completely ruled 
out. 
x
Possible:  the relationship with the use of the investigational device is weak. Alternative causes are also 
possible (e.g. an underlying or concurrent illness/ clinical condition or/and an effect of another device, 
drug or treatment). Cases where relatedness cannot be assessed should also be classified as possible. 
 
x
Probable:  the relationship with the use of the investigational device seems relevant and/or the event 
cannot reasonably be explained by another cause. 
x
Causal relationship: the event is associated with the investigational device or with procedures beyond 
reasonable doubt when: 
R the event is a known side effect of the product category the device belongs to or of similar 
devices and procedures; 
R the event has a temporal relationship with investigational device use/application or 
procedures; 

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the event involves a body-site or organ that

the investigational device or procedures are applied to; 

the investigational device or procedures have an effect on; 
R the event follows a known response pattern to the medical device (if the response pattern is 
previously known); 
R the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the event (when clinically feasible); 
R other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and an 
effect of another device, drug or treatment) have been adequately ruled out; 
R harm to the subject is due to error in use; 
R the event depends on a false result given by the investigational device used for diagnosis, 
when applicable; 
R In order to establish the relatedness, not all the criteria listed above might be met at the same 
time, depending on the type of device/procedures and the serious event. 
 
Example: A severe hyperglycemia adverse event with the following event description would have the 
following causality assessment for device relatedness:
Improved glucose without an infusion set/site change
Not related
Changed infusion set with glucose improvement 
Possible 
Infusion set fell out, bent cannula, occlusion alarm 
Causal relationship 
 
 
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If the adverse event is determined to be related to the study device the sponsor will then assess the event 
to determine if it is anticipated or unanticipated. 
x
Anticipated: the event is identified in the CIP; labeling; report of priors/IB or user guide. 

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Unanticipated: the event has not been previously identified in the CIP; labeling; report of priors/IB, 
Investigator brochure, or user guide
 
5HFRUGLQJ'DWD
In the Oracle Clinical Remote Data Capture (OC-RDC) database, the investigational centers will be identified 
numerically, i.e. from 001 to 070 (depending on center number). At the Screening visit, investigational center 
staff will assign each subject a sequential ID number that corresponds to a pre-defined casebook in the OC-RDC 
database.   
Each case book will contain all relevant Case Report Forms for each subject. Each subject will be assigned a 
unique identifier All study documents, electronic Case Report Forms (eCRFs) and correspondence will use this 
identifier sequence in lieu of a subject’s name or initials. 
 
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A deviation is any instance(s) of failure to follow, intentionally or unintentionally, the requirements of the 
protocol. It is expected that the investigator will conduct this clinical trial in compliance with the protocol and 
all applicable regulations governing the conduct of clinical research involving human subjects. Failure to do so 
could result in one or all of the following: 
x
Observation in the monitoring report 
x
Deviation to document the event 
x
Corrective action plan 
x
Investigational center disqualification  
x
Notification to the regulatory authorities / IRB/EC depending on the severity of the deviation and 
reporting requirements 
The investigator is responsible for protecting the safety and welfare of the clinical research subjects. 
 
Reporting of Deviations 
USA (to Sponsor and IRB): Any deviation from the CIP shall be recorded in eCRF together with an explanation 
for the deviation. Notice of deviations from the CIP to protect the life or physical well-being of a subject in an 

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emergency shall be given as soon as possible, but no later than 5 working days after the emergency occurred. 
(21 CFR 812.150(a)(4)) 
Europe (Sponsor, Ethics Committee and Regulatory Authority): Any deviation from the CIP shall be recorded in 
eCRF together with an explanation for the deviation. Deviations shall be reported to the sponsor who is 
responsible for analyzing them and assessing their significance.  
Note: When relevant, ECs, regulatory authorities or the appropriate regulatory bodies should be informed. (ISO 
14155:2011)  
Notice of deviations from the CIP to protect the life or physical well-being of a subject in an emergency shall be 
given as soon as possible, but no later than 5 working days after the emergency occurred.  
No waivers for deviations from CIP will be allowed. 
Canada, Australia and New Zealand (Sponsor and Ethics Committee): Any deviation from the CIP shall be 
recorded in eCRF together with an explanation for the deviation. Notice of deviations from the CIP to protect 
the life or physical well-being of a subject in an emergency shall be given as soon as possible, but no later than 
5 working days after the emergency occurred.  
  
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Subjects may choose to withdraw from the study at any time by notifying investigational center staff of their 
intent.
If a subject chooses to end his or her study participation or if a subject is removed from the study at the 
Investigator’s discretion, the reason for termination must be documented both in source documents and on 
the appropriate eCRF. All study devices and supplies must be returned and the return documented both in 
source documents and on the appropriate eCRF. 
Subjects may also be withdrawn from the study at the discretion of the Investigator. A subject will be 
withdrawn from the study if: 
x
In the opinion of the Investigator, the subject’s health or safety would be compromised by 
continuing in the study 
x
In the opinion of the Investigator, it is in the subject’s best interest to discontinue participation in 
the study 
x
During the course of the study, subject begins participation in another investigational study (drug 
or device). 

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During the study it becomes known that subjects are using own SMBG or system that replaces 
SMBG
x
During the course of the study, subject begins abusing illicit drugs or marijuana. 
x
During the course of the study subject begins abusing prescription drugs.  
x
During the course of the study subject begins abusing alcohol. 
x
During the course of the study subject begins using pramlintide (Symlin), DPP-4 inhibitors, 
liraglutide (Victoza or other GLP-1 agonists), metformin, canagliflozin (Invokana or other SGLT2 
inhibitors). 
x
During the course of the study, subject begins using hydroxyurea. 
x
During the course of the study, subject receives red blood cell transfusion or erythropoietin.       
x
During the course of the study, the subject demonstrates that he/she is not able to comprehend 
instructions for study procedures, as evaluated by the appropriate research staff.  
x
During the study, subject repeatedly activates SmartGuard when instructed otherwise (e.g. Auto 
Mode is turned on in SAP Cohort) 
x
During the course of the study, subject is taking oral, injectable, or IV glucocorticoids for 3 or more 
weeks (e.g. oral prednisone daily or weekly glucocorticoid administration) 
x
During the study, (female) subject becomes pregnant. 
x
During the study, the subject experiences two severe hypoglycemic episodes  
x
The first episode of Severe Hypoglycemia may lead to withdrawal, if it is secondary to subject non-
compliance or other individual safety concerns:   
R Subject is not using the bolus wizard 
R Subject is not checking blood glucose using finger sticks  
R Subject is non-compliant with sensor wear 
R Subject is not following protocol procedures 
x
During the study, the subject experiences one  episode of DKA  
x
During the study subject has a cardiovascular event or any vascular event such as stroke.   
Documentation of the reason(s) leading to subject withdrawal will be kept in the subject’s source file. 

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For Europe only: If patient withdrawal is due to problems related to the device safety or performance, the 
investigator shall ask for the subject's permission to follow his/her status/condition outside the clinical 
investigation. 
 
 
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VWXG\YLVLWDSSRLQWPHQWVDQGRUIDLOVWRUHVSRQGWRFRPPXQLFDWLRQVIURPWKHLQYHVWLJDWLYHVLWH$VXEMHFWLV
RQO\FRQVLGHUHGWREHORVWWRIROORZXSLQWKHHYHQWWKHLQYHVWLJDWLRQDOFHQWHULVXQDEOHWRGHWHUPLQHWKH
VWDWXVRIWKHVXEMHFW,WLVUHFRPPHQGHGWKDWWKH,QYHVWLJDWLYHVLWH
x
Document at least 2 separate attempts to contact subject by phone
x
If no response to phone contact, send the subject a registered letter with return receipt
x
Requesting the subject contact the investigational center
x
If there is no response, the subject should be considered lost to follow-up and investigative site 
would withdraw the subject 
,IWKHVXEMHFWFRQWDFWVWKHLQYHVWLJDWLRQDOFHQWHUDQGZLVKHVWRZLWKGUDZWKHVXEMHFWZRXOGQRORQJHUEHORVW
WRIROORZXSEXWLQVWHDGZRXOGEHGRFXPHQWHGDVVXEMHFWZLWKGUDZLQJFRQVHQWWRFRQWLQXHLQWKHVWXG\ 
 
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Medtronic and/or the IRB/EC retain the right to disqualify an investigational center and remove all study 
materials at any time. Specific instances, which may precipitate investigational center disqualification, include 
but are not limited to: 
x
Unsatisfactory subject enrollment with regard to quality and quantity. 
x
Persistent non-compliance to protocol procedures on the part of an Investigator/investigational 
center. Inaccurate, incomplete, and/or untimely data recording on a recurrent basis. 
x
The incidence and/or severity of adverse experiences in this or other studies indicating a potential 
health hazard caused by the device. 
x
Unsatisfactory accountability of devices. 

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A written statement fully documenting the reasons for such a termination will be provided to Medtronic, the 
Institutional Review Board (IRB) or Ethics Committee (EC) and other regulatory authorities, as required. 
 6WRSSLQJ5XOHV
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1. One episode of DKA or 2 episodes of severe hypoglycemia will result in withdrawal of subject from 
study, regardless of which arm or period they are in. 
2. The first episode of Severe Hypoglycemia may lead to withdrawal, if it is secondary to subject non-
compliance or other individual safety concerns:   
RSubject is not using the bolus wizard 
RSubject is not checking blood glucose using finger sticks  
RSubject is non-compliant with sensor wear 
RSubject is not following protocol procedures 
 
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The study will be stopped if DMC determines that there are significant safety issues. (See DMC section.)
Note: If it is decided to withdraw patients from participation in the study or if the study is stopped, subjects 
will be followed-up in accordance with standard practice. 
 
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In order to achieve safety success, the following study success criteria must be met for the HCL Arm by the end of the 
study:

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Table 14. Safety Success Criteria 
$GYHUVH(YHQW
Reference 
5HIHUHQFH5DWH> 25 
years old 
5HIHUHQFH5DWH
15-25 years old 
5HIHUHQFH5DWH<15 
years old 
Study Success Criteria 

DKA events per 100 
patient years 
STAR 3 
Bergenstal et. al  
SAP arm: 0.68
Control arm: 0 
SAP arm:  2.7
Control arm: 3.6 
SAP arm: 2.2 
Control arm: 0 
< 4 events per 100 
patient years with HCL 
arm 
530 G Adult 
inhome study CEP 
266 
(MDT on file) 
1.27 
3.4 
N/A 
530 G Pediatric  
inhome study CEP 
287 
(MDT on file) 
N/A 
N/A 
0 
Type 1 exchange 
Weinstock et. al 
4.8 
N/A 
N/A 
Type 1 exchange 
Cengiz et al 
N/A
9.9

9.9 
 
 
 
Severe hypoglycemia per 
100 patient years 
STAR 3
Bergenstal et. al  

SAP  arm: 16.5
Control arm: 20.9 

SAP arm:  5.4
Control arm: 3.9 

SAP arm:  10.2
Control arm: 3.6 
< 8 events per 100 
patient years with HCL 
arm 

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$GYHUVH(YHQW 
Reference 
5HIHUHQFH5DWH> 25 
years old
5HIHUHQFH5DWH
15-25 years old 
5HIHUHQFH5DWH<15 
years old
Study Success Criteria 
530 G Adult 
inhome study CEP 
266 
(MDT on file) 
0.85
0 
N/A
530 G Pediatric  
inhome study CEP 
287 
(MDT on file) 
N/A 
N/A 
1.42 
 
Type 1 exchange 
Weinstock et. al 
11.8
N/A 
N/A 
 
Type 1 exchange 
Cengiz et al 
N/A 
6.2 
6.2 
 

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Descriptive VXPPDU\(i.e not statistically powered) for severe hypoglycemia and DKA HYHQWV rates will be 
performed between the HCL and control arms for each age group \HDUV\HDUVDQG!\HDUV as 
well as the overall event rates. 
Severe hypoglycemia and DKA event rates were taken from the following 
1. Richard Bergenstal et.al: Effectiveness of Sensor-Augmented Insulin-Pump Therapy in Type 
1Diabetes.New England Journal of Medicine, 2010; 363:311-20 
2. Weinstock et. al: Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results 
from the T1D Exchange clinic registry. J Clin Endocrinol Metab. 2013 Aug;98(8):3411-9. 
3. Cengiz et. al: Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the 
T1D Exchange clinic registry. Pediatr Diabetes. 2013 Sep;14(6):447-54.
4. MDT on file: Statistical Analysis Plan (SAP) for CEP304, 056-F286 
 0HGLFDO2YHUVLJKW
In order to conduct the study, staffing with the appropriate training is required: 
0HGLFDO6WDII
A physician who has managed patients on both CGM and insulin pump will be included in the study as the 
principal investigator.
 
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The investigator (or designee) will need to have one of the following qualifications; Endocrinology fellowship, 
management in patients with diabetes in a clinical practice. The provider must be qualified to treat diabetic 
emergencies. 
 
([SHULHQFH
Investigator (or designee) must also have at least one year experience in managing patients with insulin 
carbohydrate ratios and insulin sensitivity ratios in his/her practice 
 

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Subjects will be instructed to use clean fingers when performing finger stick glucose testing.  Subjects 
will be instructed to test 4-6 times a day and also before driving (as applicable).  Subjects will have 
training on diabetes self-management principles.   
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x
Intervention and treatment for hypoglycemia and hyperglycemia is addressed in Section 16. 
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x
When an erroneous glucose value is used to calibrate a CGM, the bias is carried through until the next 
opportunity to re-calibrate the CGM. This can result in an incorrect bias. In order to mitigate this risk, 
every new sensor will have an initial calibration.  

5HXVH5LVN
x
All study devices (including the Serter) will be single patient use.   
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The following devices will be supplied sterilized: 
x
Infusion sets 
x
Insulin reservoirs 
x
Glucose sensors 
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x
Comprehensive training will take place for clinical staff regarding the operation of the HCL, all of its 

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functional components and all other study devices to be used during the study at the investigational 
center initiation visit.  
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7HFKQLTXHV
x
Detailed mitigations to blood sampling risk are provided in Section 15. 
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x
A Central laboratory will be used for A1C testing and a laboratory manual will be provided separately. 
A1C is a primary endpoint. For subjects 2-6 years of age, Point of Care testing is an acceptable 
alternative.
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During the course of the study, the subjects’ blood glucose, SG levels, A1C, and blood ketone, will be assessed 
using the following methods in this section (Section 15).
 
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Values will be assessed during the study by all subjects using the Study Meter. The control solution test will be 
done following the manufacturer’s IFU during Home use. Subjects will be trained on the use of the Study Meter 
per the manufacturer’s instructions for use.   
 
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Blood ketones will be determined by all subjects using the Ketone Meter during home use  The control solution 
test will be done following the manufacturer’s IFU during Home use. Study staff will be trained on the use of 

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the Ketone Meter per the manufacturer’s IFU. All ketone measurements will be recorded on the appropriate 
eCRF upon entry into the Log Book section of CareLink Personal for Clinical Research/CareLink Clinical 
Software.  
Note: In the event the blood ketone meter is not used by subjects to collect ketone values, urine ketones must 
be measured and entered appropriately into CareLink as urine ketones. 
 
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Assessed using the following methods: 
SG data collected by subject’s Study Pump and calibrated by subject’s Study Meter 
 
$&
Collected at baseline, will be used as demographic information. Also collected at various points throughout  
and at end of study.  
 
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Potential Risk with
 Infusion Sets 
Mitigation 
Potential side effects related to 
infusion sets may include:  
x
Localized infection 
x
Skin irritation/redness 
x
Bruising 
x
Discomfort/pain 
x
Bleeding 
x
Irritation 
Prevention and mitigation risks of infusion sets include: 
x
Investigational center staff and subjects will be instructed 
to follow the provided user guides for insertions and care 
of infusion sets. If an infusion site becomes irritated or 
inflamed, the infusion set should be removed and another 
placed in a new location.  
x
In case of hyperglycemia secondary to infusion set 
occlusion subjects will be instructed to remove current 
infusion set and replace with new infusion set and give 

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x
Rash 
x
Hyperglycemia secondary 
to infusion set occlusion or 
site failure 
x
Hyperglycemia secondary 
to site falling off  
correction insulin if needed with syringe. Investigational 
center staff and subjects will be instructed to follow the 
provided user guides for insulin pump management.   
x
Subjects will be trained prior to study device use and 
diabetes management principles and told to call with 
problems.  
 
Potential Risk with Insulin 
Administration and Pump Use 
Mitigation 
Potential risks associated with the 
use of an insulin infusion pump 
include the risk of malfunction of 
the components of the system 
(pump, software, infusion set and 
reservoir) as well as the risk of use 
error during use of the 
system.  Device deficiencies or use 
errors can result in administration 
of too much or too little insulin 
which can lead to the following 
clinical consequences: 
x
Hypoglycemia 
x
Hyperglycemia 
x
Diabetic ketoacidosis (DKA) 
x
Severe hypoglycemia with 
or without associated 
seizure, coma or death 
x
Kinked cannula leading to 
hyperglycemia 
x
Infusion set disconnection 
from pump leading to 
hyperglycemia 
x
Dislodged cannula leading 
to hyperglycemia 
x
A pump error indicating 
hardware failure may lead 
to under delivery 
x
Battery failure – no insulin 
Prevention and mitigation risks of infusion sets include: 
x
Investigational center staff and subjects will be instructed 
to follow the provided user guides for insulin pump 
management.   
x
Subjects will be trained prior to study device use and 
diabetes  management principles and told to call with 
problems.  
x
Subjects will be required to check SMBG 4-6  times a day 
and also before driving  (as applicable).  
x
Subjects will be told to have glucose on hand for 
hypoglycemia 
x
Subject will be told they may need to change their infusion 
set if they suspect catheter occlusion or administer insulin 
with syringe with persistent hyperglycemia especially if 
ketones develop.   

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delivered 
x
Remove a reservoir, 
without suspending and 
reconnecting after a while 
resulting in a Hypoglycemia 
x
Insulin deterioration 
leading to hyperglycemia 
x
Incomplete priming; Fails to 
priming tubing and/or 
cannula, leading to 
hyperglycemia 
x
Remove a reservoir, 
without suspending and 
reconnecting after a while 
resulting in a Hypoglycemia 
x
Patient not filling pump 
reservoir when needed 
leading to hyperglycemia 
x
Magnetic Resonance 
Imaging resulting in pump 
/MiniLink malfunction 
x
Inaccurate insulin delivery 
due to sudden altitude 
changes. 
x
Hypoglycemia or 
hyperglycemia from 
manual bolus 
x
Hypoglycemia or 
hyperglycemia from 
computer hacking  
 
Risks associated with 
hyperglycemia include  
x
DKA 
x
Symptomatic ketosis 
x
Cardiovascular event  
x
Dehydration  
Prevention and mitigation risks include: 
x
Investigational center staff and subjects will be instructed 
to follow the provided user guides for insulin pump 
management.   
x
Subjects will be trained prior to study device use and 
diabetes management principles.  
 

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x
Potassium and sodium 
imbalance 
x
Shock 
x
Altered mental status  
x
Coma  
x
Acidosis 
Risks associated with hypoglycemia 
include:
x
Seizure 
x
Coma  
x
Altered mental status  
x
Loss of consciousness  
x
Cardiovascular event  
x
Death  
x
Risk of rebound 
hyperglycemia with ketosis 
Prevention and mitigation risks include: 
x
Investigational center staff and subjects will be instructed 
to follow the provided user guides for insulin pump 
management.   
x
Subjects will be trained prior to study device use device 
and diabetes management principles.  
 
Potential Risk with Sensor  
Mitigation 
Potential risks with Sensor include: 
x
Skin irritation or reaction to 
adhesives 
x
Bruising 
x
Discomfort 
x
Redness 
x
Bleeding 
x
Pain 
x
Rash 
x
Infection 
x
Irritation from tapes used 
with glucose-sensing 
products 
x
Raised bump 
x
Appearance of a small 
"freckle-like" dot where 
needle was inserted 
Prevention and mitigation risks of Sensor include: 
x
Investigational center staff and subjects will be instructed 
to follow the provided user guides for insertions and care 
of sensors. If a sensor site becomes infected or inflamed, 
the sensor should be removed and another placed in a 
new location. 
x
Patients are instructed to use fingerstick glucose reading 
for diabetes management and diabetes management 
decisions and told to call with problems.   
 

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x
Allergic reaction
x
Syncopal episode 
secondary to needle 
insertion 
x
Soreness or tenderness 
x
Swelling at insertion site 
x
Sensor fracture, breakage 
or damage 
x
Minimal blood splatter 
associated with sensor 
needle removal 
x
Residual redness associated 
with adhesive and or tapes 
x
Scarring 
x
Incorrect SG reading results 
in incorrect diabetes 
management 
x
Subject over-treating 
secondary to alarms which 
can result in hyperglycemia 
or hypoglycemia   
 
Potential Risk with Serter 
Mitigation 
 
Potential risks with Serter use 
include: 
x
Skin infection around the 
area where the Serter is 
used. 
x
Improper insertion may 
result in device 
performance issue 
 
Prevention and mitigation risks of Serter include: 
x
Investigational center staff and subjects will be instructed 
to follow the provided user guides for insertions and care 
of Serters. The investigational centers and subjects will 
receive training on proper use of the Serter and skin 
preparation prior to insertion. 
 
 
Potential Risk with 
Finger Stick 
Mitigation 
 
Potential risks with frequent  finger 
 
Prevention and mitigation risks of finger stick testing include: 

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stick testing include:
x
Potential risks associated 
with frequent meter testing 
of blood glucose and blood 
ketones include discomfort 
and ecchymosis at tips of 
fingers 
x
Potential risks associated 
with drawing blood include 
discomfort and bruising 
x
Syncopal episode can occur 
secondary to needle 
insertion  
x
Investigational center staff and subjects will be instructed 
to follow the provided user guides for use of meter with 
fingerstick testing. The investigational centers and subjects 
will receive training on proper use of the meter and 
fingerstick testing. 
Potential Risk with HCL 
Mitigation 
 
Risks for HCL include:  
x
Hypoglycemia 
x
Severe hypoglycemia 
x
Hyperglycemia 
x
DKA 
x
User Entry Error 
R Patient administering 
boluses by entering 
false carb doses 
leading to 
hypoglycemia or 
hyperglycemia 
R Patient entering false 
glucose values for any 
reason leading to hypo 
and hyperglycemia  
R Patient entering false 
BG values for 
calibration leading to 
hypo or hyperglycemia 
x
Sensor failure resulting 
from patient failure to 
calibrate leading to hypo or 
 
Mitigations specific to the HCL System:  
x
Investigational center staff and subjects will be instructed 
to follow the provided user guides for insulin pump 
management.   
x
Subjects will be trained prior to study device use and 
diabetes management principles and told to call with 
problems.  
x
Subjects will be required to check SMBG 4-6 times a day 
and also before driving (as applicable).  
x
Subjects will be told to have glucose on hand for 
hypoglycemia 
x
Subjects will be asked to avoid  the use of products 
containing Acetaminophen 
x
If acetaminophen is taken, subjects will be instructed to 
use additional BG meter readings (they are not to calibrate 
with those readings) to verify their glucose levels.  
x
Subjects will be instructed to exit AutoMode 
 

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hyperglycemia 
x
Sensor over-reading 
resulting in hypoglycemia  
x
Sensor under-reading 
resulting in hyperglycemia 
x
Sensor missed 
transmission, or any other 
fault resulting in no SG 
value, leading to hyper or 
hypoglycemia  
x
Voluntary insulin delivery 
(with the pump or with a 
syringe) immediately prior 
to entering HCL may result 
in severe hypoglycemia 
despite shutting down 
insulin delivery by the 
algorithm 
x
Patient takes insulin via 
injection while in Closed 
Loop  
x
Hypoglycemia or 
hyperglycemia related to 
entering or exciting closed 
loop 
x
Insulin over-delivery due to 
Acetaminophen 
 

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Risks associated with 
hyperglycemia include  
 
x
DKA 
x
Symptomatic ketosis 
x
Cardiovascular event  
x
Dehydration  
x
Potassium and sodium 
imbalance 
x
Shock 
x
Altered mental status  
x
Coma  
x
Acidosis 
 
Prevention and mitigation hyperglycemic risks include: 
 
x
Investigational center staff and subjects will be instructed 
to follow the provided user guides for insulin pump 
management.   
x
Subjects and/or parent guardian will be trained on study 
device and diabetes management principles.  
x
Subjects will be trained prior to study device use and 
diabetes management principles.  
x
Subjects will be required to check SMBG 4 -6 times a day 
and also before driving (as applicable).  
 
 
Risks associated with 
Hypoglycemia include: 
 
x
Seizure 
x
Coma 
x
Altered mental status 
x
Loss of consciousness 
x
Cardiovascular event  
x
Death   
x
Rebound hyperglycemia 
with ketosis   
 
Prevention and mitigation of hypoglycemia risks include: 
x
Investigational center staff and subjects will be instructed 
to follow the provided user guides for insulin pump 
management.   
x
Subjects will be trained prior to study device use and 
diabetes management principles.  
x
Subjects will be required to check SMBG 4 -6 times a day 
and also before driving (as applicable).  
x
Subjects will be told to have glucose on hand for 
hypoglycemia 
 
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Refer to Section 16.1, Potential Risks. 
 

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Subjects are not expected to benefit from participation in this study; however, they may gain increased 
awareness of emerging technologies for diabetes management as a result of their participation. 
In Australia, inclusion of the 2-6 years of age group will expand our knowledge and provide specific data in this 
region. 
 
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See sections 14, 16.1, 16.2 and 16.3. In Australia, the Investigator Brochure (IB) will be provided to sites.
 
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Subjects will be compensated financially for their participation, as permitted by local law. 
 
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'HILQLWLRQV&ODVVLILFDWLRQV
Medtronic uses the definitions provided in ISO 14155:2011 and 21 CFR 812 for adverse event definitions. 
Where the definition indicates “device”, it refers to any device used in the study. This might be the device 
under investigation, or any market released component of the system. Medtronic will apply causality 
definitions (Section 10.7.2)  across all events, not only serious adverse events and definitions have been 
adapted accordingly. 
 

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Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal 
laboratory findings) in subjects, users or other persons, whether or not related to the investigational medical 
device. 
Note 1: This definition includes events related to the investigational medical device or the comparator. 
Note 2: This definition includes events related to the procedures involved. 

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Note 3: For users or other persons, this definition is restricted to events related to investigational medical 
devices. 
 

$GYHUVH'HYLFH(IIHFW$'(,62
Adverse event related to the use of an investigational medical device.  
Note 1: This definition includes adverse events resulting from insufficient or inadequate instructions for use, 
the deployment, the implantation, the installation, the operation, or any malfunction of the investigational  
medical device. 
Note 2: This definition includes any event that is a result of a use error or intentional misuse of the 
investigational medical device.  

6HULRXV$GYHUVH(YHQW6$(,62
Adverse event that: 
x
Led to a death 
x
Led to a serious deterioration in the health of the subject, that either resulted in 
x
a life-threatening illness or injury, or 
x
a permanent impairment of a body structure or a body function, or 
x
in-patient or prolonged hospitalization, or 
x
medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment 
to a body structure or a body function 
x
Led to fetal distress, fetal death or a congenital abnormality or birth defect.  
Note 1: A planned hospitalization for pre-existing condition, or a procedure required by the CIP, without a 
serious deterioration in health, is not considered to be a serious adverse event.  
For the purpose of this study, Inpatient Hospitalization is defined as: 24 hour acute admission to the hospital 
based on urgent medical need rather than elective admission. 
For the purpose of this study, the term "life-threatening" in the definition of "serious" refers to an event in 
which the patient was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. (ICH Topic E 2 A Clinical Safety Data 
Management: Definitions & Standards for Expedited Reporting. EMEA 2006) 

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
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Adverse device effect that has resulted in any of the consequences characteristic of a serious adverse event
 

8QDQWLFLSDWHG$GYHUVH'HYLFH(IIHFW8$'(&)5V
Any serious adverse effect on health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a supplementary plan or application), 
or any other unanticipated serious problem associated with a device that relates to the rights, safety, or 
welfare of subjects.
 
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8QDQWLFLSDWHG6HULRXV$GYHUVH'HYLFH(IIHFW86$'(,62

Serious adverse device effect which by its nature, incidence, severity or outcome has not been identified in the 
current version of the risk analysis report. 
Note 1: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, incidence, severity or 
outcome has been identified in the risk analysis report 
 

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UHSRUWLQJLQFOLQLFDOWULDOVLQYROYLQJWKHUDSHXWLFJRRGV1RYHPEHU
A safety issue that could adversely affect the safety of participants or materially impact on the continued 
ethical acceptability or conduct of the trial.  
 

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UHSRUWLQJLQFOLQLFDOWULDOVLQYROYLQJWKHUDSHXWLFJRRGV1RYHPEHU
A measure required to be taken in order to eliminate an immediate hazard to a participant’s health or safety. 
Note 1: This type of significant safety issue can be instigated by either the investigator or sponsor and can be 
implemented before seeking approval from Human Research Ethics Committee (HRECs) or institutions  
 

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5HSRUWLQJRI$GYHUVH(YHQWV
The investigator or designee will record ALL adverse events while the Subject is enrolled in the clinical study.  
Each AE needs to be assessed for its device or procedure relatedness. A device related AE is associated with the 
use of the study/Medtronic device  (e.g. infection of sensor site or infusion set occlusion resulting in DKA). A 
procedure related AE is associated with testing related to the study procedures specified in the CIP (e.g. IV 
insertion pain). 
Examples include: 
x
Device related (ADE): insertion site infection 
x
Serious adverse device effect: cellulitis at device insertion site requiring hospitalization 
x
Procedure related AE: bruising at IV insertion site 
x
Not related to procedure or device: cold, flu, appendicitis 
Subjects participating in the study have diabetes and are expected to experience hypoglycemia and or 
hyperglycemia.  These normal events are not expected to be reported to sponsor on an AE eCRF as this is not 
considered an untoward event, but rather an expected occurrence. Any glycemic excursion that meets the 
protocol definition of Severe Hypoglycemia, Severe Hyperglycemia or DKA is considered an untoward event 
and a worsening from the subject’s baseline and would be reported to sponsor on an AE eCRF.  
Baseline medical conditions should only be reported to sponsor on an AE eCRF if there is a worsening from the 
subject’s baseline.  For example, a subject previously diagnosed with Asthma is hospitalized for severe asthma 
attack would be a reportable event. 
Adverse events will be documented in the subject source file and reported to sponsor on an eCRF. The 
investigational center is responsible for documentation of adverse events including obtaining source 
documents related to the event, such as emergency medical technician/paramedic reports, hospital records 
(admission summary; lab results, test results, discharge summary) or device uploads to support the event. 
Source documents will be reviewed to determine if additional adverse events have occurred and require 
reporting.   
Narratives gathered from completed questionnaires will not provide the basis of an adverse event report 
however could lead to discussions that result in the identification of a reportable AE. 

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Adverse events that have not resolved at the time of the subject’s discontinuation or completion of the study 
should have an “outcome” of Not Recovered/Not Resolved at study end in subject source and on an eCRF. The 
investigator should ensure that subject is aware of any follow-up or additional treatment that is required for 
any ongoing AE at end of study participation; however, there will be no eCRF entry for the ongoing follow-up.  
 
Sponsor Notification: 
Investigator centers should target reporting within 24 hours of investigator or study coordinator awareness for 
all Severe Hypoglycemia; DKA; Serious Adverse Events; and Serious Adverse Device Effects to Medtronic. The 
AE eCRF will be completed with all known details within 24 hours of investigational center awareness – this will 
serve as notification to Medtronic. If the study database cannot be accessed due to technical problems, contact 
the sponsor via email at dl.diabetesclinicalresearchsafety@medtronic.com and provide the known details of 
the event. Once the access issue has been corrected the event should be entered onto an AE eCRF.  
Expedited reporting by sponsor to the regulatory authorities 
x
Device related Severe Hypoglycemia events 
x
The sponsor should report device related severe hypoglycemic events for those subjects > 6 
years of age to FDA following notification by investigator prior to enrollment of subjects 2-6 
years of age and through study completion. 
x
Once enrollment commences for 2-6 year old subjects, the sponsor should report device 
related severe hypoglycemic events to the FDA within 7 days from sponsor notification by 
investigator 
x
Unanticipated, Device related Severe Hyperglycemia events which meet SAE criteria (SADE) 
x
Sponsor will assess and if event is unanticipated, complete expedited reporting 
x
Sponsor will follow reporting requirements according to their regulatory authority requirements. 
 
Expedited Safety Reporting of UADE 
 
UADE: For device studies, investigators are required to submit a report of a UADE to the sponsor and the 
reviewing IRB/EC as soon as possible, but in no event later than 10 working days after the investigator first 
learns of the event (21 CFR 812.150(a)(1)).  
For Canada: Investigators are required, per the TPD Investigator Agreement, to report any incident that is 

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related to a failure of the device or deterioration in its effectiveness, or any inadequacy in its labeling or 
directions for use leading to death or serious deterioration in a subject’s health within 72 hours after the 
occurrence (Canada Medical Device Regulations, SOR/98-282; 77, 59.) 
For Europe, Australia and New Zealand: It is the responsibility of the investigator to follow their IRB/EC 
reporting requirements. 
For Australia: It is the responsibility of the investigator are to report USDAE to their HREC and institution 
without undue delay and no later than 72 hours of the Principal Investigator becoming aware of the event. 
(NHMRC Safety monitoring and reporting in clinical trials involving therapeutic goods November 2016 
section C.2.g) 
 For US, Canada, Europe, Australia and New Zealand: 
The Sponsor will complete safety and vigilance reporting and notify the investigator and IRB/EC of any event 
that results in a safety report to the regulatory authorities. Documentation of IRB/EC notification of any safety 
event must be kept at the investigational center and a copy sent to the Sponsor. 
Reporting of Glycemic Events  
 Severe Hypoglycemia is an event requiring assistance of another person due to altered consciousness 
to actively administer carbohydrate, glucagon, or other resuscitative actions. This means that the 
subject was impaired cognitively to the point that he/she was unable to treat his or her self, was 
unable to verbalize his or her needs, and was incoherent, disoriented and/or combative.  
These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma 
glucose measurements may not be available during such an event, but 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. (Adapted from American Diabetes 
Association Workgroup on Hypoglycemia, Diabetes Care 28:1245-1249, 2005) 
 Severe Hyperglycemia is defined as Hyperglycemia (blood glucose >300 mg/dL (16.7mmol/L)) with 
blood glucose ketones >1.5mmol/L, urine ketones moderate or large, or accompanied by symptoms of 
nausea, vomiting or abdominal pain. 
 Diabetic Ketoacidosis/DKA diagnostic criteria: blood glucose greater than (>) 250 mg/dL (or greater 
than (>) 13.9 mmol/L), arterial pH less than (<) 7.3, bicarbonate less than (<) 15mEq/L, moderate 
ketonuria or ketonemia, and requiring treatment within a health care facility. (American Diabetes 
Association-Diabetes Care, Volume 27, Supplement 1, January 2004; S94-S102) 
Hyperglycemic events will be recorded as DKA if the event includes the presence of all of the following: 
x
Arterial blood pH less than (<)  7.30 or serum bicarbonate less than (<) 15mEq/L 

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x
Blood glucose greater than (>) 250 mg/dL (or greater than (>) 13.9 mmol/L) 
x
Serum ketones or large/moderate urine ketones 
x
Symptoms such as polyuria, polydipsia, nausea, or vomiting 
x
Treatment provided in a health care facility 
 
Reporting of Use Errors  
The CEC will review adverse events (AE, including: Serious Adverse Event, Serious Adverse Device Effect, 
Unanticipated Adverse Device Effect, Severe Hypoglycemia, Diabetic Ketoacidosis, Severe Hyperglycemia) to 
assess the aspect of critical task, user error, potential harm and severity of harm. Once the adjudication is 
completed, the internal Medtronic team (e.g. clinical, regulatory, human factors, training and etc.) will assess 
the risk mitigation control and its evidence of effectiveness for each AE. A use error analysis will be provided to 
FDA every 6 months (Table 15). 
 
Table 15. Use Error Report  
Adverse 
Event # 
Critical Task
Use Error
Potential 
Harm 
Severity of 
Harm 
Risk 
Mitigation 
Control 
(Labeling or 
Training
Evidence for 
the 
Effectiveness 
of Risk 
Control 
Mitigation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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A clinical events committee (CEC) consisting of external physicians with an expertise in Endocrinology and 

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the management of diabetes including Insulin Pumps and CGM will be convened. The CEC will review all 
reports of:  
x
Serious Adverse Event 
x
Serious Adverse Device Effect 
x
Unanticipated Adverse Device Effect 
x
Severe Hypoglycemia 
x
Diabetic Ketoacidosis 
x
Severe Hyperglycemia 
 
The CEC will assess events to determine agreement or disagreement with the investigator classification of an 
event. The CEC will only provide three causality assessments for device and procedure relatedness: Not 
Related, Possible, and Causal relationship. 
 
Causality Categories for 
Investigational Center 
Causality Categories for CEC: 
x
Not Related 
x
Unlikely 
x
Possible 
x
Probable 
x
Causal relationship 
x
Not Related 
x
Possible 
x
Causal relationship 
 
'DWD0RQLWRULQJ&RPPLWWHH
A Data Monitoring Committee (DMC) consisting of external physicians with an expertise in Endocrinology 
and the management of insulin requiring diabetes including CGM, along with an external statistician will be 
convened to review study progress and safety. The Board will convene approximately every 90 days, until 
at least 2000 Auto Mode patient days in both the 2-6 year and 7-13 year age groups in the CEP302 and/or 
CEP304 study have been reviewed and approved by the DMC. After review of the patient day report(s), the 

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meeting cadence will transition to 180 days. The Board will also meet when ad hoc review is required. 
In addition, the DMC will review interim analysis data, performed by an independent statistician, per 
Cohort at the following points in time: 
x
After 80 subjects from Group 1 (baseline A1c > 8%) have completed the first 6 months of the study 
period  
x
After 80 subjects from Group Ϯ;ďĂƐĞůŝŶĞϭĐчϴйͿŚĂǀĞĐŽŵƉůĞƚĞĚƚŚĞĨŝƌƐƚϲŵŽŶƚŚƐŽĨƚŚĞƐƚƵĚǇ
period   
The DMC will perform 4 main functions:  
First: DMC will review data related to staged enrollment of subjects 2-6years of age (Ad Hoc Review) 
x
Subjects 2-6 years of age will be allowed to enroll in the post approval study, once DMC has reviewed   
data from 10 subjects age 2-4 years who have completed participation in the study period of the 
CEP302 study and has  given approval to enroll   
x
Should an Unanticipated Severe Hyperglycemia event which meets SAE criteria  or a device related 
Severe Hypoglycemia event occur, subjects 2-6 of age will not be allowed to enroll, unless FDA provides 
approval to include this age group. 
Second: DMC will track and trend the overall Safety of the study.     
Event rate, defined as number of events per 100 patient years will be reviewed by the DMC with respect to 
the following: 
x
Event rate of all SAEs.   
x
Event rate of severe hypoglycemia 
x
Event rate of severe hyperglycemia 
x
Event rate of DKA 
x
Event rate of device related adverse events.   
Applicable information for device related adverse events may include: 
x
Whether or not the event was unanticipated 
x
Review of sensor data from CareLink report (when applicable) 
x
Review of pump data from CareLink report (when applicable) 
x
Misuse of the device by the user 

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Third: Based on their meetings, DMC will recommend a decision to the sponsor regarding the following: 
x
Whether or not enrollment should be halted.
x
Whether or not the entire study will need to be stopped including for those subjects who have 
received study devices already.  
Fourth: During Interim analysis, independent statistician will perform sample size re-estimation and report it to 
DMC.  DMC will then provide a recommendation: 
x
Whether or not N of enrollment per Group should be increased 
x
Whether or not the entire study will need to be stopped for futility 
 
General guidance for DMC’s recommendations to sponsor should be based on the following:   
In general, a DMC recommendation regarding study stoppage or resumption of enrollment should be made 
to the sponsor within 1 week of the DMC meeting where the determination is made. However, if more data 
is needed, the DMC may meet again to re-assess their decision within 2 weeks or when required data 
becomes available. 
Review of events may require the following information. Final disposition may be delayed based on obtaining 
this information:  
x
Monitoring by sponsor at site 
x
Device return and failure analysis 
x
CareLink upload  and review of CareLink reports  
x
Subject clarification to site regarding details about the event 
x
Source documents that support event: Paramedic records; ER records; Lab records; Hospital admission 
and discharge summary   
The following factors should be carefully considered in the DMC’s recommendation to sponsor:  
 Was the severe hypoglycemia or DKA related to the HCL algorithm, or was it related to a known 
insulin pump risk?  For example, a question that may be considered in DKA would be whether the 
event was related to an infusion set issue or caused by the HCL algorithm.  
 Another important consideration would be if the severe hypoglycemia, severe hyperglycemia or 
DKA event was related to a device malfunction versus patient non-compliance. For example, if a 
software anomaly leading to an under-delivery of insulin is discovered versus the subject 
repeatedly ignoring alarms prompting the subject to take action.  

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
Severe hypoglycemia, severe hyperglycemia or DKA caused directly by an infusion set issue when 
the study pump is functioning as intended would likely result in acceptance to proceed with the 
study versus severe hypoglycemia or DKA that are directly caused by the HCL algorithm or a 
device malfunction might stop study enrollment or entire study altogether. 
 It should be noted that the final determination of causality related to HCL System that is made by 
the DMC may include additional factors which the members consider to be clinically relevant and 
important. 
 The DMC may take into account the thresholds listed below for the number of subjects 
experiencing hypoglycemia requiring assistance from another person or DKA to identify when the 
number of subjects experiencing these events exceeds the number that would be anticipated for 
the study population over the duration of this study. These thresholds should be interpreted with 
caution due to potential differences in study populations and study design. 
a. Rates taken from Type 1 exchange (Cengiz et. Al, and Weinstock et. Al), are higher than the 
clinical studies STAR 3, 530G adult in-home study (CEP266) and 530G Pediatric in-home 
study(CEP287).   
b. Reasons for lower rates of severe hypoglycemia and DKA in the clinical studies mentioned 
could be related to several factors including but not limited to the exclusion of those with DKA 
or severe hypoglycemia, additional attention secondary to mandatory study visits, selection 
bias of motivated patients willing to perform study procedures and access to free study devices 
during the course of the study. 
c. The CL outcome study (CEP304) will include several aspects noted above including the 
provision of free study devices during the course of the study. Therefore, the DMC should 
consider stopping study if rates of severe hypoglycemia and DKA are significantly worse (e.g. 
higher) in HCL arm than rates provided by clinical trials mentioned in Table 16.   
d. Age consideration may also be factored in by the DMC.  For example, severe hypoglycemia 
rates in those >25 years may be higher than those 25 years and below.       
e. Should DKA and/or severe hypoglycemia occur early in the study, the DMC should consider 
that the higher event rate may not necessarily represent a significant safety concern.   

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Table 16. Hyperglycemia/Hypoglycemia / DKA Threshold 
$GYHUVH(YHQW 
5HIHUHQFH 
5HIHUHQFH5DWH> 25 
years old 
5HIHUHQFH5DWH
15-25 years old
5HIHUHQFH5DWH<15 
years old 
Severe Hyperglycemia 
events per 100 patient 
years 
CER 302 
1$
1$
71.64 
DKA events per 100 patient 
years 
STAR 3 
Bergenstal et. al 
SAP arm: 0.68
Control arm: 0 
SAP arm:  2.7
Control arm: 3.6 
SAP arm: 2.2
Control arm: 0 
530 G Adult inhome study CEP 
266 
(MDT on file) 
1.27 
3.4 
N/A 
530 G Pediatric  inhome study 
CEP 287 
(MDT on file) 
N/A 
N/A 
0 
Type 1 exchange Weinstock et. 
al 
4.8 
N/A 
N/A 
Type 1 exchange Cengiz et al 
N/A 
9.9 

9.9 
Severe hypoglycemia per 
100 patient years 
STAR 3
Bergenstal et. al  

SAP  arm: 16.5 
Control arm: 20.9 

SAP arm:  5.4
Control arm: 3.9 

SAP arm:  10.2 
Control arm: 3.6 
530 G Adult inhome study CEP 
266 
0.85 
0 
N/A 

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5HIHUHQFH5DWH> 25 
years old
5HIHUHQFH5DWH
15-25 years old 
5HIHUHQFH5DWH<15 
years old
(MDT on file) 
530 G Pediatric  inhome study 
CEP 287 
(MDT on file) 
N/A 
N/A 
1.42 
Type 1 exchange Weinstock et. 
al 
11.8
N/A 
N/A 
Type 1 exchange Cengiz et al
N/A
6.2
6.2
 

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Descriptive VXPPDU\(i.e not statistically powered) for severe hypoglycemia and DKA HYHQWV rates will be 
performed between the HCL and control arms for each age group \HDUV\HDUVDQG!\HDUV as 
well as the overall event rates. 
Severe hypoglycemia and DKA event rates were taken from the following: 
1. Richard Bergenstal et.al: Effectiveness of Sensor-Augmented Insulin-Pump Therapy in Type 
1Diabetes.New England Journal of Medicine, 2010; 363:311-20 

2. Weinstock et. al: Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results 
from the T1D Exchange clinic registry. J Clin Endocrinol Metab. 2013 Aug;98(8):3411-9.

3. Cengiz et al Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the 
T1D Exchange clinic registry. 3HGLDWU'LDEHWHV 6HS
4. MDT on file: Statistical Analysis Plan (SAP) for CEP304, 056-F286 
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All endpoints are hierarchically ordered and will be evaluated in the fixed sequence from primary endpoints to 
secondary endpoints. Unless the primary endpoints hypotheses are rejected, secondary endpoints will not be 
tested.   
Effectiveness endpoints will be evaluated during the 6 month study period by individual Cohort (CSII, MDI or 
SAP), stratified by A1C; 
 
x
Group 1: Baseline A1C > 8%  
x
'ƌŽƵƉϮ͗ĂƐĞůŝŶĞϭчϴй 
 
The comparison of HCL arm vs. Control arm will be performed.  For SG-based comparison between HCL vs 
Control analyses, two weeks of CGM data collected at 3 month visit and 6 month visits will be used.   

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Primary Safety Endpoints 
The primary safety endpoint is the event rate of severe hypoglycemia and DKA from both Groups (1 & 2) during 
the first 6 months of study phase and second 6 months of continuation phase. The descriptive summary 
statistics will be presented by number of event and event rate (100 patient years) for severe hypoglycemia and 
DKA separately.  
Descriptive VXPPDU\(i.e not statistically powered) for severe hypoglycemia and DKA HYHQWV rates will be 
performed between the HCL and control arms for each age group \HDUV\HDUV and !\HDUV as 
well as the overall event rates. 
 
Co-Primary Effectiveness Endpoints 
The primary effectiveness endpoints consist of one-primary endpoint for each group.  
 
Group 1 – ĂƐĞůŝŶĞϭхϴй͗ŚĂŶŐĞŝŶϭ;ѐϭͿ 
The primary effectiveness endpoints for the baseline A1C > 8% group is change in A1C from baseline to end of 
six-month treatment period, defined as A1C measured at the six-month treatment visit minus A1C measured at 
the randomization visit. The goal is to show superiority of the HCL Arm compared to the Control Arm in 
reducing A1C from baseline to end of six-month treatment period.  
The hypothesis is mathematically expressed as: 
,Ϭ͗ђ;,>Ϳшђ;ŽŶƚƌŽůͿ 
Ha: μ(HCL) < μ(Control) 
where μ(HCL) is the mean of change in A1C (%) with the HCL Arm, μ(Control) is the mean of change in A1C (%) 
with the Control Arm.   
 
Group2 – ĂƐĞůŝŶĞϭчϴй͗dŝŵĞŝŶ,ǇƉŽŐůǇĐĞŵŝĐZĂŶŐĞ 
dŚĞƉƌŝŵĂƌǇĞĨĨĞĐƚŝǀĞŶĞƐƐĞŶĚƉŽŝŶƚĨŽƌƚŚĞďĂƐĞůŝŶĞϭчϴйŐƌŽƵƉŝƐƚŚĞƚŝŵĞǁŝƚŚ^'ďĞůŽǁϳϬŵŐͬĚ>
(3.9mmol/L) during the six-month study period, defined as percentage of SG below 70 mg/dL (3.9mmol/L) out 
of total number of available SG readings. The goal is to show superiority of the HCL Arm compared to the 
Control Arm in reducing daily time in hypoglycemic range. The hypothesis is mathematically expressed as: 

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Ha: μ(HCL) < μ(Control) 
where μ(HCL) is the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in the HCL Arm, μ(Control) is 
the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in Control Arm.   
 
Key Secondary Effectiveness Endpoints  
Group 1 – Baseline A1C > 8%: Time in Hypoglycemic Range  
The key secondary effectiveness endpoint for the baseline A1C > 8% group is the time with SG below 70 mg/dL 
(3.9mmol/L) during the six-month study period, defined as percentage of SG below 70 mg/dL (3.9mmol/L) out 
of total number of available SG readings. The goal is to show non-inferiority (with a non-inferiority margin of 
2%) of the HCL Arm compared to the Control Arm. The hypothesis of non-inferiority is mathematically 
expressed as:
,Ϭ͗ђ;,>Ϳшђ;ŽŶƚƌŽůͿнϮй 
Ha: μ(HCL) < μ(Control) + 2% 
where μ(HCL) is the subject mean of time with SG below 70 mg/dL (3.9mmol/L) in the HCL Arm, μ(Control) is 
the subject mean of time with SG below 70 mg/dL (3.9mmol/L) in the Control Arm. 
 
Group2 – ĂƐĞůŝŶĞϭчϴй͗ŚĂŶŐĞŝŶϭ;ѐϭͿ 
dŚĞŬĞǇƐĞĐŽŶĚĂƌǇĞĨĨĞĐƚŝǀĞŶĞƐƐĞŶĚƉŽŝŶƚĨŽƌƚŚĞďĂƐĞůŝŶĞϭчϴйŐƌŽƵƉŝƐĐŚĂŶŐĞŝŶϭĨƌŽŵďĂƐĞůŝŶĞƚŽ
end of six-month treatment period, defined as A1C measured at the six-month treatment visit minus A1C 
measured at the randomization visit. The goal is to show non-inferiority (with a non-inferiority margin of 0.4%) 
of the HCL Arm compared to the Control Arm in reducing A1C from baseline to end of six-month treatment 
period. The hypothesis of non-inferiority is mathematically expressed as: 
,Ϭ͗ђ;,>Ϳшђ;Control) + 0.4% 
Ha: μ(HCL) < μ(Control) + 0.4% 
 
where μ(HCL) is the mean of change in A1C (%) with the HCL Arm, μ(Control) is the mean of change in A1C (%) 
with the Control Arm.   
 

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Rest of Secondary Effectiveness Endpoints 
Group1+Group 2: Time in Hypoglycemic Range during Night 
The secondary effectiveness endpoint is the time with SG below 70 mg/dL (3.9mmol/L) during Night. The goal 
is to show superiority of the HCL Arm compared to the Control Arm reducing time in hypoglycemic range 
during night . The hypothesis is mathematically expressed as:
,Ϭ͗ђ;,>Ϳшђ;ŽŶƚƌŽůͿ 
Ha: μ(HCL) < μ(Control) 
where μ(HCL) is the subject mean of time with SG below 70 mg/dL (3.9mmol/L) in the HCL Arm during night, 
μ(Control) is the subject mean of time with SG below 70 mg/dL (3.9mmol/L) in the Control Arm during the 
night.   
 
Group1+Group 2: Time in Hypoglycemic Range during Day and Night 
The endpoint of time in hypoglycemic range below 70 mg/dL (3.9mmol/L) will be evaluated for superiority in 
the combined Groups during day and night. The goal is to show superiority of the HCL Arm compared to the 
Control Arm in reducing time in hypoglycemic range. The hypothesis is mathematically expressed as: 
,Ϭ͗ђ;,>Ϳшђ;ŽŶƚƌŽůͿ 
Ha: μ(HCL) < μ(Control) 
where μ(HCL) is the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in the HCL Arm, μ(Control) is 
the subject mean of time with SG below 70 mg/dL (3.9 mmol/L) in the Control Arm.   
 
Group1+Group 2: Time in Target Range 70mg/dL (3.9mmol/L) – 180 mg/dL (10.0mmol/L) during Night 
The endpoint of time in target range measures the time with SG in target range 70mg/dL (3.9mmol/L) – 180 
mg/dL (10.0mmol/L) during Night. The goal is to show superiority of the HCL Arm compared to the Control Arm 
in improving the time in target range. The hypothesis is mathematically expressed as:
H0: μ(HCL) ൑ μ(Control)   
Ha: μ(HCL) > μ(Control) 
where μ(HCL) is the subject mean of time with SG between 70mg/dL (3.9mmol/L) – 180 mg/dL (10.0mmol/L) 
range in the HCL Arm during Night, μ(Control) is the subject mean daily time with SG between 70mg/dL 
(3.9mmol/L) – 180 mg/dL (10.0mmol/L) range in the Control Arm. 
 
Group1+Group 2: Time in Target Range 70mg/dL (3.9mmol/L) – 180 mg/dL (10.0mmol/L) during Day and 

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Night
The endpoint of time in target range measures the time with SG in target range 70mg/dL (3.9mmol/L) – 180 
mg/dL (10.0mmol/L) during Day and Night. The goal is to show superiority of the HCL Arm compared to the 
Combined Control Arm in improving the time in target range. The hypothesis is mathematically expressed as: 
H0: μ(HCL) ൑ μ(Controls)   
Ha: μ(HCL) > μ(Controls) 
where μ(HCL) is the subject mean of time with SG between 70mg/dL (3.9mmol/L) – 180 mg/dL (10.0mmol/L) 
range in the HCL Arm during Day and Night, μ(Control) is the subject mean daily time with SG between 
70mg/dL (3.9mmol/L)  – 180 mg/dL (10.0mmol/L) range in the  Control Arm. 
 
Group1+Group 2: Change in A1C 
The endpoint of change in A1C will be evaluated for superiority in the combined groups. The goal is to show 
superiority of the HCL Arm compared to the Control Arm in reducing A1C from baseline to end of six-month 
treatment period. The hypothesis is mathematically expressed as: 
,Ϭ͗ђ;,>Ϳшђ;ŽŶƚƌŽůͿ 
Ha: μ(HCL) < μ(Control) 
where μ(HCL) is the mean of change in A1C (%) with the HCL Arm, μ(Control) is the mean of change in A1C (%) 
with the Control Arm. 
 
 
 
 
 
 
   
 
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For each Cohort (CSII, MDI or SAP) subjects will be randomized to HCL and Control Arm with a 1:1 ratio for 
greater than 6 years of age. 2-6 years of age subjects will automatically enter the HCL arm at the end of the 
run-in period.  
 
The randomization will be stratified by the diabetes management therapies at time of enrollment and baseline 
A1c categories: 
 
Diabetes Management Therapies(Cohort): 
x
CSII: Insulin pump therapy without CGM  
x
MDI   
x
SAP: Insulin pump therapy with CGM 
 
Baseline A1C categories(Group): 
x
ĂƐĞůŝŶĞϭчϴй 
x
Baseline A1C >8% 
Randomization will be based on a total of four strata per Cohort. In each stratum, block randomization will be 
used to divide potential patients into 2m blocks of size of 2n (block size can be different for each stratum). 
Please note that MDI group will be further stratified to equal number of subjects without CGM and with CGM. 
The clinical team and investigators are blind to the block size. Equal amount of subjects will be enrolled for 
ĂƐĞůŝŶĞϭчϴйŐƌŽƵƉĂŶĚĂƐĞůŝŶĞϭхϴйŐƌŽƵƉ͘ 
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The primary study population is the Intention to Treat (ITT) population, which consists of all randomized 
subjects. 
 
Per Protocol (PP) Population 
The Per Protocol (PP) population will include all randomized subjects who complete the trial without any major 
deviations, have worn the sensor for both Arms (Control ĂŶĚ,>ͿĂŶĚŚĂǀĞƵƐĞĚƵƚŽŵŽĚĞ;,>ŽŶůǇͿĨŽƌш
80% of the time. In addition, those subjects who take steroids after randomization will be excluded from PP 
population. Primary effectiveness endpoints and key secondary endpoints will be evaluated for PP Population. 
 
Safety Population 
The Safety Population will be all enrolled subjects. 
 
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Primary Effectiveness Endpoints:   
Test will be tested against the 0.025 (one-sided) significance level and both have to be met to claim success for 
the associated Cohort.  
 
Group1 – ĂƐĞůŝŶĞϭхϴй͗ŚĂŶŐĞŝŶϭ;ѐϭͿ 
The initial univariate analysis for this endpoint will be an analysis of covariance at six months.  If the computed 
F-statistic has a one-sided P<0.025 (can be computed from the two-sided F-statistic by taking the square root 
and comparing to a one-sided t-statistic), the null hypothesis will be rejected in favor of the alternative,  Other 
supporting analysis including multivariable modeling may also be done to support this finding. 
 
Group2 – ĂƐĞůŝŶĞϭчϴй͗dŝŵĞŝŶ,ǇƉŽŐůǇĐĞŵŝĐZĂŶŐĞ 
The initial univariate analysis for this endpoint will be an analysis of covariance F-test at six months.  If the 
computed F-statistic has a one-sided P<0.025 (can be computed from the two-sided F-statistic by taking the 
square root and comparing to a one-sided t-statistic), the null hypothesis will be rejected in favor of the 

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alternative.  Other supporting analysis including multivariable modeling may also be done to support this 
finding. 
 
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Adverse events will be coded based on the latest version of the Medical Dictionary for Regulatory Activities 
(MedDRA) thesaurus.  
 
 
 
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Risk Determination  
 
In the opinion of the sponsor, this study is considered to be a significant risk (SR) study.  Results of an 
evaluation of the requirements per 21 CFR Part 812.3, led to the SR determination as follows: 
x
The devices could present a potential for serious risk to subject health, safety or welfare. 
x
The devices are for a use of substantial importance in treating disease, and presents potential for 
serious risk to subject health, safety or welfare. 
Therefore, for subjects 2-13 years of age, submission of an Investigational Device Exemption (IDE) application 
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to the United States Food and Drug Administration is required
Medtronic Inc. maintains appropriate clinical study liability insurance coverage as required under applicable 
laws and regulations and will comply with applicable law and custom concerning specific insurance coverage. If 
required, a Clinical Trial Insurance statement/certificate will be provided to the IRB/EC. 
 
Institutional Review Board (IRB) / Ethics Committee (EC) 
This protocol, any subsequent amendments to this protocol, the Informed Consent/Assent form, subject 
material and any form of subject recruitment information (e.g. advertisements) relating to this study will be 
approved by the responsible EC/IRB in accordance with 21 CFR Part 56 in the US, ISO 14155:2011, Declaration 
of Helsinki and local ethic requirements, as applicable. The study will not start until IRB/EC approval has been 
granted, the Sponsor has cleared the investigational center to begin the study, and the investigational clinical 
staff has been appropriately trained to conduct the study. Copies of all relevant correspondence between the 
investigational center and the IRB/EC will be retained at investigational center and the Sponsor files. 
If the ethic committee imposes any additional requirements (e.g. safety reports, progress reports etc.), 
Medtronic will prepare the required documents and send them to the respective authority. 
 
Regulatory Submission
  
Where submission to the regulatory authority is required per local law, no patients will be enrolled in the 
clinical study until the particular regulatory authority has approved the current Clinical Investigation Plan of the 
clinical study and other documents as required according to the local requirements. 
If the regulatory authority imposes any additional requirements (e.g. safety reports, progress reports etc.), 
Medtronic will prepare the required documents and send them to the respective authority. 
Regulatory Compliance 
In Canada, Europe, Australia and New Zealand this clinical study will be conducted in compliance with the 
Declaration of Helsinki 2013, the international standard ISO 14155:2011 ('Clinical Investigation of medical 
devices for human subjects'), as well as laws and regulations of the country/ies in which the clinical study is 
conducted (including data protection laws). Europe is also compliant with FDA regulations 21 CRF Part 11 and 
21 CRF Part 54, and EU MDR.   
In Canada, SOR/98-282 will also be followed. 
In the US, this clinical study will be conducted in compliance with the Declaration of Helsinki 2013, the Clinical 
Investigation Agreement, the Clinical Investigation Plan, FDA regulations CFR, Title 21, Part 54 (Financial 
Disclosure by Clinical Investigators), CFR, Title 21, Part 11 (Electronic Records; Electronic Signatures),  21 CFR 

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Part 812 (Investigational Device Exemptions), 21 CFR Part 56 (Institutional Review Boards) , 21 CFR Part 50 
(Informed consents) and all other applicable federal and local regulatory requirements. 
All principles of the Declaration of Helsinki have been implemented in this clinical study by means of the 
informed consent process, IRB/EC approval, study training, clinical trial registration, preclinical testing, risk 
benefit assessment, publication policy, etc. 
 
Ethical Considerations 
The sponsor will avoid improper influence on, or inducement of the subject, monitor, and investigator(s) or 
other parties participating in, or contributing to, the clinical study by implementing the informed consent 
process, Clinical Investigation Agreements and IRB/EC approval. Pediatric patients (2-21 years) will be involved 
in this study and will be provided with assent as applicable. 
 
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The investigator or person designated by the investigator will document and explain any deviation from the 
approved protocol that occurs during the course of the clinical trial. The date and reason for each deviation will 
be documented. (21 CFR 812.140 Records for US/ ISO14155:2011 9.6g for Europe, Australia and New Zealand) 
The investigator should not implement any deviation from, or changes of, the protocol without agreement by 
the sponsor and prior review and documented approval/favorable opinion from the IRB/EC of an amendment, 
except where necessary to eliminate an immediate hazard(s) to trial subjects, or when the change(s) involves 
only logistical or administrative aspects of the trial (e.g., change of monitor(s), change of telephone number(s)). 
The investigator may implement a deviation from, or a change in, the protocol to eliminate an immediate 
hazard(s) to trial subjects without prior IRB/EC approval/favorable opinion. As soon as possible, the 
implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment(s) 
should be submitted: 
x
To the IRB/EC for review and approval/favorable opinion 
x
To the sponsor for agreement and, if required 
x
To the regulatory authority or authorities 
Except in an emergency, prior approval by the sponsor, regulatory authorities and IRB/EC is required for 
changes in or deviations from a plan, and if these changes or deviations may affect the scientific soundness of 
the plan or the rights, safety, or welfare of human subjects. (21 CFR 812.35(a)) for US / ISO14155:2011 4.5.4 b)) 
. 

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In any emergency situation the investigator shall exercise his/her judgment to safeguard the subject’s interest. 
The investigator shall report a deviation as soon as possible to Medtronic and the reviewing IRB/EC, according 
to IRB/EC reporting guidelines, as applicable. Medtronic will inform the regulatory authorities, if required. 
Emergency deviations must be reported to the sponsor and IRB/EC within 5 days. In Australia, clinical trials 
with unapproved medical devices require reporting of serious breaches by investigator and sponsor. 
The following examples are deviations that could impact subject safety, affect the integrity of study data 
and/or affect subject’s willingness to participate in the study. These deviations are significant and require 
immediate sponsor notification upon investigator awareness:  
x
Failure to obtain informed consent, i.e., there is no documentation of informed consent 
x
Informed consent obtained after initiation of study procedures 
x
Enrollment of a subject who did not meet all inclusion/exclusion criteria 
x
Performing study procedure not approved by the IRB/EC 
x
Failure to report serious adverse event to the IRB/EC and sponsor 
x
Investigational study device dispensed without obtaining informed consent 
Medtronic is responsible for analyzing deviations, assessing their significance, and identifying any additional 
corrective and/or preventive actions (e.g. amend the CIP, additional training, terminate the study, etc.). 
Repetitive or serious investigator compliance issues may result in the need to initiate a corrective action plan, 
and in some cases freeze enrolment or ultimately terminate the investigator’s participation in the clinical study 
(see section 10.9). 
The investigator will propose any appropriate modification(s) of the Clinical Investigation Plan or 
investigational device/product or investigational device/product use. Medtronic will review this proposal and 
decide whether the modification(s) will be implemented.  
Medtronic will submit any significant amendment to the Clinical Investigation Plan, including a justification for 
this amendment, to the appropriate regulatory authorities and to the investigators to obtain approval from 
their IRB/EC. The investigator will only implement the amendment after approval of the IRB/EC, regulatory 
authority and sponsor. Administrative amendments to the Clinical Investigation Plan will be submitted to the 
IRB/EC for notification. Furthermore investigators shall sign any approved amendment for agreement: 
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The Medtronic 24-Hour Technical Support (TS) or local service provider will be consulted for device 
troubleshooting (e.g. assistance is needed by subject to operate their device(s)). When subjects call the local 
TS, they are instructed to notify the TS operator that they are currently participating in a clinical study. All 

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device deficiencies  that are reported to the TS will be documented by the TS staff. 
Medtronic will review all device deficiencies and determine whether the deficiency requires reporting to 
regulatory agencies; vigilance reporting includes all devices that are CE marked in Europe. The sponsor will 
ensure timely Device Deficiency reporting to meet regulatory requirements. 
Note: For commercially available devices, device deficiency reporting will be documented per study and 
relevant regulatory requirements 
Depending on the country, the investigational center will be provided with a copy of all TS calls for their 
subjects. The TS calls should be reviewed for investigational center staff awareness and for the possibility of an 
AE. If an AE is detected the investigational center staff will also complete an AE eCRF. 
In the US, all device deficiencies reported directly to the investigational center staff by a subject should either 
be reported to the TS by the subject or investigational center staff.  
In Europe Canada, Australia and New Zeland all device deficiencies reported directly to the investigational 
center staff by a subject and should be documented on a Device Deficiency eCRF.  
A device deficiency is any communication that alleges inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety, or performance. NOTE: Device deficiencies include malfunctions, 
use errors, and inadequate labeling. (Adapted from ISO14155:2011 3.15) 
In the US, Canada, Europe, Australia and New Zealand: While 24-Hour TS may direct the return/replacement 
of study devices, all such transactions will be managed by investigational centers directly. Subjects are asked to 
call the 24-Hour TS for help with the troubleshooting of devices.  
It is the responsibility of the Investigator to follow the center’s IRB/EC and local regulatory authority 
reporting requirements. 
For Europe Canada, Australia and New Zealand: 
Device deficiencies that did not lead to an Adverse Event, but could have led to an SADE require immediate 
reporting to the sponsor via completion of the applicable CRF. In addition, follow the  IRB/EC and regulatory 
authority reporting requirements per ISO14155:2011 if any of the  following apply: 
a) if either suitable action had not been taken, 
b) if intervention had not been made, or 
c) if circumstances had been less fortunate  
In Australia: All device deficiencies for investigational devices with potential SADE need to be reported by 
investigator without unjustified delay (NHMRC Safety monitoring and reporting in clinical trials involving 
therapeutic goods November 2016 section C.2.b). 
 

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Monitoring will be conducted to ensure the protection and safety of human subjects, the quality and integrity 
of the clinical data, and compliance with the protocol.  The Monitoring Plan will give details on how and when 
data review will be conducted by clinical monitors. It will be updated and revised as needed due to changes in 
documents or processes.  
Employees of the Sponsor, or its designees, who have received appropriate training, will serve as the Study 
Monitor(s). Monitoring visits will be conducted based on Medtronic’s Standard Operating Procedures and the 
needs of the study. Quality documents will be followed for the conduct of all activities related to monitoring 
for this study.    
Site Qualification and Initiation Visits will be completed prior to enrollment of the first subject.  On Site study 
monitoring activities will include an inspection of completed study documents, source document verification 
and reporting, verification of database accuracy and completeness.  All subjects enrolled in the trial will be 
monitored and the eCRF data verified against the subjects’ source documents.  Following each monitoring visit, 
a report will be prepared and submitted to the Sponsor.  From initiation of study to close out visit, the Study 
Monitor(s) will assume primary responsibility for communications between the Study Investigators and the 
Sponsor. 
The Principal Investigator is responsible for ensuring that investigational center staff is appropriately trained to 
manage the protocol.  Initial and ongoing investigational center training will be provided during the Site 
Initiation Visit, subsequent monitoring visits, and regular investigational center contact.  All investigational 
center staff must complete and sign the Study Training Record(s) and maintain the record(s) in the 
investigational center regulatory binder. Prior to enrollment of the first subject, Investigators and study 
coordinators who will be participating in enrollment, eCRF completion, device insertion/application, device 
training, and consenting subjects must complete the Sponsor-required training. Investigators and staff who are 
actively engaged in the study after the start of subject enrollment must complete all required training before 
their involvement starts. 
All monitoring visits and visits from the Sponsor to the investigational center will be recorded using the 
Monitoring Visit Log. The log will be kept in the investigational center regulatory binder and the original will be 
collected and submitted to the sponsor. 
 
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All data required for analysis will be captured on eCRFs using OC-RDC module.  Original eCRFs will not be 

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considered as source data and supporting documentation will be required.  However, in cases where center-
administered, web-based subject questionnaires are considered source data, said source data is electronic and 
associated systems must comply with CRF 21 Part 11 requirements.  Electronic device data will be collected 
from the MiniMed  Pump System using Medtronic CareLink Personal for Clinical Research/CareLink Clinical 
Software. The system uses TLS technology, which encrypts all data it stores (21 CFR Part 11 compliant). Certain 
data points stored in the uploaded information may also be captured on the appropriate eCRF.  
The Investigator will ensure that all eCRFs are completed promptly, completely, and accurately. Information on 
case report forms must conform to the information in the source documents.  Medtronic will provide detailed 
instructions to assist with eCRF completion. In the event of data discrepancies, investigational centers will be 
asked to resolve queries electronically in the RDC system; otherwise, irresolvable data-related issues will be 
routed to the Sponsor for review and final disposition. An audit trail is maintained in OC-RDC to capture any 
corrections or changes of the eCRFs. If a person is only authorized to complete CRFs or to make changes to an 
already signed CRF, the investigator shall re-sign this CRF. System backups for data stored in the OC-RDC 
system will be consistent with Medtronic standard procedures. 
Medtronic will only consider eCRFs to be complete when all discrepancies between source data and eCRF have 
been resolved and eCRF content has been reviewed by a Study Monitor. In addition, specific eCRFs must also 
be reviewed and electronically signed by the Investigator, indicating his/her agreement with the accuracy of all 
recorded data. It is expected that the Investigator and his/her staff will cooperate with the monitoring team 
and provide any missing data in a timely manner. 
 
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Prior to data extraction, all collected data will undergo a final verification by Data Management.  
Documentation of this verification will be maintained in the sponsor study files.  Upon the completion of the 
verification, data will be extracted and transferred to the appropriate personnel for analysis.  
 
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Investigator Binders will be provided by the Sponsor to be maintained by the designated investigational center 
staff. Each binder will have tabs to facilitate filing of study documents. Examples include: 
x
 Medtronic Contact Information 
x
CV’s & Medical Licenses 
x
Agreement(s) 
x
Delegation of Authority Log 

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Training Records 
x
Randomization Documentation (if applicable) 
x
Laboratory Documentation 
x
Subject Identification Log 
x
Screening Log 
x
Case Report Forms (CRFs) & Instructions  
x
Sponsor/Monitor Visit Log 
x
Investigator Brochure (IB) 
x
Protocol and Amendments 
x
Device Instructions for Use (IFU) 
x
IRB/EC Documentation & Approvals 
x
IRB/EC Approved Consent Documents 
x
IRB/EC approved Investigator’s Brochure/ Report of Priors 
x
Regulatory Authority approval or notification 
x
Financial Disclosures  
x
Insurance certificates, where applicable 
x
Reports  
x
Essential Correspondence 
x
Product Accountability 
x
Regulations and Guidance Documents 
x
Site Study Materials 
x
Subject Study Materials 
x
Note to File 
x
Miscellaneous 
x
Relevant communication  
 
There will be an individual file for each subject which will include, but will not be limited to: 

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Source Documents 
x
Signed and dated Informed Consents/Assents 
x
Adverse Event Notifications, if any 
x
Questionnaires 
x
Study Logs, if any 
 
For Europe, Australia and New Zealand: The investigator will clearly mark the clinical records to indicate that 
the subject is enrolled in this clinical study.Where copies of the original source document as well as printouts of 
original electronic source documents are retained, these shall be signed and dated by a member of the 
investigational site team with a statement that it is a true reproduction of the original source document. 
 
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Medtronic reserves the right to conduct quality audits at the investigational centers in order to verify 
adherence to external regulations as well as internal policies and procedures, to assess adequacy and 
effectiveness of clinical policies and procedures, to assure compliance with critical study document 
requirements, to confirm integrity and accuracy of clinical study data and to protect the safety, rights and 
welfare of study subjects. 
These audits are done in addition to the regular monitoring visits.  
Regulatory bodies may also perform inspections at participating investigation sites. Any regulatory authority 
inspection announcements shall be forwarded immediately to the sponsor contact person. 
The investigator and/or institution shall permit Medtronic and regulatory bodies direct access to source data 
and documents, taking into account any restrictions due to local law, to perform clinical study-related 
monitoring, audits, EC/IRB review, and regulatory inspections. 
 
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The investigator will ensure that the subject’s anonymity is maintained.  Subjects will not be identified in any 
publicly released reports of this study.  All records will be kept confidential to the extent provided by federal, 
state and local law.   The study monitors and other authorized representatives of the Sponsor may inspect all 
documents and records required to be maintained by the Investigator, including but not limited to, medical 
records.  The investigator will inform the subjects that the above-named representatives will review their 

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study-related records without violating the confidentiality of the subjects. All laboratory specimens, evaluation 
forms, reports, and other records that leave the site will be identified only by the subject identification code in 
order to maintain subject confidentiality.  All records will be kept locked and all computer entry and 
networking programs will be done with coded numbers only. 
 
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Medtronic maintains appropriate clinical study liability insurance coverage as required under applicable laws 
and regulations and will comply with applicable local law and custom concerning specific insurance coverage. If 
required, a clinical study insurance statement/certificate will be provided to the EC. 
 
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When an amendment is required, the CIP will be forwarded to FDA and applicable regulatory authorities 
outside the United States for approval. Upon receipt of regulatory authority approval, the document will be 
version controlled using the next version number in succession, e.g. A to B. After the document is released by 
Medtronic’s document control system, it will be submitted to all applicable regulatory agencies, IRBs and Ethics 
Committees for review and approval. Individual investigational centers may not enroll subjects under the 
amended investigational plan until Regulatory/IRB/Ethics approvals have been obtained including, if applicable, 
a revised Informed Consent.  
 
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The Sponsor and Investigator will retain all records and documents pertaining to this study. They will be 
available for inspection by the appropriate regulatory agencies. In addition, the Investigator will retain the 
source documents from which the information entered on the eCRF was derived. These records are to be 
retained in a secure storage facility maintained by the investigational center until 2 years (or longer if local laws 
require) after approval of the above-listed study devices or termination of the study, whichever is longer. The 
Investigator should not dispose of these records without the approval of the Sponsor. The investigator should 
take measures to prevent accidental or early destruction of the clinical study related materials.  
 

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The contents of this protocol, the manuals pertaining to this study and the results of the investigation are 
confidential and may not be published or disclosed without the written consent of Medtronic Diabetes.  The 
identity of the subjects may not be disclosed, unless required by law, to any persons not immediately involved 
in the study or the study procedures. The results of the clinical study will be submitted for publication and 
handled according to Standard Operating Procedures. 
 
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This study will be conducted at up to 70 investigational centers where all study-related activities will take place; 
at each center, the study will be led by a principal investigator. Per 21 CFR 812.3(i), Investigator means an 
individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article 
is administered or dispensed to, or used involving, a subject, or, in the event of an investigation conducted by a 
team of individuals, is the responsible leader of that team.  
It is expected that the investigator(s) are familiar with the regulations governing the conduct of clinical 
research on human subjects. Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, 
and Welfare of Study Subjects provides clarification for investigators and sponsors. 
 FDA’s expectations concerning the investigator’s responsibility  
(1) to supervise a clinical study in which some study tasks are delegated to employees or colleagues of the 
investigator or other third parties and 
(2) to protect the rights, safety, and welfare of study subjects 
 
The investigator’s responsibilities include: 
x
Ensuring that a clinical investigation is conducted according to the signed investigator statement for 
clinical investigations of medical devices, the investigational plan, and applicable regulations set forth 
in 21 CFR Part 812 and all other applicable regulations, and any conditions of approval imposed by an 
IRB/EC or regulatory requirements. 
x
Medtronic contracts with participating institutions/investigators through a Clinical Trial Agreement 
that defines the scope and responsibilities and associated compensation related to carrying out the 
obligations under a clinical study sponsored by Medtronic. 
x
Protecting the rights, safety, and welfare of subjects under the investigator’s care 
R Providing reasonable medical care for study subjects for medical problems that arise during 

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participation in the trial that are, or could be, related to the study intervention
R Providing reasonable access to needed medical care, either by the investigator or by another 
identified, qualified individual (e.g., when the investigator is unavailable, when specialized care 
is needed) 
R Adhering to the protocol so that study subjects are not exposed to unreasonable risks 
x
Controlling devices under investigation (21 CFR 812.100 for US / ISO14155:2011 6.9 for Europe, 
Australia & New Zealand and in accordance with Canadian regulations where applicable). 
x
Investigator is responsible for providing adequate supervision of those to whom tasks have been 
delegated. The investigator is accountable for regulatory violations resulting from failure to adequately 
supervise the conduct of a clinical study.  
x
Ensuring that informed consent is obtained from each subject in accordance with 21CFR Part 50 for the 
US, Tri-Council Policy Statement, Article 3.2 for Canada and ISO14155:2011 for Europe, Australia & 
New Zealand and that the study is not commenced until regulatory authority and IRB/EC approvals 
have been obtained.  
x
Supervising the use of investigational device. In US, an investigator shall permit an investigational 
device to be used only with subjects under the investigator’s supervision. In US, an investigator shall 
not supply an investigational device to any person not authorized under 21 CFR Part 812 to receive it. 
In Europe and Australia, the investigational devices shall only be used in the clinical investigation and 
according to the protocol (ISO14155:2011 6.9). 
x
Disposing of device properly. Upon completion or termination of a clinical investigation or the 
investigator’s part of an investigation, or at the sponsor’s request, an investigator shall return to the 
sponsor any remaining supply of the device or otherwise dispose of the device as the sponsor directs.  
x
Continuously monitoring, assessing and documenting risks  
x
An investigator shall maintain at a minimum the following accurate, complete and current records 
relating to the investigator’s participation in an investigation (21 CFR 812.140 140 for US, 
ISO14155:2011 7.4 for Europe, Australia and New Zealand):
x
Correspondence with another investigator, an IRB/EC, the sponsor, a monitor or FDA/ local regulatory 
authority in Europe, Australia and New Zealand. 
x
Records of receipt, use or disposition of study devices 
x
Records of each subject’s case history and exposure to the study devices 
x
Documents showing the dates of and reasons for each deviation from the protocol 
x
Any other records the FDA/ local regulatory authority in Europe, Australia & New Zealand requires to 
be maintained by regulations or by specific requirement for a category of investigations or a particular 

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investigation
x
Investigators are required to permit FDA/ local regulatory authority to inspect and copy any records 
pertaining to the investigation including, in certain situations, those which identify subjects.(21 CFR 
812.145 in US / ISO14155:2011 6.7) 
x
An investigator shall prepare and submit the following complete, accurate, and timely reports 
 
Table 17. Investigator records and reporting responsibilities applicable to the United States 
Report 
Submit To 
Description/Constraints 
Withdrawal of IRB 
approval (either 
suspension or 
termination)  
Sponsor  
An investigator shall report to the sponsor, within 5 working 
days, a withdrawal of approval by the reviewing IRB of the 
investigator's part of an investigation. (21 CFR 
812.150(a)(2)).  
Progress report  
Sponsor and IRB  The investigator must submit this report to the sponsor and 
IRB at regular intervals, but in no event less than yearly. (21 
CFR 812.150 (3)).  
Study deviations  
Sponsor and IRB  Notice of deviations from the CIP to protect the life or 
physical well-being of a subject in an emergency shall be 
given as soon as possible, but no later than 5 working days 
after the emergency occurred. (21 CFR 812.150(a)(4))  
Failure to obtain IC 
prior to investigational 
device use  
Sponsor and 
IRBs  
If an investigator uses a device without obtaining informed 
consent, the investigator shall report such use within 5 
working days after device use. (21 CFR 812.150(a)(5))  
Final investigator 
report 
Sponsor, IRB s 
and Relevant 
Authorities  
This report must be submitted within 3 months of study 
completion or termination of the investigation or the 
investigator’s part of the investigation. (21 CFR 
812.150(a)(6))  
Other 
IRB and FDA 
An investigator shall, upon request by a reviewing IRB, FDA 
or any other regulatory agency, provide accurate, complete, 
and current information about any aspect of the 
investigation. (21 CFR 812.150(a)(7))  
 

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Table 18. Investigator Reports Applicable to Europe 
Report 
Submit To 
Description/Constraints 
Withdrawal of MEC 
approval 
Sponsor  
The investigator must report a withdrawal of approval by 
the reviewing MEC of the investigator’s part of the 
investigation within 5 working days of the date of 
withdrawal. (Medtronic Requirement)  
Progress Report  
Sponsor and Ethics 
Committee 
Provide if required by local law or EC.  
(ISO 14155:2011)  
Study Deviations  
Sponsor and Ethics 
Committee and 
Regulatory 
Authority  
Any deviation from the CIP shall be recorded together with 
an explanation for the deviation. Deviations shall be 
reported to the sponsor who is responsible for analyzing 
them and assessing their significance.  
Note: When relevant, ECs, regulatory authorities or the 
appropriate regulatory bodies should be informed. (ISO 
14155:2011)  
Notice of deviations from the CIP to protect the life or 
physical well-being of a subject in an emergency shall be 
given as soon as possible, but no later than 5 working days 
after the emergency occurred.  
Final investigator 
report 
Ethics Committee 
and Relevant 
Authorities  
This report must be submitted within 3 months of study 
completion or termination of the investigation or the 
investigator’s part of the investigation.  
Table 19. Investigator Reports Applicable to Canada 
Report 
Submit To 
Description/Constraints 
Withdrawal of 
Ethics Committee 
approval 
Sponsor  
The investigator must report a withdrawal of approval by 
the reviewing Ethics Committee of the investigator’s part of 
the investigation within 5 working days of the date of 
withdrawal. (Medtronic Requirement)  

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Report 
Submit To 
Description/Constraints 
Progress Report  
Sponsor and Ethics 
Committee  
Provide if required by local law or EC.   
Study Deviations  
Sponsor and Ethics 
Committee  
Any deviation from the CIP shall be recorded together with 
an explanation for the deviation.  
Notice of deviations from the CIP to protect the life or 
physical well-being of a subject in an emergency shall be 
given as soon as possible, but no later than 5 working days 
after the emergency occurred.  (Medtronic Requirement)  
Final investigator 
report 
Ethics Committee 
and Relevant 
Authorities  
This report must be submitted within 3 months of study 
completion or termination of the investigation or the 
investigator’s part of the investigation. (Medtronic 
Requirement)  
 
Table 20 Investigator Reports Applicable to Australia  
Report 
Submit To 
Description/Constraints 
Withdrawal of 
Ethics Committee 
approval 
Sponsor  
The investigator must report a withdrawal of approval by the 
reviewing Ethics Committee of the investigator’s part of the 
investigation within 5 working days of the date of withdrawal.  
Progress Report  
Sponsor and 
Ethics 
Committee  
Provide if required by local law or EC.   
Study Deviations  
Sponsor and 
Ethics 
Committee 
Any deviation from the CIP shall be recorded together with an 
explanation for the deviation. Notice of deviations from the 
CIP to protect the life or physical well-being of a subject in an 
emergency shall be given as soon as possible, but no later 
than 5 working days after the emergency occurred.   
Final Investigator 
Report  
Ethics 
Committee and 
Relevant 
Authorities  
This report must be submitted within 3 months of study 
completion or termination of the investigation or the 
investigator’s part of the investigation.  
Serious Breaches by 
Sponsor, 
Investigator shall report any suspected breaches to the 

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Report 
Submit To 
Description/Constraints 
Investigator or 
Sponsor 
(Pre-market 
requirement) 
Institution’s 
Research 
Governance 
Office, Ethics 
Committee, or 
Principal 
Investigator as 
applicable 
sponsor and confirmed serious breaches to their institution 
(research governance office) within 72 hours of becoming 
aware or notified of the same; provide any follow-up 
information as required and work with the institution or 
sponsor, as appropriate, to implement any corrective and 
preventative actions by sponsor shall report serious breaches 
to the reviewing HREC and PI within 7 calendar days of 
confirming a serious breach has occurred and provide follow-
up reports when required 
Australia - Serious Breach: A breach of Good Clinical Practice 
or the protocol that is likely to affect to a significant degree:  
a) The safety or rights of a trial participant,or b) The reliability 
and robustness of the data generated in the clinical trial. 
Significant Safety 
Issues
(Pre-market 
requirement) 
Sponsor, HREC 
and institution
Urgent Safety Measure (USMs): Within 24 hours (NHMRC 
Safety monitoring and reporting in clinical trials involving 
therapeutic goods November 2016 section C.2.c) 
All other significant safety issues: without undue delay and no 
later than 72 hours of the principal investigator becoming 
aware of the event (NHMRC Safety monitoring and reporting 
in clinical trials involving therapeutic goods November 2016 
section C.2.g) 
 
 
Table 21 Investigator Reports Applicable to New Zealand 
Report 
Submit To 
Description/Constraints 
Withdrawal of 
Ethics Committee 
approval 
Sponsor  
The investigator must report a withdrawal of approval by 
the reviewing Ethics Committee of the investigator’s part of 
the investigation within 5 working days of the date of 
withdrawal. (Medtronic Requirement)  
Progress Report  
Sponsor and Ethics 
Committee  
Provide if required by local law or EC.   

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Report 
Submit To 
Description/Constraints 
Study Deviations  
Sponsor and Ethics 
Committee  
Any deviation from the CIP shall be recorded together with 
an explanation for the deviation.  
Notice of deviations from the CIP to protect the life or 
physical well-being of a subject in an emergency shall be 
given as soon as possible, but no later than 5 working days 
after the emergency occurred.   
Final investigator 
report 
Ethics Committee 
and Relevant 
Authorities  
This report must be submitted within 3 months of study 
completion or termination of the investigation or the 
investigator’s part of the investigation.   
 
 
x
To the sponsor and IRB/EC (per their requirements): 
R Any unanticipated adverse device effect occurring during an investigation. (Due no later than 
24 hours after the investigator first learns of the effect) 
x
It is prohibited to promote and commercialize a device that has not been first cleared or approved for 
marketing by the FDA (per IDE regulations) or local regulatory authority in Europe,Canada, Australia or 
New Zealand.  
x
The principal investigator(s) are required to assess whether or not to continue the clinical study at the 
respective investigation site.  
x
The principal investigator(s), his/her delegate(s) and the study coordinator(s) shall be accessible to 
Medtronic personnel. This accessibility is of particular importance for reviewing data in the Case 
Report Form (CRF). Direct access to patient medical files for source data verification will need to be 
granted and prepared prior to any monitoring visits 
x
Sponsor will inform the clinical investigators of termination or suspension and the reasons and inform 
the regulatory authorities, where required. 
The investigator’s signature on the Investigator Statement confirms that the investigator is familiar with the 
protocol in its entirety and agrees to conduct this study in accordance with the provisions of the protocol and 
all applicable regulations.  The investigator, prior to the initiation of any study related activity, will sign the 
Investigator Statement. If the Sponsor discovers that an Investigator is not complying with the Investigator 
Statement, investigational protocol, or other regulatory requirements, the Sponsor shall promptly secure 
compliance or discontinue that Investigator’s participation in the study. 
 

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Upon completion of the study, when all subjects have completed their visit schedules (all eCRFs have been 
entered and all related queries have been resolved), all study devices, unused study materials and equipment 
will be collected and returned to Medtronic and/or its designees. Medtronic and/or its designees will notify the 
investigational center of its intention to close out the study and a close-out visit will be conducted. The 
Monitor will ensure that the Investigator’s regulatory files are up-to-date and complete and that any 
outstanding issues from previous visits have been resolved. Other issues that will be reviewed at this visit 
include discussing retention of study files, possibility of investigational center audits, and notifying the IRB/EC 
of study closure. 
 
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American Diabetes Association. Hyperglycemic Crises in Diabetes. Diabetes Care. 2004; 27(1) S94-S102. 
American Diabetes Association Workgroup on Hypoglycemia. Defining and Reporting Hypoglycemia in 
Diabetes, Diabetes Care. 2005. 28: 1245-9. 
Diabetes Research in Children Network (DirecNet) Study Group; Type 1 Diabetes TrialNet Study Group, 
Buckingham BA, Beck RW, Ruedy KJ, Cheng P, Kollman C, Weinzimer SA, DiMeglio LA, Bremer AA, Slover R, 
Cantwell M. The effects of inpatient hybrid closed-loop therapy initiated within 1 week of type 1 diabetes 
diagnosis. Diabetes Technol Ther. 2013. May;15(5):401-8. 
Medtronic, HCL Outcomes Study Clinical Study Training Protocol.Weinzimer et. al: Fully Automated Closed 
Loop Delivery versus Semi-Automated Hybrid Control in Pediatric Patients with Type 1 diabetes using the 
Artificial Pancreas. Diabetes Care, 2008, 31:934-939. 
 

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A 
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Not applicable, New Document 
 
 
B
x
Corrected visit schedule  
x
Revised Statistical Section 
x
Updated Visit Tables 
x
Revised Subject Stopping Rules 
x
Revised Safety Section according to new Meddev 
regulations  
x
Deleted redundancies 
x
Revised Visit Schedule 
x
Revised DMC Section 
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Revised Study and Continuation Period 
Summaries 
x
Updated Inclusion Criteria 
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Revised Safety Success Criteria table 
 
 
C 
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Updated device classifications 
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Revised inclusion/exclusion criteria 
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Revised device accountability tables 
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Revised Risk/Mitigations tables 
 
 
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numbers 
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Updated and corrected Visit Schedule Tables and 
transferred visit tables into Appendix. 
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Updated study procedures (includes run-in period 
window and additional study visits for each group 
after Auto Mode is turned on) 
x
Revised inclusion/exclusion criteria 
x
Updated subject withdrawal or discontinuation 
criterias 
x
Updated subject stopping rules 
x
Revised device accountability tables 
x
Updated Adverse Events Assessment section 
x
Removed statement about regulatory submission 
in Israel 
x
Modified pediatric distribution for enrollment in 
CSII cohort. 
x
Transferred to updated version of Medtronic 
corporate branded form CIP template (Version 
3.0) 
x
Moved CIP version history table to end of 
document 
x
Updated Packaging section– removed 
investigational labeling statement for US and 
added statement that copies of labeling for study 
devices will be provided under separate cover 
x
Updated device descriptions for infusion sets, 
reservoirs and infusion set serter devices 
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Provided information about subjects who are 
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the sites  
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Added Liability section to align with CIP required 
elements 
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Updated IRB/Ethics requirements  
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Updated Device Deficiencies and Troubleshooting 
section 
E 
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Statement updated to reflect investigational 
devices in US for subjects 2-6 years age group  
x
Updated protocol to reflect CE marked devices 
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Updated Run-in and Study period - additional 
clarification to the blinded CGM section 
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Permitted MDI subjects with concurrent CGM to 
enroll 
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Updated sample size number during study period 
for Cohort 2: MDI subjects 
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Added sensor insertions should proceed with 
approved User Guide 
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Inclusion criteria #6 updated 
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Removed exclusion criteria #1 
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Added Early withdrawal procedures  
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Updated Visit Schedule Tables 
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Made changes to Exploratory analysis section 
regarding alert performance  
x
Added statement regarding SMBG confirmation 
upon low alert 
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Added statement regarding investigational 
labeling requirement to visit table attachments in 
each cohort 
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Re-arranged devices according to age group in 
synopsis and Table 7.2 
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Deleted references to the 670G system to allow 
for inclusion of the 770G system. 
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Added 770G system and devices to reflect 770G 
system approval and use in the US and other 
geographies. 
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Updated study duration to 6.5 years, enrollment 
completion to 54 months, Table 5 and Table 6 to 
account for a slow-down in pediatric enrollment. 
Deleted Chart 1 and Chart 2. 
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requirement for subjects 2-13 years of age. 
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all enrolled subjects will participate in the study 
group only 
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Updated telemedicine requirements 
x
Updated Medtronic CareLink Clinical Therapy 
Management Software name to reflect the 
correct product name. 
x
Updated the treatment cohort statement to allow 
for transition to the 770G system in US and 
Canada. 
x
Added the Contour Next Link 2.4 Blood Glucose 
Meter to the list of investigational devices for US 
subjects 2-6 years. 
x
Updated product status headings and bullets for 
clarity. 
x
Deleted note on StartRight program. 
x
Updated visit scheduling to avoid visit window 
overlap. 
x
Added explanation of remote monitoring for 
pediatric patients. 
x
Updated Table 7 to reflect correct numbers for 
parts distributed in Canada. Added footnotes for 
clarity. 
x
Added Table 8 to reflect addition of 770G to the 
study. 
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Updated Table 9 to incorporate 770G pump and 
related devices. Split Guardian Sensor (3) into 2 
rows to account for difference in disbursement to 
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Canada and update device disposition. 
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rows, correct part numbers and update 
disbursement to subject. 
x
Added Table 12 and 13 to reflect Australian and 
New Zealand requirements. 
x
Added Reporting of Use Errors section per FDA 
guidance. 
x
Updated document to align new EUMDR 
guidelines which includes name of the local 
sponsor contact, specific language related to 
public databases (e.g., clinicaltrials.gov), product 
accountability, deviations, Europe record 
retention requirement, regulatory compliance 
statement, glossary, and investigator statement. 
x
Updated Investigator Statement name to reflect 
the correct name of form. 
x
Updated trademark notation to conform with 
updated trademarking by Ascensia. Contour Next 
Link is no longer owned by Bayer. 
x
Updated Clinical Study Type for clarity. 
x
Updated Schedule of Events introduction 
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Updated Early Withdrawal description for clarity. 
x
Corrected MDI Cohort Visit 7 description.  
x
Updated document to reflect new CIP 
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template requirements, including Study Site 
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to Follow-up definition, Risk Minimization section, 
updated document footer, study binder tab list, 
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Updated AE Assessment section headings for 
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Updated AE, SAE, and ADE definitions for clarity. 
x
Updated Sponsor Notification for clarity. 
x
Updated Introduction  to include recent study 
results. 
x
Updated Blue Adapter CareLink Clinical 
Application and Guardian Link (3) descriptions for 
clarity. 
x
Updated glossary to reflect new abbreviations. 
x
Update 24-Hour HelpLine to 24-Hour Technical 
Support. 
x
Updated Device Deficiencies and Troubleshooting 
section for clarity. 
x
Added new reference to References section. 
x
Updated Appendix section to reflect the correct 
file names. 
x
Updated the Cohort Appendices to remove the 
TSH, A1C, and c-peptide requirement for subjects 
2-13 years of age.  
x
Corrected small typographical errors throughout 
the document. 
x
Updated date and version number to reflect new 
version of CEP. 
x
Updated Version History. 
x
For detailed information, see “CEP304 Summary 
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x
Updated sponsor contacts to correct titles. 
x
Removed sponsor contact name/title for Canada. 
x
Updated Section 1 heading to conform to 
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x
Updated Primary Objective section to include 
additional detail. 
x
Added Data Collection section to conform to 
template. 
x
Updated Sample Size Considerations to include 
updated subject availability statement.  
x
Added number of subjects currently enrolled to 
synopsis and study design sections to address FDA 
request 
x
Corrected small typographical errors throughout 
the document. 
x
Updated date, version number and document 
footer to reflect new version of CEP. 
x
Updated Version History. 
x
Updated page headers, and section titles to 
conform to corporate template updates.  
x
For detailed information, see “CEP304 Summary 
of Protocol Changes, Version G to H”. 
 
 
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