Multi-Center, Prospective, Observational Study of the TS (Threshold Suspend) Feature With a Sensor-Augmented Pump System in Pediatric Patients With Type 1 Diabetes
Phase: NA
Conditions: Type 1 Diabetes
Sponsor: Medtronic MiniMed, Inc.

 
ClinicalTrials.gov Uploaded Document Cover Page 
 
 
 
Study Title  Multi-Center, Prospective, Observational Study of the TS (Threshold 
Suspend) Feature with a Sensor-Augmented Pump System in Pediatric 
Patients with Type 1 Diabetes 
NCT Number NCT02120794 
Document Description Study Protocol (Version C) 
Document Date 17 August 2015 
 

 
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Title: 
 
Multi-Center, Prospective, Observational Study of the TS (Threshold 
Suspend) Feature with a Sensor-Augmented Pump System in 
Pediatric Patients with Type 1 Diabetes
 
Protocol Number: 
 
CEP287/Z25/C (FDA version C.3) 
Sponsor: 
 
Medtronic MiniMed, Inc. 
(“Medtronic”) 
18000 Devonshire St 
Northridge, CA 91325 
866.948.6633 
 
Date of Protocol: 
 
17 Aug 2015 
 
 
 
Confidential Information 
This document contains proprietary and confidential information and may not be used, divulged, published, or 
otherwise disclosed without the prior written consent of Medtronic, Inc. 
 
 
 
 
 
 

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TABLE OF CONTENTS  
 
 
1. 
Background ......................................................................................................................................... 9 
2. 
Devices and Supplies ........................................................................................................................ 10 
3. 
Objective and Hypothesis ................................................................................................................. 12 
4. 
Study Design ..................................................................................................................................... 12 
5. 
Study Population ............................................................................................................................... 13 
6. 
Statistical Methods and Data Analysis............................................................................................. 14 
7. 
Institutional Review Board ............................................................................................................... 21 
8. 
Subject Confidentiality ..................................................................................................................... 21 
9. 
Investigator Responsibilities ............................................................................................................. 22 
1 
DOCUMENT HISTORY .................................................................................................................. 44 
 

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Synopsis   
 
Study Design: 
 
This study is a longitudinal, multi-center trial that aims to observe the Threshold Suspend 
(TS) feature with a sensor-augmented insulin pump in patients 7–15 years with Type 1 
diabetes. The study will measure the change in A1C from baseline over a period of one 
year while subjects are wearing the study pump. 
 
Devices: 
Investigational Devices 
 
Medtronic MiniMed® 530G (MMT-551, MMT-751) Insulin Pump, referred to as the 
study pump in the protocol.   
 
Medtronic MiniMed Enlite™ Glucose Sensor (MMT-7008), referred to as glucose 
sensor in the protocol 
 
Medtronic MiniMed MiniLink® 2 REAL-Time Transmitter (MMT- 7713), referred to as 
MiniLink 2 throughout this protocol 
 
Enlite™ Serter (MMT-7510), referred to as Enlite serter in the protocol 
 
Medtronic CareLink® Therapy Management Software for Diabetes (MMT-7334) – 
referred to as CareLink Clinical in the protocol 
 
Non-Investigational Devices  
 
Paradigm Remote Control/Programmer (MMT-503) - Optional 
 
Medtronic MiniMed charger (MMT-7705) 
 
Medtronic MiniMed CareLink® USB (MMT-7305) 
 
Medtronic MiniMed Test Plug (MMT-7706) 
 
Bayer CONTOUR™ Next Link RF enabled Blood Glucose Meter (HMS 9740) 
 
Study Objective: 
  
The study objective is to demonstrate that home use of Threshold Suspend (TS) is not 
associated with glycemic deterioration in pediatric patients with type 1 diabetes, as 
measured by change in A1C. 
 
 
Primary Study 
Endpoint and 
Hypothesis:  
 
The overall mean change in A1C from baseline will be estimated and compared by a 
non-inferiority test with an A1C margin of 0.4% and a significance level of 0.025 (one-
sided). 
Secondary 
Endpoint 
 
The mean change in A1C from baseline to end of study for each individual A1C cohort 
 
Baseline A1C 
o 
A1C less than 7.0% (Minimum N=50) 
o 
A1C between 7.0% to 9.0% (Minimum N=50) 
o 
A1C greater than 9.0% (Minimum N=50) 
 
 
Safety Endpoints: 
 
 
The following Safety information will be collected: 
 
Serious Adverse Events (SAE) 
 
Unanticipated Adverse Device Effects (UADE) 
 
Incidence of Severe Hypoglycemia 
 
Incidence of Severe Hyperglycemia 
 
Incidence of Diabetic Ketoacidosis (DKA) 
 
Adverse Events will be stratified by age, ethnicity, baseline BMI, gender, duration 
of diabetes, hypoglycemia awareness, frequency and average duration of 
hypoglycemic event (based on two weeks prior to the adverse event) 
 
 
 
 

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Number of 
Subjects and 
Study Population: 
  
Up to 300 subjects will be enrolled so that there will be 200 subjects who are eligible to 
participate in the study.    
 
Up to 20 Investigational centers will be selected across the United States. Selection is 
based on each Investigator’s experience and qualifications, availability of sufficient 
resources to carry out the required study procedures and the investigator’s ability to 
recruit subjects into the study.  
 
Subjects will be grouped by baseline demographics:  Baseline A1C, age, ethnicity, body 
mass index (BMI), gender and duration of diabetes and hypoglycemic awareness. 
Sponsor will oversee distribution of subjects across study sites.   
 
 
Baseline A1C 
o 
A1C less than 7.0% (Minimum N=50) 
o 
A1C between 7.0% to 9.0% (Minimum N=50) 
A1C greater than 9.0% (Minimum N=50) 
 
 
Race  
o 
American Indian/Alaska Native  
o 
Black/African-American  
o 
White - anticipated maximum  80%  
o 
Native Hawaiian/Other Pacific  Islander  
o 
Asian   
o 
Subject Refused 
 
Ethnicity 
o 
Hispanic/Latino  
o 
Non-Hispanic/Non-Latino  
o 
Subject refused 
 
 
Diabetes cohorts based on BMI percentile: 
 

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Weight Status 
Category 
Percentile Range 
N=Minimum 
Underweight 
Less than the 5th percentile 
2 
Healthy weight 
5th percentile to less than the 85th 
percentile
30 
Overweight 
85th to less than the 95th percentile 
4 
Obese 
Equal to or greater than the 95th 
percentile
1 
 
BMI Percentiles according to CDC: 
http://www.cdc.gov/healthyweight/assessing/bmi/childrens_bmi/about_childrens_bmi.html
 
 
Gender 
o 
Male (minimum  N=80) 
o 
Female (minimum  N=80) 
 
 
Hypoglycemic awareness 
o 
Patients with intact hypoglycemic awareness (minimum N=60) 
o 
Patients who have impaired hypoglycemic awareness (minimum 
N=40) 
 
Inclusion Criteria: 
 
 
1. Subject is age 7 to 15 at time of screening 
2. Subject has been diagnosed with type 1 diabetes mellitus  and must have 
been diagnosed for at least one year prior to screening 
3. Subject is currently transitioning from  pump therapy, with or without 
continued glucose monitoring (CGM), to the 530G insulin pump system. 
4. Subject is willing to perform greater than or equal to 4 finger stick blood 
glucose measurements daily  
5. Subject is willing to perform required sensor calibrations  
6. Subject is willing to wear the system (Pump, glucose sensors, meter) 
continuously throughout the study  
7. Subject is willing to upload data every 21 days from the study pump 
8. Subject must have Internet access and access to a computer system that 
meets the requirements for uploading the pumps. This may include use of 
family or friend’s computer system with Internet access. 
9. Subject is using either Humalog or Novolog at time of Screening and plans 
to use either of those insulins throughout the study 
 
Exclusion Criteria: 
 
 
1. Subject is actively participating in an investigational study (drug or device) 
wherein he/she is receiving treatment from an investigational study drug or 
investigational study device.  
2. Women of child-bearing potential who have a positive pregnancy test at 
screening or plan to become pregnant during the course of the study  
3. Subject is being treated for hyperthyroidism at time of screening 
4. Subject has an abnormality (>1.8mg/dL) in creatinine at time of screening 
visit 
5. Subject has an abnormality (out of reference range)  in thyroid-stimulating 
hormone (TSH) at time of screening visit 
 
If TSH is out of range, Free T3 and Free T4 will be tested 
 
Subject may be included with TSH out of range as long as Free T3 
and Free T4 are in normal reference range.   
6. Subject has taken any oral, injectable, or IV steroids within 8 weeks from 
time of screening visit, or plans to take any oral, injectable, or IV steroids 
during the course of the study 
7. Subject is currently abusing illicit drugs 
8. Subject is currently abusing prescription drugs   

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9. Subject is currently abusing alcohol 
10. Subject is using pramlintide (Symlin) at time of screening 
11. Subject has a sickle cell disease, hemoglobinopathy; or has received red 
blood cell transfusion or erythropoietin within 3 months prior to time of 
screening  
12. Subject plans to receive red blood cell transfusion or erythropoietin over the 
course of study participation     
13. Subject diagnosed with current eating disorder such as anorexia or bulimia 
14. Subject has been diagnosed with chronic kidney disease that results in 
chronic anemia  
15. Subject is on dialysis 
16. Subject is already on a 530G system with CGM for 8 days or more. 
 
Visit Schedule: 
 
 
Subjects will attend 5 study visits 
 
The schedule for  subjects is planned out as follows:  
Details are in Table 1: Visit Plan and Study Activities 
Visit 1 
Day 0  
Visit 2 
Day 90 (±21) 
Visit 3 
Day 180 (±30) 
Visit 4 
Day 270 (±30) 
Visit 5 
Day 365 (+30) 
Consent 
Screening 
A1C 
Device 
Disbursement  
EQ5-5DYouth 
questionnaire 
HFS Parent 
questionnaire 
HFS Child/Teen 
questionnaire 
Hypoglycemia 
Unawareness 
questionnaire 
Study Pump 
training 
CGM training 
 
A1C 
Device 
Disbursement  
CareLink upload 
 
A1C 
Device 
Disbursement  
CareLink upload 
  
A1C  
Device 
Disbursement  
CareLink upload 
  
End of Study 
CareLink upload 
A1C 
EQ5-5DYouth 
questionnaire 
HFS Parent 
questionnaire 
HFS Child/Teen 
questionnaire 
Hypoglycemia 
Unawareness 
questionnaire 
Return of Study 
Devices and 
supplies 
 

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1. 
Background 
Continuous Subcutaneous Insulin Infusion (CSII), or pump therapy, allows for insulin to be delivered 
continuously into the body, as opposed to delivery at specific times. Rapid-acting insulin is infused into 
the body at constant/basal rates throughout a 24-hr period via the insulin pump which mimics normal 
insulin secretion from the pancreas. Additional rapid-acting insulin can be delivered in boluses to 
compensate for anticipated fluctuations in blood glucose in response to meals.  
 
Frequent self-monitoring of blood glucose (SMBG) is also an important part of the management of Type 1 
diabetes.  Careful attention to blood glucose values throughout the day allows patients to more precisely 
adjust insulin dosages. However, because SMBG values are taken only at specific time points and 
measure brief instances of time within a 24-hour period, there are limits to the usefulness of this 
information. The “snap-shot” effect of SMBG proves to be a challenge for tracking of blood glucose (BG) 
trends which can be overcome through the addition of continuous interstitial glucose monitoring to the 
SMBG regimen. 
 
Current methods of continuous glucose monitoring (CGM) include the use of subcutaneous glucose 
sensors worn by the user which convert glucose from the subject’s interstitial fluid into an electronic 
signal, the strength of which is proportional to the amount of glucose present in the fluid.  The Paradigm® 
System, which received market approval from FDA on April 7, 2006 (P980022/S013), combined the 
technology of the Paradigm Insulin Pump (Models 522/722) with that of the MiniMed Guardian® REAL-
Time Clinical device. The Paradigm System represents a combination of innovative therapies for the 
treatment of Type 1 diabetes mellitus: Pump therapy in conjunction with continuous interstitial glucose 
monitoring, as well as SMBG to perfect treat-to-glycemic–target approach.  
 
In this study, the sensor is attached to a transmitter which sends interstitial glucose information to the 
study Pump via radio signals. The pump screen is the data collection/user interface of the system and 
provides continuous real-time glucose values to the user, as well as high/low glucose alerts set according 
to the individual patient’s needs. The Diabetes Control and Complications Trial (DCCT) convincingly 
established the benefits of tight glucose control in the avoidance of long-term diabetic complications. 
However, a pitfall of the aggressive management of diabetes using intensive insulin regimens is an 
increased frequency of hypoglycemia. Surveys investigating the prevalence of hypoglycemia have 
provided some alarming results. The DCCT reported a threefold increase in severe hypoglycemia and 
coma in intensively treated patients versus conventionally treated patients [DCCT Research Group, 
1991]. 
 
For many individuals with diabetes, episodes of severe hypoglycemia are the major obstacle to the 
achievement of euglycemia and the prevention of long-term complications. Hypoglycemia is frightening to 
patients and their families. It has been estimated that about 55% of severe hypoglycemic episodes occur 
during sleep. Acutely diminished brain function during a hypoglycemic episode poses potential physical 
danger to the patient. In addition, recurrent hypoglycemia may impose long-lasting damaging effects on 
the brain, resulting in impairment of memory or other cognitive functions.   
 
In addition to adversely affecting cognition, recurrent hypoglycemia also impairs the body’s defense 
mechanisms against hypoglycemia, creating a vicious cycle for the patient. Normally, hypoglycemia 
triggers a series of hormonal and neural responses designed to restore glucose concentration towards 
normal, to maintain brain metabolism.  A component of this counter-regulatory response is the secretion 
of epinephrine, which generates “neurogenic” symptoms (e.g., palpitations, sweating, and anxiety) that 
serve to warn the patient of the drop in blood glucose.  The patient can then take action (i.e., eat) to help 
reverse the hypoglycemia.  After an episode of severe hypoglycemia the body’s natural responses are 
impaired further increasing the patient’s risk of another hypoglycemic episode. 
 
Terms regarding TS used in this protocol:  
 
 
Threshold Suspend (TS) refers to low glucose suspend which allows for the suspension of insulin 
when a preset sensor glucose threshold has been set.   
 

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 
Threshold Suspend ON (TS ON) refers to low glucose suspend wherein the preset sensor 
glucose threshold has been set and turned ON.   
 
 
Threshold Suspend OFF (TS OFF) refers to low glucose suspend wherein the preset sensor 
glucose threshold is turned OFF.       
 
 
Threshold Suspend triggered (TS triggered) refers to the suspension of insulin secondary to 
meeting the preset sensor glucose threshold.   
 
2. 
Devices and Supplies 
2.1 Names and Intended Use of Devices  
2.1.1 
Medtronic MiniMed® 530G Pump (MMT-551, MMT-751) – Investigational  
The Medtronic MiniMed® 530G Pump model (MMT-551, MMT-751) used in this 
study is an approved device in the United States. This insulin pump is equipped 
with a number of features to actively manage the user’s glucose levels. The 
Threshold Suspend (TS) feature automatically stops insulin delivery based on a 
low Sensor Glucose Value (SGV). The TS feature is only available when the 
pump is used in conjunction with continuous glucose monitoring (CGM) which 
consists of a subcutaneous glucose sensor and transmitter to communicate 
sensor glucose readings to the insulin pump. 
2.1.2 
Paradigm Remote Control/Programmer (MMT-503) – Approved under 
510(k) K001829 
The Paradigm Remote Controller is a hand-held, reusable accessory device that 
uses radio frequency to transmit a signal to Paradigm Infusion Pumps for limited 
pump programming.  Using this accessory, a pump user can program a normal 
bolus, suspend or restart the pump. The device is considered an accessory to 
the Paradigm Infusion Pump family 
2.1.3 
Medtronic MiniMed Enlite™ Glucose Sensor (MMT-7008) – 
Investigational 
The Medtronic MiniMed Enlite Sensor is a sensor that is similar in design and 
materials to the Medtronic MiniMed Glucose Sof-Sensor. The sensor includes a 
microelectrode with a thin coating of glucose oxidase beneath several layers of 
biocompatible membrane. It is intended to penetrate the skin at a 90-degree 
angle and is smaller than the Medtronic MiniMed Glucose Sof-Sensor. 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, 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. 
2.1.4 
Medtronic MiniMed MiniLink®  2 REAL-Time Transmitter (MMT-7713) – 
Investigational 
The MiniLink 2 is an investigational small transmitter device. The hardware of this 
transmitter is identical to MiniLink transmitter approved under (PMA supplement 
approval number P980022/S018). The only difference between the two devices 
is the addition of the Artifact Detection software feature. Once the sensor has 
been inserted, the MiniLink 2 is connected directly to the sensor where it receives 
the electronic signal from the sensor electrode, converts signals into glucose 
data, and transmits the data to the pump. When a sensor is attached to the 

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MiniLink 2, it enters an initialization period. After two hours, it begins to 
periodically transmit glucose data to the pump, using a radio signal. 
 
The MiniLink 2 contains a rechargeable battery, sensor electronics, and a radio 
frequency (RF) transmitter. A fully charged battery provides up to 14 days of 
transmitter use. The system includes a battery charger that will recharge the 
device according to the user guide.  For additional information on the MiniLink 2 
REAL-Time Transmitter, refer to the MiniLink REAL-Time Transmitter User 
Guide. 
2.1.5 
Medtronic CareLink® Therapy Management Software for Diabetes 
(MMT-7334) – Investigational – referred to as CareLink Clinical in the 
protocol 
Carelink Clinical is an Internet based software system which allows data to be 
viewed and is easily evaluated by the subject and his/her physician but should 
not be used by research site or subject for data analysis or diabetes 
management. A Personal Computer (PC) is used to access CareLink Clinical via 
the Internet, which then allows subjects/parents/caregivers to upload data from 
Medtronic MiniMed insulin pumps and a range of system-supported, third-party 
blood glucose meters. Carelink Clinical was developed for use by clinical trial 
subjects only. The data contained in CareLink Clinical is accessible to users 
using a standard browser, e.g., Microsoft® Internet Explorer on an Internet 
enabled PC. 
  
CareLink Clinical uses standard Secure Socket Layer (SSL) technology. SSL 
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: 
 
1. 
The internet to the web server; 
2. 
Web server to the application server; 
3. 
Application server to the database server. 
This software has been developed especially for use in clinical trials. 
2.1.6 
Medtronic MiniMed charger (MMT-7705) – FDA approval P980022/S018 
This charger will used to charge the MiniLink 2 transmitter. The MiniLink 2 
contains a non-replaceable, rechargeable battery that can be recharged as 
needed. The charger has a green light to indicate the charging status and a red 
light that indicates problems during charging. Before using MiniLink 2, it must be 
fully charged, which will take up to 8 hours. A full charge lasts for up to 14 days 
of continuous use. After 14 days of use, the MiniLink 2 will fully recharge in less 
than 2 hours.  
2.1.7 
Medtronic MiniMed Test plug (MMT-7706) - FDA approval 
P980022/S018 
The Test Plug 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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2.1.8 
Enlite™ Serter (MMT-7510) – Investigational 
The Enlite Serter is an insertion device used to ensure correct placement of the 
Medtronic MiniMed Enlite Glucose Sensor. The Serter injects the sensor into the 
insertion site when the button is released.   
2.1.9 
Medtronic MiniMed CareLink™ USB (MMT-7305) - FDA approval 
K070438 
The Medtronic CareLink USB (510 (k) clearance number K070438) is indicated 
for use commercially by patients at home and for clinicians in a medical office 
setting as a means of facilitating communication between Medtronic diabetes 
therapy management devices that use Paradigm-compatible RF telemetry and a 
personal computer that uses data management application software. The 
CareLink USB device will enable data from the Medtronic MiniMed® 530G to be 
uploaded to CareLink Clinical. 
2.1.10 Bayer CONTOUR™ Next Link Blood Glucose Meter (HMS 9740) – FDA 
approval K110894 
The Bayer Contour Next Link RF enabled BG Meter measures a subject’s 
capillary blood glucose level, which is then used to calibrate the pump. The 
Medtronic MiniMed® 530G pump uses the calibration point in the real-time 
algorithm which calculates the sensor glucose values that are displayed to the 
subject. In a normal setting, the result of the SMBG reading is transmitted to the 
pump via radiofrequency (RF) and can be stored in its memory as a glucose 
calibration point. The pump asks the user every time if the user wants to use the 
linked meter BG for calibration. If accepted, the glucose value will be stored in 
the pump’s memory as a calibration point.  
 
3. 
Objective and Hypothesis  
3.1. 
Study Objective 
 
The study objective is to demonstrate that home use of Threshold Suspend (TS) is not associated with 
glycemic deterioration in pediatric patients with type 1 diabetes, as measured by change in A1C. 
3.2. 
Study Hypothesis 
Change in A1C is defined as A1C measured at the end of 12-month study period minus A1C measured at 
the baseline visit. The hypothesis is mathematically expressed as: 
Ho: µ ≥ 0.4%  
Ha: µ < 0.4%   
 
Where 0.4% is the pre-specified non-inferiority margin, µ is the mean of change in A1C (%). 
 
4. 
Study Design 
 
This study is a longitudinal, multi-center trial that aims to observe the Threshold Suspend (TS) feature 
with a sensor-augmented insulin pump in patients 7–15 years with Type 1 diabetes. The study will 
measure the change in A1C from baseline over a period of one year while subjects are wearing the study 
pump. 
 

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5. 
Study Population 
5.1 
Number of Subjects and Study Population: 
Up to 300 subjects will be enrolled so that there will be 200 subjects who are eligible to participate in the 
study.    
 
Up to 20 Investigational centers will be selected across the United States. Selection is based on each 
Investigator’s experience and qualifications, availability of sufficient resources to carry out the required 
study procedures and the investigator’s ability to recruit subjects into the study.  
 
Subjects will be grouped by baseline demographics:  Baseline A1C, age, ethnicity, body mass index 
(BMI), gender and duration of diabetes and hypoglycemic awareness. Sponsor will oversee distribution of 
subjects across study sites.   
 
 
Baseline A1C 
o 
A1C less than 7.0% (Minimum N=50) 
o 
A1C between 7.0% to 9.0% (Minimum N=50) 
A1C greater than 9.0% (Minimum N=50) 
 
 
Race  
o 
American Indian/Alaska Native  
o 
Black/African-American  
o 
White  - anticipated maximum  80%  
o 
Native Hawaiian/Other Pacific  Islander  
o 
Asian  
o 
Subject refused 
 
 
Ethnicity 
o 
Hispanic/Latino  
o 
Non-Hispanic/Non-Latino  
o 
Subject refused 
 
 
Diabetes cohorts based on BMI percentile: 
 
Weight Status 
Category 
Percentile Range 
N=Minimum 
Underweight 
Less than the 5th percentile 
2 
Healthy weight 
5th percentile to less than the 85th 
percentile
30 
Overweight 
85th to less than the 95th percentile 
4 
Obese 
Equal to or greater than the 95th 
percentile
1 
 
 
BMI Percentiles according to CDC: 
http://www.cdc.gov/healthyweight/assessing/bmi/childrens_bmi/about_childrens_bmi.html 
 
 
Gender 
o 
Male (minimum  N=80) 
o 
Female (minimum  N=80) 
 
 
Hypoglycemic awareness 
o 
Patients with intact hypoglycemic awareness (minimum N=60) 
o 
Patients who have impaired hypoglycemic awareness (minimum N=40) 
 
 

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5.2 
Study Schedule / Duration 
Each subject’s participation in the study will be comprised of 5 scheduled office visits over approximately 
12 months. The entire study is expected to be completed within approximately 24 months from approval 
of the study protocol and the study device. 
5.3 
Inclusion Criteria  
1. Subject is age 7 to 15 at time of screening 
2. Subject has been diagnosed with type 1 diabetes mellitus  and must have been diagnosed for at 
least one year prior to screening 
3. Subject is currently transitioning from  pump therapy, with or without continued glucose monitoring 
(CGM), to the 530G insulin pump system. 
4. Subject is willing to perform greater than or equal to 4 finger stick blood glucose measurements daily  
5. Subject is willing to perform required sensor calibrations  
6. Subject is willing to wear the system (Pump, glucose sensors, meter) continuously throughout the 
study  
7. Subject is willing to upload data every 21 days from the study pump 
8. Subject must have Internet access and access to a computer system that meets the requirements for 
uploading the pumps. This may include use of family or friend’s computer system with Internet 
access. 
9. Subject is using either Humalog or Novolog at time of Screening and plans to use either of those 
insulins throughout the study 
5.4 
Exclusion Criteria 
1. Subject is actively participating in an investigational study (drug or device) wherein he/she is 
receiving treatment from an investigational study drug or investigational study device. 
2. Women of child-bearing potential who have a positive pregnancy test at screening or plan to become 
pregnant during the course of the study  
3. Subject is being treated for hyperthyroidism at time of screening 
4. Subject has an abnormality (>1.8mg/dL,) in creatinine at time of screening visit 
5. Subject has an abnormality (out of reference range) in thyroid-stimulating hormone (TSH) at time of 
screening visit 
 
If TSH is out of range, Free T3 and Free T4 will be tested 
 
Subject may be included with TSH out of range as long as Free T3 and Free T4 are in 
normal reference range.   
6. Subject has taken any oral, injectable, or IV steroids within 8 weeks from time of screening visit, or 
plans to take any oral, injectable, or IV steroids during the course of the study 
7. Subject is currently abusing illicit drugs 
8. Subject is currently abusing prescription drugs   
9. Subject is currently abusing alcohol 
10. Subject is using pramlintide (Symlin) at time of screening 
11. Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or 
erythropoietin within 3 months prior to time of screening  
12. Subject plans to receive red blood cell transfusion or erythropoietin over the course of study 
participation  
13. Subject diagnosed with current eating disorder such as anorexia or bulimia 
14. Subject has been diagnosed with chronic kidney disease that results in chronic anemia  
15. Subject is on dialysis 
16. Subject is already on a 530G system with CGM for 8 days or more. 
6. 
Statistical Methods and Data Analysis  
6.1. 
Sample Size Calculation 
  
 
6.1.1 
Sample Size for Primary Endpoint 
The overall mean change in A1C from baseline to the end of study will be 
estimated and compared by a non-inferiority test with an A1C margin of 0.4% 

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and a significance level of 0.025 (one-sided). The null hypothesis will be rejected 
if the one-sided 97.5% upper confidence limit of the mean change in A1C is less 
than 0.4% 
 
The hypothesis is mathematically expressed as: 
Ho: µ ≥ 0.4%  
Ha: µ < 0.4%   
 
Where 0.4% is the pre-specified non-inferiority margin, µ is the mean of change 
in A1C (%).  
 
Assuming the mean of change in A1C from baseline to the 12-month follow-up 
visit is zero, the standard deviation of change in A1C is 1%, SAS power and 
sample size calculator shows that a total of 100 subjects will provide over 95% 
power to detect the non-inferiority with a margin of 0.4% and with one-sided type 
I error of 0.025. 
  
 
6.1.2 
Overall Consideration 
The above calculations suggest a sample size of 100 subjects who complete the 
study. For the drop-out rate, a conservative estimate of 20% is adopted (based 
on STAR3, IDE G060159, the percentage of subjects not completing study in the 
SAP group is 9.3%); assume 65% of subjects would wear the system most of the 
time. Then a total of 193 subjects needs to be recruited. In general, a number of 
200 will be eligible to participate in the study, with up to 300 subjects enrolled. 
 
6.2. 
Study Populations 
6.2.1. 
Intention to Treat (ITT) Population  
The Intention to Treat (ITT) population will include all enrolled subjects. 
6.2.2 
Completed Case (CC) Population 
The Completed Cases (CC) population is all subjects who complete the trial.  
6.2.3 
Efficacy Population 
The primary efficacy analysis will be performed on the CC population.   
6.2.4 
Safety Population 
The Safety Population will be the ITT population (include all enrolled subjects). 
 
6.3 
Analysis of Primary Endpoint 
6.3.1 
Primary Efficacy Analysis 
A mixed effects model be used to produce the estimate and confidence interval 
of the overall mean change in A1C while accounting for inter-site variability. The 
97.5% upper confidence interval of A1C will be calculated and compared to the 
0.4% non-inferiority margin. As for endpoint analysis, the proposed mixed effects 
model using all A1C measurements has more power than the model only using 
Change in A1C from baseline to one-year visit. 
 
 
 
 
 

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where 
 
is the A1C measurement vector for the jth subject in the ith 
site; 
is a the covariate vector for the jth subject in the ith 
site; 
 
is the coefficient vector, 
 estimate the mean A1C at baseline, 
 estimate the mean change of A1C from baseline to one-year visit; 
 
is the random effect vector for the ith site; 
is the random effect vector for the jth subject in the ith site; 
 
is the random error term; 
 
“The mean of baseline A1C measurement is estimated by 
, mean of 3-month 
A1C measurement estimated by 
, …, mean of 12-month A1C 
measurement estimated by 
, i.e., 
 estimate the mean change of A1C 
from baseline to one-year visit; the 97.5% upper confidence interval of 
 will be 
calculated and compared the 0.4% non-inferiority margin.” 

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6.4 
Safety Analysis 
All site reported adverse events for enrolled subjects will be summarized. The summary will include all 
adverse events and adverse events by: Insulin Pump Infusion set; Insulin administration and pump use; 
Sensor Use; Severe Hypoglycemia; Severe Hyperglycemia; Diabetic Ketoacidosis; Adverse Device 
Event; Serious Adverse Event and Unanticipated Adverse Device Effect. Adverse Events by Investigator 
will also be provided. No formal statistical analysis will be carried out.  
 
In addition, data will be collected for a descriptive summary of device disposition; adverse events; device 
performance and user acceptance. Safety analysis will include a summary of the following:   
 
All adverse events including 
 
Serious Adverse Events (SAE) 
 
Unanticipated Adverse Device Effects (UADE) 
 
Incidence of Severe (clinical) Hypoglycemia 
 
Incidence of Severe Hyperglycemia 
 
Incidence of Diabetic Ketoacidosis (DKA) 
 
Adverse Events will be stratified by 
 
Age 
o 
Children age 7-12 years 
o 
Children age 13-15 years 
 
Race 
o 
American Indian/Alaska Native  
o 
Black/African-American  
o 
White - anticipated maximum 80%  
o 
Native Hawaiian/Other Pacific  Islander  
o 
Asian  
o 
Subject Refused  
 
Ethnicity 
o 
Hispanic/Latino 
o 
Non-Hispanic/Non-Latino 
o 
Subject Refused  
 
 
Diabetes cohorts based on BMI percentile: 
 
Weight Status 
Category 
Percentile Range 
N=Minimum 
Underweight 
Less than the 5th percentile 
2 
Healthy weight 
5th percentile to less than the 85th 
percentile
30 
Overweight 
85th to less than the 95th percentile 
4 
Obese 
Equal to or greater than the 95th 
percentile
2 
 
BMI Percentiles according to CDC: 
http://www.cdc.gov/healthyweight/assessing/bmi/childrens_bmi/about_childrens_bmi.html 
 
 
Gender 
o 
Male  
o 
Female 
 
Hypoglycemic awareness at Baseline Questionnaire 
o 
Patients with intact hypoglycemic awareness (95% confidence interval will be provided) 
o 
Patients who have impaired hypoglycemic awareness (95% confidence interval will be 
provided) 
 
Frequency and average duration of hypoglycemic event (based on two weeks prior to the adverse 
event) 

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 
The one-sided 95% upper confidence limit of severe adverse event incidence rate (DKA and 
severe hypoglycemia) will be calculated. Individual one-sided 95% confidence limit for DKA only 
and severe hypoglycemia only will also be provided. 
6.5 
Secondary Endpoint 
The mean change in A1C from baseline to 3-month, 6-month, 9-month and 12-month will be summarized 
individually for each of the three baseline A1C cohorts: 
 
 
A1C less than 7.0%;  
 
A1C between 7.0% to 9.0; 
 
A1C greater than 9.0% 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 

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 Re
 
 
 
7. 
Institutional Review Board  
This protocol, any subsequent amendments to this protocol, the Informed Consent form, subject material 
and any form of subject recruitment information (e.g. advertisements) relating to this study will be 
approved by the responsible IRB in accordance with 21 CFR Part 56.  The study will not start until IRB 
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 will be retained on-site with copies 
forwarded to the Sponsor for their files.  
 
8. 
Subject Confidentiality 
8.1 
Subject Identification 
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. All correspondence between the Investigational Center and 
Medtronic that refers to individual study subjects will use unique identifiers that are specific to each 

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subject in lieu of subject names. Furthermore, all subject names will be redacted from reports, safety 
updates, and source documents that are forwarded to the Medtronic. 
8.2 
Subject Database Assignment 
In the Oracle Clinical database, the Investigational Centers will be identified numerically, i.e. from 01 to 25 
(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 Oracle database.   
Each case book will contain all relevant Case Report Forms for each subject. Subjects will be assigned a 
unique 9-digit identifier that will be structured such that the first 3 digits correspond to the study number 
(287), the next 3 digits correspond to the Investigational Center number, and the final 3 digits correspond 
to the subject number. An example of a typical subject’s unique identifier is shown in the following 
example: The numerical sequence 287001001 translates into: Study number (287), Investigational Center 
number (001), Subject number (001).  
 
All study documents, eCRFs and correspondence will use this identifier sequence in lieu of a subject’s 
name or initials. 
8.3 
Informed Consent 
Informed Consent/ Assent will be obtained in accordance with the Code of Federal Regulations (CFR) 
Title 21, Part 50. Prior to entry into the study the California Experimental Subject’s Bill of Rights (if 
applicable), the IRB- and Medtronic-approved Informed Consent Form (ICF)/Assent, and the HIPAA 
Authorization Form will be given to each subject. Subjects/parents/caregivers will be offered the 
opportunity to review these documents away from the Investigational Center. Pediatric subjects 7-15 
years of age should provide informed assent to participate in this research even if their parents or 
guardians have given permission for their participation through informed consent. A subject’s participation 
in study procedures cannot start before the consent process has been properly executed. 
9. 
Investigator Responsibilities 
This study will be conducted at up to 20 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 56.102, an Investigator is “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.” Specific responsibilities of the principal investigator are 
described in 21 CFR 812.100 and in the FDA guidance document dated October, 2009 (see Regulatory Binder). 

 
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10. 
Study Visits  
 
Chart 1: Visit 1-5 
 
 
 
 
 
 

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Table 1: Visit Plan and Study Activities 
 
 
Visit 1 
Screening 
Visit 2 
90 Day A1C 
Visit 3 
180 Day A1C 
Visit 4 
270 Day A1C 
Visit 5 
365 Day A1C 
End of Study 
Study Activities at Site during 
visit 
 
Informed Consent 
Eligibility Assessment 
Subject Demography 
Record Concomitant 
medications 
Screening A1C 
Lab Draw 
Administer Questionnaires 
Case Report Forms 
Distribute devices and 
supplies (e.g., pump, 
transmitter, Bayer meter, 
glucose sensors, meter 
strips, ketone strips) to each 
subject  
Dislodgement Subject Diary 
Study Pump Training 
CareLink Registration 
Help Line Training 
Case Report Forms 
EQ5‐5DYouth 
questionnaire 
HFS Parent questionnaire 
HFS Child/Teen 
questionnaire 
Hypoglycemia Unawareness 
questionnaire 
Upload insulin pump 
Instruct subjects to use 
either Humalog or Novolog 
insulins 
Instruct Subjects to use the 
Bayer Contour Link meter 
for all calibrations 
 
 
Adverse Event Check 
CareLink Upload 
A1C Test 
Case Report Forms 
Distribute devices and 
supplies (e.g., glucose 
sensors, meter strips, ketone 
strips) that need replenishing 
to each subject  
Review Sensor Dislodgement 
Diary 
Distribute Urine Ketone Test 
strips 
Remind subjects to use either 
Humalog or Novolog insulin 
Remind Subjects to use the 
Bayer Contour Link meter for 
all calibrations 
 
Adverse Event Check 
CareLink Upload 
A1C Test 
Case Report Forms 
Distribute devices and 
supplies that need 
replenishing  (e.g., glucose 
sensors, meter strips, ketone 
strips) to each subject  
Review Sensor dislodgement 
Diary  
Distribute Urine Ketone Test 
strips 
Remind subjects to use either 
Humalog or Novolog insulin 
Remind Subjects to use the 
Bayer Contour Link meter for 
all calibrations 
 
Adverse Event Check  
CareLink Upload 
A1C Test 
Case Report Forms 
Distribute  devices and 
supplies  that need 
replenishing (e.g., glucose 
sensors, meter strips, ketone 
strips) to each subject  
Review Sensor dislodgement 
Diary 
Distribute Urine Ketone Test 
strips 
Remind subjects to use either 
Humalog or Novolog insulin 
Remind  Subjects to use the 
Bayer Contour Link meter for 
all calibrations 
 
Adverse Event Check 
CareLink Upload 
A1C Test 
Case Report Forms 
EQ5‐5DYouth 
questionnaire 
HFS Parent questionnaire 
HFS Child/Teen 
questionnaire 
Hypoglycemia Unawareness 
questionnaire  
Review Sensor dislodgement 
Diary 
Return of Study Devices and 
supplies 

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Visit 1 
Screening 
Visit 2 
90 Day A1C 
Visit 3 
180 Day A1C 
Visit 4 
270 Day A1C 
Visit 5 
365 Day A1C 
End of Study 
Study Activities at Home 
between visits 
 
Upload the Pump every 21 
days 
Change Sensors as required 
Test urine ketones daily and 
enter test results into 
CareLink Clinical 
Call the study doctor and his 
staff if you are experiencing 
any medical problem either 
related to your diabetes or 
unrelated to your diabetes 
Call the Medtronic 24 Hr 
helpline if you have a device 
problem  
Fill out a Sensor Dislodgement 
Diary as needed 
 
 
Upload the Pump every 21 
days 
Change Sensors as required 
Test urine ketones daily and 
enter test results into 
CareLink Clinical 
Call the study doctor and his 
staff if you are experiencing 
any medical problem either 
related to your diabetes or 
unrelated to your diabetes  
Call the Medtronic 24 Hr 
helpline if you have a device 
problem  
Fill out a Sensor 
Dislodgement Diary as 
needed 
 
 
Upload the Pump every 21 
days 
Change Sensors as required 
Test urine ketones daily and 
enter test results into 
CareLink Clinical 
Call the study doctor and his 
staff if you are experiencing 
any medical problem either 
related to your diabetes or 
unrelated to your diabetes  
Call the Medtronic 24 Hr 
helpline if you have a device 
problem  
Fill out a Sensor Dislodgement 
Diary as needed 
 
 
 
 
 

 
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10.1 
Visit 1 - Day 0: Consent and Screening   
General  
Eligibility: 
This study is open to all individuals who meet the eligibility criteria. Subjects will 
be considered enrolled after they have signed the Informed Consent form. The 
Investigational Center will be responsible for making adequate source 
documentation available to the sponsor to verify subject eligibility.  
 
General 
Standard Care: 
It is expected that subjects will continue to undergo their routine diabetes care as 
per clinic standard.  During routine quarterly visits data collection for the study 
will be obtained by the designated staff.  
 
General  
Investigational Center staff will: 
 
Obtain informed consent/Assent from subject/parent/caregiver  
o Subjects 7-15 years should provide assent in addition to Informed 
Consent from parent/caregiver 
 
Assess eligibility of subjects to participate in the study 
 
Collect demographic information and baseline characteristics, including 
age, gender, race, ethnicity and medical diagnosis, duration of diabetes 
(Screening eCRF). 
 
Record concomitant medications on appropriate CRF 
 
Obtain blood sample(s) to complete required screening A1C test, if all 
eligibility criteria (excluding those involving blood test results) are met: 
Note: All collected blood specimens will be sent to and tested by a 
NGSP certified Central Laboratory.  A1C testing must follow 
National Glycohemoglobin Standardization Program (NGSP) 
standards. This A1C will be used for data analysis. 
 
Obtain blood samples to complete required screening tests, i.e.TSH (also 
T3, T4 if TSH is abnormal), Creatinine 
 
Perform screening labs including urine or serum pregnancy test 
 
Subjects may be rescreened up to a maximum of two times if they do not 
meet inclusion/exclusion criteria at the time of their original screening 
 
Register subjects in CareLink Clinical (see Investigator/Coordinator 
binder for details) and upload insulin pump 
 
Disburse devices and supplies (e.g., pump, transmitter, glucose sensors, 
Bayer meter, meter strips, ketone strips) to each study subject  
 
Administer the following questionnaires: 
o Hypoglycemia awareness questionnaire 
 
Score of 4 or more is impaired awareness. It means that 
subjects with this score will be assigned to the impaired 
hypoglycemic awareness cohort.  
 
Score of 3 or less is aware. It means that subjects with 
this score will be assigned to the intact hypoglycemic 
awareness cohort. 
o EQ-5D Youth  
o Hypoglycemia Fear Scale (HFS) – Child/Teen  
o Hypoglycemia Fear Scale (HFS) – Parent 
 
 
Tell subject/parent/caregiver that they should call site as soon as possible 
with any changes to their health status (adverse events) 
 
Schedule the next visit date and time. 
 
Enter eCRFs into the study database as appropriate. 
 

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Device Disbursement 
Investigational Center staff will: 
 
Disburse devices and supplies (e.g., pump, transmitter, glucose sensors, 
Bayer meter, meter strips, ketone strips)  
 
Training and Instructions 
Notes:  
1. All device training for this study should be consistent with the training 
plan in place for patients who receive a new study pump system 
through commercial channels.  
a. Subjects should only use the Bayer meter  
2. Training on study procedures will be performed 
 
Designated Training staff will: 
 
Train subject/parent/caregiver on the use of the Medtronic study pump.  
o Subject/parent/caregiver will be instructed to record carbohydrate 
intake and exercise into the insulin pump as part of the study 
requirements  
 
Train subject/parent/caregiver on how to upload the pumps as part of 
study requirements.  
o Uploads of all study pumps into CareLink Clinical should occur 
every 21 days throughout the study.  
o Subject/parent/caregiver will receive an automated reminder (e-
mail, text, or voice message) twice a month to remind them to 
upload pumps. 
o In addition to the 21 day upload requirement, 
subject/parent/caregiver will be instructed to upload the pumps 
prior to each study visit. Investigational Center staff will again 
upload pump data at the time of the visit. 
 
Instruct subject/parent/caregiver per User Guide to calibrate the study 
pump at least every 12 hours after the second calibration.  For best 
calibration results per User Guide, subject/parent/caregiver will be 
instructed to calibrate 3-4 times, spread throughout the day.  
 
Instruct subject/parent/caregiver to use the Bayer Contour Link meter for 
all calibrations 
 
Instruct subject/parent/caregiver to test blood glucose per User Guide at 
least 4 times per day 
o 
Although the pump has multiple safety alarms, it cannot notify the 
subject if the set is leaking or the insulin has lost its potency. It is 
essential, therefore, that the subject test his or her blood glucose 
levels at least 4 times per day. If the subject’s blood glucose is 
out of range, he/she should check the pump and the infusion set 
to ensure that the necessary amount of insulin is being delivered. 
 
Instruct subject/parent/caregiver on the use of the Sensor dislodgement 
Diary 
 
o 
Subject/parent/caregiver will be instructed to record sensor 
dislodgement occurrences in the Sensor dislodgement Diary. 
 
Discuss glucose sensor wear requirement.  
o 
Glucose sensors should be worn throughout the course of the 
study 
 
Train subject/parent/caregiver on the use of CareLink Clinical which 
includes that this application should only be used to upload the study 
pump and not for data analysis or diabetes management.  
 
Instruct subject/parent/caregiver to use either Humalog or Novolog 
insulin 

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 
Instruct subject/parent/caregiver to contact the Medtronic 24hr HelpLine 
in the event they experience problems with their study devices. 
 
Instruct subject/parent/caregiver to test for urine ketones daily and to 
record results in CareLink Clinical.  
o 
Urine ketone test strips will be provided by sponsor free of charge 
to subjects.  
o 
The urine ketone strips will not be tracked by sponsor. 
 
Instruct subject/parent/caregiver to report all adverse events as soon as 
possible. This would include any new medical problem or deterioration of 
an existing medical problem, such as sickness or glycemic problems. If 
necessary refer subject/parent/caregiver to the subject’s own providers 
or an emergency facility for treatment. 
 
10.2 
Visit 2 - Day 90 (± 21 days): 90 Day A1C Test 
General 
Investigational Center staff will:  
 
Ask subject/parent/caregiver about the occurrence of adverse events  
 
Record adverse events on the appropriate eCRF, if 
subject/parent/caregiver reports health status changes that result in a 
new medical condition or deterioration of an existing medical condition 
 
Review the Sensor Dislodgement Diary  
 
Upload pump into CareLink Clinical. 
 
Sponsor will provide surveillance report on device uploads. 
 
Collect blood sample for A1C. 
Note: All collected blood specimens will be sent to and tested by a 
NGSP certified Central Laboratory.  A1C testing must followNational 
Glycohemoglobin Standardization Program (NGSP) standards. This 
A1C will be used for data analysis.   
 
Provide subject/parent/caregiver with the opportunity to bring up study-
related questions and concerns. 
 
Remind subject/parent/caregiver about the need to wear glucose 
sensors consistently. 
 
Remind subject/parent/caregiver to use the Bayer Contour Link meter for 
all calibrations 
 
Remind subject/parent/caregiver to use either Humalog or Novolog 
insulin 
 
Remind subject/parent/caregiver to upload the pump every 21 days 
 
Perform accuracy testing with study meter 
 
Enter eCRFs into the study database as appropriate. 
 
Schedule the next visit date and time. Disburse devices and supplies 
(e.g., glucose sensors, meter strips, ketone strips) that need replenishing  
 
Remind subject/parent/caregiver to record carbohydrate intake and 
exercise into the insulin pump as part of the study requirements. 
10.3 
Visit 3 - Day 180 (± 30 days): 180 Day A1C Test 
General 
Investigational Center staff will:  
 
Ask subject/parent/caregiver about the occurrence of adverse events  
 
Record adverse events on the appropriate eCRF, if 
subject/parent/caregiver reports health status changes that result in a 
new medical condition or deterioration of an existing medical condition. 
 
Review the Sensor Dislodgement Diary  
 
Upload pump into CareLink Clinical. 
 
Sponsor will provide surveillance report on device uploads. 
 
Collect blood sample for A1C. 

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Note: All collected blood specimens will be sent to and tested by a 
NGSP certified Central Laboratory.  A1C testing must follow 
National Glycohemoglobin Standardization Program (NGSP) 
standards. This A1C will be used for data analysis.   
 
Provide subject/parent/caregiver with the opportunity to bring up study-
related questions and concerns. 
 
Remind subject/parent/caregiver about the need to wear glucose 
sensors consistently. 
 
Remind subject/parent/caregiver to use the Bayer Contour Link meter for 
all calibrations 
 
Remind subject/parent/caregiver to use either Humalog or Novolog 
insulin 
 
Remind subject/parent/caregiver to upload the pump every 21 days 
 
Perform accuracy testing with study meter 
 
Enter eCRFs into the study database as appropriate. 
 
Schedule the next visit date and time. Disburse devices and supplies 
(e.g., glucose sensors, meter strips, ketone strips) that need replenishing 
 
Remind subject/parent/caregiver to record carbohydrate intake and 
exercise into the insulin pump as part of the study requirements. 
 
10.4 
Visit 4 - Day 270 (± 30 days): 270 Day A1C Test 
General 
Investigational Center staff will:  
 
Ask subject/parent/caregiver about the occurrence of adverse events  
 
Record adverse events on the appropriate eCRF, if 
subject/parent/caregiver reports health status changes that result in a 
new medical condition or deterioration of an existing medical condition. 
 
Review the Sensor Dislodgement Diary  
 
Upload pump into CareLink Clinical. 
 
Sponsor will provide surveillance report on device uploads. 
 
Collect blood sample for A1C. 
Note: All collected blood specimens will be sent to and tested by a 
NGSP certified Central Laboratory.  A1C testing must follow 
National Glycohemoglobin Standardization Program (NGSP) 
standards. This A1C will be used for data analysis.   
 
Provide subject/parent/caregiver with the opportunity to bring up study-
related questions and concerns. 
 
Remind subject/parent/caregiver about the need to wear glucose 
sensors consistently. 
 
Remind subject/parent/caregiver to use the Bayer Contour Link meter for 
all calibrations 
 
Remind subject/parent/caregiver to use either Humalog or Novolog 
insulin 
 
Remind subject/parent/caregiver to upload the pump every 21 days 
 
Perform accuracy testing with study meter 
 
Enter eCRFs into the study database as appropriate. 
 
Schedule the next visit date and time. Disburse devices and supplies 
(e.g., glucose sensors, meter strips, ketone strips) that need replenishing 
 
Remind subject/parent/caregiver to record carbohydrate intake and 
exercise into the insulin pump as part of the study requirements. 
10.5 
Visit 5 – Day 365 (+ 30 days): End of study; 365 Day A1C Test 
General 
Investigational Center staff will:  
 
Ask subject/parent/caregiver about the occurrence of adverse events  

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 
Record adverse events on the appropriate eCRF, if 
subject/parent/caregiver reports health status changes that result in a 
new medical condition or deterioration of an existing medical condition. 
 
Upload pump into CareLink Clinical. 
 
Sponsor will provide surveillance report on device uploads. 
 
Collect blood sample for A1C. 
Note: All collected blood specimens will be sent to and tested by a 
NGSP certified Central Laboratory.  A1C testing must follow 
National Glycohemoglobin Standardization Program (NGSP) 
standards. This A1C will be used for data analysis.   
 
Provide subject/parent/caregiver with the opportunity to bring up study-
related questions and concerns. 
 
Administer the following questionnaires: 
o 
Hypoglycemia awareness questionnaire 
 
Score of 4 or more is impaired awareness.   
 
Score of 3 or less is aware.  
o 
EQ-5D Youth  
o 
Hypoglycemia Fear Scale (HFS) Child Teen 
o 
Hypoglycemia Fear Scale (HFS) Parent 
 
Review the Sensor Dislodgement Diary 
 
Enter eCRFs into the study database as appropriate 
 
“Remove and return all study devices and supplies from subjects 
per Section 11 of the protocol.” 
 
Discharge subject from the study 
 
Return or Disposal of Study Devices 
 
At the end of Visit 5, the investigational center is expected to accept and 
retain all devices as described in Table 2 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 2, will be returned by subjects to the 
investigational center and then to the sponsor.  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 devices 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 consumable devices (i.e., reservoirs, infusion sets, alcohol wipes, 
Study Meter supplies, overtape, 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 testing strips and supplies, reservoirs, infusion sets and adhesive 
overtape.   
 

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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. 
 
10.6 
Minimizing subject withdrawal 
It may be reasonable to expect that subjects will not consistently comply with study requirements during 
the study. In this study, continuous sensor wear is a key component in the collection of TS safety data.  
For this reason, the strategy will be to select investigational centers that have the experience and 
expertise to manage subjects for an extended period of time in the context of a clinical study. 
Furthermore, as a means of providing encouragement to study subjects, the following will be 
implemented: 
Subjects will be provided  devices and supplies (e.g., glucose sensors, meter strips, ketone strips) that 
need replenishing free of charge at every study visit.  
 
10.7 
Subject Withdrawal  
Subject/parent/caregiver 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.  
 
A subject will be withdrawn from the study by the investigator if: 
 
 
In the opinion of the Investigator, the subject’s health or safety would be compromised by 
continuing in the study 
 
In the opinion of the Investigator, it is in the subject’s best interest to discontinue participation 
in the study 
 
During the course of the study, subject has 2 episodes of DKA (see definition in section 14.4) 
 
During the course of the study, subject experiences 2 episodes of severe hypoglycemia  
 
During the course of the study, subject begins abusing illicit drugs.  
 
During the course of the study subject begins abusing prescription drugs.  
 
During the course of the study subject begins abusing alcohol. 
 
During the course of the study subject begins using pramlintide (Symlin).     
 
During the course of the study, subject receives red blood cell transfusion or erythropoietin.       
 
During the course of the study, subject takes any oral, injectable, or IV steroids. 
 
Documentation of the reason(s) leading to subject withdrawal will be kept in the subject’s source file. 
10.8 
Study Closure  
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, 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 of study closure. 
 

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11. 
Devices and Supplies 
Subjects will be given all study devices and supplies at each scheduled visit (except final study visit). 
Investigational sensors that are provided by the sponsor will be tracked from Sponsor to investigational 
center. 
11.1 
Investigational Devices  
 Investigational devices to be used in this study include: 
 
 
Minimed MM530G Pump (labeled as Medtronic MiniMed Paradigm® Insulin Pump, MMT-
751); referred to as study pump in the protocol  
 
Medtronic CareLink® Therapy Management Software for Diabetes (MMT-7334) –referred to 
as CareLink Clinical in the protocol 
 
Medtronic MiniMed Enlite™ Glucose Sensor (MMT-7008); referred to as glucose sensor in 
the protocol 
 
Medtronic MiniMed MiniLink® 2 REAL-Time Transmitter (MMT-7713) 
 
Enlite™ Serter (MMT-7510) 
11.2 
Non-Investigational Devices  
 
Medtronic MiniMed charger (MMT-7705) 
 
Medtronic MiniMed CareLink®  USB (MMT-7305) 
 
Test Plug (MMT-7706) 
 
Bayer CONTOUR™ Next Link Blood Glucose Meter. 
11.3 
Non-Investigational Supplies  
 
Urine Ketone sticks  
 
Infusion Sets 
 
IV3000 tape 
 
Lancet device 
 
Lancets 
 
Batteries for Meter 
 
Alcohol swabs 
 
AAA Energizer batteries 
11.4 
Study Materials 
 
User Guides for study devices 
 
Study instructions 
 
Subject Questionnaires 
 
Study supplies must be securely stored during the study. 
 
11.5 
Device Accountability 
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 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. This includes 
keeping records of:  
 
 
Center receipt and inventory management  
 
Storage  

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 
Subject disbursement  
 
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 2: List of Study Devices 
 
Device 
Center 
Receipt 
(Packing 
Slip)
Disbursement to 
Site (eCRF) 
Site 
Return to 
MDT 
(eCRF)
Center Return 
to Sponsor 
(eCRF, Packing 
Slip) 
Medtronic MiniMed 
530G Insulin Pump  
(MMT-551, MMT-751) 
Yes 
Yes 
Yes 
Yes 
Medtronic MiniMed 
Enlite Glucose Sensor 
(MMT-7008) 
Yes 
Yes 
Unused 
Yes 
Unused 
Yes 
Enlite Serter (MMT-
7510) 
Yes 
Yes 
Yes 
Yes 
Medtronic MiniMed 
MiniLink 2 REAL-Time 
Transmitter (MMT-
7713) 
Yes 
Yes 
Yes 
Yes 
Paradigm Remote 
Control/Programmer 
(MMT-503) 
Yes 
Yes 
Yes 
Yes 
Charger (MMT-7705) 
Yes
Yes
Yes
Yes 
Bayer CONTOUR 
Next Link RF-Enabled 
Blood Glucose Meter 
(HMS 9740)  
Yes 
Yes 
Yes 
Yes 
Medtronic MiniMed 
CareLink USB (MMT-
7305) 
Yes 
Yes 
Yes 
Yes 
Medtronic MiniMed 
Test Plug (MMT-7706) 
Yes 
Yes 
Yes 
Yes 
 
The investigational center will promptly notify the sponsor of any device handling violation that might 
impact either the safety and welfare of subjects or data integrity. 
 
Please note that study devices which were provided to subjects through commercial channels (ie. Early 
protocol version which allowed study devices through commercial channels)  do not apply to device 
accountability section.    
 
12. 
Quality Assurance and Control 
12.1 
Monitoring Plan 
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 be updated and 
revised as needed due to changes in documents or processes.  The review of processes and documents 
will be ongoing throughout the course of the study. The most recent version of the Monitoring Plan will 
take precedence over any previous versions.  
 

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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.  Interim 
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 the study 
to the final 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, all 
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. 
 
All monitoring visits and visits from the Sponsor to the Investigational Center will be recorded using the 
Site Visit Sign-In Log and co-signed by Investigational Center staff.  The log will be kept in the 
Investigational Center regulatory binder and the original will collected at the end of the study and 
submitted to the sponsor.  
12.2 
Quality Audits 
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. 
12.3 
Investigational Center Disqualification 
Medtronic and/or the IRB 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: 
 
 
Unsatisfactory subject enrollment with regard to quality and quantity. 
 
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. 
 
The incidence and/or severity of adverse experiences in this or other studies indicating a potential 
health hazard caused by the device. 
 
A written statement fully documenting the reasons for such a termination will be provided to Medtronic, 
the Institutional Review Board (IRB) and other regulatory authorities, as required. 
12.4 
Protocol Deviations 
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: 
 
 
observation in the monitoring report 
 
deviation to document the event 
 
corrective action plan 

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 
site disqualification  
 
notification to the regulatory authorities depending on the severity of the deviation  
 
The investigator is responsible for protecting the safety and welfare of the clinical research subjects.   
 
Compliance with Protocol: 
 
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. (CFR 21 812.140 Records)  
 
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/IEC 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/IEC 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: 
 
(a) To the IRB/IEC for review and approval/favorable opinion; 
(b) To the sponsor for agreement and, if required; 
(c) To the regulatory authority(ies). 
 
21 CFR 812.150 (4) states “….except in such an emergency, prior approval by the sponsor 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, FDA and IRB in accordance 
with 21 CFR 812.35(a) also is required”.   
 
Emergency deviations must be reported to the sponsor and IRB within 5 days. 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:  
 
 
 
Failure to obtain informed consent, i.e., there is no documentation of informed consent 
 
Informed consent obtained after initiation of study procedures 
 
Enrollment of a subject who did not meet all inclusion/exclusion criteria 
 
Performing study procedure not approved by the IRB 
 
Failure to report serious adverse event to the IRB and sponsor 
 
Investigational study device dispensed without obtaining informed consent 
 
13. 
Device Complaints and Troubleshooting 
 
The Medtronic 24 Hour Help Line (HL) or appropriate investigational center staff will be consulted for 
device troubleshooting (e.g. assistance is needed by subject to operate their device(s)). If 
subject/parent/caregivers call the HL, they are instructed to notify the HL operator that they are currently 
participating in a clinical research study. All device complaints that are reported to the HL will be 
documented by the HL staff.  
 
The investigational center will be provided with a copy of all HL calls for their subjects. The HL calls 
should be reviewed for investigational center staff awareness for the possibility of an AE. If an AE is 
detected the investigational center staff will also complete an AE eCRF.   

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All device deficiencies reported directly to the investigational center staff by a subject should either be 
reported to the HL by the subject or investigational center staff. 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. 
 
All Device returns will follow the 24 HL procedures. To return a study device as part of a complaint the 
investigational center and or subject are to call the 24 HL. 
  
Descriptive discussion of device performance issues and complaints will be performed.   
 
It is the responsibility of the Investigator to abide by the device malfunction & complaint 
reporting requirements stipulated by the reviewing IRB and the sponsor. 
 
14. 
Safety 
14.1 
Potential Risks  
14.1.1 Potential side effects related to insulin pump infusion set may include  
 
Infection 
 
Skin irritation/ Redness 
 
Bruising 
 
Discomfort/ Pain 
 
Bleeding 
 
Irritation 
 
Rash 
 
Investigational Centers and subjects/parents/caregivers 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. 
14.1.2 Potential risks with insulin administration and pump use 
Due to the use of insulin, there is a potential for adverse events related to the 
infusion of insulin and the potential interruptions of insulin delivery. These risks 
all may include: 
 
 
Hypoglycemia 
 
Diabetic Ketoacidosis (DKA) 
 
Hyperglycemia 
 
Severe Hypoglycemia with or without associated seizure, coma or death. 
14.1.3 Potential risks with sensor use 
Potential risks include the following: 
 
 
 
Skin Irritation or reaction to adhesives 
 
Bruising 
 
Discomfort 
 
Redness 
 
Bleeding 
 
Pain 
 
Rash 
 
Infection 
 
Irritation from tapes used with glucose-sensing products 

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 
Raised Bump 
 
Appearance of a small "freckle-like" dot where needle was inserted 
 
Allergic reaction 
 
Syncopal episode secondary to needle insertion 
 
Soreness or tenderness  
 
Swelling at insertion site 
 
Sensor fracture, breakage or damage 
 
Minimal blood splatter associated with sensor needle removal 
14.1.4 Potential adverse events with serter use: 
 
Skin infection around area where serter is used 
14.1.5 Potential risks specific to TS Feature: 
 
When TS is turned ON, the feature may not activate when the blood 
sugar is low.  
 
When TS is turned ON, the feature may falsely activate when the 
subject’s blood sugar is not low.  
 
The TS feature is not intended to prevent or treat hypoglycemia. 
14.1.6 Potential risks related to frequent finger stick testing 
 
Potential risks associated with frequent meter testing of blood glucose 
and ketones include discomfort and bruising at tips of fingers.  
14.1.7 Potential risks related to venous blood sampling 
 
Potential risks associated with drawing blood include discomfort and 
bruising.  
 
Syncopal episode can occur secondary to needle insertion. 
14.1.8 Potential risks and mitigations for pediatric subject population 
The pediatric subject population has an increased risk for hypoglycemia, 
including severe hypoglycemia.  
Standard mitigations in pediatric subjects include: 
 
Training of primary caregivers will be conducted in addition to subject 
training. 
 
Subject instruction to test BG via finger stick testing 4-6 times a day.  
 
Subject instruction to adhere to 100% sensor wear.  
 
Subject instruction to use the bolus wizard when determining meal or 
correction bolus. 
14.2 
Reporting of Adverse Events  
The Medtronic Clinical Research Department, in conjunction with the Medtronic Regulatory Affairs 
Department, in Northridge, California will monitor and manage adverse event reporting for the study.  
 
A complete description of the event including treatment and interventions provided by medical 
professionals will be included on the AE eCRF. It is expected that the investigator will provide the sponsor 
with the necessary medical records to support the adverse event. 
 
Throughout the course of the study, Investigational Center staff will make all efforts to remain alert to 
possible reportable adverse events or untoward findings. Reports of adverse events will be requested 
from subjects/parents/caregivers at each visit and adverse event eCRFs will be completed as required. 
Investigational Center staff will assess the intensity of each adverse event and its relationship to study 
procedures or devices. 
 

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Adverse events that are assessed to have a relationship to a study procedure or study device will be 
analyzed by the Human Factors group at Medtronic Diabetes to determine whether or not there is a 
connection to mis-use of the device(s) or user error.   
 
Events that are moderate and severe in intensity, all SAE, SADE and UADE that have not resolved at the 
time of the subject’s discontinuation or completion of the study will be followed until the medical outcome 
is determined or until no further change in the condition is expected. All adverse events that have not 
resolved will have a final status of ‘ongoing’. 
Adverse Events reported to sponsor: 
The Investigator or designee will report all adverse events to the sponsor: 
 
 Adverse Events not related to the study device or study procedure 
 Adverse Events related to the study device 
 Adverse Events related to study procedures 
 UADE (Unanticipated Adverse Device Effect) 
 All SAE (Serious Adverse Events) 
 Severe Hypoglycemia 
 DKA (Diabetic Ketoacidosis) 
 
A pre-existing medical condition will only be documented as an adverse event if the condition worsens 
during the course of the subject’s participation in the study. Non-serious Adverse events should be 
entered on the appropriate Electronic Case Report Form (eCRF) within 14 days of subject report to the 
site. For serious adverse events, reporting is required to sponsor within 24 hours of site awareness.  
14.3 
Review of Severe Hypoglycemia and DKA.  
Severe hypoglycemia, and DKA will be adjudicated by the Clinical events committee (CEC) 
comprised of external physicians.  The adjudication will include device relatedness and whether 
the event was considered to be serious or not. The CEC may use Carelink reports, medical 
records and information on CRF to make determination.   
14.4 
Definitions  
Adverse Event (AE) (ISO14155: 2011) 
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. 
Note 3: For users or other persons, this definition is restricted to events related to investigational medical 
devices. 
 
Adverse Device Effect (ADE) (ISO 14155: 2011) 
Any untoward and unintended response to a medical device.  
Note 1: This includes any adverse event resulting from insufficiencies or inadequacies in the instructions 
for use, the deployment, the implantation, the installation, the operation, or any malfunction of the 
medical device. 
 
Note 2: This includes any event that is a result of a use error or intentional misuse.   
 
Serious Adverse Event (SAE) (ISO 14155: 2011) 
An adverse event that  
(a) Led to a death 
(b) Led to a serious deterioration in the health of the subject that 

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 
resulted in life threatening illness or injury, 
 
resulted in a permanent impairment of a body structure or a body function 
 
required in-patient hospitalization* or prolongation of existing hospitalization 
 
resulted in medical or surgical intervention to prevent permanent impairment to a body structure 
or a body function  
(c) Led to fetal distress, fetal death or a congenital abnormality or birth defect  
*Inpatient Hospitalization is defined as: 24 hour acute admission to the hospital based on urgent medical 
need rather than elective admission. 
Note: 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.  
 
Serious Adverse Device Effect (SADE) (ISO 14155: 2011) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious adverse 
event.  
 
Unanticipated Adverse Device Effect (UADE) (21 CFR 812.3(s)) 
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. 
 
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 the American Diabetes Association 
Workgroup on Hypoglycemia, 2005)  
 
“Severe Hyperglycemia” is defined as Hyperglycemia (blood glucose >300 mg/dL) with blood glucose 
ketones >0.6mmol/L or accompanied by symptoms of nausea, vomiting or abdominal pain. 
 
“Diabetic Ketoacidosis/DKA” is defined as: Hyperglycemia (blood glucose greater than 250 mg/dL or 
greater than 13.9 mmol/L) with either low serum bicarbonate (less than 15 mEq/L) and/or low pH (less 
than or equal to 7.24) Anion gap (greater than 12) and either ketonemia or ketonuria and requiring 
treatment within a health-care facility. (American Diabetes Association-Diabetes Care, Volume 27, 
Supplement 1, January 2004) 
14.5 
Device or Procedure Relatedness:  
The relatedness of the event to the study device or procedures will be determined for each adverse 
event. Subjects participating in this study have type 1 diabetes and it is expected that due to the disease 
subjects will have adverse events that are part of their disease. It is expected that the investigator will 
assess all events to determine if the event was related to the disease or if the event was related to the 
device or study procedure. An adverse event is not automatically related to the study device or procedure 
simply because the subject is 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.  
 
The investigator will review all elements surrounding the event to properly determine relatedness – this 
would include the subjects/parents/caregivers description of the event, study device downloads and 
medical records (if applicable) from the treating facility. These records will be made available to the 

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sponsor and the Clinical Events Committee at the request of the sponsor. The following definitions should 
be considered when determining the relationship of the event to the device or study procedure: 
 
Definite – clearly related to the device or procedure 
Probable – likely related to the device or procedure 
Possible – may be related to the device or procedure 
Unlikely – doubtfully related to the device or procedure 
Not Related – clearly not related to the device or procedure 
 
If the investigator determines the event meets the definition of definite, probable or possible the event 
should be considered related and the Yes box on the AE eCRF would be checked for the question related 
to. If the investigator determines the event meets the definition of unlikely, not related or unknown the 
event should be considered unrelated and the NO box would be checked on the AE eCRF for the 
question was the event related to.  
14.6 
Event Intensity (severity): 
Mild: Transient, needing no special treatment, and/or does not interfere with the subject’s daily 
activity. 
 
Moderate: Low level of inconvenience or concern to the subject and may interfere with daily 
activities, but is usually improved by simple therapeutic remedy. 
 
Severe*: Interrupts a subject’s daily activity and typically requires intervening treatment. 
 
Please Note*: The terms “serious” and “severe” are not synonymous.  Severe is often used to 
describe the intensity (severity) of a specific event (as in mild, moderate, or severe myocardial 
infarction); the event itself, however, may be of relatively minor medical significance (such as severe 
headache). This is NOT the same as “serious” which is based on the definition of “serious criteria” 
which have been provided. 
 
14.7 
Clinical Events Committee 
A clinical events committee consisting of external physicians with an expertise in Endocrinology and the 
management of Type 1 diabetes including CGM will be convened. The CEC will review all reports of: 
 
Diabetic Ketoacidosis 
 
Severe Hypoglycemia 
 
Serious Adverse Event 
 
Serious Adverse Device Effect 
 
Unanticipated Adverse Device Effect 
 
The CEC will assess these events to determine agreement or disagreement with the investigator 
determination of the event. The investigator will be notified of any disagreement in assessment of an 
event by the CEC.  
 
 
  
 
 
 
 
 
  
 
 
 
 
 

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15. Administrative Considerations 
15.1 
Document Storage and Retention 
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 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. 
15.2 
Data Handling 
All data required for analysis will be captured on electronic Case Report Forms (eCRFs) using Oracle 
Clinical’s 21 CFR Part 11 compliant Remote Data Capture (RDC) module. Original eCRFs will not be 
used as source data and supporting documentation will be required. Electronic device data will be 
collected from the study pump using Medtronic CareLink Clinical, which is 21 CFR Part 11 compliant.  
 
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 CRF 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 Oracle Clinical to capture any corrections or changes of the eCRFs. System backups for 
data stored in the Oracle Clinical system will be consistent with Medtronic standard procedures. 
 

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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. 
15.3 
Data Preparation 
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.   
15.4 
Training of Clinical Staff  
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. 
15.5 
Study Binders 
A Regulatory Binder and an Investigator/Coordinator Manual will be provided by the Sponsor to be 
maintained by Investigational Center staff.  At a minimum, each Regulatory Binder will include: 
 
 
Study Contact Sheet 
 
Clinical Study Agreement(s) 
 
Signed/dated CV of Investigator(s)  
 
IRB Correspondence  
 
IRB-approved Protocol(s) and Informed Consent Form(s), including all amendments 
 
Clinical Bulletins- A brief official update or summary of current study news on a matter of 
immediate interest and high importance to Investigational Center surrounding the study protocol. 
 
Site Visit Sign-In Log 
 
Study Correspondence 
 
Site Signature and Study Delegation Log 
 
Training Records 
 
Sound Bites 
 
At a minimum, the Investigator/Coordinator Manual will include: 
 
 
Sample Coordinator Worksheets 
 
User Guide(s), Instructions for Use, and/or User Manual as applicable 
 
Quick Reference Guide 
 
Training materials 
15.6 
Publication Policy 
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. 
16. Sponsor Contact Information 
 
Sponsor 
Medtronic MiniMed, Inc.
(“Medtronic”) 
18000 Devonshire St 
Northridge, CA 91325 
866.948.6633 
 

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17. References  
 
Ly T, Davis E, Gallego P, and Jones T. Impaired Awareness of Hypoglycemia in a Population-
Based Sample of Children and Adolescents With Type 1 Diabetes. Diabetes Care Diabetes Care 
2009; 32:1802–1806 
 
Clarke WL, Cox DJ, Gonder-Frederick LA, et al. Reduced awareness of hypoglycemia in adults 
with IDDM: a prospective study of hypoglycemic frequency and associated symptoms. Diabetes 
Care 1995; 18:517–522 
 
Streja D. Can continuous glucose monitoring provide objective documentation of hypoglycemia 
unawareness? Endocr Pract. 2005;11(2):83-90. 
 
Juvenile Diabetes Research Foundation, Continuous Glucose Monitoring Study Group. The Effect of 
Continuous Glucose Monitoring in Well-Controlled Type 1 Diabetes. Diabetes Care, Volume 32, Number 
8, August 2009: 1378-1383 
 
 
18. Appendices  
None 
 
 
 
 
 

 
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