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

 
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Page 1 of 41 
 
  
Signature Page 
 Tandem Freedom Feasibility Trial #1 
Protocol Identifying Number: TP-0017517 
Sponsor: Tandem Diabetes Care, Inc. 
Version Number: v2.0 
30 APR 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 
Director, Clinical Affairs, Tandem Diabetes Care 
Signature/Date 
 
 
Martin de bock (May 15, 2024 17:57 GMT+12)
May 15, 2024
Jordan Pinsker (May 15, 2024 10:35 GMT+1)
Jordan Pinsker
May 15, 2024
Ravid Katchalski (May 15, 2024 07:41 PDT)
Ravid Katchalski
May 15, 2024

 
 
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Protocol Revision History 
Version 
Number 
Date 
Brief Description of Changes 
1.0 
27 FEB 2024 
Initial Version 
2.0 
30 APR 2024 
Amended wording to provide further clarity where 
safety and feasibility were used interchangeably.   
 
Clarification that if there is a discrepancy between the 
Sponsor’s Medical Monitor and the Coordinating 
Investigator when classifying an AE, it will be reported 
to HDEC. 
 
Removed two erroneous references to User Guide. 
 
Clarified all wording of Ethics Board to HDEC. 
 
 

 
 
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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 ................................................................................................................. 14 
1.3.1.1 Blood Draw .......................................................................................................................... 14 
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 ..................................................................................... 15 
1.3.1.7 Other Risks .......................................................................................................................... 15 
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 3 Nights ..................................................................................... 20 
3.2.1 General Guidelines ....................................................................................................................... 20 
3.2.2 Day 1 ............................................................................................................................................ 22 
3.2.3 Day 2 – Full Day .......................................................................................................................... 23 

 
 
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3.2.4 Day 3 – Full Day .......................................................................................................................... 23 
3.2.5 Day 4 – Morning .......................................................................................................................... 24 
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 

 
 
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7.3 Prohibited Medications, Devices, Treatments, and Procedures ......................................................... 34 
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 ........................................................................................................... 36 
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-0017517 
Protocol Name: 
Tandem Freedom Feasibility Trial #1 
Protocol Version / Date: 
2.0 / 30 APRIL 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-0017517 
Protocol Title 
Tandem Freedom Feasibility Trial #1 
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 
weekend 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. 
7. 
Have current glucagon product to treat severe hypoglycemia (injectable or nasal) 
at home (site will provide prescription if they do not have one) 
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 

 
 
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8. 
History of heart, liver, lung or kidney disease determined by investigator to 
interfere with the study 
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 weekend 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 
3. 
Number of unanticipated adverse device effects 
4. 
Number of other serious device-related adverse events 
 
Secondary Endpoints for each period: 
1. 
All device-related adverse events 
2. 
CGM hypoglycemia outcomes 
a. 
Overall % time <54 mg/dL 
b. 
Overall % time <70 mg/dL 
3. 
Times in ranges-overall (70-180 mg/dL, >180 mg/dL, >250 mg/dL, 70-140 
mg/dL) 
4. 
Mean glucose 
5. 
Glycemic variability (CV and SD) 
6. 
Secondary endpoints 2 - 5 daytime and nighttime  
 
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 ~ 1 week 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 3 nights. 
On Day 1, participants will arrive before lunch, where they will skip a meal bolus for a meal 
of at least 50 grams of carbohydrates under staff supervision with their Control-IQ pump. 
Participants will be switched the Tandem Freedom system on the evening of Day 1, 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 with open loop settings, a sleep 
schedule, and then enable Tandem Freedom for closed-loop.  
On Day 2, participants will bolus for at least 3 meals that day. At least 2 meals will have at 
least 50 grams of carbohydrate. The lunchtime meal will be the same as the Day 1 lunchtime 
meal. 
On Day 3, participants will not bolus for at least 3 meals that day. All meals will be similar 
to the prior day as much as possible. At least 2 meals will have at least 50 grams of 
carbohydrate. The lunchtime meal will be the same as the Day 1/2 lunchtime meal. 

 
 
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Snacks with carbohydrates will not be allowed other than for treatment of hypoglycemia, as 
per the study safety guidelines. 
Participants will also perform a supervised brisk walk or similar exercise of at least 45 
minutes each full day (Day 2 and Day 3), at approximately the same time each day. 
On the morning of Day 4, participants will switch back to their home pump and complete 
their participation in the study. 
No alcohol will be allowed during the hotel 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 adjust insulin delivery profile settings 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. 
2Participants 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 3 Nights 
Visit (V) or Contact (C) 
V 
C2 
V 
 
Informed Consent 
X 
 
 
Eligibility Assessment 
X 
 
 
Medical history/ 
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 
 
 
Meal Challenge 
 
 
At least 50 gram carbohydrate unannounced lunch with Control-IQ on Day 1 
At least 3 announced meals with Tandem Freedom on Day 2, same lunch as Day 1  
At least 3 unannounced meals with Tandem Freedom on Day 3, same lunch as Day 1/2 
Exercise Challenge 
 
 
At least 45 minutes of exercise per day on Days 2 and 3 
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, is now being evaluated to remove the burden of 
14 
meal bolusing. The algorithm is designed to not require meal insulin boluses as part of its design. This 
15 
algorithm is now running in the t:slim X2 insulin pump. 
16 
1.2 Rationale 
17 
The objective of this study is to assess the feasibility of the Tandem Freedom system, by assessing safety 
18 
and performance in a short-term supervised first in-human study. The study will occur in a supervised, 
19 
hotel setting with medical staff present, with existing Control-IQ users with type 1 diabetes already 
20 
familiar with the t:slim X2 insulin pump, to determine how Tandem Freedom functions with unbolused 
21 
meals and exercise. 
22 
1.3 Potential Risks and Benefits 
23 
Risks and Benefits are detailed below. Loss of confidentiality is a potential risk; however, data are 
24 
handled to minimize this risk. Hypoglycemia, hyperglycemia and ketone formation are always a risk in 
25 
participants with type 1 diabetes and participants will be monitored for these events. As all participants 
26 
will be existing Control-IQ users, and familiar with infusion set care and pump use, this helps to minimize 
27 
risk. 
28 
1.3.1 Known Potential Risks 
29 
1.3.1.1 Blood Draw 
30 
A venipuncture and/or fingerstick will be performed to obtain blood for HbA1c measurement. 
31 
Venipuncture can cause common reactions like pain, bruising, or redness at the sampling site. 
32 
Less common reactions include bleeding from the sampling site, formation of a small blood clot or 
33 
swelling of the vein and surrounding tissues, and fainting. A fingerstick frequently causes transient pain 
34 
and there may be a small, localized bruise, which may be followed by a small scar that may persist for 
35 
several weeks. The risk of local infection is less than 1 in 1000 with either venipuncture or fingerstick. 
36 

 
 
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1.3.1.2 CGM and Pump Catheter Risks 
37 
There is a small risk of bleeding where the sensor or infusion set is inserted. There is a small risk for 
38 
developing a local skin infection at the site of Continuous Glucose Monitoring (CGM) sensor placement 
39 
and at the pump infusion set placement. This may be associated with swelling, redness and pain; and may 
40 
require antibiotic therapy. Rarely, a CGM sensor may break and leave a small portion of the sensor under 
41 
the skin that may cause redness, swelling or pain at the insertion site. 
42 
Some participants may develop skin irritation or allergic reactions to the adhesives used to secure the 
43 
CGM, or to secure the insulin infusion sets for the continuous subcutaneous insulin infusion. If these 
44 
reactions occur, different adhesives or “under-taping” (such as with IV 3000, Tegaderm, etc.) will be 
45 
tried, sites will be rotated frequently, and a mild topical steroid cream or other medication may be 
46 
required.  
47 
1.3.1.3 Hypoglycemia 
48 
As with any person having type 1 diabetes and using insulin, there is always a risk of having 
49 
hypoglycemia. The frequency of hypoglycemia should be no more and possibly less than it would be 
50 
as part of daily living. Symptoms of hypoglycemia can include sweating, jitteriness, and not feeling well. 
51 
There is the possibility of fainting or seizures (convulsions) and that for a few days the participant may 
52 
not be as aware of symptoms of hypoglycemia. A CGM functioning poorly and significantly over-
53 
reading glucose values could lead to inappropriate insulin delivery. The study exercise challenges could 
54 
increase the risk of hypoglycemia. 
55 
1.3.1.4 Risk of Hyperglycemia 
56 
Hyperglycemia and ketonemia could occur if insulin delivery is attenuated or suspended for an 
57 
extended period or if the pump or infusion set is not working properly. A CGM functioning poorly 
58 
and significantly under-reading glucose values could lead to inappropriate suspension of insulin delivery. 
59 
The study meal challenges and not performing premeal insulin boluses in the hotel setting could increase 
60 
the risk of hyperglycemia. 
61 
1.3.1.5 Risk of Device Reuse 
62 
All devices will be used by a single study participant only. There will be no device reuse. 
63 
1.3.1.6 Potential Risks of the CLC System 
64 
Even though the study system has been tested prior to this study, there is still a risk that parts of the 
65 
system may not function properly. The following are possible reasons the system may deliver too much 
66 
insulin or incorrectly stop insulin delivery: 
67 
• 
CGM sensor reads higher or lower than the actual glucose level which increases risk for 
68 
hypoglycemia and hyperglycemia with automated insulin delivery system; 
69 
• 
Device malfunctions that could produce a suspension of insulin delivery or over delivery of insulin. 
70 
1.3.1.7 Other Risks 
71 
Data downloaded from pump (to include CGM values) will be collected for the study. The downloaded 
72 
data from the participant’s home devices at the screening visit may include data from the period beyond 
73 
the last 2 weeks prior to screening, although the de-identified data export will be limited to the prior 2 
74 
weeks. Data from the home glucose and ketone meters will be reviewed for adverse events only, and an 
75 
export of those devices is not required for the study. Some people may be uncomfortable with the 
76 
researchers' having such detailed information about their daily diabetes habits. 
77 

 
 
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1.3.2 Benefits 
78 
Participants may achieve better glucose control than they are currently achieving using their home insulin 
79 
pump.  
80 
The individual participant may not benefit from study participation. 
81 
1.3.3 Risk Assessment 
82 
Based on the facts that (1) individuals with diabetes experience mild hypoglycemia and hyperglycemia 
83 
frequently as a consequence of the disease and its management, (2) mitigations are in place, including 
84 
direct medical supervision in the hotel setting and all participants are current Control-UQ users, that limit 
85 
the likelihood of excessive insulin dosing or prolonged withdrawal of insulin, and (3) rapid reversal of 
86 
hypoglycemia and hyperglycemia can be achieved, it is the assessment of the Sponsor that this protocol is 
87 
an investigation involving a minor increase over minimal risk. In addition, it is the belief of the Sponsor 
88 
that this study also presents prospect of direct benefit to the participants and general benefit to others with 
89 
diabetes. 
90 
1.4 General Considerations 
91 
The study is being conducted in compliance with the ethical principles that have their origin in the 
92 
Declaration of Helsinki, with the protocol described herein, and with the standards of Good Clinical 
93 
Practice (GCP). 
94 
Per Medsafe guidelines Part 11, the investigator device in the study will be labelled “To be used by 
95 
qualified investigators only”. 
96 
 
97 

 
 
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Chapter 2: Study Enrollment and Lead-in Period 
98 
2.1 Participant Recruitment and Enrollment 
99 
Enrollment will proceed with the goal of having up to 20 participants screened, so that at least 10 
100 
complete the study. 
101 
All participants will be existing Control-IQ users to assure familiarity with the t:slim X2 insulin pump. 
102 
Study participants will be recruited from a single clinical center as a convenience sample. 
103 
2.1.1 Informed Consent and Authorization Procedures 
104 
Potential eligibility may be assessed as part of a routine-care examination. Before completing any 
105 
procedures or collecting any data that are not part of usual care, written informed consent will be 
106 
obtained. 
107 
For potential study participants, the study protocol will be discussed with the potential study participant 
108 
by study staff. The potential study participant will be given the Informed Consent Form to read. Potential 
109 
study participants will be encouraged to discuss the study with family members and their personal 
110 
physicians(s) before deciding whether to participate in the study.  
111 
A copy of the consent form will be provided to the participant, and another copy will be added to the 
112 
participant’s study record. 
113 
A participant is considered enrolled when the informed consent form has been signed. 
114 
2.2 Participant Eligibility Criteria 
115 
2.2.1 Inclusion Criteria 
116 
Individuals must meet all of the following inclusion criteria in order to be eligible to participate in the 
117 
study. 
118 
1. Age ≥18 years old 
119 
2. Diagnosis of type 1 diabetes for at least 1 year 
120 
3. Current Control-IQ user, having been prescribed Control-IQ for at least 3 months 
121 
4. HbA1c ≤ 10% 
122 
5. Investigator has confidence that the participant can successfully operate all study devices and is 
123 
capable of adhering to the protocol, including performing the weekend hotel observed setting 
124 
portion of the study. 
125 
6. Willing to use only aspart (novorapid) or lispro (humalog) insulin with the study pump, with no 
126 
use of long-acting basal insulin injections, or inhaled insulin with the study pump. 
127 
7. Have current glucagon product to treat severe hypoglycemia (injectable or nasal) at home (site 
128 
will provide prescription if they do not have one) 
129 
2.2.2 Exclusion Criteria 
130 
Individuals meeting any of the following exclusion criteria at baseline will be excluded from study 
131 
participation. 
132 
1. More than 1 episode of diabetic ketoacidosis (DKA) in the past 6 months 
133 
2. More than 1 episode of severe hypoglycemia (needing assistance) in the past 6 months 
134 

 
 
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3. Inpatient psychiatric treatment in the past 6 months  
135 
4. For Female: Currently pregnant or planning to become pregnant during the time period of study 
136 
participation 
137 
a. A negative pregnancy test will be required for all females of child-bearing potential 
138 
b. Counseling on appropriate birth control options will be provided to all females of child-
139 
bearing potential 
140 
5. Concurrent use of any non-insulin glucose-lowering agent, other than metformin (for example, 
141 
GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas). 
142 
6. Hemophilia or any other bleeding disorder 
143 
7. Hemoglobinopathy 
144 
8. History of heart, liver, lung or kidney disease determined by investigator to interfere with the 
145 
study 
146 
9. History of allergic reaction to Humalog or Novorapid 
147 
10. Use of any medications determined by investigator to interfere with study 
148 
11. Significant chronic kidney disease (which could impact CGM accuracy in investigator’s 
149 
judgment) or hemodialysis 
150 
12. Concurrent use of any medication that could interfere with the study CGM, such as hydroxyurea 
151 
13. History of adrenal insufficiency 
152 
14. History of abnormal TSH consistent with hypothyroidism or hyperthyroidism that is not 
153 
appropriately treated 
154 
15. History of gastroparesis 
155 
16. A condition, which in the opinion of the investigator or designee, would put the participant or 
156 
study at risk 
157 
17. Participation in another pharmaceutical or device trial at the time of enrollment or anticipated for 
158 
during the time period of study participation 
159 
18. Employed by, or having immediate family members employed by Tandem Diabetes Care, Inc., or 
160 
having a direct supervisor at place of employment who is also directly involved in conducting the 
161 
clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is 
162 
directly involved in conducting the clinical trial 
163 
2.3 Visit 1: Screening Visit 
164 
After informed consent has been signed, a potential participant will be evaluated for study eligibility 
165 
through the elicitation of a medical history, performance of a physical examination by study personnel 
166 
and local laboratory testing if needed to screen for exclusionary medical conditions. 
167 
2.3.1 Data Collection and Testing 
168 
A standard physical exam (including vital signs and height and weight measurements) will be performed 
169 
by the study investigator or designee (a physician, fellow, nurse practitioner or a physician assistant). 
170 
Height, weight and vital signs may be recorded by appropriately delegated office staff. 
171 
The following procedures will be performed/data collected/eligibility criteria checked and documented: 
172 
• 
Inclusion and exclusion criteria assessed 
173 

 
 
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• 
Demographics (age, sex, ethnicity and socioeconomic information) 
174 
• 
Participant initials to verify electronic case report form (eCRF) entry is associated with the correct 
175 
individual  
176 
• 
Contact information (retained at the site and not entered into study database) 
177 
• 
Medical history 
178 
• 
Concomitant medications 
179 
• 
Physical examination to include: 
180 
 
Weight, height 
181 
 
Vital signs including measurement of blood pressure and pulse 
182 
• 
Blood draw (venipuncture or fingerstick) for local HbA1c measurement 
183 
• 
Urine pregnancy test for all females of childbearing potential who are premenopausal and not 
184 
surgically sterile 
185 
• 
Current device download of the participant’s home insulin pump (with included CGM device data), 
186 
for up to the last two weeks of data if available. A de-identified CSV file will be exported from the 
187 
home pump data. Site will also record average total daily dose, average percent basal, and average 
188 
percent bolus insulin from the last 2 weeks. 
189 
Screening procedures will last approximately 1-2 hours. The screening visit must occur in clinic and 
190 
cannot be performed remotely. 
191 
2.4 Screen Failures 
192 
Individuals who do not initially meet study eligibility requirements may be rescreened one more time at a 
193 
later date per investigator discretion. 
194 
 
195 

 
 
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Chapter 3: Study Visits 
196 
3.1 Visit 2: Start Control-IQ Run-In 
197 
After screening, participants will have a clinic visit at which they will be given the study CGM (Dexcom 
198 
G6) and begin the run-in period. The run-in period will be 7 +/- 3 days. 
199 
This device training visit should be completed within 2 weeks of screening, and may be performed the 
200 
same day as the screening visit. If not completed within 2 weeks of screening, re-review of screening 
201 
results by the investigator should be performed, who may ask for repeated testing as per investigator 
202 
judgement. The device training visit must occur in clinic and cannot be performed remotely. 
203 
A urine pregnancy test for all females of childbearing potential (postmenarchal) who are premenopausal 
204 
and not surgically sterile will be completed. 
205 
Participants will receive additional supplies for blood glucose and ketone testing if needed. Quality 
206 
Control (QC) testing will be performed on the participants’ meters prior to starting the run-in period. 
207 
Participants will continue to use their home insulin pump (t:slim X2 insulin pump with Control-IQ 
208 
technology) during the run-in phase. Participants will switch the CGM to the study provided CGM sensor 
209 
and transmitter. 
210 
Participants may contact study providers at any time for questions during the Control-IQ Run-In period.  
211 
Participants will be required to change their CGM sensor 48 +/- 12 hours before the hotel study. 
212 
3.2 Visit 3: Hotel Supervised Study for 3 Nights 
213 
3.2.1 General Guidelines 
214 
Upon arrival, the following procedures will be performed: 
215 
• Current device download of the participant’s home insulin pump (with included CGM device data), for 
216 
the Run-In period. A de-identified CSV file will be exported from the home pump. Site will also record 
217 
average total daily dose, average percent basal, and average percent bolus insulin from the last 2 weeks. 
218 
• Assessment of device issues that have occurred. 
219 
• Assessment of adverse events, using open ended questions to capture hyperglycemic and hypoglycemic 
220 
events during the Run-In Phase.  
221 
For lunch on day 1 after arrival, participants will consume a meal of at least 50 gram carbohydrates, and 
222 
not bolus for it while wearing their home Control-IQ pump. This same meal will be used for lunch on day 
223 
2 and day 3. 
224 
After a 5 hour postprandial observation period is complete, participants will then be switched by study 
225 
staff to the Tandem Freedom pump (Investigational Device). Study staff will copy over pump settings 
226 
from the participants Control-IQ pump or make any settings changes they feel are indicated. A sleep 
227 
schedule will be set from 11 PM to 6 AM so sleep activity automatically activates in the evening and 
228 
deactivates in the morning. 
229 
During this phase of the study, participants will be monitored in person by study staff, and remotely 
230 
monitored by the study team with Dexcom Follow, 24 hours per day. Pump and CGM alerts will be set to 
231 
annunciate throughout the study. Dexcom follow alerts will be sent to study staff for CGM values <3.9 
232 
mmol/L mg/dL and >16.7 mmol/L mg/dL at any time. 
233 
Food diary showing the start and stop time of all meals, as well as the number of carbohydrates, fat and 
234 
protein consumed, and amount and time of any insulin doses given, will be recorded by study staff. 
235 

 
 
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During the hotel study, the following hyper and hypoglycemic treatment plan will be used: 
236 
Table 1. Hypoglycemia and Hyperglycemia Prevention and Treatment Plan during the supervised, hotel 
237 
study. 
238 
Condition  
Action Taken  
CGM reading <3.9 mmol/L 
A confirmatory fingerstick measurement will be 
performed.  
If fingerstick glucose ≥3.9 mmol/L, treatment may be 
initiated by the investigator (~4-16 g fast acting 
carbohydrate), adjusted per investigator discretion.  
Participants will then perform a follow-up fingerstick 
measurement 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 (~4-16 g fast acting 
carbohydrate) per investigator discretion.  Participants 
will then perform a follow-up fingerstick measurement 15 
minutes after treatment if CGM <3.9 mmol/L .  
This protocol will be repeated until 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.  
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. 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 
replace the participant’s infusion set with a new infusion 
set and the correction bolus will be repeated per the 
investigator’s discretion.  
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. Fingerstick BG and ketone measurements will 
be repeated after 1 hour. The correction dose given may 
be adjusted by the investigator. 

 
 
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239 
Meal boluses and all interaction with the pump will be supervised by study staff to ensure that the correct 
240 
number of carbohydrate grams are entered into the bolus calculator and the correct dose is given. 
241 
When meal boluses are given, participants will give the bolus per their usual meal bolus timing, but not 
242 
more than 15 minutes before the meal. 
243 
No alcohol will be consumed during the hotel phase of the study. 
244 
At least one member of the study medical staff (Physician, NP, PA, or other qualified clinician) will 
245 
always be present on site. 
246 
During the study session, participants may change our their study sensor or their infusion site as needed 
247 
per their usual care. 
248 
Insulin and glucose data from the screening visit, as well as follow up visits and at the start of the hotel 
249 
session, will be reviewed and the site investigator may adjust insulin delivery profile settings as needed in 
250 
accordance with their clinical practice. 
251 
3.2.2 Day 1 
252 
Following the Control-IQ run-in phase, participants will commence the hotel supervised phase.  
253 
For lunch on day 1 after arrival, participants will consume a meal of at least 50 gram carbohydrates, and 
254 
not bolus for it while wearing their home Control-IQ pump. This same meal will be used for lunch on day 
255 
2 and day 3. 
256 
After a 5 hour postprandial observation period is complete, participants will then be switched by study 
257 
staff to the Tandem Freedom pump (Investigational Device). Study staff will copy over pump settings 
258 
from the participants Control-IQ pump or make any settings changes they feel are indicated. A sleep 
259 
schedule will be set from 11 PM to 6 AM so sleep activity automatically activates in the evening and 
260 
deactivates in the morning. 
261 
After switching to the Tandem Freedom pump, participants may have dinner at the hotel and bolus as they 
262 
normally would for the dinner meal.  
263 
Participants may have a snack at any time, but it should be without carbohydrates. Snacks with 
264 
carbohydrates are not allowed. 
265 
Participants may perform low-intensity activity (e.g., walking) at any time during the hotel study. 
266 
No meals should occur after sleep activity is enabled. 
267 
The study staff will replace the participant’s infusion set 
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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3.2.3 Day 2 – Full Day 
268 
Sleep activity will be disabled upon waking up if not already automatically de-activated per the sleep 
269 
schedule. 
270 
Participants will bolus for at least 3 meals on Day 2. The lunch meal should be the same meal participants 
271 
used for their unbolused meal with Control-IQ on Day 1. The meals should be as similar as possible, and 
272 
eaten at as close to the same time as possible, to the meals to be used on Day 3. At least 2 meals will have 
273 
at least 50 grams of carbohydrate. 
274 
Participants may have a snack at any time, but it should be without carbohydrates. Snacks with 
275 
carbohydrates are not allowed. 
276 
Participants will perform a brisk walk of at least 45 minutes or similar exercise on Day 2 under staff 
277 
supervision, at approximately the same time as on Day 3. Exercise activity should be used for this 
278 
exercise, to start 30-90 minutes before exercise, and turned off after exercise is complete, as determined 
279 
by the investigator. Only begin exercise if CGM glucose is ≥6.0 mmol/L and CGM glucose is not 
280 
trending downward. 
281 
Exercise will be stopped at any point for injury or development of new symptoms (development of chest 
282 
pain/pressure, feeling unwell, development of hypoglycemic symptoms, undue shortness of breath, signs 
283 
of poor perfusion (leg pain/claudication), or any other severe symptoms, as determined by the 
284 
investigator.  
285 
Participants may perform low-intensity activity (e.g., walking) at any time during the hotel study. 
286 
No meals should occur after sleep activity is enabled. 
287 
3.2.4 Day 3 – Full Day 
288 
Sleep activity will be disabled upon waking up if not already automatically de-activated per the sleep 
289 
schedule. 
290 
Participants will NOT bolus for at least 3 meals on Day 3. The lunch meal should be the same meal 
291 
participants used for their unbolused meal with Control-IQ on Day 1. The meals should be as similar as 
292 
possible, and eaten at as close to the same time as possible, to the meals to be used on Day 2. At least 2 
293 
meals will have at least 50 grams of carbohydrate. 
294 
Participants may have a snack at any time, but it should be without carbohydrates. Snacks with 
295 
carbohydrates are not allowed. 
296 
Participants will perform a brisk walk of at least 45 minutes or similar exercise on Day 3 under staff 
297 
supervision, at approximately the same time as on Day 2. Exercise activity should be used for this 
298 
exercise, to start 30-90 minutes before exercise, and turned off after exercise is complete, as determined 
299 
by the investigator. Only begin exercise if CGM glucose is ≥6.0 mmol/L and CGM glucose is not 
300 
trending downward. 
301 
Exercise will be stopped at any point for injury or development of new symptoms (development of chest 
302 
pain/pressure, feeling unwell, development of hypoglycemic symptoms, undue shortness of breath, signs 
303 
of poor perfusion (leg pain/claudication), or any other severe symptoms, as determined by the 
304 
investigator. 
305 
Participants may perform low-intensity activity (e.g., walking) at any time during the hotel study. 
306 
No meals should occur after sleep activity is enabled in the evening. 
307 

 
 
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3.2.5 Day 4 – Morning 
308 
Sleep activity will be disabled upon waking up if not already automatically de-activated per the sleep 
309 
schedule. 
310 
After waking up, participants will switch back to their home Control-IQ pump, and may have breakfast 
311 
prior to leaving the hotel. 
312 
Participants may be discharged if their CGM is ≥4.4 mmol/L for at least 15 minutes. 
313 
3.3 Unscheduled Visits 
314 
Participants may have unscheduled visits during the study run-in period if required for additional 
315 
questions or other unanticipated needs per the study investigator discretion. 
316 
At each contact, study staff will perform an: 
317 
• Assessment of device issues that have occurred 
318 
• Assessment of adverse events, using open ended questions to capture hyperglycemic and hypoglycemic 
319 
events during the Run-In Phase.  
320 

 
 
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Chapter 4: Study Devices and Drugs 
321 
4.1 Study Devices 
322 
4.1.1 Insulin Pump 
323 
For the hotel supervised session, participants will use the study provided Tandem t:slim X2 insulin pump 
324 
with the Tandem Freedom algorithm (Investigational Device). 
325 
4.1.2 Continuous Glucose Monitoring 
326 
The study CGM is the commercial version of the Dexcom G6 (Dexcom, Inc), which includes a 
327 
transmitter and sensors. The CGM sensor will be replaced at least once every 10 days. 
328 
4.1.3 Blood Glucose and Ketone Meter 
329 
For blood glucose and ketone testing, participants will use their home meter, the CareSens Dual Blood 
330 
Glucose and Ketone Testing Monitor (i-SENS, Inc). 
331 
Blood glucose levels will be measured using the blood glucose meter (glucometer) and the CGM device 
332 
will be calibrated if needed using the glucometer and strips in accordance with the manufacturer’s 
333 
labeling. 
334 
Blood ketone levels will be measured when needed to evaluate prolonged hyperglycemia. 
335 
4.1.4 Study Device and Drug Accountability Procedures 
336 
Device accountability and inventory will be documented to include detailed inventory records of the study 
337 
CGM supplies, and Tandem insulin pump system. 
338 
4.1.5 Participant Access to Study Device at Study Closure 
339 
Participant will return the investigational study device (insulin pump) at study closure. Participant may 
340 
keep any extra ketone and glucose testing strips they were issued, and any issued remaining pump and 
341 
CGM supplies that are not marked for investigational use. 
342 

 
 
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Chapter 5: Testing Procedures 
343 
5.1 Laboratory Testing 
344 
5.1.1 HbA1c 
345 
HbA1c measurement will be performed locally in clinic or at a laboratory at the screening visit if no prior 
346 
HbA1c measurement is available from the last 3 months. 
347 
5.1.2 Urine Pregnancy 
348 
Urine pregnancy testing performed locally at clinical site for females of child-bearing potential at the 
349 
screening visit, and anytime pregnancy is suspected. 
350 

 
 
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Chapter 6: Unanticipated Problem, Adverse Event, and 
351 
Device Issue Reporting 
352 
6.1 Unanticipated Problems 
353 
Site investigators will promptly report to the Sponsor on an eCRF all unanticipated problems meeting the 
354 
criteria below. For this protocol, an unanticipated problem is an incident, experience, or outcome that 
355 
meets all of the following criteria: 
356 
• 
Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are 
357 
described in the protocol related documents, such as the HDEC (Health and Disability Ethics 
358 
Committees)-approved research protocol and informed consent document; and (b) the characteristics 
359 
of the subject population being studied 
360 
• 
Related or possibly related to participation in the research (possibly related means there is a 
361 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
362 
procedures involved in the research) 
363 
• 
Suggests that the research places participants or others at a greater risk of harm than was previously 
364 
known or recognized (including physical, psychological, economic, or social harm) 
365 
The Sponsor will report to the appropriate regulatory authorities if the HDEC determines that the event 
366 
indeed meets the criteria of an Unanticipated Problem requiring additional reporting. 
367 
6.2 Adverse Events 
368 
6.2.1 Definitions 
369 
Adverse Event (AE): Any untoward medical occurrence (including laboratory findings) associated with 
370 
study procedures, the use of a device, biologic in a study participant, including any comparator used, 
371 
irrespective of the relationship between the adverse event and the device(s) under investigation (referred 
372 
to as Adverse Reaction when caused by a drug). 
373 
Serious Adverse Event (SAE): Any untoward medical occurrence that meets at least one of the following: 
374 
• 
Results in death. 
375 
• 
Is life-threatening; (a non-life-threatening event which, had it been more severe, might have become 
376 
life-threatening, is not necessarily considered a serious adverse event). 
377 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
378 
• 
Results in persistent or significant disability/incapacity or substantial disruption of the ability 
379 
to conduct normal life functions (sight threatening). 
380 
• 
Is a congenital anomaly or birth defect. 
381 
• 
Is considered a significant medical event by the investigator based on medical judgment (e.g., may 
382 
jeopardize the participant or may require medical/surgical intervention to prevent one of the outcomes 
383 
listed above). 
384 
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety or any 
385 
life -threatening problem or death caused by, or associated with, a device, if that effect, problem, or death 
386 
was not previously identified in nature, severity, or degree of incidence in the investigational plan or 
387 
application (including a supplementary plan or application), or any other unanticipated serious problem 
388 
associated with a device that relates to the rights, safety, or welfare of participants (21 CFR 812.3(s)). 
389 

 
 
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Adverse Device Effect (ADE): Any untoward medical occurrence in a study participant which the device 
390 
may have caused or to which the device may have contributed (Note that an Adverse Event Form is to be 
391 
completed in addition to a Device Issues Form, unless excluded from reporting as defined in section 
392 
6.2.2). 
393 
Comparator: Medical device, therapy (e.g. active treatment, normal clinical practice), placebo or no 
394 
treatment, used in the control group in a clinical investigation. (ISO 14155:2020) 
395 
Device Complaints and Malfunctions: A device malfunction or complaint is something that happens 
396 
to a device or related to device performance, whereas an adverse event happens to a participant. A device 
397 
complaint may occur independently from an AE, or along with an AE. An AE may occur without a 
398 
device complaint or there may be an AE related to a device complaint. A device malfunction is any 
399 
failure of a device to meet its performance specifications or otherwise perform as intended. 
400 
Performance specifications include all claims made in the labeling for the device. The intended 
401 
performance of a device refers to the intended use for which the device is labeled or marketed. 
402 
(21 CFR 803.3). Note: for reporting purposes, sites will not be asked to distinguish between device 
403 
complaints and malfunctions. 
404 
Use Error: User action or lack of user action while using the medical device that leads to a different result 
405 
than that intended by the manufacturer or expected by the user. Includes the inability of the user to 
406 
complete a task. Use errors can result from a mismatch between the characteristics of the user, user 
407 
interface, task or use environment. Users might be aware or unaware that a use error has occurred. An 
408 
unexpected physiological response of the patient is not by itself considered a use error. A malfunction of 
409 
a medical device that causes an unexpected result is not considered a use error. (ISO 14155:2020) 
410 
6.2.2 Reportable Adverse Events 
411 
A reportable adverse event includes all events meeting the definition of an adverse event, except for the 
412 
following: 
413 
• 
Hypoglycemia and hyperglycemia not meeting the criteria below will not be recorded as adverse 
414 
events unless associated with an Adverse Device Effect or discontinuation of the study device.  
415 
• 
Skin reactions from sensor or pump infusion set placement are only reportable if severe and/or 
416 
required treatment. 
417 

 
 
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All reportable AEs—whether volunteered by the participant, discovered by study personnel during 
418 
questioning, or detected through physical examination, laboratory test, or other means—will be reported 
419 
on an AE form online. Each AE form is reviewed by the Medical Monitor to assess safety and to verify 
420 
the coding and the reporting that is required. 
421 
6.2.3 Hypoglycemic Events 
422 
Hypoglycemia is only reportable as an adverse event when one of the following criteria is met: 
423 
• 
a hypoglycemic event occurred meeting the following definition of severe hypoglycemia: the event 
424 
required assistance of another person due to altered consciousness, and required another person to 
425 
actively administer carbohydrate, glucagon, or other resuscitative actions. This means that the 
426 
participant was impaired cognitively to the point that he/she was unable to treat himself/herself, was 
427 
unable to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or experienced 
428 
seizure or loss of consciousness. These episodes may be associated with sufficient neuroglycopenia to 
429 
induce seizure or loss of consciousness. If glucose measurements are not available during such an 
430 
event, neurological recovery attributable to the restoration of glucose to normal is considered 
431 
sufficient evidence that the event was induced by a low glucose concentration. 
432 
• 
evaluation or treatment was obtained at a health care provider facility for an acute event involving 
433 
hypoglycemia, or the participant contacted the site and received guidance following the occurrence of 
434 
an acute event involving hypoglycemia 
435 
When a severe hypoglycemia event occurs (as defined above), an Adverse Event Form should be 
436 
completed. Severe hypoglycemia events should be considered to be serious adverse events with respect to 
437 
reporting requirements. When a severe hypoglycemia event occurs during use of a study device, it 
438 
generally will be considered to be unrelated to the device (per section 6.2.5) if the device functioned as 
439 
intended and there does not appear to be a flaw in how the device is intended to function. 
440 
6.2.4 Hyperglycemic/Ketotic Events 
441 
Hyperglycemia is only reportable as an adverse event when one of the following criteria is met:   
442 
• 
the event involved DKA, as defined by the Diabetes Control and Complications Trial (DCCT) and 
443 
described below 
444 
• 
evaluation or treatment was obtained at a health care provider facility for an acute event involving 
445 
hyperglycemia or ketosis, or the participant contacted the site and received guidance on how to 
446 
manage the hyperglycemia/ketosis 
447 
• 
blood ketone level ≥1.0 mmol/L, even if there was no communication with a health care provider at 
448 
the time of the event 
449 
Hyperglycemic events are classified as DKA if all of the following are present, or judged likely to have 
450 
been present based on available data: 
451 
• 
Symptoms such as polyuria, polydipsia, nausea, or vomiting; 
452 
• 
Serum ketones >1.5 mmol/L or large/moderate urine ketones; 
453 
• 
Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate (or CO2) <15; and 
454 
• 
Treatment provided in a health care facility 
455 
When a hyperglycemia/ketotic event qualifies as an AE, or as a SAE as defined in section 6.2.1, an 
456 
Adverse Event Form should be completed. Events meeting DKA criteria should be considered to be 
457 
serious adverse events with respect to reporting requirements. Hyperglycemia events not meeting criteria 
458 

 
 
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for DKA generally will not be considered as serious adverse events unless one of the SAE criteria in 
459 
section 6.2.1 is met. 
460 
When a hyperglycemia/DKA event occurs during use of a study device, it generally will be considered to 
461 
be unrelated to the device (per section 6.2.5) if the device functioned as intended and there does not 
462 
appear to be a flaw in how the device is intended to function. 
463 
6.2.5 Relationship of Adverse Event to Study Investigational Device 
464 
The study investigator will assess the relationship of any adverse event to the study device or study drug. 
465 
The Medical Monitor also will make this assessment, which may or may not agree with that of the study 
466 
investigator. Reporting requirements will be based on the Medical Monitor’s assessment. 
467 
To ensure consistency of adverse event causality assessments, investigators should apply the following 
468 
general guidelines when determining whether an adverse event is related to a study device or study drug: 
469 
Unrelated: The AE is clearly not related to a study drug/device and a likely alternative etiology exists 
470 
such as an underlying disease, environmental or toxic factors or other therapy. 
471 
Unlikely Related: The AE does not follow a reasonable temporal sequence during or after use of study 
472 
drug/device and a more likely alternative etiology exists such as an underlying disease, environmental or 
473 
toxic factors, or other therapy.  
474 
Possibly Related: The AE occurred in a reasonable time during or after use of study drug/device; but 
475 
could be related to another factor such as an underlying disease, environmental or toxic factors, or other 
476 
therapy; and there is a possible, though weak, scientific basis for establishing a causal association 
477 
between the AE and the study drug/device. 
478 
Probably Related: The AE occurred in a reasonable time during or after use of study drug/device; is 
479 
unlikely to be related to another factor such as an underlying disease, environmental or toxic factors, or 
480 
other therapy; and there is a plausible, though not strong, scientific basis for establishing a causal 
481 
association between the AE and the study drug/device.  
482 
Definitely Related: The AE occurred in a reasonable time during or after use of study drug/device; 
483 
cannot be explained by another factor such as an underlying disease, environmental or toxic factors, or 
484 
therapy; and there is a strong scientific basis for establishing a causal association between the AE and the 
485 
study drug/device.  
486 
Events determined to be Possibly Related, Probably Related, or Definitely Related will be considered 
487 
‘Related’ with respect to any required HDEC and Medsafe reporting. 
488 
6.2.6 Severity (Intensity) of Adverse Events 
489 
The severity (intensity) of an adverse event will be rated on a three-point scale: (1) mild, (2) moderate, 
490 
or (3) severe. A severity assessment is a clinical determination of the intensity of an event. Thus, a severe 
491 
adverse event is not necessarily serious. For example, itching for several days may be rated as severe, but 
492 
may not be clinically serious. 
493 
MILD: Usually transient, requires no special treatment, and does not interfere with the participant’s daily 
494 
activities. 
495 
MODERATE: Usually causes a low level of inconvenience, discomfort or concern to the participant 
496 
and may interfere with daily activities, but is usually ameliorated by simple therapeutic measures and 
497 
participant is able to continue in study. 
498 
SEVERE: Interrupts a participant’s usual daily activities, causes severe discomfort, may cause 
499 
discontinuation of study device, and generally requires systemic drug therapy or other treatment. 
500 

 
 
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6.2.7 Expectedness 
501 
For a serious adverse event that is considered possibly related to study device, the Medical Monitor will 
502 
classify the event as unexpected if the nature, severity, or frequency of the event is not consistent with the 
503 
risk information previously described in the protocol, labeling, or Investigator Brochure. 
504 
6.2.8 Coding of Adverse Events 
505 
Adverse events will be coded using the MedDRA dictionary. 
506 
6.2.9 Outcome of Adverse Events 
507 
The outcome of each reportable adverse event will be classified by the investigator as follows: 
508 
• 
RECOVERED/RESOLVED – The participant recovered from the AE/SAE without sequelae. Record 
509 
the AE/SAE stop date. 
510 
• 
RECOVERED/RESOLVED WITH SEQUELAE – The event persisted and had stabilized without 
511 
change in the event anticipated. Record the AE/SAE stop date. 
512 
• 
FATAL – A fatal outcome is defined as the SAE that resulted in death. Only the event that was the 
513 
cause of death should be reported as fatal. AEs/SAEs that were ongoing at the time of death; 
514 
however, were not the cause of death, will be recorded as “resolved” at the time of death. 
515 
• 
NOT RECOVERED/NOT RESOLVED (ONGOING) – An ongoing AE/SAE is defined as the event 
516 
was ongoing with an undetermined outcome. 
517 
An ongoing outcome will require follow-up by the site in order to determine the final outcome 
518 
of the AE/SAE. The outcome of an ongoing event at the time of death that was not the cause of 
519 
death, will be updated and recorded as “resolved” with the date of death recorded as the stop 
520 
date. 
521 
• 
UNKNOWN – An unknown outcome is defined as an inability to access the participant or the 
522 
participant’s records to determine the outcome (for example, a participant that was lost to follow-up). 
523 
If any reported adverse events are ongoing when a participant completes the study (or withdraws), 
524 
adverse events classified as UADEs or related SAEs or SUSARs will be followed until they are either 
525 
resolved, or have no prospect of improvement or change, even after the participant has completed all 
526 
applicable study visits/contacts. For all other adverse events, data collection will end at the time the 
527 
participant completes the study. Note: participants should continue to receive appropriate medical care 
528 
for an adverse event after their participation in the study ends. 
529 
6.3 Reportable Device Issues 
530 
All UADEs and ADEs as defined in section 6.2.1 will be reported as both ‘device issues’ and adverse 
531 
events, except for skin reactions from CGM sensor placement or pump infusion set placement that do not 
532 
require pharmacologic treatment. 
533 
Device issues will be reported except in the following circumstances. These occurrences are expected and 
534 
will not be reported on a Device Issue Form assuming criteria for a UADE or ADE have not been met: 
535 
• 
CGM sensor lasting fewer days than expected per manufacturer 
536 
• 
CGM tape adherence issues 
537 
• 
Pump infusion set insertion lasting fewer days than expected per manufacturer 
538 
• 
Battery lifespan deficiency due to inadequate charging or extensive wireless communication 
539 

 
 
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• 
Intermittent device component disconnections/communication failures not requiring system 
540 
replacement or workaround/resolution not specified in protocol. 
541 
• 
Device issues clearly addressed in the protocol that do not require additional troubleshooting 
542 
6.4 Timing of Event Reporting 
543 
SAEs possibly related to a study device, study drug, or study participation and UADEs must be reported 
544 
by the site to the Sponsor within 1 working day of the site becoming aware of the event. This can occur 
545 
via phone or email, or by completion of the appropriate eCRFs as applicable. If the form(s) are not 
546 
initially completed, they should be competed as soon as possible after there is sufficient information to 
547 
evaluate the event. All other reportable ADEs and other reportable AEs should be submitted by 
548 
completion on the eCRF(s) within 7 days of the site becoming aware of the event.  
549 
The Sponsor will notify all participating investigators of any adverse event that is serious, related, and 
550 
unexpected. Notification will be made within 10 working days after the Sponsor becomes aware of the 
551 
event. 
552 
Each principal investigator is responsible for reporting serious study-related adverse events and abiding 
553 
by any other reporting requirements specific to his/her Institutional Review Board or Ethics Committee.  
554 
Upon receipt of a qualifying event, the Sponsor will investigate the event to determine if a UADE has 
555 
occurred, and if indicated, report the results of the investigation to the HDEC, and Medsafe within 10 
556 
working days of the Sponsor becoming aware of the UADE. The Sponsor must determine if the UADE 
557 
presents an unreasonable risk to participants. If so, the Sponsor must ensure that all investigations, or 
558 
parts of investigations presenting that risk, are terminated as soon as possible but no later than 5 working 
559 
days after the Sponsor makes this determination and no later than 15 working days after first receipt 
560 
notice of the UADE. 
561 
The investigators are also required to report, without unjustified delay, all device complaints and 
562 
malfunctions that could have led to a UADE, including device complaints and malfunctions, irrespective 
563 
of whether an adverse event occurred. 
564 
6.5 Safety Oversight 
565 
The study Sponsor’s Medical Director or Chief Medical Officer will serve as Medical Monitor, and will 
566 
review all reported adverse events, including all cases of severe hypoglycemia and DKA, and adverse 
567 
device effects that are reported during the study. SAEs typically will be reviewed within 1 working day of 
568 
reporting. Other AEs typically will be reviewed on a weekly basis.  
569 
The Medical Monitor will determine if the events require expedited reporting to Medsafe, HDEC and/or 
570 
all participating sites. In addition, the Medical Monitor will confirm the MedDRA code assigned and 
571 
adjudicate events as specified in the safety management plan for relatedness to the study procedure and 
572 
investigational device, assess seriousness and severity, and determine if the event the event is anticipated 
573 
or unanticipated. Both the investigators and Medical Monitor’s assessments will be recorded, however, 
574 
the adjudication decision of the Medical Monitor will be used for the final classification of events, 
575 
including relatedness to the study procedures and/or the investigational device, for the determination of 
576 
safety endpoints and for all regulatory reports, product labeling, and publications or presentations. If there 
577 
has been a discrepancy between the Medical Monitor and Coordinating Investigator when classifying an 
578 
AE, it will be reported to HDEC.  
579 

 
 
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6.6 Stopping Criteria 
580 
6.6.1 Participant Discontinuation of Study Device 
581 
In the case of an unanticipated system malfunction resulting in a severe hypoglycemia or DKA event 
582 
(or a malfunction that could have led to severe hypoglycemia or DKA), use of the study device will be 
583 
suspended for that participant while the problem is diagnosed. The UADE will be reported to HDEC and 
584 
Medsafe. After assessment of the problem and any correction, use of the study device will not be restarted 
585 
until approval is received from HDEC and Medsafe. 
586 
In the absence of a device malfunction, use of the study device by a participant will be discontinued if 
587 
any of the following occur:  
588 
• 
The investigator believes it is unsafe for the participant to continue on the intervention. This could be 
589 
due to the development of a new medical condition or worsening of an existing condition; or 
590 
participant behavior contrary to the indications for use of the device that imposes on the participant’s 
591 
safety 
592 
• 
The participant requests that the treatment be stopped 
593 
• 
Participant pregnancy 
594 
• 
One distinct episode of DKA in the study treatment period as defined in section 6.2.4 
595 
• 
One distinct severe hypoglycemia event in the study treatment period as defined in section 6.2.3 
596 
Each DKA or severe hypoglycemia event will be reviewed by the Medical Monitor with respect to 
597 
determination of cause and whether the occurrence of the event can be attributed to use of the study 
598 
device.  
599 
6.6.2 Criteria for Suspending or Stopping Overall Study 
600 
In addition to the suspension of device use due to a UADE as described in section 6.6.1, study activities 
601 
could be similarly suspended if the manufacturer of any constituent study device requires stoppage of 
602 
device use for safety reasons (e.g. product recall). The affected study activities may resume if the 
603 
underlying problem can be corrected by a protocol or system modification that will not invalidate the 
604 
results obtained prior to suspension. 
605 
Closed-loop system use will also be suspended if there are three or more cases of severe hypoglycemia or 
606 
three or more cases of DKA across the entire study in participants who have initiated Tandem Freedom 
607 
use. The HDEC and Medsafe will be notified. After assessment of the problem and any corrections are 
608 
implemented, use of the closed-loop system may be restarted if approval is received from the HDEC and 
609 
Medsafe. 
610 
 
611 

 
 
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Chapter 7: Miscellaneous Considerations 
612 
7.1 Drugs Used as Part of the Protocol 
613 
Participants will use their own Humalog (insulin lispro) or Novorapid (insulin aspart) during the Run In 
614 
and Treatment Period with the study devices. 
615 
7.2 Collection of Medical Conditions and Medications 
616 
Pre-Existing Conditions: Any medical condition that is either present at screening, a chronic disease, 
617 
or a prior condition that could impact the participant’s health during the course of the study (e.g., prior 
618 
myocardial infarction or stroke) will be recorded. 
619 
Medical Conditions Developing During the Study: Medical conditions developing during the study will 
620 
be reviewed by the investigator for their relationship to the study device. 
621 
Medications: All medications in use at the time of screening or added during the course of the study will 
622 
be recorded. Nutraceuticals and preventative treatment also will be recorded. Medications only taken as 
623 
needed either can be recorded when prescribed or only recorded if used during the study. Glucagon for 
624 
treatment of severe hypoglycemia will only be recorded if used during the study. 
625 
7.3 Prohibited Medications, Devices, Treatments, and Procedures 
626 
Treatment with any insulin other than Humalog or Novorapid insulin with the study pumps is not 
627 
permitted. Treatment with a non-insulin glucose -lowering agent, other than metformin, is not permitted, 
628 
including GLP-1 receptor agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, or sulfonylureas. 
629 
The investigational study device (t:slim X2 insulin pump with Tandem Freedom algorithm) and study 
630 
sensor and transmitter (Dexcom CGM sensor and transmitter) must be removed before magnetic 
631 
resonance imaging (MRI), computed tomography (CT), X-Rays, or diathermy treatment. Participants may 
632 
continue in the trial after temporarily discontinuing use if requiring one of the above. 
633 
7.4 Rescue Medications, Treatments, and Procedures 
634 
Each participant will be required to have a glucagon preparation for rescue therapy for severe 
635 
hypoglycemia. 
636 
7.5 Pregnancy Reporting 
637 
If pregnancy occurs, the participant will be discontinued from the study. The occurrence of pregnancy 
638 
will be reported to the Coordinating Center within seven days and to the HDEC as an Unanticipated 
639 
Problem within seven calendar days. 
640 
7.6 Participant Compensation 
641 
Participant compensation will be specified in the informed consent form. 
642 
7.7 Participant Withdrawal 
643 
Participation in the study is voluntary, and a participant may withdraw at any time. For participants who 
644 
withdraw, their data will be used up until the time of withdrawal. 
645 
 
646 

 
 
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Chapter 8: Statistical Considerations 
647 
8.1 General Statistical Considerations 
648 
Summary statistics will be generated for all relevant variables. In the comparison of continuous variables, 
649 
distributions will be tested for the normality assumption. If standard parametric techniques are found to be 
650 
inadequate, an appropriate non-parametric technique will be used. Categorical variables will be presented 
651 
using frequencies and percentages and compared using differences in proportions unless stated otherwise. 
652 
For safety/adverse event reporting, both the number of overall events and the number of participants 
653 
experiencing that event will be tabulated. No corrections will be made for multiple testing procedures. 
654 
8.2 Statistical Hypotheses 
655 
The primary objective of the study is assessment of safety. Therefore, there are no formal statistical 
656 
hypotheses associated with any of the endpoints. Outcomes will be primary descriptive in nature. 
657 
8.3 Sample Size 
658 
The sample size of at least 10 participants completing the trial is required. As this is a feasibility study 
659 
assessing safety, this sample size is for a convenience sample and is not based on a power analysis.  
660 
8.4 Outcome Measures 
661 
The two study periods are: 
662 
1) 
Control-IQ at home run-in period. 
663 
2) 
The Tandem Freedom hotel observed weekend period. 
664 
Primary Endpoints for each period: 
665 
1. Severe hypoglycemia (with cognitive impairment such that assistance of another individual is needed 
666 
for treatment) 
667 
2. Number of diabetic ketoacidosis events  
668 
3. Number of unanticipated adverse device effects 
669 
4. Number of other serious device-related adverse events 
670 
Secondary Endpoints for each period: 
671 
1. All device-related adverse events 
672 
2. CGM hypoglycemia outcomes 
673 
a. Overall % time <3.0 mmol/L 
674 
b. Overall % time <3.9 mmol/L 
675 
3. Times in ranges-overall (3.9-10 mmol/L, >10 mmol/L, >13.9 mmol/L, 3.9-7.9 mmol/L)  
676 
4. Mean glucose 
677 
5. Overall variability (CV and SD)  
678 
6. Secondary endpoints 2 - 5 daytime and nighttime 
679 
Due to the small sample size and feasibility nature of the study, primarily descriptive statistics will be 
680 
used. 
681 

 
 
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8.5 Baseline Descriptive Statistics 
682 
Baseline demographic and clinical characteristics of the cohort of participants will be summarized in a 
683 
table using summary statistics appropriate to the distribution of each variable. Descriptive statistics will 
684 
be displayed by treatment group for the following: 
685 
• 
Age 
686 
• 
Sex 
687 
• 
Ethnicity 
688 
• 
Socio-economic factors (household income, education) 
689 
• 
Diabetes duration 
690 
• 
HbA1c 
691 
• 
Body Mass Index 
692 
• 
Total daily insulin 
693 
• 
Prior severe hypoglycemia and DKA events in the last 6 months 
694 
8.6 Additional Tabulations and Analyses 
695 
The following data will be tabulated at baseline, for the run-in period, and for the hotel supervised period 
696 
• 
Insulin metrics (units/kg): total daily insulin, total daily manual insulin. 
697 
8.7 Device Issues 
698 
The following tabulations will be performed with respect to device issues: 
699 
• 
Number of device issues by type, and number of unique participants with each type of device issue 
700 
8.8 Multiple Comparison/Multiplicity 
701 
There are no adjustments performed for multiple comparisons.  
702 
8.9 Handling of Missing Data 
703 
All practical monitoring and follow-up steps will be taken to ensure complete and accurate data 
704 
collection. All analyses will be based on available data only; no imputation for missing data is planned.  
705 
 
 
706 

 
 
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Chapter 9: Data Collection and Monitoring 
707 
9.1 Case Report Forms and Other Data Collection 
708 
The main study data are collected on electronic case report forms (eCRFs). Original source 
709 
documentation will be maintained in the participant’s study chart or medical record. This source must be 
710 
readily verifiable against the values entered into eCRF.  
711 
Electronic device data files are obtained from the study software and individual hardware components. 
712 
These electronic device files are considered the primary source documentation. 
713 
9.2 Study Records Retention 
714 
Each participating site will maintain appropriate medical and research records for this trial, in 
715 
compliance with GCP and regulatory and institutional requirements for the protection of confidentiality of 
716 
participants. 
717 
Study documents should be retained for a minimum of 10 years after the last approval of a marketing 
718 
application in an ICH region and until there are no pending or contemplated marketing applications in an 
719 
ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical development 
720 
of the investigational product. These documents should be retained for a longer period, however, 
721 
if required by local regulations. No records will be destroyed without the written consent of the sponsor, 
722 
if applicable. It is the responsibility of the sponsor to inform the investigator when these documents no 
723 
longer need to be retained. 
724 
9.3 Quality Assurance and Monitoring 
725 
Designated personnel from the Coordinating Center will be responsible for maintaining quality 
726 
assurance (QA) and QC systems to ensure that the clinical portion of the trial is conducted and data are 
727 
generated, documented and reported in compliance with the protocol, GCP and the applicable regulatory 
728 
requirements, as well as to ensure that the rights and wellbeing of trial participants are protected and that 
729 
the reported trial data are accurate, complete, and verifiable. Adverse events will be prioritized for 
730 
monitoring. 
731 
A monitoring plan will be developed and revised as needed during the course of the study. Study conduct 
732 
and monitoring will conform with 21 Code of Federal Regulations (CFR) 812 and Guideline on the 
733 
Regulation of Therapeutic Products in New Zealand Part 11: Clinical trials – regulatory approval and 
734 
good clinical practice requirements, including the Guideline for Good Clinical Practice E6(R2) 
735 
(EMA/CHMP/ICH/135/1995). This plan will describe in detail who will conduct the monitoring, at what 
736 
frequency monitoring will be done, at what level of detail monitoring will be performed, and the 
737 
distribution of monitoring reports. 
738 
A data management plan will be also be developed and revised as needed during the course of the study. 
739 
The data of most importance for monitoring at the site are participant eligibility and adverse events. 
740 
Therefore, the monitoring plan will focus on these areas. As much as possible, remote monitoring will be 
741 
performed in real-time with on-site monitoring performed to evaluate the verity and completeness of 
742 
the key site data. Elements of the monitoring may include: 
743 

 
 
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• 
Qualification assessment, training, and certification for sites and site personnel 
744 
• 
Oversight of HDEC coverage and informed consent procedures 
745 
• 
On-site monitoring (site visit): source data verification, data edits/audit trail, protocol review of 
746 
entered data and edits, statistical monitoring, study closeout, site visit report 
747 
• 
Agent/Device accountability 
748 
• 
Communications with site staff 
749 
• 
Patient retention and visit completion 
750 
• 
Management of noncompliance 
751 
• 
Documenting monitoring activities 
752 
• 
Adverse event reporting and monitoring 
753 
Sponsor representatives or their designees may visit the study facilities at any time in order to maintain 
754 
current and personal knowledge of the study through review of the records, comparison with source 
755 
documents, observation and discussion of the conduct and progress of the study. The investigational site 
756 
will provide direct access to all trial related source data/documents, and reports for the purpose of 
757 
monitoring and auditing by the sponsor, and inspection by local and regulatory authorities. 
758 
9.4 Protocol Deviations 
759 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or procedure 
760 
requirements. The noncompliance may be either on the part of the participant, the investigator, or the 
761 
study site staff. A significant (or major) deviation is any deviation that departs from the established 
762 
materials in such a way that it poses an increase in the risk to participants, adversely affects the welfare, 
763 
rights, or safety of the research participants, or negatively influences the scientific study integrity. As a 
764 
result of a significant deviation, a corrective and preventive action plan shall be developed by the site 
765 
and implemented promptly. 
766 
The site PI/study staff is responsible for knowing and adhering to HDEC requirements. Further details 
767 
about the handling of protocol deviations will be included in the monitoring plan. 
768 
 
769 

 
 
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Chapter 10: Ethics/Protection of Human Participants 
770 
10.1 Ethical Standard 
771 
The investigator agrees that the study will be conducted according to the applicable New Zealand 
772 
regulations (Medsafe and Health and Disability Ethics Committee), International Conference on 
773 
Harmonization (ICH) guidelines on Good Clinical Practice (GCP) and the principles of the World 
774 
Medical Association Declaration of Helsinki 2008. The investigator will conduct all aspects of this study 
775 
in accordance with all national, state, and local laws or regulations. 
776 
10.2 Institutional Review Boards 
777 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
778 
submitted to the Health and Disability Ethics Committee (HDEC) for review and approval. Full HDEC 
779 
approval must be obtained before any participant is enrolled. Only substantial amendments to the protocol 
780 
will require HDEC review and approval before the changes are implemented to the study. All substantial 
781 
changes to the consent form will be HDEC approved.  
782 
10.3 Informed Consent Process 
783 
10.3.1 Consent Procedures and Documentation 
784 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study 
785 
and continues throughout the individual’s study participation. Extensive discussion of risks and possible 
786 
benefits of participation will be provided to the participants and their families. Consent forms will be 
787 
HDEC-approved and the participant will be asked to read and review the document. The investigator will 
788 
explain the research study to the participant and answer any questions that may arise. All participants 
789 
will receive a verbal explanation in terms suited to their comprehension of the purposes, procedures, 
790 
and potential risks of the study and of their rights as research participants. Participants will have the 
791 
opportunity to carefully review the written consent form and ask questions prior to signing. 
792 
The participants should have the opportunity to discuss the study with their surrogates or think about 
793 
it prior to agreeing to participate. The participant will sign the informed consent document prior to any 
794 
procedures being done specifically for the study. The participants may withdraw consent at any time 
795 
throughout the course of the trial. A copy of the informed consent document will be given to the 
796 
participants for their records. The rights and welfare of the participants will be protected by emphasizing 
797 
to them that the quality of their medical care will not be adversely affected if they decline to participate 
798 
in this study. 
799 
10.3.2 Participant and Data Confidentiality 
800 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
801 
sponsor(s) and their agents. This confidentiality is extended to cover testing of biological samples and 
802 
genetic tests in addition to the clinical information relating to participants. Therefore, the study protocol, 
803 
documentation, data, and all other information generated will be held in strict confidence. No information 
804 
concerning the study or the data will be released to any unauthorized third party without prior written 
805 
approval of the sponsor. 
806 
The study monitor, other authorized representatives of the sponsor, representatives of HDEC, regulatory 
807 
agencies or company supplying study product may inspect all documents and records required to be 
808 
maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) 
809 
and pharmacy records for the participants in this study. The clinical study site will permit access to such 
810 
records. 
811 

 
 
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The study participant’s contact information will be securely stored at each clinical site for internal use 
812 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
813 
long a period as dictated by the reviewing HDEC, institutional policies, sponsor requirements, and 
814 
applicable regulations. 
815 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
816 
be transmitted to and stored by the study sponsor. This will not include the participant’s contact or 
817 
identifying information, unless otherwise specified in the informed consent form. Rather, individual 
818 
participants and their research data will be identified by a unique study identification number. The study 
819 
data entry and study management systems used by clinical sites will be secured and password protected. 
820 
At the end of the study, all study databases will be de-identified and archived at the Sponsor. 
821 
10.3.3 Future Use of Stored Specimens and Data 
822 
After the study is completed, a de-identified dataset will be provided to the study Sponsor. 
823 
No biologic specimens will be stored. 
824 
 
825 

 
 
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Chapter 11: References 
826 
 
827 
1. Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, 
828 
Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ 3rd, Anderson SM, Church MM, 
829 
Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW; iDCL 
830 
Trial Research Group.  Six-month randomized, multicenter trial of closed-loop control in 
831 
type 1 diabetes. N Engl J Med. 2019; 381:1707-1717. 
832 
2. Breton MD, Kanapka LG, Beck RW, Ekhlaspour L, Forlenza GP, Cengiz E, Schoelwer M, 
833 
Ruedy KJ, Jost E, Carria L, Emory E, Hsu LJ, Oliveri M, Kollman CC, Dokken BB, 
834 
Weinzimer SA, DeBoer MD, Buckingham BA, Cherñavvsky D, Wadwa RP; iDCL Trial 
835 
Research Group. A randomized trial of closed-loop control in children with type 1 diabetes. 
836 
N Engl J Med. 2020; 383:836-845. 
837 
3. Breton M, Kovatchev B. One year real-world use of the Control-IQ advanced hybrid closed 
838 
loop technology. Diabetes Technol Ther. 2021;23:601-608. 
839 
 
840