Study of MiniMed™ 640G Insulin Pump With SmartGuard™ in Prevention of Low Glucose Events in Adults With Type 1 Diabetes
Phase: NA
Conditions: Type 1 Diabetes
Sponsor: Medtronic MiniMed, Inc.

 
 
Clinical Investigation Plan 
 
 
 
Version 1.0 
SMILE CEP 311 
Page 1 of 69  
15FEB2016 
Medtronic Confidential 
 
 
 
         BRC_T432 V5.0 
 
 
 
 
 
 
 
 
 
 
SMILE 
Study of MiniMed™ 640G Insulin Pump with SmartGuard™  
in prevention of Low Glucose Events  
in adults with Type 1 diabetes 
 
Clinical Investigation Plan 
Version 1.0 
15FEB2016 
CEP 311 
 
Sponsor Europe 
Sponsor Canada 
Medtronic International Trading 
Sàrl. (“Medtronic”) 
Route du Molliau 31 
1131 Tolochenaz, Switzerland  
Medtronic of Canada 
99 Hereford St.  
Brampton ON L6Y 0R3 
 Canada 
 
 

 
 
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Approval sheet for participating investigator: 
 
 
 
 
 
(name) 
(city/country) 
 
 
 
(signature) 
(date) (DD MMM YYYY) 
 
 
 
 
 
(name) 
(city/country) 
 
 
 
(signature) 
(date) (DD MMM YYYY) 

 
 
Clinical Investigation Plan 
 
 
 
 
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Change History record 
 
CIP Change History 
Version 
Summary of Changes 
Author 
1.0 
initial release 
 
 

 
 
Clinical Investigation Plan 
 
 
 
 
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TABLE OF CONTENTS 
 
A 
SYNOPSIS ............................................................................................... 11 
B 
GENERAL INFORMATION ..................................................................... 16 
B.1 
Introduction ........................................................................................................................ 16 
B.2 
Device information ............................................................................................................. 18 
 Medtronic MiniMed 640G Insulin Pump .................................................................. 19 
B.2.1
 Continuous Glucose Monitoring (CGM) .................................................................. 20 
B.2.2
 The Enlite 3 Sensor (MMT-7020) and Enlite One-Press Serter (MMT-7512) ......... 20 
B.2.3
 CONTOUR NEXT LINK 2.4 Blood Glucose Meter ........................................................ 21 
B.2.4
 Medtronic CareLink™ Therapy Management Software (MMT-7334) ..................... 22 
B.2.5
 Medtronic CareLink™ USB 2 (MMT-7306) ............................................................. 22 
B.2.6
B.3 
Comparator information ..................................................................................................... 22 
 GST3C System for blinded continuous glucose monitoring .................................... 22 
B.3.1
C 
STUDY PLAN .......................................................................................... 25 
C.1 
Study objectives ................................................................................................................. 25 
 Primary objective ..................................................................................................... 25 
C.1.1
 Secondary objectives .............................................................................................. 25 
C.1.2
C.2 
Clinical endpoints ............................................................................................................... 25 
 Primary endpoint ..................................................................................................... 25 
C.2.1
 Secondary endpoints ............................................................................................... 25 
C.2.2
 Tertiary endpoints / descriptive analysis: ................................................................ 26 
C.2.3
C.3 
Study Hypothesis ............................................................................................................... 27 
C.4 
Study population ................................................................................................................ 27 
C.5 
Study design ...................................................................................................................... 27 
C.6 
Randomization ................................................................................................................... 28 
C.7 
Sample size ....................................................................................................................... 28 
C.8 
Number of investigational sites and study duration ........................................................... 28 
D 
SUBJECT SELECTION ........................................................................... 29 
D.1 
Inclusion criteria at screening ............................................................................................ 29 
D.2 
Exclusion criteria ................................................................................................................ 29 
D.3 
Randomization criteria ....................................................................................................... 29 
E 
STUDY PREPARATION PROCEDURES ................................................ 30 
E.1 
Investigator/Investigation site selection ............................................................................. 30 
 Investigator selection criteria ................................................................................... 30 
E.1.1
 Investigation site selection criteria .......................................................................... 30 
E.1.2
 Clinical Investigation Agreement ............................................................................. 30 
E.1.3
 Curriculum Vitae ...................................................................................................... 30 
E.1.4
E.2 
Ethics ................................................................................................................................. 31 
 EC/IRB approval ...................................................................................................... 31 
E.2.1
 Informed consent process ....................................................................................... 31 
E.2.2
 Revisions in Patient Information and Informed Consent Form ............................... 31 
E.2.3
 Regulatory submission ............................................................................................ 32 
E.2.4
E.3 
Regulatory compliance ...................................................................................................... 32 
E.4 
Training requirements ........................................................................................................ 32 
E.5 
Clinical study materials and clinical study-specific equipment .......................................... 32 
E.6 
Study device/product traceability ....................................................................................... 32 

 
 
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 Supply of devices/products ..................................................................................... 32 
E.6.1
 Storage & handling of study devices/products ........................................................ 33 
E.6.2
 Device/product return procedures ........................................................................... 33 
E.6.3
 Device/product disposition requirements ................................................................ 33 
E.6.4
F 
STUDY METHODS .................................................................................. 33 
F.1 
Point of enrollment ............................................................................................................. 33 
F.2 
Procedure aspects ............................................................................................................. 33 
 Pump and CGM Trainings ....................................................................................... 34 
F.2.1
 Glucose targets ....................................................................................................... 34 
F.2.2
 GST3C blinded recorder Training ........................................................................... 34 
F.2.3
 Patient Questionnaires ............................................................................................ 35 
F.2.4
F.3 
Details of Procedures and Data Collection requirements per visit .................................... 36 
 Visit 1: Enrollment ................................................................................................... 37 
F.3.1
 Visit 2: Screening .................................................................................................... 38 
F.3.2
 Visit 3: Start Run-in  [Visit 2 (+7 days max)] ........................................................... 39 
F.3.3
 Visit 4: Call  [Visit 3 + 7 days (+3 days max)] .......................................................... 39 
F.3.4
 Visit 5: Randomization  [Visit 4 + 7 days (+7 days max)] ........................................ 40 
F.3.5
 Visit 6: Start Treatment  [Visit 5 (+14 days max)] .................................................... 41 
F.3.6
 Visit 7: 1 week Follow-Up Visit or Call  [Visit 6 + 7 days (±3 days max)] ................ 41 
F.3.7
 Visit 8: 2 week Follow-Up Call     [Visit 6 + 14 days  (±3 days max)] ...................... 42 
F.3.8
 Visit 9: 6 week Follow-up Visit    [Visit 6 + 42 days (±7 days max)] ........................ 42 
F.3.9
 Visit 10: 10 week Follow-Up Call    [Visit 6 + 70 days  (±7 days max)] ................... 43 
F.3.10
 Visit 11: 12 week Follow-up Visit   [Visit 10 + 14 days (+7 days max)] ................... 43 
F.3.11
 Visit 12: 16 week Follow-Up Call    [Visit 6 + 112 days (±7 days max)] .................. 44 
F.3.12
 Visit 13: 18 week Follow-up Visit     [Visit 12 + 14 days (+7 days max)] ................. 45 
F.3.13
 Visit 14: 22 week Follow-Up Call     [Visit 6 + 154 days (±7 days max)] ................. 46 
F.3.14
 Visit 15: 24 week End of study Visit    [Visit 14 + 14 days (+ 7 days max)] ............ 47 
F.3.15
 Unscheduled visit: ................................................................................................... 48 
F.3.16
 Early Termination visit: ............................................................................................ 48 
F.3.17
F.4 
Role of the sponsor’s representatives ............................................................................... 49 
F.5 
Source documents ............................................................................................................. 49 
F.6 
Adverse events .................................................................................................................. 49 
 Definitions ................................................................................................................ 49 
F.6.1
 Definitions of Diabetes related events ..................................................................... 50 
F.6.2
 Recording and reporting of Adverse Events ........................................................... 51 
F.6.3
 Recording and reporting of Device Deficiencies ..................................................... 51 
F.6.4
 Adverse Event and Device Deficiency review process ........................................... 51 
F.6.5
 Clinical events Committee ....................................................................................... 53 
F.6.6
 Data Safety Monitoring Board ................................................................................. 53 
F.6.7
 Emergency contact details in case of serious AEs ................................................. 53 
F.6.8
F.7 
Subject accountability ........................................................................................................ 54 
F.8 
Study deviations and CIP changes .................................................................................... 54 
 Request for approval of study deviations ................................................................ 54 
F.8.1
 Reporting requirements for study deviations ........................................................... 54 
F.8.2
 Amendments to the Clinical Investigation Plan ....................................................... 55 
F.8.3
G 
QUALITY CONTROL PROCEDURES .................................................... 55 
G.1 
Procedures for database management ............................................................................. 55 
 Data collection ......................................................................................................... 55 
G.1.1
 Time windows for completion and submission of Case Report Forms ................... 56 
G.1.2
 Data review and processing .................................................................................... 56 
G.1.3

 
 
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G.2 
Monitoring procedures ....................................................................................................... 56 
 Accessibility of investigation site staff and study materials ..................................... 56 
G.2.1
 Audits and investigation site inspections ................................................................. 56 
G.2.2
G.3 
Study suspension or early termination .............................................................................. 57 
 Early study suspension or termination .................................................................... 57 
G.3.1
 Early investigation site suspension or termination .................................................. 57 
G.3.2
 Subject follow-up in case of termination .................................................................. 57 
G.3.3
G.4 
Study close out .................................................................................................................. 57 
H 
DATA ANALYSIS AND REPORTING ..................................................... 57 
H.1 
Analysis of clinical data ..................................................................................................... 57 
H.2 
Publication Policy ............................................................................................................... 58 
I 
STUDY MANAGEMENT .......................................................................... 58 
I.1 
Study staff .......................................................................................................................... 58 
I.2 
Advisory committees.......................................................................................................... 59 
 Steering Committee ................................................................................................. 59 
I.2.1
 Clinical Events Committee (CEC) (section F.6.6) ................................................... 59 
I.2.2
 Data Safety Monitoring Board (DSMB) (section F.6.7) ........................................... 59 
I.2.3
I.3 
Records and reports .......................................................................................................... 59 
 Investigator Records ............................................................................................... 59 
I.3.1
 Investigator reporting responsibilities ...................................................................... 60 
I.3.2
 Sponsor records ...................................................................................................... 60 
I.3.3
 Sponsor reporting responsibilities ........................................................................... 61 
I.3.4
 Record retention ...................................................................................................... 61 
I.3.5
I.4 
Miscellaneous .................................................................................................................... 61 
 Insurance ................................................................................................................. 61 
I.4.1
 Subject compensation and indemnification ............................................................. 61 
I.4.2
 Subject confidentiality .............................................................................................. 61 
I.4.3
J 
RISKS AND BENEFITS ........................................................................... 62 
J.1 
Anticipated Clinical Benefits .............................................................................................. 62 
J.2 
Risks .................................................................................................................................. 62 
 Potential risks associated with the use of the Enlite 3 Sensor ................................ 62 
J.2.1
 Potential risks associated with the use of the GST3C Transmitter ......................... 63 
J.2.2
 Potential risks associated with the use of other investigational devices ................. 63 
J.2.3
 Potential risks associated with the use of MiniMed 640G Insulin pump: ................ 63 
J.2.4
 Potential risks associated with the use of SmartGuard Feature ............................. 64 
J.2.5
 Potential risks associated with the use of CONTOUR NEXT LINK 2.4 meter .............. 64 
J.2.6
J.3 
Risk-to-benefit rationale ..................................................................................................... 64 
K 
REFERENCES ......................................................................................... 65 
L 
APPENDICES .......................................................................................... 66 
L.1 
Names and addresses ....................................................................................................... 66 
 List of contact persons ............................................................................................ 66 
L.1.1
L.2 
Case Report Forms ........................................................................................................... 67 
L.3 
Sample Investigator Agreement ........................................................................................ 67 
L.4 
List of consumables ........................................................................................................... 67 
L.5 
Sample Questionnaires ..................................................................................................... 68 
L.6 
Abbreviations ..................................................................................................................... 69 
 
 
 

 
 
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FIGURES 
Figure 1: Study design overview ............................................................................................................... 15 
Figure 2: Medtronic MiniMed 640G insulin pump ...................................................................................... 20 
Figure 3: Enlite 3 Sensor and One-Press serter........................................................................................ 21 
Figure 4: GST3C Transmitte and GST3C Charger ................................................................................... 21 
Figure 5: CONTOUR NEXT LINK 2.4 meter.................................................................................................... 21 
Figure 6: CareLink USB 2 .......................................................................................................................... 22 
Figure 7: Watertight Tester ........................................................................................................................ 24 
Figure 8: Study design overview ............................................................................................................... 36 
 
TABLES 
Table 1 Study procedures and data collection .......................................................................................... 15 
Table 2 Clinical evidence SAP therapy with SmartGuard ......................................................................... 17 
Table 3: Number of devices per subject .................................................................................................... 24 
Table 4 Summary of glycemic recommendations for non-pregnant adults with diabetes ......................... 34 
Table 5: Study procedures and Data collection ......................................................................................... 37 
Table 6 Adverse Event Reporting Requirements ...................................................................................... 52 
 
 

 
 
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A SYNOPSIS 
Title 
SMILE - Study of MiniMed™ 640G Insulin Pump with SmartGuard™ in prevention of Low Glucose Events 
in adults with Type 1 diabetes (CEP311). 
Purpose 
The aim of the study is to evaluate the efficacy of sensor augmented pump (SAP) therapy with MiniMed™ 
640G and SmartGuard™ in preventing hypoglycemic events in comparison with continuous subcutaneous 
insulin infusion (CSII) therapy in type 1 diabetes adults with an increased risk of hypoglycemia. 
Design 
A pre-market, multi-center, prospective, open label, adaptive, randomized controlled study. 
Medical device/product 
The following CE-marked products will be provided during the course of the study:  
- 
MiniMed™ 640G Insulin Pump (MMT-1711,mmol/L) or (MMT-1712,mg/dL). 
Subjects already using a MiniMed™ 640G pump will not be provided with a pump for the purpose of 
this study and will continue using their own pump. 
- 
CareLink™ USB 2 (MMT-7306) 
- 
CareLink™ Clinical Therapy Management Software version 5.1 (MMT-7334) or subsequent versions 
- 
MiniMed™ Quick-set™, MiniMed™ Mio™, MiniMed™ Silhouette™, MiniMed™ Sure-T™ and 
MiniMed™ Mio™ 30 infusion sets (detailed list in appendix L.4). 
- 
MiniMed™ Reservoirs: 1.8 mL (180-unit, MMT-326A) or 3.0 mL (300-unit, MMT-332A)  
- 
Enlite™ One-Press serter (MMT-7512) 
- 
CONTOUR™ NEXT LINK 2.4 meter by Ascencia (MTT-1151,mmol/L) or (MMT-1152,mg/dL) referred to 
as the study meter throughout this protocol  
Subjects already using a CONTOUR™ Next Link 2.4 meter will not be provided with a meter for the 
purpose of this study and will continue using their own meter.  
- 
CONTOUR™ NEXT Strips by Ascencia 
- 
CONTOUR™ NEXT Control Solution by Ascencia 
- 
GST3C transmitter accessories: 
- 
Charger (MMT-7715)  
- 
Watertight Tester (MMT-7726)  
- 
USB cable and Wall-powered adapter (MMT-7747)  
 
 
The following investigational products will be provided during the course of the study: 
- 
Enlite™ 3 sensor (MMT-7020) 
- 
GST3C transmitter (MMT-7811) 
- 
GST3C transmitter accessories: 
- 
GST3C Dock (T8381) 
- 
GST3C Download Utility (9029393) 
 
The following CE-marked products are not licensed in Canada and will be considered investigational in 
Canada: 
- 
MiniMed™ 640G Insulin Pump (MMT-1711, mmol/L) or (MMT-1712, mg/dL). 
- 
CONTOUR™ NEXT LINK 2.4 meter by Ascencia (MTT-1151, mmol/L) or (MMT-1152, mg/dL). 

 
 
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Objectives and endpoints 
 
Primary Objective:  
The primary study objective is to demonstrate a reduction in the mean number of hypoglycemic events 
when using the MiniMed 640G system with the SmartGuard algorithm:   
The between group difference in the incidence of hypoglycemic events below or equal 55 mg/dL (3.0 
mmol/L) during 6 months of SAP therapy with SmartGuard, as compared to patients on CSII therapy 
alone over the same period of time, in a population of T1 diabetic patients with an increased risk of 
hypoglycemia, will be evaluated. A reduction in the mean number of hypoglycemic events below the 
threshold of 55 mg/dL (3.0 mmol/L) is estimated to be of clinical value.   
The evaluation will be made by comparing subject sensor data collected in both groups.  
 
Secondary objectives: 
Secondary objectives will aim at evaluating the difference in glycemic parameters and HbA1c.  
 
Primary endpoint: 
Mean number of sensor glucose hypoglycaemic events below or equal to 55 mg/dL (3.0 mmol/L) per 
patient/week. The mean number of sensor glucose hypoglycaemic events will be calculated in each study 
arm and a between group comparison will be performed.  Sensor glucose data for the primary endpoint 
will consist of 6 weeks of sensor readings in both arms in the randomization phase (as illustrated in 
Figure 1 (2 weeks (Visit 10 to 11) + 2 weeks (Visit 12 to 13) + 2 weeks (Visit 14 to 15)). 
A hypoglycemic event is defined as sensor glucose values of 55 mg/dL (3.0 mmol/L) or less for more 
than 20 consecutive minutes. When the time between two successive events is less than 30 minutes, 
they will be combined and counted as one event.  
 
Secondary endpoints: 
• 
Mean number of sensor glucose hypoglycemic events ≤ 40 mg/dL (2.2 mmol/L), ≤ 55 mg/dL (3.0 
mmol/L) and ≤ 70 mg/dL (3.9mmol/L) and categorized by starting at daytime (08:01 to 21:59) and 
night-time (22:00 to 08:00).  
• 
Mean Time spent and AUC of sensor glucose values below or equal 40 mg/dL (2.2 mmol/L), 55 
mg/dL (3.0mmol/L) and 70 mg/dL (3.9mmol/L) and categorized by starting at daytime (08:01 to 
21:59) and night-time (22:00 to 08:00).  
• 
Mean Time spent and AUC of sensor glucose values above 180 mg/dL (10.0 mmol/L), 240 mg/dL 
(13.3 mmol/L), and 300 mg/dL (16.7 mmol/L) and categorized by starting at daytime (08:01 to 
21:59) and night-time (22:00 to 08:00). 
• 
Mean Time spent of sensor glucose values within range and including 70-140 mg/dL (3.9 -7.8 
mmol/L) and 70-180 mg/dL (3.9-10.0 mmol/L) and categorized by starting at daytime (08:01 to 
21:59) and night-time (22:00 to 08:00). 
• 
Mean sensor glucose values surrounding SmartGuard triggered insulin suspensions lasting <30, 
≥30 to <90, and ≥90 to 120 minutes. Mean sensor glucose values 60 min before and up to 360 min 
after suspend before low is activated categorized by suspensions lasting less than 30, ≥30 to <90, 
≥90 to 120 minutes, and categorized by starting at daytime (08:01 to 21:59) and night-time (22:00 
to 08:00). 
• 
Proportion of Suspend before low events that reached the pre-set Low Limit calculated, as per the 
individualised Low Limit settings at any given time point. 
• 
Excursion amplitudes of the glucose values measured by mean amplitude of glycaemic excursions 
(MAGE), 24-hour standard deviation (SD) of glucose values.  
• 
Mean HbA1c change from baseline to 6 months and stratified by baseline HbA1c level ≤7.5% and 
>7.5%. 
 
 
 

 
 
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Tertiary endpoints / descriptive analyses:  
These will include and are not limited to the following (and also described in the Statistical Analysis Plan): 
• 
Safety endpoints: Number of severe hypoglycemic events, diabetic ketoacidosis events, (Serious) 
Adverse Events, (Serious) Adverse Device Effects and Device Deficiencies (see F.6 for definitions). 
• 
Hypoglycemia-related number and mean duration of hospitalizations, number and mean duration 
ICU (intensive care unit) care, number of emergency room admissions, number of events requiring 
ambulance assistance and number of lost days from school or work. 
• 
Mean HbA1c level and mean number of sensor hypoglycemia events per week will be reported  by 
age group, duration of diabetes, duration of pump therapy at time of screening, type of insulin 
analog used in study  
• 
Mean number of SMBG  
• 
Mean Clarke, Gold, HFS and DTSQ questionnaire score. 
• 
Mean weight and mean insulin total daily delivery dose. 
 
Subject population 
Adults (aged 24 to 75 years) diagnosed with Type 1 Diabetes Mellitus with disease duration of 10 years 
or more before screening and currently on CSII therapy for at least 6 months will be included in this 
study. Subjects can be naïve or experienced with the MiniMed 640G insulin pump, but should not have 
been on CGM therapy for at least 3 months prior to screening. 
Sample size calculations have shown that 136 subjects (68 in each arm) need to complete the study. 
Taking into account the anticipated drop-out of 10% at screening, 15% at run-in and 15% during the 6 
month follow-up period, it is calculated that 210 subjects need to be screened, in order to have 189 
subjects starting the run-in phase, and 160 randomized subjects.  
This study is an adaptive design.  Adjustment to the required number of patients will be re-assessed by 
an independent DSMB at interim analysis. 
Up to 25 study centers across Europe, Canada and potentially other geographic regions will be selected 
at study start, based on each investigator’s experience and qualifications, availability of sufficient 
resources to carry out the required study procedures, and their potential to randomize an average of 9 
subjects within the 6 month enrollment period. The number of investigational sites or period of enrollment 
may be increased to accommodate a quicker or larger enrollment. 
Overall study duration from first subject enrollment until the last subject exits the study is expected to be 
18 months, including an estimated period of 6 months to activate all sites, a 6 month enrollment period, 
and a 6 month follow-up period for each subject.  
Treatment 
All enrolled subjects will start a run-in phase, receive training and start CSII therapy with the MiniMed 
640G insulin pump and usage of blinded Continuous Glucose Monitoring (CGM). Eligible subjects that 
meet the randomization criteria assessed after the run-in phase will be randomized into the treatment 
phase of 6 months: 
• 
Treatment Arm: training and start of Sensor Augmented Pump therapy with Suspend before Low 
feature of SmartGuard turned ON. 
• 
Control Arm: continuation of CSII therapy alone with blinded CGM usage for a total of 6 weeks 
during the treatment phase. 
 

 
 
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Inclusion criteria 
Subjects will be considered for enrollment in the study, if they meet all of the following criteria, assessed 
after subject has signed informed consent: 
1. Age 24-75 years old at time of screening. 
2. Diagnosed with Type 1 diabetes ≥10 years prior to screening. 
3. On CSII therapy for ≥ 6 months prior to screening. 
4. Not on Real Time Continuous Glucose Monitoring for ≥ 3 months prior to screening. 
5. HbA1c value ≥5.8% and ≤10.0% as assessed by local lab ≤ 15 days prior to screening or 
performed at screening. 
6. A documented Severe Hypoglycemia event ≤ 12 months prior to screening, OR 
Clarke score ≥4 assessed at time of screening, OR 
Gold score ≥4 assessed at time of screening. 
7. Subject is willing to sign and date informed consent, comply with all study procedures and wear all 
study devices as required during the study. 
 
Exclusion criteria 
A subject who meets any of the following criteria will be excluded from participation in this study. 
1. Untreated Addison’s disease, thyroid disorder, growth hormone deficiency, hypopituitarism or 
definite gastroparesis, per investigator judgment.  
2. Renal failure defined by creatinine clearance <30 ml/min, as assessed by local lab test ≤ 3 months 
before screening or performed at screening at local lab, as defined by the creatinine-based 
Cockcroft or MDRD equations. 
3. Hearing or vision impairment hindering perception of glucose display and alarms, or otherwise 
incapable of using the study devices, per investigator judgment. 
4. Current pregnancy or intention to conceive. 
5. Any unresolved adverse skin condition in the area of sensor placement (e.g. psoriasis, rash, 
Staphylococcus infection). 
6. Alcohol or drug abuse, other than nicotine, per investigator judgment. 
7. Any other disease or condition that may preclude the patient from participating in the study, per 
investigator judgment. 
8. Legally incompetent, illiterate or vulnerable person. 
 
Randomization criteria 
If subjects meet the above criteria, as well as all of the following criteria assessed at the end of the run-in 
period, they may continue to participate in the treatment period of the study: 
1. Subject has worn two weeks the sensor with transmitter during the run-in period. 
2. Subject has shown acceptable tolerance of Enlite 3 sensor wear, per investigator judgment. 
3. Subject performed ≥ 4 finger stick blood glucose measurements daily, as determined by CareLink 
Clinical data upload as the mean number of SMBG/day over the past 14 days (SMBG number / day 
≥ 3.5 rounds up to 4). 
4. Subject showed ability to comprehend the pump training and study procedures, per investigator 
judgment. 
 
 

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Procedures and 
 Data collection 
Enrollment1 
Screening1
Start Run-in1
Call 
End Run-in/ 
Randomization2 
Start Treatment2 
1w call/visit
2w  call 
6 w Visit
10w call
12w visit
16w call
18w visit 
22w call
End of Study 
Early Termination6 
Visit number  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
 14 
  15 
 
Target week 
w0 
w0 
w0 
-3w 
w0 
-2w 
w0 
-1w 
w0 
w1 
w2 
w6 
w10 
w12 
w16 
w18 
w22 
w24 
Target day 
d0 
d0 
V2 
V3+ 
7d 
V4+ 
7d 
V5 
 
V6+ 
d7 
V6+ 
d14 
V6+ 
d42 
V6+ 
d70 
V10+ 
d14 
V6+ 
d112 
V12+ 
d14 
V6+ 
d154 
V14+ 
d14 
Window 
- 
- 
+7d 
+3d 
+7d 
+14d 
±3d 
±3d 
±7d 
±7d 
+7d 
±7d 
+7d 
±7d 
+7d 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization criteria 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A1c (local lab)  
 
O3 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
Creatinine test (local) 
 
O3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Device Accountability 
 
 
X
 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
X 
MiniMed640G training 
 
 
X
 
 
 
  
 
 
 
 
 
 
 
 
 
CGM training 
 
 
 
 
 
T4 
 
 
 
 
 
 
 
 
 
 
Blinded CGM training  
 
 
X
 
 
 
 
 
C5 
 
 
 
 
 
 
 
Blinded CGM placement 
 
 
X
X
 
 
 
 
 
C 
 
C 
 
C 
 
 
Blinded CGM upload 
 
 
 
 
X 
 
 
 
 
 
C 
 
C 
 
C 
C 
CareLink Clinical upload 
 
 
 
 
X 
X 
T 
 
X 
 
X 
 
X 
 
X 
X 
Distribution supplies 
 
 
X
 
X 
X 
 
 
X 
 
X 
 
X 
 
 
 
Clarke questionnaire 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
Gold Questionnaire 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
HFS  questionnaire 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
DTSQs  questionnaire  
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
DTSQc  questionnaire 
 
 
 
 
 
 
 
 
 

 
 
 
X 
 
X 
AEs and Deficiencies  
 
Reported upon occurrence or at a site visit and CareLink Clinical data upload, if possible. 
Study deviations  
 

 
 
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B  GENERAL INFORMATION 
B.1 Introduction 
Managing type 1 diabetes requires constant vigilance and attention to diet, exercise, and insulin 
regimens, and depends on consistently delivering the right amount of insulin at the right time. Medtronic’s 
insulin delivery systems have been helping type 1 diabetes patients with their diabetes management for 
more than 30 years. The insulin pump system is indicated for the continuous delivery of insulin, at set and 
variable rates, for the management of diabetes mellitus in persons requiring insulin. Technological 
advances in insulin pump delivery systems and key clinical trials have established the value of this 
therapy in helping patients with their daily diabetes management. 
First improvement was real-time continuous glucose monitoring (CGM) data, used in conjunction with 
insulin pump therapy, allowing patients to safely reduce their HbA1c values in comparison with multiple 
daily injection (MDI) therapy [1] and continuous subcutaneous insulin injections (CSII) alone [2] by using 
CGM data to guide them in their insulin dosing regimen. Thereafter a feature was introduced, called Low 
Glucose Suspend (LGS), allowing the pump to automatically suspend insulin delivery when a pre-set 
sensor glucose threshold was reached. When this LGS feature is enabled in a Paradigm® Veo™ pump 
and a sensor glucose value at or below the pre-specified value is detected, the pump will stop insulin 
delivery for up to 2 hours, if not restarted earlier by the user. The benefits of sensor-augmented pump 
(SAP) therapy using this feature has been proven in several clinical trials, showing reduction in the 
incidence, severity and duration of hypoglycemic events [3, 4, 5]. In addition, also data analyses based on 
routine real world use of pumps with the LGS feature confirm significant reductions in hypoglycemia [6, 7]. 
The most recent advancement in SAP therapy is SmartGuard™. Medtronic’s SmartGuard technology is 
implemented in the recently commercialized MiniMed™ 640G system and consists of the algorithms 
called, suspend on low, and suspend before low. The suspend on low is similar to the LGS algorithm in 
the Paradigm Veo pump and the Suspend before low feature, also called Predictive Low Glucose 
Management (PLGM), is the newest sensor algorithm that can suspend insulin delivery when the sensor 
glucose value is predicted to reach or fall below a pre-set low glucose limit within 30 minutes. In addition, 
the Suspend before low algorithm allows for automatic resumption of basal insulin delivery after 30-120 
minutes, if the system predicts patient’s recovery from hypoglycemia. During the suspension, insulin 
delivery can be manually resumed by the user at any time, and settings and alerts are customizable 
within multiple time blocks depending on the patient’s needs in the MiniMed™ 640G system.   
Suspending insulin delivery in response to predicted hypoglycemia has been tested in several in-clinic 
studies employing various investigational configurations of pumps, sensors, induction protocols, and 
algorithms [8, 9, 10]. One of these studies involving increases in basal insulin delivery rates, noted 
overnight hypoglycemia in 9 of 10 participants in the control arm, compared to 2 of 10 participants in the 
predictive pump suspension arm [9]. Another report noted that exercise induced hypoglycemia was 
prevented with the predictive suspension feature in 80% of the successful experiments [10]. Furthermore, 
this data was confirmed in a user evaluation study of the MiniMed 640G system (four weeks follow-up 
period, 40 Type 1 patients) demonstrating that, following 83% of suspend before low activations (out of 
2300 suspend before low activations) the pre-set low limit threshold was not reached [11].  
 
Hypoglycemia is an important barrier in achieving tight glycaemic control. Even mild events of 
hypoglycemia have been shown to disrupt sleep, impair memory, and cause inflammatory reactions, with 
impacts on driving, work and daily living. Approximately one-third of patients with type 1 diabetes have 
evidence of impaired hypoglycemia awareness [12, 13, 14], further increasing their risk of severe 
hypoglycemia. However, avoidance of hypoglycemia in these patients has been shown to restore 
awareness in small scale proof of concept studies [15, 16]. Till now, most studies of CSII and CGM 

 
 
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therapy have excluded these patients, and therefore, there are few studies to demonstrate if these 
technologies can provide an improvement specifically in this population. 
The SMILE study will specifically recruit subjects with impaired awareness of hypoglycaemia and aim to 
investigate if this technology can reduce the incidence of hypoglycemia in this group of high risk patients. 
 
Despite the available clinical evidence, as described above, SAP therapy is not widely adopted, partly 
because CGM is not yet reimbursed in many countries. The current clinical evidence on the ability of SAP 
to reduce the risk of hypoglycemic events [3, 4, 5] could be considered as not robust enough (e.g. short 
study duration, small number of subjects, not the right comparator, sub-optimal randomization process). 
Additional clinical evidence on the ability of SAP with SmartGuard technology to reduce the risk of 
hypoglycemic events can potentially lead to wider adoption and reimbursement of CGM technology to 
benefit patients’ needs. 
 
In-clinic studies  on MiniMed 640G with the Suspend before low feature of SmartGuard demonstrated the  
safety and the efficacy of  the investigational configuration of this system after induced hypoglycemia [8] 
[9] [10]. Additional clinical evidence with the MiniMed 640G system and SmartGuard algorithm are 
required to evaluate the efficacy in in-home settings for a longer duration and with more 'real life’ 
variables inducing hypoglycemia, in comparison  with CSII therapy, as the current standard of care, to 
support SAP therapy adoption and CGM reimbursement. 
 
 
Table 2 Clinical evidence SAP therapy with SmartGuard  
Study 
Design 
Primary endpoint 
Status 
Buckingham 
42-night RCT,  Investigational 
PLGM algorithm ON overnight vs 
OFF  N= 81 pediatrics 
Test PLGM algorithm overnight 
Percent time 
Published. Diabetes Care 
2010;33:1013-1017 
PILGRIM  
1 day in clinic , Investigational 
PLGM algorithm, N=22 pediatrics 
Test PLGM algorithm after  
exercise induced hypoglycemia 
Published. DTT  
Jun2014;16(6):338-47 
T. Jones 
1 day in clinic, 
N=21 pediatrics 
Test algorithm with bolus and 
exercise induced hypoglycaemia 
Published.  DTT Feb 2014; 
16(Suppl 1): A-1-A-162, 
IJPE 2015; (Suppl 1):O36. 
User Evaluation 
4wk Observational SmartGuard 
ON, N=24 adults +16 pediatrics 
User acceptance MiniMed 640G 
(1.8ml pump) 
Publication accepted DTT 
2016 
SportGuard 
2w RCT, SmartGuard ON vs OFF 
N=98 pediatrics 
Event rate events <65 mg/dL 
(<3.6mmol/L)  
Completed 
T. Jones 
6m RCT, SmartGuard ON vs OFF 
N ~176 pediatrics 
Time spent in events <3.5 
mmol/L, 40% reduction 
Ongoing 
T. Danne 
8w RCT, SmartGuard 2w OFF  
then 6w ON, N ~24 pediatrics 
AUC <70 mg/dl (3,9 mmol/L) 
Ongoing 
S. Lablanche 
6m RCT, SmartGuard ON vs OFF,  
N ~20 adults 
Event rate events <65 mg/dL 
(<3.6mmol/L) 
Ongoing 
 

 
 
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B.2 Device information 
The Medtronic MiniMed™ 640G System evaluated in this study includes investigational and CE-
marked, commercially available, device components, which will all be used within their intended use.  
 
The following CE-marked products will be provided during the course of the study:  
- 
MiniMed™ 640G Insulin Pump (MMT-1711, mmol/L) or (MMT-1712, mg/dL). 
Subjects already using a MiniMed™ 640G pump will not be provided with a pump for the purpose of 
this study and will continue using their own pump. 
- 
CareLink™ USB 2 (MMT-7306) 
- 
CareLink™ Clinical Therapy Management Software version 5.1 (MMT-7334) or subsequent versions 
- 
MiniMed™ Quick-set™, MiniMed™ Mio™, MiniMed™ Silhouette™, MiniMed™ Sure-T™ and 
MiniMed™ Mio™ 30 infusion sets (detailed list in appendix L.4). 
- 
MiniMed™ Reservoirs: 1.8 mL (180-unit, MMT-326A) or 3.0 mL (300-unit, MMT-332A)  
- 
Enlite™ One-Press serter (MMT-7512) 
- 
CONTOUR™ NEXT LINK 2.4 meter by Ascencia (MTT-1151, mmol/L) or (MMT-1152, mg/dL), referred 
to as the study meter throughout this protocol  
Subjects already using a CONTOUR™ Next Link 2.4 meter will not be provided with a meter for the 
purpose of this study and will continue using their own meter.  
- 
CONTOUR™ NEXT Strips by Ascencia 
- 
CONTOUR™ NEXT Control Solution by Ascencia 
- 
GST3C transmitter accessories: 
- 
Charger (MMT-7715)  
- 
Watertight Tester (MMT-7726)  
- 
USB cable and Wall-powered adapter (MMT-7747)  
 
 
The following investigational products will be provided during the course of the study: 
- 
Enlite™ 3 sensor (MMT-7020) 
- 
GST3C transmitter (MMT-7811) 
- 
GST3C transmitter accessories: 
- 
GST3C Dock (T8381) 
- 
GST3C Download Utility (9029393) 
 
The following CE-marked products are not licensed in Canada, and will be considered investigational in 
Canada: 
- 
MiniMed™ 640G Insulin Pump MMT-1711 (mmol/L) or MMT-1712 (mg/dL)  
- 
CONTOUR™ NEXT LINK 2.4 meter by Ascencia (MTT-1151, mmol/L) or (MMT-1152, mg/dL). 
 
All devices and consumables for diabetes pump therapy mentioned above and in appendix L.4 will be 
provided to the subjects for the duration of the study except for the subjects already using a MiniMed™ 
640G insulin pump and/or a CONTOUR™ NEXT LINK 2.4 meter, who will continue with their own device(s) 
for the study. 
Any subsequent model of the above mentioned devices is also eligible, as soon as it becomes 
commercially available in the participating countries. 
Usage of CareLink™ Personal and CareLink™ Pro  Therapy Management Software is optional per 
routine practice by the subjects and sites. Usage of other market released infusion sets and consumables 
(e.g. Lancets) are optional and prescribed per routine practice.  
For additional product information on software applications, correct classification and regulatory status, 
materials used, installations for use, storage and handling, and the necessary medical procedures 
involved in the use of each device system/product, refer to the Instructions for Use or Investigator 
Brochure of each product.  
 

 
 
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The labeling of the Investigational devices and CE marked devices will be provided in accordance with 
local language requirements. 
Investigational devices and consumables will be labeled as required by national regulations, in local 
language(s) as follow:  
 
- 
UK: ”Investigational Device. To be Used by Qualified Investigators Only” 
- 
Canada: “Investigational Device. To be Used by Qualified Investigators Only” “Instrument de 
recherche. Réservé uniquement à l’usage de chercheurs compétents” 
- 
Italy: “Esclusivamente per indagini cliniche”  
- 
The Netherlands: "uitsluitend voor klinisch onderzoek" 
- 
France: ”Usage réservé aux études cliniques” 
 
Previous training and experience on the MiniMed 640G system is preferred for the participating centers, 
as assessed during site qualification.  
The subject can use any rapid-acting analogue insulin (e.g. Lispro, Aspart or Glulisine) compatible with 
CSII during the study, which will be prescribed per routine practice.  
The site personnel will be requested to upload subjects’ MiniMed 640G insulin pump data using the 
CareLink Clinical Therapy Management Software at each subject’s visit. 
 
 Medtronic MiniMed 640G Insulin Pump  
B.2.1
The device evaluated in this study is the Medtronic MiniMed 640G insulin pump, which is the latest 
commercialized version of Medtronic’s MiniMed insulin pumps (Figure 2). The MiniMed 640G system is 
indicated for the continuous delivery of insulin, at set and variable rates, for the management of diabetes 
mellitus in persons requiring insulin. 
In addition, the pump system is indicated for continuous or periodic monitoring of glucose levels in the 
fluid under the skin, and possible low and high blood glucose events. The pump displays continuous 
glucose values and stores this data so that it can be analyzed to track patterns and improve diabetes 
management. Pump history can be downloaded to a computer for analysis of historical glucose values. 
This new pump system has, in comparison to the previous models, an enhanced personalized 
convenience (e.g. preset bolus, basal pattern options, louder and volume-adjustable alerts) and a more 
patient-friendly design (e.g. waterproof, color- and auto-brightness display, intuitive screen navigation, 
ergonomic design).  
The MiniMed 640G insulin pump also includes the new SmartGuard technology, which can be 
programmed with the usage of the Continuous Glucose Monitoring (CGM) components (see section 
B.2.2). The MiniMed 640G Insulin pump (MMT1711 (mmol/L) or MMT1712 (mg/dL)) is a CE-marked 
medical device and is commercially available in the countries where the study will be conducted with the 
exception of Canada, where the device will be investigational.   
Contraindications:  
Pump therapy is not recommended for people who are unwilling or unable to perform a minimum of four 
blood glucose tests per day; who are unwilling or unable to maintain contact with their healthcare 
professional; and/or whose vision or hearing does not allow recognition of pump signals and alarms. 
 
 

 
 
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Figure 2: Medtronic MiniMed 640G insulin pump 
 
 Continuous Glucose Monitoring (CGM)  
B.2.2
The MiniMed 640G insulin pump can combine insulin delivery and Continuous Glucose Monitoring 
(CGM). The CGM system used in this study includes an Enlite 3 sensor measuring glucose levels in the 
interstitial fluid and the GST3C transmitter, which connects to the sensor and sends glucose readings to 
the MiniMed 640G insulin pump, where the glucose readings are displayed on the monitor (Figure 3 and 
Figure 4). Using a Enlite 3 sensor allows users to receive up to 288 sensor glucose readings every 24 
hours for a period of 7 days. CGM alert features can help diabetes patients by making them aware of 
high and low glucose values. The graphs and trend arrows on the pump display show users the direction 
glucose levels are moving towards.  
Furthermore, the MiniMed 640G insulin pump includes SmartGuard technology. With SmartGuard, basal 
delivery can be suspended to minimize hypoglycemia, if the sensor glucose level is less than 70 mg/dL 
(3.9 mmol/L) above the preset low limit and predicted to reach 20 mg/dL (1.1 mmol/L) above the low limit 
within 30 minutes. The suspended basal insulin delivery can be resumed if the patient manually resumes 
it, or the sensor value is at least 20 mg/dL (1.1 mmol/L) above the preset low limit and predicted to be 
greater than 40 mg/dL (2.2 mmol/L) above the preset low limit within 30 minutes, or insulin delivery has 
been suspended for 2 hours. 
 The Enlite 3 Sensor (MMT-7020) and Enlite One-Press Serter (MMT-7512) 
B.2.3
The Enlite 3 sensor, referred to as the “sensor” in this protocol, is an investigational medical device. It 
may become CE-marked and commercially available during the course of the study.  
The Enlite 3 Sensor is intended for use with Medtronic Diabetes glucose sensing systems to continuously 
monitor glucose levels in persons with diabetes.   
The Enlite 3 Sensor is an electrochemical sensor that contains microelectrodes 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, similar to the currently market released Enlite sensor (MMT-7008). The sensor is 
tubeless and as a result has a smaller volume than previous Medtronic MiniMed sensors. An introducer 
needle penetrates the skin surface and provides support for the sensor microelectrode during insertion. 
The device is affixed to the skin with an adhesive and is attached to a transmitter. The sensor 
continuously converts small amounts of glucose from the subject’s interstitial fluid into an electronic 
signal that is received by a transmitter, 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. 
 
Contraindication: None known.  
 
The Enlite One-Press serter (MMT-7512) is CE-marked in Europe and licensed in Canada 
It is used to ensure correct placement of the Enlite 3 Sensor into the user’s subcutaneous tissue. 
Insertion is triggered when the two spring-loaded buttons on the sides of the Serter are pressed 
simultaneously. The serter is intended as a single-patient, non-sterile and multi-use device. 
. 

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 Medtronic CareLink™ Therapy Management Software (MMT-7334)  
B.2.5
Medtronic CareLink™ Therapy Management Software for Diabetes is a CE-marked medical device. This 
web-based CareLink system allows device data (e.g. feature settings, insulin delivery and glucose 
information) to be viewed and easily evaluated by the patient and physician. A computer links to the 
Medtronic CareLink™ system via the Internet and allows for upload of data from Medtronic MiniMed 
640G Systems.  
All references to CareLink are meant to imply the clinical support version of Medtronic CareLink™ 
Therapy Management Software and throughout the protocol will be referred to as ‘CareLink Clinical’. 
For the purpose of this study, uploads are performed by study site personnel during each subject’s site 
visit. The data contained in CareLink Clinical is accessible to study site personnel in a secured manner, 
using a standard browser (i.e., Microsoft Internet Explorer on an Internet enabled personal computer) and 
a unique study username (i.e., 311-XXX-XXX) and password created for each subject.   
 
 Medtronic CareLink™ USB 2 (MMT-7306) 
B.2.6
The Medtronic CareLink™ USB 2 device enables data from the MiniMed 640G insulin pump to be 
uploaded into the Medtronic CareLink™ Therapy Management Software. CareLink USB 2 is only 
compatible with the MiniMed 640G insulin pump and cannot be used with prior Medtronic Paradigm 
pumps.  CareLink™ USB 2 and the study meter are the only devices capable of uploading pump data to 
CareLink from the MiniMed 640G insulin pump. The Medtronic CareLink™ USB 2 will be provided to 
each center and is CE marked (Figure 6). 
 
Figure 6: CareLink USB 2 
 
 
 
 
 
B.3 Comparator information 
 
Subjects in the control arm will be using CSII therapy with the MiniMed 640G insulin pump without CGM, 
which represents the most common use of CSII therapy across Europe. The goal is to demonstrate the 
added value and benefit of adding CGM with the Suspend before low feature of SmartGuard to the 
Minimed 640G pump therapy.  
The GST3C device (MMT-7811) will be used as a blinded continuous glucose recording system for study 
purposes during the run-in phase for all subjects, and during the treatment phase in the control arm for a 
total period of 6 weeks, to collect sensor glucose data. 
 
 GST3C System for blinded continuous glucose monitoring  
B.3.1
The GST3C system consists of the following components: 
- 
GST3C transmitter (MMT-7811) used in a blinded recording mode – Investigational  
- 
Enlite 3 Sensor (MMT-7020) - Investigational 
- 
GST3C Dock (T8381) - Investigational 
- 
GST3C Download Utility Software for GST3C Transmitter (9029393) – Investigational 
- 
Charger (MMT-7715)  
- 
USB cable and Wall-powered adapter (MMT-7747)  
- 
Watertight Tester  (MMT-7726)  
 
 
 

 
 
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GST3C Transmitter, GST3C charger and Enlite 3 Sensor - Investigational 
B.3.1.1
The GST3C transmitter attached to the Enlite 3 sensor will be used as a blinded continuous glucose 
recording system for the control arm recording and storing sensor glucose data. The GST3C transmitter 
will not be linked to the Minimed 640G pump, and therefore sensor data will not  be transmitted to the 
pump.  The sensor data the GST3C transmitter contains will be downloaded with the GST3C Download 
Utility software to a site computer. The recorded and transferred sensor data are blinded and not 
available to subjects and healthcare professionals. Therefore, this data cannot be used for therapy 
adjustment during the study, and will only be used for comparison with the treatment arm during study 
data analysis.  
Contraindications: GST3C Transmitter must not be exposed to MRI equipment, diathermy devices, or 
other devices that generate strong magnetic fields. 
 
Dock for GST3C Transmitters (T8381) - Investigational 
B.3.1.2
The Dock for the GST3C Transmitter (T8381), referred to as GST3C Dock in this protocol, is an 
investigational device serving two functions: 
1. It creates a communication link between the GST3C Transmitter and a computer to be used for 
uploading the data stored on the devices and clearing the data. In this function, a cable connects the 
GST3C Dock to a USB port on the computer. 
2. It charges the internal battery of the GST3C Transmitter while it is docked in the Charger that is 
either connected to a computer (while the computer is on) or to a wall-powered adapter. The wall-
powered adaptor configuration will only charge the recorder and will not provide the upload 
functionality. 
When the GST3C Transmitter is removed from the sensor, a Watertight Tester (MMT-7726) is attached 
and then it is disinfected (see Figure 7). Once the Watertight Tester is removed, the GST3C Transmitter 
is connected to the GST3C Dock. The GST3C Dock is connected to the computer using a USB cable. 
The user can upload data from the GST3C Transmitter via the GST3C Download Utility. For the 
purposes of this study, uploads of the GST3C Transmitter are performed by  the investigational study 
staff. 
Contraindications: Not known 
 
GST3C Download Utility (9029393) - Investigational 
B.3.1.3
The GST3C Download Utility for use with the GST3C Transmitter is an investigational computer-based 
program used to set time, upload data and clear data for the GST3C Transmitter. Communication 
between the GST3C Transmitter and the computer is done via the GST3C Dock.  
The data contained in the GST3C Download Utility is transferred to a secured database by site 
personnel, using a standard browser, i.e., Microsoft Internet Explorer on an Internet enabled  computer 
and a unique username and password for each site. The GST3C Download Utility provides encrypted 
data that can’t be used during the study for therapy adjustments. 
Contraindications: Not known 
 
USB cable and Wall-powered adapter (MMT-7747) for GST3C Dock  
B.3.1.4
The USB cable and Wall-powered adapter (MMT-7747) is commercially available.  
The small end of the Universal Serial Bus (USB) cable connects to the GST3C Dock. The other end of 
the cable connects to a USB port on a computer, so that the user can upload data using the GST3C 
Download Utility and charge the GST3C Transmitter. The USB cable can also be connected to a wall- 
powered adapter.  
The wall-powered adapter lets the user charge the GST3C Transmitter by connecting the GST3C Dock 
to a regular socket, instead of a computer. It comes with 4 interchangeable power plugs. The appropriate 
power plug needs to be connected to the wall-powered adapter.  
Contraindications: Not known 
 
Watertight Tester (MMT-7726) – CE-marked 
B.3.1.5
The Watertight Tester (MMT-7726) is a CE-marked and commercially available device that operates as a 
sensor simulator creating signal current at a level that is within the range of an in-vivo sensor during 
normal operation (see Figure 7). It is used as a tester at initiation of the GST3C Transmitter. 
Contraindications: Not known 
 

 
 
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Figure 7: Watertight Tester  
 
 
 
 
 
 
 
Table 3 describes the total number of devices and consumables to be used on average by one subject 
for during the 6 months treatment phase: 
 
Table 3: Number of devices per subject 
 
Item 
Units per Subject  
(Treatment Arm) 
Units per Subject  
(Control Arm) 
640G pump (3.0 mL) 
1 
1 
Reservoir 
100 
100 
Infusion Set 
100 
100 
Infusion Set Serter (if applicable) 
1 
1 
AA Alkaline Battery 
28 
28 
CONTOUR NExt LINK 2.4 meter 
1 
1 
CONTOUR NEXT Strips 
1700 
1700 
Enlite 3  
44 
16 
Enlite One-press Serter 
1 
1 
GST3C Transmitter 
2 
2 
 
 
 

 
 
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C STUDY PLAN 
C.1 Study objectives 
The purpose of the study is to evaluate the efficacy of sensor augmented pump (SAP) therapy with 
MiniMed 640G and SmartGuard technology in preventing hypoglycemia events in comparison with 
continuous subcutaneous insulin infusion (CSII) therapy alone in Type 1 diabetes adults with an 
increased risk of hypoglycemia. 
As previously described in Section B.2, the new MiniMed 640G system includes a Suspend before low 
feature of SmartGuard,  which is intended to reduce the frequency and duration of hypoglycemic events 
by suspending insulin delivery before hypoglycemia occurs. 
Regarding safety, all adverse events will be collected and an Clinical Events Committee  (CEC) will be in 
charge of assessing all SAEs, SADEs, UADEs, Severe Hypoglycemia and Severe Hyperglycemia 
events, DKA and deaths (see section  F.6.6).  
As subject participation will be up to a maximum of 6 months, the determination of potential long-term 
effects is not planned in this study.  
 Primary objective 
C.1.1
The primary study objective is to demonstrate a reduction in the mean number of hypoglycemic events 
when using the MiniMed 640G system with the Suspend before low feature of SmartGuard in a group of 
high risk patients with impaired awareness of hypoglycaemia. The between group difference in the 
incidence of hypoglycemic events below or equal 55 mg/dL (3.0 mmol/L) during 6 months of SAP therapy 
with  SmartGuard, as compared to patients on CSII therapy alone over the same period of time, in a 
population of T1 diabetic patients with an increased risk of hypoglycemia, will be evaluated. A reduction 
in the mean number of hypoglycemic events below 55 mg/dL (3.0 mmol/L) is thought to be of clinical 
value.  The evaluation will be made by comparing subject sensor data collected in both groups.  
 Secondary objectives 
C.1.2
Secondary objectives will aim at evaluating the difference in glycemic parameters and HbA1c.  
 
Difference in glycemic parameters 
C.1.2.1
To evaluate the difference in glycemic parameters after 6 months between arms (see section C.2.2). 
 
Between group HbA1c difference 
C.1.2.2
To evaluate the change from baseline and the difference in HbA1c after 6 months between arms (see 
section (see section C.2.2). 
C.2 Clinical endpoints 
 Primary endpoint 
C.2.1
The primary endpoint is defined as the mean number of sensor glucose hypoglycaemic events below or 
equal to 55 mg/dL (3.0 mmol/L) per patient/week. The mean number of sensor glucose hypoglycaemic 
events will be calculated in each study arm and a between group comparison will be performed.  Sensor 
glucose data for the primary endpoint will consist of 6 weeks of sensor readings in both arms in the 
randomization phase (as illustrated in Figure 1 (2 weeks (from Call 10 to Visit 11) + 2 weeks (from Call 
12 to Visit13) + 2 weeks (from Call 14 to Visit 15)). 
The average of the mean number of sensor glucose hypoglycaemic events will be calculated in each 
study arm and a between group comparison will be performed.   
A hypoglycaemic event is defined as sensor glucose values of 55 mg/dL (3.0 mmol/L) or less for more 
than 20 consecutive minutes. When the time between two successive events is less than 30 minutes, 
they will be combined and counted as one event. 
Sensor glucose data will be collected during the 6 months of the study follow-up using the GST3C 
Transmitter + Enlite 3 sensor, used continuously in the treatment arm. A blinded CGM system with the 
GST3C transmitter + Enlite 3 sensor will be used for subjects in the control arm to collect sensor glucose 
data for 14 days at 10, 16 and 22 weeks. 
 Secondary endpoints 
C.2.2

 
 
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Frequency of hypoglycemic events 
C.2.2.1
- 
Mean number of sensor glucose hypoglycemic events ≤ 40 mg/dL (2.2 mmol/L), ≤ 55 mg/dL (3.0 
mmol/L) and ≤70 mg/dL (3.9mmol/L) and categorized by starting at daytime (08:01 to 21:59) and 
night-time (22:00 to 08:00). Sensor glucose hypoglycemic events are defined as sensor glucose 
values equal or less than the predefined threshold that occur for more than 20 consecutive minutes. 
When the time between two successive events is less than 30 minutes, they will be combined and 
counted as one event. 
 
Time spent and AUC in hypoglycemia 
C.2.2.2
- 
Mean Time spent and AUC of sensor glucose values below 40 mg/dL (2.2 mmol/L), 55 mg/dL 
(3.0mmol/L) and 70 mg/dL (3.9mmol/L) and categorized by starting at daytime (08:01 to 21:59) and 
night-time (22:00 to 08:00). 
 
Time spent and AUC in hyperglycemia  
C.2.2.3
- 
Mean Time spent and AUC of sensor glucose values above 180 mg/dL (10.0 mmol/L), 240 mg/dL 
(13.3 mmol/L), and 300 mg/dL (16.7 mmol/L) and categorized by starting at daytime (08:01 to 
21:59) and night-time (22:00 to 08:00). 
 
Time spent and AUC in euglycemia  
C.2.2.4
- 
Mean Time spent of sensor glucose values within range and including 70-140 mg/dL (3.9 -7.8 
mmol/L) and 70-180 mg/dL (3.9-10.0 mmol/L) and categorized by starting at daytime (08:01 to 
21:59) and night-time (22:00 to 08:00). 
 
HbA1c 
C.2.2.5
- 
Mean HbA1c change from baseline to 6 months and stratified by baseline HbA1c level ≤7.5% and 
>7.5%. 
 
Sensor glucose values surrounding SmartGuard events 
C.2.2.6
- 
Mean sensor glucose values surrounding SmartGuard triggered insulin suspensions lasting <30, 
≥30 to <90, and ≥90 to 120 minutes. Mean sensor glucose values 60 min before and up to 360 min 
after suspend before low is activated categorized by suspensions lasting less than 30, ≥30 to <90, 
≥90 to 120 minutes, and categorized by starting at daytime (08:01 to 21:59) and night-time (22:00 
to 08:00). 
- 
Proportion of Suspend before low events that reached the pre-set Low Limit calculated, as per the 
individualised Low Limit settings at any given time point. 
 
Change in glycemic variability  
C.2.2.7
- 
Excursion amplitudes of the glucose values measured by mean amplitude of glycaemic excursions 
(MAGE), 24-hour standard deviation (SD) of glucose values.  
 
 Tertiary endpoints / descriptive analysis:  
C.2.3
 
These will include and are not limited to the following (and described in the Statistical Analysis Plan): 
- 
Safety endpoints: Number of severe hypoglycemic events, diabetic ketoacidosis events, (Serious) 
Adverse Events, (Serious) Adverse Device Effects and Device Deficiencies (see F.6 for definitions). 
- 
Hypoglycemia-related number and mean duration of hospitalizations, number and mean duration of 
ICU care, number of emergency room admissions, number of events requiring ambulance 
assistance and number of lost days from school or work. 
- 
HbA1c level and mean number of sensor glucose hypoglycemic events per week will be reported  
by age groups, duration of diabetes, duration of pump therapy at time of screening, type of insulin 
analog used in study  
- 
Mean number of SMBG  
- 
Mean Clarke, Gold, HFS and DTSQ questionnaires scores. 
- 
Mean Weight and mean insulin total daily delivery dose. 
 

 
 
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C.3 Study Hypothesis 
The primary study hypothesis is described as follow:  
Mean number of sensor glucose hypoglycaemic events below or equal to 55 mg/dL (3.0 mmol/L) per 
patient/week (MNSHE) will be calculated in the TREATMENT arm (SAP with MiniMed 640G and 
SmartGuard) and the CONTROL arm (CSII with MiniMed 640G) and will be compared using the next 
hypotheses: 
Null-hypothesis:  Ho: MNSHE TREATMENT  =  MNSHE CONTROL 
Alternative hypothesis:  HA: MNSHE TREATMENT  ≠ MNSHE CONTROL 
The null-hypothesis will be rejected in favor of the alternative hypothesis if the p-value of the two-sided 
two-sample t-test is less than 0.05.  Once the null hypothesis is rejected a nested superiority test in favor 
of the treatment group will be performed while maintaining the overall type 1 error. 
 
C.4 Study population 
Adults (aged 24-75 years) diagnosed with Type 1 Diabetes Mellitus with disease duration of 10 years or 
more before screening and currently on CSII therapy for at least 6 months will be enrolled. Subjects 
present an increased risk of hypoglycemia. Subjects can be naïve or experienced with the MiniMed 640G 
insulin pump, but should not have been on CGM therapy for at least 3 months prior to screening. 
Sample size calculations have shown that 136 subjects (68 in each arm) need to complete the study 
(section C.7). Taking into account an anticipated drop-out rate of 10% at screening, 15% at run-in and 
15% during the 6 month follow-up period, it is calculated that 210 subjects need to be screened, in order 
to have 189 subjects starting the run-in phase, and160 randomized subjects. 
Up to 25 study centers across Europe, Canada and potentially other geographic regions will be selected 
at study start, based on each investigator’s experience and qualifications, availability of sufficient 
resources to carry out the required study procedures, and their potential to randomize an average of 9 
subjects within the 6 month enrollment period. The number of investigational sites and period of 
enrollment may be increased to accommodate a quicker and/or larger enrollment. 
C.5 Study design 
This is an international, multi-center, prospective, open–label, adaptive, randomized, controlled, pre-
market clinical investigation with parallel groups. The study is designed to compare CGM-based 
hypoglycemic events in a treatment group to a control group. Groups are defined as: 
• 
Treatment group: CSII with MiniMed 640G with CGM and Suspend before Low feature of 
SmartGuard turned ON (T) 
• 
Control group: CSII with MiniMed 640G alone (C)  
This study has an adaptive design. Due to the uncertainty about the hypoglycemic event rate and the 
magnitude of the true effect of treatment, the sample size will be re-estimated by Data Safety Monitoring 
Board (DSMB) in an interim assessment after a total of 60 subjects (30 treatment and 30 control group) 
have been randomized and followed up for 6 months. An interim analysis for sample size re-estimation 
will be based on the conditional power approach by Li et al. [17] and a method of by Chen et al. [18] as 
extended by Mehta and Pocock [19].   
The interim analysis will be performed by a statistician unaffiliated with the sponsor or study statistician 
and member of the DSMB.  Detailed instructions will be given to this statistician concerning the analysis, 
because it involves both the primary safety and efficacy endpoints.   
The DSMB will share no data or results of analyses with the sponsor or sponsor’s statistician, and 
present one of following messages to the sponsor after the interim analysis: 
- 
Study has reached the futility boundary and it is recommended to be terminated for futility. 
- 
Continue the study to its conclusion without modification of sample size or inclusion criteria. 
- 
Increase the numbers of patients in each treatment group.  
- 
Revise the inclusion criteria. 
 
The statistician will prepare and save a report of the interim analysis. This report will be sent to the 
sponsor on completion of the study.  

 
 
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C.6 Randomization  
The randomization will follow a block randomization with blocks of different sizes. At site level, the order 
of the block sizes will be selected randomly and a random 1:1 treatment allocation will be performed 
within each block.  
Investigators will be blinded to the number and size of the blocks.  
Randomization will be performed via the electronic CRF.  
In case technical issues occur with the electronic CRF (i.e. Internet access, system maintenance), a 
randomization list will be generated for each site by the statistician and the statistician will be able to 
communicate the randomization arm to the study team and site staff.  
C.7 Sample size 
The sample size calculation was performed based on assumptions from the results from the ASPIRE 
study [3]. In particular, the mean number of sensor glucose hypoglycemic events below or equal to 55 
mg/dL (3.0 mmol/L) per patient/week is expected to be 2 in the arm with  CSII with MiniMed 640G alone 
(control group) and standard deviation of 1.56. 
 
Assuming alpha=0.05, power=80% and 40% reduction in the mean number of sensor glucose 
hypoglycaemic events per patient/week in the treatment arm, as compared to the control arm, the 
required sample size is 136 subjects (68 in each arm). 
 
The drop-out rate during the 6 month follow-up after randomization has been estimated to be 15%. 
Incorporating this drop-out rate, a total of 160 subjects will be randomized in a 1:1 ratio to either the arm 
using MiniMed 640G with CGM and SmartGuard or the arm using CSII with MiniMed 640G alone. 
The following drop-out assumptions have been taken into account, based on experience with previous 
studies: 
• 
At screening:  10%  
• 
After run-in: 15%  
• 
During 6 months follow-up: 15%   
Based on these assumptions, the following estimations can be made:  in total  210 subjects need to be 
screened, in order to have 189 starting the run-in phase and 160 randomized to start the treatment 
phase.   
Due to the uncertainty about the magnitude of the effect of treatment, the sample size will be re-
estimated by the independent DSMB in an interim assessment soon after a total of 60 subjects(30 
treatment and 30 control group) have been randomized and followed up for 6 months. 
Enrollment period is expected to be 6 months. It may be extended based on the outcome of the interim 
analyses. 
C.8 Number of investigational sites and study duration 
The study is planned to be conducted in Europe in the following countries: Netherlands, France, Italy, 
and the UK, where the MiniMed 640G system is commercially available. The study will also be conducted 
in Canada, where the MiniMed 640G system is not licensed and therefore will be investigational.  Other 
geographic regions are also being considered. At the time this Clinical Investigation Plan was finalized, 
not all participating investigation sites were identified. A list of participating investigation sites will be 
available under a separate cover.  
It is estimated that 205 subjects will have to be enrolled in up to 25 study centers, which will be activated 
over a period of 6 months (see also section C.7). 
The recruitment period will be 6 months, but could be extended if needed. At the finalization of this 
document, recruitment of 11 subjects on average at each site is expected. 
It is expected that each site should enroll a minimum of 7 subjects, to ensure each site has sufficient 
study execution knowledge and to minimize differences in center practice to avoid bias. In addition, 
limiting the number of sites should reduce time for site activation and recruitment.  A maximum of 20 
subjects per site is recommended.  
The number of investigational sites may be increased to accommodate a quicker enrollment rate.   
Overall study duration from first subject enrollment until the last subject exits the study is expected to be 
18 months, including an estimated period of 6 months to activate all sites, 6 months enrollment period, 
and a 6 months follow-up period for each subject. 

 
 
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D SUBJECT SELECTION 
D.1 Inclusion criteria at screening  
Subjects will be considered for enrollment in the study, if they meet all of the following criteria, assessed 
after subject has signed informed consent: 
1. Age 24-75 years old at time of screening. 
2. Diagnosed with Type 1 diabetes ≥10 years prior to screening. 
3. On CSII therapy for ≥ 6 months prior to screening. 
4. Not on Real Time Continuous Glucose Monitoring for ≥ 3 months prior to screening. 
5. HbA1c value ≥5.8% and ≤10.0% as assessed by local lab ≤ 15 days prior to screening or 
performed at screening. 
6. A documented Severe Hypoglycemia event ≤ 12 months prior to screening  
(see F.6.2 for definition), OR Clarke score ≥4 assessed at time of screening, OR 
Gold score ≥4 assessed at time of screening. 
7. Subject is willing to sign and date informed consent, comply with all study procedures and wear all 
study devices as required during the study. 
D.2 Exclusion criteria 
A subject who meets any of the following criteria will be excluded from participation in this study. 
1. 
Untreated Addison’s disease, thyroid disorder, growth hormone deficiency; hypopituitarism, or 
definite gastroparesis, per investigator judgment.  
2. 
Renal failure defined by creatinine clearance <30 ml/min, as assessed by local lab test ≤ 3 months 
before screening or performed at screening at local lab, as defined by the creatinine-based 
Cockcroft or MDRD equations. 
3. 
Hearing or vision impairment hindering perception of glucose display and alarms, or otherwise 
incapable of using CGM, in the opinion of the investigator. 
4. 
Current pregnancy or intention to conceive. 
5. 
Any unresolved adverse skin condition in the area of sensor placement (e.g. psoriasis, rash, 
Staphylococcus infection). 
6. 
Alcohol or drug abuse, other than nicotine, per investigator judgment. 
7. 
Any other disease or condition that, in the opinion of the Investigator, may preclude the patient 
from participating in the study. 
8. 
Legally incompetent, illiterate or vulnerable person. 
 
D.3 Randomization criteria 
If subjects meet the above criteria, as well as all of the following criteria assessed at the end of the run-in 
period, they may continue to participate in the treatment period of the study: 
1. Subject has worn two weeks  the Enlite 3 sensor with blinded GST3C transmitter during the run-in 
period. 
2. Subject has shown acceptable tolerance of Enlite 3 sensor wear, per investigator judgment. 
3. CareLink data shows subject performed ≥ 4 finger stick blood glucose measurements daily, as 
determined by CareLink Clinical data upload as the mean number of SMBG/day over the past 14 
days (SMBG number / day ≥3.5 round up to 4). 
4. Subject showed ability to comprehend the pump training and study procedures, in the opinion of the 
investigator. 
 

 
 
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E STUDY PREPARATION PROCEDURES 
E.1 Investigator/Investigation site selection 
 Investigator selection criteria 
E.1.1
The role of the principal investigator is to implement and manage the day-to-day conduct of the clinical 
study as well as ensure data integrity and the rights, safety and well-being of the subjects involved in the 
clinical study. 
The following requirements will be evaluated for each investigator considered for participation in the 
clinical study: 
• 
Medtronic MiniMed 640G System experience is preferred 
• 
Past experience in conducting clinical studies 
• 
Availability for study execution  
• 
Interest in participating in pre-market interventional studies with devices.  
 
 Investigation site selection criteria 
E.1.2
• 
The following requirements will be evaluated for each investigation site considered for participation in 
the clinical study:  
• 
Site staff experience with using the Medtronic MiniMed 640G system is preferred* 
• 
Past experience of site staff in conducting clinical studies 
• 
Adequate resources (including study nurse or coordinator), facilities and administrative support for 
the total study duration of at least 18 months 
• 
Site has the capacity to recruit enough subjects for the study as defined in section D.1: Expected 
recruitment of 11 subjects on average, with a minimum of 7 subjects and  a maximum of 20 subjects 
in a 6 month enrollment period.  
• 
Preferable experience with the use of CareLink Diabetes software systems (CareLink Personal or 
CareLink Pro)  
• 
Computer with Internet access for EDC system and CareLink Diabetes software systems (ensuring 
authorized access in case of firewall) 
 
 
*For sites not having experience with Medtronic MiniMed 640G System (e.g. Canadian sites will 
have limited experience as the MiniMed 640G is not yet commercialized in Canada), an intensified 
training of the site staff will be performed before enrollment starts and at start of the follow-up period.
 
 
 Clinical Investigation Agreement 
E.1.3
A Clinical Investigation Agreement shall be in place, signed by the participating investigation site and/or 
principal investigator of each investigation site, as per the local legal requirements, and returned to 
Medtronic prior to the commencement of any clinical study activities. The investigator is indicating 
approval of the Clinical Investigation Plan and subsequent amendments, by a fully executed agreement. 
Amendments to this Clinical Investigation Plan shall be agreed upon between Medtronic and 
investigator(s) and be recorded with a justification for the amendments.  
 Curriculum Vitae  
E.1.4
An up to date signed and dated Curriculum Vitae from all key members of the investigation site team 
participating in this clinical study as listed on the Delegated task List shall be obtained, preferably in 
English, evidencing the required qualifications, including the year and where obtained, and  including 
their current position at the investigation site. The signature on the CV must be dated within 3 years prior 
to the date of activation of the investigation site.  
If the CV is not in English, a summary of the Curriculum Vitae template will be provided by Medtronic.  

 
 
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E.2 Ethics 
 EC/IRB approval 
E.2.1
Prior to enrolling subjects in this clinical study, each investigation site’s EC/IRB will be required to 
approve the current Clinical Investigation Plan, the Patient Information and Informed Consent form, 
including any other written information to be provided to the subjects and, if applicable. EC/IRB approval 
of the clinical study must be received in the form of a letter and provided to Medtronic before 
commencement of the clinical study at an investigation site. The approval letter must contain enough 
information to identify the version or date of the documents approved. If this information is not contained 
in the approval letter, it must be retrievable from the corresponding submission letter. In addition, the 
approval letter needs to be accompanied by an EC/IRB roster or letter of compliance, to allow verification 
that the investigator, other investigation site personnel, and/or Medtronic personnel are not members of 
the EC/IRB. If they are members of the EC/IRB, written documentation is required stating that he/she did 
not participate in the approval process. If the EC/IRB imposes any additional requirements (e.g. safety 
reports, progress reports etc.), Medtronic will prepare the required documents and send them to the 
investigator for reporting to the EC/IRB. Investigators must inform Medtronic of any change in status of 
EC/IRB approval once the investigation site has started enrollment. If any action is taken by an EC/IRB 
with respect to the investigation, that information will be forwarded to Medtronic by the respective 
investigator. 
 Informed consent process 
E.2.2
The investigator or authorized designee must obtain written informed consent before any clinical study 
related activity takes place.   
Well in advance of the consent discussion, the patient should receive the EC/IRB approved Patient 
Information and Informed Consent Form (PIC). During the consent discussion the investigator or his/her 
authorized designee must fully inform the patient of all aspects of the clinical study that are relevant to 
the patient’s decision to participate in the clinical study. If a patient is illiterate, an impartial witness must 
be present during the entire informed consent discussion. All items addressed in the Patient Information 
and the Informed Consent Form must be explained. The language used shall be as non-technical as 
possible and must be understandable to the patient and the impartial witness, where applicable.  
The patient must have ample time and opportunity to read and understand the Patient Information and 
the Informed Consent Form, to inquire about details of the clinical study, and to decide whether or not to 
participate in the clinical study. All questions about the clinical study should be answered to the 
satisfaction of the patient. 
Neither the investigator, nor the investigation site staff shall coerce or unduly influence a patient to 
participate or to continue to participate in the clinical study. The informed consent process shall not waive 
or appear to waive the patient’s rights. 
When the patient decides to participate in the clinical study, the Informed Consent Form must be signed 
and personally dated by the patient and investigator or authorized designee. If applicable, the witness 
shall also sign and personally date the consent form to attest that the information in the Patient 
Information and Informed Consent Form was accurately explained and clearly understood by the patient, 
and that informed consent was freely given. 
After all persons have signed and dated the Informed Consent Form, the investigator must provide the 
patient with a copy of the Patient Information and the signed and dated Informed Consent Form.  
A patient contact card will be made available to the patient. 
 Revisions in Patient Information and Informed Consent Form 
E.2.3
Medtronic will inform the investigators whenever information becomes available that may be relevant to 
the subject’s confirmed participation in the clinical study. The investigator or his/her authorized designee 
should inform the subject in a timely manner.  
Medtronic will revise the written Patient Information and Informed Consent Form whenever new 
information becomes available that may be relevant to the subject’s confirmed participation in the clinical 
study. The revised information will be sent to the investigator for approval by the EC/IRB. After approval 
by the EC/IRB, a copy of this information must be provided to the participating subjects, and the informed 
consent process as described above needs to be repeated.  

 
 
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 Regulatory submission 
E.2.4
In countries where submission to the regulatory authority is required per local law, no patients will be 
enrolled in the clinical study until the particular regulatory authority has approved the current Clinical 
Investigation Plan of the clinical study and other documents as required according to the local 
requirements. 
If the regulatory authority imposes any additional requirements (e.g. safety reports, progress reports etc.), 
Medtronic will prepare the required documents and send them to the respective authority. 
Other documents that are referred to in this Clinical Investigation Plan are listed below and will be made 
available upon request: 
• 
Monitoring Plan 
• 
Data Management Plan 
• 
Statistical Analysis Plan 
• 
Patient Information and Informed Consent Form 
• 
Case Report Forms 
• 
Instructions for Use of study devices 
E.3 Regulatory compliance 
This clinical study will be conducted in compliance with the latest version of the Declaration of Helsinki, 
the international standard ISO 14155:2011 ('Clinical Investigation of medical devices for human 
subjects'), laws and regulations of the countries in which the clinical study is conducted, including data 
protection laws, the Clinical Investigation Agreement and the Clinical Investigation Plan.  
All principles of the Declaration of Helsinki have been implemented in this clinical study by means of the 
informed consent process, EC/IRB approval, study training, clinical trial registration, preclinical testing, 
risk benefit assessment, publication policy, etc.  
Following Declaration of Helsinki and ISO14155:2011, legally incompetent and illiterate persons, or 
vulnerable populations will not be included in this clinical study.  
The sponsor will avoid improper influence on, or inducement of the subject, monitor, and investigator(s) 
or other parties participating in, or contributing to, the clinical study by implementing the informed consent 
process, Clinical Investigation Agreements and EC/IRB approval. 
E.4 Training requirements 
Prior to investigation site activation or subsequent involvement in clinical study activities, Medtronic will 
provide relevant clinical study training relevant and pertinent to the involvement of personnel conducting 
clinical study activities, as a minimum, investigator responsibilities, ISO 14155:2011, the CIP, the PIC, 
use of data collection tools, and applicable local regulations must be reviewed.  
Previous training and experience on the MiniMed 640G system is preferred for the participating centers, 
as assessed during site qualification, with the exception of Canada where it will be investigational.  
Study-specific training will be documented prior to site activation. 
E.5 Clinical study materials and clinical study-specific equipment 
Medtronic will provide study documentation (e.g. Investigator Site File, eCRF access, Study Worksheets, 
etc.) and study devices to the site personnel.  
The site personnel are responsible to send an acknowledgment of receipt to the sponsor after receiving 
the study devices (via email or fax). 
Computer and Internet access are required and are a pre-requisite for site participation (see section 
E.1.2) 
E.6 Study device/product traceability 
 Supply of devices/products 
E.6.1
All serialized devices will be provided as free-of-charge loaners to each subject for the duration of the 
study, except for the subjects already using a MiniMed 640G insulin pump and/or a CONTOUR NEXT LINK 
2.4 meter, who will continue using their own device(s) for the study. 
Consumable products will be granted free-of-charge to all subjects for the duration of the study. All 
devices/products will be shipped to the investigational sites using the commercial supply chain 
infrastructure when practical. All shipments, no matter the origin, will include an invoice.  

 
 
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Medtronic will only allow shipment of study devices/products to the investigational sites or investigator 
after the Clinical Study Manager has declared the investigational site ready to start the clinical study. 
An initial batch of devices/products will be shipped to each site, after site activation. Based on the 
number of subjects who have been enrolled at the site, additional devices/products will be shipped as 
needed; quantities will be discussed with the site staff to adapt to site recruitment.  
 Storage & handling of study devices/products 
E.6.2
The devices/products, as listed in section B.2 will be provided free of charge by the sponsor. Full tracking 
must be performed as soon as the device/product is received by the investigator/investigation site. 
The study devices/products must be stored in a secured area. The method of storage shall prevent the 
use of study devices/products for other applications than mentioned in this Clinical Investigation Plan. In 
addition, all information for the use, storage and handling of the investigational device/product as 
indicated in the Investigator’s Brochure or Instructions for use must be taken into account. 
Standard Medtronic practice is not to re-package, re-label or sticker commercially-released 
devices/products used in clinical studies. Investigational devices and consumables will be labeled for 
investigational use only or as required by national regulations, in local language (as described in section 
B.2).  
The GST3C Download utility, as investigational software will be installed on the sites computer to 
download the subject data.  
 Device/product return procedures 
E.6.3
Non-functioning devices/products must be returned to Medtronic as soon as possible for investigation. 
At the end of the study, all serialized devices must be returned to the Medtronic warehouse. The site 
Monitor/Clinical Research Specialist will ensure all applicable products are returned to Medtronic. All 
unused consumables (expired and non-expired) may be destroyed at study site or returned to Medtronic, 
as required by national regulation. The destruction or return shall be documented respectively on study 
specific Products Destruction form or Products Return form signed by the responsible person at the site.  
 Device/product disposition requirements 
E.6.4
Devices/products provided by Medtronic will be traced during the clinical study by assigning specific lot 
numbers, batch numbers, or serial numbers to each device/product.  Devices/products reception by the 
Site will be confirmed on the shipping documents. Devices/products returned from the Site to Medtronic 
will be documented on a study specific Products Return form. 
Devices/products provided to the subjects will be traced on the Subject Products Tracking log in the 
eCRF which must be approved by the principal investigator at the end of the study. 
Investigational software will be traced during the clinical study. Dates of installation and uninstallation on 
the investigational site computer will be documented in the initiation and close-out visits reports; dates of 
data download and subject ID will be documented in the electronic CRFs.  
F STUDY METHODS 
F.1 Point of enrollment 
A subject is considered enrolled in the clinical study at the time at which he/she signs the Informed 
Consent Form.  
A subject will be assigned a unique study subject ID via the eCRF, which is a 9-digit code (311-xxx-xxx).    
The investigator will maintain a log of all subjects enrolled in the clinical study, assigning a study subject 
ID linked to their names, alternative subject identification or contact information. 
F.2 Procedure aspects 
The SMILE study is comprised of a run-in phase and a treatment phase. Subjects must successfully 
complete the run-in phase by demonstrating appropriate self-management and compliance with blinded 
Continuous Glucose Monitoring prior to being randomized for the treatment period, in which subjects will 
either be using the MiniMed 640G Pump with the SmartGuard feature programmed turned ON 
(Treatment Arm = T) or will use the MiniMed 640G Pump without CGM (Control Arm = C).  
After the study has been completed, the subjects will continue to be treated following the routine practice 
of each center.  

 
 
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 Pump and CGM Trainings  
F.2.1
A training will be provided to all participating subjects, including topics such as initial pump and threshold 
settings, alarms and alerts, Bolus Wizard usage, blinded CGM and calibration requirements.  
Sensor compliance:  
Compliance for sensor usage is expected to be at least above 70%. This will be verified at each study 
visit for subjects in treatment arm. Deviations will need to be reported if compliance is not respected. 
SmartGuard (Suspend before Low) settings:  
The low limit threshold of Suspend before Low need to be programmed at for all subjects at start CGM 
(Visit 6) at: 60 or 65 mg/dL (3.4 or 3.6 mmol/L) for 24 hours. 
Adjustments to this low limit and 24 hour time segment are allowed upon Visit 7 based on the subject’s 
needs per investigator’s judgment within the following range: 55 to 70 mg/dL (3.2 to 4.0 mmol/L) 
If changes are made to low limit threshold and selected time segments, the rationale for the changes will 
be described in the eCRF.  
The  SmartGuard set-up training materials  are available as separate documents. 
SMBG:  
The study staff will review the number of SMBG at each visit, and remind subjects to perform a minimum 
of 4 SMBG per day throughout the study. 
Bolus Wizard:  
The study staff will train all subjects on and carb counting and use of Bolus Wizard, if additional training is 
needed. A maximum use of the Bolus Wizard is strongly recommended and will be reviewed at each 
study visit. The study staff will remind subjects to regularly use the Bolus Wizard throughout the study. 
 
 Glucose targets  
F.2.2
During the course of the study, the following glucose targets (Table 4) from the American Diabetes 
Association guidelines [20], should be used for all subjects. Insulin titration will be performed to achieve 
these targets.  
 
 
HbA1c at local lab  
F.2.2.1
During the study, HbA1c will be collected at the local laboratory of the subject, as per routine practice at 
baseline, 3 months- and 6 months follow-up. If possible, the subject should use the same laboratory for 
the collection and analysis of all HbA1c samples throughout the study.  
Maintenance or calibration certificates of the local laboratories (as they can vary and are numerous) will 
not be required, as HbA1c is a secondary endpoint and renal failure, assessed by creatinine clearance 
test, is not a study endpoint. 
 
Table 4 Summary of glycemic recommendations for non-pregnant adults with diabetes 
 
HbA1C  
< 7.0% 
Preprandial capillary plasma glucose  
80–130 mg/dL (4.4–7.2 mmol/L) 
Peak postprandial capillary plasma glucose† 
180 mg/dL (10.0 mmol/L) 
† Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial glucose goals. Postprandial glucose 
measurements should be made 1–2 h after the beginning of the meal, generally peak levels in patients with diabetes. 
 
 GST3C blinded recorder Training  
F.2.3
The GST3C blinded recorder training is available as a separate document.  
 

 
 
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 Patient Questionnaires 
F.2.4
The following validated Patient Reported Outcome (PRO) questionnaires are included in this study: 
• 
Clarke Questionnaire  
• 
Gold Questionnaire 
• 
Hypoglycemia Fear Survey (HFS) 
• 
Diabetes Treatment Satisfaction Questionnaire (DTSQ)  
 
Clarke Questionnaire 
F.2.4.1
The Clarke method [21] comprises eight questions characterizing the participant's exposure to events of 
moderate and severe hypoglycemia. It also examines the glycemic threshold for, and symptomatic 
responses to, hypoglycemia. A score of four or more implies impaired awareness of hypoglycemia. 
All subjects will be asked to complete the Clarke questionnaire (paper version) at screening (Visit 2), at 
visit 11 (3 months of follow-up) and at visit 15 (6 months of follow-up), which is also the end of study. In 
case the subject withdraws early from the study, it is important to ensure that he/she is asked to complete 
the Clarke Questionnaire at the time of study exit. Data collected from the paper questionnaire will be 
copied by the site staff into the electronic database. 
 
Gold Questionnaire 
F.2.4.2
The Gold questionnaire is a 7-point visual analogue scale that is validated to characterize the participant's 
impaired awareness of hypoglycemia as confirmed by a score of ≥ 4 in the Gold score. All subjects will be 
asked to complete the Gold question (paper version) at screening (Visit 2), at visit 11 (3 months of follow-
up) and at visit 15 (6 months of follow-up), which is also the end of study. In case the subject withdraws 
early from the study, it is important to ensure that he/she is asked to complete the Gold Questionnaire at 
the time of study exit. Data collected from the paper questionnaire will be entered by the site staff into the 
electronic database. 
 
Hypoglycemia Fear Survey (HFS) 
F.2.4.3
Hypoglycemia can lead to various aversive symptomatic, affective, cognitive, physiological, and social 
consequences, which in turn can lead to the development of possible phobic avoidance behaviors 
associated with hypoglycemia. The hypoglycemia fear survey (HFS) is a psychometric instrument 
designed to quantify this fear [22]. The instrument has internal consistency and test-retest stability, and 
varies with elevated glycosylated hemoglobin. The HFS has in most translations two subscales, the 
behavior subscale and the worry subscale and has a recollection period of 6 months. 
All subjects will be asked to complete the HFS at screening (Visit 2); at visit 11 (3 months of follow-up) 
and at visit 15 (6 months of follow-up), which is also the end of study. In case the subject withdraws from 
the study early, it is important to ensure that he/she is asked to complete the HFS at the time of study 
exit. Data collected from the paper questionnaire will be copied by the site staff into the electronic 
database. 
 
Diabetes Treatment Satisfaction Questionnaire (status version and change version) : 
F.2.4.4
The DTSQ has been specifically designed to measure satisfaction with diabetes treatment regimen in 
people with diabetes [23]. The DTSQ [status version (DTSQs)] is an eight-item questionnaire, in which 
six questions assess treatment satisfaction and the other two assess perceived frequency of hyper- and 
hypoglycemia [23, 24, 25] 
Each item is scored from 6 (very satisfied) to 0 (very dissatisfied) such that the Treatment Satisfaction 
scale can range from 36 (very satisfied) to 0 (very dissatisfied) and the perceived frequency of hyper- and 
hypoglycemia scores range from 6 (most of the time) to 0 (none of the time).  
The DTSQs has been extensively used and is sensitive to changes in response to a variety of 
interventions, including the start of insulin or the switch between insulin regimens [20, 21, 22].  
Although the DTSQs has proved highly sensitive to change, in many studies where patients are very 
satisfied with treatment used at baseline, the DTSQs cannot show improvements when they switch to a 
new treatment, even though they might be even more satisfied with the new treatment. To overcome this 
limitation of the DTSQs, a change version (DTSQc) has also been developed, which asks participants to 
rate how their current treatment compared with their previous treatment [26, 27] 
This instrument contains the same 8 items as the DTSQs version. The difference lies in the wording of 
the response options and instructions, which, in the DTSQc, direct the respondent to compare their 
experience of treatment before the study began.  
The DTSQc, used in conjunction with the DTSQs, overcomes the problem of ceiling effects that are often 
encountered when the status measure is used alone. The DTSQc has been shown to exhibit greater 
sensitivity to changes in treatment than the DTSQs and is particularly valuable when ceiling effects occur 

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Clinical Investigation Plan 
 
 
 
 
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Table 5: Study procedures and Data collection 
 
1 Visit 1-2, 2-3, 1-2-3 can be combined;  2  Visits 5-6 can be combined;  3 O = Optional. Only for subjects who did not have a recent test 
(see Visit 2: Screening for details), 4 T = Treatment arm; 5 C = Control arm; 6 Early Termination visit should be performed at any time if 
patient withdraws after randomization (Visit 5) and before the end of the study (Visit 15).  
 
 
 Visit 1: Enrollment 
F.3.1
Note: If convenient, visits 1-2, 2-3 or 1-2-3 can be combined.  
 
Visit 1 Procedures:  
• 
Conduct Informed Consent Process as described in E.2.2.  
Subject will be enrolled in the study once Informed Consent is obtained.  
 
 
 
 
 
 
 
Procedures and 
 Data collection 
Enrollment1 
Screening1 
Start Run-in1 
Call  
End Run-in/ 
Randomization2 
Start Treatment2 
1w call/visit 
2w  call 
6w Visit 
10w call 
12w visit 
16w call 
18w visit 
22w call 
End of Study 
Early Termination6 
Visit number  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
 14 
  15 
 
Target week 
w0 
w0 
w0 
-3w 
w0 
-2w 
w0 
-1w 
w0 
w1 
w2 
w6 
w10 
w12 
w16 
w18 
w22 
w24  
Target day 
d0 
d0 
V2 
V3+ 
7d 
V4+ 
7d 
V5 
 
V6+ 
d7 
V6+ 
d14 
V6+ 
d42 
V6+ 
d70 
V10+ 
d14 
V6+ 
d112 
V12+ 
d14 
V6+ 
d154 
V14+ 
d14  
Window 
- 
- 
+7d 
+3d 
+7d 
+14d 
±3d 
±3d 
±7d 
±7d 
+7d 
±7d 
+7d 
±7d 
+7d  
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization criteria 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A1c (local lab)  
 
O3 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
Creatinine test (local) 
 
O3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Device Accountability 
 
 
X 
 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
X 
MiniMed640G training 
 
 
X 
 
 
 
  
 
 
 
 
 
 
 
 
 
CGM training 
 
 
 
 
 
T4 
 
 
 
 
 
 
 
 
 
 
Blinded CGM training  
 
 
X 
 
 
 
 
 
C5 
 
 
 
 
 
 
 
Blinded CGM placement 
 
 
X 
X 
 
 
 
 
 
C 
 
C 
 
C 
 
 
Blinded CGM upload 
 
 
 
 
X 
 
 
 
 
 
C 
 
C 
 
C 
C 
CareLink Clinical upload 
 
 
 
 
X 
X 
T 
 
X 
 
X 
 
X 
 
X 
X 
Distribution supplies 
 
 
X 
 
X 
X 
 
 
X 
 
X 
 
X 
 
 
 
Clarke questionnaire 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
Gold Questionnaire 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
HFS  questionnaire 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
DTSQs  questionnaire  
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
DTSQc  questionnaire 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
AEs and Deficiencies  
 
Reported upon occurrence or at a site visit and CareLink Clinical data upload, if possible. 
Study deviations  
 
Visit 1 Data collection:  
o 
Enrollment eCRF: add date of signature Patient Informed Consent  
Note: data collection Visit 1 and Visit 2 are combined on one Enrollment eCRF. 

 
 
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 Visit 2: Screening  
F.3.2
 
Visit 2 Procedures: 
• 
The investigator will determine if subject meets eligibility criteria (see D.1 and D.2). 
• 
Collect demographic information (age, gender) 
• 
Measure height and weight 
• 
Perform blood sample collection for HbA1c at local lab.  
o 
If already performed ≤ 15 days prior to screening, only confirm date of collection by local 
lab and HbA1c value.   
Reminder: HbA1c value for inclusion ≥5.8% and ≤10.0% 
• 
Perform blood sample collection for creatinine clearance at local lab.  
o 
If already performed ≤ 3 months prior to screening, only confirm date of collection by local 
lab and creatinine clearance value.   
Reminder; creatinine clearance threshold for exclusion< 30 mL/min 
• 
Confirm Subject Medical History: including date of T1DM diagnosis, indication,  length of time on 
pump therapy, previous pump model, mean daily insulin dose. insulin molecule, mean number 
SMBGs/day (based on subject’s record or CareLink data if available), and diabetes-related 
complications. 
• 
Collect information regarding: 
o 
Level of education  
o 
Subject to complete Clarke Questionnaire  
o 
Subject to complete Gold Questionnaire  
o 
Subject to complete HFS 
 
o 
Subject to complete DTSQs 
o 
Report any Adverse Events, if applicable 
 
 
Visit 2 Data collection: 
o 
Enrollment eCRF: 
- 
Eligibility: validation of inclusion- and exclusion criteria  
- 
Demographics: age, gender, height, weight, level of education, HbA1c, creatinine clearance 
- 
Medical History: year of T1DM diagnosis, current pump model, indication and time on pump 
therapy, mean daily insulin dose and insulin type, mean number SMBGs/day, number and 
diabetes-related complications. 
o 
Clarke eCRF 
o 
Gold eCRF 
o 
HFS eCRF 
o 
DTSQs eCRF 
o 
Adverse Event eCRF, if applicable 

 
 
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 Visit 3: Start Run-in  [Visit 2 (+7 days max)] 
F.3.3
Once eligibility has been confirmed at Visit 2, subject will start a 2 week run-in phase at Visit 3.  
The objective of the 2 week run-in phase is to train the subjects on the MiniMed 640G insulin pump, 
assess subjects’ compliance and ability to comprehend the study procedures and tolerance of wearing 
the sensor and transmitter continuously.    
 
Visit 3 Procedures: 
• 
Subject will receive training on:  
o 
MiniMed 640G pump therapy, according to the training guidelines (the training may be 
performed over several days). 
o 
Performing at least 4 finger stick blood glucose measurements per day.  
o 
Regular Bolus Wizard use and carb counting, if needed. 
o 
Use of the Enlite 3 and GST3C transmitter in a blinded manner. 
• 
Report any Adverse Event or Device Deficiency, if applicable 
• 
Study staff needs to create a CareLink Clinical account for the subject, with a unique Subject ID 
Number (311-XXX-XXX) and password.  
• 
Site staff will dispense to subject (for 2 weeks):  
o 
1 MiniMed 640G pump (if subject is not using already a MiniMed 640G pump) 
o 
1 CONTOUR NEXT LINK 2.4 meter by Ascencia (if subject is not using already this meter)  
o 
2 GST3C transmitters (1 is back-up) 
o 
1 GST3C charger  
o 
1 GST3C watertight tester 
o 
4 Enlite sensors (2 are back-up)  
o 
1 Enlite One-Press serter 
o 
150 Strips 
o 
10 Infusion sets (1 box of 10) 
o 
10 Reservoirs (1 box of 10) 
o 
4 AA batteries (1 pack) 
• 
Plan next call with subject in 1 week (Visit 4) and 2 weeks (Visit 5). 
 
Visit 3 Data collection: 
o 
Visit 3 eCRF 
o 
Subject Products Tracking Log eCRF to record products allocated to subject.  
o 
Adverse Event or Device Deficiency eCRFs, if applicable. 
 Visit 4: Call  
[Visit 3 + 7 days (+3 days max)] 
F.3.4
 
Visit 4 Procedures:  
Study staff will call the subject to:  
• 
Evaluate sensor/transmitter tolerance since Visit 3 
• 
Confirm that new transmitter is started adequately with proper sensor insertion. 
• 
Evaluate MiniMed 640G use; remind the subject about SMBG and Bolus Wizard use.  
• 
Ask if any adverse event or device deficiency occurred.  
• 
Confirm with subject next scheduled visit in 1 week (Visit 5). 
• 
Remind subject to bring back all devices and unused consumables for the next visit to the site.  
Visit 4 Data collection: 
 
o 
Visit 4 eCRF 
o 
Adverse Event or Device Deficiency eCRF, if applicable 

 
 
Clinical Investigation Plan 
 
 
 
 
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 Visit 5: Randomization  
[Visit 4 + 7 days (+7 days max)] 
F.3.5
Note: If convenient, visits 5 and 6 can be combined.  
Visit 5 Procedures: 
• 
Upload data of the MiniMed 640G into CareLink Clinical. Use correct Subject ID (311-XXX-XXX). 
• 
Upload data of the 2 used GST3C transmitters using the GST3C Download utility. Use correct file 
name (Subject ID_XXX_DATE). 
Note: data from the GST3C upload via the GST3C Download utility remains blinded to the site staff 
and subjects and therefore, it cannot be used for therapy adjustment.  
• 
Investigator will review randomization criteria per section D.3.  
If eligible: subject will be randomized after completion of the Visit 5 eCRF to one of the 2 arms: 
- 
Treatment arm: MiniMed 640G with CGM and Suspend before low feature turned ON. 
- 
Control arm: MiniMed 640G alone 
• 
Site staff will collect from the subject: 
- 
2 GST3C transmitters 
- 
1 GST3C charger  
- 
1 GST3C watertight tester 
• 
Site staff will dispense to subject for 2 weeks:  
- 
150 Strips  
- 
10 Infusion Sets (1 box of 10) 
- 
10 Reservoirs (1 box of 10) 
• 
Site staff plans the following visits with subject:  
- 
Visit 6 within 2 weeks of the Visit 5 Randomization, or Visit 5 will be combined with 
Visit 6 on the same day. 
- 
It is strongly recommended to schedule all study visits and calls  (Visit 6 to Visit 15) 
with the subject. 
Note: the electronic database can be used to generate the schedule of the 
remaining study visits in compliance with target dates. 
 
If not eligible: subject will be withdrawn from the study. All devices and unused consumables 
will have to be returned to the site. 
 
Visit 5 Data collection: 
o 
Pump data upload in CareLink Clinical. 
o 
Transmitter data upload using GST3C Download utility. 
o 
Visit 5 eCRF (including arm allocation)  
o 
Subjects Products Tracking Log eCRF to record products allocated to subject. 
o 
Adverse Event or Device Deficiency eCRF, if applicable.  
If subject is not eligible:  
o 
Study Exit eCRF: date and reason for withdrawal.  
 

 
 
Clinical Investigation Plan 
 
 
 
 
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 Visit 6: Start Treatment  
[Visit 5 (+14 days max)] 
F.3.6
Visit 6 Procedures Treatment arm: 
Start CGM Visit 
Subject will come to the site and be trained on 
CGM use, following section F.2.1. 
Site staff will: 
• 
Upload the MiniMed 640G into CareLink 
Clinical. Use correct Subject ID  
(311-XXX-XXX). 
• 
Review MiniMed 640G use  
• 
Review SMBG/Bolus Wizard use 
• 
Review adverse event or device 
deficiency, if any. 
• 
Dispense supplies to subjects for 6 
weeks: 
o 
2 GST3C transmitter (1 is back-up) 
o 
10 Enlite 3 Sensors (2 box of 5)  
o 
350 Strips 
o 
20 Infusion sets (2 box of 10) 
o 
20 Reservoirs (2 box of 10) 
o 
8 AA batteries (2 pack of 4) 
• 
Plan next visit with subject in 1 week. 
 
Visit 6 Procedures Control  arm: 
Follow-Up Visit 
Subject will come to the site.  
 
Site staff will: 
 
• 
Upload the MiniMed 640G into CareLink 
Clinical. Use correct Subject ID  
(311-XXX-XXX). 
• 
Review  MiniMed 640G use  
• 
Review SMBG/Bolus Wizard use  
• 
Review adverse event or device 
deficiency, if any  
• 
Dispense supplies to subjects for 6 
weeks: 
o 
350 Strips 
o 
20 Infusion sets (2 box of 10) 
o 
20 Reservoirs (2 box of 10) 
o 
8 AA batteries (2 pack of 4) 
• 
Plan next call with subject in 1 week 
 
Visit 6 Data collection: 
• Visit 6 eCRF 
• Subjects Products Tracking log eCRF 
• CareLink Clinical pump data upload. 
• Adverse Event or Device Deficiency 
eCRF, if applicable.  
 
Visit 6 Data collection: 
• Visit 6 eCRF 
• Subjects Products Tracking log eCRF 
• CareLink Clinical pump data upload 
• Adverse Event or Device Deficiency 
eCRF, if applicable.  
 
 Visit 7: 1 week Follow-Up Visit or Call  [Visit 6 + 7 days (±3 days max)] 
F.3.7
Visit 7 Procedures Treatment Arm: 
1 week Follow-up Visit   
Subject will come to the site.  
Study staff will:  
• 
Upload the MiniMed 640G into CareLink 
Clinical. Use correct Subject ID  
(311-XXX-XXX). 
• 
Review MiniMed 640G and sensor use 
• 
Review SMBG/Bolus Wizard use 
• 
Review adverse event or device 
deficiency, if any 
• 
Plan next call with subject in 1 week 
Visit 7 Data collection: 
• Visit 7 eCRF 
• CareLink clinical data upload  
• Adverse Event or Device Deficiency 
eCRF, if applicable.  
 
Visit 7 Procedures Control Arm: 
1 week Follow-Up Call  
Study staff will call the subject: 
Study staff will:  
• 
Review MiniMed 640G use  
• 
Review SMBG/Bolus Wizard use  
• 
Review adverse event or device 
deficiency, if any  
• 
Plan next call with subject in 1 week 
 
 
Visit 7 Data collection: 
• Visit 7 eCRF 
• Adverse Event or Device Deficiency 
eCRF, if applicable.  

 
 
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 Visit 8: 2 week Follow-Up Call     [Visit 6 + 14 days  (±3 days max)] 
F.3.8
Visit 8 Procedures Treatment Arm: 
2 week Follow-Up Call  
Study staff will call the subject 
 
• 
Review MiniMed 640G and sensor use  
• 
Review SMBG/Bolus Wizard use  
• 
Review adverse event or device 
deficiency, if any 
• 
Plan next visit with subject in 4 week 
Visit 8 Data collection: 
• Visit 8 eCRF 
• Adverse Event or Device Deficiency 
eCRF, if applicable.  
 
 
Visit 8 Procedures Control Arm: 
2 week Follow-Up Call  
Study staff will call the subject 
 
• 
Review MiniMed 640G use 
• 
Review SMBG/Bolus Wizard use 
• 
Review adverse event or device 
deficiency, if any  
• 
Plan next visit with subject in 4 week 
Visit 8 Data collection: 
• Visit 8 eCRF 
• Adverse Event or Device Deficiency 
eCRF, if applicable.  
 Visit 9: 6 week Follow-up Visit    [Visit 6 + 42 days (±7 days max)] 
F.3.9
 
Visit 9 Procedures Treatment Arm: 
6 week Follow-up Visit  
Subject will come to the site.  
Study staff will:  
• 
Upload the MiniMed 640G into CareLink 
Clinical. Use correct Subject ID  
(311-XXX-XXX). 
• 
Review subject’s sensor compliance  
[70-100%]. Retrain subject if needed. 
• 
Review subject therapy and make 
adjustments, per investigator judgment  
• 
Review SMBG/Bolus Wizard use 
• 
Review adverse event or device 
deficiency, if any 
• 
Dispense supplies for 6 weeks: 
o 
10 Enlite sensors (2 box of 5)  
o 
350 Strips 
o 
20 Infusion sets (2 box of 10) 
o 
20 Reservoirs (2 box of 10) 
o 
4 AA batteries (1 pack of 4) 
• 
Plan next call with subject in 4 weeks. 
 
 
 
Visit 9 Data collection 
• Visit 9 eCRF 
• CareLink clinical data upload  
• Subjects Products Tracking log eCRF 
• Adverse Event or Device Deficiency 
eCRF, if applicable. 
 
 
Visit 9 Procedures Control Arm: 
6 week Follow-up Visit  
Subject will come to the site 
Study staff will:  
o 
Upload the MiniMed 640G into CareLink 
Clinical. Use correct Subject ID  
(311-XXX-XXX). 
o 
Review subject therapy and make 
adjustments, per investigator judgment  
o 
Review SMBG/Bolus Wizard use 
o 
Review adverse event or device 
deficiency, if any  
o 
Provide a refresher training on sensor 
insertion, replacement and blinded 
recording with the GST3C transmitter. 
o 
Dispense supplies for 6 weeks: 
o 
2 GST3C transmitter (1 back-up) 
o 
1 GST3C charger  
o 
1 GST3C watertight tester 
o 
1 Enlite One-Press serter 
o 
4 Enlite sensors (2 back-up) 
o 
350 Strips 
o 
20 Infusion sets (2 box of 10) 
o 
20 Reservoirs (2 box of 10) 
o 
4 AA batteries (1 pack of 4) 
o 
Plan next call with subject in 4 weeks. 
Visit 9 Data collection 
• Visit 9 eCRF 
• CareLink clinical data upload  
• Subjects Products Tracking log eCRF. 
• Adverse Event or Device Deficiency 
eCRF, if applicable. 
 

 
 
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 Visit 10: 10 week Follow-Up Call    [Visit 6 + 70 days  (±7 days max)] 
F.3.10
Visit 10 Procedures Treatment Arm: 
10 week Follow-Up Call  
Study staff will call the subject to:   
• 
Review MiniMed 640G and sensor use.  
• 
Review SMBG/Bolus Wizard use. 
• 
Review adverse event or device 
deficiency, if any. 
• 
Plan next visit with subject in 2 weeks. 
 
 
 
 
 
 
Visit 10 Data collection: 
• Visit 10 eCRF 
• Adverse Event or Device Deficiency 
eCRF, if applicable. 
Visit 10 Procedures Control Arm: 
10 week Follow-Up Call  
Study staff will call the subject to:  
• 
Review MiniMed 640G use.  
• 
Review SMBG/Bolus Wizard use.  
• 
Ensure blinded GST3C transmitter 
recording is started adequately with 
proper sensor insertion, and will be 
continued until next clinic visit. 
• 
Remind subject to replace the sensor 
after maximum 7 days of wear. 
• 
Review adverse event or device 
deficiency, if any. 
• 
Plan next visit with subject in 2 weeks. 
 
Visit 10 Data collection 
• Visit 10 eCRF 
• Adverse Event or Device Deficiency 
eCRF, if applicable. 
 
 
 Visit 11: 12 week Follow-up Visit   [Visit 10 + 14 days (+7 days max)] 
F.3.11
Visit 11 Procedures Treatment Arm: 
 
12 week Follow-up Visit 
Subject will come to the site.  
Study staff will:  
• 
Upload the MiniMed 640G into CareLink 
Clinical. Use correct Subject ID  
(311-XXX-XXX). 
 
• 
Review subject’s sensor compliance   
[70-100%]. Retrain subject if needed. 
• 
Collect blood sample for HbA1c. 
• 
Review subject therapy and make 
adjustments, per investigator judgment. 
• 
Review SMBG/Bolus Wizard use  
• 
Review adverse event or device 
deficiency, if any. 
• 
Ask subject to complete 3 questionnaires 
(Clarke, Gold, HFS)  
• 
Dispense supplies for 6 weeks:  
o 
10 Enlite 3 sensors 
o 
350 Strips (7 boxes of 50) 
o 
20 Infusion Sets (2 boxes of 10) 
o 
20 Reservoirs (2 boxes of 10) 
o 
8 AA batteries (2 pack of 4) 
• 
Plan next call with subject in 4 weeks 
 
Visit 11 Procedures Control Arm: 
12 week Follow-up Visit  
Subject will come to the site. 
Study staff will:  
• 
Upload the MiniMed 640G into CareLink 
Clinical. Use correct Subject ID  
(311-XXX-XXX). 
• 
Upload the GST3C transmitter using 
GST3C Download utility. Use correct file 
name (Subject ID_XXX_DATE).  
• 
Collect blood sample for HbA1c. 
• 
Review subject therapy and make 
adjustments, per investigator judgment.  
• 
Review SMBG/Bolus Wizard use. 
• 
Review adverse event or device 
deficiency, if any. 
• 
Ask subject to complete 3 questionnaires 
(Clarke, Gold, HFS)  
• 
Dispense supplies for 6 weeks: 
o 
4 Enlite sensors (2 back-up) 
o 
350 Strips (7 boxes of 50) 
o 
20 Infusion Sets (2 boxes of 10) 
o 
20 Reservoirs (2 boxes of 10) 
o 
8 AA batteries (2 pack of 4) 
• 
Plan next call for subject in 4 weeks. 

 
 
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Visit 11 Data collection 
• Visit 11 eCRF with HbA1c value 
• Clarke eCRF  
• Gold eCRF 
• HFS eCRF 
• Subjects Products Tracking log eCRF.  
• Adverse Event or Device Deficiency 
eCRF, if applicable. 
• Pump data upload in CareLink Clinical. 
 
Visit 11 Data collection 
• Visit 11 eCRF with HbA1c value 
• Clarke eCRF 
• Gold eCRF 
• HFS eCRF  
• Subjects Products Tracking log eCRF.  
• Adverse Event or Device Deficiency 
eCRF, if applicable. 
• Pump data upload in CareLink Clinical. 
• Transmitter data upload using GST3C 
Download utility. 
 Visit 12: 16 week Follow-Up Call    [Visit 6 + 112 days (±7 days max)] 
F.3.12
 
Visit 12 Procedures Treatment Arm:  
16 week Follow-Up Call 
Study staff will call the subject 
 
• 
Review MiniMed 640G and sensor use.  
• 
Review SMBG/Bolus Wizard use. 
• 
Review adverse event or device 
deficiency, if any. 
• 
Plan next visit with subject in 2 weeks 
 
 
 
 
 
Visit 12 Data collection 
• Visit 12 eCRF 
• Adverse Event or Device Deficiency 
eCRF, if applicable. 
 
Visit 12 Procedures Control Arm:  
16 week Follow-Up Call 
Study staff will call the subject 
 
• 
Review MiniMed 640G use. 
• 
Review SMBG/Bolus Wizard use.  
• 
Ensure blinded GST3C transmitter 
recording is started adequately with 
proper sensor insertion, and will be 
continued until next clinic visit. 
• 
Remind subject to replace the sensor 
after maximum 7 days of wear. 
• 
Review adverse event or device 
deficiency, if any. 
• 
Plan next visit with subject in 2 weeks 
 
Visit 12 Data collection 
• Visit 12 eCRF 
• Adverse Event or Device Deficiency 
eCRF, if applicable. 

 
 
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 Visit 13: 18 week Follow-up Visit     [Visit 12 + 14 days (+7 days max)] 
F.3.13
 
Visit 13 Procedures Treatment Arm: 
18 week Follow-up visit  
Subject will come to the site.  
Study staff will:  
• 
Upload the MiniMed 640G into CareLink 
Clinical. Use correct Subject ID  
(311-XXX-XXX). 
• 
Review subject’s sensor compliance   
[70-100%]. Retrain subject if needed. 
• 
Review subject therapy and make 
adjustments, per investigator judgment. 
• 
Review SMBG/Bolus Wizard use . 
• 
Review adverse event or device 
deficiency, if any. 
• 
Dispense supplies for 6 weeks:  
o 
10 Enlite 3 sensors (2 boxes of 5) 
o 
350 Strips (7 boxes of 50) 
o 
20 Infusion Sets (2 boxes of 10) 
o 
20 Reservoirs (2 boxes of 10) 
o 
4 AA batteries (1 pack of 4) 
• 
Provide subject DTSQs and DTSQc 
questionnaires to be completed at home 
in 4 weeks (Call14). 
• 
Plan next call with subject in 4 weeks. 
 
 
Visit 13 Data collection 
• Visit 13 eCRF  
• Subjects Products Tracking log eCRF.  
• Adverse Event or Device Deficiency 
eCRF, if applicable. 
• Pump data upload in CareLink Clinical 
 
Visit 13 Procedures Control Arm: 
18 week Follow-up visit  
Subject will come to the site 
Study staff will:  
• 
Upload the MiniMed 640G into CareLink 
Clinical. Use correct Subject ID  
(311-XXX-XXX). 
• 
Upload the GST3C transmitters using 
GST3C Download utility. Use correct file 
name (Subject ID_XXX_DATE). 
• 
Review subject therapy and make 
adjustments, per investigator judgment.  
• 
Review SMBG/Bolus Wizard use. 
• 
Review adverse event or device 
deficiency, if any. 
• 
Dispense supplies for 6 weeks: 
o 
4 Enlite 3 sensors (2 back-up) 
o 
350 Strips (7 boxes of 50) 
o 
20 Infusion Sets (2 boxes of 10) 
o 
20 Reservoirs (2 boxes of 10) 
o 
4 AA batteries (1 pack of 4) 
• 
Provide subject DTSQs and DTSQc 
questionnaires to be completed at home 
in 4 weeks (Call14). 
• 
Plan next call with subject in 4 weeks. 
 
Visit 13 Data collection 
• Visit 13 eCRF  
• Subjects Products Tracking log eCRF.  
• Adverse Event or Device Deficiency 
eCRF, if applicable. 
• Pump data upload in CareLink Clinical 
• Transmitter data upload using GST3C 
Download utility. 
 
 
 

 
 
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 Visit 14: 22 week Follow-Up Call     [Visit 6 + 154 days (±7 days max)] 
F.3.14
 
Visit 14 Procedures Treatment Arm: 
22 week Follow-Up Call  
Study staff will call the subject 
 
• 
Review MiniMed 640G and sensor use. 
• 
Review SMBG/Bolus Wizard use. 
• 
Review adverse event or device 
deficiency, if any 
• 
Remind subject to complete DTSQs and 
DTSQc questionnaires and to return 
them at next clinic  visit. 
• 
Plan End of Study visit in 2 weeks 
• 
Remind subject to bring back all study 
materials at End of Study visit. 
 
 
 
 
 
Visit 14 Data collection 
• Visit 14 eCRF 
• DTSQs completion by subject at home 
• DTSQc completion by subject at home 
• Adverse Event or Device Deficiency  
eCRF, if applicable. 
 
Visit 14 Procedures Control Arm: 
22 week Follow-Up Call 
Study staff will call the subject 
 
• 
Review MiniMed 640G use  
• 
Review SMBG/Bolus Wizard use  
• 
Ensure blinded GST3C transmitter 
recording is started adequately with 
proper sensor insertion, and will be 
continued until next clinic visit. 
• 
Remind subject to replace the sensor 
after maximum 7 days of wear. 
• 
Review adverse event or device 
deficiency, if any 
• 
Remind subject to complete DTSQs and 
DTSQc questionnaires and to return 
them at next clinic  visit 
• 
Plan End of Study visit in 2 weeks. 
• 
Remind subject to bring back all study 
materials at next clinic visit. 
 
Visit 14 Data collection 
• Visit 14 eCRF 
• DTSQs completion by subject at home 
• DTSQc completion by subject at home 
• Adverse Event or Device Deficiency 
eCRF, if applicable 
 
 
 

 
 
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 Visit 15: 24 week End of study Visit    [Visit 14 + 14 days (+ 7 days max)] 
F.3.15
Visit 15 Procedures Treatment Arm: 
End of study visit  
Subject will come to the site.  
Study staff will:  
• 
Upload the MiniMed 640G into CareLink 
Clinical. Use correct Subject ID  
(311-XXX-XXX). 
• 
Review subject’s sensor compliance   
[70-100%]. Retrain subject if needed. 
• 
Review adverse event or device 
deficiency, if any. 
• 
Collect blood sample for HbA1c at local 
lab. 
• 
Ask subject to complete Clarke 
questionnaire.  
• 
Ask subject to complete Gold 
questionnaire. 
• 
Ask Subject to complete HFS 
questionnaire. 
• 
Collect DTSQs and DTSQc paper 
questionnaires completed by subject at 
Visit 14 at home. 
• 
Retrieve all study related devices and 
material. 
• 
After the study end, subjects will continue 
to be followed per routine practice, 
according to their doctor advice.  
 
Visit 15 Data collection 
• Visit 15 eCRF with HbA1c value 
• Study Exit eCRF  
• Pump data upload in CareLink Clinical. 
• Clarke eCRF 
• Gold eCRF 
• HFS eCRF 
• DTSQs eCRF 
• DTSQc eCRF 
• Subjects Products Tracking log eCRF 
with all return dates of study products. 
• Adverse Event or Device Deficiency 
eCRF, if applicable. 
 
Visit 15 Procedures Control  Arm: 
End of study visit  
Subject will come to the site 
Study staff will:  
• 
Upload the MiniMed 640G into CareLink 
Clinical. Use correct Subject ID  
(311-XXX-XXX). 
• 
Upload the GST3C transmitters using 
GST3C Download utility. Use correct file 
name (Subject ID_XXX_DATE). 
• 
Review adverse event or device 
deficiency, if any. 
• 
Collect blood sample for HbA1c at local 
lab. 
• 
Ask subject to complete Clarke 
questionnaire. 
• 
Ask subject to complete Gold questionnaire
• 
Ask Subject to complete HFS 
questionnaire. 
• 
Collect DTSQs and DTSQc paper 
questionnaires completed by subject at 
Visit 14 at home. 
• 
Retrieve all study related devices and 
material. 
• 
After the study end, subjects will continue 
to be followed per routine practice, 
according to their doctor advice.  
 
Visit 15 Data collection 
• Visit 15 eCRF with HbA1c value 
• Study Exit eCRF  
• Pump data upload in CareLink Clinical. 
• Transmitter data upload using GST3C 
Download utility. 
• Clarke eCRF Gold eCRF 
• HFS eCRF 
• DTSQs eCRF 
• DTSQc eCRF Subjects Products 
Tracking log eCRF with all return dates 
of study products. 
• Adverse Event or Device Deficiency 
eCRF, if applicable. 
 
 

 
 
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 Unscheduled visit: 
F.3.16
In case additional data need to be reported, unscheduled visit can be used (i.e. in case of early 
termination outside of a normal protocol visit) 
 
Unscheduled visit Procedures: could include, but are not limited to:  
• 
Upload the MiniMed 640G into CareLink Clinical. Use correct Subject ID (311-XXX-XXX). 
• 
Upload GST3C transmitters using GST3C Download utility, if applicable (Control Arm only). Use 
correct Subject ID (Subject ID_XXX_DATE). 
• 
Review adverse event or device deficiency, if any. 
 
Unscheduled visit Data collection 
• Unscheduled visit eCRF  
• Pump data upload in CareLink Clinical. 
• Transmitter data upload using GST3C Download utility (control arm only) 
• Subjects Products Tracking log eCRF  
• Adverse Event or Device Deficiency eCRF, if applicable. 
 
 Early Termination visit:  
F.3.17
Whenever possible, the study staff will perform an Early Termination visit when a subject decides to 
withdraw from the study early or if the subject is withdrawn early upon decision of investigator (during a 
normal study visit or an unscheduled visit).  
 
Early Termination Procedures:  
• 
Upload the MiniMed 640G into CareLink Clinical. Use correct Subject ID (311-XXX-XXX). 
• 
Upload GST3C transmitters using GST3C Download utility, if applicable.  
Use correct Subject ID (Subject ID_XXXX_DATE). 
• 
Collect blood sample for HbA1c at local lab, if applicable  
• 
Ask subject to complete Clarke questionnaire, if applicable  
• 
Ask subject to complete Gold questionnaire, if applicable. Ask Subject to complete HFS 
questionnaire, if applicable  
• 
Ask subject to complete DTSQs and DTSQc questionnaires, if applicable  
• 
Review adverse event or device deficiency, if any  
• 
Retrieve all study related devices and material . 
 
Early Termination Data collection: 
• Unscheduled Visit eCRF, if withdrawal occurred in between scheduled study visits.  
• Study Exit eCRF: with date and reason for withdrawal; last available HbA1c value, if applicable,  
• Subjects Products Tracking log eCRF to record all returned devices and dates.  
• Pump data upload in CareLink Clinical. 
• Transmitter data upload using GST3C Download utility, if applicable 
• Clarke eCRF, if available. 
• Gold eCRF, if available 
• HFS eCRF, if available. 
• DTSQs eCRF, if available. 
• DTSQc eCRF, if available. 
• Adverse Event or Device Deficiency eCRF, if applicable. 

 
 
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F.4 Role of the sponsor’s representatives 
Sponsor’s representatives may provide technical support following routine practice in the participating 
countries (i.e. pump or CGM training) and for study specific activities (i.e. data uploads, IT support). In 
the applicable participating sites where sponsor is involved in subject device trainings, the sponsor’s 
representatives providing technical support will be listed on the sponsor technical support list.   
F.5 Source documents 
The patient’s hospital/clinic file, CareLink data, HbA1c laboratory reports, data collected on the paper 
questionnaires are handled as source data.  
The investigator will mark the clinical records to indicate that the subject is enrolled in this clinical study. 
In addition, the site personnel will receive paper worksheets that detail all required data collection to be 
performed during the patient visits and copied in the CRFs. The objective of these paper worksheets is to 
remind the center of all study-related procedures to be performed and items to be recorded, before data 
is actually entered into the study database. Worksheets can serve as source document for study specific 
data.  
Collected data of each subject will need to be recorded on electronic Case Report Forms (eCRFs), which 
access will be provided via Internet based electronic data collection (EDC) software. 
For monitoring purposes, audit or inspection, Medtronic clinical representatives or delegates, monitors, 
auditors and inspectors will be granted access by the site to all source documents including electronic 
source documents, if applicable. Where copies of the original source document as well as printouts of 
original electronic source documents are retained, these shall be signed and dated by a member of the 
investigation site team with a statement that it is a true reproduction of the original source document. 
F.6 Adverse events 
 Definitions 
F.6.1
For the purposes of the clinical report, Medtronic will classify each adverse event according to ISO 
14155:2011. 
Where the definition indicates “device”, it refers to any device used in the study. This might be the device 
under investigation, or any market released component of the system. 
Adverse Event (AE): (ISO14155:2011 3.2) 
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): (ISO14155:2011 3.1) 
Adverse event related to the use of an investigational medical device 
 
NOTE 1: This definition includes adverse events resulting from insufficient or inadequate instructions for use, 
deployment, implantation, installation, or operation, or any malfunction of the investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or from intentional misuse of the investigational 
medical device 

 
 
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Serious Adverse Event (SAE): (ISO 14155:2011 3.37) 
An adverse event that  
a) 
led to death, 
b) 
led to serious deterioration in the health of the subject, that either resulted in  
1) 
a life-threatening illness or injury, or 
2) 
a permanent impairment of a body structure or a body function, or 
3) 
in-patient or prolonged hospitalization, or  
4) 
medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function, 
c) 
led to foetal distress, foetal death or a congenital abnormality or birth defect.   
 
NOTE:  Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, without serious 
deterioration in health, is not considered a serious adverse event. 
Serious Adverse Device Effect (SADE): (ISO 14155:2011 3.36) 
Adverse device effect that has resulted in any of the consequences characteristic of a Serious Adverse 
Event.   
Unanticipated Serious Adverse Device Effect (USADE): (ISO 14155:2011 3.42) 
Serious adverse device effect which by its nature, incidence, severity or outcome has not been identified 
in the current version of the risk analysis report 
 
NOTE:  Anticipated serious adverse device effect (ASADE) is an effect which by its nature, incidence, severity or 
outcome has been identified in the risk analysis report. 
Device deficiency: (ISO 14155:2011 3.15) 
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 labelling. 
 Definitions of Diabetes related events  
F.6.2
Since it is inherent to the disease of diabetes that patients may daily experience variations in their blood 
sugar levels above and below the normal range, hypoglycemia and hyperglycemic events should not be 
defined and reported as an adverse event. Only Severe Hypoglycemic, Severe Hyperglycemia, and 
Diabetic Ketoacidosis need to be reported in this study. See the definitions of these events in the 
following paragraphs. 
Severe Hypoglycemia is an event requiring assistance of another person due to altered consciousness 
to actively administer carbohydrate, glucagon, or other resuscitative actions. This means that the subject 
was impaired cognitively to the point that he/she was unable to treat his or her self, was unable to 
verbalize his or her needs, and was incoherent, disoriented and/or combative.  
These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma 
glucose measurements may not be available during such an event, but neurological recovery attributable 
to the restoration of plasma glucose to normal is considered sufficient evidence that the event was 
induced by a low plasma glucose concentration. (Adapted from American Diabetes Association 
Workgroup on Hypoglycemia, Diabetes Care 28:1245-1249, 2005) 
 
Severe Hyperglycemia is defined as hyperglycemia (blood glucose >300 mg/dL) with blood glucose 
ketones >0.6mmol/L or accompanied by symptoms of nausea, vomiting or abdominal pain. 
 
Diabetic Ketoacidosis/DKA diagnostic criteria: blood glucose greater than 250 mg/dL (or greater than 
13.9 mmol/L), arterial pH less than 7.3, bicarbonate less than 15mEq/l, Anion gap greater than 12, 
moderate ketonuria or ketonemia and requiring treatment within a health care facility.  (American 
Diabetes Association-Diabetes Care, Volume 27, Supplement 1, January 2004; S94-S102) 
 
DKA will be recorded as an adverse event in the presence of all of the following: 
• 
Symptoms such as polyuria, polydipsia, nausea, or vomiting 
• 
Serum ketones or large/moderate urine ketones 
• 
Arterial blood pH less than 7.30 or serum bicarbonate less than 15mEq/l 
• 
Treatment provided in a health care facility 

 
 
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 Recording and reporting of Adverse Events 
F.6.3
In this study all adverse events will be collected (including at minimum the following information: date of 
the adverse event, date of first awareness by investigator, action taken, outcome status and resolution, 
and assessment of both the seriousness and the relationship to the investigational device and 
procedure). 
The Adverse Event (AE) information will be collected throughout the study and reported to Medtronic on 
an Adverse Event eCRF.  One Adverse Event eCRF will be completed for each adverse event, including 
AEs that require immediate reporting. The Adverse Event eCRF must be validated and saved “complete”, 
for submission to Medtronic. See the Adverse Event eCRF for the information to be reported for each 
Adverse Event.  
In the event the database is not functioning for any reason, the site will inform the Medtronic MCO Safety 
Specialist (see Sponsor list for contact details) and the site staff will manually complete the AE CRF and 
email the form, as soon as possible and/or within reporting guidelines outlined in this document (see 
Table 6), to Medtronic Safety team at the following email address for all geographies: 
rs.mstsafetydiabetes@medtronic.com. In the event the internet is not functioning, the site will inform the 
Medtronic Study Manager via phone (see Sponsor list for contact details).  
In case the Adverse Event is related to a non-Medtronic market released device (i.e. study meter by 
Ascencia) used during the study, post market surveillance is also applicable and the investigator is 
responsible for immediate reporting of the product complaint via the regular channels for market released 
products. 
In case the investigator requires information from the sponsor in an emergency situation, the investigator 
can contact their local clinical referent or the Study Manager. Contact details of the Study Manager are 
given in the Sponsor List. 
 Recording and reporting of Device Deficiencies 
F.6.4
Device Deficiency information will be collected throughout the study and reported to Medtronic, via the 
electronic CRF. Vigilance reporting will be done for CE-Marked devices, according to these reported 
data. 
Device Deficiencies that did not lead to an Adverse Event should be reported on a Device Deficiency 
eCRF, one for each Device Deficiency, completing as much information as is available. This Device 
Deficiency eCRF must be validated / saved “complete” for submission to Medtronic.  
The site should contact their local clinical referent or the study manager in case of questions. Contact 
details are given in the Sponsor List. 
See the Device Deficiency eCRF for the information to be reported for each Device Deficiency that did 
not lead to an Adverse Event.   
Device deficiencies that did not lead to an Adverse Event, but could have led to an SADE require 
immediate reporting (see Table 6).  
a) if either suitable action had not been taken, 
b) if intervention had not been made, or 
c) if circumstances had been less fortunate, 
Initial reporting will be done on the eCRF completing as much information as is available. The Device 
Deficiency eCRF must be validated and saved “complete”, for submission to Medtronic. 
In case technical issue occurs with the electronic CRF (i.e. Internet access, system maintenance…),  
initial reporting for Device Deficiencies that require immediate reporting (see Table 6), may be done via 
email: rs.mstsafetydiabetes@medtronic.com. In the event the internet is not functioning, the site will 
inform Medtronic Study Manager via phone (see Sponsor list for contact details). 
 Adverse Event and Device Deficiency review process 
F.6.5
The potential adverse events (risks) and their mitigations associated with the use of these devices are 
identified 
in 
the 
Instructions 
for 
Use 
(IFU) 
for 
the 
CE-marked 
commercially 
available 
devices/consumables and in the Investigator Brochure (IB) for the pre-market devices/consumables (also 
see Section J.2 of this CIP). 
All Adverse Events and Device Deficiencies will be reviewed by Medtronic MCO Safety Specialist or 
designee. This review will include the determination whether the Adverse Event/Device Deficiency meets 
regulatory reporting requirements (see Table 6 Adverse Event Reporting Requirements). The sponsor 
will ensure timely Adverse Event/Device Deficiency reporting to meet global regulatory requirements. 

 
 
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The Medtronic MCO Safety Specialist or designee will immediately report any Adverse Events/Device 
Deficiencies that are associated with the device to the Medtronic Diabetes Complaint Handling Unit. The 
Diabetes Complaint Handling Unit will ensure prompt review, and appropriate reporting.  
 
Table 6 Adverse Event Reporting Requirements  
Serious Adverse Device Effects (SADE), including Unanticipated Serious Adverse Device Effect (USADE): 
Investigator submit to: 
 
Medtronic 
Immediately after the investigator first learns of the event or of new information in 
relation with an already reported event.  
Regulatory Authority 
As per local reporting requirement.  
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities  
Reporting timeframe as per local requirement. 
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Serious Adverse Events (SAE) 
Investigator submit to: 
 
Medtronic 
Immediately after the investigator first learns of the event or of new information in 
relation with an already reported event.  
Regulatory Authority 
As per local reporting requirement.  
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities  
Reporting timeframe as per local requirement. 
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Adverse Device Effects (ADE) 
Investigator submit to: 
 
Medtronic 
Immediately after the investigator first learns of the event.  
Regulatory Authority 
As per local reporting requirement.  
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement 
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
All other AEs 
Investigator submit to: 
 
Medtronic 
Submit in a timely manner after the investigator first learns of the event. 
Regulatory Authority 
As per local reporting requirement.  
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Device Deficiency with SADE potential 
Investigator submit to: 
 
Medtronic 
Immediately after the investigator first learns of the deficiency or of new 
information in relation with an already reported deficiency.  
Regulatory Authority 
As per local reporting requirement.  
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement 
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
All other Device Deficiencies 
Investigator submit to: 
 
Medtronic 
Submit in a timely manner after the investigator first learns of the deficiency. 
Regulatory Authority 
As per local reporting requirement.  
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement 
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
 

 
 
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 Clinical events Committee  
F.6.6
An independent Clinical events Committee (CEC) consisting of external physicians with an expertise in 
endocrinology and the management of diabetes, including insulin pumps and CGM will be convened. The 
CEC will review all reports of: 
• 
Serious Adverse Event (SAE) 
• 
Serious Adverse Device Effect (SADE) 
• 
Unanticipated Adverse Device Effect (UADE) 
• 
Severe Hypoglycemia 
• 
Severe Hyperglycemia 
• 
Diabetic Ketoacidosis  (DKA) 
• 
Death 
The responsibilities of an CEC committee are:  
• 
Review all reported SAE, SADE, UADE, Severe Hypoglycemia, Severe Hyperglycemia, DKA and 
deaths, and determines event classification (e.g. seriousness, severity, relatedness to device and 
procedure, unanticipated/anticipated) on a periodic basis. 
• 
Upon request advise Sponsor about the potential clinical impact of an observed unintended device 
performance. 
• 
Advise Sponsor in cases of SADEs. 
 
A CEC charter will be established to indicate explicit rules outlining the minimum amount of data required 
and the algorithm followed in order to classify/adjudicate an event.  
The CEC will assess these events to determine agreement or disagreement with the Investigator 
classification of the event. CEC decisions will be documented in meeting minutes. The Sponsor will notify 
the Investigator of any disagreement in assessment of an event by the CEC. 
All other events will be reviewed and classified by the Sponsor’s qualified internal safety individual(s) to 
ensure they should not be adjudicated by the CEC and that the events are appropriately classified by the 
investigator.  
 
 Data Safety Monitoring Board 
F.6.7
The purpose of a data monitoring committee is to protect the safety of trial participants, the credibility of 
the study and the validity of study results. An independent Data Safety Monitoring Board (DSMB) will 
reassess the study sample size at the moment of the planned interim analysis.  
 
The DSMB is established by the sponsor to oversee the following responsibilities: 
- 
Review the interim analysis of effectiveness and safety measures after 60 subjects(30 treatment 
and 30 control group) have been randomized and followed up for 6 months.  
- 
Following predefined rules in the DSMB chart, implement the assessment of modifications to the 
trial design.  
The primary planned modification is a sample size re-estimation. 
- 
Monitor baseline comparability. 
- 
Monitoring adverse events: review aggregate subject data. 
- 
Provide recommendations to continue or terminate the trial depending upon these analyses. 
 
 Emergency contact details in case of serious AEs 
F.6.8
In case of an immediately reportable Adverse Event the investigators can contact the Medtronic study 
manager. Should the team members change during the course of the study, you may contact the current 
study manager. 

 
 
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F.7 Subject accountability 
Subjects who are unwilling to participate in the follow up visits or complete study procedures should be 
withdrawn.  
If a subject is withdrawn from the clinical study, the reason for withdrawal shall be recorded in the eCRF 
and in the subject’s hospital/clinic record. If discontinuation is because of safety, the subject shall be 
asked to be followed to collect safety data outside the clinical study. 
In case follow-up visits are missed, a study deviation should be completed on the eCRF to document this.  
If a subject does not return to the site for required follow-up visit(s) and cannot be reached, the 
investigation site personnel should make 3 attempts to contact the subject by phone to verify if the 
subject should be considered “lost-to follow up”. In the event the subject is not able to perform follow-up 
visits at the investigation site, subject will be considered “lost to follow up” and this needs to be 
documented in the Study Exit eCRF. 
F.8 Study deviations and CIP changes 
A study deviation is an event where the investigator or investigation site personnel did not conduct the 
clinical study according to the Clinical Investigation Plan or Clinical Investigation Agreement. The 
investigator is not allowed to deviate from the above mentioned documents except with prior approval 
and under emergency circumstances. All deviations shall be documented and explained, regardless the 
reason for the deviation. 
Medtronic will assess the significance of all deviations and evaluate the need to amend the Clinical 
Investigation Plan or to early terminate the investigation, in accordance with Medtronic SOPs. 
 Request for approval of study deviations 
F.8.1
The investigator shall obtain documented approval from Medtronic, before implementation, for any 
change in- or deviation from the Clinical Investigation Plan. In case of study deviations that can affect the 
subject’s rights, safety and well-being or the scientific integrity of the clinical study, approval from the 
EC/IRB and regulatory authority must also be obtained before implementation. The investigator shall 
timely contact the Clinical Study Manager for review of the proposed change/deviation. 
Prior approval is not always realistic in situations where unforeseen circumstances are beyond the 
investigator’s control. However, also in these cases, the event is considered a deviation, and shall be 
reported.  
In any emergency situation the investigator shall exercise his/her judgment to safeguard the subject’s 
interest. Such deviations from the Clinical Investigation Plan do not require the prior approval of 
Medtronic. The investigator shall report the deviation as soon as possible to Medtronic and the reviewing 
EC/IRB, if applicable. Medtronic will inform the regulatory authorities, if required. 
 Reporting requirements for study deviations 
F.8.2
All deviations will be reported on the Deviation eCRF by the Investigation site staff. The description of the 
deviation and justification must be documented and submitted to Medtronic via the eCRF. Once a 
deviation has been identified, it should be reported to Medtronic promptly. Deviations may be identified 
through numerous sources, including but not limited to: telephone conversations, site monitoring, patient 
record, or data review.  
The investigator shall adhere to EC/IRB requirements and procedures for reporting study deviations. 
Medtronic is responsible for analyzing deviations, assessing their significance, and identifying any 
additional corrective and/or preventive actions (e.g. amend the CIP, additional training, terminate the 
study, etc.). Repetitive or serious investigator compliance issues may result in the need to initiate a 
corrective action plan, and in some cases freeze enrolment or ultimately terminate the investigator’s 
participation in the clinical study. Medtronic will provide investigation site-specific reports to the 
investigators on a periodic basis summarizing information on deviations that occurred at the investigation 
site.  

 
 
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 Amendments to the Clinical Investigation Plan (CIP) 
F.8.3
An investigator or study team member can propose any appropriate modification(s) of the Clinical 
Investigation Plan or investigational device/product or investigational device/product use. Medtronic will 
review this proposal and decide whether the modification(s) will be implemented.  
Medtronic can decide to review the CIP based on new information (i.e. from an Investigator, the Steering 
Committee, the CEC or the study team) and will submit any significant amendment to the Clinical 
Investigation Plan, including a justification for this amendment, to the appropriate regulatory authorities 
and to the investigators to obtain approval from their EC/IRB. The investigator will only implement the 
amendment after approval of the EC/IRB, regulatory authority and sponsor. Administrative amendments 
to the Clinical Investigation Plan will be submitted to the EC/IRB for notification. Furthermore 
investigators shall sign any approved amendment for agreement.  
G QUALITY CONTROL PROCEDURES 
G.1 Procedures for database management 
 Data collection 
G.1.1
 Electronic Case Report Forms (CRFs): 
G.1.1.1
The investigator must ensure accuracy, completeness and timeliness of the data reported in the CRFs 
and in all other required reports. Data reported on the CRFs which are derived from source documents 
must be consistent with the source documents and discrepancies need to be justified in a documented 
rationale, signed and dated by the (principal) investigator, and filed in the patient medical file. 
Only authorized persons can complete electronic CRFs (eCRF). eCRFs shall be signed by investigators 
(physicians only) as specified on the Delegated Tasks List. 
The Electronic Data Capture (EDC) system maintains an audit trail on entries, changes or corrections in 
the eCRFs. If a person is only authorized to complete eCRFs or to make changes to an already signed 
eCRF, the investigator shall re-sign this eCRF. 
A copy of the CRFs to be used in this clinical study is available under a separate cover, upon request to 
the Sponsor and in the Investigator Site File.  
Investigation site will be trained for use of the eCRF prior, or at latest during, site initiation visit, on a 
training database. Access to final CRFs for study conduct will be granted after training is performed and 
prior to patient’s enrollment.  
 Paper Study Worksheets: 
G.1.1.2
All investigation sites will receive paper worksheets, which specify the required data collection in the 
CRFs, and some additional instructions to ensure correct completion. The study worksheets are a 
supplement of the patient’s hospital/clinic file and will be considered as source documents. Only 
authorized persons can complete the Worksheets as specified on the Delegated Tasks List (DTL) 
included in the Investigator Site File. 
 Medtronic CareLink Therapy Management System: 
G.1.1.3
The MiniMed 640G insulin pump data needs to be uploaded in Medtronic’s CareLink Clinical database by 
the investigator or designated person. This system uses Secure Sockets Layers (SSL) technology, which 
encrypts all data it stores (21 CFR Part 11 compliant).  
The data in the different databases are linked to each other via the subjects ID, which is a 9-digit code 
(311-xxx-xxx) to prevent patient identification by the sponsor. 
 GST3C Download Utility Software – Investigational: 
G.1.1.4
The Download Utility Software for use with the GST3C Transmitter(s) is an investigational computer-
based program used to set time, upload data and clear data for the GST3C Transmitter(s) (described in 
section B.3.1.3). Communication between the GST3C Transmitter(s) and the computer is done via the 
GST3C Dock. Once the GST3C data is downloaded, each site uses a specific username and password 
to access the site’s database and upload the device data.  
Refer to the Download Utility guidelines for more details.  

 
 
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 Patient Questionnaires: 
G.1.1.5
The Clarke, Gold, HFS and DTSQ questionnaires will be provided in local language in the countries. The 
data will initially be collected on paper questionnaires that will be kept at the site.  
The investigator, or designated site personnel, will then copy the answers of the subject from the paper 
questionnaires into the EDC system. It is important that the investigator, or designated site personnel 
verifies the questionnaires for completeness, because missing answers for some questions would 
prevent calculations of total scores.  
 Time windows for completion and submission of Case Report Forms 
G.1.2
It is expected that CRFs are completed in a timely manner, approximately within 5 to 10 days of data 
collection on source documents and/or the worksheets, with the exception of serious adverse events and 
(unanticipated) serious adverse device effects and Device deficiencies with SADE potential, which need 
to be recorded immediately after awareness of the site staff on the Adverse Event or Device Deficiency 
eCRFs. Most CRFs should be submitted in final form, i.e. saved as complete upon data entry, so that 
study monitors can proceed with data verification without delay. Exceptions to this rule apply for CRF 
forms that need to be accessed on multiple occasions before they can be finalized (i.e. Device/ 
Consumables Accountability eCRF). 
 Data review and processing 
G.1.3
Data management will be done according to Medtronic SOPs and the Data Management Plan for this 
clinical study. These documents will be made available on request. 
Collected data will be reviewed for completeness, correctness and consistency, as per monitoring plan. 
In case of issues, queries will be sent to the investigator to complete, correct or comment the data.  
G.2 Monitoring procedures 
Monitoring visits will be conducted at the start, during and at the closure of the clinical study in 
accordance with Medtronic SOPs and the Monitoring Plan. At minimum, it will be verified whether signed 
and dated informed consent forms have been obtained from each subject at the point of enrollment and 
that all SAEs and ADEs were reported via completion of the Adverse Event CRFs. More details regarding 
the monitoring activities (frequency of monitoring visits, planned extent of source data verification) are 
described in the Monitoring Plan. 
 Accessibility of investigation site staff and study materials 
G.2.1
The principal investigator(s), his/her delegate(s) and the study coordinator(s) shall be accessible to 
Medtronic field personnel and the Clinical Study Manager. This accessibility is of particular importance for 
reviewing data in the Case Report Form (CRF). Direct access to patient medical files for source data 
verification will need to be granted and prepared prior to any monitoring visits.  
 Audits and investigation site inspections  
G.2.2
In addition to regular monitoring visits, Medtronic may conduct audits at participating investigation sites. 
The purpose of an audit is to verify the adequate performance of the clinical study related activities. 
Independent of the employees involved in the clinical study. Regulatory bodies may also perform 
inspections at participating investigation sites. Any regulatory authority inspection announcements shall 
be forwarded immediately to the Clinical Study Manager. 
The investigator and/or institution shall permit Medtronic and regulatory bodies direct access to source 
data and documents, taking into account any restrictions due to local law, to perform clinical study-related 
monitoring, audits, EC/IRB review, and regulatory inspections. 

 
 
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G.3 Study suspension or early termination 
 Early study suspension or termination 
G.3.1
Medtronic or Regulatory Authority may decide to suspend or prematurely terminate the clinical study (e.g. 
if information becomes available that the risk to study subject is higher than initially indicated, lack of 
enrollment, if interim analysis indicates that the results significantly differ from expectations relative to 
study objectives or statistical endpoints,  or because of a business decision). If the clinical study is 
terminated prematurely or suspended, Medtronic shall promptly inform the investigators of the 
termination or suspension and the reason(s) for this. The investigator shall then promptly inform the 
reviewing EC/IRB and the study subjects.  
 Early investigation site suspension or termination 
G.3.2
Medtronic, EC/IRB or Regulatory Authority may decide to suspend or prematurely terminate an 
investigation site (e.g. in case of expiring approval of the reviewing EC/IRB, non-compliance to the 
Clinical Investigation Plan or lack of enrollment). If an investigation site is suspended or prematurely 
terminated, Medtronic shall promptly inform the investigator(s) of the termination or suspension and the 
reason(s) for this. The investigator shall then promptly inform the reviewing EC/IRB and the study 
subjects.  
When the risks are found to outweigh the potential benefits or when there is conclusive proof of definite 
outcomes, investigators must assess whether to continue, modify or immediately stop the clinical study in 
the respective investigation site and immediately inform the sponsor and EC/IRB, if applicable. 
 Subject follow-up in case of termination 
G.3.3
In case of early investigational site suspension or termination, all subjects should be called to plan an 
early Termination visit (see section F.3) at the site. All efforts will be made to complete and report all 
study observations at the time of termination. The subject will return the study devices to the site (unless 
subject is allowed to keep them per country requirement).  
G.4 Study close out 
In case of a study close-out, the Investigators will be notified by Medtronic. Appropriate notification/report 
to EC/IRB and Competent Authorities will be provided, if required per local laws and regulations. 
After study close-out, the follow-up treatment and medical care of the subjects will continue to be as per 
routine practice of the site.  
H DATA ANALYSIS AND REPORTING 
A detailed description of the data analyses and timing will be provided in a separate Statistical Analyses 
Plan (SAP).  
Any deviations from this section and/or the Statistical Analysis Plan will be described and justified in the 
Final Clinical Study Report, as appropriate. 
H.1 Analysis of clinical data 
A detailed statistical analysis will be outlined in a separate statistical analysis plan (SAP). The SAP will 
include information on the following items:  
• 
Patient demographics and baseline characteristics will be presented using appropriate summary 
statistics (mean, standard deviation, median, minimum and maximum for continuous variables; 
frequency counts and percentages for categorical variables).  
• 
The criteria for selection of subjects as described in section D.  
• 
A Consort diagram will describe the number of subjects that were enrolled, randomized, completed 
follow-up, early terminated the study, and number of subjects included for analysis.  
• 
Statistical methods to be used including a description of the statistical test (see section C.3) for 
testing of the null-hypothesis of the primary endpoint and statistical test for secondary endpoints and 
multiple imputation method for missing data. 
• 
Between groups comparison of secondary and tertiary endpoints 
• 
Subgroups for analysis by baseline HbA1c level ≤7.5% and >7.5% (as a threshold for “well-
controlled” patients below this value) 

 
 
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• 
An interim analysis for sample size re-estimation will use the method described in the SAP when 
approximately 60 subjects have reached the 6 months of follow-up.  The independent DSMB will re-
estimate the sample size taking into account the observed treatment effect and the estimated 
standard deviation. The board will be able to recommend one of the following to the sponsor after 
the interim analysis:  
- 
Study has reached the futility boundary and it is recommended to be terminated for futility.  
- 
Continue the study to its conclusion without modification of sample size or inclusion criteria.  
- 
Increase the numbers of patients in each treatment group.  
- 
Revise the inclusion criteria.  
• 
Detailed description of the Intention To Treat (ITT) analysis: Analysis will be performed on the Intent 
to Treat (ITT) basis. The ITT set will be composed of randomized subjects who underwent at least 
two week of CGM (blinded CGM in the Control arm and unblinded CGM in the Treatment arm). 
These subjects will be followed up, assessed and analyzed as members of the intended randomized 
arm, irrespective of their compliance to the planned course of treatment or deviations from protocol. 
Imputation of missing data in the ITT analysis will be performed using multiple imputation.    
• 
Additional ad-hoc analysis may be performed and will be described as such in the report of study 
results.  
 
H.2 Publication Policy 
Publications and presentations referring to this clinical study will be coordinated by Medtronic with the 
Study Steering Committee to allow the use of all available data. The following publication policy will have 
to be adhered to by all participating investigation sites.  
Medtronic intends to publish the results of the clinical study in a scientific journal.  
A separate Publication Plan will describe the publication strategy and processes for publications of the 
SMILE study.  
Authorship on any publication(s) resulting from this clinical study will be assigned according to substantial 
contributions to conception and design, acquisition of data, or analysis and interpretation of data, drafting 
the article or revising it critically for important intellectual content, final approval of the version to be 
published and agreement to be accountable for all aspects of the work in ensuring that questions related 
to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This is in 
accordance with the International Committee of Medical Journal Editors (ICMJE) published guidelines 
(JAMA 2013), as agreed upon by the editors of all major medical journals.  
The number of authors will be dependent on the regulations of the concerning journal with a maximum of 
10 authors. Names of all participating investigators will appear in the Acknowledgment of the paper. 
Based on the principle that Medtronic owns the data of this clinical study, a single investigation site may 
access and use the data provided by itself for scientific publications following prior approval by the 
Steering Committee. 
Pooling data from several investigation sites for publication purposes, national projects and international 
projects all require prior approval from the Steering Committee. 
Medtronic as the owner of the data can use the data and/or any results derived from the data or 
publications based on that data for marketing purposes, further research and development of devices or 
educational use. 
The study sponsor will collect data in such way that no subject can be identified, and monitor study 
records. 
Participating subjects will not be identified by name in any published reports about the clinical study.  
I 
STUDY MANAGEMENT 
I.1 
Study staff 
This study is sponsored by Medtronic International Trading Sàrl and Medtronic of Canada. 
A list of sponsor staff involved in the study is available from the sponsor; it will be kept under separate 
cover and provided upon request.  

 
 
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I.2 
Advisory committees 
 
Steering Committee  
I.2.1
A steering committee composed of physicians (section L.1.1) and Medtronic representatives has been 
set up to coordinate the study, as defined in the Steering Committee charter. The Steering Committee 
Charter is available under a separate cover.  
 
Clinical Events Committee (CEC) (section F.6.6) 
I.2.2
An independent Clinical Events Committee (CEC) consisting of external physicians with an expertise in 
endocrinology and diabetes management will review the reported safety events, as defined in the CEC 
Charter. This Clinical Steering Committee Charter is available under a separate cover.  
 
Data Safety Monitoring Board (DSMB) (section F.6.7) 
I.2.3
An independent DSMB, consisting of external physicians and at least one statistician, will protect the 
safety of trial participants, the credibility of the study and the validity of study results, as defined in the 
DSMB Charter. This DSMB Charter is available under a separate cover. 
I.3 
Records and reports 
 
Investigator Records 
I.3.1
At a minimum, the following records must be kept by the investigator:  
• 
Clinical Investigation Plan and, if applicable, any amendments 
• 
Investigator’s Brochure and/or Instructions for Use 
• 
Medtronic and EC/IRB approved Patient Informed Consent form 
• 
Regulatory Authority approval or notification 
• 
Fully signed Clinical Investigation Agreement and confidentiality agreement (if not included in the 
Clinical Investigation Agreement) 
• 
Insurance certificates 
• 
Completed Delegated Task List and Curriculum Vitae  
• 
Training documentation of all investigation site personnel 
• 
Relevant communications 
• 
Subject screening log and/or subject identification log  
• 
Signed, dated and fully executed Patient Informed Consent forms 
• 
Completed worksheets 
• 
Fully executed CRFs and corrections, including Randomization CRFs  
• 
Reports of Adverse Events and Device Deficiencies 
• 
Device accountability records 

 
 
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Investigator reporting responsibilities  
I.3.2
Report 
Submitted to 
Description 
Adverse Events 
Sponsor, EC/IRB, and 
local regulatory authority, 
where applicable 
Refer to sections F.6.3, F.6.4, F.6.5 for reporting 
requirements. 
Withdrawal of 
EC/IRB approval 
Sponsor 
Investigator will inform Medtronic in case EC/IRB 
approval is withdrawn. 
Final Clinical 
Study Report 
EC/IRB 
A copy of the Final Clinical Study Report will be 
provided to the EC/IRB. 
Deviations from Investigational Plan 
Emergency Use 
Sponsor, EC/IRB, 
regulatory authority 
Investigator will report deviation as soon as possible 
to the sponsor and EC/IRB. 
Planned 
deviation 
Sponsor, EC/IRB, 
regulatory authority 
Prior any deviation, approval must always be 
obtained from Medtronic. If the deviation affects 
scientific soundness of the clinical study or the rights, 
safety, or welfare of the subject and is not an 
emergency, prior approval must be obtained from the 
EC/IRB and regulatory authority. 
Other Deviations 
Sponsor 
Deviations that are beyond the control of the 
investigator (such as subject who fails to return to 
follow-up visit) or deviations that do not affect the 
scientific soundness of the clinical study or the rights, 
safety, or welfare of the subject and are not an 
emergency, should be submitted as they are 
identified by the investigation site or Medtronic staff. 
 
 
Sponsor records 
I.3.3
At a minimum, the sponsor will keep the following records: 
• 
All essential study documents and correspondence that pertains to the clinical study 
• 
CIP and any amendments, if applicable 
• 
Investigator Brochure and/or Instructions for Use 
• 
Sample of labeling attached to the investigational device 
• 
Curriculum Vitae of site staff  
• 
Delegated Task Lists and training records of investigators and investigation site personnel 
• 
EC/IRB approvals/notifications and regulatory approvals/notifications 
• 
Signed Clinical Investigation Agreements and signed agreements with third parties 
• 
Insurance certificates, 
• 
Shipping records for investigational devices and clinical-investigation related documents and 
materials 
• 
Medtronic and EC/IRC approved Patient Informed Consents 
• 
Site selection reports, site initiation reports and monitoring visit reports  
• 
Adverse event and Device Deficiency reports 
• 
Fully executed CRFs and corrections  (including randomization CRFs). 
 

 
 
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Sponsor reporting responsibilities 
I.3.4
Report 
Submit to 
Description 
Adverse Events 
EC/IRB, Investigators, 
and regulatory authorities, 
where applicable 
Medtronic will report adverse events as 
required and in compliance with local 
regulatory requirements, as applicable. 
Refer to sections F.6.3, F.6.4, F.6.5 for 
reporting requirements. 
Withdrawal of EC/IRB 
approval 
EC/IRB, Investigators, 
and regulatory authorities, 
where applicable 
In case of withdrawal of EC/IRB approval 
Medtronic will suspend the clinical study as 
described below. 
Premature termination 
or suspension of study 
EC/IRB, Investigators, 
and regulatory authorities, 
where applicable 
Medtronic will provide prompt notification of 
termination or suspension and reason(s) to 
investigator and where required to EC/IRB 
and regulatory authorities. 
Final Report 
Investigators, and 
regulatory authorities, 
where applicable 
Medtronic will provide all investigators with a 
copy of the Final Clinical Study Report of the 
clinical study.  
EC/IRBs and regulatory authorities will be 
informed when required. 
Emergency Deviations 
from Investigational 
Plan 
Regulatory authorities, 
where applicable 
If required, Medtronic will inform regulatory 
authorities as soon as possible about any 
emergency deviations that affect scientific 
soundness of the clinical study or the rights, 
safety, or welfare of the subject. 
 
Record retention  
I.3.5
The investigator must retain the Investigator Site File, patient medical files and CRFs in accordance with 
local law and regulations for a minimum period of 2 year (or longer if local laws require) after market-
release in his/her region. The investigator should take measures to prevent accidental or early 
destruction of the clinical study related materials. 
I.4 
Miscellaneous 
 
Insurance 
I.4.1
The Medtronic International Trading Sàrl and Medtronic of Canada is a wholly owned subsidiary of 
Medtronic Inc., which as the parent company of such entity maintains appropriate clinical study liability 
insurance coverage as required under applicable laws and regulations and will comply with applicable 
law and custom concerning specific insurance coverage. If required, a Clinical Trial Insurance 
statement/certificate will be provided to the EC/IRB or regulatory authority.  
 
Subject compensation and indemnification 
I.4.2
The subjects will not receive any compensation for participation in this study. Travel fees to the site may 
be reimbursed for study specific visits if required by local regulations.   
 
Subject confidentiality 
I.4.3
All records and other information about subjects participating in this clinical study will be treated as 
confidential.  
Subject confidentiality will be maintained throughout the clinical study to the extent permitted by law. That 
is, every attempt will be made to remove subject identifiers from clinical study documents. For this 
purpose, a unique subject identification code (study - site - subject number) will be assigned and used to 
allow identification of all data reported for each subject.  
This will also ensure that the information can be tracked back to the source data. 
Study data may be made available to third parties, e.g., in the case of an audit or inspection performed 
by regulatory authorities, provided the data are treated confidentially and that the subject’s privacy is 
guaranteed. The identity of a subject will never be disclosed in the event that study data are published. 
Only anonymized data will be analyzed and published.   
 

 
 
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J 
RISKS AND BENEFITS 
J.1 Anticipated Clinical Benefits 
The goal of the study is to demonstrate the impact of the SmartGuard feature of the new MiniMed 640G 
system on the incidence of hypoglycemia. It is anticipated that this new system will allow reducing 
hypoglycemia in this selected population of patients. Previous studies are supporting this hypothesis: it 
was shown in the PILGRIM study [10] that hypoglycemic events were decreased by 80% using 
SmartGuard during physical excercise. In a MiniMed 640G user evaluation [11] 83.1% of the SmartGuard 
events where the pump stopped delivering insulin, the sensor glucose value never reached the pre-set 
low limit.   
The study will give the opportunity to subjects of the treatment arm to have access to CGM therapy, 
which may not be reimbursed in all countries.  
It is possible that the subjects of control arm do not get any benefit in participating in this study, 
nevertheless, it gives them the opportunity to use the last generation pump MiniMed 640G, with new 
features (e.g. new user interface, easier adjustment of insulin doses…). 
The information gathered in this study may help the patients and physicians determine the best treatment 
options in the future. The experience of participating in this study may also help other patients benefit 
from improved diabetes management learned by patients and investigational staff using the MiniMed 
640G System. Furthermore, results from this study may address potential device and clinical issues not 
identified in previous studies, support the development of new devices and therapies, and may facilitate 
reimbursement of the device components (and subsequent systems) in countries where they are not 
currently reimbursed. 
J.2 Risks 
Subjects participating in this study have a medical diagnosis of Type 1 diabetes requiring the daily use of 
insulin infusion or injections. There are risks inherent to Type 1 diabetes that are independent from their 
participation in the study:  
- 
Hypoglycemia  
- 
Severe Hypoglycemia  
- 
Hyperglycemia  
- 
Diabetic Ketoacidosis 
The potential side effects related to the insulin administration and pump use, insulin pump infusion sets 
and finger sticks are anticipated to be the same as per standard of care for the study participants. 
Standard risks associated with the medical device used in this clinical study and analyses of Adverse 
Device Effects are listed in the Instructions for Use or Investigator Brochure.  
Possible interactions of the devices used in the study with concomitant medical treatments are not 
known.  
The history of recall of the investigational devices is described in the Investigator Brochure, if applicable.   
 
Potential risks associated with the use of the Enlite 3 Sensor  
J.2.1
Serious Adverse Events during past studies involving glucose sensor use were relatively rare. Usually 
side effects are often limited to reactions to the sensor insertion site, adhesives or tape associated with 
device placement and device irritation on the skin. These 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, Raised bump, Appearance of a small “freckle-
like” dot where needle was inserted, Allergic reaction, Fainting secondary to needle insertion, Soreness 
or tenderness, Swelling at insertion site, Sensor fracture, breakage or damage, Minimal blood splatter 
associated with sensor needle removal, Residual redness associated with adhesive and or tapes and 
Scarring. 
 
Either the subject or investigational center may remove a sensor if they are concerned with skin irritation 
or skin discomfort.  Also, the possibility of infection is minimized by aseptic technique of sensor insertion 
and site rotation. Subjects should base their diabetes management on fingerstick readings and not 
sensor glucose values. 
While there is no evidence of an Enlite sensor breaking in a patient’s body, if there is suspicion of sensor 
breakage, subject should contact his healthcare professional for assistance in removing the sensor. 

 
 
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The same risks apply for the subjects in the treatment arm and those in the control arm with the use of 
the GST3C transmitter device and sensor, with a reduced frequency of use for the control arm.  
 
Potential risks associated with the use of the GST3C Transmitter 
J.2.2
The GST3C transmitter is similar to the Guardian 2 Link transmitter which is CE-marked and 
commercially available.  
There are no anticipated risks with the use of the GST3C at this stage.   
Contra-indications:   
Transmitter must not be exposed to MRI equipment, diathermy devices, or other devices that generate 
strong magnetic fields. If the transmitter is inadvertently exposed to a strong magnetic field, its use must 
be discontinued and it must be replaced. 
 
Potential risks associated with the use of other investigational devices  
J.2.3
No risks are known or anticipated at this stage with the other investigational study devices: 
- 
GST3C Dock (T8381)  
- 
GST3C Download Utility (9029393)  
 
Potential risks associated with the use of MiniMed 640G Insulin pump:  
J.2.4
Potential risks associated with the use of an insulin infusion pump include the risk of malfunction of the 
components of the system (pump, software, infusion set and reservoir) as well as the risk of use error 
during use of the system. Device deficiencies or use errors can result in administration of too much or too 
little insulin which can lead to the following clinical consequences:  
- 
Hypoglycemia  
- 
Hyperglycemia  
- 
Diabetic ketoacidosis (DKA)  
- 
Severe hypoglycemia with or without associated seizure, coma or death  
- 
Kinked cannula leading to hyper or hypoglycemia  
- 
Infusion set disconnection from pump leading to hypo or hyperglycemia  
- 
Dislodged cannula leading to hypo or hyperglycemia  
- 
A pump error indicating hardware failure may lead to under delivery  
- 
Battery failure – no insulin delivered  
- 
Remove a reservoir, without suspending and reconnecting after a while resulting in a  
 
Hypoglycemia  
- 
Insulin deterioration leading to hyperglycemia  
- 
Incomplete priming; Fails to priming tubing and/or cannula, leading to hyperglycemia  
- 
Remove a reservoir, without suspending and reconnecting after a while resulting in a  
 
Hypoglycemia  
- 
Patient not filling pump reservoir when needed leading to hyperglycemia 
- 
Magnetic Resonance Imaging resulting in pump /Transmitter malfunction 
- 
Inaccurate insulin delivery due to sudden altitude changes. 
- 
Hypoglycemia or hyperglycemia from manual bolus 
- 
Hypoglycemia or hyperglycemia from computer hacking 
 
Risks associated with hyperglycemia include: 
- 
DKA  
- 
Symptomatic ketosis  
- 
Cardiovascular event  
- 
Dehydration  
- 
Potassium and sodium imbalance  
- 
Shock  
- 
Altered mental status  
- 
Coma  
- 
Acidosis  
 

 
 
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Risks associated with hypoglycemia include:  
- 
Seizure  
- 
Coma  
- 
Altered mental status  
- 
Loss of consciousness  
- 
Cardiovascular event  
- 
Death  
- 
Risk of rebound hyperglycemia with ketosis  
 
Prevention and mitigation risks include: 
- 
Investigational center staff and subjects will be instructed to follow the provided user guides for 
insulin pump management. 
- 
Subjects will be trained prior to study device use and diabetes management principles and told to 
call with problems. 
- 
Subjects will be required to check SMBG at least 4 times a day and before driving. 
- 
Subjects will be told to have glucose on hand for hypoglycemia 
- 
Subject with persistent hyperglycemia especially if ketones develop will be told they may need to 
change their infusion set if they suspect catheter occlusion or administer insulin with syringe. 
 
Warning:  
Exposure to magnetic fields and radiation: Pump must not be exposed to X-ray, MRI, diathermy 
treatment, CT scan, or other type of devices that generates radiation. The magnetic fields and radiation in 
the immediate vicinity of this equipment can make the device non-functional or damage the part of the 
pump that regulates insulin delivery, possibly resulting in over delivery and severe hypoglycemia. 
The pump must not be exposed to a permanent magnet, such as pump cases that have a magnetic 
clasp. Exposure to a permanent magnet may interfere with the motor inside the pump. 
This device complies with Industry Canada licence-exempt RSS standard(s). Operation is subject to the 
following two conditions: (1) this device may not cause interference, and (2) this device must accept any 
interference, including interference that may cause undesired operation of the device. 
 
Potential risks associated with the use of SmartGuard Feature 
J.2.5
- 
When SmartGuard is turned ON, the feature may not activate when the blood sugar is low. 
- 
When SmartGuard is turned ON, the feature may falsely activate when the subject’s blood sugar is 
not low. 
- 
When SmartGuard is turned ON, it cannot always reduce the severity and duration of hypoglycemia 
(for example over-bolusing with insulin). 
- 
Standard mitigations include: 
- 
Subject instruction to test BG via finger stick testing > 4 times a day. 
- 
Subject instruction to adhere to 100% sensor wear. 
- 
Subject instruction to use the bolus wizard when determining meal or correction bolus. 
 
Potential risks associated with the use of CONTOUR NEXT LINK 2.4 meter 
J.2.6
The risks are not any different than the risk associated with the commercially available meters in Europe. 
For use of the meter, refer to the instructions for use.  
 
All these risks must be continuously monitored, assessed and documented by the investigator in the 
Adverse Event eCRF. 
J.3 Risk-to-benefit rationale 
The results of risk analysis, balancing benefits against risks associated with both the device system itself 
and procedures involved in its use, is included in the Instructions for Use and Investigator’s Brochure. 
The present study devices are all used within their intended use.  
Provided that patients will use the MiniMed 640G system as it is intended to be used in routine practice, 
the anticipated risks for a patient to be in the study is not expected to be higher than in routine practice in 
Europe.  
The patients will be followed with higher frequency of visits, which will allow a closer medical follow-up 
when compared to standard of care.   

 
 
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With the use of continuous glucose monitoring by the patients in treatment group, it is anticipated to see 
a reduction of hypoglycemia. The risks associated with the use of the sensor as described in section 
J.2.1 are often limited to skin irritation. Serious Adverse Events that occurred in past studies involving the 
glucose sensor use were relatively rare. One goal of the run-in phase is to identify patients who would not 
tolerate sensor wear and therefore, they would not be eligible to be randomized into the study. As CGM 
is not reimbursed in all the participating countries, it can be a benefit for patients in the treatment arm to 
have access to this therapy within the course of the study.  
K REFERENCES 
 
[1]  
Bergenstal, «Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes,» N 
Engl J Med, 2010.  
[2]  
Battelino, «The use and efficacy of continuous glucose monitoring in type 1 diabetes treated 
with insulin pump therapy: a randomised controlled trial,» Diabetologia, 2012.  
[3]  
Bergenstal, «Threshold-based insulin-pump interruption for reduction of hypoglycemia,» N 
Engl J Med, 2013.  
[4]  
Choudhary, «Insulin pump therapy with automated insulin suspension in response to 
hypoglycemia: reduction in nocturnal hypoglycemia in those at greatest risk,» Diabetes Care, 
2011.  
[5]  
Ly, «Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs 
standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: A 
randomized clinical trial,» JAMA, 2013.  
[6]  
Agrawal, «Usage and effectiveness of the low glucose suspend feature of the Medtronic 
Paradigm Veo insulin pump,» J Diabetes Sci Technol, 2011.  
[7]  
Agrawal, «Retrospective analysis of the real-world use of the threshold suspend feature of 
sensor-augmented insulin pumps,» Diabetes Technol Ther, 2015.  
[8]  
Buckingham, «Prevention of nocturnal hypoglycemia using predictive alarm algorithms and 
insulin pump suspension,» Diabetes Care, 2010.  
[9]  
DeBock, «Performance of a predictive insulin pump suspension algorithm for prevention of 
overnight hypoglycaemia,» Diabetes, 2014.  
[10] 
Danne, «The PILGRIM Study: In Silico Modeling of a Predictive Low Glucose Management 
System and Feasibility in Youth with Type 1 Diabetes During Exercise,» Diabetes Technol 
Ther, 2014.  
[11] 
Choudhary, «Performance of the predictive low glucose management feature of the MiniMed 
640G system in a user evaluation study. ADA Poster,» Diabetes, p. 64:A27, 2015.  
[12] 
Barkai, «Prospective assessment of severe hypoglycaemia in diabetic children and 
adolescents with impaired and normal awareness of hypoglycaemia,» Diabetologia, 1998.  
[13] 
t. Braak, «Clinical characteristics of type 1 diabetic patients with and without severe 
hypoglycemia,» Diabetes Care, 2000.  
[14] 
Geddes, «Prevalence of impaired awareness of hypoglycaemia in adults with type 1 
diabetes,» Diabet Med, 2008.  
[15] 
Fanelli, «Meticulous prevention of hypoglycemia normalizes the glycemic thresholds and 
magnitude of neuroendocrine responses to, symptoms of, and cognitive function during 
hypoglycemia in intensively treated patients with short-term IDDM.,» Diabetes, 1993.  
[16] 
Cranston, «Restoration of hypoglycaemia awareness in patients with long-duration insulin-
dependent diabetes,» Lancet, 1994.  
[17] 
Li et al., «A sample size adjustment procedure for clinical trials based on conditional power,» 
Biostatistics, 2002.  

 
 
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[18] 
Chen et al., «Increasing the sample size when the unblinded interim result is promising.,» 
Statistics in Medicine, 2004.  
[19] 
Mehta and Pocock, «Adaptive increase in sample size when interim results are promising: A 
practical guide with examples,» Statistics in Medicine, 2011.  
[20] 
ADA, «Standards of Medical Care in Diabetes,» 2015.  
[21] 
Clarke, «Reduced awareness of hypoglycemia in adults with IDDM: a prospective study of 
hypoglycemic frequency and associated symptoms,» Diabetes Care, 1995.  
[22] 
Cox, «Fear of Hypoglycemia: Quantification, Validation, and Utilization,» Diabetes Care, 1987. 
[23] 
Bradley, «The Diabetes Treatment Satisfaction Questionnaire: DTSQ,» Handbook of 
Psychology and Diabetes, 1994.  
[24] 
Bradley, «Diabetes Treatment Satisfaction Questionnaire. Change version for use alongside 
status version provides appropriate solution where ceiling effects occur,» Diabetes Care, 
1999.  
[25] 
Bradley, «Measures of psychological wellbeing and treatment satisfaction developed from the 
responses of people with tablet-treated diabetes,» Diabet Med, 1990.  
[26] 
Howorka, «Dealing with ceiling baseline treatment satisfaction level in patients with diabetes 
under flexible, functional insulin treatment: assessment of improvements in treatment 
satisfaction with a new insulin analogue,» Qual Life Res , 2000.  
[27] 
Bradley, «Diabetes Treatment Satisfaction Questionnaire. Change version for use alongside 
status version provides appropriate solution where ceiling effects occur,» Diabetes Care , 
1999.  
[28] 
Bradley, «The Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) 
evaluated in insulin glargine trials shows greater responsiveness to improvements than the 
original DTSQ,» Health Qual Life Outcomes, 2007.  
[29] 
Ly, «Predictive Low Glucose Insulin Suspension With The Medtronic Predictive Low Glucose 
Management System: Can It Prevent Exercise‐induced Hypoglycemia?,» ATTD Poster, 2013.  
 
L APPENDICES 
L.1 Names and addresses 
 List of contact persons 
L.1.1
Coordinating investigators: 
 
 
 
 
 
 
 
  
 
 
 
 

 
 
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Other contacts 
The names and addresses of sponsor team, monitors, investigators and participating investigational 
centers will be kept under separate cover. These lists will be provided to the participating investigators 
and sponsor shall inform the investigators in case changes occur in the list of participating sites. The 
most current lists of the contact persons (Sponsor List ; Monitors List ; Investigators List) are available 
upon request.  
L.2 Case Report Forms 
The Case Report Form is provided under a separate cover upon request to the Sponsor.  
 
L.3 Sample Investigator Agreement 
Sample Investigator Agreement will be provided under a separate cover upon request to the Sponsor.  
L.4 List of consumables  
INFUSION SETS  EUROPE 
MMT-399 
MiniMed™ Quick-set™ 60cm tubing with 6 mm cannula (box of 10) 
MMT-387 
MiniMed™ Quick-set™ 80cm tubing with 6 mm cannula (box of 10) 
MMT-398 
MiniMed™ Quick-set™110cm tubing with 6 mm cannula (box of 10) 
MMT-397 
MiniMed™ Quick-set™60cm tubing with 9 mm cannula (box of 10) 
MMT-386 
MiniMed™ Quick-set™ 80cm tubing with 9 mm cannula (box of 10) 
MMT-396 
MiniMed™ Quick-set™110cm tubing with 9 mm cannula (box of 10) 
MMT-921/941 
MiniMed™ Mio™ 45cm tubing with 6mm cannula (Pink/Blue) (box of 10) 
MMT-923/943 
MiniMed™ Mio™ 60cm tubing with 6mm cannula (Pink/Blue) (box of 10) 
MMT-965 
MiniMed™ Mio™ 80cm tubing with 6mm cannula (box of 10) 
MMT-975 
MiniMed™ Mio™ 80cm tubing with 9mm cannula (box of 10) 
MMT-368 
MiniMed™ Silhouette™ 45cm tubing with 13mm cannula (box of 10) 
MMT-381 
MiniMed™ Silhouette™ 60cm tubing with 13mm cannula (box of 10) 
MMT-383 
MiniMed™ Silhouette™ 80cm tubing with 13mm cannula (box of 10) 
MMT-382 
MiniMed™ Silhouette™ 110cm tubing with 13mm cannula (box of 10) 
MMT-378 
MiniMed™ Silhouette™ 60cm tubing with 17mm cannula (box of 10) 
MMT-384 
MiniMed™ Silhouette™ 80cm tubing with 17mm cannula (box of 10) 
MMT-377 
MiniMed™ Silhouette™ 110cm tubing with 17mm cannula (box of 10) 
MMT-864 
MiniMed™ Sure-T™ 60cm tubing with 6mm cannula (box of 10) 
MMT-866 
MiniMed™ Sure-T™ 80cm tubing with 6mm cannula (box of 10) 
MMT-874 
MiniMed™ Sure-T™ 60cm tubing with 8mm cannula (box of 10) 
MMT-876 
MiniMed™ Sure-T™ 80cm tubing with 8mm cannula (box of 10) 
MMT-884 
MiniMed™ Sure-T™ 60cm tubing with 10mm cannula (box of 10) 
MMT-886 
MiniMed™ Sure-T™ 80cm tubing with 10mm cannula (box of 10) 
MMT-905 
MiniMed™ Mio™ 30 60cm tubing with 13mm cannula (box of 10) 
MMT-906 
MiniMed™ Mio™ 30 100cm tubing with 13mm cannula (box of 10) 
 
 

 
 
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INFUSION SETS CANADA 
MMT-921600 
MiniMed™ Mio Pink 18” tubing with 6mm cannula (box of 10) 
MMT-941600 
MiniMed™ Mio Blue 18” tubing with 6mm cannula (box of 10) 
MMT-923600 
MiniMed™ Mio Pink 23” tubing with 6mm cannula (box of 10) 
MMT-943600 
MiniMed™ Mio Blue 23” tubing with 6mm cannula (box of 10) 
MMT-965600 
MiniMed™ Mio Clear 32” tubing with 6mm cannula (box of 10) 
MMT-975600 
MiniMed™ Mio Clear 32” tubing with 9mm cannula (box of 10) 
MMT-905600 
MiniMed™ Mio30 23” tubing with 13mm cannula (box of 10) 
MMT-900660 
MiniMed™ Mio30 43” tubing with 13mm cannula (box of 10) 
MMT-394600 
MiniMed™ Quick Set 18” tubing with 6 mm cannula (box of 10) 
MMT-399600 
MiniMed™ Quick Set 23” tubing with 6 mm cannula (box of 10) 
MMT-387600 
MiniMed™ Quick Set 32” tubing with 6 mm cannula (box of 10) 
MMT-398600 
MiniMed™ Quick Set 43” tubing with 6 mm cannula (box of 10) 
MMT-397600 
MiniMed™ Quick Set 23” tubing with 9 mm cannula (box of 10) 
MMT-386600 
MiniMed™ Quick Set 32” tubing with 9 mm cannula (box of 10) 
MMT-396600 
MiniMed™ Quick Set 43” tubing with 9 mm cannula (box of 10) 
MMT-368600 
MiniMed™ Silhouette 18” tubing with 13mm cannula (box of 10) 
MMT-381600 
MiniMed™ Silhouette 23” tubing with 13mm cannula (box of 10) 
MMT-383600 
MiniMed™ Silhouette 32” tubing with 13mm cannula (box of 10) 
MMT-382600 
MiniMed™ Silhouette 43” tubing with 13mm cannula (box of 10) 
MMT-378600 
MiniMed™ Silhouette 23” tubing with 17mm cannula (box of 10) 
MMT-384600 
MiniMed™ Silhouette 32” tubing with 17mm cannula (box of 10) 
MMT-377600 
MiniMed™ Silhouette 43” tubing with 17mm cannula (box of 10) 
MMT-862 
MiniMed™ Sure-T 18” tubing with 6mm cannula (box of 10) 
MMT-864 
MiniMed™ Sure-T 23” tubing with 6mm cannula (box of 10) 
MMT-874 
MiniMed™ Sure-T 23” tubing with 8mm cannula (box of 10) 
 
INFUSION SET  
 
INSERTION DEVICES 
MMT-395 
MiniMed™ Quick-serter™ (for use with Quick Set Infusion Sets) 
MMT-385 
MiniMed™ Sil-serter™ (for use with Silhouette Infusion Sets) 
 
RESERVOIRS 
 
MMT-326A 
1.8 mL reservoirs (box of 10) 
MMT-332A 
3.0 mL reservoirs (box of 10) 
 
OTHERS 
 
ACC-LR6 
AA Battery (Alkaline) 
MMT-174 
Tape HMS-174 ADH IV3000 1-hand 13L 
7005739-006 
Standard tape 
HMS-180 
Skin Tac Adhesive Wipe (box of 50) 
MMT-173 
Skin preparation wipes  
L.5 Sample Questionnaires 
The Clarke, Gold, HFS and DTSQ questionnaires are available in local language and will be provided 
under a separate cover upon request to the Sponsor.   
 
 

 
 
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L.6 Abbreviations 
ADE 
 
Adverse Device Effect 
AE 
 
Adverse event 
CEC 
  
Clinical Events Committee 
AUC 
 
Area Under the Curve 
BG 
 
Blood Glucose  
BP 
 
Blood pressure 
CIP 
 
Clinical Investigation Plan 
C 
 
Control Arm 
CGM 
 
Continuous Glucose Monitoring 
CRF 
 
Case Report Form 
CSII 
 
Continuous Subcutaneous Insulin Infusion 
d  
 
day 
DD 
 
Device Deficiency 
DM 
 
Diabetes Mellitus 
DMC 
 
Data Monitoring Committee 
EC 
 
Ethical Committee  
eCRF 
 
Electronic Case Report Form 
EDC 
 
Electronic Data Capture (Oracle Clinical) 
FDA 
 
Food and Drug Administration 
FU 
 
Follow up 
HFS 
 
Hypoglycemia Fear Survey 
IFU 
 
Instruction For Use 
ICH-GCP 
International Conference on Harmonization – Good Clinical Practice 
IRB  
 
Institutional Review Board  
ISF 
 
Investigator Site File 
m 
 
months 
MAGE  
 
Mean Amplitude Glucose Excursion 
MDD 
 
Medical Device Directive 
MDI 
 
Multiple Daily Injection 
PIC 
 
Patient Informed Consent 
PRO 
 
Patient Reported Outcome 
RA 
 
Regulatory Affairs 
RAE 
 
Regulatory Affairs Europe 
SADE 
 
Serious Adverse Device Effect 
SAE 
 
Serious Adverse Event 
SAP 
 
Sensor Augmented Pump 
SMBG 
 
Self-Monitoring Blood Glucose 
SOP 
 
Standard operating procedure 
T  
 
Treatment arm 
T1DM 
 
Type 1 Diabetes Mellitus 
USADE   
Unanticipated Serious Adverse Device Effect 
w 
 
week 
WECAN  
West Europe and Canada 
yrs 
 
Years