Tandem Freedom - Feasibility Trial 2
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Sponsor: Tandem Diabetes Care, Inc.

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Signature Page 
 Tandem Freedom Feasibility Trial #2 
Protocol Identifying Number: TP-0020402 
Sponsor: Tandem Diabetes Care, Inc. 
Version Number: v1.0 
20 NOV 2024 
Principal Investigator 
 
Name, degree 
Title 
Martin de Bock, FRACP PhD 
Associate Professor, University of Otago, Christchurch 
Signature/Date 
 
Medical Monitor 
 
Name, degree 
Title 
Jordan Pinsker, MD 
Chief Medical Officer, Tandem Diabetes Care 
Signature/Date 
 
Sponsor Representative 
 
Name, degree 
Title 
Ravid Sasson-Katchalski, PhD 
Senior Director, Clinical Affairs, Tandem Diabetes Care 
Signature/Date 
 
 
Martin de Bock (Nov 22, 2024 13:28 GMT+13)
Martin de Bock
Nov 22, 2024
Jordan Pinsker (Nov 21, 2024 16:30 PST)
Jordan Pinsker
Nov 21, 2024
Ravid Katchalski (Nov 21, 2024 16:54 PST)
Ravid Katchalski
Nov 21, 2024

 
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Protocol Revision History 
Version 
Number 
Date 
Brief Description of Changes 
1.0 
20 NOV 2024 
Initial Version 
 
 

 
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TABLE OF CONTENTS 
SITE PRINCIPAL INVESTIGATOR STATEMENT OF COMPLIANCE .............................................................. 7 
CHAPTER 1: BACKGROUND INFORMATION .............................................................................................. 14 
1.1 Introduction ........................................................................................................................................ 14 
1.1.1 Disease Background ..................................................................................................................... 14 
1.1.2 Tandem X2 Insulin Pump and Tandem Freedom Control Algorithm ......................................... 14 
1.2 Rationale ............................................................................................................................................. 14 
1.3 Potential Risks and Benefits ............................................................................................................... 14 
1.3.1 Known Potential Risks ................................................................................................................. 15 
1.3.1.1 Blood Draw .......................................................................................................................... 15 
1.3.1.2 CGM and Pump Catheter Risks ........................................................................................... 15 
1.3.1.3 Hypoglycemia ...................................................................................................................... 15 
1.3.1.4 Risk of Hyperglycemia ........................................................................................................ 15 
1.3.1.5 Risk of Device Reuse ........................................................................................................... 15 
1.3.1.6 Potential Risks of the CLC System ..................................................................................... 16 
1.3.1.7 Other Risks .......................................................................................................................... 16 
1.3.2 Benefits ........................................................................................................................................ 16 
1.3.3 Risk Assessment ........................................................................................................................... 16 
1.4 General Considerations ...................................................................................................................... 16 
CHAPTER 2: STUDY ENROLLMENT AND LEAD-IN PERIOD ...................................................................... 17 
2.1 Participant Recruitment and Enrollment ............................................................................................ 17 
2.1.1 Informed Consent and Authorization Procedures ........................................................................ 17 
2.2 Participant Eligibility Criteria ............................................................................................................ 17 
2.2.1 Inclusion Criteria .......................................................................................................................... 17 
2.2.2 Exclusion Criteria ......................................................................................................................... 17 
2.3 Visit 1: Screening Visit ...................................................................................................................... 18 
2.3.1 Data Collection and Testing ......................................................................................................... 18 
2.4 Screen Failures ................................................................................................................................... 19 
CHAPTER 3: STUDY VISITS ........................................................................................................................ 20 
3.1 Visit 2: Start Control-IQ Run-In ........................................................................................................ 20 
3.2 Visit 3: Hotel Supervised Study for 4 Nights ..................................................................................... 20 
3.2.1 General Guidelines ....................................................................................................................... 20 
3.2.2 Day 1 ............................................................................................................................................ 22 
3.2.3 Days 2 through 4 – Full Days ...................................................................................................... 23 

 
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3.2.4 Day 5 – Morning .......................................................................................................................... 23 
3.3 Unscheduled Visits ............................................................................................................................. 24 
CHAPTER 4: STUDY DEVICES AND DRUGS ................................................................................................ 25 
4.1 Study Devices ..................................................................................................................................... 25 
4.1.1 Insulin Pump ................................................................................................................................ 25 
4.1.2 Continuous Glucose Monitoring .................................................................................................. 25 
4.1.3 Blood Glucose and Ketone Meter ................................................................................................ 25 
4.1.4 Study Device and Drug Accountability Procedures ..................................................................... 25 
4.1.5 Participant Access to Study Device at Study Closure .................................................................. 25 
CHAPTER 5: TESTING PROCEDURES ......................................................................................................... 26 
5.1 Laboratory Testing ............................................................................................................................. 26 
5.1.1 HbA1c .......................................................................................................................................... 26 
5.1.2 Urine Pregnancy ........................................................................................................................... 26 
CHAPTER 6: UNANTICIPATED PROBLEM, ADVERSE EVENT, AND DEVICE ISSUE REPORTING ............. 27 
6.1 Unanticipated Problems ..................................................................................................................... 27 
6.2 Adverse Events ................................................................................................................................... 27 
6.2.1 Definitions .................................................................................................................................... 27 
6.2.2 Reportable Adverse Events .......................................................................................................... 28 
6.2.3 Hypoglycemic Events .................................................................................................................. 29 
6.2.4 Hyperglycemic/Ketotic Events .................................................................................................... 29 
6.2.5 Relationship of Adverse Event to Study Investigational Device ................................................. 30 
6.2.6 Severity (Intensity) of Adverse Events ........................................................................................ 30 
6.2.7 Expectedness ................................................................................................................................ 31 
6.2.8 Coding of Adverse Events ........................................................................................................... 31 
6.2.9 Outcome of Adverse Events ......................................................................................................... 31 
6.3 Reportable Device Issues ................................................................................................................... 31 
6.4 Timing of Event Reporting................................................................................................................. 32 
6.5 Safety Oversight ................................................................................................................................. 32 
6.6 Stopping Criteria ................................................................................................................................ 33 
6.6.1 Participant Discontinuation of Study Device ............................................................................... 33 
6.6.2 Criteria for Suspending or Stopping Overall Study ..................................................................... 33 
CHAPTER 7: MISCELLANEOUS CONSIDERATIONS ................................................................................... 34 
7.1 Drugs Used as Part of the Protocol .................................................................................................... 34 
7.2 Collection of Medical Conditions and Medications ........................................................................... 34 
7.3 Prohibited Medications, Devices, Treatments, and Procedures ......................................................... 34 

 
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7.4 Rescue Medications, Treatments, and Procedures ............................................................................. 34 
7.5 Pregnancy Reporting .......................................................................................................................... 34 
7.6 Participant Compensation................................................................................................................... 34 
7.7 Participant Withdrawal ....................................................................................................................... 34 
CHAPTER 8: STATISTICAL CONSIDERATIONS .......................................................................................... 35 
8.1 General Statistical Considerations...................................................................................................... 35 
8.2 Statistical Hypotheses......................................................................................................................... 35 
8.3 Sample Size ........................................................................................................................................ 35 
8.4 Outcome Measures ............................................................................................................................. 35 
8.5 Baseline Descriptive Statistics ........................................................................................................... 35 
8.6 Additional Tabulations and Analyses................................................................................................. 36 
8.7 Device Issues ...................................................................................................................................... 36 
8.8 Multiple Comparison/Multiplicity ..................................................................................................... 36 
8.9 Handling of Missing Data .................................................................................................................. 36 
CHAPTER 9: DATA COLLECTION AND MONITORING............................................................................... 37 
9.1 Case Report Forms and Other Data Collection .................................................................................. 37 
9.2 Study Records Retention .................................................................................................................... 37 
9.3 Quality Assurance and Monitoring .................................................................................................... 37 
9.4 Protocol Deviations ............................................................................................................................ 38 
CHAPTER 10: ETHICS/PROTECTION OF HUMAN PARTICIPANTS ............................................................ 39 
10.1 Ethical Standard ............................................................................................................................... 39 
10.2 Institutional Review Boards ............................................................................................................. 39 
10.3 Informed Consent Process ................................................................................................................ 39 
10.3.1 Consent Procedures and Documentation ................................................................................... 39 
10.3.2 Participant and Data Confidentiality .......................................................................................... 39 
10.3.3 Future Use of Stored Specimens and Data ................................................................................. 40 
CHAPTER 11: REFERENCES ....................................................................................................................... 41 
 
 

 
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LIST OF ABBREVIATIONS 
 
 
ABBREVIATION 
DEFINITION 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CGM 
Continuous Glucose Monitoring  
CLC 
Closed-Loop Control 
DKA 
Diabetic Ketoacidosis 
eCRF 
Electronic Case Report Form 
GCP 
Good Clinical Practice 
HbA1c 
Hemoglobin A1c 
HDEC 
Health and Disability Ethics Committees 
ICH 
International Conference of Harmonisation 
QC 
Quality Control 
SAE 
Serious Adverse Event 
UADE 
Unanticipated Adverse Device Effect 
 

 
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Site Principal Investigator Statement of Compliance 
Protocol Identifying Number: 
TP-0020402 
Protocol Name: 
Tandem Freedom Feasibility Trial #2 
Protocol Version / Date: 
1.0 / 20 NOV 2024 
 
The Principal Investigators (undersigned) hereby declare that they have read this protocol and 
agree to its contents. 
The investigator agrees that the study will be conducted according to the applicable New Zealand 
regulations (Medsafe and Health and Disability Ethics Committee), International Conference on 
Harmonization (ICH) guidelines on Good Clinical Practice (GCP) and the principles of the 
World Medical Association Declaration of Helsinki 2008. The investigator will conduct all 
aspects of this study in accordance with all national, state, and local laws or regulations. 
By written consent to this protocol, the investigators agree to the above and to fully co-operate 
with all monitoring and audits in relation to this trial by allowing direct access to all 
documentation, including source data, by authorized individuals representing Tandem Diabetes 
Care, Inc., HDEC, Medsafe New Zealand, and/or by the US Federal, State and local regulatory 
authorities. 
 
Investigator Name: ___________________________________________ 
 
Investigator Signature: ________________________________________ 
 
Date (DD/MMM/YYYY): ______________________________________ 
 

 
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PROTOCOL SUMMARY 
Study Sponsor 
Tandem Diabetes Care, Inc. 
Protocol Number 
TP-0020402 
Protocol Title 
Tandem Freedom Feasibility Trial #2 
Précis 
This feasibility study is a prospective, single arm study evaluating the Tandem Freedom 
system compared to a Control-IQ technology run-in phase in adults with type 1 diabetes.  
Existing Control-IQ technology users will use Control-IQ technology at home for 1 week, 
then will use Tandem Freedom in a supervised hotel setting with Dexcom follow active. 
The goal of Tandem Freedom is to use the system without requiring meal boluses. 
Products 
Investigational Device: t:slim X2 insulin pump with Tandem Freedom Algorithm 
Objectives 
The objective of the study is to assess the feasibility of the Tandem Freedom system, by 
assessing safety and performance in a short-term supervised setting in adults with type 1 
diabetes under direct clinical supervision. 
Number of Sites 
1 Clinical Site in New Zealand 
Study Design 
Single arm, prospective feasibility study to assess safety.  
Number of Participants 
Up to 20 participants signing consent to use the study devices, with a goal that at least 10 
complete the study.                                                                                                  
Participant Population: 
Eligibility to enroll in the study will be assessed based on the following inclusion 
criteria: 
1. 
Age ≥18 years old 
2. 
Diagnosis of type 1 diabetes for at least 1 year 
3. 
Current Control-IQ user, having been prescribed Control-IQ for at least 3 months 
4. 
HbA1c ≤ 10%, recorded in the last 3 months 
5. 
Investigator has confidence that the participant can successfully operate all study 
devices and is capable of adhering to the protocol, including performing the hotel 
observed setting portion of the study. 
6. 
Willing to use only aspart (novorapid) or lispro (humalog) insulin with the study 
pump, with no use of long-acting basal insulin injections, or inhaled insulin with 
the study pump. 
Eligibility to enroll in the study will be assessed based on the following exclusion 
criteria:  
1. 
More than 1 episode of diabetic ketoacidosis (DKA) in the past 6 months 
2. 
More than 1 episode of severe hypoglycemia (needing assistance) in the past 6 
months 
3. 
Inpatient psychiatric treatment in the past 6 months  
4. 
For Female: Currently pregnant or planning to become pregnant during the time 
period of study participation 
a. 
A negative pregnancy test will be required for all females of child-
bearing potential 
b. 
Counseling on appropriate birth control options will be provided to all 
females of child-bearing potential 
5. 
Concurrent use of any non-insulin glucose-lowering agent, other than metformin 
(for example, GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, 
sulfonylureas). 
6. 
Hemophilia or any other bleeding disorder 
7. 
Hemoglobinopathy 
8. 
History of heart, liver, lung or kidney disease determined by investigator to 
interfere with the study 

 
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9. 
History of allergic reaction to Humalog or Novorapid 
10. Use of any medications determined by investigator to interfere with study 
11. Significant chronic kidney disease (which could impact continuous glucose 
monitoring (CGM) accuracy in investigator’s judgment) or hemodialysis 
12. Concurrent use of any medication that could interfere with the study CGM, such as 
hydroxyurea 
13. History of adrenal insufficiency 
14. History of abnormal TSH consistent with hypothyroidism or hyperthyroidism that 
is not appropriately treated 
15. History of gastroparesis 
16. A condition, which in the opinion of the investigator or designee, would put the 
participant or study at risk 
17. Participation in another pharmaceutical or device trial at the time of enrollment or 
anticipated for during the time period of study participation 
18. Employed by, or having immediate family members employed by Tandem 
Diabetes Care, Inc., or having a direct supervisor at place of employment who is 
also directly involved in conducting the clinical trial (as a study investigator, 
coordinator, etc.); or having a first-degree relative who is directly involved in 
conducting the clinical trial 
                                                    
Participant Duration 
Approximately 2 weeks 

 
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Study Endpoints 
The two study periods are: 
1) 
Control-IQ run-in period 
2) 
The Tandem Freedom hotel observed period 
 
Primary Endpoints for each period: 
1. 
Number of severe hypoglycemia events (with cognitive impairment such that 
assistance of another individual is needed for treatment) 
2. 
Number of diabetic ketoacidosis events 
 
Secondary Endpoints for each period: 
1. 
All device-related adverse events 
2. 
CGM hypoglycemia outcomes 
a. 
Overall % time <3.0 mmol/L 
b. 
Overall % time <3.9 mmol/L 
3. 
Times in ranges-overall (3.9 - 10.0 mmol/L, >10.0 mmol/L, >13.9 mmol/L, 3.9 - 
7.9 mmol/L) 
4. 
Mean glucose 
5. 
Glycemic variability (CV and SD) 
 
Due to the small sample size and feasibility nature of the study, primarily descriptive 
statistics will be used. 
Protocol Overview/Synopsis 
After consent is signed, eligibility will be assessed.  
 
Run-In Period: 
After eligibility is assessed, participants will be given a study Dexcom G6 sensor, and will 
continue to use their Control-IQ system for 7 +/- 3 days at home. 
Participants will be instructed to bolus for meals as they normally do. 
Participants will be required to change their CGM sensor 48 +/- 12 hours before the hotel 
study. 
 
Hotel Observed Session 
Participants will then be admitted for the hotel observed setting for 4 nights. 
On Day 1, participants will arrive before lunch, where they will bolus for the lunchtime meal 
as per their usual carb ratio and bolus routine with their home pump. 
Participants will be switched the Tandem Freedom system, waiting for at least 2 hours after 
lunch before starting the Freedom system , which uses a t:slim X2 insulin pump and a nearly 
identical interface participants are familiar with from their home pump, but is now running a 
new algorithm that is designed to be used without a requirement for meal boluses.  
Study staff will enable Dexcom follow from participants phones to study medical providers, 
who will also be physically present. 
Study staff will program the Tandem Freedom pump TDI average from the last 7-days as 
shown in their home Control-IQ pump, a sleep schedule, and then enable Tandem Freedom 
for closed-loop. All participants will be encouraged to use TruSteel infusion sets to minimize 
chance of occlusion during the study, 
Participants will bolus for all meals for the remainder of Day 1, entering carbohydrates as 
they would usually estimate and adjusting their overall bolus amount if needed. All boluses 
will be reviewed with study staff. 
On Day 2 - 4, participants will eat meals and snacks as they usually would, but will be 
encouraged to not bolus for any meals. If a user or study staff feel a meal or correction bolus 
is needed, the investigator will make this determination and allow for boluses as they 
determine are needed. 

 
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Participants will be provided 3 meals a day plus may have snacks per their normal routine. 
Participants may adjust their meals per their normal routine. 
Participants will also be encouraged to perform a supervised brisk walk or similar exercise 
of at least 45 minutes each full day (Day 2 to Day 4), at approximately the same time each 
day. Additional exercise per the participants usual routine will be allowed as long as study 
staff are notified. 
On the morning of Day 5, participants will switch back to their home pump and complete 
their participation in the study. 
Study Safety Plan:  
Participants will use their personal blood glucose and ketone meter throughout the study.  
Fingerstick blood glucose readings will be performed in accordance with the study protocol 
and as per CGM manufacturer instructions. 
Ketone readings will be performed per the study protocol. 
Site investigators may reset the TDI derived insulin delivery profile as needed throughout 
the study in accordance with their clinical practice. 
Real-time CGM alerts will be sent to study staff during the inpatient observed hotel phase 
per the study safety guidelines. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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SCHEMATIC OF STUDY DESIGN 
 

 
 
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SCHEDULE OF STUDY VISITS AND PROCEDURES 
1May use prior HbA1c value recorded in the last 3 months. 
2Participants have up to 2 weeks after screening to begin the Control-IQ Run-In Period. 
3Participants will call study staff for any issues related to the protocol or devices during the Control-IQ run in period. 
Visit Number 
1 
2 
3 
 
Screenin
g Visit 
Control-IQ Run-In 
Period2 
7 Days (+/- 3 days) 
Hotel Study for 4 Nights 
Visit (V) or Contact (C) 
V 
C2 
V 
 
Informed Consent 
X 
 
 
Eligibility Assessment 
X 
 
 
Medical history/demographics/ 
physical exam 
X 
 
 
Height, weight, blood pressure and 
pulse 
X 
 
 
HbA1c (point of care or local lab)1 
X 
 
 
Pregnancy test (females of child-
bearing potential) 
X 
 
 
Exercise Challenge 
 
 
Encourage 45 minutes of exercise per day on Days 2 - 4 
AE/Device Issue Assessment 
 
X3 
X 
Upload and Review Device Data 
X 
X 
X 

 
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Chapter 1: Background Information 
1 
1.1 Introduction 
2 
1.1.1 Disease Background 
3 
Type 1 diabetes affects 1.25 million people in the United States. Approximately 70% of individuals with 
4 
type 1 diabetes report poor metabolic control, and do not meet the American Diabetes Association’s 
5 
recommended goal of hemoglobin A1c (HbA1c) level of 7.0%. These findings indicate the need for better 
6 
approaches to type 1 diabetes management. 
7 
1.1.2 Tandem X2 Insulin Pump and Tandem Freedom Control Algorithm 
8 
The Tandem X2 insulin pump with Control-IQ technology is an approved closed-loop control (CLC) 
9 
system. Use of the Control-IQ system has been extensively tested in adults and children with type 1 
10 
diabetes, demonstrating its efficacy and safety when used with insulin lispro (Humalog) or insulin aspart 
11 
(Novorapid).1,2 A recent evaluation of real-world use of the system in 9,451 users age >6 years with at 
12 
least 12 months of system use found results comparable to those found in the randomized trials.3  
13 
A next generation CLC algorithm, the Tandem Freedom System, is now being evaluated to remove the 
14 
burden of meal bolusing. The system is designed to not require meal insulin boluses as part of its design. 
15 
This algorithm is now running in the t:slim X2 insulin pump. 
16 
A prior study with the Tandem Freedom system was completed in the supervised setting in New Zealand 
17 
in June 2024 (NCT06428591). Ten adults with type 1 diabetes (average age 30 years old [range 18 – 64 
18 
years old], duration of diabetes 18 +/- 13 years, total daily insulin 62 +/- 23 units/day [range 28 – 106 
19 
units/day], current Control-IQ users for 1.4 +/- 0.5 years, HbA1c 6.8 +/- 0.7% [range 6.0 – 7.9] completed 
20 
the study. After a Control-IQ run-in period at home, participants were admitted to the hotel for the 
21 
supervised study, where they used the Tandem Freedom system first with boluses for one day, then 
22 
without boluses for one, eating large meals and performing exercise each day. 
23 
The study showed participants achieved 61.8% time in range 3.9-10.0 mmol/L at home using Control-IQ 
24 
technology during the run-in week, 82.4% time in range 3.9-10.0 mmol/L using Freedom for 24 hours 
25 
with boluses, and 54.7% time in range 3.9-10.0 mmol/L using Freedom for 24 hours without meal 
26 
boluses. There were no severe hypoglycemia or DKA events, and no serious adverse events. As 
27 
participants were able to achieve nearly the same time in range without bolusing with Freedom as they 
28 
achieved with bolusing with Control-IQ, the results from this study support continued development and 
29 
evaluation in a second study. 
30 
1.2 Rationale 
31 
The objective of this study is to assess the feasibility of the Tandem Freedom system, by assessing safety 
32 
and performance in a short-term supervised second feasibility study. The study will occur in a supervised, 
33 
hotel setting with medical staff present, with existing Control-IQ users with type 1 diabetes already 
34 
familiar with the t:slim X2 insulin pump, to further determine how Tandem Freedom functions with 
35 
unbolused meals and exercise. 
36 
1.3 Potential Risks and Benefits 
37 
Risks and Benefits are detailed below. Loss of confidentiality is a potential risk; however, data are 
38 
handled to minimize this risk. Hypoglycemia, hyperglycemia and ketone formation are always a risk in 
39 
participants with type 1 diabetes and participants will be monitored for these events. As all participants 
40 

 
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will be existing Control-IQ users, and familiar with infusion set care and pump use, this helps to minimize 
41 
risk. 
42 
1.3.1 Known Potential Risks 
43 
1.3.1.1 Blood Draw 
44 
A venipuncture and/or fingerstick will be performed to obtain blood for HbA1c measurement. 
45 
Venipuncture can cause common reactions like pain, bruising, or redness at the sampling site. 
46 
Less common reactions include bleeding from the sampling site, formation of a small blood clot or 
47 
swelling of the vein and surrounding tissues, and fainting. A fingerstick frequently causes transient pain 
48 
and there may be a small, localized bruise, which may be followed by a small scar that may persist for 
49 
several weeks. The risk of local infection is less than 1 in 1000 with either venipuncture or fingerstick. 
50 
1.3.1.2 CGM and Pump Catheter Risks 
51 
There is a small risk of bleeding where the sensor or infusion set is inserted. There is a small risk for 
52 
developing a local skin infection at the site of Continuous Glucose Monitoring (CGM) sensor placement 
53 
and at the pump infusion set placement. This may be associated with swelling, redness and pain; and may 
54 
require antibiotic therapy. Rarely, a CGM sensor may break and leave a small portion of the sensor under 
55 
the skin that may cause redness, swelling or pain at the insertion site. 
56 
Some participants may develop skin irritation or allergic reactions to the adhesives used to secure the 
57 
CGM, or to secure the insulin infusion sets for the continuous subcutaneous insulin infusion. If these 
58 
reactions occur, different adhesives or “under-taping” (such as with IV 3000, Tegaderm, etc.) will be 
59 
tried, sites will be rotated frequently, and a mild topical steroid cream or other medication may be 
60 
required.  
61 
1.3.1.3 Hypoglycemia 
62 
As with any person having type 1 diabetes and using insulin, there is always a risk of having 
63 
hypoglycemia. The frequency of hypoglycemia should be no more and possibly less than it would be 
64 
as part of daily living. Symptoms of hypoglycemia can include sweating, jitteriness, and not feeling well. 
65 
There is the possibility of fainting or seizures (convulsions) and that for a few days the participant may 
66 
not be as aware of symptoms of hypoglycemia. A CGM functioning poorly and significantly over-
67 
reading glucose values could lead to inappropriate insulin delivery. The study exercise challenges could 
68 
increase the risk of hypoglycemia. 
69 
1.3.1.4 Risk of Hyperglycemia 
70 
Hyperglycemia and ketonemia could occur if insulin delivery is attenuated or suspended for an 
71 
extended period or if the pump or infusion set is not working properly. A CGM functioning poorly 
72 
and significantly under-reading glucose values could lead to inappropriate suspension of insulin delivery. 
73 
Not performing premeal insulin boluses in the hotel setting could increase the risk of hyperglycemia. 
74 
Encouraging participants to use TruSteel infusion sets in the study will minimize the risk of 
75 
hyperglycemia from occlusions. 
76 
1.3.1.5 Risk of Device Reuse 
77 
All devices will be used by a single study participant only. There will be no device reuse. 
78 

 
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1.3.1.6 Potential Risks of the CLC System 
79 
Even though the study system has been tested prior to this study, including completion of a prior 10 
80 
participant first in human study, there is still a risk that parts of the system may not function properly. The 
81 
following are possible reasons the system may deliver too much insulin or incorrectly stop insulin 
82 
delivery: 
83 
• 
CGM sensor reads higher or lower than the actual glucose level which increases risk for 
84 
hypoglycemia and hyperglycemia with automated insulin delivery system; 
85 
• 
Device malfunctions that could produce a suspension of insulin delivery or over delivery of insulin. 
86 
1.3.1.7 Other Risks 
87 
Data downloaded from pump (to include CGM values) will be collected for the study. The downloaded 
88 
data from the participant’s home devices at the screening visit may include data from the period beyond 
89 
the last 2 weeks prior to screening, but will be de-identified. Data from the home glucose and ketone 
90 
meters will be reviewed for adverse events only, and an export of those devices is not required for the 
91 
study. Some people may be uncomfortable with the researchers' having such detailed information about 
92 
their daily diabetes habits. 
93 
1.3.2 Benefits 
94 
Participants may achieve better glucose control than they are currently achieving using their home insulin 
95 
pump.  
96 
The individual participant may not benefit from study participation. 
97 
1.3.3 Risk Assessment 
98 
Based on the facts that (1) individuals with diabetes experience mild hypoglycemia and hyperglycemia 
99 
frequently as a consequence of the disease and its management, (2) mitigations are in place, including 
100 
direct medical supervision in the hotel setting and all participants are current Control-IQ users, that limit 
101 
the likelihood of excessive insulin dosing or prolonged withdrawal of insulin, and (3) rapid reversal of 
102 
hypoglycemia and hyperglycemia can be achieved, it is the assessment of the Sponsor that this protocol is 
103 
an investigation involving a minor increase over minimal risk. In addition, it is the belief of the Sponsor 
104 
that this study also presents prospect of direct benefit to the participants and general benefit to others with 
105 
diabetes. 
106 
1.4 General Considerations 
107 
The study is being conducted in compliance with the ethical principles that have their origin in the 
108 
Declaration of Helsinki, with the protocol described herein, and with the standards of Good Clinical 
109 
Practice (GCP). 
110 
Per Medsafe guidelines Part 11, the investigator device (Tandem Freedom System) in the study will be 
111 
labelled “To be used by qualified investigators only”. 
112 
 
113 

 
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Chapter 2: Study Enrollment and Lead-in Period 
114 
2.1 Participant Recruitment and Enrollment 
115 
Enrollment will proceed with the goal of having up to 20 participants screened, so that at least 10 
116 
complete the study. 
117 
All participants will be existing Control-IQ users to assure familiarity with the t:slim X2 insulin pump. 
118 
Study participants will be recruited from a single clinical center as a convenience sample. 
119 
2.1.1 Informed Consent and Authorization Procedures 
120 
Potential eligibility may be assessed as part of a routine-care examination. Before completing any 
121 
procedures or collecting any data that are not part of usual care, written informed consent will be 
122 
obtained. 
123 
For potential study participants, the study protocol will be discussed with the potential study participant 
124 
by study staff. The potential study participant will be given the Informed Consent Form to read. Potential 
125 
study participants will be encouraged to discuss the study with family members and their personal 
126 
physicians(s) before deciding whether to participate in the study.  
127 
A copy of the consent form will be provided to the participant, and another copy will be added to the 
128 
participant’s study record. 
129 
A participant is considered enrolled when the informed consent form has been signed. 
130 
2.2 Participant Eligibility Criteria 
131 
2.2.1 Inclusion Criteria 
132 
Individuals must meet all of the following inclusion criteria in order to be eligible to participate in the 
133 
study. 
134 
1. Age ≥18 years old 
135 
2. Diagnosis of type 1 diabetes for at least 1 year 
136 
3. Current Control-IQ user, having been prescribed Control-IQ for at least 3 months 
137 
4. HbA1c ≤ 10% 
138 
5. Investigator has confidence that the participant can successfully operate all study devices and is 
139 
capable of adhering to the protocol, including performing the hotel observed setting portion of the 
140 
study. 
141 
6. Willing to use only aspart (novorapid) or lispro (humalog) insulin with the study pump, with no 
142 
use of long-acting basal insulin injections, or inhaled insulin with the study pump. 
143 
2.2.2 Exclusion Criteria 
144 
Individuals meeting any of the following exclusion criteria at baseline will be excluded from study 
145 
participation. 
146 
1. More than 1 episode of diabetic ketoacidosis (DKA) in the past 6 months 
147 
2. More than 1 episode of severe hypoglycemia (needing assistance) in the past 6 months 
148 
3. Inpatient psychiatric treatment in the past 6 months  
149 

 
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4. For Female: Currently pregnant or planning to become pregnant during the time period of study 
150 
participation 
151 
a. A negative pregnancy test will be required for all females of child-bearing potential 
152 
b. Counseling on appropriate birth control options will be provided to all females of child-
153 
bearing potential 
154 
5. Concurrent use of any non-insulin glucose-lowering agent, other than metformin (for example, 
155 
GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas). 
156 
6. Hemophilia or any other bleeding disorder 
157 
7. Hemoglobinopathy 
158 
8. History of heart, liver, lung or kidney disease determined by investigator to interfere with the 
159 
study 
160 
9. History of allergic reaction to Humalog or Novorapid 
161 
10. Use of any medications determined by investigator to interfere with study 
162 
11. Significant chronic kidney disease (which could impact CGM accuracy in investigator’s 
163 
judgment) or hemodialysis 
164 
12. Concurrent use of any medication that could interfere with the study CGM, such as hydroxyurea 
165 
13. History of adrenal insufficiency 
166 
14. History of abnormal TSH consistent with hypothyroidism or hyperthyroidism that is not 
167 
appropriately treated 
168 
15. History of gastroparesis 
169 
16. A condition, which in the opinion of the investigator or designee, would put the participant or 
170 
study at risk 
171 
17. Participation in another pharmaceutical or device trial at the time of enrollment or anticipated for 
172 
during the time period of study participation 
173 
18. Employed by, or having immediate family members employed by Tandem Diabetes Care, Inc., or 
174 
having a direct supervisor at place of employment who is also directly involved in conducting the 
175 
clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is 
176 
directly involved in conducting the clinical trial 
177 
2.3 Visit 1: Screening Visit 
178 
After informed consent has been signed, a potential participant will be evaluated for study eligibility 
179 
through the elicitation of a medical history, performance of a physical examination by study personnel 
180 
and local laboratory testing if needed to screen for exclusionary medical conditions. 
181 
2.3.1 Data Collection and Testing 
182 
A standard physical exam (including vital signs and height and weight measurements) will be performed 
183 
by the study investigator or designee (study nurse). Height, weight and vital signs may be recorded by 
184 
appropriately delegated office staff. 
185 
The following procedures will be performed/data collected/eligibility criteria checked and documented: 
186 
• 
Inclusion and exclusion criteria assessed 
187 
• 
Demographics (age, sex, ethnicity and socioeconomic information) 
188 

 
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• 
Participant initials to verify electronic case report form (eCRF) entry is associated with the correct 
189 
individual  
190 
• 
Contact information (retained at the site and not entered into study database) 
191 
• 
Medical history 
192 
• 
Concomitant medications 
193 
• 
Physical examination to include: 
194 
 
Weight, height 
195 
 
Vital signs including measurement of blood pressure and pulse 
196 
• 
Blood draw (venipuncture or fingerstick) for local HbA1c measurement 
197 
• 
Urine pregnancy test for all females of childbearing potential who are premenopausal and not 
198 
surgically sterile 
199 
• 
Current device download of the participant’s home insulin pump (with included CGM device data), 
200 
for up to the last two weeks of data if available. Site will also record average total daily dose, average 
201 
percent basal, and average percent bolus insulin from the last 2 weeks. 
202 
Screening procedures will last approximately 1-2 hours. The screening visit must occur in clinic and 
203 
cannot be performed remotely. 
204 
2.4 Screen Failures 
205 
Individuals who do not initially meet study eligibility requirements may be rescreened one more time at a 
206 
later date per investigator discretion. 
207 
 
208 

 
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Chapter 3: Study Visits 
209 
3.1 Visit 2: Start Control-IQ Run-In 
210 
After screening, participants will have a clinic visit at which they will be given the study CGM (Dexcom 
211 
G6) and begin the run-in period. The run-in period will be 7 +/- 3 days. 
212 
This device training visit should be completed within 2 weeks of screening, and may be performed the 
213 
same day as the screening visit. If not completed within 2 weeks of screening, re-review of screening 
214 
results by the investigator should be performed, who may ask for repeated testing as per investigator 
215 
judgement. The device training visit must occur in clinic and cannot be performed remotely. 
216 
Participants will receive additional supplies for blood glucose and ketone testing if needed.  
217 
Participants will continue to use their home insulin pump (t:slim X2 insulin pump with Control-IQ 
218 
technology) during the run-in phase. Participants will switch the CGM to the study provided CGM sensor 
219 
and transmitter. 
220 
Participants may contact study providers at any time for questions during the Control-IQ Run-In period.  
221 
Participants will be required to change their CGM sensor 48 +/- 12 hours before the hotel study. 
222 
3.2 Visit 3: Hotel Supervised Study for 4 Nights 
223 
3.2.1 General Guidelines 
224 
Upon arrival, the following procedures will be performed: 
225 
• Current device download of the participant’s home insulin pump (with included CGM device data). Site 
226 
will record average total daily dose, average percent basal, and average percent bolus insulin from the last 
227 
7 days from the pump screen. 
228 
• Assessment of device issues that have occurred. 
229 
• Assessment of adverse events, using open ended questions to capture hyperglycemic and hypoglycemic 
230 
events during the Run-In Phase.  
231 
On Day 1, participants will arrive before lunch, where they will bolus for the lunchtime meal as per their 
232 
usual carb ratio and bolus routine with their home pump. 
233 
Participants will be switched the Tandem Freedom system, waiting for at least 2 hours after lunch before 
234 
starting the Freedom pump (Investigational Device).  
235 
Study staff will use the TDI from the last 7 days as shown on the participants home pump to initialize the 
236 
system, although they may adjust this value per clinical judgement, and re-initialize the system based on 
237 
an updated TDI use at any time during the study.  
238 
A sleep schedule will be set from 11 PM to 6 AM so sleep activity automatically activates in the evening 
239 
and deactivates in the morning. 
240 
During this phase of the study, participants will be monitored in person by study staff, and remotely 
241 
monitored by the study team with Dexcom Follow, 24 hours per day. Pump and CGM alerts will be set to 
242 
annunciate throughout the study. Dexcom follow alerts will be sent to study staff for CGM values <3.9 
243 
mmol/L mg/dL and >16.7 mmol/L mg/dL at any time. 
244 
Participants will be provided 3 meals a day plus may have snacks per their normal routine. Participants 
245 
may adjust their meals per their normal routine. 
246 

 
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Food diary showing the start time of all meals, as well as the number of carbohydrates, fat and protein 
247 
consumed, will be recorded by study staff. 
248 
During the hotel study, the following hyper and hypoglycemic treatment plan will be used: 
249 
Table 1. Hypoglycemia and Hyperglycemia Prevention and Treatment Plan during the supervised, hotel 
250 
study. 
251 
Condition  
Action Taken  
CGM reading <3.9 mmol/L 
A confirmatory fingerstick measurement will be 
performed.  
If fingerstick glucose ≥3.9 mmol/L, and participant is not 
having any symptoms, no treatment is required. However, 
treatment may be initiated by the investigator 
(recommended ~4-16 g fast acting carbohydrate, but may 
be adjusted per investigator discretion). Participants will 
then perform a follow-up fingerstick measurement 10 to 
15 minutes after treatment if CGM <3.9 mmol/L mg/dL.  
If fingerstick glucose <3.9 mmol/L, treatment will be 
initiated by the investigator (recommended ~4-16 g fast 
acting carbohydrate, but may be adjusted per investigator 
discretion). Participants will then perform a follow-up 
fingerstick measurement 10 to 15 minutes after treatment 
if CGM <3.9 mmol/L.  
This protocol will be repeated until CGM is ≥ 3.9 mmol/L 
or the fingerstick is ≥3.9 mmol/L per standard clinical 
treatment for hypoglycemia. 
Any time a participant has subjective 
symptoms of hypoglycemia  
A fingerstick blood glucose measurement will be 
performed. Fast-acting carbohydrates may be given to any 
participant who is symptomatic or requests treatment, 
even before a confirmatory fingerstick is performed.  
CGM reading is >16.7 mmol/L for more 
than 2 hours 
A confirmatory fingerstick measurement will be 
performed.  
If the participant ’s BG is confirmed to be >16.7 mmol/L, 
then ketones will be checked using the study-approved 
ketone meter. 
BG confirmed >16.7 mmol/L mg/dL for 
more than 2 hours and ketones are <0.6 
mmol/L 
A manual correction bolus may be delivered via the pump 
if BG is not beginning to trend downward, but this may be 
adjusted as per investigator discretion, based on insulin-
on-board and clinical judgement. Fingerstick BG and 
ketone measurements will be repeated after 1 hour. If a 
correction dose of insulin is given, the dose may be 
adjusted by the investigator. 
If BG fails to decrease by a minimum of 2.8 mmol/L in 1 
hour after a correction dose is given, then study staff will 

 
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252 
Meal boluses and all interaction with the pump will be supervised by study staff to ensure that the correct 
253 
number of carbohydrate grams are entered into the bolus calculator and the correct dose is given. 
254 
When meal boluses are given, participants will give the bolus per their usual meal bolus timing, but not 
255 
more than 15 minutes before the meal. 
256 
At least one member of the study medical staff (Physician, NP, PA, or other qualified clinician) will 
257 
always be present on site. 
258 
During the study session, participants may change our their study sensor or their infusion site as needed 
259 
per their usual care. Participants will be encouraged to use TruSteel infusion sets for the duration of the 
260 
study. 
261 
Insulin and glucose data from the screening visit, as well as follow up visits and at the start of the hotel 
262 
session, will be reviewed and the site investigator may adjust insulin delivery profile settings as needed in 
263 
accordance with their clinical practice. 
264 
3.2.2 Day 1 
265 
Following the Control-IQ run-in phase, participants will commence the hotel supervised phase.  
266 
replace the participant’s infusion set with a new infusion 
set and the correction bolus will be repeated, per the 
investigator’s discretion. The decision to change out the 
infusion set and giving a correction dose may adjusted per 
investigator discretion, based on insulin-on-board and 
clinical judgement. 
BG confirmed >16.7 mmol/L for more 
than 2 hours and ketones are ≥0.6 mmol/L 
A manual correction bolus may be delivered via injection 
to assure proper absorption in the setting of likely infusion 
set failure. The decision to give a manual correction bolus 
by injection may be adjusted by investigator discretion, 
based on insulin-on-board and clinical judgement.  
Fingerstick BG and ketone measurements will be repeated 
after approximately 1 hour.  
After a manual correction bolus, the study staff will 
replace the participant’s infusion set, if they believe it is 
contributing to the hyperglycemia, with a new infusion set 
and the correction bolus will be repeated per the 
investigator’s discretion. Closed loop will be disabled by 
the investigator for the next 4 hours and until BG has 
returned to <10 mmol/L.  
Participant loses consciousness or has a 
seizure, or participant is unable to take oral 
carbohydrates  
1 mg of IM glucagon or 3 mg nasal glucagon will be 
administered and 111 will be called. The study will be 
stopped immediately until sponsor conducts a full 
investigation to determine the root cause for the 
compromised system performance and is able to address 
all issues. Sponsor will also communicate the results of 
this root cause investigation to regulatory bodies and to 
study investigators.  

 
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On Day 1, participants will arrive before lunch, where they will bolus for the lunchtime meal as per their 
267 
usual carb ratio and bolus routine with their home pump. 
268 
Participants will be switched the Tandem Freedom system and be encouraged to use the TruSteel infusion 
269 
set, waiting for at least 2 hours after lunch before starting the Freedom pump (Investigational Device).  
270 
Study staff will use the TDI from the last 7 days as shown on the participants home pump to initialize the 
271 
system, although they may adjust this value per clinical judgement, and re-initialize the system based on 
272 
an updated TDI at any time during the study.  
273 
A sleep schedule will be set from 11 PM to 6 AM so sleep activity automatically activates in the evening 
274 
and deactivates in the morning. 
275 
Participants will bolus for all meals for the remainder of Day 1, entering carbohydrates as they would 
276 
usually estimate and adjusting their overall bolus amount if needed.  
277 
Participants may perform low-intensity activity (e.g., walking) at any time during day 1. 
278 
No meals should occur after sleep activity is enabled. 
279 
3.2.3 Days 2 through 4 – Full Days 
280 
Sleep activity will be disabled upon waking up if not already automatically de-activated per the sleep 
281 
schedule. 
282 
On Days 2 - 4, participants will eat meals and snacks as they usually would, but will be encouraged to 
283 
NOT BOLUS for all meals and snacks. If a user or study staff feel a meal or correction bolus is needed, 
284 
the investigator will make this determination and allow for boluses as they determine are needed. 
285 
Participants will also be encouraged to perform a supervised brisk walk or similar exercise of at least 45 
286 
minutes each full day (Day 2 to Day 4) under staff supervision, at approximately the same time each day. 
287 
Additional exercise per the participants usual routine will be allowed as long as study staff are notified. 
288 
Exercise activity should be used for this exercise, to start 30-90 minutes before exercise, and turned off 
289 
after exercise is complete, as determined by the investigator.  
290 
Exercise does not have to be performed, but will be encouraged. Exercise will be cancelled or stopped at 
291 
any point for injury or development of new symptoms (development of chest pain/pressure, feeling 
292 
unwell, development of hypoglycemic symptoms, undue shortness of breath, signs of poor perfusion (leg 
293 
pain/claudication), or any other symptoms, as determined by the investigator.  
294 
Participants may perform low-intensity activity (e.g., walking) at any time during the hotel study. 
295 
Supervised outings may occur with study staff present to areas outside of the hotel during the daytime. 
296 
Realtime CGM alerts will remain in place, and the same hypoglycemia/hyperglycemia treatment 
297 
guidelines apply as in the hotel setting. 
298 
No meals should occur after sleep activity is enabled. 
299 
3.2.4 Day 5 – Morning 
300 
Sleep activity will be disabled upon waking up if not already automatically de-activated per the sleep 
301 
schedule. 
302 
After waking up, participants will switch back to their home Control-IQ pump, and may have breakfast 
303 
prior to leaving the hotel. 
304 
Participants may be discharged if their CGM is ≥4.4 mmol/L for at least 15 minutes. 
305 

 
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3.3 Unscheduled Visits 
306 
Participants may have unscheduled visits during the study run-in period if required for additional 
307 
questions or other unanticipated needs per the study investigator discretion. 
308 
At each contact, study staff will perform an: 
309 
• Assessment of device issues that have occurred 
310 
• Assessment of adverse events, using open ended questions to capture hyperglycemic and hypoglycemic 
311 
events during the Run-In Phase.  
312 

 
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Chapter 4: Study Devices and Drugs 
313 
4.1 Study Devices 
314 
4.1.1 Insulin Pump 
315 
For the hotel supervised session, participants will use the study provided Tandem t:slim X2 insulin pump 
316 
with the Tandem Freedom System/algorithm (Investigational Device). 
317 
4.1.2 Continuous Glucose Monitoring 
318 
The study CGM is the commercial version of the Dexcom G6 (Dexcom, Inc), which includes a 
319 
transmitter and sensors. The CGM sensor will be replaced at least once every 10 days. 
320 
4.1.3 Blood Glucose and Ketone Meter 
321 
For blood glucose and ketone testing, participants will use their home meter, the CareSens Dual Blood 
322 
Glucose and Ketone Testing Monitor (i-SENS, Inc). 
323 
Blood glucose levels will be measured using the blood glucose meter (glucometer) and the CGM device 
324 
will be calibrated if needed using the glucometer and strips in accordance with the manufacturer’s 
325 
labeling. 
326 
Blood ketone levels will be measured when needed to evaluate prolonged hyperglycemia. 
327 
4.1.4 Study Device and Drug Accountability Procedures 
328 
Device accountability and inventory will be documented to include detailed inventory records of the study 
329 
CGM supplies, and Tandem insulin pump system. 
330 
4.1.5 Participant Access to Study Device at Study Closure 
331 
Participant will return the investigational study device (insulin pump) at study closure. Participant may 
332 
keep any extra ketone and glucose testing strips they were issued, and any issued remaining pump and 
333 
CGM supplies that are not marked for investigational use. 
334 

 
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Chapter 5: Testing Procedures 
335 
5.1 Laboratory Testing 
336 
5.1.1 HbA1c 
337 
HbA1c measurement will be performed locally in clinic or at a laboratory at the screening visit if no prior 
338 
HbA1c measurement is available from the last 3 months. 
339 
5.1.2 Urine Pregnancy 
340 
Urine pregnancy testing performed locally at clinical site for females of child-bearing potential at the 
341 
screening visit, and anytime pregnancy is suspected. 
342 

 
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Chapter 6: Unanticipated Problem, Adverse Event, and 
343 
Device Issue Reporting 
344 
6.1 Unanticipated Problems 
345 
Site investigators will promptly report to the Sponsor on an eCRF all unanticipated problems meeting the 
346 
criteria below. For this protocol, an unanticipated problem is an incident, experience, or outcome that 
347 
meets all of the following criteria: 
348 
• 
Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are 
349 
described in the protocol related documents, such as the HDEC (Health and Disability Ethics 
350 
Committees)-approved research protocol and informed consent document; and (b) the characteristics 
351 
of the subject population being studied 
352 
• 
Related or possibly related to participation in the research (possibly related means there is a 
353 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
354 
procedures involved in the research) 
355 
• 
Suggests that the research places participants or others at a greater risk of harm than was previously 
356 
known or recognized (including physical, psychological, economic, or social harm) 
357 
The Sponsor will report to the appropriate regulatory authorities if the event meets the criteria of an 
358 
Unanticipated Problem requiring additional reporting. 
359 
6.2 Adverse Events 
360 
6.2.1 Definitions 
361 
Adverse Event (AE): Any untoward medical occurrence (including laboratory findings) associated with 
362 
study procedures, the use of a device, biologic in a study participant, including any comparator used, 
363 
irrespective of the relationship between the adverse event and the device(s) under investigation (referred 
364 
to as Adverse Reaction when caused by a drug). 
365 
Serious Adverse Event (SAE): Any untoward medical occurrence that meets at least one of the following: 
366 
• 
Results in death. 
367 
• 
Is life-threatening; (a non-life-threatening event which, had it been more severe, might have become 
368 
life-threatening, is not necessarily considered a serious adverse event). 
369 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
370 
• 
Results in persistent or significant disability/incapacity or substantial disruption of the ability 
371 
to conduct normal life functions (sight threatening). 
372 
• 
Is a congenital anomaly or birth defect. 
373 
• 
Is considered a significant medical event by the investigator based on medical judgment (e.g., may 
374 
jeopardize the participant or may require medical/surgical intervention to prevent one of the outcomes 
375 
listed above). 
376 
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety or any 
377 
life -threatening problem or death caused by, or associated with, a device, if that effect, problem, or death 
378 
was not previously identified in nature, severity, or degree of incidence in the investigational plan or 
379 
application (including a supplementary plan or application), or any other unanticipated serious problem 
380 
associated with a device that relates to the rights, safety, or welfare of participants (21 CFR 812.3(s)). 
381 

 
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Adverse Device Effect (ADE): Any untoward medical occurrence in a study participant which the device 
382 
may have caused or to which the device may have contributed (Note that an Adverse Event Form is to be 
383 
completed in addition to a Device Issues Form, unless excluded from reporting as defined in section 
384 
6.2.2). 
385 
Comparator: Medical device, therapy (e.g. active treatment, normal clinical practice), placebo or no 
386 
treatment, used in the control group in a clinical investigation. (ISO 14155:2020) 
387 
Device Complaints and Malfunctions: A device malfunction or complaint is something that happens 
388 
to a device or related to device performance, whereas an adverse event happens to a participant. A device 
389 
complaint may occur independently from an AE, or along with an AE. An AE may occur without a 
390 
device complaint or there may be an AE related to a device complaint. A device malfunction is any 
391 
failure of a device to meet its performance specifications or otherwise perform as intended. 
392 
Performance specifications include all claims made in the labeling for the device. The intended 
393 
performance of a device refers to the intended use for which the device is labeled or marketed. 
394 
(21 CFR 803.3). Note: for reporting purposes, sites will not be asked to distinguish between device 
395 
complaints and malfunctions. 
396 
Use Error: User action or lack of user action while using the medical device that leads to a different result 
397 
than that intended by the manufacturer or expected by the user. Includes the inability of the user to 
398 
complete a task. Use errors can result from a mismatch between the characteristics of the user, user 
399 
interface, task or use environment. Users might be aware or unaware that a use error has occurred. An 
400 
unexpected physiological response of the patient is not by itself considered a use error. A malfunction of 
401 
a medical device that causes an unexpected result is not considered a use error. (ISO 14155:2020) 
402 
6.2.2 Reportable Adverse Events 
403 
A reportable adverse event includes all events meeting the definition of an adverse event, except for the 
404 
following: 
405 
• 
Hypoglycemia and hyperglycemia not meeting the criteria below will not be recorded as adverse 
406 
events unless associated with an Adverse Device Effect or discontinuation of the study device.  
407 
• 
Skin reactions from sensor or pump infusion set placement are only reportable if severe and/or 
408 
required treatment. 
409 

 
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All reportable AEs—whether volunteered by the participant, discovered by study personnel during 
410 
questioning, or detected through physical examination, laboratory test, or other means—will be reported 
411 
on an AE form online. Each AE form is reviewed by the Medical Monitor to assess safety and to verify 
412 
the coding and the reporting that is required. 
413 
6.2.3 Hypoglycemic Events 
414 
Hypoglycemia is only reportable as an adverse event when one of the following criteria is met: 
415 
• 
a hypoglycemic event occurred meeting the following definition of severe hypoglycemia: the event 
416 
required assistance of another person due to altered consciousness, and required another person to 
417 
actively administer carbohydrate, glucagon, or other resuscitative actions. This means that the 
418 
participant was impaired cognitively to the point that he/she was unable to treat himself/herself, was 
419 
unable to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or experienced 
420 
seizure or loss of consciousness. These episodes may be associated with sufficient neuroglycopenia to 
421 
induce seizure or loss of consciousness. If glucose measurements are not available during such an 
422 
event, neurological recovery attributable to the restoration of glucose to normal is considered 
423 
sufficient evidence that the event was induced by a low glucose concentration. 
424 
• 
evaluation or treatment was obtained at a health care provider facility for an acute event involving 
425 
hypoglycemia, or the participant contacted the site and received guidance following the occurrence of 
426 
an acute event involving hypoglycemia 
427 
When a severe hypoglycemia event occurs (as defined above), an Adverse Event Form should be 
428 
completed. Severe hypoglycemia events should be considered to be serious adverse events with respect to 
429 
reporting requirements. When a severe hypoglycemia event occurs during use of a study device, it 
430 
generally will be considered to be unrelated to the device (per section 6.2.5) if the device functioned as 
431 
intended and there does not appear to be a flaw in how the device is intended to function. 
432 
6.2.4 Hyperglycemic/Ketotic Events 
433 
Hyperglycemia is only reportable as an adverse event when one of the following criteria is met:   
434 
• 
the event involved DKA, as defined by the Diabetes Control and Complications Trial (DCCT) and 
435 
described below 
436 
• 
evaluation or treatment was obtained at a health care provider facility for an acute event involving 
437 
hyperglycemia or ketosis, or the participant contacted the site and received guidance on how to 
438 
manage the hyperglycemia/ketosis 
439 
• 
blood ketone level ≥1.0 mmol/L, even if there was no communication with a health care provider at 
440 
the time of the event 
441 
Hyperglycemic events are classified as DKA if all of the following are present, or judged likely to have 
442 
been present based on available data: 
443 
• 
Symptoms such as polyuria, polydipsia, nausea, or vomiting; 
444 
• 
Serum ketones >1.5 mmol/L or large/moderate urine ketones; 
445 
• 
Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate (or CO2) <15; and 
446 
• 
Treatment provided in a health care facility 
447 
When a hyperglycemia/ketotic event qualifies as an AE, or as a SAE as defined in section 6.2.1, an 
448 
Adverse Event Form should be completed. Events meeting DKA criteria should be considered to be 
449 
serious adverse events with respect to reporting requirements. Hyperglycemia events not meeting criteria 
450 

 
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for DKA generally will not be considered as serious adverse events unless one of the SAE criteria in 
451 
section 6.2.1 is met. 
452 
When a hyperglycemia/DKA event occurs during use of a study device, it generally will be considered to 
453 
be unrelated to the device (per section 6.2.5) if the device functioned as intended and there does not 
454 
appear to be a flaw in how the device is intended to function. 
455 
6.2.5 Relationship of Adverse Event to Study Investigational Device 
456 
The study investigator will assess the relationship of any adverse event to the study device or study drug. 
457 
The Medical Monitor also will make this assessment, which may or may not agree with that of the study 
458 
investigator. Reporting requirements will be based on the Medical Monitor’s assessment. 
459 
To ensure consistency of adverse event causality assessments, investigators should apply the following 
460 
general guidelines when determining whether an adverse event is related to a study device or study drug: 
461 
Unrelated: The AE is clearly not related to a study drug/device and a likely alternative etiology exists 
462 
such as an underlying disease, environmental or toxic factors or other therapy. 
463 
Unlikely Related: The AE does not follow a reasonable temporal sequence during or after use of study 
464 
drug/device and a more likely alternative etiology exists such as an underlying disease, environmental or 
465 
toxic factors, or other therapy.  
466 
Possibly Related: The AE occurred in a reasonable time during or after use of study drug/device; but 
467 
could be related to another factor such as an underlying disease, environmental or toxic factors, or other 
468 
therapy; and there is a possible, though weak, scientific basis for establishing a causal association 
469 
between the AE and the study drug/device. 
470 
Probably Related: The AE occurred in a reasonable time during or after use of study drug/device; is 
471 
unlikely to be related to another factor such as an underlying disease, environmental or toxic factors, or 
472 
other therapy; and there is a plausible, though not strong, scientific basis for establishing a causal 
473 
association between the AE and the study drug/device.  
474 
Definitely Related: The AE occurred in a reasonable time during or after use of study drug/device; 
475 
cannot be explained by another factor such as an underlying disease, environmental or toxic factors, or 
476 
therapy; and there is a strong scientific basis for establishing a causal association between the AE and the 
477 
study drug/device.  
478 
Events determined to be Possibly Related, Probably Related, or Definitely Related will be considered 
479 
‘Related’ with respect to any required HDEC and Medsafe reporting. 
480 
6.2.6 Severity (Intensity) of Adverse Events 
481 
The severity (intensity) of an adverse event will be rated on a three-point scale: (1) mild, (2) moderate, 
482 
or (3) severe. A severity assessment is a clinical determination of the intensity of an event. Thus, a severe 
483 
adverse event is not necessarily serious. For example, itching for several days may be rated as severe, but 
484 
may not be clinically serious. 
485 
MILD: Usually transient, requires no special treatment, and does not interfere with the participant’s daily 
486 
activities. 
487 
MODERATE: Usually causes a low level of inconvenience, discomfort or concern to the participant 
488 
and may interfere with daily activities, but is usually ameliorated by simple therapeutic measures and 
489 
participant is able to continue in study. 
490 
SEVERE: Interrupts a participant’s usual daily activities, causes severe discomfort, may cause 
491 
discontinuation of study device, and generally requires systemic drug therapy or other treatment. 
492 

 
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6.2.7 Expectedness 
493 
For a serious adverse event that is considered possibly related to study device, the Medical Monitor will 
494 
classify the event as unexpected if the nature, severity, or frequency of the event is not consistent with the 
495 
risk information previously described in the protocol, labeling, or Investigator Brochure. 
496 
6.2.8 Coding of Adverse Events 
497 
Adverse events will be coded using the MedDRA dictionary. 
498 
6.2.9 Outcome of Adverse Events 
499 
The outcome of each reportable adverse event will be classified by the investigator as follows: 
500 
• 
RECOVERED/RESOLVED – The participant recovered from the AE/SAE without sequelae. Record 
501 
the AE/SAE stop date. 
502 
• 
RECOVERED/RESOLVED WITH SEQUELAE – The event persisted and had stabilized without 
503 
change in the event anticipated. Record the AE/SAE stop date. 
504 
• 
FATAL – A fatal outcome is defined as the SAE that resulted in death. Only the event that was the 
505 
cause of death should be reported as fatal. AEs/SAEs that were ongoing at the time of death; 
506 
however, were not the cause of death, will be recorded as “resolved” at the time of death. 
507 
• 
NOT RECOVERED/NOT RESOLVED (ONGOING) – An ongoing AE/SAE is defined as the event 
508 
was ongoing with an undetermined outcome. 
509 
An ongoing outcome will require follow-up by the site in order to determine the final outcome 
510 
of the AE/SAE. The outcome of an ongoing event at the time of death that was not the cause of 
511 
death, will be updated and recorded as “resolved” with the date of death recorded as the stop 
512 
date. 
513 
• 
UNKNOWN – An unknown outcome is defined as an inability to access the participant or the 
514 
participant’s records to determine the outcome (for example, a participant that was lost to follow-up). 
515 
If any reported adverse events are ongoing when a participant completes the study (or withdraws), 
516 
adverse events classified as UADEs or related SAEs or SUSARs will be followed until they are either 
517 
resolved, or have no prospect of improvement or change, even after the participant has completed all 
518 
applicable study visits/contacts. For all other adverse events, data collection will end at the time the 
519 
participant completes the study. Note: participants should continue to receive appropriate medical care 
520 
for an adverse event after their participation in the study ends. 
521 
6.3 Reportable Device Issues 
522 
All UADEs and ADEs as defined in section 6.2.1 will be reported as both ‘device issues’ and adverse 
523 
events, except for skin reactions from CGM sensor placement or pump infusion set placement that do not 
524 
require pharmacologic treatment. 
525 
Device issues will be reported except in the following circumstances. These occurrences are expected and 
526 
will not be reported on a Device Issue Form assuming criteria for a UADE or ADE have not been met: 
527 
• 
CGM sensor lasting fewer days than expected per manufacturer 
528 
• 
CGM tape adherence issues 
529 
• 
Pump infusion set insertion lasting fewer days than expected per manufacturer 
530 
• 
Battery lifespan deficiency due to inadequate charging or extensive wireless communication 
531 

 
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• 
Intermittent device component disconnections/communication failures not requiring system 
532 
replacement or workaround/resolution not specified in protocol. 
533 
• 
Device issues clearly addressed in the protocol that do not require additional troubleshooting 
534 
6.4 Timing of Event Reporting 
535 
SAEs possibly related to a study device, study drug, or study participation and UADEs must be reported 
536 
by the site to the Sponsor within 1 working day of the site becoming aware of the event. This can occur 
537 
via phone or email, or by completion of the appropriate eCRFs as applicable. If the form(s) are not 
538 
initially completed, they should be competed as soon as possible after there is sufficient information to 
539 
evaluate the event. All other reportable ADEs and other reportable AEs should be submitted by 
540 
completion on the eCRF(s) within 7 days of the site becoming aware of the event.  
541 
The Sponsor will notify all participating investigators of any adverse event that is serious, related, and 
542 
unexpected. Notification will be made within 10 working days after the Sponsor becomes aware of the 
543 
event. 
544 
Each principal investigator is responsible for reporting serious study-related adverse events and abiding 
545 
by any other reporting requirements specific to his/her Institutional Review Board or Ethics Committee.  
546 
Upon receipt of a qualifying event, the Sponsor will investigate the event to determine if a UADE has 
547 
occurred, and if indicated, report the results of the investigation to the HDEC, and Medsafe within 10 
548 
working days of the Sponsor becoming aware of the UADE. The Sponsor must determine if the UADE 
549 
presents an unreasonable risk to participants. If so, the Sponsor must ensure that all investigations, or 
550 
parts of investigations presenting that risk, are terminated as soon as possible but no later than 5 working 
551 
days after the Sponsor makes this determination and no later than 15 working days after first receipt 
552 
notice of the UADE. 
553 
The investigators are also required to report, without unjustified delay, all device complaints and 
554 
malfunctions that could have led to a UADE, including device complaints and malfunctions, irrespective 
555 
of whether an adverse event occurred. 
556 
6.5 Safety Oversight 
557 
The study Sponsor’s Medical Director or Chief Medical Officer will serve as Medical Monitor, and will 
558 
review all reported adverse events, including all cases of severe hypoglycemia and DKA, and adverse 
559 
device effects that are reported during the study. SAEs typically will be reviewed within 1 working day of 
560 
reporting. Other AEs typically will be reviewed on a weekly basis.  
561 
The Medical Monitor will confirm the MedDRA code assigned and adjudicate events as specified in the 
562 
safety management plan for relatedness to the study procedure and investigational device, assess 
563 
seriousness and severity, and determine if the event the event is anticipated or unanticipated. Both the 
564 
investigators and Medical Monitor’s assessments will be recorded, however, the adjudication decision of 
565 
the Medical Monitor will be used for the final classification of events, including relatedness to the study 
566 
procedures and/or the investigational device, for the determination of safety endpoints and for all 
567 
regulatory reports, product labeling, and publications or presentations. If there has been a discrepancy 
568 
between the Medical Monitor and Coordinating Investigator when classifying an AE, it will be reported to 
569 
HDEC.  
570 

 
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6.6 Stopping Criteria 
571 
6.6.1 Participant Discontinuation of Study Device 
572 
In the case of an unanticipated system malfunction resulting in a severe hypoglycemia or DKA event 
573 
(or a malfunction that could have led to severe hypoglycemia or DKA), use of the study device will be 
574 
suspended for that participant while the problem is diagnosed.  
575 
In the absence of a device malfunction, use of the study device by a participant will be discontinued if 
576 
any of the following occur:  
577 
• 
The investigator believes it is unsafe for the participant to continue on the intervention. This could be 
578 
due to the development of a new medical condition or worsening of an existing condition; or 
579 
participant behavior contrary to the indications for use of the device that imposes on the participant’s 
580 
safety 
581 
• 
The participant requests that the treatment be stopped 
582 
• 
Participant pregnancy 
583 
• 
One distinct episode of DKA in the study treatment period as defined in section 6.2.4 
584 
• 
One distinct severe hypoglycemia event in the study treatment period as defined in section 6.2.3 
585 
Each DKA or severe hypoglycemia event will be reviewed by the Medical Monitor with respect to 
586 
determination of cause and whether the occurrence of the event can be attributed to use of the study 
587 
device.  
588 
6.6.2 Criteria for Suspending or Stopping Overall Study 
589 
In addition to the suspension of device use due to a UADE as described in section 6.6.1, study activities 
590 
could be similarly suspended if the manufacturer of any constituent study device requires stoppage of 
591 
device use for safety reasons (e.g. product recall). The affected study activities may resume if the 
592 
underlying problem can be corrected by a protocol or system modification that will not invalidate the 
593 
results obtained prior to suspension. 
594 
Closed-loop system use will also be suspended if there are three or more cases of severe hypoglycemia or 
595 
three or more cases of DKA across the entire study in participants who have initiated Tandem Freedom 
596 
use. The HDEC and Medsafe will be notified. After assessment of the problem and any corrections are 
597 
implemented, use of the closed-loop system may be restarted if approval is received from the HDEC and 
598 
Medsafe. 
599 
 
600 

 
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QSF-0009225_C  
Chapter 7: Miscellaneous Considerations 
601 
7.1 Drugs Used as Part of the Protocol 
602 
Participants will use their own Humalog (insulin lispro) or Novorapid (insulin aspart) during the Run In 
603 
and Treatment Period with the study devices. 
604 
7.2 Collection of Medical Conditions and Medications 
605 
Pre-Existing Conditions: Any medical condition that is either present at screening, a chronic disease, 
606 
or a prior condition that could impact the participant’s health during the course of the study (e.g., prior 
607 
myocardial infarction or stroke) will be recorded. 
608 
Medical Conditions Developing During the Study: Medical conditions developing during the study will 
609 
be reviewed by the investigator for their relationship to the study device. 
610 
Medications: All medications in use at the time of screening or added during the course of the study will 
611 
be recorded. Nutraceuticals and preventative treatment also will be recorded. Medications only taken as 
612 
needed either can be recorded when prescribed or only recorded if used during the study. Glucagon for 
613 
treatment of severe hypoglycemia will only be recorded if used during the study. 
614 
7.3 Prohibited Medications, Devices, Treatments, and Procedures 
615 
Treatment with any insulin other than Humalog or Novorapid insulin with the study pumps is not 
616 
permitted. Treatment with a non-insulin glucose -lowering agent, other than metformin, is not permitted, 
617 
including GLP-1 receptor agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, or sulfonylureas. 
618 
The investigational study device (t:slim X2 insulin pump with Tandem Freedom algorithm) and study 
619 
sensor and transmitter (Dexcom CGM sensor and transmitter) must be removed before magnetic 
620 
resonance imaging (MRI), computed tomography (CT), X-Rays, or diathermy treatment. Participants may 
621 
continue in the trial after temporarily discontinuing use if requiring one of the above. 
622 
7.4 Rescue Medications, Treatments, and Procedures 
623 
Each participant will be required to have a glucagon preparation for rescue therapy for severe 
624 
hypoglycemia. 
625 
7.5 Pregnancy Reporting 
626 
If pregnancy occurs, the participant will be discontinued from the study. The occurrence of pregnancy 
627 
will be reported to the Coordinating Center within seven days and to the HDEC as an Unanticipated 
628 
Problem within seven calendar days. 
629 
7.6 Participant Compensation 
630 
Participant compensation will be specified in the informed consent form. 
631 
7.7 Participant Withdrawal 
632 
Participation in the study is voluntary, and a participant may withdraw at any time. For participants who 
633 
withdraw, their data will be used up until the time of withdrawal. 
634 
 
635 

 
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QSF-0009225_C  
Chapter 8: Statistical Considerations 
636 
8.1 General Statistical Considerations 
637 
Summary statistics will be generated for all relevant variables. In the comparison of continuous variables, 
638 
distributions will be tested for the normality assumption. If standard parametric techniques are found to be 
639 
inadequate, an appropriate non-parametric technique will be used. Categorical variables will be presented 
640 
using frequencies and percentages and compared using differences in proportions unless stated otherwise. 
641 
For safety/adverse event reporting, both the number of overall events and the number of participants 
642 
experiencing that event will be tabulated. No corrections will be made for multiple testing procedures. 
643 
8.2 Statistical Hypotheses 
644 
The primary objective of the study is assessment of safety. Therefore, there are no formal statistical 
645 
hypotheses associated with any of the endpoints. Outcomes will be primary descriptive in nature. 
646 
8.3 Sample Size 
647 
The sample size of at least 10 participants completing the trial is required. As this is a feasibility study 
648 
assessing safety, this sample size is for a convenience sample and is not based on a power analysis.  
649 
8.4 Outcome Measures 
650 
The two study periods are: 
651 
1) 
Control-IQ at home run-in period. 
652 
2) 
The Tandem Freedom hotel observed period. 
653 
Primary Endpoints for each period: 
654 
1. Severe hypoglycemia (with cognitive impairment such that assistance of another individual is needed 
655 
for treatment) 
656 
2. Number of diabetic ketoacidosis events  
657 
Secondary Endpoints for each period: 
658 
1. All device-related adverse events 
659 
2. CGM hypoglycemia outcomes 
660 
a. Overall % time <3.0 mmol/L 
661 
b. Overall % time <3.9 mmol/L 
662 
3. Times in ranges-overall (3.9-10 mmol/L, >10 mmol/L, >13.9 mmol/L, 3.9-7.9 mmol/L)  
663 
4. Mean glucose 
664 
5. Overall variability (CV and SD)  
665 
Due to the small sample size and feasibility nature of the study, primarily descriptive statistics will be 
666 
used. 
667 
8.5 Baseline Descriptive Statistics 
668 
Baseline demographic and clinical characteristics of the cohort of participants will be summarized in a 
669 
table using summary statistics appropriate to the distribution of each variable.  
670 

 
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QSF-0009225_C  
8.6 Additional Tabulations and Analyses 
671 
The following data will be tabulated at baseline, for the run-in period, and for the hotel supervised period 
672 
• 
Insulin metrics (units/kg): total daily insulin, total daily manual insulin. 
673 
8.7 Device Issues 
674 
The following tabulations will be performed with respect to device issues: 
675 
• 
Number of device issues by type, and number of unique participants with each type of device issue 
676 
8.8 Multiple Comparison/Multiplicity 
677 
There are no adjustments performed for multiple comparisons.  
678 
8.9 Handling of Missing Data 
679 
All practical monitoring and follow-up steps will be taken to ensure complete and accurate data 
680 
collection. All analyses will be based on available data only; no imputation for missing data is planned.  
681 
 
 
682 

 
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QSF-0009225_C  
Chapter 9: Data Collection and Monitoring 
683 
9.1 Case Report Forms and Other Data Collection 
684 
The main study data are collected on electronic case report forms (eCRFs). Original source 
685 
documentation will be maintained in the participant’s study chart or medical record. This source must be 
686 
readily verifiable against the values entered into eCRF.  
687 
Electronic device data files are obtained from the study software and individual hardware components. 
688 
These electronic device files are considered the primary source documentation. 
689 
9.2 Study Records Retention 
690 
Each participating site will maintain appropriate medical and research records for this trial, in 
691 
compliance with GCP and regulatory and institutional requirements for the protection of confidentiality of 
692 
participants. 
693 
Study documents should be retained for a minimum of 10 years after the last approval of a marketing 
694 
application in an ICH region and until there are no pending or contemplated marketing applications in an 
695 
ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical development 
696 
of the investigational product. These documents should be retained for a longer period, however, 
697 
if required by local regulations. No records will be destroyed without the written consent of the sponsor, 
698 
if applicable. It is the responsibility of the sponsor to inform the investigator when these documents no 
699 
longer need to be retained. 
700 
9.3 Quality Assurance and Monitoring 
701 
Designated personnel from the Coordinating Center will be responsible for maintaining quality 
702 
assurance (QA) and QC systems to ensure that the clinical portion of the trial is conducted and data are 
703 
generated, documented and reported in compliance with the protocol, GCP and the applicable regulatory 
704 
requirements, as well as to ensure that the rights and wellbeing of trial participants are protected and that 
705 
the reported trial data are accurate, complete, and verifiable. Adverse events will be prioritized for 
706 
monitoring. 
707 
A monitoring plan will be developed and revised as needed during the course of the study. Study conduct 
708 
and monitoring will conform with 21 Code of Federal Regulations (CFR) 812 and Guideline on the 
709 
Regulation of Therapeutic Products in New Zealand Part 11: Clinical trials – regulatory approval and 
710 
good clinical practice requirements, including the Guideline for Good Clinical Practice E6(R2) 
711 
(EMA/CHMP/ICH/135/1995). This plan will describe in detail who will conduct the monitoring, at what 
712 
frequency monitoring will be done, at what level of detail monitoring will be performed, and the 
713 
distribution of monitoring reports. 
714 
A data management plan will be also be developed and revised as needed during the course of the study. 
715 
The data of most importance for monitoring at the site are participant eligibility and adverse events. 
716 
Therefore, the monitoring plan will focus on these areas. As much as possible, remote monitoring will be 
717 
performed in real-time with on-site monitoring performed to evaluate the verity and completeness of 
718 
the key site data. Elements of the monitoring may include: 
719 

 
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QSF-0009225_C  
• 
Qualification assessment, training, and certification for sites and site personnel 
720 
• 
Oversight of HDEC coverage and informed consent procedures 
721 
• 
On-site monitoring (site visit): source data verification, data edits/audit trail, protocol review of 
722 
entered data and edits, statistical monitoring, study closeout, site visit report 
723 
• 
Agent/Device accountability 
724 
• 
Communications with site staff 
725 
• 
Patient retention and visit completion 
726 
• 
Management of noncompliance 
727 
• 
Documenting monitoring activities 
728 
• 
Adverse event reporting and monitoring 
729 
Sponsor representatives or their designees may visit the study facilities at any time in order to maintain 
730 
current and personal knowledge of the study through review of the records, comparison with source 
731 
documents, observation and discussion of the conduct and progress of the study. The investigational site 
732 
will provide direct access to all trial related source data/documents, and reports for the purpose of 
733 
monitoring and auditing by the sponsor, and inspection by local and regulatory authorities. 
734 
9.4 Protocol Deviations 
735 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or procedure 
736 
requirements. The noncompliance may be either on the part of the participant, the investigator, or the 
737 
study site staff. A significant (or major) deviation is any deviation that departs from the established 
738 
materials in such a way that it poses an increase in the risk to participants, adversely affects the welfare, 
739 
rights, or safety of the research participants, or negatively influences the scientific study integrity. As a 
740 
result of a significant deviation, a corrective and preventive action plan shall be developed by the site 
741 
and implemented promptly. 
742 
The site PI/study staff is responsible for knowing and adhering to HDEC requirements. Further details 
743 
about the handling of protocol deviations will be included in the monitoring plan. 
744 
 
745 

 
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QSF-0009225_C  
Chapter 10: Ethics/Protection of Human Participants 
746 
10.1 Ethical Standard 
747 
The investigator agrees that the study will be conducted according to the applicable New Zealand 
748 
regulations (Medsafe and Health and Disability Ethics Committee), International Conference on 
749 
Harmonization (ICH) guidelines on Good Clinical Practice (GCP) and the principles of the World 
750 
Medical Association Declaration of Helsinki 2008. The investigator will conduct all aspects of this study 
751 
in accordance with all national, state, and local laws or regulations. 
752 
10.2 Institutional Review Boards 
753 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
754 
submitted to the Health and Disability Ethics Committee (HDEC) for review and approval. Full HDEC 
755 
approval must be obtained before any participant is enrolled. Only substantial amendments to the protocol 
756 
will require HDEC review and approval before the changes are implemented to the study. All substantial 
757 
changes to the consent form will be HDEC approved.  
758 
10.3 Informed Consent Process 
759 
10.3.1 Consent Procedures and Documentation 
760 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study 
761 
and continues throughout the individual’s study participation. Extensive discussion of risks and possible 
762 
benefits of participation will be provided to the participants and their families. Consent forms will be 
763 
HDEC-approved and the participant will be asked to read and review the document. The investigator will 
764 
explain the research study to the participant and answer any questions that may arise. All participants 
765 
will receive a verbal explanation in terms suited to their comprehension of the purposes, procedures, 
766 
and potential risks of the study and of their rights as research participants. Participants will have the 
767 
opportunity to carefully review the written consent form and ask questions prior to signing. 
768 
The participants should have the opportunity to discuss the study with their surrogates or think about 
769 
it prior to agreeing to participate. The participant will sign the informed consent document prior to any 
770 
procedures being done specifically for the study. The participants may withdraw consent at any time 
771 
throughout the course of the trial. A copy of the informed consent document will be given to the 
772 
participants for their records. The rights and welfare of the participants will be protected by emphasizing 
773 
to them that the quality of their medical care will not be adversely affected if they decline to participate 
774 
in this study. 
775 
10.3.2 Participant and Data Confidentiality 
776 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
777 
sponsor(s) and their agents. This confidentiality is extended to cover testing of biological samples and 
778 
genetic tests in addition to the clinical information relating to participants. Therefore, the study protocol, 
779 
documentation, data, and all other information generated will be held in strict confidence. No information 
780 
concerning the study or the data will be released to any unauthorized third party without prior written 
781 
approval of the sponsor. 
782 
The study monitor, other authorized representatives of the sponsor, representatives of HDEC, regulatory 
783 
agencies or company supplying study product may inspect all documents and records required to be 
784 
maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) 
785 
and pharmacy records for the participants in this study. The clinical study site will permit access to such 
786 
records. 
787 

 
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QSF-0009225_C  
The study participant’s contact information will be securely stored at each clinical site for internal use 
788 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
789 
long a period as dictated by the reviewing HDEC, institutional policies, sponsor requirements, and 
790 
applicable regulations. 
791 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
792 
be transmitted to and stored by the study sponsor. This will not include the participant’s contact or 
793 
identifying information, unless otherwise specified in the informed consent form. Rather, individual 
794 
participants and their research data will be identified by a unique study identification number. The study 
795 
data entry and study management systems used by clinical sites will be secured and password protected. 
796 
At the end of the study, all study databases will be de-identified and archived at the Sponsor. 
797 
10.3.3 Future Use of Stored Specimens and Data 
798 
After the study is completed, a de-identified dataset will be provided to the study Sponsor. 
799 
No biologic specimens will be stored. 
800 
 
801 

 
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QSF-0009225_C  
Chapter 11: References 
802 
 
803 
1. Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, 
804 
Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ 3rd, Anderson SM, Church MM, 
805 
Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW; iDCL 
806 
Trial Research Group.  Six-month randomized, multicenter trial of closed-loop control in 
807 
type 1 diabetes. N Engl J Med. 2019; 381:1707-1717. 
808 
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