Control-IQ Technology for High Insulin Users With Type 1 Diabetes (Higher-IQ)
Phase: NA
Conditions: Type 1 Diabetes
Sponsor: Tandem Diabetes Care, Inc.

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Contains trade secrets and/or confidential information exempt from disclosure from 21 CFR 20.61 
Signature Page 
Control-IQ Technology for High Insulin Users with Type 1 
Diabetes (Higher-IQ) 
Protocol Identifying Number: TP-0009856 
IDE Number: G210300 
IDE Sponsor: Tandem Diabetes Care, Inc. 
Version Number: v 5.0 
21 MAR 2022 
Medical Monitor and Protocol Chair 
Name, degree 
Title 
Jordan Pinsker, MD 
Vice President & Medical Director, Tandem Diabetes Care 
Signature/Date 
Sponsor Representative 
Name, degree 
Title 
Ravid Sasson-Katchalski, PhD 
Associate Director, Clinical Affairs, Tandem Diabetes Care 
Signature/Date 
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SIGN
SIGN

 
 
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Protocol Revision History 
Version 
Number 
Amendment 
Date 
Brief Description of Changes 
1.0 
12 OCT 2021 
Initial Version Submitted to FDA 
2.0 
10 NOV 2021 
First Version Approved by FDA 
3.0 
18 JAN 2022 
• Added IDE number to cover page 
• Added protocol revision history table 
• Clarified Stats Analysis Plan endpoints, with detailed 
description of time periods for meal and exercise 
challenge analysis 
• Clarified sponsor responsibilities in AE/device issue 
reporting 
• Clarified exercise/meal challenge instructions 
• Removed SUSAR and other definitions not related to 
this trial, as investigational insulin will not be used 
• Clarified the sponsor’s Medical Director will serve as 
the Medical Monitor 
• Other minor clarifications on wording for consistency 
throughout the protocol 
4.0 
01 MAR 2022 
• Clarified participant will plan to use at least one basal 
rate > 3 units/hr with the study pump. 
• Clarified participants using SGLT-2 inhibitors, GLP-
1 analogs, or other non-insulin glucose medications 
other than metformin must be on a stable dose over the 
last 3 months prior to enrollment. 
• Clarified abnormal screening electrocardiogram 
consistent with increased risk during study exercise 
activities, and that investigator will review all 
electrocardiograms. 
• Clarified procedures for verifying subject identifiers. 
• Added to section 7.1 that Humalog or Novolog will 
be provided to participants. 
• Clarified details of monitoring plan, and specific data 
that would be considered source material that could be 
monitored. 
• Other minor clarifications on wording for consistency 
throughout the protocol. 
5.0 
21 MAR 2022 
• Added Special Considerations for Participants Taking 
SGLT-2 inhibitors, GLP-1 Receptor Agonists, or DPP-
IV Inhibitors to add scheduled ketone checks for 
participants using SGLT-2 inhibitors, when to stop 
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SGLT-2 inhibitors, and updated hyperglycemia 
treatment guidelines. 
• Updated exclusion criteria to address adjuvant 
medication use of glucose lowering agents and weight 
loss agents. 
• Updated prohibited medications. 
• Updated section 6.6.1 discontinuation of study 
device. 
• Updated inclusion criteria to note goal enrollment of 
at least 25% of participants using a basal rate above 3 
units/hr for substantially all day 
• Added definition of euglycemic DKA. 
 
 
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TABLE OF CONTENTS 
SITE PRINCIPAL INVESTIGATOR STATEMENT OF COMPLIANCE .............................................................. 9 
CHAPTER 1: BACKGROUND INFORMATION ............................................................................................. 15 
1.1 Introduction ....................................................................................................................................... 15 
1.1.1 Disease Background .................................................................................................................... 15 
1.1.2 Tandem X2 Insulin Pump with Control-IQ Technology ............................................................. 15 
1.2 Rationale ............................................................................................................................................ 15 
1.3 Potential Risks and Benefits .............................................................................................................. 15 
1.3.1 Known Potential Risks ................................................................................................................ 15 
1.3.1.1 Blood Draw ......................................................................................................................... 15 
1.3.1.2 CGM and Pump Catheter Risks .......................................................................................... 16 
1.3.1.3 Hypoglycemia ..................................................................................................................... 16 
1.3.1.4 Risk of Hyperglycemia ....................................................................................................... 16 
1.3.1.5 Risk of Device Reuse .......................................................................................................... 16 
1.3.1.6 Potential Risks of the CLC System ..................................................................................... 16 
1.3.1.7 Other Risks .......................................................................................................................... 17 
1.3.2 Benefits ........................................................................................................................................ 17 
1.3.3 Risk Assessment .......................................................................................................................... 17 
1.4 General Considerations ...................................................................................................................... 17 
CHAPTER 2: STUDY ENROLLMENT AND LEAD-IN PERIOD ...................................................................... 18 
2.1 Participant Recruitment and Enrollment ........................................................................................... 18 
2.1.1 Informed Consent and Authorization Procedures ....................................................................... 18 
2.2 Participant Eligibility Criteria ........................................................................................................... 18 
2.2.1 Inclusion Criteria ......................................................................................................................... 18 
2.2.2 Exclusion Criteria ........................................................................................................................ 19 
2.3 Screening Procedures ........................................................................................................................ 20 
2.3.1 Data Collection and Testing ........................................................................................................ 20 
2.4 Screen Failures .................................................................................................................................. 21 
CHAPTER 3: TREATMENT PERIOD ............................................................................................................ 22 
3.1 Control-IQ 1.5 Training Visit ............................................................................................................ 22 
3.1.1 Training on System Use .............................................................................................................. 22 
3.1.2 Training on Management of Hypoglycemia ................................................................................ 23 
3.1.3 Training on Management of Hyperglycemia ............................................................................... 23 
3.1.4 Adjustments in Insulin Pump Settings ........................................................................................ 24 
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3.2 Study Visits and Phone Contacts ....................................................................................................... 25 
3.2.1 Procedures at Study Visits ........................................................................................................... 25 
3.2.2 Unscheduled Visits ...................................................................................................................... 26 
3.2.3 Exercise and Meal Challenges ..................................................................................................... 26 
3.3 Early Discontinuation of Study Device ............................................................................................. 26 
CHAPTER 4: STUDY DEVICES AND DRUGS ............................................................................................... 27 
4.1 Study Devices .................................................................................................................................... 27 
4.1.1 Insulin Pump ................................................................................................................................ 27 
4.1.2 Continuous Glucose Monitoring ................................................................................................. 27 
4.1.3 Blood Glucose Meter ................................................................................................................... 27 
4.1.4 Ketone Meter ............................................................................................................................... 27 
4.2 Study Device and Drug Accountability Procedures .......................................................................... 27 
4.3 Participant Access to Study Device at Study Closure ....................................................................... 27 
CHAPTER 5: TESTING PROCEDURES AND QUESTIONNAIRES.................................................................. 28 
5.1 Meal and Exercise Challenges ........................................................................................................... 28 
5.1.1 Meal Challenges .......................................................................................................................... 28 
5.1.2 Exercise Challenges..................................................................................................................... 29 
5.2 Laboratory Testing ............................................................................................................................ 29 
5.2.1 HbA1c ......................................................................................................................................... 29 
5.2.2 Urine Pregnancy .......................................................................................................................... 29 
CHAPTER 6: UNANTICIPATED PROBLEM, ADVERSE EVENT, AND DEVICE ISSUE REPORTING ............ 30 
6.1 Unanticipated Problems ..................................................................................................................... 30 
6.2 Adverse Events .................................................................................................................................. 30 
6.2.1 Definitions ................................................................................................................................... 30 
6.2.2 Reportable Adverse Events ......................................................................................................... 31 
6.2.3 Hypoglycemic Events .................................................................................................................. 32 
6.2.4 Hyperglycemic/Ketotic Events .................................................................................................... 32 
6.2.5 Relationship of Adverse Event to Study Investigational Device ................................................. 33 
6.2.6 Severity (Intensity) of Adverse Events ........................................................................................ 33 
6.2.7 Expectedness ............................................................................................................................... 34 
6.2.8 Coding of Adverse Events ........................................................................................................... 34 
6.2.9 Outcome of Adverse Events ........................................................................................................ 34 
6.3 Reportable Device Issues ................................................................................................................... 34 
6.4 Timing of Event Reporting ................................................................................................................ 35 
6.5 Safety Oversight ................................................................................................................................ 35 
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6.6 Stopping Criteria ............................................................................................................................... 36 
6.6.1 Participant Discontinuation of Study Device .............................................................................. 36 
6.6.2 Criteria for Suspending or Stopping Overall Study ..................................................................... 36 
CHAPTER 7: MISCELLANEOUS CONSIDERATIONS ................................................................................... 38 
7.1 Drugs Used as Part of the Protocol .................................................................................................... 38 
7.2 Collection of Medical Conditions and Medications .......................................................................... 38 
7.3 Prohibited Medications, Devices, Treatments, and Procedures ......................................................... 38 
7.4 Rescue Medications, Treatments, and Procedures ............................................................................ 38 
7.5 Pregnancy Reporting ......................................................................................................................... 38 
7.6 Participant Compensation .................................................................................................................. 39 
7.7 Participant Withdrawal ...................................................................................................................... 39 
CHAPTER 8: STATISTICAL CONSIDERATIONS .......................................................................................... 40 
8.1 Statistical Hypotheses ........................................................................................................................ 40 
8.2 Sample Size ....................................................................................................................................... 40 
8.3 Outcome Measures ............................................................................................................................ 40 
8.4 Analysis Datasets ............................................................................................................................... 40 
8.5 Statistical Methods ............................................................................................................................ 41 
8.5.1 Analysis of the Safety Event Endpoints ...................................................................................... 41 
8.5.2 Analysis of CGM Endpoints ....................................................................................................... 41 
8.5.3 Intervention Adherence ............................................................................................................... 41 
8.6 Protocol Adherence and Retention .................................................................................................... 41 
8.7 Baseline Descriptive Statistics ........................................................................................................... 41 
8.8 Additional Tabulations and Analyses ................................................................................................ 42 
8.9 Device Issues ..................................................................................................................................... 42 
8.10 Planned Interim Analyses ................................................................................................................ 42 
8.11 Subgroup Analyses .......................................................................................................................... 42 
8.12 Multiple Comparison/Multiplicity ................................................................................................... 42 
8.13 Analysis of Meal and Exercise Challenges ..................................................................................... 42 
CHAPTER 9: DATA COLLECTION AND MONITORING .............................................................................. 43 
9.1 Case Report Forms and Other Data Collection ................................................................................. 43 
9.2 Study Records Retention ................................................................................................................... 43 
9.3 Quality Assurance and Monitoring .................................................................................................... 43 
9.4 Protocol Deviations ........................................................................................................................... 44 
CHAPTER 10: ETHICS/PROTECTION OF HUMAN PARTICIPANTS ............................................................ 45 
10.1 Ethical Standard ............................................................................................................................... 45 
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10.2 Institutional Review Boards ............................................................................................................ 45 
10.3 Informed Consent Process ............................................................................................................... 45 
10.3.1 Consent Procedures and Documentation ................................................................................... 45 
10.3.2 Participant and Data Confidentiality ......................................................................................... 45 
10.3.3 Future Use of Stored Specimens and Data ................................................................................ 46 
CHAPTER 11: REFERENCES ....................................................................................................................... 47 
 
 
 
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LIST OF ABBREVIATIONS 
 
 
ABBREVIATION 
DEFINITION 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AID 
Automated Insulin Delivery 
BGM 
Blood Glucose Meter 
BMI 
Body Mass Index 
CFR 
Code of Federal Regulations 
CGM 
Continuous Glucose Monitoring  
CLC 
Closed-Loop Control 
DCCT 
Diabetes Control & Complications Trial 
DKA 
Diabetic Ketoacidosis 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HbA1c 
Hemoglobin A1c 
ICF 
Informed consent form 
ICH 
International Conference of Harmonisation 
IDE  
Investigational Device Exemption 
IRB 
Institutional Review Board 
RBM 
Risk-Based Monitoring 
SAE 
Serious Adverse Event 
T1D 
Type 1 Diabetes 
UADE 
Unanticipated Adverse Device Effect 
 
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Site Principal Investigator Statement of Compliance 
Protocol Identifying Number: 
TP-0009856 
Protocol Name: 
Control-IQ Technology for High Insulin Users with 
Type 1 Diabetes (Higher-IQ) 
Protocol Version / Date: 
5.0 / 21 MAR 2022 
 
The Principal Investigators (undersigned) hereby declare that they have read this protocol and 
agree to its contents. 
This trial will be carried out in accordance with the principles of Good Clinical Practice (GCP) 
and as required by the following, as applicable: United States (US) Code of Federal Regulations 
(CFR) (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 
812). 
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., IRBs 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-0009856 
Protocol Title 
Control-IQ Technology for High Insulin Users with Type 1 Diabetes (Higher-IQ) 
Précis 
A prospective, single-arm study of 13 weeks of home use of the Control-IQ automated 
insulin delivery (AID) system in individuals with type 1 diabetes who will plan to use at 
least one basal rate > 3 units/hr, age 18 and older. Subjects will use the Control-IQ 1.5 
System. Exercise and meal challenges will be performed during the study. 
Products 
t:slim X2 insulin pump with Control-IQ technology v1.5 (Control-IQ System) 
Objectives 
The objectives of the study are to assess safety and explore glycemic outcomes with use of 
an automated insulin delivery (AID) system (t:slim X2 with Control-IQ Technology v1.5) in 
adults with type 1 diabetes who will plan to use at least one basal rate > 3 units/hr. 
Number of Sites 
Up to 5 clinical sites in the US. 
Study Design 
Existing insulin pump users (to include AID users) will use the study system (pump and 
CGM) in closed-loop mode for 13 weeks. 
Number of Participants 
Up to 60 adults with type 1 diabetes may be screened, so at least 30 finish closed-loop use.      
Participant Population: 
Eligibility to enroll in the study will be assessed based on the following inclusion 
criteria: 
1. 
Age ≥ 18 years 
2. 
Diagnosis of type 1 diabetes for at least 1 year 
3. 
Currently using an insulin pump (of any brand) for at least 3 months, and will plan 
to use at least one basal rate above 3 units/hr with the study pump 
a. 
Goal is at least 25% of study participants are on a basal rate above 3 
units/hr for substantially all day 
4. 
HbA1c < 10.5% 
5. 
Weight ≤ 200 kg 
6. 
Residing full-time in the United States, with no anticipated travel outside the 
United States during the period of study participation.  
7. 
Participant has agreed to participate in the study; and has read, understood and 
signed the informed consent form (ICF); and has agreed to follow all study 
procedures, including suspending use of any personal CGM for the duration of the 
clinical trial once the study CGM is in use. 
8. 
Willing to use only aspart (novolog) or lispro (humalog) insulin with the study 
pump, with no use of concentrated insulin above U-100, long-acting basal insulin 
injections, or inhaled insulin with the study pump 
9. 
Have current glucagon product to treat severe hypoglycemia (injectable or nasal) 
at home (will provide prescription if they do not have one) 
10. Willing and able to perform the study exercise and meal challenges. 
11. Have a care partner, trained in hypoglycemia and hyperglycemia treatment 
guidelines, present during the challenges and until the next day.  
12. Investigator has confidence that the participant can successfully operate all study 
devices and is capable of adhering to the protocol, including ability to respond to 
alerts and alarms, and to provide basic diabetes self-management. 
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 
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3. 
Inpatient psychiatric treatment in the past 6 months  
4. 
History of drug abuse (defined as any illicit drug use) or history of alcohol abuse 
prior to screening or unwillingness to agree to abstain from illicit drugs throughout 
the study.  
5. 
For Female: Currently pregnant or planning to become pregnant during the time 
period of study participation 
• 
A negative pregnancy test will be required for all females of child-
bearing potential 
• 
Counseling on appropriate birth control options will be provided to all 
females of child-bearing potential 
6. 
Use of sulfonylureas, meglitinides, Symlin or other medications specifically listed 
in section 7.3 of the protocol or determined by investigator to interfere with the 
study 
7. 
Unstable dose of SGLT-2 inhibitor, GLP-1 receptor agonist, DPP-IV inhibitor, as 
listed in section 7.3 of the protocol, or starting a new non-insulin glucose lowering 
or weight loss agent during the trial 
8. 
Hemophilia or any other bleeding disorder 
9. 
History of heart, liver, lung or kidney disease determined by investigator to 
interfere with the study 
10. History of allergic reaction to Humalog or Novolog 
11. Use of glucocorticoids other medications determined by investigator to interfere 
with study 
12. Abnormal screening electrocardiogram consistent with increased risk during study 
exercise activities, such as arrhythmia, ischemia, or prolonged QTc interval. 
Investigator will review all electrocardiograms 
13. Significant chronic kidney disease (which could impact CGM accuracy in 
investigator’s judgment) or hemodialysis 
14. History of adrenal insufficiency 
15. History of abnormal TSH consistent with hypothyroidism or hyperthyroidism that 
is not appropriately treated 
16. History of gastroparesis 
17. A condition, which in the opinion of the investigator or designee, would put the 
participant or study at risk 
18. Participation in another pharmaceutical or device trial at the time of enrollment or 
anticipated for during the time period of study participation 
19. 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 13-15 weeks. 
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Study Endpoints 
Primary Safety Endpoints: 
• Severe hypoglycemia (with cognitive impairment such that assistance of another 
individual is needed for treatment) during study compared with data on severe 
hypoglycemic events reported by T1D Exchange clinic registry over a 3-month time 
period 
• Diabetic ketoacidosis (event rate) 
• Number of unanticipated adverse device effects 
• Number of other serious adverse events 
Secondary Safety Endpoints: 
• All adverse events 
• CGM hypoglycemia outcomes  
◆ Overall % time <54 mg/dL 
◆ Overall % time <70 mg/dL 
Exploratory: 
• Times in ranges-overall (70-180 mg/dL, >180 mg/dL, >250 mg/dL, 70-140 mg/dL) 
• Mean glucose 
• Overall variability (CV and SD) 
• HbA1c change from baseline   
• CGM metrics for hypoglycemia, hyperglycemia, and variability during daytime and 
nighttime 
Protocol Overview/Synopsis 
After consent is signed, eligibility will be assessed.  
 
Treatment Period: 
Participants will return to clinic to undergo device training with the study CGM and study 
pump. 
Participants will then use the study pump for ~90 days during the study period. Participants 
will have a phone follow up visit at 3 days, 1 week, 3 weeks, an in clinic visit at 6 weeks, a 
phone follow up visit at 9 weeks, and a final clinic visit at ~13 weeks. 
Participants will use the t:slim X2 insulin pump with Control-IQ technology 1.5 turned on. It 
is acceptable to use manual mode when there is a loss of CGM data. 
Each participant will perform 3 meal and 3 exercise challenges during the study. 
An assessment of adverse events, using open ended questions to capture hyperglycemic and 
hypoglycemic events, and their underlying cause and relationship to the study device or 
other parts of the system (such as the infusion set), will occur at all visits/contacts. 
Study Safety Plan:  
Participants will be given a blood glucose and ketone meter to use throughout the study, and 
will be trained on their use by qualified staff. BGM readings will be performed 
in accordance with the study participant instruction sheet and per CGM manufacturer 
instructions. Ketone readings will be performed per the study participant instruction sheet. 
Site investigators may adjust insulin delivery profile settings as needed throughout the study 
in accordance with their clinical practice. 
 
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SCHEMATIC OF STUDY DESIGN 
 
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SCHEDULE OF STUDY VISITS AND PROCEDURES 
1End of study visit or upon early withdrawal of the subject from the study. Note, HbA1c (Central Lab) 
will only be drawn if the subject has reached at least 6 weeks of follow-up.  
2Pregnancy test does not need to be repeated if screening and Control-IQ training visits are performed on 
the same day.
 
Screening 
Visit 
Control-IQ 
1.5 Training 
Visit  
Control-IQ Use 
 
 
Up to 2 
weeks after 
screening 
3d 
1w 
3w 
6w 
9w 
13w1 
UV 
Visit (V) or Contact (C) 
V 
V 
C 
C 
C 
V 
C 
V 
V/C 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Eligibility Assessment 
X 
 
 
 
 
 
 
 
 
Medical history/ 
physical exam 
X 
 
 
 
 
 
 
 
 
Height, weight, 
blood pressure and pulse 
X 
 
 
 
 
 
 
 
 
HbAlc (POC or local lab) 
X 
 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
 
 
Pregnancy test (females 
of child-bearing potential) 
X 
X2 
 
 
 
 
 
 
 
Assessment of Device Use 
X 
 
 
 
 
 
 
 
 
Study system training 
 
X 
 
 
 
 
 
 
 
HbA1c (Central Lab) 
 
X 
 
 
 
 
 
X 
 
AE Assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
Upload and Review Study 
Device Data 
 
 
X 
X 
X 
X 
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 with Control-IQ Technology 
8 
The Tandem X2 insulin pump with Control-IQ technology is an FDA-approved closed-loop control 
9 
(CLC) system based on the control algorithm developed and initially tested in the University of 
10 
Virginia’s DiAs system and then implemented in the inControl system (TypeZero, Technologies, Inc.). 
11 
Use of the Control-IQ system has been extensively tested in adults and children with type 1 diabetes 
12 
(T1D), demonstrating its efficacy and safety when used with insulin lispro (Humalog) or insulin aspart 
13 
(Novolog).1,2 The system is currently approved for ages 6 years and older and use in younger children is 
14 
currently being studied (clinical trials.gov NCT04796779). There are over 150,000 users of the 
15 
system since it became commercially available in 2020. A recent evaluation of real-world use of the 
16 
system in 9,451 users age >6 years with at least 12 months of system use found results comparable to 
17 
those found in the randomized trials.3  
18 
Since the initial approval of the system, modifications have been made in the software, which is referred 
19 
to as version 1.5. These modifications include modest usability improvements and other enhancements 
20 
intended to further reduce risk. The Control-IQ 1.5 system also removes the 3 units/hr basal clipping, 
21 
allowing the pump to deliver programmed user profile basal rates above 3 units/hr when 30 minute 
22 
predicted glucose is expected to be in the target range. This has the potential to further improve outcomes 
23 
in individuals using basal rates at or above this threshold. 
24 
1.2 Rationale 
25 
The objective of this single-arm, prospective study is to assess safety and explore glycemic outcomes 
26 
associated with use of the Control-IQ 1.5 system in adults with type 1 diabetes using basal rates > 3 
27 
units/hr for at least part of the day.  
28 
1.3 Potential Risks and Benefits 
29 
Risks and Benefits are detailed below. Loss of confidentiality is a potential risk; however, data are 
30 
handled to minimize this risk. Hypoglycemia, hyperglycemia and ketone formation are always a risk in 
31 
participants with type 1 diabetes and participants will be monitored for these events. 
32 
1.3.1 Known Potential Risks 
33 
1.3.1.1 Blood Draw 
34 
A venipuncture and/or fingerstick will be performed to obtain blood for HbA1c measurement. 
35 
Venipuncture can cause common reactions like pain, bruising, or redness at the sampling site. 
36 
Less common reactions include bleeding from the sampling site, formation of a small blood clot or 
37 
swelling of the vein and surrounding tissues, and fainting. A fingerstick frequently causes transient pain 
38 
and there may be a small, localized bruise, which may be followed by a small scar that may persist for 
39 
several weeks. The risk of local infection is less than 1 in 1000 with either venipuncture or fingerstick. 
40 
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1.3.1.2 CGM and Pump Catheter Risks 
41 
There is a small risk of bleeding where the sensor or infusion set is inserted. There is a small risk for 
42 
developing a local skin infection at the site of CGM sensor placement of pump infusion set placement. 
43 
This may be associated with swelling, redness and pain; and may require antibiotic therapy. Rarely, a 
44 
CGM sensor may break and leave a small portion of the sensor under the skin that may cause redness, 
45 
swelling or pain at the insertion site. 
46 
Some participants may develop skin irritation or allergic reactions to the adhesives used to secure the 
47 
CGM, or to secure the insulin infusion sets for the continuous subcutaneous insulin infusion. If these 
48 
reactions occur, different adhesives or “under-taping” (such as with IV 3000, Tegaderm, etc.) will be 
49 
tried, sites will be rotated frequently, and a mild topical steroid cream or other medication may be 
50 
required.  
51 
1.3.1.3 Hypoglycemia 
52 
As with any person having type 1 diabetes and using insulin, there is always a risk of having 
53 
hypoglycemia. The frequency of hypoglycemia should be no more and possibly less than it would be 
54 
as part of daily living. Symptoms of hypoglycemia can include sweating, jitteriness, and not feeling well. 
55 
There is the possibility of fainting or seizures (convulsions) and that for a few days the participant may 
56 
not be as aware of symptoms of hypoglycemia. A CGM functioning poorly and significantly over-
57 
reading glucose values could lead to inappropriate insulin delivery. 
58 
1.3.1.4 Risk of Hyperglycemia 
59 
Hyperglycemia and ketonemia could occur if insulin delivery is attenuated or suspended for an 
60 
extended period or if the pump or infusion set is not working properly. A CGM functioning poorly 
61 
and significantly under-reading glucose values could lead to inappropriate suspension of insulin delivery. 
62 
1.3.1.5 Risk of Device Reuse 
63 
All devices will be used by a single study participant only. There will be no device reuse. 
64 
1.3.1.6 Potential Risks of the CLC System 
65 
Even though the study system has been tested prior to this study, there is still a risk that parts of the 
66 
system may not function properly. The following are possible reasons the system may deliver too much 
67 
insulin or incorrectly stop insulin delivery: 
68 
• 
CGM sensor reads higher or lower than the actual glucose level which increases risk for 
69 
hypoglycemia and hyperglycemia with automated insulin delivery system; 
70 
• 
Device malfunctions that could produce a suspension of insulin delivery or over delivery of insulin. 
71 
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1.3.1.7 Other Risks 
72 
Data downloaded from the study CGM and study pump will be collected for the study. The downloaded 
73 
data from the participant’s home pump and CGM (if available) at the screening visit will include data 
74 
from prior to the date of the screening visit and will include data from the period beyond the last 2 weeks 
75 
prior to screening. Some people may be uncomfortable with the researchers' having such detailed 
76 
information about their daily diabetes habits. 
77 
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, and have 
84 
been tested in prior studies using the investigational device system in the home setting, that limit the 
85 
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 
There is no restriction on the number of participants to be enrolled by each clinical center toward the 
95 
overall recruitment goal. 
96 
In accordance with 21 CFR 812.66, the protocol is considered a significant risk device study, due to the 
97 
fact that the intervention is investigational. Therefore, an investigational device exemption (IDE) from the 
98 
U.S. Food and Drug Administration (FDA) is required to conduct the study. 
99 
 
100 
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Chapter 2: Study Enrollment and Lead-in Period 
101 
2.1 Participant Recruitment and Enrollment 
102 
Enrollment will proceed with the goal of having up to 60 subjects screened, so that at least 30 complete 
103 
closed loop use. 
104 
Study participants will be recruited from up to 5 clinical centers in the United States without regard to 
105 
gender, race, or ethnicity. There is no restriction on the number of participants to be enrolled by each site 
106 
toward the overall recruitment goal.                                                                                                                                           
107 
2.1.1 Informed Consent and Authorization Procedures 
108 
Potential eligibility may be assessed as part of a routine-care examination. Before completing any 
109 
procedures or collecting any data that are not part of usual care, written or electronic informed consent 
110 
will be obtained. 
111 
For potential study participants, the study protocol will be discussed with the potential study participant 
112 
by study staff. The potential study participant will be given the Informed Consent Form to read. Potential 
113 
study participants will be encouraged to discuss the study with family members and their personal 
114 
physicians(s) before deciding whether to participate in the study. 
115 
A copy of the consent form will be provided to the participant, and a copy will be added to the 
116 
participant’s study record. 
117 
As part of the informed consent process, each participant will be asked to sign an authorization for 
118 
release of personal information. The investigator, or his or her designee, will review the study-specific 
119 
information that will be collected and to whom that information will be disclosed. After speaking with 
120 
the participant, questions will be answered about the details regarding authorization. 
121 
A participant is considered enrolled when the informed consent form has been signed. 
122 
2.2 Participant Eligibility Criteria 
123 
2.2.1 Inclusion Criteria 
124 
Individuals must meet all of the following inclusion criteria in order to be eligible to participate in the 
125 
study. 
126 
1. Age ≥ 18 years 
127 
2. Diagnosis of type 1 diabetes for at least 1 year 
128 
3. Currently using an insulin pump (of any brand) for at least 3 months, and will plan to use at least 
129 
one basal rate above 3 units/hr with the study pump 
130 
a. Goal is at least 25% of study participants are on a basal rate above 3 units/hr for 
131 
substantially all day 
132 
4. HbA1c < 10.5% 
133 
5. Weight ≤ 200 kg 
134 
6. Residing full-time in the United States, with no anticipated travel outside the United States during 
135 
the period of study participation. 
136 
7. Participant has agreed to participate in the study; and has read, understood and signed the 
137 
informed consent form (ICF); and has agreed to follow all study procedures, including 
138 
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suspending use of any personal CGM for the duration of the clinical trial once the study CGM is 
139 
in use. 
140 
8. Willing to use only aspart (novolog) or lispro (humalog) insulin with the study pump, with no use 
141 
of concentrated insulin above U-100, long-acting basal insulin injections, or inhaled insulin with 
142 
the study pump. 
143 
9. Have current glucagon product to treat severe hypoglycemia (injectable or nasal) at home (will 
144 
provide prescription if they do not have one) 
145 
10. Willing and able to perform the study exercise and meal challenges. 
146 
11. Have a care partner, trained in hypoglycemia and hyperglycemia treatment guidelines, present 
147 
during the challenges and until the next day.  
148 
12. Investigator has confidence that the participant can successfully operate all study devices and is 
149 
capable of adhering to the protocol, including ability to respond to alerts and alarms, and to 
150 
provide basic diabetes self-management. 
151 
2.2.2 Exclusion Criteria 
152 
Individuals meeting any of the following exclusion criteria at baseline will be excluded from study 
153 
participation. 
154 
1. More than 1 episode of diabetic ketoacidosis (DKA) in the past 6 months 
155 
2. More than 1 episode of severe hypoglycemia (needing assistance) in the past 6 months 
156 
3. Inpatient psychiatric treatment in the past 6 months 
157 
4. History of drug abuse (defined as any illicit drug use) or history of alcohol abuse prior to 
158 
screening or unwillingness to agree to abstain from illicit drugs throughout the study. 
159 
5. For Female: Currently pregnant or planning to become pregnant during the time period of study 
160 
participation 
161 
• 
A negative pregnancy test will be required for all females of child-bearing potential  
162 
• 
Counseling on appropriate birth control options will be provided to all females of child-
163 
bearing potential 
164 
6. Use of sulfonylureas, meglitinides or other medications specifically listed in section 7.3 of the 
165 
protocol or determined by investigator to interfere with the study 
166 
7. Unstable dose of SGLT-2 inhibitor, GLP-1 receptor agonist, or DPP-4 inhibitor as listed in 
167 
section 7.3 of the protocol, or starting a new non-insulin glucose lowering or weight loss agent 
168 
during the trial 
169 
8. Hemophilia or any other bleeding disorder 
170 
9. History of heart, liver, lung or kidney disease determined by investigator to interfere with the 
171 
study 
172 
10. History of allergic reaction to Humalog or Novolog 
173 
11. Use of glucocorticoids or other medications determined by investigator to interfere with study 
174 
12. Abnormal screening electrocardiogram consistent with increased risk during study exercise 
175 
activities, such as arrhythmia, ischemia, or prolonged QTc interval. Investigator will review all 
176 
electrocardiograms 
177 
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13. Significant chronic kidney disease (which could impact CGM accuracy in investigator’s 
178 
judgment) or hemodialysis 
179 
14. History of adrenal insufficiency 
180 
15. History of abnormal TSH consistent with hypothyroidism or hyperthyroidism that is not 
181 
appropriately treated 
182 
16. History of gastroparesis 
183 
17. A condition, which in the opinion of the investigator or designee, would put the participant or 
184 
study at risk 
185 
18. Participation in another pharmaceutical or device trial at the time of enrollment or anticipated for 
186 
during the time period of study participation 
187 
19. Employed by, or having immediate family members employed by Tandem Diabetes Care, Inc., or 
188 
having a direct supervisor at place of employment who is also directly involved in conducting the 
189 
clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is 
190 
directly involved in conducting the clinical trial 
191 
2.3 Screening Procedures 
192 
After informed consent has been signed, a potential participant will be evaluated for study eligibility 
193 
through the elicitation of a medical history, performance of a physical examination by study personnel 
194 
and local laboratory testing if needed to screen for exclusionary medical conditions. 
195 
2.3.1 Data Collection and Testing 
196 
A standard physical exam (including vital signs and height and weight measurements) will be performed 
197 
by the study investigator or designee (a physician, fellow, nurse practitioner or a physician assistant). 
198 
Height, weight and vital signs may be recorded by appropriately delegated office staff. 
199 
The following procedures will be performed/data collected/eligibility criteria checked and documented: 
200 
• 
Inclusion and exclusion criteria assessed 
201 
• 
Demographics (age, sex, race and ethnicity and socioeconomic information) 
202 
• 
Subject initials to verify downloaded device data and eCRF entry is associated with the correct 
203 
individual  
204 
• 
Contact information (retained at the site and not entered into study database) 
205 
• 
Medical history 
206 
• 
Substance use history (drinking, smoking, and drug habits) 
207 
• 
Concomitant medications 
208 
• 
Physical examination to include: 
209 
 
Weight, height 
210 
 
Vital signs including measurement of blood pressure and pulse 
211 
• 
Blood draw (venipuncture or fingerstick) for local HbA1c measurement 
212 
• 
Urine pregnancy test for all females who are premenopausal and not surgically sterile 
213 
• 
ECG performed at screening for all participants 
214 
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• 
Current device download, to include insulin pump and CGM device data, for up to the last 90 days of 
215 
data 
216 
Screening procedures will last approximately 1-2 hours. The screening visit must occur in clinic and 
217 
cannot be performed remotely. 
218 
2.4 Screen Failures 
219 
Individuals who do not initially meet study eligibility requirements may be rescreened one more time at a 
220 
later date per investigator discretion. 
221 
 
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Chapter 3: Treatment Period 
223 
3.1 Control-IQ 1.5 Training Visit 
224 
After screening, participants will have a clinic visit at which they will undergo CGM and study pump 
225 
device training.  
226 
The device training visit should be completed within 2 weeks of screening, and may be performed the 
227 
same day as the screening visit. If not completed within 2 weeks of screening, re-review of screening 
228 
results by the investigator should be performed, who may ask for repeated testing as per investigator 
229 
judgement. The device training visit may be extended over the course of more than 1 session if needed. 
230 
The device training visit must occur in clinic and cannot be performed remotely. 
231 
A blood sample (venipuncture or fingerstick) will be obtained to send to the central laboratory for 
232 
HbA1c measurement. 
233 
A urine pregnancy test for all females who are premenopausal and not surgically sterile will be 
234 
completed. 
235 
Participants will receive supplies for blood glucose and ketone testing. Quality Control (QC) testing will 
236 
be performed on the meters before they are dispensed. 
237 
As all study participants are existing pump users (of any brand pump), pump settings will be transferred 
238 
over from the participant’s current pump. The study investigator may then further adjust insulin delivery 
239 
profile settings as clinically indicated.  
240 
3.1.1 Training on System Use 
241 
All participants will receive study system training from a qualified trainer.  
242 
At a minimum training will include the following: 
243 
• 
Calibration of the CGM in accordance with manufacturer labeling 
244 
• 
Procedures for treating severe hypoglycemia 
245 
• 
Procedures for identifying potential infusion set failure and steps to take including the checking of the 
246 
blood ketone level and changing the infusion set 
247 
The participant will be given a User Guide as a reference as well as Hypoglycemia and Hyperglycemia 
248 
Treatment Guidelines as part of the Study Participant Instruction Sheet. 
249 
Participants will be instructed to download the study device prior to each phone contact or office visit. 
250 
The participant will be instructed to use the system in closed-loop mode except 1) when no calibrated 
251 
CGM sensor is available or 2) if insulin is delivered by any means other than the study pump (e.g. 
252 
injection of subcutaneous insulin via syringe in the event of infusion site failure). If insulin is delivered 
253 
by any means other than the study pump, participant will be instructed to turn off Control-IQ for 
254 
approximately four hours. 
255 
The participant will also be instructed to contact study staff during periods of illness with an elevated 
256 
temperature >101.5 degrees Fahrenheit (38.6 degrees Celsius), periods of significant illness, or during 
257 
periods of use of medications such as epinephrine for the emergency treatment of a severe allergic 
258 
reaction or asthma attack in addition to use of oral or injectable glucocorticoids to determine if closed-
259 
loop use should be temporarily discontinued. 
260 
Participants taking SGLT-2 inhibitors will be instructed to discontinue use of their SGLT-2 inhibitor 
261 
during times of illness where they are at higher risk to develop ketones, to include temperature >101.5 
262 
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degrees Fahrenheit (38.6 degrees Celsius), any gastrointestinal illness, dehydration, decreased PO intake, 
263 
fasting, or periods of significant illness. 
264 
Participants will be provided with contact information and will be asked to call the study clinical staff 
265 
for any health-related issues and for technical issues with the system. Participants may use the study 
266 
pump without Control-IQ activated and study CGM during periods of component disconnections or 
267 
technical difficulties. 
268 
Participants may use available manufacturer-provided CGM software and features of the study CGM 
269 
related to mobile data access or remote monitoring, but will be instructed not to use any third-party 
270 
components for this purpose. The t:connect mobile app from Tandem Diabetes Care will not be 
271 
available for use during the trial, and will not pair to the study pump. 
272 
Study staff will discuss with the participant that routine contact is required as per the study visit schedule 
273 
and will make arrangements with the participant for the contacts. If the participant cannot be reached, the 
274 
participant’s other contact methods will be utilized, including the emergency contact. Participants who are 
275 
not compliant with the arranged contacts on two separate occasions may be discontinued at the discretion 
276 
of the investigator. 
277 
Participants will be instructed that they must have a care partner, trained in the study hypoglycemia and 
278 
hyperglycemia treatment guidelines, present during the study meal and exercise challenges, and present 
279 
overnight after the challenges. These hypoglycemia and hyperglycemia treatment guidelines will be 
280 
reviewed with the care partner prior to initiating any challenges. 
281 
Following the Control-IQ 1.5 Training Visit, participants will use the study pump for ~90 days during the 
282 
Treatment Period. 
283 
3.1.2 Training on Management of Hypoglycemia 
284 
The t:slim X2 with Control-IQ system will issue a predictive hypoglycemia alert (Control-IQ Low Alert) 
285 
when the system predicts BG <70 mg/dL within the next 15 minutes (<80 mg/dL when exercise mode is 
286 
activated). Participants will be permitted to change the CGM low glucose threshold alert setting on their 
287 
device or mobile app, but will be instructed to choose a value no less than 70 mg/dL. 
288 
If the participant receives a Control-IQ Low Alert, a message appears on the user interface that is 
289 
accompanied by vibration followed by vibrations and/or sound if not acknowledged by the user in 5 
290 
minutes. This alert remains on the screen until acknowledged by the participant. The user is prompted 
291 
to test blood glucose and treat with carbohydrate. 
292 
Participants on GLP-1 receptor agonists and DPP-4 inhibitors will be reminded to carefully monitor post 
293 
prandial blood sugars, as use of GLP-1 receptor agonists can have lower blood glucose levels after meals. 
294 
The participant and companion if available will be instructed that if severe hypoglycemia occurs, the 
295 
study pump’s insulin delivery should be suspended and glucagon administration if the participant is 
296 
unable to consume carbohydrate. 
297 
Participants will be required to have a home glucagon emergency kit. Participants who currently do not 
298 
have one will be given a prescription for the glucagon emergency kit. 
299 
3.1.3 Training on Management of Hyperglycemia 
300 
The t:slim X2 with Control-IQ system will issue a predictive hyperglycemia alert (Control-IQ High Alert) 
301 
when the system has increased insulin delivery, but detects a CGM value above 200 mg/dL and does not 
302 
predict the value will decrease in the next 30 minutes. During the course of the study, participants will be 
303 
permitted to change the CGM high glucose threshold alert setting on their device or mobile app, but will 
304 
be instructed to choose a value no greater than 300 mg/dL. 
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If the participant receives a Control-IQ High Alert, a prompt appears on the user interface to check the 
306 
site for occlusion and test blood glucose. 
307 
If a participant’s CGM reading is >300 mg/dL for more than 60 minutes or is ≥400 mg/dL at any point, 
308 
the participant will be instructed to take the following steps: 
309 
• 
Perform a blood glucose meter check. 
310 
• 
If the blood glucose is >300 mg/dL, check for blood ketones with the study ketone meter. 
311 
• 
If the ketone level is ≥ 0.6 mmol/L (or ≥ 2.5 mmol\L at any time), take correction insulin, change 
312 
insulin (pump) infusion site and contact study staff. Continue to monitor their glucose and blood 
313 
ketone levels until they return to normoglycemia and ketones are < 0.6 mmol/l. 
314 
 
If ketones are <0.6 mmol/l, they will be advised to continue to monitor their glucose until it 
315 
returns to normoglycemia and to repeat the ketone measurement in 90 minutes if necessary 
316 
• 
If correction insulin is administered via insulin syringe, turn Control-IQ off for four hours and until 
317 
glucose level has returned to <180 mg/dL. 
318 
 
319 
Special Considerations for Participants Taking SGLT-2 inhibitors, GLP-1 Receptor Agonists, or 
320 
DPP-IV Inhibitors 
321 
 
322 
Participants taking any SGLT-2 inhibitor will be instructed to perform scheduled ketone checks at least 
323 
twice a day (morning and evening) during the first two weeks of study device use, and at least once a day 
324 
thereafter. If a participant taking an SGLT-2 inhibitor develop ketones > 0.6 on two successive occasions 
325 
during these 2 weeks (the first testing upon waking in a fasted state), they will be withdrawn from the 
326 
study. 
327 
 
328 
For participants taking any SGLT-2 inhibitor, GLP-1 Receptor Agonist, or DPP-4 inhibitor, if a 
329 
participant’s CGM reading is >250 mg/dL for more than 60 minutes or is ≥400 mg/dL at any point, the 
330 
participant will be instructed to take the following steps: 
331 
• 
Perform a blood glucose meter check. 
332 
• 
If the blood glucose is >250 mg/dL, check for blood ketones with the study ketone meter. 
333 
• 
If the ketone level is ≥ 0.6 mmol/L (or ≥ 2.5 mmol\L at any time), take correction insulin, change 
334 
insulin (pump) infusion site and contact study staff. Continue to monitor their glucose and blood 
335 
ketone levels until they return to normoglycemia and ketones are < 0.6 mmol/l. 
336 
 
If ketones are <0.6 mmol/l, they will be advised to continue to monitor their glucose until it 
337 
returns to normoglycemia and to repeat the ketone measurement in 90 minutes if necessary 
338 
• 
If correction insulin is administered via insulin syringe, turn Control-IQ off for four hours and until 
339 
glucose level has returned to <180 mg/dL. 
340 
3.1.4 Adjustments in Insulin Pump Settings 
341 
Insulin and glucose data from the screening visit, as well as follow up visits, will be reviewed and the site 
342 
investigator may adjust insulin delivery profile settings as needed in accordance with their clinical 
343 
practice. 
344 
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3.2 Study Visits and Phone Contacts 
345 
Participants will have a phone (or video-conference) follow-up visit at 3 days, 1 week and 3 weeks, a 
346 
clinic follow-up visit at 6 weeks, a phone follow-up visit at 9 weeks, and a final clinic visit at 13 weeks, 
347 
within the windows specified below. 
348 
TARGET 
DAY/WEEK 
VISIT OR 
PHONE 
TARGET WINDOW 
(AROUND TARGET 
DAY/WEEK) 
3 days 
P 
+1 day 
1 week 
P 
+2 days 
3 weeks 
P 
+7 days 
6 weeks 
V 
+7 days 
9 weeks 
P 
+7 days 
13 weeks 
V 
91-98 days 
If necessary, visits should be completed out-of-window rather than missed. A visit is not considered 
349 
missed until the next visit/phone window opens.  
350 
The goal will be for all participants to complete all scheduled visits. However, participants who 
351 
(because of unforeseen circumstances or due to changes in contact precautions that may be needed 
352 
during the evolving COVID-19 pandemic) are unable or unwilling to return for all follow-up visits 
353 
will be permitted to return for key visits only (screening visit, device training visit) as an alternative to 
354 
withdrawal from the study. Remote (phone) visits will still be performed as scheduled. When a participant 
355 
is placed into this status, remote visits will not be recorded as protocol deviations. 
356 
Additional phone and office visits may occur as needed. 
357 
For the 6 and 13 week visits, if a clinical site believes these visits need to be performed remotely, the 
358 
following approvals must be obtained prior to conducting the visit remotely: 
359 
• 
Sponsor approval for the reason the visit cannot be performed in person 
360 
• 
Investigator approval at the site level for the reason the visit cannot be performed in person 
361 
In addition, all study procedures listed in section 3.2.1 are to be completed, including upload of the study 
362 
device and review of the device data. If the final visit is performed remotely, participant will mail in the 
363 
A1c kit from home and mail back the study devices to the study site. 
364 
3.2.1 Procedures at Study Visits 
365 
The following procedures will be performed at each visit, unless otherwise specified: 
366 
• 
Review of study device data 
367 
• 
Assessment of compliance with study device use by review of any available device data 
368 
• 
Assessment of device issues that have occurred 
369 
• 
Assessment of adverse events, using open ended questions to capture hyperglycemic and 
370 
hypoglycemic events, and their underlying cause and relationship to the study device or other parts of 
371 
the system (such as the infusion set). 
372 
At 13 weeks (or if at subject withdrawal), the study staff will then supervise the participants transition 
373 
back to their standard of care therapy as follows: 
374 
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• 
Study staff will re-evaluate the subject’s baseline therapy doses, noting changes in basal rates, 
375 
carbohydrate ratios, and correction factors in use at the end of the trial. 
376 
• 
The study investigator will supervise and confirm the entry of settings in the insulin delivery profile 
377 
of the participant’s home pump at the end of the study. 
378 
• 
Blood draw (venipuncture or fingerstick) for HbA1c measurement at central lab (Device Training 
379 
Visit and 13 weeks only) 
380 
3.2.2 Unscheduled Visits 
381 
Participants may have unscheduled visits during the study period if required for additional device training 
382 
or other unanticipated needs per the study investigator discretion. Study participants will be instructed to 
383 
upload their study device any time the participant changes device profile settings, and study staff will 
384 
document review of these changes as an unscheduled visit. Documentation of the review must occur as an 
385 
unscheduled visit if these changes are not being performed in window/part of the scheduled study visits 
386 
and are not captured as part of a scheduled study visit. 
387 
3.2.3 Exercise and Meal Challenges 
388 
Participants will complete 3 meal and 3 exercise challenges during the study. Procedures are described in 
389 
section 5.1. 
390 
3.3 Early Discontinuation of Study Device 
391 
Participants who discontinue the study device prior to 13 weeks, either by choice or by investigator 
392 
decision, will be asked to come for an end of study visit and then will be dropped from the study. 
393 
If the visit occurs at 6 weeks or after, blood will be drawn for the central laboratory HbA1c measurement. 
394 
 
395 
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Chapter 4: Study Devices and Drugs 
396 
4.1 Study Devices 
397 
The investigational device (CLC system) includes an insulin pump and a continuous glucose monitor. 
398 
4.1.1 Insulin Pump 
399 
The study system will include the Tandem t:slim X2 with Control-IQ 1.5 technology. 
400 
4.1.2 Continuous Glucose Monitoring 
401 
The study CGM that is part of the CLC system is the Dexcom G6, which includes a transmitter and 
402 
sensors. The CGM sensor will be replaced at least once every 10 days. 
403 
4.1.3 Blood Glucose Meter 
404 
The study blood glucose meter is the Contour® NEXT (Ascencia Diabetes Care). 
405 
Blood glucose levels will be measured using the study’s blood glucose meter (glucometer) and the 
406 
CGM device will be calibrated if needed using the study glucometer and strips in accordance with the 
407 
manufacturer’s labeling. 
408 
4.1.4 Ketone Meter 
409 
The study blood ketone meter is the Precision Xtra Blood Glucose and Ketone Monitoring System 
410 
(Abbott Diabetes Care). 
411 
Blood ketone levels will be measured when needed to evaluate prolonged hyperglycemia. The blood 
412 
glucose meter component of the Precision Xtra device will not be used. 
413 
  
414 
4.2 Study Device and Drug Accountability Procedures 
415 
Device accountability and inventory will be documented to include detailed inventory records of the study 
416 
study CGM supplies, and Tandem insulin pump system. 
417 
4.3 Participant Access to Study Device at Study Closure 
418 
Participant will return all investigational study devices and supplies (insulin pump, CGM and related 
419 
supplies) at study closure. Participant may keep the study ketone meter and study glucometer if these 
420 
devices are not marked for investigational use only. 
421 
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Chapter 5: Testing Procedures and Questionnaires 
422 
5.1 Meal and Exercise Challenges 
423 
Participants will complete 3 meal and 3 exercise challenges with the study device.  
424 
A minimum of 48 hours will occur between all challenges for each participant. Challenges may be 
425 
performed in any order. 
426 
Participants will be instructed to communicate with study staff within one day prior to each challenge to 
427 
review procedures and to have a contact with study staff after the completion of each challenge.  
428 
Hyperglycemia and Hypoglycemia treatment guidelines (sections 3.1.3 and 3.1.2) remain in effect for the 
429 
challenges, and will be reviewed with participants prior to each challenge.  
430 
Participants will be reminded they must have a care partner, trained in these hypoglycemia and 
431 
hyperglycemia treatment guidelines, present during the challenges and overnight until 6 AM the next day. 
432 
Site staff will directly contact the participant if they do not receive a follow up contact from participants 
433 
when 24 hours have passed since the time of completion of the planned challenge. 
434 
5.1.1 Meal Challenges 
435 
The same meal should be used for each of the three meal challenges—either lunch or dinner (participant 
436 
choice).  
437 
During study device use, the three meal challenges will consist of: 
438 
• 
No bolus for the meal 
439 
• 
50% bolus - calculate the bolus dose using the bolus calculator, and deliver half the 
440 
recommended dose of insulin. 
441 
• 
Full bolus for the meal based on calculated bolus dose using the bolus calculator. 
442 
 For each meal challenge, participants will: 
443 
1. Be in a fasting state for two hours prior to consuming the meal and the last manual insulin bolus 
444 
more than two hours prior to the meal.   
445 
2. Only begin the meal challenge if CGM glucose is between 70 mg/dL and 200 mg/dL.  Subjects 
446 
with hyperglycemia > 200mg/dL will reschedule their challenge for another time. If < 70 mg/dL, 
447 
carbohydrate treatment can be given, after which the meal challenge can continue. 
448 
3. Consume at least 50 grams carbohydrate for the meal. Each participant will use the same meal 
449 
for all of their meal challenges in the study. Participants will be encouraged to use the same 
450 
frozen entrée of their choice for consistency. 
451 
4. Write down the start and end time of eating the meal, as well as the meal content (to include 
452 
amount of carbohydrate, protein and fat) on the study provided logbook. 
453 
5. Not give an additional bolus for up to 3 hours after the meal challenge, unless BG is above 300 
454 
mg/dL for more than 1 hour, or symptoms of hyperglycemia develop. 
455 
6. Not take additional carbohydrates for up to 3 hours after the meal challenge, unless BG is < 70 
456 
mg/dL, or symptoms of hypoglycemia develop. 
457 
7. Not exercise for 3 hours after the meal challenge. 
458 
8. After the meal is completed, perform an SMBG (fingerstick) glucose check 1 hour after, prior to 
459 
bed, and once overnight. 
460 
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9. Notify the site within 24 hours after completion of each meal challenge. 
461 
10. The meal challenge will end 3 hours after the meal is completed. 
462 
5.1.2 Exercise Challenges 
463 
For each exercise challenge, participants will: 
464 
1. Have extra carbohydrate containing snacks and glucagon on hand during and after exercise. 
465 
2. Per their usual routine and investigator guidance, consider activation of “exercise activity” on the 
466 
pump up to 45 minutes ahead of actual exercise, to allow for less insulin on board when starting 
467 
exercise. 
468 
3. Consider reducing the last meal bolus prior to exercise as a way to reduce insulin on board and 
469 
limit hypoglycemia. 
470 
4. Perform one hour of exercise, including at least half an hour of moderate activity. Exercise does 
471 
not need to be the same activity each time. 
472 
5. Only begin exercise if CGM glucose is ≥ 120 mg/dL and CGM glucose is not trending 
473 
downward.  
474 
6. Write down the start time of last meal and amount and time of last insulin dose, type of exercise 
475 
performed, as well as the start and stop time of each exercise session in the study logbook (as this 
476 
may not correlate exactly with exercise activity use on the pump). Participants may take breaks if 
477 
needed, as long as the full hour of activity is completed. 
478 
7. Stop the exercise challenges at any point for injury or development of new symptoms; 
479 
development of chest pain/pressure, feeling unwell, development of hypoglycemic symptoms, 
480 
undue shortness of breath, signs of poor perfusion (leg pain/claudication), or for any other reason. 
481 
8. After the exercise challenge is completed, perform an SMBG (fingerstick) glucose check 1 hour 
482 
after, prior to bed, and once overnight. 
483 
9. Notify the site within 24 hours after completion of each exercise challenge. Participants will be 
484 
asked if they developed new symptoms and review guidance on the need to stop future exercise 
485 
challenges if any adverse events or new symptoms occurred per clinician judgement based on the 
486 
severity of symptoms. 
487 
10. The exercise challenge will end after 1 hour of the required activity is completed. 
488 
5.2 Laboratory Testing 
489 
5.2.1 HbA1c 
490 
HbA1c measurement will be performed locally at the Screening visit. 
491 
An additional blood sample will be obtained (venipuncture or fingerstick) and sent to the central 
492 
laboratory at the Control-IQ 1.5 Training visit and at the 13-week visit (or at early withdrawal of the 
493 
subject from the study providing they have completed at least 6 weeks of follow-up). 
494 
5.2.2 Urine Pregnancy 
495 
Urine pregnancy testing performed locally at clinical site for females of child-bearing potential at the 
496 
screening visit, at the start of study device use, and anytime pregnancy is suspected. 
497 
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Chapter 6: Unanticipated Problem, Adverse Event, and 
498 
Device Issue Reporting 
499 
6.1 Unanticipated Problems 
500 
Site investigators will promptly report to the Coordinating Center and Sponsor on an eCRF all 
501 
unanticipated problems meeting the criteria below. For this protocol, an unanticipated problem is an 
502 
incident, experience, or outcome that meets all of the following criteria: 
503 
• 
Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are 
504 
described in the protocol related documents, such as the IRB-approved research protocol and 
505 
informed consent document; and (b) the characteristics of the subject population being studied 
506 
• 
Related or possibly related to participation in the research (possibly related means there is a 
507 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
508 
procedures involved in the research) 
509 
• 
Suggests that the research places participants or others at a greater risk of harm than was previously 
510 
known or recognized (including physical, psychological, economic, or social harm) 
511 
The Coordinating Center will report to the IRB all unanticipated problems not directly involving a 
512 
specific site such as unanticipated problems that occur at another participating entity such as a pharmacy 
513 
or laboratory. These instances must be reported to the study IRB within seven calendar days of 
514 
recognition. The Sponsor will report to the appropriate regulatory authorities if the IRB determines that 
515 
the event indeed meets the criteria of an Unanticipated Problem requiring additional reporting. 
516 
6.2 Adverse Events 
517 
6.2.1 Definitions 
518 
Adverse Event (AE): Any untoward medical occurrence (including laboratory findings) associated with 
519 
study procedures, the use of a device, biologic in a study participant, including any comparator used, 
520 
irrespective of the relationship between the adverse event and the device(s) under investigation (referred 
521 
to as Adverse Reaction when caused by a drug). 
522 
Serious Adverse Event (SAE): Any untoward medical occurrence that meets at least one of the following: 
523 
• 
Results in death. 
524 
• 
Is life-threatening; (a non-life-threatening event which, had it been more severe, might have become 
525 
life-threatening, is not necessarily considered a serious adverse event). 
526 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
527 
• 
Results in persistent or significant disability/incapacity or substantial disruption of the ability 
528 
to conduct normal life functions (sight threatening). 
529 
• 
Is a congenital anomaly or birth defect. 
530 
• 
Is considered a significant medical event by the investigator based on medical judgment (e.g., may 
531 
jeopardize the participant or may require medical/surgical intervention to prevent one of the outcomes 
532 
listed above). 
533 
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety or any 
534 
life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death 
535 
was not previously identified in nature, severity, or degree of incidence in the investigational plan or 
536 
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application (including a supplementary plan or application), or any other unanticipated serious problem 
537 
associated with a device that relates to the rights, safety, or welfare of participants (21 CFR 812.3(s)). 
538 
Adverse Device Effect (ADE): Any untoward medical occurrence in a study participant which the device 
539 
may have caused or to which the device may have contributed (Note that an Adverse Event Form is to be 
540 
completed in addition to a Device Issues Form, unless excluded from reporting as defined in section 
541 
6.2.2). 
542 
Comparator: Medical device, therapy (e.g. active treatment, normal clinical practice), placebo or no 
543 
treatment, used in the control group in a clinical investigation. (ISO 14155:2020) 
544 
Device Complaints and Malfunctions: A device complication or complaint is something that happens 
545 
to a device or related to device performance, whereas an adverse event happens to a participant. A device 
546 
complaint may occur independently from an AE, or along with an AE. An AE may occur without a 
547 
device complaint or there may be an AE related to a device complaint. A device malfunction is any 
548 
failure of a device to meet its performance specifications or otherwise perform as intended. 
549 
Performance specifications include all claims made in the labeling for the device. The intended 
550 
performance of a device refers to the intended use for which the device is labeled or marketed. 
551 
(21 CFR 803.3). Note: for reporting purposes, sites will not be asked to distinguish between device 
552 
complaints and malfunctions. 
553 
Use Error: User action or lack of user action while using the medical device (3.34) that leads to a 
554 
different result than that intended by the manufacturer or expected by the user. Includes the inability of 
555 
the user to complete a task. Use errors can result from a mismatch between the characteristics of the user, 
556 
user interface, task or use environment. Users might be aware or unaware that a use error has occurred. 
557 
An unexpected physiological response of the patient is not by itself considered a use error. A malfunction 
558 
of a medical device that causes an unexpected result is not considered a use error. (ISO 14155:2020) 
559 
6.2.2 Reportable Adverse Events 
560 
A reportable adverse event includes all events meeting the definition of an adverse event, except for the 
561 
following: 
562 
• 
Hypoglycemia and hyperglycemia not meeting the criteria below will not be recorded as adverse 
563 
events unless associated with an Adverse Device Effect or discontinuation of the study device or 
564 
study drug.  
565 
• 
Skin reactions from sensor or pump infusion set placement are only reportable if severe and/or 
566 
required treatment. 
567 
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All reportable AEs—whether volunteered by the participant, discovered by study personnel during 
568 
questioning, or detected through physical examination, laboratory test, or other means—will be reported 
569 
on an AE form online. Each AE form is reviewed by the Medical Monitor to assess safety and to verify 
570 
the coding and the reporting that is required. 
571 
6.2.3 Hypoglycemic Events 
572 
Hypoglycemia is only reportable as an adverse event when one of the following criteria is met: 
573 
• 
a hypoglycemic event occurred meeting the following definition of severe hypoglycemia:  the event 
574 
required assistance of another person due to altered consciousness, and required another person to 
575 
actively administer carbohydrate, glucagon, or other resuscitative actions. This means that the 
576 
participant was impaired cognitively to the point that he/she was unable to treat himself/herself, was 
577 
unable to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or experienced 
578 
seizure or loss of consciousness. These episodes may be associated with sufficient neuroglycopenia to 
579 
induce seizure or loss of consciousness. If glucose measurements are not available during such an 
580 
event, neurological recovery attributable to the restoration of glucose to normal is considered 
581 
sufficient evidence that the event was induced by a low glucose concentration. 
582 
• 
evaluation or treatment was obtained at a health care provider facility for an acute event involving 
583 
hypoglycemia, or the participant contacted the site and received guidance following the occurrence of 
584 
an acute event involving hypoglycemia 
585 
When a severe hypoglycemia event occurs (as defined above), an Adverse Event Form should be 
586 
completed. Severe hypoglycemia events should be considered to be serious adverse events with respect to 
587 
reporting requirements. When a severe hypoglycemia event occurs during use of a study device, it 
588 
generally will be considered to be unrelated to the device (per section 6.2.5) if the device functioned as 
589 
intended and there does not appear to be a flaw in how the device is intended to function. 
590 
6.2.4 Hyperglycemic/Ketotic Events 
591 
Hyperglycemia is only reportable as an adverse event when one of the following criteria is met:   
592 
• 
the event involved DKA, as defined by the Diabetes Control and Complications Trial (DCCT) and 
593 
described below 
594 
• 
evaluation or treatment was obtained at a health care provider facility for an acute event involving 
595 
hyperglycemia or ketosis, or the participant contacted the site and received guidance on how to 
596 
manage the hyperglycemia/ketosis 
597 
• 
blood ketone level ≥0.6 mmol/L, even if there was no communication with a health care provider at 
598 
the time of the event 
599 
Hyperglycemic events are classified as DKA if the following are present: 
600 
• 
Symptoms such as polyuria, polydipsia, nausea, or vomiting; 
601 
• 
Serum ketones >1.5 mmol/L or large/moderate urine ketones; 
602 
• 
Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate (or CO2) <15; and 
603 
• 
Treatment provided in a health care facility 
604 
When a hyperglycemia/ketotic event qualifies as an SAE as defined in section 6.2.1, an Adverse Event 
605 
Form should be completed. Events meeting DKA criteria should be considered to be serious adverse 
606 
events with respect to reporting requirements. Hyperglycemia events not meeting criteria  for DKA 
607 
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generally will not be considered as serious adverse events unless one of the SAE criteria in section 6.2.1 
608 
is met. 
609 
DKA can occur at “euglycemic” glucose levels less than 250 mg/dL, and may occur more commonly in 
610 
individuals taking adjuvant medications for glucose control such as SGLT-2 inhibitors. This should be 
611 
reported as a DKA event if it occurs. 
612 
When a hyperglycemia/DKA event occurs during use of a study device, it generally will be considered to 
613 
be unrelated to the device (per section 6.2.5) if the device functioned as intended and there does not 
614 
appear to be a flaw in how the device is intended to function. 
615 
6.2.5 Relationship of Adverse Event to Study Investigational Device 
616 
The study investigator will assess the relationship of any adverse event to the study device or study drug. 
617 
The Medical Monitor also will make this assessment, which may or may not agree with that of the study 
618 
investigator. Reporting requirements will be based on the Medical Monitor’s assessment. 
619 
To ensure consistency of adverse event causality assessments, investigators should apply the following 
620 
general guidelines when determining whether an adverse event is related to a study device or study drug: 
621 
Unrelated: The AE is clearly not related to a study drug/device and a likely alternative etiology exists 
622 
such as an underlying disease, environmental or toxic factors or other therapy. 
623 
Unlikely Related: The AE does not follow a reasonable temporal sequence during or after use of study 
624 
drug/device and a more likely alternative etiology exists such as an underlying disease, environmental or 
625 
toxic factors, or other therapy.  
626 
Possibly Related: The AE occurred in a reasonable time during or after use of study drug/device; but 
627 
could be related to another factor such as an underlying disease, environmental or toxic factors, or other 
628 
therapy; and there is a possible, though weak, scientific basis for establishing a causal association 
629 
between the AE and the study drug/device. 
630 
Probably Related: The AE occurred in a reasonable time during or after use of study drug/device; is 
631 
unlikely to be related to another factor such as an underlying disease, environmental or toxic factors, or 
632 
other therapy; and there is a plausible, though not strong, scientific basis for establishing a causal 
633 
association between the AE and the study drug/device.  
634 
Definitely Related: The AE occurred in a reasonable time during or after use of study drug/device; 
635 
cannot be explained by another factor such as an underlying disease, environmental or toxic factors, or 
636 
therapy; and there is a strong scientific basis for establishing a causal association between the AE and the 
637 
study drug/device.  
638 
Events determined to be Possibly Related, Probably Related, or Definitely Related will be considered 
639 
‘Related’ with respect to any required IRB and FDA reporting. 
640 
6.2.6 Severity (Intensity) of Adverse Events 
641 
The severity (intensity) of an adverse event will be rated on a three-point scale: (1) mild, (2) moderate, 
642 
or (3) severe. A severity assessment is a clinical determination of the intensity of an event. Thus, a severe 
643 
adverse event is not necessarily serious. For example, itching for several days may be rated as severe, but 
644 
may not be clinically serious. 
645 
MILD: Usually transient, requires no special treatment, and does not interfere with the participant’s daily 
646 
activities. 
647 
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MODERATE: Usually causes a low level of inconvenience, discomfort or concern to the participant 
648 
and may interfere with daily activities, but is usually ameliorated by simple therapeutic measures and 
649 
participant is able to continue in study. 
650 
SEVERE: Interrupts a participant’s usual daily activities, causes severe discomfort, may cause 
651 
discontinuation of study device, and generally requires systemic drug therapy or other treatment. 
652 
6.2.7 Expectedness 
653 
For a serious adverse event that is considered possibly related to study device, the Medical Monitor will 
654 
classify the event as unexpected if the nature, severity, or frequency of the event is not consistent with the 
655 
risk information previously described in the protocol, labeling, or Investigator Brochure. 
656 
6.2.8 Coding of Adverse Events 
657 
Adverse events will be coded using the MedDRA dictionary.  
658 
6.2.9 Outcome of Adverse Events 
659 
The outcome of each reportable adverse event will be classified by the investigator as follows: 
660 
• 
RECOVERED/RESOLVED – The participant recovered from the AE/SAE without sequelae. Record 
661 
the AE/SAE stop date. 
662 
• 
RECOVERED/RESOLVED WITH SEQUELAE – The event persisted and had stabilized without 
663 
change in the event anticipated. Record the AE/SAE stop date. 
664 
• 
FATAL – A fatal outcome is defined as the SAE that resulted in death. Only the event that was the 
665 
cause of death should be reported as fatal. AEs/SAEs that were ongoing at the time of death; 
666 
however, were not the cause of death, will be recorded as “resolved” at the time of death. 
667 
• 
NOT RECOVERED/NOT RESOLVED (ONGOING) – An ongoing AE/SAE is defined as the event 
668 
was ongoing with an undetermined outcome. 
669 
An ongoing outcome will require follow-up by the site in order to determine the final outcome 
670 
of the AE/SAE. The outcome of an ongoing event at the time of death that was not the cause of 
671 
death, will be updated and recorded as “resolved” with the date of death recorded as the stop 
672 
date. 
673 
• 
UNKNOWN – An unknown outcome is defined as an inability to access the participant or the 
674 
participant’s records to determine the outcome (for example, a participant that was lost to follow-up). 
675 
If any reported adverse events are ongoing when a participant completes the study (or withdraws), 
676 
adverse events classified as UADEs or related SAEs or SUSARs will be followed until they are either 
677 
resolved, or have no prospect of improvement or change, even after the participant has completed all 
678 
applicable study visits/contacts. For all other adverse events, data collection will end at the time the 
679 
participant completes the study. Note: participants should continue to receive appropriate medical care 
680 
for an adverse event after their participation in the study ends. 
681 
6.3 Reportable Device Issues 
682 
All UADEs and ADEs as defined in section 6.2.1 will be reported as both a ‘device issues’ and ‘adverse 
683 
event’, except for skin reactions from CGM sensor placement or pump infusion set placement that do not 
684 
require pharmacologic treatment. 
685 
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Device complaints and device malfunctions will be reported except in the following circumstances. 
686 
These occurrences are expected and will not be reported on a Device Issue Form assuming criteria for 
687 
a UADE or ADE have not been met: 
688 
• 
CGM sensor lasting fewer days than expected per manufacturer 
689 
• 
CGM tape adherence issues 
690 
• 
Pump infusion set insertion lasting fewer days than expected per manufacturer 
691 
• 
Battery lifespan deficiency due to inadequate charging or extensive wireless communication 
692 
• 
Intermittent device component disconnections/communication failures not requiring system 
693 
replacement or workaround/resolution not specified in user guide/manual. 
694 
• 
Device issues clearly addressed in the user guide manual that do not require additional 
695 
troubleshooting 
696 
6.4 Timing of Event Reporting 
697 
SAEs possibly related to a study device, study drug, or study participation and UADEs must be reported 
698 
by the site to the Sponsor within 1 working day of the site becoming aware of the event. This can occur 
699 
via phone or email, or by completion of the appropriate eCRFs as applicable. If the form(s) are not 
700 
initially completed, they should be competed as soon as possible after there is sufficient information to 
701 
evaluate the event. All other reportable ADEs and other reportable AEs should be submitted by 
702 
completion on the eCRF(s) within 7 days of the site becoming aware of the event.  
703 
The Sponsor will notify all participating investigators of any adverse event that is serious, related, and 
704 
unexpected. Notification will be made within 10 working days after the Sponsor becomes aware of the 
705 
event. 
706 
Each principal investigator is responsible for reporting serious study-related adverse events and abiding 
707 
by any other reporting requirements specific to his/her Institutional Review Board or Ethics Committee.  
708 
Upon receipt of a qualifying event, the Sponsor will investigate the event to determine if a UADE has 
709 
occurred, and if indicated, report the results of the investigation to all overseeing IRBs, and the FDA 
710 
within 10 working days of the Sponsor becoming aware of the UADE per 21CFR 812.46(b). The Sponsor 
711 
must determine if the UADE presents an unreasonable risk to participants. If so, the Sponsor must ensure 
712 
that all investigations, or parts of investigations presenting that risk, are terminated as soon as possible but 
713 
no later than 5 working days after the Sponsor makes this determination and no later than 15 working 
714 
days after first receipt notice of the UADE. 
715 
The investigators are also required to report, without unjustified delay, all device complaints and 
716 
malfunctions that could have led to a UADE, including device complaints and malfunctions, irrespective 
717 
of whether an adverse event occurred. 
718 
6.5 Safety Oversight 
719 
The study Sponsor’s Medical Director will serve as Medical Monitor, and will review all adverse events, 
720 
including all cases of severe hypoglycemia and DKA, and adverse device events that are reported during 
721 
the study. SAEs typically will be reviewed within 1 working day of reporting. Other AEs typically will be 
722 
reviewed on a weekly basis, as per the study safety management plan. 
723 
The Medical Monitor will determine if the events require expedited reporting to FDA, IRB and/or all 
724 
participating sites. In addition, the Medical Monitor will confirm the MedDRA code assigned and 
725 
adjudicate events for relatedness to the study procedure and investigational device, assess seriousness and 
726 
severity, and determine if the event the event is anticipated or unanticipated. Both the investigator’s and 
727 
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Medical Monitor’s assessments will be recorded, however, the adjudication decision of the Medical 
728 
Monitor will be used for the final classification of events, including relatedness to the study procedures 
729 
and/or the investigational device, for the determination of safety endpoints and for all regulatory reports, 
730 
product labeling, and publications or presentations.   
731 
6.6 Stopping Criteria 
732 
6.6.1 Participant Discontinuation of Study Device 
733 
In the case of an unanticipated system malfunction resulting in a severe hypoglycemia or DKA event 
734 
(or a malfunction that could have led to severe hypoglycemia or DKA), use of the study device will be 
735 
suspended for that participant while the problem is diagnosed. The UADE will be reported to the IRB and 
736 
FDA. After assessment of the problem and any correction, use of the study device will not be restarted 
737 
until approval is received from the IRB and FDA. 
738 
In the absence of a device malfunction, use of the study device by a participant will be discontinued if 
739 
any of the following occur:  
740 
• 
The investigator believes it is unsafe for the participant to continue on the intervention. This could be 
741 
due to the development of a new medical condition or worsening of an existing condition; or 
742 
participant behavior contrary to the indications for use of the device that imposes on the participant’s 
743 
safety 
744 
• 
The participant requests that the treatment be stopped 
745 
• 
Participant pregnancy 
746 
• 
Two distinct episodes of DKA as defined in section 6.2.4 
747 
• 
Two distinct severe hypoglycemia events as defined in section 6.2.3 
748 
• 
One episode of DKA as defined in section 6.2.4 and one severe hypoglycemia event as defined in 
749 
section 6.2.3 
750 
Each DKA or severe hypoglycemia event will be reviewed by the Medical Monitor with respect to 
751 
determination of cause and whether the occurrence of the event can be attributed to use of the study 
752 
device or study drug.  
753 
An additional requirement for continued study device use following a single DKA or severe 
754 
hypoglycemia event will be that the site investigator believes that the event is unlikely to recur and that 
755 
it is safe for the participant to continue to use the system. Additionally, if the Medical Monitor determines 
756 
that the occurrence of the event indicates that it is not safe for the participant to continue to use the study 
757 
device, use will be discontinued. 
758 
6.6.2 Criteria for Suspending or Stopping Overall Study 
759 
In addition to the suspension of device use due to a UADE as described in section 6.6.1, study activities 
760 
could be similarly suspended if the manufacturer of any constituent study device requires stoppage of 
761 
device use for safety reasons (e.g. product recall). The affected study activities may resume if the 
762 
underlying problem can be corrected by a protocol or system modification that will not invalidate the 
763 
results obtained prior to suspension. 
764 
Closed-loop system use will also be suspended if there are three or more cases of severe hypoglycemia or 
765 
three or more cases of hyperglycemia/ketotic events qualifying as SAEs across the entire study in 
766 
participants who have initiated Control-IQ technology use. The IRBs and FDA will be notified. After 
767 
assessment of the problem and any corrections are implemented, use of the closed-loop system may be 
768 
restarted if approval is received from the IRBs and FDA. 
769 
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770 
 
771 
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Chapter 7: Miscellaneous Considerations 
772 
7.1 Drugs Used as Part of the Protocol 
773 
Subjects may use their own Humalog (insulin lispro) or Novolog (insulin aspart) during the Treatment 
774 
Period, however, Humalog or Novolog will be provided to the subject as part of the study. 
775 
7.2 Collection of Medical Conditions and Medications 
776 
Pre-Existing Conditions: Any medical condition that is either present at screening, a chronic disease, 
777 
or a prior condition that could impact the participant’s health during the course of the study (e.g., prior 
778 
myocardial infarction or stroke) will be recorded. 
779 
Medical Conditions Developing During the Study: Medical conditions developing during the study will 
780 
be reviewed by the investigator for their relationship to the study device. 
781 
Medications: All medications in use at the time of screening or added during the course of the study will 
782 
be recorded. Nutraceuticals and preventative treatment also will be recorded. Medications only taken as 
783 
needed either can be recorded when prescribed or only recorded if used during the study. Glucagon for 
784 
treatment of severe hypoglycemia will only be recorded if used during the study. 
785 
7.3 Prohibited Medications, Devices, Treatments, and Procedures 
786 
Treatment with any insulin other than Humalog or Novolog insulin is not permitted with the study device. 
787 
Treatment with sulfonylureas, meglitinides or Symlin is not permitted. 
788 
No new additional non-insulin glucose lowering medications may be added during the trial.  
789 
Participants taking GLP-1 receptor agonists, DPP-4 inhibitors, and/or SGLT-2 inhibitors will be allowed 
790 
to continue these medications if they are on a stable dose of such medication for the last 3 months. These 
791 
participants will be instructed to perform additional glucose and ketone monitoring as specified in section 
792 
3.1.3 Training on Management of Hyperglycemia and 3.1.2 Training on Management of Hypoglycemia. 
793 
Medications used for weight loss will be allowed if the participant is on a stable dose of such medication 
794 
for the last 3 months. No new medications for weight loss may be added during the trial.  
795 
Additional medications may be excluded per judgement of the investigator.  
796 
The investigational study devices (t:slim X2 insulin pump, Dexcom CGM sensor) must be removed 
797 
before magnetic resonance imaging (MRI), computed tomography (CT) or diathermy treatment. 
798 
Participants may continue in the trial after temporarily discontinuing use if requiring one of the above. 
799 
7.4 Rescue Medications, Treatments, and Procedures 
800 
Each participant will be required to have a glucagon preparation for rescue therapy for severe 
801 
hypoglycemia. 
802 
7.5 Pregnancy Reporting 
803 
If pregnancy occurs, the participant will be discontinued from the study. The occurrence of pregnancy 
804 
will be reported to the Coordinating Center within seven days and to the IRB as an Unanticipated 
805 
Problem within seven calendar days. 
806 
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7.6 Participant Compensation 
807 
Participant compensation will be specified in the informed consent form. 
808 
7.7 Participant Withdrawal 
809 
Participation in the study is voluntary, and a participant may withdraw at any time. For participants who 
810 
withdraw, their data will be used up until the time of withdrawal. 
811 
 
812 
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Chapter 8: Statistical Considerations 
813 
8.1 Statistical Hypotheses 
814 
The primary objective of the study is assessment of safety. Therefore, there is no formal statistical 
815 
hypothesis testing for efficacy. Safety endpoints will be compared with historical published data. 
816 
8.2 Sample Size 
817 
The sample size of at least 30 completers of the trial was selected to have a reasonable number of hours of 
818 
use, with each subject completing approximately 3 months use of the study system with the removal of 
819 
the basal clipping feature, and not for assessing safety endpoints and is not based on statistical principles. 
820 
8.3 Outcome Measures 
821 
Primary Safety Endpoints 
822 
• 
Rate of severe hypoglycemia as defined in section 6.2.3 
823 
• 
Rate of diabetic ketoacidosis as defined in section 6.2.4 
824 
• 
Number of unanticipated adverse device effects 
825 
• 
Number of other serious adverse events 
826 
Secondary Safety Endpoints 
827 
• 
All reportable adverse events 
828 
• 
CGM hypoglycemia outcomes 
829 
 
Overall % time <54 mg/dL 
830 
 
Overall % time <70 mg/dL 
831 
Exploratory Endpoints 
832 
• 
Times in ranges-overall (70-180 mg/dL, >180 mg/dL, >250 mg/dL, 70-140 mg/dL) 
833 
• 
Mean glucose 
834 
• 
Overall variability (CV and SD) 
835 
• 
HbA1c change from baseline 
836 
• 
CGM metrics for hypoglycemia, hyperglycemia, and variability during daytime and nighttime 
837 
8.4 Analysis Datasets  
838 
Safety analysis set: All participants who initiate the Treatment Period and use the study device 
839 
CGM analysis set: Any member of the Safety Analysis Set who has at least 24 hours of CGM data during 
840 
the Treatment Period. CGM data occurring within the meal and exercise challenge windows will not be 
841 
included in this set. 
842 
Meal and exercise challenge set: Any member of the Safety Analysis Set who has at least 24 hours of 
843 
CGM data during the Treatment Period. Only CGM data occurring within the meal and exercise challenge 
844 
windows will be included in this set. 
845 
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8.5 Statistical Methods 
846 
8.5.1 Analysis of the Safety Event Endpoints 
847 
Safety events (ie, not including CGM defined events) will be tabulated for each type of event as the 
848 
number of events per participant, the number of participants with > 1 event, and the rate of events per 
849 
100 person-years. 
850 
Since study eligibility excluded participants with 2 or more severe hypoglycemia or DKA events in the 
851 
prior 6 months, an unbiased comparison of the event rate during the Treatment Period with the pre-study 
852 
event rate is not possible. Therefore, the severe hypoglycemia and DKA event rates will be compared 
853 
with the T1D Exchange data,4 which reported the frequency of 1 or more severe hypoglycemia and DKA 
854 
events in the prior 3 months. The proportion of participants with events during the Treatment Period will 
855 
be compared with the T1D Exchange frequency. 
856 
8.5.2 Analysis of CGM Endpoints 
857 
CGM metrics will be computed for the Treatment Period. CGM metrics will be computed over 24 hours, 
858 
during daytime (6am-11:59pm), and during nighttime (12am-5:59am). 
859 
The main statistical comparison will be made between the Treatment Period and historical data. 
860 
8.5.3 Intervention Adherence 
861 
The following tabulations will be performed: 
862 
• 
Sensor use–percent time of use as a function of overall treatment period 
863 
• 
Closed loop system use–percent time of use as a function of overall treatment period 
864 
• 
% time in different operational modes as a function of overall treatment period 
865 
8.6 Protocol Adherence and Retention 
866 
The following tabulations and analyses will be performed to assess protocol adherence for the study: 
867 
• 
Number of protocol deviations  
868 
• 
Flow chart accounting for all enrolled participants  
869 
• 
Number of and reasons for unscheduled visits and phone calls 
870 
• 
Number of participants who were enrolled but did not enter the Treatment Period and reasons 
871 
• 
Number of participants who stopped treatment and reasons 
872 
8.7 Baseline Descriptive Statistics 
873 
Baseline demographic and clinical characteristics of the cohort of participants who initiate the Treatment 
874 
Period will be summarized in a table using summary statistics appropriate to the distribution of each 
875 
variable. Descriptive statistics will be displayed by treatment group for the following: 
876 
• 
Age 
877 
• 
Sex 
878 
• 
Race/Ethnicity 
879 
• 
Socio-economic factors (income, education, and/or insurance status) 
880 
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• 
Diabetes duration 
881 
• 
HbA1c 
882 
• 
BMI 
883 
• 
Total daily insulin 
884 
• 
Prior severe hypoglycemia and DKA events 
885 
8.8 Additional Tabulations and Analyses 
886 
The following data will be tabulated at baseline and at or over 13 weeks 
887 
• 
Insulin metrics (units/kg): total daily insulin, total daily basal insulin, total daily bolus insulin (plus 
888 
total daily manual bolus, total daily automated bolus) 
889 
8.9 Device Issues 
890 
The following tabulations will be performed with respect to device issues: 
891 
• 
Reported device issues according to type of issue 
892 
8.10 Planned Interim Analyses 
893 
No formal interim analyses are planned. 
894 
8.11 Subgroup Analyses 
895 
Results will be tabulated according to baseline HbA1c and total daily insulin. 
896 
8.12 Multiple Comparison/Multiplicity 
897 
Safety event endpoints will not be corrected for multiple comparisons.  
898 
8.13 Analysis of Meal and Exercise Challenges 
899 
The meal and exercise challenges will be analyzed with the same CGM metrics and safety outcomes 
900 
above to be tabulated during and after (specifically to include the time period through 3 hours after each 
901 
meal challenge [end of meal challenge] and through 2 hours after the completion of each exercise 
902 
challenge) and overnight (12am-5:59am) after each challenge performed. Separate analysis will be 
903 
conducted for each type of challenge. These challenge analysis periods will be excluded from the analysis 
904 
of main CGM metrics.
905 
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Chapter 9: Data Collection and Monitoring 
906 
9.1 Case Report Forms and Other Data Collection 
907 
The main study data are collected on electronic case report forms (eCRFs). When data are directly 
908 
collected in electronic case report forms, this will be considered the source data. For any data points 
909 
for which the eCRF is not considered source (e.g. lab results that are transcribed from a printed report 
910 
into the eCRF, data collected in the electronic medical record, study specific source worksheets, etc.), the 
911 
original source documentation will be maintained in the participant’s study chart or medical record. This 
912 
source must be readily verifiable against the values entered into eCRF.  
913 
Electronic device data files are obtained from the study software and individual hardware components. 
914 
These electronic device files are considered the primary source documentation. 
915 
HbA1c measurements will be performed locally for the screening visit, and by the central laboratory prior 
916 
to closed-loop start and at end of study. 
917 
9.2 Study Records Retention 
918 
Each participating site will maintain appropriate medical and research records for this trial, in 
919 
compliance with GCP and regulatory and institutional requirements for the protection of confidentiality of 
920 
participants. 
921 
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
922 
application in an ICH region and until there are no pending or contemplated marketing applications in an 
923 
ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical development 
924 
of the investigational product. These documents should be retained for a longer period, however, 
925 
if required by local regulations. No records will be destroyed without the written consent of the sponsor, 
926 
if applicable. It is the responsibility of the sponsor to inform the investigator when these documents no 
927 
longer need to be retained. 
928 
9.3 Quality Assurance and Monitoring 
929 
Designated personnel from the Coordinating Center will be responsible for maintaining quality 
930 
assurance (QA) and QC systems to ensure that the clinical portion of the trial is conducted and data are 
931 
generated, documented and reported in compliance with the protocol, GCP and the applicable regulatory 
932 
requirements, as well as to ensure that the rights and wellbeing of trial participants are protected and that 
933 
the reported trial data are accurate, complete, and verifiable. Adverse events will be prioritized for 
934 
monitoring. 
935 
A monitoring plan will be developed and revised as needed during the course of the study. Study conduct 
936 
and monitoring will conform with 21 Code of Federal Regulations (CFR) 812. This plan will describe in 
937 
detail who will conduct the monitoring, at what frequency monitoring will be done, at what level of detail 
938 
monitoring will be performed, and the distribution of monitoring reports. 
939 
The data of most importance for monitoring at the site are participant eligibility and adverse events. 
940 
Therefore, the monitoring plan will focus on these areas. As much as possible, remote monitoring will be 
941 
performed in real-time with on-site monitoring performed to evaluate the verity and completeness of 
942 
the key site data. Elements of the monitoring plan may include: 
943 
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• 
Qualification assessment, training, and certification for sites and site personnel 
944 
• 
Oversight of Institutional Review Board (IRB) coverage and informed consent procedures 
945 
• 
Central (remote) data monitoring: validation of data entry, data edits/audit trail, protocol review of 
946 
entered data and edits, statistical monitoring, study closeout 
947 
• 
On-site monitoring (site visits): source data verification, site visit report 
948 
• 
Agent/Device accountability 
949 
• 
Communications with site staff 
950 
• 
Patient retention and visit completion 
951 
• 
Quality control reports 
952 
• 
Management of noncompliance 
953 
• 
Documenting monitoring activities 
954 
• 
Adverse event reporting and monitoring 
955 
Coordinating Center representatives or their designees may visit the study facilities at any time in order 
956 
to maintain current and personal knowledge of the study through review of the records, comparison 
957 
with source documents, observation and discussion of the conduct and progress of the study. 
958 
The investigational site will provide direct access to all trial related source data/documents, and reports 
959 
for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory 
960 
authorities. 
961 
9.4 Protocol Deviations 
962 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or procedure 
963 
requirements. The noncompliance may be either on the part of the participant, the investigator, or the 
964 
study site staff. A significant (or major) deviation is any deviation that departs from the established 
965 
materials in such a way that it poses an increase in the risk to subjects, adversely affects the welfare, 
966 
rights, or safety of the research subjects, or negatively influences the scientific study integrity. As a 
967 
result of a significant deviation, a corrective and preventive action plan shall be developed by the site 
968 
and implemented promptly. 
969 
The site PI/study staff is responsible for knowing and adhering to their IRB requirements. Further details 
970 
about the handling of protocol deviations will be included in the monitoring plan. 
971 
 
972 
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Chapter 10: Ethics/Protection of Human Participants 
973 
10.1 Ethical Standard 
974 
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
975 
Protection of Human Participants of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR 
976 
Part 56, and/or the ICH E6. 
977 
10.2 Institutional Review Boards 
978 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
979 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must 
980 
be obtained before any participant is enrolled. Any amendment to the protocol will require review and 
981 
approval by the IRB before the changes are implemented to the study. All changes to the consent form 
982 
will be IRB approved; a determination will be made regarding whether previously consented participants 
983 
need to be re-consented. 
984 
10.3 Informed Consent Process 
985 
10.3.1 Consent Procedures and Documentation 
986 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study 
987 
and continues throughout the individual’s study participation. Extensive discussion of risks and possible 
988 
benefits of participation will be provided to the participants and their families. Consent forms will be 
989 
IRB-approved and the participant will be asked to read and review the document. The investigator will 
990 
explain the research study to the participant and answer any questions that may arise. All participants 
991 
will receive a verbal explanation in terms suited to their comprehension of the purposes, procedures, 
992 
and potential risks of the study and of their rights as research participants. Participants will have the 
993 
opportunity to carefully review the written consent form and ask questions prior to signing. 
994 
The participants should have the opportunity to discuss the study with their surrogates or think about 
995 
it prior to agreeing to participate. The participant will sign the informed consent document prior to any 
996 
procedures being done specifically for the study. The participants may withdraw consent at any time 
997 
throughout the course of the trial. A copy of the informed consent document will be given to the 
998 
participants for their records. The rights and welfare of the participants will be protected by emphasizing 
999 
to them that the quality of their medical care will not be adversely affected if they decline to participate 
1000 
in this study. 
1001 
10.3.2 Participant and Data Confidentiality 
1002 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
1003 
sponsor(s) and their agents. This confidentiality is extended to cover testing of biological samples and 
1004 
genetic tests in addition to the clinical information relating to participants. Therefore, the study protocol, 
1005 
documentation, data, and all other information generated will be held in strict confidence. No information 
1006 
concerning the study or the data will be released to any unauthorized third party without prior written 
1007 
approval of the sponsor. 
1008 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB, regulatory 
1009 
agencies or company supplying study product may inspect all documents and records required to be 
1010 
maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) 
1011 
and pharmacy records for the participants in this study. The clinical study site will permit access to such 
1012 
records. 
1013 
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The study participant’s contact information will be securely stored at each clinical site for internal use 
1014 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
1015 
long a period as dictated by the reviewing IRB, institutional policies, sponsor requirements and applicable 
1016 
regulations. 
1017 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
1018 
be transmitted to and stored at the Coordinating Center. This will not include the participant’s contact or 
1019 
identifying information, unless otherwise specified in the informed consent form. Rather, individual 
1020 
participants and their research data will be identified by a unique study identification number. The study 
1021 
data entry and study management systems used by clinical sites and by the Coordinating Center research 
1022 
staff will be secured and password protected. At the end of the study, all study databases will be de-
1023 
identified and archived at the Coordinating Center. 
1024 
10.3.3 Future Use of Stored Specimens and Data 
1025 
Data collected for this study will be analyzed and stored at the Coordinating Center. After the study is 
1026 
completed, a dataset will be provided to the study Sponsor. 
1027 
No biologic specimens will be stored. 
1028 
 
1029 
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Contains trade secrets and/or confidential information exempt from disclosure from 21 CFR 20.61 
Chapter 11: References 
1030 
 
1031 
1. Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, 
1032 
Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ 3rd, Anderson SM, Church MM, 
1033 
Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW; iDCL 
1034 
Trial Research Group.  Six-month randomized, multicenter trial of closed-loop control in 
1035 
type 1 diabetes. N Engl J Med. 2019; 381:1707-1717. 
1036 
2. Breton MD, Kanapka LG, Beck RW, Ekhlaspour L, Forlenza GP, Cengiz E, Schoelwer M, 
1037 
Ruedy KJ, Jost E, Carria L, Emory E, Hsu LJ, Oliveri M, Kollman CC, Dokken BB, 
1038 
Weinzimer SA, DeBoer MD, Buckingham BA, Cherñavvsky D, Wadwa RP; iDCL Trial 
1039 
Research Group. A randomized trial of closed-loop control in children with type 1 diabetes. 
1040 
N Engl J Med. 2020; 383:836-845. 
1041 
3. Breton M, Kovatchev B. One year real-world use of the Control-IQ advanced hybrid closed 
1042 
loop technology. Diabetes Technol Ther. 2021;23:601-608. 
1043 
4. Foster et al. State of type 1 diabetes management and outcomes from the T1D Exchange in 
1044 
2016-2018. Diabetes Technol Ther. 2019; 21:66-72. 
1045 
 
1046 
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