Adaptation of Insulin Delivery Settings to Improve Clinical Outcomes With AID Use
Phase: NA
Conditions: Type 1 Diabetes
Sponsor: Tandem Diabetes Care, Inc.

 
 
  Confidential 
 
  
   Contains trade secrets and/or confidential information exempt from disclosure from 21 CFR 20.61 
 
1 
 
2 
Adaptation of Insulin Delivery Settings to Improve Clinical Outcomes with 
AID Use 
 
 
Study Sponsor: 
Tandem Diabetes Care, Inc. 
11075 Roselle Street 
San Diego, CA 92121 
 
Study Number:  
TP-0009348 
 
Study Phase:  
Feasibility 
 
IDE Number:  
G210262 
 
Study Device: 
1) t:slim X2 Insulin Pump with Control-IQ 1.0 technology 
2) Settings initializer and adaptation algorithm 
 
Protocol Chair: 
Jordan Pinsker, MD 
 
Date: 
01 OCT 2021 
 
Version:  
2.0 
 
3 
Confidentiality Statement 
4 
================================================================================== 
5 
The information contained herein is confidential information that is the sole and exclusive 
6 
property of Tandem Diabetes Care, Inc. and may not be divulged to any person (except as 
7 
required by law) without the prior written consent of Tandem Diabetes Care, Inc. No part of it 
8 
may be transmitted, reproduced, published, or used by other persons without prior written 
9 
permission. 
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Protocol Revision History 
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Version 
Number 
Amendment 
Date 
Brief Description of Changes 
1.0 
06 SEP 2021 
Initial Version Submitted to FDA 
2.0 
01 OCT 2021 
First Version Approved by FDA 
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TABLE OF CONTENTS 
14 
1 
SITE PRINCIPAL INVESTIGATOR STATEMENT OF COMPLIANCE ...................................................................... 5 
15 
2 
TERMS, ACRONYMS, ABBREVIATIONS ........................................................................................................... 6 
16 
3 
PROTOCOL SYNOPSIS .................................................................................................................................... 7 
17 
4 
BACKGROUND ............................................................................................................................................. 11 
18 
4.1 
DISEASE BACKGROUND ........................................................................................................................................ 11 
19 
4.2 
DEVICE BACKGROUND ......................................................................................................................................... 11 
20 
4.3 
SETTINGS OPTIMIZER .......................................................................................................................................... 11 
21 
5 
STUDY OBJECTIVES, DESIGNS AND ENDPOINTS ........................................................................................... 15 
22 
5.1 
STUDY OBJECTIVES ............................................................................................................................................. 15 
23 
5.2 
STUDY DESIGN ................................................................................................................................................... 15 
24 
5.3 
STUDY ENDPOINTS.............................................................................................................................................. 16 
25 
6 
SUBJECT SELECTION ..................................................................................................................................... 17 
26 
6.1 
SUBJECT POPULATION ......................................................................................................................................... 17 
27 
6.1.1 
Inclusion Criteria: ................................................................................................................................. 17 
28 
6.1.2 
Exclusion Criteria:................................................................................................................................. 17 
29 
6.2 
SUBJECT WITHDRAWAL OR TERMINATION ............................................................................................................... 18 
30 
7 
TREATMENT OF SUBJECTS ........................................................................................................................... 19 
31 
7.1 
THE T:SLIM X2 INSULIN PUMP WITH CONTROL-IQ TECHNOLOGY .................................................................................. 19 
32 
7.2 
ENROLLMENT PROCEDURE: ................................................................................................................................... 19 
33 
7.3 
DURATION OF THERAPY AND FOLLOW-UP: ............................................................................................................... 19 
34 
7.4 
STUDY PROCEDURES:........................................................................................................................................... 19 
35 
7.5 
EARLY TERMINATION VISIT (IF APPLICABLE) ............................................................................................................. 22 
36 
7.6 
UNSCHEDULED VISITS.......................................................................................................................................... 22 
37 
7.7 
FINAL CLINIC VISIT .............................................................................................................................................. 22 
38 
7.8 
POST STUDY PHONE CALL .................................................................................................................................... 23 
39 
8 
STATISTICAL CONSIDERATIONS ................................................................................................................... 24 
40 
8.1 
STATISTICAL ANALYSIS: ........................................................................................................................................ 24 
41 
9 
RISKS AND BENEFITS.................................................................................................................................... 25 
42 
9.1 
POTENTIAL RISKS AND BENEFITS OF THE DEVICE ....................................................................................................... 25 
43 
9.2 
VENIPUNCTURE RISKS ......................................................................................................................................... 25 
44 
9.3 
FINGERSTICK RISKS ............................................................................................................................................. 25 
45 
9.4 
SUBCUTANEOUS CATHETER RISKS (CGM) ............................................................................................................... 25 
46 
9.5 
RISK OF HYPOGLYCEMIA ...................................................................................................................................... 25 
47 
9.6 
RISK OF HYPERGLYCEMIA ..................................................................................................................................... 26 
48 
9.7 
RISK OF DEVICE REUSE ........................................................................................................................................ 26 
49 
9.8 
OTHER RISKS ..................................................................................................................................................... 26 
50 
9.9 
KNOWN POTENTIAL BENEFITS ............................................................................................................................... 26 
51 
9.10 
RISK ASSESSMENT .......................................................................................................................................... 26 
52 
9.11 
GENERAL CONSIDERATIONS ............................................................................................................................. 27 
53 
10 
DESCRIPTION OF THE STUDY DEVICES AND USE .......................................................................................... 28 
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10.1 
INSULIN PUMP .............................................................................................................................................. 28 
55 
10.2 
CONTINUOUS GLUCOSE MONITORING ............................................................................................................... 28 
56 
10.3 
BLOOD GLUCOSE METER AND STRIPS ................................................................................................................ 28 
57 
10.4 
KETONE METER AND STRIPS ............................................................................................................................ 28 
58 
10.5 
STUDY DEVICE ACCOUNTABILITY PROCEDURES .................................................................................................... 28 
59 
10.6 
BLOOD GLUCOSE METER TESTING .................................................................................................................... 28 
60 
10.7 
BLOOD KETONE TESTING ................................................................................................................................. 29 
61 
10.8 
CGM CALIBRATION ....................................................................................................................................... 29 
62 
10.9 
HYPERGLYCEMIA SAFETY PROTOCOL .................................................................................................................. 29 
63 
10.10 
HYPOGLYCEMIA SAFETY PROTOCOL ................................................................................................................... 29 
64 
11 
ADVERSE EVENTS, DEVICE ISSUES, AND STOPPING RULES ........................................................................... 30 
65 
11.1 
ADVERSE EVENTS........................................................................................................................................... 30 
66 
11.2 
REPORTABLE ADVERSE EVENTS ......................................................................................................................... 31 
67 
11.3 
HYPOGLYCEMIC EVENTS .................................................................................................................................. 31 
68 
11.4 
HYPERGLYCEMIC EVENTS/DIABETIC KETOACIDOSIS............................................................................................... 31 
69 
11.5 
RELATIONSHIP OF ADVERSE EVENT TO STUDY DEVICE ........................................................................................... 32 
70 
11.6 
INTENSITY OF ADVERSE EVENT ......................................................................................................................... 32 
71 
11.7 
CODING OF ADVERSE EVENTS .......................................................................................................................... 33 
72 
11.8 
OUTCOME OF ADVERSE EVENT ......................................................................................................................... 33 
73 
11.9 
REPORTABLE DEVICE ISSUES............................................................................................................................. 34 
74 
11.10 
PREGNANCY REPORTING ................................................................................................................................. 34 
75 
11.11 
TIMING OF EVENT REPORTING ......................................................................................................................... 34 
76 
11.12 
PARTICIPANT DISCONTINUATION OF STUDY DEVICE .............................................................................................. 35 
77 
11.13 
CRITERIA FOR SUSPENDING OR STOPPING OVERALL STUDY .................................................................................... 35 
78 
11.14 
SAFETY OVERSIGHT ........................................................................................................................................ 36 
79 
12 
MISCELLANEOUS CONSIDERATIONS ............................................................................................................ 37 
80 
12.1 
DRUGS USED AS PART OF THE PROTOCOL ........................................................................................................... 37 
81 
12.2 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES ................................................................................ 37 
82 
12.3 
PARTICIPANT COMPENSATION .......................................................................................................................... 37 
83 
12.1 
PARTICIPANT ACCESS TO STUDY DEVICE AT STUDY CLOSURE .................................................................................. 37 
84 
13 
DATA COLLECTION AND MONITORING ........................................................................................................ 38 
85 
13.1 
CASE REPORT FORMS AND DEVICE DATA ........................................................................................................... 38 
86 
13.2 
STUDY RECORDS RETENTION ............................................................................................................................ 38 
87 
13.3 
PROTOCOL DEVIATIONS .................................................................................................................................. 38 
88 
13.4 
ETHICAL STANDARD ....................................................................................................................................... 38 
89 
13.5 
INSTITUTIONAL REVIEW BOARDS ...................................................................................................................... 38 
90 
13.6 
CONSENT PROCEDURES AND DOCUMENTATION ................................................................................................... 39 
91 
13.7 
PARTICIPANT AND DATA CONFIDENTIALITY ......................................................................................................... 39 
92 
13.8 
PARTICIPANT WITHDRAWAL ............................................................................................................................ 40 
93 
13.9 
CONFIDENTIALITY .......................................................................................................................................... 40 
94 
14 
REFERENCES ................................................................................................................................................ 41 
95 
 
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1 SITE PRINCIPAL INVESTIGATOR STATEMENT OF 
98 
COMPLIANCE 
99 
Protocol Identifying Number: 
TP-0009348 
Protocol Name: 
Adaptation of Insulin Delivery Settings to Improve 
Clinical Outcomes with AID Use 
Protocol Version / Date: 
2.0 / 01 OCT 2021 
 
100 
The Principal Investigators (undersigned) hereby declare that they have read this protocol and 
101 
agree to its contents. 
102 
The undersigned confirms that the trial will be conducted and documented in accordance with 
103 
the US Federal, State and Local requirements for a post-market human clinical study, the 
104 
protocol, and the stipulations of the clinical trial agreement. 
105 
By written consent to this protocol, the investigators agree to the above and to fully co-operate 
106 
with all monitoring and audits in relation to this trial by allowing direct access to all 
107 
documentation, including source data, by authorized individuals representing Tandem Diabetes 
108 
Care, Inc., IRBs and/or by the US Federal, State and local regulatory authorities. 
109 
 
110 
Investigator Name: ___________________________________________ 
111 
 
112 
Investigator Signature: ________________________________________ 
113 
 
114 
Date (DD/MMM/YYYY): ______________________________________ 
115 
 
 
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2 TERMS, ACRONYMS, ABBREVIATIONS 
118 
Abbreviation 
Definition 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
CGM 
Continuous Glucose Monitoring 
CRF 
Case Report Form 
Control-IQ System 
t:slim X2 insulin pump with Control-IQ technology 
DKA 
Diabetic Ketoacidosis 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HbA1c 
Hemoglobin A1c 
HCL 
Hybrid Closed-loop 
ICF 
Informed Consent Form 
QC 
Quality Control 
SAE 
Serious Adverse Event 
t:connect 
t:connect diabetes management system  
T1D 
Type 1 diabetes 
TDD 
Total Daily Dose 
UADE 
Unanticipated Adverse Device Effect 
 
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3 PROTOCOL SYNOPSIS 
121 
Protocol Title 
Initialization and Adaptation of Insulin Delivery Settings to 
Improve Clinical Outcomes with AID Use 
Device 
1) t:slim X2 insulin pump with Control-IQ technology (Control-IQ 
System) 
2) An automatic settings initializer and adaptation system running 
on the server 
Type of Study 
Prospective, Single Arm, Single Center Feasibility Study 
Rational 
The purpose of this study is to obtain preliminary safety and 
performance data on a settings initialization and adaptation 
algorithm used in conjunction with closed-loop control. Based on 
data from simulations and current system use, an algorithm to 
more accurately initialize settings and adapt them over time, faster 
than typical HCP visits, would benefit users onboarding from 
multiple daily injections (MDI) and help them reach optimal 
glycemic outcomes faster. Outcomes of this study will allow for 
the determination of an optimal product configuration for adaptive 
settings and the ability to clinically test a commercial version of 
the new product for effectiveness. 
Objectives 
Primary objective: To demonstrate the safety of the system, by 
assessing the number of severe hypoglycemic events (needing 
assistance) compared to expected incidence 
 
Secondary objective: Compare time in range metrics and adverse 
events in the full 24 hour period, overnight and during the day, 
after each week of settings adaptation. The number of physician 
overrides/physician initiated changes in pump settings will also be 
tracked. 
Primary Endpoints 
1) Primary Endpoint: 
a. To demonstrate the safety of the system, by assessing 
the number of severe hypoglycemic events (needing 
assistance) compared to expected incidence 
2) Secondary Endpoints: 
a. Time in range 70-180 mg/dL 
b. Time < 54 mg/dL 
c. Time < 70 mg/dL 
d. Time > 180 mg/dL 
e. Time > 250 mg/dL 
f. Time in tight glycemic range 70-140 mg/dL 
g. Post-prandial glycemic peak  
h. 4-hour post meal glucose AUC 
i. Sensor glucose median and interquartile range 
j. CGM metrics daytime vs. nighttime 
k. CGM metrics compared each week after adaptation 
l. DKA 
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m. Adverse Device Effects 
n. Serious Adverse Events 
o. Change in total daily insulin use, basal and bolus 
p. Number of physician overrides/physician initiated 
changes in pump settings 
q. Patient Reported Outcomes 
Duration of Study 
Up to 17 weeks total, to allow for 2 to 4 weeks of CGM run-in if 
needed, then 13 weeks of pump/AID use with weekly settings 
adaptation 
Study Design 
$GXOWVDJH\HDUVRIDJHZLWKW\SHGLDEHWHVZKRDUHusing 
multiple daily injections, will be required to collect baseline CGM 
data for the first 2 weeks if not already Dexcom G6 users with at 
least 11 of 14 days of CGM use for the 14 days prior to 
enrollment. They may repeat this 14 day run-in period if adequate 
CGM data is not collected, or study staff feel it is necessary to 
continue to monitor their insulin dose. 
 
Subjects will then proceed to pump/Control-IQ training, where an 
algorithm performed on a paper worksheet will be used to 
recommend initial basal rate, carbohydrate ratio and correction 
factor settings.  
 
Subjects will then wear the insulin pump with Control-IQ 
technology active for 13 weeks, and at day 3 and at the end of 
each week will: 
1) Upload their pump using the USB uploader  
2) Have their study physician review the settings 
recommendations on the pump download report that will 
appear after each download. 
3) Change their settings after being called by the study 
physician to match the new recommendations. 
4) Upload their pump again so the study physician can verify 
the settings have been changed appropriately, and verify 
the correct settings have been applied to the correct pump 
assigned to the subject by verifying the serial number on 
the recommendations report to the changes in t:connect. 
5) Physicians can at any time adjust pump settings and 
override the settings adaptation recommendations for 
safety concerns, and convert scheduled phone follow-up 
visits to in clinic visit at their discretion. 
 
A semi-structured one-on-one interview may be completed 
concurrent with the 13-Week Visit or within a 28-day period 
following that visit. The interview will last approximately 30 
minutes and will be conducted by Tandem staff using a script of 
open-ended questions to gather feedback and reactions to the 
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automated initialization and adaptation system, as well as the use 
of Closed-Loop Control.  
Study Population 
0DOHDQGIHPDOHVXEMHFWV\HDUVRIDJHZLWKW\SHGLDEHWHV
who are current MDI users, who have a baseline A1c at screening 
between 7.5 to 11% 
Number of Subjects 
Up to 45 subjects may sign the consent form and be screened, with 
the goal that 30 subjects start use of the study device, and at least 
20 subjects complete the trial. 
Number of Sites 
1 clinical site in the United States 
Main Criteria for 
Inclusion 
Eligibility to enroll in the study will be assessed based on the 
following inclusion criteria:  
1. $GXOWVXEMHFWVDJH\HDUV 
2. Clinical diagnosis of type 1 diabetes for at least one year 
3. Using a basal/bolus regimen by injection (MDI therapy) 
4. Total daily dose 10 units/day 
5. Willing to use only aspart (novolog) or lispro (humalog) 
U-100 insulin with the study pump.  
6. $F5DQG11% at screening 
7. Not pregnant or planning a pregnancy during the time 
period of the study. 
8. Has current glucagon product to treat severe hypoglycemia 
(injectable or nasal) at home (will provide prescription if 
they do not have one) 
9. Willingness to follow study procedures and a signed  
informed consent form  
Main Criteria for 
Exclusion 
Eligibility to enroll in the study will be assessed based on the 
following exclusion criteria:  
1. Two or more episodes of severe hypoglycemia (needing 
assistance) in the past 6 months 
2. Two or more episodes of diabetic ketoacidosis in the past 6 
months 
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. Significant chronic kidney disease or hemodialysis  
6. Significant liver disease  
7. History of adrenal insufficiency  
8. History of abnormal TSH consistent with hypothyroidism 
or hyperthyroidism that is not appropriately treated  
9. Other chronic disease/condition determined by investigator 
to interfere with participation in the study 
10. Use of glucocorticoids, beta blockers or other medications 
determined by investigator to interfere with study 
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11. Use of long-acting insulin, inhaled insulin (Afrezza), or use 
of any non-insulin glucose lowering agents (i.e. SGLT-2 
inhibitor) other than Metformin with the study pump 
12. Subject is pregnant or lactating or intending to become 
pregnant before or during participation in this study. 
13. Investigator judgement that subject would not be able to 
complete the trial. 
Procedures in 
Screening/Baseline 
Period 
At screening, baseline data will be collected. For Decom G6 users, 
mean/median sensor glucose, TIR and all glycemic outcomes will 
be recorded as baseline data if data is available for the at least 11 
of the last 14 days. Those without adequate baseline data will 
collect Dexcom G6 sensor data to establish a baseline over the 
next 2 weeks. 
Management of Adverse 
Events 
Safety information will be collected weekly during study clinic 
phone calls, or more frequently if a severe AE occurs. The event, 
date of onset, severity, seriousness, duration and relationship to the 
device/adaptation system will be documented. All reported device-
related AEs will be followed until they are adequately resolved or 
stabilized, or until study completion/termination, whichever comes 
first. 
Statistical Analysis  
Descriptive statistics will be used to evaluate rates of AEs as well 
as glycemic outcomes over time as the algorithm adapts insulin 
delivery settings.  
 
122 
The study will be conducted and documented in accordance with the IRB, FDA, ICH and GCP 
123 
guidelines. 
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4 BACKGROUND 
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4.1 DISEASE BACKGROUND 
128 
Type 1 diabetes affects 1.25 million people in the United States. Approximately 70% of 
129 
individuals with type 1 diabetes report poor metabolic control, and do not meet the American 
130 
Diabetes Association’s recommended goal of hemoglobin A1c (HbA1c) level of 7.0% for children 
131 
and adults. These findings indicate the need for better approaches to type 1 diabetes 
132 
management. 
133 
Recent estimates suggest that approximately 400,000 U.S. patients with type 1 diabetes (T1D) 
134 
use insulin pumps. Adoption of pump therapy varies by geography and may be related to 
135 
healthcare provider preference or patient characteristics and socioeconomic status. Use of insulin 
136 
pumps is more common in individuals of higher socioeconomic status as reflected by 
137 
race/ethnicity, private health insurance, family income, and education. Additionally, referrals 
138 
from healthcare providers and insurance approvals are critical determinants for who becomes a 
139 
pump user in the United States. 
140 
However, a main barrier to starting pump therapy and staying on it is having to enter insulin 
141 
delivery settings into the pump (ie basal rate, carbohydrate ratio, correction factor) and 
142 
optimizing those settings for each individual. In this trial, we will test the safety and feasibility of 
143 
using a settings initializer for individuals onboarding to the t:slim X2 pump with Control-IQ 
144 
technology, with weekly adaptations of insulin delivery settings over ~13 weeks. 
145 
4.2 DEVICE BACKGROUND 
146 
The t:slim X2 insulin pump with Control-IQ technology is an advanced hybrid closed-loop 
147 
(HCL) system, developed and manufactured by Tandem Diabetes Care, Inc. and cleared in the 
148 
U.S. by the FDA for individuals with type 1 diabetes. Control-IQ is integrated with the Dexcom 
149 
G6 continuous glucose monitor (CGM) and uses CGM values to predict glucose values 30 
150 
minutes in the future. Based on the predicted glucose, Control-IQ modulates basal insulin 
151 
delivery, and delivers automated correction boluses to mitigate impending hyperglycemia. The 
152 
current Control-IQ system is FDA approved down to age 6 years old for individuals with type 1 
153 
diabetes, and has been found to improve time in range (70-180 mg/dL) and decrease both time < 
154 
70 mg/dL and time >180 mg/dL (1,2). 
155 
4.3 SETTINGS OPTIMIZER 
156 
For this study, insulin delivery settings initialization will use a paper worksheet (Figure 1) to 
157 
guide initial settings.  
158 
 
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161 
Figure 1. Insulin pump initiation settings worksheet 
162 
Adaptation will be recommended by the automated system, emailing written recommendations 
163 
for settings changes to physicians for their review. The automated settings adaptation system will 
164 
recommend a single basal rate, carbohydrate ratio and correction factor throughout the day 
165 
(Figure 2), and will limit recommendations to a maximum 5% change at a time. 
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Figure 2. Sample E-Mailed Adaptation Settings Recommendations 
168 
If the user or study staff has manually changed settings to more than one timepoint per day, the 
169 
settings adaptation system will continue to adapt back to one setting per day for basal rate, 
170 
carbohydrate ratio and correction factor as shown in Figure 3. 
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Figure 3. Sample E-Mailed Adaptation Settings Recommendations where more than one time 
173 
point was entered, and the system has changed back to one time point to continue adaptation. 
174 
The report notes all the dates and times settings were changed since the last report. 
175 
Physician overrides of the system, or changes to pump settings between emailed 
176 
recommendations, will be documented with the reason for the override/settings change on the 
177 
study case report form.  
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5 STUDY OBJECTIVES, DESIGNS AND ENDPOINTS 
180 
5.1 STUDY OBJECTIVES 
181 
Primary objective: To demonstrate the safety of the settings initialization and adaptation 
182 
algorithm when in conjunction with Control-IQ technology, by assessing the number of severe 
183 
hypoglycemic events (needing assistance) compared to expected incidence  
184 
Secondary objective: Compare time in range metrics and adverse events in the full 24 hour period, 
185 
overnight and during the day, after each week of settings adaptation. The number of physician 
186 
overrides/physician initiated changes in pump settings will also be tracked. 
187 
5.2 STUDY DESIGN 
188 
This feasibility study is a prospective, single arm study, evaluating an algorithm to recommend 
189 
insulin pump settings at pump start (initialization) and then adjust settings at 3 days, at 7 days, 
190 
and then weekly through 13 weeks. 
191 
$GXOWVDJH\HDUVRIDJHZLWKW\SHGLDEHWHVZKRDUHXVLQJPXOWLSOHGDLO\LQMHFWLRQVZLOO
192 
be required to collect baseline CGM data for the first 2 weeks if not already Dexcom G6 users 
193 
with at least 11 of 14 days of CGM use for the 14 days prior to enrollment. They may repeat this 
194 
14 day run-in period if adequate CGM data is not collected, or study staff feel it is necessary to 
195 
continue to monitor their insulin dose.  
196 
Up to 45 subjects may sign the consent form and be screened, with the goal that up to 30 subjects 
197 
start use of the study device, and at least 20 subjects complete the trial. 
198 
Enrollment goals for baseline A1c at screening are: 
199 
• At least 5 subjects with A1c 8% - 8.9% 
200 
• At least 5 subjects with A1c  9% 
201 
 
202 
Subjects will then proceed to pump/Control-IQ training, where an algorithm based worksheet 
203 
will be used to recommend initial basal rate, carbohydrate ratio and correction factor settings.  
204 
Subjects will then wear the insulin pump with Control-IQ technology active, and at 3 days after 
205 
training, 7 days after training, and then every 7 days will: 
206 
1) Upload their pump using the USB uploader  
207 
2) Have their study physician review the settings recommendations on the pump download 
208 
report that will appear after each download. 
209 
3) Change their settings after being called by the study physician to match the new 
210 
recommendations. 
211 
4) Upload their pump again so the study physician can verify the settings have been changed 
212 
appropriately, and the correct settings changes were implemented on the correctly 
213 
assigned pump by looking at the pump serial number on the settings report. 
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Physicians can at any time adjust pump settings and override the settings adaptation 
215 
recommendations for safety concerns, and convert scheduled phone follow-up visits to in clinic 
216 
visit at their discretion. 
217 
After 13 weeks (3 months) of use, subjects will return to clinic for a final visit. 
218 
Subjects who agree to provide their contact information will be offered an open ended interview 
219 
at the end of the study to discuss their confidence in the automated settings recommendations 
220 
and how it worked for them. 
221 
The data collected in this study will be directly entered into the eCRF (as applicable) or paper 
222 
source forms. Subject data will include demographics, focused medical history, therapy data, and 
223 
baseline and follow-up measures. All device data will be collected digitally and downloaded 
224 
directly into the manufacturer provided software for the study devices. 
225 
5.3 STUDY ENDPOINTS 
226 
1) Primary Endpoint: 
227 
a. To demonstrate the safety of the system, by assessing the number of severe 
228 
hypoglycemic events (needing assistance) compared to expected incidence 
229 
2) Secondary Endpoints: 
230 
a. Time in range 70-180 mg/dL 
231 
b. Time < 54 mg/dL 
232 
c. Time < 70 mg/dL 
233 
d. Time > 180 mg/dL 
234 
e. Time > 250 mg/dL 
235 
f. Time in tight glycemic range 70-140 mg/dL 
236 
g. Post-prandial glycemic peak  
237 
h. 4-hour post meal glucose AUC 
238 
i. Sensor glucose median and interquartile range 
239 
j. CGM metrics daytime vs. nighttime 
240 
k. CGM metrics compared each week after adaptation 
241 
l. DKA 
242 
m. Serious Adverse Events 
243 
n. Adverse Device Effects 
244 
o. Change in total daily insulin use, basal and bolus 
245 
p. Number of physician overrides/physician initiated changes in pump settings  
246 
q. Patient Reported Outcomes 
 
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6 SUBJECT SELECTION 
248 
6.1 SUBJECT POPULATION 
249 
6.1.1 INCLUSION CRITERIA:  
250 
Eligibility to enroll in the study will be assessed based on the following inclusion criteria:  
251 
1) $GXOWVXEMHFWVDJH\HDUV 
252 
2) Clinical diagnosis of type 1 diabetes for at least one year 
253 
3) Using a basal/bolus regimen by injection (MDI therapy) 
254 
4) Total daily dose 10 units/day 
255 
5) Willing to use only aspart (novolog) or lispro (humalog) U-100 insulin with the study 
256 
pump.  
257 
6) $F5DQG1% at screening 
258 
7) Not pregnant or planning a pregnancy during the time period of the study. 
259 
8) Has current glucagon product to treat severe hypoglycemia (injectable or nasal) at home 
260 
(will provide prescription if they do not have one) 
261 
9) Willingness to follow study procedures and a signed informed consent form  
262 
6.1.2 EXCLUSION CRITERIA:  
263 
Eligibility to enroll in the study will be assessed based on the following exclusion criteria:  
264 
1) Two or more episodes of severe hypoglycemia (needing assistance) in the past 6 months 
265 
2) Two or more episodes of diabetic ketoacidosis in the past 6 months 
266 
3) Inpatient psychiatric treatment in the past 6 months 
267 
4) History of drug abuse (defined as any illicit drug use) or history of alcohol abuse prior to 
268 
screening or unwillingness to agree to abstain from illicit drugs throughout the study 
269 
5) Significant chronic kidney disease or hemodialysis  
270 
6) Significant liver disease  
271 
7) History of adrenal insufficiency  
272 
8) Hypothyroidism or hyperthyroidism that is not appropriately treated 
273 
9) Other chronic disease/condition determined by investigator to interfere with participation 
274 
in the study 
275 
10) Use of glucocorticoids, beta blockers or other medications determined by investigator to 
276 
interfere with study 
277 
11) Use of long-acting insulin, inhaled insulin (Afrezza), or use of any non-insulin glucose 
278 
lowering agents (i.e. SGLT-2 inhibitor) other than Metformin with the study pump 
279 
12) Subject is pregnant or lactating or intending to become pregnant before or during 
280 
participation in this study. 
281 
13) Investigator judgement that subject would not be able to complete the trial. 
282 
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6.2 SUBJECT WITHDRAWAL OR TERMINATION 
283 
Subjects are free to withdraw from the study at any time and will be withdrawn if they inform the 
284 
study team that they no longer wish to participate. Data collected prior to the subject’s 
285 
withdrawal will remain part of the study record and will be included in the analyses. 
286 
 
287 
288 
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7 TREATMENT OF SUBJECTS 
289 
7.1 THE T:SLIM X2 INSULIN PUMP WITH CONTROL-IQ 
290 
TECHNOLOGY 
291 
The Control-IQ System is a US FDA approved device indicated for the treatment of type 1 
292 
diabetes in people age 6 years and older. The Control-IQ System is integrated with the Dexcom 
293 
G6 CGM and uses CGM values to adjust insulin delivery with the goal of improving glucose 
294 
control (time in range of 70-180 mg/dL).  
295 
For the current study, subjects will use t:slim X2 pump with Control-IQ technology cleared 
296 
under K201214 and K200467, respectively. 
297 
7.2 ENROLLMENT PROCEDURE:  
298 
Potential study subjects will be recruited by the clinical site. After a description of the study is 
299 
provided by the study team, the subject will be asked to sign the informed consent form (ICF). 
300 
Eligibility to enroll in the study will be assessed based on the inclusion/exclusion criteria. 
301 
Enrollment information will be entered onto the study case report forms. In addition, 
302 
demographic and relevant medical history will be collected at this time and entered onto the 
303 
study case report forms.  
304 
7.3 DURATION OF THERAPY AND FOLLOW-UP:  
305 
Each enrolled subject may participate for ~17 weeks total, to allow for 2 to 4 weeks of CGM 
306 
run-in if needed, then 13 weeks of pump/AID use with weekly settings adaptation. 
307 
7.4 STUDY PROCEDURES: 
308 
Event Schedule: The CRFs will be completed by the investigator (or an authorized member of 
309 
the investigator’s staff) per the event schedule described below. 
310 
 
 
311 
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Table 1. Schedule of Visits and Procedures 
312 
 
313 
Baseline Data Collection: $GXOWVDJH\HDUVRIDJHZLWKW\SHGLDEHWHVZKRDUHXVLQJ
314 
multiple daily injections, will be required to collect baseline CGM data for the first 2 weeks if 
315 
not already Dexcom G6 users with at least 11 of 14 days of CGM use for the 14 days prior to 
316 
enrollment. They may repeat this 14 day run-in period if adequate CGM data is not collected.  
317 
Subject Completion or Early Withdrawal: The subject completes the study approximately 17-
318 
21 weeks after enrollment, or when they choose to withdraw from the study, if earlier than the 
319 
final visit 
320 
Data Collection: Investigators will assign a de-identified number to each subject and will be 
321 
required to keep any study paperwork or electronic files in a secure private area. Monitoring will 
322 
be conducted to help ensure that data is secure and entered within reasonable limits, consistent 
323 
with a risk-based monitoring approach. 
324 
 
Screening 
Visit 
CGM 
Run-in Visit 
(may be 
repeated 
after 2 
weeks) 
Pump and 
Control-IQ 
Training 
Visit 
Control-IQ Use 
 
 
2-4 weeks 
 
3d 
7d 
Weekly 
13w 
F/U Call 
UV 
Visit (V) or Contact (C) 
V 
V 
V 
C 
C 
C 
V 
C 
C/V 
Informed Consent  
X 
 
 
 
 
 
 
 
 
Eligibility Assessment 
X 
 
 
 
 
 
 
 
 
Medical history/ 
physical exam 
X 
 
 
 
 
 
 
 
 
Vital Signs 
X 
 
 
 
 
 
 
 
 
HbAlc (POC or local lab for 
inclusion criteria 
confirmation) 
X 
 
 
 
 
 
 
 
 
HbA1c (Central lab)  
 
 
X 
 
 
 
X 
 
 
Pregnancy test (females 
of child-bearing potential) 
X 
 
X 
 
 
 
 
 
 
Assessment of CGM use 
X 
X 
 
 
 
 
 
 
 
Study system training 
 
X 
X 
 
 
 
 
 
 
AE Assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
Upload device data 
from home 
 
 
 
X 
X 
X 
 
 
X 
Download device data 
at clinic visit 
X 
X 
X 
 
 
 
X 
 
X 
Open Ended Interview 
 
 
 
 
 
 
X 
 
 
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Demographics: The following demographic data will be obtained: date of birth, gender, race, 
325 
ethnicity, educational level, socioeconomic status, residence, employment status, weight, height, 
326 
blood pressure, pulse, and type of health insurance.   
327 
Medical History: Medical history, including existing comorbidities deemed clinically relevant 
328 
(e.g. retinopathy, nephropathy, neuropathy, history of cardiovascular events) will be collected at 
329 
baseline. In addition, details specific to type 1 diabetes, including age at diagnosis, duration of 
330 
disease, and previous therapy will be collected from the study subject and documented in the 
331 
subject’s eCRF. A new hemoglobin A1c will also be obtained at the screening visit, at 
332 
randomization and at end of study. 
333 
Pregnancy: In order to reduce the risk of pregnancy, subjects of childbearing potential must 
334 
agree to use an effective method of birth control while participating in this study. Acceptable 
335 
methods of birth control for use in this study are barrier methods, intrauterine devices, or oral 
336 
contraceptive pills. The Investigator or study staff will discuss this with the subject. 
337 
Device Training: All subjects will complete study device training before starting use of the 
338 
study device. Subjects will be trained by qualified study staff using the study approved device 
339 
training checklists, and will be given a copy of the Study Participant Instruction Sheet. In 
340 
addition to device training, the Study Participant Instruction Sheet reviews procedures for 
341 
checking ketones, and when to contact study staff for assistance. 
342 
All subjects will complete CGM training. Subjects who are not already Dexcom G6 users with at 
343 
least 11 of 14 days of CGM use for the 14 days prior to enrollment will complete CGM run-in. 
344 
They may repeat this 14 day run-in period if adequate CGM data is not collected. 
345 
All subjects will complete insulin pump training. The pump training visit may be extended over 
346 
more than one day if needed in the judgement of the investigator. Initial pump settings will be 
347 
configured by following the study settings algorithm worksheet. At the end of the pump training 
348 
visit, subjects will activate Control-IQ technology 
349 
Subjects will wear the insulin pump with Control-IQ technology active in the outpatient setting, 
350 
and have scheduled phone follow up visits at 3 days (+/- 1 day), 7 days (+/- 2 days), then weekly 
351 
(+/- 3 days). A final visit in clinic will occur at 13 weeks (+/- 7 days). A post final clinic visit 
352 
phone call will occur 3 days (+/- 1 day) after changing back to MDI therapy after the study 
353 
devices are returned. 
354 
At each visit, the study pump and CGM data will be downloaded, and insulin delivery settings as 
355 
recommend by the algorithm will be emailed to study staff for provider review. Providers will 
356 
call the subjects for their scheduled appointment, and have the subjects enter the new pump 
357 
settings, and then re-upload their pump to confirm the changes were implemented correctly, 
358 
verifying the settings were applied to the correct pump serial number as assigned to that subject. 
359 
At any time, study staff providers may override the algorithm settings recommendations, either 
360 
at or in between scheduled visits for safety concerns. The reason for any changes to override 
361 
pump settings will be documented.  
362 
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Unscheduled visits may occur at any time, and may be initiated by stuff stay or by study 
363 
subjects.  
364 
A semi-structured one-on-one interview may be completed concurrent with the 13-Week Visit or 
365 
within a 28-day period following that visit. The interview will last approximately 30 minutes and 
366 
will be conducted by Tandem staff using a script of open-ended questions to gather feedback and 
367 
reactions to the automated initialization and adaptation system, as well as the use of Closed-Loop 
368 
Control. 
369 
Interview sessions may be audio- or video-taped and transcribed by a professional transcription 
370 
service. Otherwise, these recordings will not be shared for any non-study purposes. 
371 
Transcriptions will use a code for participants, such as “Participant 1”, and will not contain 
372 
names or other identifiers of participants. 
373 
Observation and Recording of Adverse Events: Subjects will be required to report AEs. Open-
374 
ended questions and questions specific to SH and DKA will be included in all subject visits. An 
375 
AE form will be completed for every adverse event reported by a subject. Any medical 
376 
management of an event and the resolution of the event must be recorded in source 
377 
documentation and on the appropriate eCRF using medical terminology. 
378 
Treatment of hyper- and hypoglycemia: Procedures in Section 10.9 and 10.10 will be 
379 
followed by study staff and by subjects. 
380 
7.5 EARLY TERMINATION VISIT (IF APPLICABLE) 
381 
Participants will be asked to come for an end of study visit in the event of withdrawal or early 
382 
termination.  
383 
7.6 UNSCHEDULED VISITS 
384 
Participants may have unscheduled visits during the study period if required for additional device 
385 
training or other unanticipated needs per the study investigator discretion. Study staff may adjust 
386 
insulin delivery settings on the study pump at any time, and override the algorithm 
387 
recommendations for safety concerns, and will document these changes. 
388 
7.7 FINAL CLINIC VISIT 
389 
Subjects will return all study supplies and complete the study surveys.  
390 
A final central lab HbA1c will be drawn.  
391 
All study devices (glucose meter, ketone meter, insulin pump and CGM) will be downloaded.  
392 
Participants will be permitted to keep the blood glucometer, blood ketone meter and any 
393 
remaining CGM sensors at the end of the study, but will need to return all other devices, 
394 
including insulin pump and related supplies.  
395 
Subjects will complete the Diabetes Impact and Device Satisfaction (DIDS) Scale, and be asked 
396 
to provide their contact information for a final interview phone call. 
397 
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Study staff will then supervise the participants transition back to their standard of care therapy. 
398 
x Study staff will re-evaluate the subject’s baseline therapy doses, noting changes in basal 
399 
rates, carbohydrate ratios, and correction factors in use at the end of the trial. 
400 
x Doses will be adjusted to best match the current daily insulin requirements from CSII 
401 
use, typically = (total daily dose + 20%)/2, with further modification as per clinical site 
402 
usual practice.  
403 
x Study staff will confirm subjects have carbohydrates on hand for their drive back home, 
404 
and instruct subjects to check their glucose levels when they arrive at home, prior to 
405 
bedtime, and at least one time overnight on the first night to monitor for hypoglycemia, 
406 
reminding subjects that insulin on board can be active for the next few hours even after 
407 
stopping their pump. 
408 
7.8 POST STUDY PHONE CALL 
409 
All participants will have a post-study phone call 3 (±1) days after the date of their final visit and 
410 
transition back to their prior insulin therapy, during which the following will occur: 
411 
x Check on transition back to usual home diabetes care 
412 
x Assessment of adverse events 
413 
 
 
414 
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8 STATISTICAL CONSIDERATIONS  
415 
8.1 STATISTICAL ANALYSIS:  
416 
This feasibility study is a prospective, single arm study, evaluating al algorithm to recommend 
417 
insulin pump settings at pump start (initialization) and then weekly for 13 weeks. 
418 
Descriptive statistics of the rates of severe hypoglycemia, DKA, and serious adverse events will 
419 
be reported for baseline (with CGM run-in data) and compared to changes after each weekly 
420 
adaptation. Additionally, descriptive statistics of glycemic outcomes will for baseline and each 
421 
intervention configuration will be provided.  
422 
The statistics will include all primary and secondary outcomes of the study as listed in section 
423 
5.3. These statistics will be calculated at the patient-level, and a sub-analysis of daytime vs. 
424 
nighttime statistics will be provided.  
425 
 
426 
 
 
427 
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9 RISKS AND BENEFITS 
428 
9.1 POTENTIAL RISKS AND BENEFITS OF THE DEVICE 
429 
Risks and Benefits are detailed below. Loss of confidentiality is a potential risk; however, data 
430 
are handled to minimize this risk. Hypoglycemia, hyperglycemia and ketone formation are 
431 
always a risk in participants with diabetes and participants will be monitored for this. 
432 
9.2 VENIPUNCTURE RISKS 
433 
A hollow needle/plastic tube may be placed in the arm for taking blood samples. Blood draws 
434 
can cause some common reactions like pain, bruising, or redness at the sampling site. Less 
435 
common reactions include bleeding from the sampling site, formation of a small blood clot or 
436 
swelling of the vein and surrounding tissues, and fainting. 
437 
9.3 FINGERSTICK RISKS 
438 
About 1 drop of blood will be removed by fingerstick for measuring blood glucose and 
439 
sometimes Hemoglobin A1c (HbA1c) or other tests. This is a standard method used to obtain 
440 
blood for routine hospital laboratory tests. Pain is common at the time of lancing. In about 1 in 
441 
10 cases, a small amount of bleeding under the skin will produce a bruise. A small scar may 
442 
persist for several weeks. The risk of local infection is less than 1 in 1000. This should not be a 
443 
significant contributor to risks in this study as fingersticks are part of the usual care for people 
444 
with diabetes. 
445 
9.4 SUBCUTANEOUS CATHETER RISKS (CGM) 
446 
With CGM use participants are at low risk for developing a local skin infection at the site of the 
447 
sensor needle placement. If a catheter is left under the skin for more than 24 hours, it is possible 
448 
to get an infection where it goes into the skin, with swelling, redness and pain. There may be 
449 
bleeding where the catheter is put in and bleeding under the skin causes a bruise (1 in 10 risk). 
450 
On rare occasions, the CGM may break and leave a small portion of the sensor probe under the 
451 
skin that may cause redness, swelling or pain at the insertion site. The participant will be 
452 
instructed to notify the study coordinator immediately if this occurs. 
453 
9.5 RISK OF HYPOGLYCEMIA 
454 
As with any person having diabetes and using insulin, there is always a risk of having a low 
455 
blood sugar (hypoglycemia). The frequency of hypoglycemia should be no more and possibly 
456 
less than it would be as part of daily living. Symptoms of hypoglycemia can include sweating, 
457 
jitteriness, and not feeling well. Just as at home, there is the possibility of fainting or seizures 
458 
(convulsions) and that for a few days the participant may not be as aware of symptoms of 
459 
hypoglycemia. A CGM functioning poorly and significantly over-reading glucose values could 
460 
lead to inappropriate insulin delivery. 
461 
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9.6  RISK OF HYPERGLYCEMIA 
462 
Hyperglycemia and ketonemia could occur if insulin delivery is attenuated or suspended for an 
463 
extended period or if the pump or infusion set is not working properly. A CGM functioning 
464 
poorly and significantly under-reading glucose values could lead to inappropriate suspension of 
465 
insulin delivery. All subjects will be issued a glucose meter and glucose test strips, and a ketone 
466 
meter and ketone strips to use to carefully monitor for hyperglycemia and be given instructions 
467 
on how to mitigate hyperglycemia should it occur. 
468 
9.7 RISK OF DEVICE REUSE 
469 
All devices will be used by a single study participant only. There will be no device re-use. 
470 
9.8 OTHER RISKS 
471 
Some participants may develop skin irritation or allergic reactions to the adhesives used to secure 
472 
the CGM, or from tape to secure the insulin infusion sets for the continuous subcutaneous insulin 
473 
infusion.  If these reactions occur, different adhesives or “under-taping” (such as with IV 3000, 
474 
Tegaderm, etc.) will be tried, sites will be rotated frequently, and a mild topical steroid cream or 
475 
other medication may be required.  
476 
Whenever the skin is broken there is the possibility of an infection. The CGM and pump infusion 
477 
sites are inserted under the skin. It is possible that any part that is inserted under the skin may 
478 
cause an infection. These occur very infrequently, but, if an infection was to occur, oral and/or 
479 
topical antibiotics can be used. The risk of skin problems could be greater if you use a sensor for 
480 
longer than it is supposed to be used. Therefore, participants will be carefully instructed about 
481 
proper use of the sensor. 
482 
Data downloaded from the CGM, pump, and the home glucose and ketone meter will be 
483 
collected for the study as measures of diabetes self-management behaviors. The downloaded data 
484 
from the subject’s home pump will include data from prior to the date of the screening visit. 
485 
Some people may be uncomfortable with the researchers' having such detailed information about 
486 
their daily diabetes habits. 
487 
9.9 KNOWN POTENTIAL BENEFITS 
488 
Participants may experience a significant improvement in glucose control. Hypoglycemia is the 
489 
number one fear of many individuals taking insulin and this fear often prevents optimal glycemic 
490 
control. Hyperglycemia will likely be reduced as well.  
491 
It is expected that this protocol will yield increased knowledge about using an automated 
492 
closed-loop to control glucose levels in people with type 1 diabetes. The individual participant 
493 
may or may not benefit from study participation. 
494 
9.10 RISK ASSESSMENT 
495 
Based on the facts that (1) adults and adolescents with type 1 diabetes experience mild 
496 
hypoglycemia and hyperglycemia frequently as a consequence of the disease and its 
497 
management, (2) the study intervention involves periodic automated insulin dosing that may 
498 
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increase the likelihood of hypoglycemia, and periodic automated attenuation of insulin delivery 
499 
that may increase the likelihood of hyperglycemia, (3) mitigations are in place, and have been 
500 
tested in prior studies using the investigational device system in the home setting, that limit the 
501 
likelihood of excessive insulin dosing or prolonged withdrawal of insulin, (4) rapid reversal of 
502 
hypoglycemia and hyperglycemia can be achieved, and (5) the Control algorithm (Control-IQ) is 
503 
already FDA approved for and has shown significant (10+%) TIR improvements in individuals 
504 
with type 1 diabetes, it is the assessment of the investigators that this protocol falls under DHHS 
505 
46.405 which is a minor increase over minimal risk. In addition, it is the belief of the 
506 
investigators that this study also presents prospect of direct benefit to the participants and general 
507 
benefit to others with diabetes. 
508 
9.11 GENERAL CONSIDERATIONS 
509 
The study is being conducted in compliance with the policies described in the study policies 
510 
document, with the ethical principles that have their origin in the Declaration of Helsinki, with 
511 
the protocol described herein, and with the standards of Good Clinical Practice (GCP). 
512 
 
 
513 
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10 DESCRIPTION OF THE STUDY DEVICES AND USE 
514 
All study supplies will be provided by Tandem Diabetes Care, Inc. 
515 
10.1 INSULIN PUMP 
516 
The study system will include the Tandem t:slim X2 insulin pump with Control-IQ technology 
517 
cleared under K201214 and K200467 respectively (Tandem Diabetes Care, San Diego, CA). 
518 
10.2 CONTINUOUS GLUCOSE MONITORING 
519 
The study CGM will include Dexcom G6 transmitter and sensors. The CGM sensor will be 
520 
replaced at least once every 10 days or as per manufacturer instructions. 
521 
10.3 BLOOD GLUCOSE METER AND STRIPS 
522 
Blood glucose levels will be measured using the study-assigned blood glucose meter 
523 
(glucometer) and the CGM device will be calibrated if needed using the study glucometer 
524 
and strips in accordance with the manufacturer’s labeling. (Contour NEXT or Contour NEXT 
525 
ONE, Ascensia Diabetes Care US, Inc., 5 Wood Hollow Rd, Parsippany, NJ 07054 USA) 
526 
10.4 KETONE METER AND STRIPS 
527 
Blood ketone levels will be measured using the Abbott Precision Xtra meter and strips in 
528 
accordance with the manufacturer’s labeling. The blood glucose meter component of the 
529 
Precision Xtra device will not be used. (Abbott Diabetes Care Inc., 1360 South Loop Road, 
530 
Alameda, CA 94502 USA) 
531 
10.5 STUDY DEVICE ACCOUNTABILITY PROCEDURES 
532 
Device accountability and inventory will be documented in each subject’s study chart, to include 
533 
detailed inventory records of the study glucose meter, study ketone meter, study CGM supplies, 
534 
and Tandem insulin pump system. 
535 
10.6 BLOOD GLUCOSE METER TESTING 
536 
x QC testing will be performed before issuing the blood glucose meter to a subject. Additional 
537 
QC testing may be performed per manufacturer guidelines. 
538 
x A tested meter will not be used in a study if it does not read within the target range 
539 
concentration per manufacturer labeling.  
540 
x Participants will be reminded to use the study blood glucose meter for all fingerstick blood 
541 
glucose measurements. 
542 
x Participants will be asked to perform fingerstick blood glucose measurements in accordance 
543 
with the labelling of the study CGM device. 
544 
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10.7 BLOOD KETONE TESTING 
545 
x QC testing will be performed before issuing the blood ketone meter to a subject. Additional 
546 
QC testing may be performed per manufacturer guidelines. 
547 
x A tested meter will not be used in a study if it does not read within the target range 
548 
concentration per manufacturer labeling.  
549 
x Participants will be instructed on how to perform blood ketone testing. 
550 
x Participants will be given guidelines for treatment of elevated blood ketones. 
551 
10.8 CGM CALIBRATION 
552 
Throughout the study, participants will be instructed to calibrate the study CGM in accordance 
553 
with manufacturer labelling. 
554 
10.9 HYPERGLYCEMIA SAFETY PROTOCOL 
555 
The t:slim X2 with Control-IQ system will issue a predictive hyperglycemia alert (Control-IQ 
556 
High Alert) when the system has increased insulin delivery, but detects a CGM value above 200 
557 
mg/dL and does not predict the value will decrease in the next 30 minutes. During the course of 
558 
the study, participants will be permitted to change the CGM high glucose threshold alert setting 
559 
on their device or mobile app, but will be instructed to choose a value no greater than 300 
560 
mg/dL. 
561 
If the participant receives a Control-IQ High Alert, a prompt appears on the user interface to 
562 
check the site for occlusion and test blood glucose. 
563 
If a participant’s CGM reading is >300 mg/dL for more than 60 minutes RULVPJG/DWDQ\
564 
point, the participant will be instructed to take the following steps: 
565 
x Perform a blood glucose meter check. 
566 
x If the blood glucose is >300 mg/dL, check for blood ketones with the study ketone meter. 
567 
x ,IWKHNHWRQHOHYHOLVPPRO/ RUPPRO\L at any time), take correction insulin, 
568 
change insulin (pump) infusion site and contact study staff. Continue to monitor their glucose 
569 
and blood ketone levels until they return to normoglycemia and ketones are < 0.6 mmol/l. 
570 
x 
If ketones are <0.6 mmol/l, they will be advised to continue to monitor their glucose until it 
571 
returns to normoglycemia and to repeat the ketone measurement in 90 minutes if necessary 
572 
x If correction insulin is administered via insulin syringe, turn Control-IQ off for four hours 
573 
and until glucose level has returned to <180 mg/dL. 
574 
10.10 
HYPOGLYCEMIA SAFETY PROTOCOL 
575 
When using the study device, hypoglycemia low threshold alerts will be set to no lower than 70 
576 
mg/dL, and if a participant’s CGM reading is <70 mg/dL, subjects will be instructed to treat with 
577 
~15 grams of carbohydrate, and perform fingerstick testing as necessary per CGM manufacturer 
578 
instructions. 
579 
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11 ADVERSE EVENTS, DEVICE ISSUES, AND STOPPING 
580 
RULES 
581 
11.1 ADVERSE EVENTS 
582 
Adverse Event (AE): Any untoward medical occurrence in a study participant, irrespective of the 
583 
relationship between the adverse event and the device(s) under investigation (see section 11.2 for 
584 
reportable adverse events for this protocol). 
585 
Serious Adverse Event (SAE): Any untoward medical occurrence that: 
586 
Results in death. 
587 
Is life-threatening; (a non-life-threatening event which, had it been more severe, might have 
588 
become life-threatening, is not necessarily considered a serious adverse event). 
589 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
590 
Results in persistent or significant disability/incapacity or substantial disruption of the ability to 
591 
conduct normal life functions (sight threatening). 
592 
Is a congenital anomaly or birth defect. 
593 
Is considered a significant medical event by the investigator based on medical judgment (e.g., 
594 
may jeopardize the participant or may require medical/surgical intervention to prevent one of the 
595 
outcomes listed above). 
596 
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety or 
597 
any life-threatening problem or death caused by, or associated with, a device, if that effect, 
598 
problem, or death was not previously identified in nature, severity, or degree of incidence in the 
599 
investigational plan or application (including a supplementary plan or application), or any other 
600 
unanticipated serious problem associated with a device that relates to the rights, safety, or 
601 
welfare of participants (21 CFR 812.3(s)). 
602 
Adverse Device Effect (ADE): Any untoward medical occurrence in a study participant which 
603 
the device may have caused or to which the device may have contributed (Note that an Adverse 
604 
Event Form is to be completed in addition to a Device Deficiency or Issue Form). 
605 
Device Complaints and Malfunctions: A device complication or complaint is something that 
606 
happens to a device or related to device performance, whereas an adverse event happens to a 
607 
participant. A device complaint may occur independently from an AE, or along with an AE. 
608 
An AE may occur without a device complaint or there may be an AE related to a device 
609 
complaint. A device malfunction is any failure of a device to meet its performance specifications 
610 
or otherwise perform as intended. Performance specifications include all claims made in the 
611 
labeling for the device. The intended performance of a device refers to the intended use for 
612 
which the device is labeled or marketed. (21 CFR 803.3). Note: for reporting purposes, sites 
613 
will not be asked to distinguish between device complaints and malfunctions. 
614 
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11.2 REPORTABLE ADVERSE EVENTS 
615 
For this protocol, a reportable adverse event includes any untoward medical occurrence that 
616 
meets one of the following criteria: 
617 
1. A serious adverse event 
618 
2. An Adverse Device Effect as defined in section 11.1, unless excluded from reporting in 
619 
section 11.9 
620 
3. An Adverse Event occurring in association with a study procedure 
621 
4. Hypoglycemia meeting the definition of severe hypoglycemia as defined below  
622 
5. Diabetic ketoacidosis (DKA) as defined below or in the absence of DKA, a 
623 
hyperglycemic or ketosis event meeting the criteria defined below 
624 
Hypoglycemia and hyperglycemia not meeting the criteria below will not be recorded as adverse 
625 
events unless associated with an Adverse Device Effect. Skin reactions from sensor placement 
626 
are only reportable if severe and/or required treatment.  
627 
Pregnancy occurring during the study will be recorded. 
628 
11.3 HYPOGLYCEMIC EVENTS 
629 
Hypoglycemia not associated with an Adverse Device Effect is only reportable as an adverse 
630 
event when the following definition for severe hypoglycemia is met: the event required 
631 
assistance of another person due to altered consciousness, and required another person to actively 
632 
administer carbohydrate, glucagon, or other resuscitative actions. This means that the participant 
633 
was impaired cognitively to the point that he/she was unable to treat himself/herself, was unable 
634 
to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or experienced seizure 
635 
or coma. These episodes may be associated with sufficient neuroglycopenia to induce seizure or 
636 
coma. If plasma glucose measurements are not available during such an event, neurological 
637 
recovery attributable to the restoration of plasma glucose to normal is considered sufficient 
638 
evidence that the event was induced by a low plasma glucose concentration. 
639 
11.4 HYPERGLYCEMIC EVENTS/DIABETIC KETOACIDOSIS 
640 
Hyperglycemia not associated with an Adverse Device Effect is only reportable as an adverse 
641 
event when one of the following 4 criteria is met:  
642 
the event involved DKA, as defined by the Diabetes Control and Complications Trial 
643 
(DCCT) and described below 
644 
evaluation or treatment was obtained at a health care provider facility for an acute event 
645 
involving hyperglycemia or ketosis 
646 
EORRGNHWRQHOHYHO0.6 mmol/L and communication occurred with a health care provider at 
647 
the time of the event 
648 
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EORRGNHWRQHOHYHO2.5 mmol/L, even if there was no communication with a health care 
649 
provider 
650 
Hyperglycemic events are classified as DKA if the following are present: 
651 
Symptoms such as polyuria, polydipsia, nausea, or vomiting; 
652 
Serum ketones >1.5 mmol/L or large/moderate urine ketones; 
653 
Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate <15; and 
654 
Treatment provided in a health care facility 
655 
All reportable Adverse Events—whether volunteered by the participant, discovered by study 
656 
personnel during questioning, or detected through physical examination, laboratory test, or other 
657 
means—will be reported on an adverse event form online. Each adverse event form is reviewed 
658 
by the Sponsor to verify the coding and the reporting that is required. 
659 
11.5 RELATIONSHIP OF ADVERSE EVENT TO STUDY DEVICE 
660 
The study investigator will assess the relationship of any adverse event to be related or unrelated 
661 
by determining if there is a reasonable possibility that the adverse event may have been caused 
662 
by the study device. 
663 
To ensure consistency of adverse event causality assessments, investigators should apply the 
664 
following general guideline when determining whether an adverse event is related: 
665 
Yes 
666 
There is a plausible temporal relationship between the onset of the adverse event and the study 
667 
intervention, and the adverse event cannot be readily explained by the participant’s clinical state, 
668 
intercurrent illness, or concomitant therapies; and/or the adverse event follows a known pattern 
669 
of response to the study intervention; and/or the adverse event abates or resolves upon 
670 
discontinuation of the study intervention or dose reduction and, if applicable, reappears upon 
671 
re-challenge. 
672 
No 
673 
Evidence exists that the adverse event has an etiology other than the study intervention (e.g., 
674 
preexisting medical condition, underlying disease, intercurrent illness, or concomitant 
675 
medication); and/or the adverse event has no plausible temporal relationship to study 
676 
intervention. 
677 
11.6 INTENSITY OF ADVERSE EVENT 
678 
The intensity of an adverse event will be rated on a three point scale: (1) mild, (2) moderate, or 
679 
(3) severe. It is emphasized that the term severe is a measure of intensity: thus a severe adverse 
680 
event is not necessarily serious. For example, itching for several days may be rated as severe, but 
681 
may not be clinically serious. 
682 
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MILD: Usually transient, requires no special treatment, and does not interfere with the participant’s 
683 
daily activities. 
684 
MODERATE: Usually causes a low level of inconvenience or concern to the participant and may interfere 
685 
with daily activities, but is usually ameliorated by simple therapeutic measures. 
686 
SEVERE: Interrupts a participant’s usual daily activities and generally requires systemic drug therapy or 
687 
other treatment. 
688 
11.7 CODING OF ADVERSE EVENTS 
689 
Adverse events will be coded using the MedDRA dictionary. The investigator’s assessment will 
690 
be recorded.  
691 
Adverse events that continue after the participant’s discontinuation or completion of the study 
692 
will be followed until their medical outcome is determined or until no further change in the 
693 
condition is expected. 
694 
11.8 OUTCOME OF ADVERSE EVENT 
695 
The outcome of each reportable adverse event will be classified by the investigator as follows: 
696 
RECOVERED/RESOLVED – The participant recovered from the AE/SAE without sequelae. 
697 
Record the AE/SAE stop date. 
698 
RECOVERED/RESOLVED WITH SEQUELAE – The event persisted and had stabilized 
699 
without change in the event anticipated. Record the AE/SAE stop date. 
700 
FATAL – A fatal outcome is defined as the SAE that resulted in death. Only the event that was 
701 
the cause of death should be reported as fatal. AEs/SAEs that were ongoing at the time of death; 
702 
however, were not the cause of death, will be recorded as “resolved” at the time of death. 
703 
NOT RECOVERED/NOT RESOLVED (ONGOING) – An ongoing AE/SAE is defined as the 
704 
event was ongoing with an undetermined outcome. 
705 
An ongoing outcome will require follow-up by the site in order to determine the final outcome of 
706 
the AE/SAE. 
707 
The outcome of an ongoing event at the time of death that was not the cause of death, will be 
708 
updated and recorded as “resolved” with the date of death recorded as the stop date. 
709 
UNKNOWN – An unknown outcome is defined as an inability to access the participant or the 
710 
participant’s records to determine the outcome (for example, a participant that was lost to follow-
711 
up). 
712 
All clinically significant abnormalities of clinical laboratory measurements or adverse events 
713 
occurring during the study and continuing at study termination should be followed by the 
714 
participant’s physician and evaluated with additional tests (if necessary) until diagnosis of the 
715 
underlying cause, or resolution. Follow-up information should be recorded on source documents. 
716 
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If any reported adverse events are present when a participant completes the study, or if a 
717 
participant is withdrawn from the study due to an adverse event, the participant will be contacted 
718 
for re-evaluation within 2 weeks. If the adverse event has not resolved, additional follow-up will 
719 
be performed as appropriate. Every effort should be made by the Investigator or delegate to 
720 
contact the participant until the adverse event has resolved or stabilized. 
721 
11.9 REPORTABLE DEVICE ISSUES 
722 
All UADEs, ADEs, device complaints, and device malfunctions will be reported irrespective of 
723 
whether an adverse event occurred, except in the following circumstances. 
724 
The following device issues are anticipated and will not be reported on a Device Issue Form but 
725 
will reported as an Adverse Event if the criteria for AE reporting described above are met: 
726 
1) Component disconnections 
727 
2) CGM sensors lasting fewer than the number of days expected per CGM labeling 
728 
3) CGM tape adherence issues 
729 
4) Pump infusion set occlusion not leading to ketosis 
730 
5) Battery lifespan deficiency due to inadequate charging or extensive wireless 
731 
communication 
732 
6) Intermittent device component disconnections/communication failures not leading to 
733 
system replacement 
734 
7) Device issues clearly addressed in the user guide manual that do not require additional 
735 
troubleshooting 
736 
8) Skin reactions from CGM sensor placement or pump infusion set placement that do not 
737 
meet criteria for AE reporting 
738 
11.10 
PREGNANCY REPORTING 
739 
If pregnancy occurs, the participant will be discontinued from the study. The occurrence of 
740 
pregnancy will be reported on an AE Form. 
741 
11.11 
TIMING OF EVENT REPORTING 
742 
SAEs and UADEs must be recorded within 24 hours via completion of the serious adverse event 
743 
form and sponsor notification. 
744 
Other reportable adverse events, device malfunctions (with or without an adverse event), and 
745 
device complaints should be reported promptly by completion of the relevant case report form, 
746 
but there is no formal required reporting period. 
747 
The principal investigator is responsible for reporting serious study-related adverse events and 
748 
abiding by any other reporting requirements specific to the Institutional Review Board or Ethics 
749 
Committee. 
750 
Upon receipt of a UADE report, the study principal investigators will investigate the UADE and 
751 
if indicated, report the results of the investigation to the sites’ IRBs, and the Sponsor (Tandem 
752 
Diabetes Care) within ten working days of becoming aware of the UADE per 21CFR 812.46(b) 
753 
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(2). The Sponsor must determine if the UADE presents an unreasonable risk to participants. If 
754 
so, all investigations, or parts of investigations presenting that risk, will be terminated as soon as 
755 
possible but no later than 5 working days after the Sponsor makes this determination and no later 
756 
than 15 working days after first receipt notice of the UADE. 
757 
In the case of a device system component malfunction (e.g. pump, CGM, control algorithm), 
758 
information will be forwarded to the responsible company by the site personnel, to be handled 
759 
by its complaint management system. 
760 
11.12 
PARTICIPANT DISCONTINUATION OF STUDY DEVICE 
761 
Rules for discontinuing study device use are described below. 
762 
1) The investigator believes it is unsafe for the participant to continue on the intervention. 
763 
This could be due to the development of a new medical condition or worsening of an 
764 
existing condition; or participant behavior contrary to the indications for use of the 
765 
device that imposes on the participant’s safety 
766 
2) The participant requests that the treatment be stopped 
767 
3) Participant pregnancy 
768 
If pregnancy occurs, the participant will be discontinued from the study entirely. 
769 
Otherwise, even if the study device system is discontinued, the participant will be 
770 
encouraged to remain in the study through the final study visit. 
771 
4) Two distinct episodes of DKA as defined in section 11.4 
772 
5) Two distinct episodes of severe hypoglycemia as defined in section 11.3 
773 
6) The investigator may have a subject temporarily stop use of Control-IQ during: periods 
774 
of significant illness, temperature >101.5, use of oral or injectable glucocorticoids, use of 
775 
epinephrine for the emergency treatment of a severe allergic reaction or asthma attack, or 
776 
if a subject is going to the hospital for any reason. If the investigator believes the period if 
777 
illness may be prolonged or put the safety of the subject or the overall study at risk, the 
778 
investigator may withdraw the subject from the study. 
779 
11.13 
CRITERIA FOR SUSPENDING OR STOPPING OVERALL 
780 
STUDY 
781 
1) In the case of a system malfunction resulting in a severe hypoglycemia or severe 
782 
hyperglycemia event (as defined in sections 11.3 and 11.4), use of the study device 
783 
system will be suspended while the problem is diagnosed. 
784 
2) Three or more cases of severe hypoglycemia or three or more cases of severe 
785 
hyperglycemia (as defined in sections 11.3 and 11.4) across the entire study. 
786 
3) In addition, study activities could be similarly suspended if the manufacturer of any 
787 
constituent study device requires stoppage of device use for safety reasons (e.g. product 
788 
recall). The affected study activities may resume if the underlying problem can be 
789 
corrected by a protocol or system modification that will not invalidate the results 
790 
obtained prior to suspension. 
791 
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The Sponsor (Tandem Diabetes Care) will be informed of all serious adverse events and 
792 
any unanticipated adverse device events that occur during the study and will review 
793 
compiled safety data at periodic intervals. The Sponsor will request suspension of study 
794 
activities or stoppage of the study if deemed necessary based on the totality of safety data 
795 
available. 
796 
11.14 
SAFETY OVERSIGHT 
797 
The clinical site principal investigator will review all reported adverse events and adverse device 
798 
effects, and report them to the study sponsor. 
799 
As this is a single site clinical feasibility study, the Medical Director from the study sponsor will 
800 
carefully review all adverse event reports, and adjudicate their relationship the study device 
801 
based on the site principal investigator’s report and all available information. 
802 
 
803 
 
 
804 
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12 MISCELLANEOUS CONSIDERATIONS 
805 
12.1 DRUGS USED AS PART OF THE PROTOCOL 
806 
Participants will use either lispro or aspart insulin prescribed by their personal physician. 
807 
Participants not using lispro or aspart insulin at the time of screening may not start use of the 
808 
study device until they have one of these insulins available to them for use. 
809 
12.2 PROHIBITED MEDICATIONS, TREATMENTS, AND 
810 
PROCEDURES 
811 
Participants using other insulins at the time of enrollment will be asked to contact their personal 
812 
physician to change their prescribed personal insulin to lispro or aspart for the duration of the 
813 
trial. 
814 
Treatment with any non-insulin glucose-lowering agent other than metformin (including GLP-1 
815 
agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas and naturaceuticals) or 
816 
Afrezza will not be permitted during the trial. 
817 
The investigational study devices (study insulin pump, study phone, study CGM systems) must 
818 
be removed before Magnetic Resonance Imaging (MRI), Computed Tomography (CT) or 
819 
diathermy treatment. Participants may continue in the trial after temporarily discontinuing use if 
820 
requiring one of the treatments above. 
821 
12.3 PARTICIPANT COMPENSATION 
822 
Participant compensation will be specified in the informed consent form. 
823 
12.1 PARTICIPANT ACCESS TO STUDY DEVICE AT STUDY 
824 
CLOSURE 
825 
Participant will return all study devices and supplies (insulin pump, CGM and related supplies) 
826 
at study closure. Participant may keep the study ketone meter and study glucometer if these 
827 
devices are not marked for investigational use only. 
828 
 
829 
 
 
830 
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13 DATA COLLECTION AND MONITORING 
831 
13.1 CASE REPORT FORMS AND DEVICE DATA 
832 
The main study data are collected through a combination of paper/electronic case report forms 
833 
(CRFs) and electronic device data files obtained from the study software and individual 
834 
hardware components. These electronic device files and paper/electronic CRFs are considered 
835 
the primary source documentation.  
836 
When data are directly collected in electronically, this will be considered the source data. The 
837 
clinical site will maintain appropriate medical and research records for this trial, in compliance 
838 
with ICH E6 and regulatory and institutional requirements for the protection of confidentiality of 
839 
participants. 
840 
Whenever possible, data will be directly collected in electronic form, which will be considered 
841 
the source data. Otherwise the paper case report forms will be considered the source data. 
842 
13.2 STUDY RECORDS RETENTION 
843 
Study documents should be retained for a minimum of 2 years after the last approval of a 
844 
marketing application in an ICH region and until there are no pending or contemplated marketing 
845 
applications in an ICH region or until at least 2 years have elapsed since the formal 
846 
discontinuation of clinical development of the investigational product. These documents should 
847 
be retained for a longer period, however, if required by local regulations. No records will be 
848 
destroyed without the written consent of the sponsor, if applicable. It is the responsibility of the 
849 
sponsor to inform the investigator when these documents no longer need to be retained. 
850 
13.3 PROTOCOL DEVIATIONS 
851 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or procedure 
852 
requirements. The noncompliance may be either on the part of the participant, the investigator, or 
853 
the study site staff. As a result of deviations, corrective actions are to be developed by the site 
854 
and implemented promptly. The site PI/study staff is responsible for knowing and adhering to 
855 
their IRB reporting requirements.  
856 
13.4 ETHICAL STANDARD 
857 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
858 
the Protection of Human Participants of Research codified in 45 CFR Part 46, 21 CFR Part 50, 
859 
21 CFR Part 56, and/or the ICH E6. 
860 
13.5 INSTITUTIONAL REVIEW BOARDS 
861 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
862 
be submitted to the IRB for review and approval. Approval of both the protocol and the consent 
863 
form must be obtained before any participant is enrolled. Any amendment to the protocol will 
864 
require review and approval by the IRB before the changes are implemented to the study. All 
865 
changes to the consent form will be IRB approved; a determination will be made regarding 
866 
whether previously consented participants need to be re-consented. 
867 
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13.6 CONSENT PROCEDURES AND DOCUMENTATION 
868 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
869 
the study and continues throughout the individual’s study participation. Extensive discussion of 
870 
risks and possible benefits of participation will be provided to the participants and their families. 
871 
Consent forms will be IRB-approved, and the participant will be asked to read and review the 
872 
document. The investigator will explain the research study to the participant and answer any 
873 
questions that may arise. All participants will receive a verbal explanation in terms suited to their 
874 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
875 
research participants. Participants will have the opportunity to carefully review the written 
876 
consent form and ask questions prior to signing. 
877 
The participants should have the opportunity to discuss the study with their surrogates or think 
878 
about it prior to agreeing to participate. The participant will sign the informed consent document 
879 
prior to any procedures being done specifically for the study. The participants may withdraw 
880 
consent at any time throughout the course of the trial. A copy of the informed consent document 
881 
will be given to the participants for their records. The rights and welfare of the participants will 
882 
be protected by emphasizing to them that the quality of their medical care will not be adversely 
883 
affected if they decline to participate in this study. 
884 
13.7 PARTICIPANT AND DATA CONFIDENTIALITY 
885 
The study monitor, other authorized representatives of the sponsor, such as the study 
886 
coordinating center, representatives of the IRB or authorized representatives from the clinical 
887 
site(s) or Tandem Diabetes Care, Inc., may inspect all documents and records required to be 
888 
maintained by the investigator, including but not limited to, medical records (office, clinic, or 
889 
hospital) for the participants in this study. The clinical study sites will permit access to such 
890 
records. 
891 
The study participant’s contact information will be securely stored at each clinical site for 
892 
internal use during the study. At the end of the study, all records will continue to be kept in a 
893 
secure location for as long a period as dictated by local IRB and Institutional regulations. 
894 
Study participant research data, which is for purposes of statistical analysis and scientific 
895 
reporting, will be transmitted from the clinical site(s) and sent to Tandem Diabetes Care. This 
896 
will not include the participant’s contact or identifying information. Rather, individual 
897 
participants and their research data will be identified by a unique study identification number. 
898 
The study data entry and study management systems used by the clinical site will be secured and 
899 
password protected. At the end of the study, all study databases will be de-identified and 
900 
archived at the clinical site(s). Permission to transmit data will be included in the informed 
901 
consent. 
902 
Subject information will be managed according to the Health Insurance Portability and 
903 
Accountability Act of 1996 (HIPAA). In addition, all personal data will be handled in 
904 
accordance with the EU directive e95/46/EC and as of 25 May 2018 in accordance with the 
905 
GDPR. All data will be de-identified at each site before being entered into the case report forms. 
906 
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Only the investigator and site coordinator will have access to the de-identified data. The 
907 
Informed Consent Form must include information letting the subject know: 
908 
x What protected health information (PHI) will be collected during the study; 
909 
x Who will have access to that information; 
910 
x Who will use or disclose that information; 
911 
x The rights of the research subject to revoke their authorization for use of their PHI. 
912 
 
913 
13.8 PARTICIPANT WITHDRAWAL 
914 
Participation in the study is voluntary, and a participant may withdraw at any time. 
915 
For participants who withdraw, their data will be used up until the time of withdrawal. 
916 
13.9 CONFIDENTIALITY 
917 
For security and confidentiality purposes, participants will be assigned an identifier that will 
918 
be used instead of their name. Protected health information gathered for this study will be 
919 
VHFXUHO\VWRUHGDWWKHFOLQLFDOVLWH'HဩLGHQWLILHGSDUWLFLSDQWLQIRUPDWLRQPD\DOVREHSURYLGHGWR
920 
the Sponsor consistent with these guidelines.
921 
Page B41

 
41 
 
14 REFERENCES 
1. Brown SA, Kovatchev BP, Raghinaru D, Lum JW et al. Six-month randomized, 
multicenter trial of closed-loop control in type 1 diabetes. N Engl J Med. 2019; 
381(18):1707-1717.  
2. Breton MD, Kanapka LG, Beck RW, Ekhlaspour L et al. A randomized trial of closed-
loop control in children with type 1 diabetes. N Engl J Med. 2020; 383(9):836-845.  
 
 
 
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