Tandem PLGS Pivotal Trial: A Randomized Clinical Trial to Assess the Efficacy of Predictive Low Glucose Suspend Versus Sensor-augmented Pump Therapy in the Management of Type 1 Diabetes
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Sponsor: Tandem Diabetes Care, Inc.

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
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Tandem PLGS Pivotal Trial: 
A randomized clinical trial to assess the efficacy of predictive low glucose suspend 
versus sensor-augmented pump therapy in the management of type 1 diabetes 
 
 
 
IDE Sponsor: Tandem Diabetes Care, Inc. 
 
 
 
 
 
 
 
 
 
Version 6.0 
 
21/February/2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
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KEY ROLES 
1 
 
2 
 
3 
Lead Clinical Investigator 
Name, Degree 
Bruce Buckingham, MD 
Institution Name 
Stanford University 
JCHR Coordinating Center Director 
Name, Degree 
John Lum, M.S. 
Institution Name 
Jaeb Center for Health Research 
Medical Monitor 
Name, Degree 
Roy Beck, M.D., Ph.D. 
Institution Name 
Jaeb Center for Health Research 
Sponsor 
Name, Degree 
Vance Swanson 
Institution Name 
Tandem Diabetes Care, Inc 
 
4 
 
5 
 
6 
 
7 
 
 
8 
 
9 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
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Table of Contents 
10 
 BACKGROUND INFORMATION ........................................................................................................... 12 
11 
 Introduction ................................................................................................................................................................ 12 
12 
 Hypoglycemia Minimization Strategy ........................................................................................................................ 12 
13 
 PLGS System........................................................................................................................................................... 12 
14 
 Rationale ..................................................................................................................................................................... 13 
15 
 Potential Risks and Benefits of the Investigational Device and Study Participation .................................................. 13 
16 
 Risk of Hyperglycemia ............................................................................................................................................ 13 
17 
 Known Potential Benefits ........................................................................................................................................ 13 
18 
 Risk Assessment ...................................................................................................................................................... 14 
19 
 General Considerations............................................................................................................................................... 14 
20 
 STUDY RECRUITMENT, ENROLLMENT, AND SCREENING......................................................... 15 
21 
 Participant Recruitment and Enrollment..................................................................................................................... 15 
22 
 Informed Consent and Authorization Procedures .................................................................................................... 15 
23 
 Participant Inclusion Criteria ...................................................................................................................................... 16 
24 
 Participant Exclusion Criteria ..................................................................................................................................... 16 
25 
 Screening Procedures ................................................................................................................................................. 17 
26 
 Data Collection and Testing .................................................................................................................................... 17 
27 
 CGM AND SAP TRAINING PHASES ..................................................................................................... 18 
28 
 Introduction ................................................................................................................................................................ 18 
29 
 CGM Training Period (10-14 Days) ........................................................................................................................... 18 
30 
 CGM Training Contact and Visit Schedule ............................................................................................................. 19 
31 
 SAP Training Period (14-28 days) ............................................................................................................................. 19 
32 
 SAP Training Contact and Visit Schedule ............................................................................................................... 20 
33 
 Assessment of SAP Training Period ........................................................................................................................ 20 
34 
 PLGS PILOT PERIOD ............................................................................................................................... 21 
35 
 PLGS Pilot Period Overview ...................................................................................................................................... 21 
36 
 Initiation of PLGS ...................................................................................................................................................... 21 
37 
 Visit and Contact Schedule ......................................................................................................................................... 21 
38 
 PLGS Pilot Period Data Review ................................................................................................................................. 21 
39 
 CROSSOVER TRIAL ................................................................................................................................. 22 
40 
 Crossover Trial Overview .......................................................................................................................................... 22 
41 
 Crossover Trial Initiation............................................................................................................................................ 22 
42 
 Crossover Study Periods .......................................................................................................................................... 22 
43 
 Home Procedures during the Study Periods ............................................................................................................... 22 
44 
 Prohibited Medications, Treatments, and Procedures ................................................................................................. 23 
45 
 Study Visits and Contacts ........................................................................................................................................... 23 
46 
 Crossover Trial Randomization Visit (Beginning of Study Period 1) ........................................................................ 23 
47 
 End of Study Period 1 Follow-up Clinic Visit and Beginning of Study Period 2.................................................... 24 
48 
 End of Study Period 2 and Final Visit ..................................................................................................................... 24 
49 
 STUDY DEVICES ....................................................................................................................................... 25 
50 
 Description of the Investigational Device .................................................................................................................. 25 
51 
 Insulin Pump ............................................................................................................................................................ 25 
52 
 Continuous Glucose Monitoring.............................................................................................................................. 25 
53 
 Blood Glucose Meter and Strips .............................................................................................................................. 25 
54 
 Ketone Meter and Strips .......................................................................................................................................... 25 
55 
 Study Device Accountability Procedures ................................................................................................................... 26 
56 
 Blood Glucose Meter Testing .................................................................................................................................. 26 
57 
 Blood Ketone Testing .............................................................................................................................................. 26 
58 
 Safety Measures.......................................................................................................................................................... 26 
59 
 CGM Calibration ..................................................................................................................................................... 26 
60 
 PLGS Suspend and Resume Alerts .......................................................................................................................... 26 
61 
 Low Glucose Alert and Safety Protocol .................................................................................................................. 26 
62 
 High Glucose Alert and Safety Protocol.................................................................................................................. 27 
63 
 TESTING PROCEDURES AND QUESTIONNAIRES .......................................................................... 28 
64 
 Testing Procedures ..................................................................................................................................................... 28 
65 

 
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 Questionnaire .............................................................................................................................................................. 28 
66 
 Usability Questionnaire ........................................................................................................................................... 28 
67 
 ADVERSE EVENTS, REPORTING, AND STOPPING RULES ........................................................... 29 
68 
 Definitions .................................................................................................................................................................. 29 
69 
 Reportable Adverse Events ........................................................................................................................................ 29 
70 
 Hypoglycemic Events .............................................................................................................................................. 30 
71 
 Hyperglycemic Events/Diabetic Ketoacidosis ......................................................................................................... 30 
72 
 Relationship of Adverse Event to Study Device...................................................................................................... 30 
73 
 Intensity of Adverse Event ...................................................................................................................................... 31 
74 
 Coding of Adverse Events ....................................................................................................................................... 31 
75 
 Outcome of Adverse Event ...................................................................................................................................... 31 
76 
 Reportable Device Issues............................................................................................................................................ 32 
77 
 Pregnancy Reporting .................................................................................................................................................. 32 
78 
 Timing of Event Reporting ......................................................................................................................................... 32 
79 
 Stopping Criteria ........................................................................................................................................................ 33 
80 
 Participant Discontinuation of Study Device ........................................................................................................... 33 
81 
 Criteria for Suspending or Stopping Overall Study ................................................................................................. 33 
82 
 Risks ........................................................................................................................................................................... 34 
83 
 MISCELLANEOUS CONSIDERATIONS ............................................................................................... 35 
84 
 Participant Compensation ........................................................................................................................................... 35 
85 
 Participant Withdrawal ............................................................................................................................................... 35 
86 
 Confidentiality ............................................................................................................................................................ 35 
87 
 STATISTICAL CONSIDERATIONS ..................................................................................................... 36 
88 
 Statistical and Analytical Plans ................................................................................................................................ 36 
89 
 Statistical Hypotheses ............................................................................................................................................... 36 
90 
 Sample Size .............................................................................................................................................................. 36 
91 
 Outcome Measures ................................................................................................................................................... 36 
92 
 Description of Statistical Methods............................................................................................................................ 37 
93 
 General Approach .................................................................................................................................................. 37 
94 
 Analysis Cohorts ................................................................................................................................................... 37 
95 
 Analysis of the Primary Efficacy Endpoint .............................................................................................................. 37 
96 
 Analysis of the Secondary Endpoints ....................................................................................................................... 37 
97 
 Safety Analyses ........................................................................................................................................................ 37 
98 
 Other Analyses ......................................................................................................................................................... 38 
99 
 Baseline Descriptive Statistics ................................................................................................................................ 38 
100 
 Planned Interim Analyses ....................................................................................................................................... 38 
101 
 Sub-Group Analyses ............................................................................................................................................... 39 
102 
 Multiple Comparison/Multiplicity .......................................................................................................................... 39 
103 
 Exploratory Analyses ............................................................................................................................................. 39 
104 
 DATA COLLECTION AND MONITORING ........................................................................................ 40 
105 
 Case Report Forms and Device Data ........................................................................................................................ 40 
106 
 Study Records Retention .......................................................................................................................................... 40 
107 
 Quality Assurance and Monitoring ........................................................................................................................... 40 
108 
 Protocol Deviations .................................................................................................................................................. 41 
109 
 ETHICS AND PROTECTION OF HUMAN PARTICIPANTS ........................................................... 42 
110 
 Ethical Standard........................................................................................................................................................ 42 
111 
 Institutional Review Boards ..................................................................................................................................... 42 
112 
 Informed Consent Process ........................................................................................................................................ 42 
113 
 Consent Procedures and Documentation ............................................................................................................... 42 
114 
 Participant and Data Confidentiality ..................................................................................................................... 42 
115 
 Future Use of Stored Specimens............................................................................................................................ 43 
116 
 INVESTIGATOR AND SPONSOR OBLIGATIONS ............................................................................ 44 
117 
 Role of Sponsor ........................................................................................................................................................ 44 
118 
 Medical Supervision and Investigator Responsibility .............................................................................................. 44 
119 
 Study Initiation and Sponsor Discontinuation .......................................................................................................... 44 
120 
 APPENDIX A – EXTENSION PHASE ................................................................................................... 46 
121 
 REFERENCES .......................................................................................................................................... 47 
122 

 
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123 
LIST OF ABBREVIATIONS 
124 
Abbreviation 
Definition 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AUC 
Area Under the Curve 
BG 
Blood Glucose 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CGM 
Continuous Glucose Monitoring 
DCCT 
Diabetes Control and Complications Trial 
DKA 
Diabetic Ketoacidosis 
EGV 
Estimated Glucose Values 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HbA1c 
Hemoglobin A1c 
HIPAA 
Health Insurance Portability and Accountability Act 
IDE 
Investigational Device Exemption 
ICH 
International Conference on Harmonization 
IOB 
Insulin-on-Board 
 IRB 
Institutional Review Board 
IV 
Intravenous 
JCHR 
Jaeb Center for Health Research 
MDI 
Multiple Daily Injections of insulin 
PGV 
Predicted Glucose Values 
PLGS 
Predictive Low Glucose Suspend 
POC 
Point-of-Care 
QA 
Quality Assurance 
QC 
Quality Control 
RMB 
Risk-Based Monitoring 
SAE 
Serious Adverse Event 
SAP 
Sensor-Augmented Pump 
SD 
Standard Deviation 
SMBG 
Self-Monitoring of Blood Glucose 
T1D 
Type 1 Diabetes 
UADE 
Unanticipated Adverse Device Effect 
UI 
User Interface 
 
125 

 
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SITE PRINCIPAL INVESTIGATOR STATEMENT OF COMPLIANCE 
126 
 
127 
Protocol Title: Tandem PLGS Pivotal Trial: A randomized clinical trial to assess the efficacy of 
128 
predictive low glucose suspend versus sensor-augmented pump therapy in the management of type 1 
129 
diabetes 
130 
 
131 
Protocol Version/Date: v6.0 02-21-2017 
132 
 
133 
I have read the protocol specified above. In my formal capacity as a Site Principal Investigator, my 
134 
duties include ensuring the safety of the study participants enrolled under my supervision and 
135 
providing the Jaeb Center for Health Research, which serves as the Coordinating Center for the 
136 
protocol, with complete and timely information, as required in the conduct of the protocol. It is 
137 
understood that all information pertaining to the study will be held strictly confidential and that this 
138 
confidentiality requirement applies to all study staff at this site. 
139 
 
140 
This trial will be carried out in accordance with ICH E6 Good Clinical Practice (GCP) and as required 
141 
by the following: United States (US) Code of Federal Regulations (CFR) applicable to clinical studies 
142 
(45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21, and 21 CFR Part 812). 
143 
 
144 
As the Principal Investigator, I will assure that no deviation from, or changes to the protocol will take 
145 
place without prior agreement from the sponsor and documented approval from the Institutional 
146 
Review Board (IRB), except where necessary to eliminate an immediate hazard(s) to the trial 
147 
participants. 
148 
 
149 
All key personnel at my site have completed Human Participants Protection Training and Good 
150 
Clinical Practice Training. Further, I agree to ensure that all staff members involved in the conduct of 
151 
this study are informed about their obligations in meeting the above commitments. 
152 
 
153 
 
154 
Investigator’s Signature: __________________________________Date: _____ / _____ / _____ 
155 
 
156 
 
dd 
mmm 
yyyy 
157 
Investigator’s Name: ____________________________________ 
158 
 
159 
 
160 
Site Name/Number: _____________________________________ 
161 
 
162 

 
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PROTOCOL SUMMARY 
163 
 
164 
PARTICIPANT 
AREA 
DESCRIPTION 
Title 
Tandem PLGS Pivotal Trial: A randomized clinical trial to assess the efficacy of 
predictive low glucose suspend versus sensor-augmented pump therapy in the 
management of type 1 diabetes. 
Précis 
A 6-week crossover study will compare PLGS to SAP outcomes in adults and youth 
> 6 years old with type 1 diabetes (T1D). 
 
An extension phase listed in CHAPTER 14: will include participants who have 
completed the crossover study. These participants will use the PLGS pump for two 
years or when the product becomes commercially available, whichever comes first. 
Additional details can be found in CHAPTER 14:. 
Investigational 
Device 
The intervention arm (use of PLGS feature) will utilize Tandem Diabetes Care’s 
ambulatory insulin infusion pump with integrated Dexcom G5 CGM and predictive 
low glucose suspend function. This pump is called the “t:slim X2 with Basal-IQ 
Technology” and is referred to in the protocol as the Tandem PLGS pump. 
 
The control arm (SAP only) will utilize an identical pump in functionality as the 
Tandem PLGS pump except for the lack of the PLGS feature and the associated UI. 
This pump is called the t:slim X2 Dexcom G5 Mobile CGM Enabled pump, and is 
referred to in the protocol as the Tandem SAP pump. 
Objectives 
To assess the efficacy and safety of a predictive low glucose suspend (PLGS) system 
that uses continuous glucose monitoring (CGM) measurements to suspend basal 
insulin delivery when hypoglycemia is predicted as well as resume basal insulin 
delivery once CGM values begin to increase.  
Study Design 
Multi-center, randomized, crossover design, consisting of two 3-week periods, with 
the PLGS System used during one period and SAP therapy used during the other 
period. The crossover trial will be preceded by a run-in phase in which participants 
may receive training using the study devices. 
 
For 10 adult participants, a PLGS Pilot Period will proceed to the crossover trial to 
ensure safety and usability objectives are met prior to the start of the crossover trial. 
Number of Sites 
4-6 in the United States 
Endpoint 
Primary Efficacy Outcome: Percentage of sensor glucose values <70 mg/dL 
Key Secondary Efficacy Outcomes:  
Hypoglycemia 
• 
Percentage of values <60 mg/dL  
• 
Percentage of values <50 mg/dL  
• 
AUC <70 mg/dL 
• 
Low blood glucose index 
• 
Frequency of CGM-measured hypoglycemic events (see below):  
Glucose Control 
• 
Mean glucose 
• 
Percentage of values 70 to 180 mg/dL 
Hyperglycemia 
• 
Percentage of values >250 mg/dL 
• 
Percentage of values >180 mg/dL 
• 
AUC glucose >180 mg/dL 
• 
High blood glucose index 

 
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PARTICIPANT 
AREA 
DESCRIPTION 
 
Key Safety Outcomes: 
• 
Diabetic ketoacidosis (DKA), as defined by the Diabetes Control and 
Complications Trial (DCCT).  
• 
Severe clinical hypoglycemic events such that the participant required 
assistance from another person to actively administer carbohydrate, glucagon, 
or engage in other resuscitative actions; note severe hypoglycemia could be 
considered both and efficacy and safety outcome 
• 
Ketosis events (blood ketone level >1.0 mmol/L) 
• 
All other reported adverse events 
• 
Unanticipated adverse device effects 
Population 
Key Inclusion Criteria: 
• 
Clinical diagnosis of type 1 diabetes treated with insulin via an insulin pump 
or injections for at least 1 year 
• 
Age ≥6.0 years old 
• 
For participants <18 years old, living with one or more parents or guardians 
committed to participating in training and able to contact the participant in 
case of an emergency 
• 
For females, not currently known to be pregnant 
 
Key Exclusion Criteria: 
• 
Anticipated need to use acetaminophen during study participation 
• 
Participation in another pharmaceutical or device trial 
• 
A condition, which in the opinion of the investigator or designee, would put 
the participant or study at risk including any contraindication to the use of 
any of the study devices per FDA labelling  
Sample Size 
At least 90 participants completing the crossover trial 
Treatment Group 
Random assignment (1:1) to (A) PLGS in period 1 and SAP in period 2 or (B) SAP 
in period 1 and PLGS in period 2.  
Participant 
Duration 
2-6 months 
Protocol 
Overview/Synopsis 
1) Screening and Enrollment 
• 
Informed consent will be signed and eligibility will be assessed 
• 
History and physical examination 
• 
HbA1c measurement  
• 
Urine or serum pregnancy test (if applicable) 
• 
Evaluation of CGM and pump experience 
 
2) CGM and SAP Training Period at Home 
All eligible participants will be assessed based on their CGM and pump experience 
to determine if the CGM Training Period, the SAP Training Period, or both are 
required. 
a. CGM Training Period (10-14 days): Participants currently using a CGM may 
skip the CGM Training Period per investigator discretion, generally 
requiring that CGM has been used on at least 85% of days during the prior 4 
weeks. 

 
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PARTICIPANT 
AREA 
DESCRIPTION 
b. SAP Training Period (14-28 days): Participants currently using a Tandem 
pump concomitantly with a Dexcom CGM may skip both the CGM Training 
and the SAP Training periods per investigator discretion.  
i. The Tandem SAP pump will be used during the SAP Training Period 
and pump training will be customized based on prior pump experience 
 
3) PLGS Pilot Phase 
Prior to the initiation of the crossover trial, 10 adult participants will use the Tandem 
PLGS pump and CGM system in a 10-day Pilot Period. Data will be evaluated for 
system usability and predetermined safety metrics before participants ≥12 years old 
can be randomized into the crossover trial. 
 
4) Randomized Crossover Trial 
The crossover trial will begin after the data from the Pilot Period have been 
reviewed. Enrollment of participants 6 to 11 years old will be deferred until data 
from 100 post-randomization PLGS participant-days have been evaluated from 
participants 12 to 17 years old and the same predetermined safety metrics used to 
evaluate the Pilot Period have been satisfied. 
 
At the Crossover Trial initiation visit, the following will be done: 
 
• 
The clinician will confirm the participant’s willingness to participate in the 
crossover trial 
• 
The participant’s HbA1c level will be measured 
• 
Random assignment to Group A or Group B 
Group A: intervention period first (PLGS), control period second (SAP) 
Group B: control period first (SAP), intervention period second (PLGS) 
 
During each of the two 3-week periods, a phone, email, or text contact will occur at 
2 and 14 days, and a clinic visit at 7 and 21 days. HbA1c will be measured at the end 
of each period. 
 
165 

 
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Figure 1 – SCHEMATIC OF STUDY DESIGN 
166 
 
167 
 
168 
 
169 

 
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Table 1 - SCHEDULE OF STUDY VISITS3, CONTACTS, AND PROCEDURES 
170 
Procedure 
Screening 
Visit 
CGM and SAP 
Training-
related Visits 
and Contact 
Randomization 
Visit 
(Week 0) 
Study Period 1 (SP1), Followed by Identical Schedule 
for Study Period 2 (SP2) 
Day 2 
Follow Up 
Day 7 
Follow Up 
Day 14 
Follow Up 
Day 21 
End of SP1 
or SP2 
Time from 
Randomization (SP1) or 
Crossover (SP2) 
0-6w prior 
2-6w prior 
0 
2d ± 1d 
7d ± 2d 
14d ± 3d 
21+7d  
Visit (V) or Contact (C) 
V 
V,C 
V 
C 
V 
C 
V 
Eligibility Assessment 
X 
 
X 
 
 
 
 
Point-of-Care HbA1c 
X 
 
X 
 
 
 
X 
Pregnancy test 
X 
 
X 
 
 
 
 
Device Data Downloads 
X 
X 
X 
 
X 
 
X 
PLGS System Training 
 
 
X 
 
 
 
X1 
System Usability Scale 
 
 
 
 
 
 
X2 
 
171 
1 – PLGS System Training performed only at end of SP1 for participants who did not use PLGS in SP1  
172 
2 – For participants who used PLGS in the preceding study period  
173 
3 – Additional visits associated with a study Extension Period are described in Appendix A  
174 

 
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 BACKGROUND INFORMATION 
175 
 
176 
 Introduction 
177 
The goal of this study is to assess the functionality of an integrated predictive low glucose 
178 
suspend system designed to minimize the incidence and duration of hypoglycemia by suspending 
179 
insulin delivery if hypoglycemia is projected. The hypothesis is that the system, utilizing CGM 
180 
and predictive algorithms, can safely reduce hypoglycemia exposure, especially during sleep. 
181 
 
182 
Most episodes of severe hypoglycemia occur during the night, specifically during sleep (1, 2).  
183 
Even with the advent of real-time CGM, patients do not awaken to over 70% of nocturnal alarms 
184 
(3). Certain studies have demonstrated that reducing nocturnal hypoglycemia by using a CGM 
185 
device with hypoglycemic prediction algorithms to suspend basal insulin delivery is both safe 
186 
and effective (4-6). However, this benefit has been accompanied by modest increases in mean 
187 
overnight sensor glucose and morning fasting blood glucose. A 10-subject CRC-based pilot 
188 
study was conducted using a prototype version of the PLGS system to be used in the current 
189 
study. The pilot study demonstrated that the system suspended and restarted the insulin pump 
190 
appropriately in response to falling and rising CGM sensor glucose levels (abstract accepted at 
191 
ADA 2017). 
192 
 
193 
This protocol is designed to test the safety and efficacy of a predictive low glucose suspend 
194 
system (PLGS) compared to a sensor-augmented pump (SAP) system during day and night use at 
195 
home under normal conditions. The study data are intended to be used to support a Premarket 
196 
Approval (PMA) application.    
197 
 
198 
 Hypoglycemia Minimization Strategy 
199 
A predictive low glucose suspend algorithm (PLGS) is used to respond to low glucose readings.  
200 
The Predicted Glucose Values (PGV) are based on current Estimated Glucose Values (EGV) 
201 
(i.e., glucose readings) produced by the Dexcom G5 CGM System every 5 minutes. Specifically, 
202 
the last 4 EGVs are combined using linear regression and used to project future glucose values. 
203 
Using the calculated rate of change, the resulting PGV extends the past trend into the future by 
204 
30 minutes. At least 3 of the last 4 EGV data points must be available in order to provide a 
205 
prediction. 
206 
 
207 
Both EGV and PGV values are used to regulate insulin delivery. If the PGV is less than 80 
208 
mg/dL the system will suspend insulin delivery. If the observed EGV falls below the suspension 
209 
threshold (70 mg/dL), the system will also suspend insulin delivery, even if a PGV cannot be 
210 
generated. Insulin will resume when the system detects that EGVs are rising (i.e., when the most 
211 
recent EGV is 1 mg/dL greater than the previous EGV). Additionally, the insulin will resume if 
212 
the system has been suspended for more than 120 minutes in the last 150 minutes. These specific 
213 
rules for suspension and resumption of insulin are applied after each 5-minute CGM reading, are 
214 
active 24-hours a day, and have been adopted from previously published clinical studies by 
215 
Buckingham et al. (4-6). 
216 
 
217 
 PLGS System 
218 
Tandem Diabetes Care’s ambulatory insulin infusion pump with integrated Dexcom G5 CGM 
219 
and predictive low glucose suspend (PLGS) function, “t:slim X2 with Basal-IQ Technology,” is 
220 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
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intended for subcutaneous delivery of insulin, for the management of diabetes mellitus in persons 
221 
requiring insulin. The PLGS System includes the Dexcom continuous glucose monitoring 
222 
(CGM) device indicated for detecting trends and tracking patterns in persons with diabetes. The 
223 
PLGS System is able to stop and resume basal insulin delivery automatically in response to low 
224 
sensor glucose values, thereby reducing the incidence and duration of hypoglycemic episodes. 
225 
 
226 
The system used in this study is a modified version of the previously approved t:slim G4 system 
227 
(P140015) and is comprised of a CGM sensor and transmitter along with an insulin pump with 
228 
user interface (UI) for display of system information. The sensor is inserted subcutaneously and 
229 
transmits data every 5 minutes to the pump via the transmitter. The pump includes the 
230 
hypoglycemia minimization strategy described in Section 1.2 that will issue insulin delivery 
231 
commands. 
232 
 
233 
Figure 2 - The Tandem insulin infusion pump with integrated Dexcom G5 CGM and 
234 
predictive low glucose suspend function (PLGS): t:slim X2 with Basal-IQ Technology 
235 
 
236 
 
237 
 Rationale 
238 
Hypoglycemia is a significant problem for adults and children with type 1 diabetes (T1D). A 
239 
system that can reduce insulin delivery when the hypoglycemia is predicted will be very 
240 
beneficial to reduce the risk of severe hypoglycemia and improve quality of life. 
241 
 
242 
 Potential Risks and Benefits of the Investigational Device and Study Participation 
243 
 Risk of Hyperglycemia 
244 
The main risk of using the PLGS system is hyperglycemia, which could occur if insulin delivery 
245 
is suspended for an extended period during the operation of the PLGS system. Prior studies have 
246 
demonstrated that an increase in mild hyperglycemia is likely with prolonged pump suspension 
247 
(4-6). With prolonged pump suspension, ketonemia may occur, but the risk of DKA should not 
248 
be increased (7-8). A CGM functioning poorly and significantly underestimating glucose 
249 
concentrations could lead to inappropriate suspension of insulin delivery. 
250 
 
251 
 Known Potential Benefits 
252 
One purpose of this research is to reduce the frequency and duration of hypoglycemia in addition 
253 
to severe hypoglycemic events. Hypoglycemia is a major fear of many individuals with T1D and 
254 
their families and this fear often prevents optimal glycemic control.  
255 
 
256 

 
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It is expected that this protocol will yield increased knowledge about using a predictive low 
257 
glucose suspend system to control blood glucose level in persons with T1D. In addition, it is the 
258 
belief of the investigators that this study also presents prospect of direct benefit to the 
259 
participants and general benefit to others with T1D. 
260 
 
261 
 Risk Assessment 
262 
Based on the facts that (1) adults and adolescents with diabetes experience frequent 
263 
hypoglycemia as a consequence of the disease and its management, (2) the study intervention is 
264 
expected to reduce hypoglycemia without a substantial increase in hyperglycemia, and (3) a 
265 
similar system has been extensively tested in prior studies, the investigators believe that this 
266 
protocol falls under DHHS 46.405 which is a minor increase over minimal risk. In addition, it is 
267 
the belief of the investigators that this study also presents the prospect of direct benefit to the 
268 
participants and general benefit to others with T1D. 
269 
 
270 
 General Considerations 
271 
The study is being conducted in compliance with the ethical principles that have their origin in 
272 
the Declaration of Helsinki, with the protocol described herein, and with the standards of Good 
273 
Clinical Practice (GCP). 
274 
 
275 
Data will be directly collected in electronic case report forms, which will be considered the 
276 
source data. 
277 
 
278 
The protocol is considered a significant risk device study, due to the fact that the predictive low 
279 
glucose suspend system is experimental. Therefore, an investigational device exemption (IDE) 
280 
from the U.S. Food and Drug Administration (FDA) is required to conduct the study. 
281 
 
282 
 
283 

 
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 STUDY RECRUITMENT, ENROLLMENT, AND SCREENING 
284 
 
285 
 Participant Recruitment and Enrollment 
286 
Enrollment will proceed with the goal of at randomizing approximately 100 participants so that 
287 
least 90 participants complete the crossover trial with sufficient data to include in the primary 
288 
analysis. A maximum of 200 individuals may be enrolled in the study in order to achieve this 
289 
goal and potentially support an increase in sample size per the interim analysis described in 
290 
Chapter 10. Participants who have signed consent and started the screening process will be 
291 
permitted to continue into the trial, if eligible, even if the trial completion goal has been reached. 
292 
 
293 
Study participants will be recruited from 4-6 clinical centers in the United States. All eligible 
294 
participants will be included without regard to gender, race, religion, or ethnicity. There is no 
295 
restriction on the number of participants to be enrolled by each site towards the overall 
296 
recruitment goal. 
297 
 
298 
The approximate distribution of participants completing the crossover trial is as follows: 
299 
• 45 participants ≥18 years old 
300 
• 45 participants <18 years old, with the goal of recruiting a target of: 
301 
o At least 15 participants 12-17 years old 
302 
o At least 15 participants 6-11 years old 
303 
 
304 
The above numbers generally will be minimums but could vary depending on the need for 
305 
participants to successfully complete the run-in, training phase, or both and to complete the 
306 
crossover trial. 
307 
 
308 
The crossover trial will include the following minimum numbers of participants: 
309 
• 15 pump users 
310 
• 15 multiple daily injection of insulin (MDI) users 
311 
• 15 CGM naïve users (may be pump or MDI) 
312 
• 15 experienced CGM users (may be pump or MDI) 
313 
 
314 
Each participant’s percentage of sensor glucose values <70 mg/dL during an approximate two-
315 
week period prior to initiation of the crossover trial will be assessed, with a study goal that no 
316 
more than 25% of crossover trial participants will have a value <3%. As the study progresses, 
317 
participation in the crossover trial may be restricted to participants with values ≥3% if crossover 
318 
trial participation is projected to exceed the 25% threshold. 
319 
 
320 
Ten eligible adult participants ≥18 years old will use the PLGS system in a 10-day Pilot Period. 
321 
 
322 
 Informed Consent and Authorization Procedures 
323 
Potential eligibility may be assessed as part of a routine-care examination. Prior to completing 
324 
any procedures or collecting any data that are not part of usual care, written informed consent 
325 
will be obtained.  
326 
 
327 
For potential study participants ≥18 years old, the study protocol will be discussed with the 
328 
potential study participant by study staff and an Informed Consent Form will be given. Potential 
329 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 16 of 47 
 
 
study participants will be encouraged to discuss the study with family members and their 
330 
personal physicians(s) before deciding whether to participate in the study. 
331 
 
332 
For potential participants <18 years old, a parent or legal guardian (referred to subsequently as 
333 
“parent”) will be provided with the Informed Consent Form to read and will be given the 
334 
opportunity to ask questions. Potential participants meeting the IRB’s minimum age of assent 
335 
will be given a Child Assent Form to read and discuss with their parents and study personnel. If 
336 
the parent and child agree to participate, the Informed Consent Form and Child Assent Form will 
337 
be signed. A copy of the consent form(s) will be provided to the participant and their parent and 
338 
another copy will be added to the participant’s study record. 
339 
 
340 
As part of the informed consent process and described in either the same document or a separate 
341 
document, the potential participant will be informed with respect to the study-specific 
342 
information that will be collected and to whom that information will be disclosed (i.e., HIPAA 
343 
requirements).  
344 
 
345 
A participant is considered enrolled when the informed consent form and assent form, if 
346 
applicable, have been signed. 
347 
 
348 
 Participant Inclusion Criteria 
349 
Individuals must meet all of the following inclusion criteria to be eligible to participate in the 
350 
study: 
351 
1. Clinical diagnosis, based on investigator assessment, of T1D treated with insulin via an 
352 
insulin pump or injections for at least 1 year, with no major change in the intensity of 
353 
insulin therapy in the past 3 months (e.g. switching from injections to pump) 
354 
2. Age ≥6.0 years old 
355 
3. For participants <18 years old, living with one or more parents or guardians committed to 
356 
participating in training and able to contact the participant in case of an emergency 
357 
4. For females, not currently known to be pregnant 
358 
o If female and sexually active, must agree to use a form of contraception to prevent 
359 
pregnancy while a participant in the study. A negative serum or urine pregnancy 
360 
test will be required for all females of child-bearing potential. Participants who 
361 
become pregnant will be discontinued from the study. Also, participants who 
362 
during the study develop and express the intention to become pregnant within the 
363 
timespan of the study will be discontinued. 
364 
5. Investigator has confidence that the participant can successfully use all study devices and 
365 
is capable of adhering to the protocol 
366 
 
367 
 Participant Exclusion Criteria 
368 
Individuals meeting any of the following exclusion criteria will be excluded from study 
369 
participation: 
370 
1. Anticipated need to use acetaminophen during study participation 
371 
2. Participation in another pharmaceutical or device trial at the time of enrollment or plan to 
372 
participate in another study during the time period of participation in this study 
373 
3. Employed by, or having immediate family members employed by Tandem; or having a 
374 
direct supervisor at place of employment who is also directly involved in conducting the 
375 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 17 of 47 
 
 
clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative 
376 
who is directly involved in conducting the clinical trial 
377 
4. A condition, which in the opinion of the investigator or designee, would put the 
378 
participant or study at risk including any contraindication to the use of any of the study 
379 
devices per FDA labelling  
380 
o Individuals should not be enrolled with uncontrolled thyroid disease, renal failure 
381 
(e.g., dialysis or eGFR <30), hemophilia or another major bleeding disorder, or 
382 
unstable cardiovascular disease.  
383 
o Laboratory testing and other work up needed to determine that an individual is a 
384 
suitable candidate for the study should be performed as part of usual care. 
385 
 
386 
 Screening Procedures 
387 
Potential participants will be evaluated for study eligibility through the elicitation of a medical 
388 
history, performance of a physical examination by study personnel, and local laboratory testing if 
389 
needed to screen for exclusionary medical conditions. Participant exclusion will be at the 
390 
discretion of the investigator based on study inclusion criteria and exclusion criteria. 
391 
 
392 
Participants who do not initially meet study eligibility requirements may be rescreened once later 
393 
per investigator discretion. 
394 
 
395 
 Data Collection and Testing 
396 
After enrollment (informed consent signed), the following procedures will be performed/data 
397 
collected/eligibility criteria checked and documented: 
398 
• Inclusion and exclusion criteria assessed 
399 
• Demographics (date of birth, sex, race, ethnicity, socioeconomic status) 
400 
• Contact information (retained at the site and not entered into study database) 
401 
• Diabetic history, including CGM, insulin, and pump use 
402 
• Medical history 
403 
• Concomitant medications 
404 
• Standard physical exam (including vital signs and height and weight measurements) by 
405 
the study investigator or designee (a physician, nurse, nurse practitioner or a physician 
406 
assistant). 
407 
• Blood draw for HbA1c measurement (point-of-care measurement acceptable)  
408 
o HbA1c within 4 weeks of screening visit is acceptable 
409 
• Urine or serum pregnancy test for all women of child-bearing potential 
410 
 
411 
Screening procedures will last approximately 1 hour.
412 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 18 of 47 
 
 
 CGM AND SAP TRAINING PHASES 
413 
 
414 
 Introduction 
415 
The run-in phase consists of a CGM training period and SAP training period. The CGM training 
416 
period will last approximately 10-14 days followed by the SAP training period, which will last 
417 
approximately 14-28 days. 
418 
 
419 
Eligible participants may complete the CGM training period and the SAP training period, or may 
420 
skip one or both based on the participants’ device use at the time of enrollment, as described in 
421 
the table below.  
422 
• Participants currently using a CGM may skip the CGM Training Period per investigator 
423 
discretion, generally requiring that the CGM has been used on at least 85% of days 
424 
during the prior 4 weeks.  
425 
• Participants currently using a Tandem pump concomitantly with a Dexcom CGM may 
426 
skip both the CGM Training and the SAP Training periods per investigator discretion.  
427 
o These participants will proceed to the next visit, which can either be the 
428 
Crossover Trial Randomization Visit, or the 10-day PLGS Pilot Period (see 
429 
Chapter 4).  
430 
• Participants must complete the SAP Training Period if they are either: 
431 
o Not using a CGM 
432 
o Not currently using a Tandem insulin pump 
433 
 
434 
Table 2 - CGM and SAP Training Requirements Based on Device Status at Enrollment 
435 
 
CGM Use Insulin Delivery 
Mode 
CGM Training Period: 
10-14 days 
SAP Training Period: 14-28 
days 
Device Use 
Current 
use of 
CGM 
Current use of 
pump 
Skip per investigator’s 
discretion, generally requiring 
that CGM has been used on at 
least 85% of days during the 
prior 4 weeks. 
Skip if participant’s personal 
pump is Tandem; else 
participate using Dexcom study 
CGM and Tandem study pump 
MDI (No current 
use of pump) 
Participate using Dexcom study 
CGM and Tandem study pump 
No 
current 
use of 
CGM 
Current use of 
pump or MDI 
Participate using Dexcom 
study CGM while continuing 
personal pump or MDI 
Participate using Dexcom study 
CGM and Tandem study pump 
 
 
436 
 CGM Training Period (10-14 Days) 
437 
Participants not currently using a CGM as described above will complete 10-14 days of study 
438 
CGM use at home with their current form of insulin therapy (personal pump or MDI).  
439 
 
440 
CGM training will include the following: 
441 
• Approximately 1-2 hours of training on sensor insertion, transmitter placement, sensor 
442 
calibration, and the use of CGM in daily diabetes management per manufacturer 
443 
guidelines 
444 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
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• Participants will be provided with information regarding the potential risk of sensor site 
445 
infection and bleeding, sensor needle fracture and sensor failure 
446 
• Participants will be provided with written instructions on using the CGM 
447 
 
448 
Participants will be provided with a CGM system and sensors; a blood glucose meter, test strips, 
449 
lancets, and control solution; and a blood ketone meter, test strips, and control solution. 
450 
 
451 
 CGM Training Contact and Visit Schedule 
452 
Participants will be contacted after 6±1 days to review any issues with CGM use.  
453 
 
454 
Participants will use the CGM for at least 10 days and will return to the clinic after 10+4 days. 
455 
Participants may continue in the study if the investigator judges that the participant can use the 
456 
CGM safely and consistently in the remainder of the study. 
457 
 
458 
 SAP Training Period (14-28 days) 
459 
Participants not currently using a CGM or not currently using a Tandem insulin pump must 
460 
complete the SAP Training Period. Participants will use the study Dexcom CGM and the 
461 
Tandem pump called the “t:slim X2 Dexcom G5 Mobile CGM Enabled (referred to subsequently 
462 
as the Tandem SAP pump) at home for 14-28 days. 
463 
 
464 
For participants currently on insulin pump therapy, the Tandem SAP pump will be programmed 
465 
so that basal insulin delivery and other settings match the participant’s personal pump settings. 
466 
Participants will be expected to use the Tandem SAP pump daily. 
467 
 
468 
Participants may use commercially available features of the study CGM system related to mobile 
469 
data access or remote monitoring, but will be instructed not to use any third-party components 
470 
for this purpose. 
471 
 
472 
For participants not currently on insulin pump therapy, an initial basal insulin profile will be 
473 
customized on a per-participant basis. Total daily insulin dose will be reduced by approximately 
474 
20% as a general rule, with a recommended method outlined in a separate procedures manual. 
475 
Further adjustments to total daily dose and intraday basal rate profile may be made during the 
476 
course of the SAP Training Period. 
477 
 
478 
Pump training will take approximately 1-2 hours and will be customized based on participant’s 
479 
pump experience. General guidelines are as follows: 
480 
• Participants who are pump-naïve will receive standard insulin pump therapy training 
481 
including use of the bolus wizard, and will provide a return demonstration of use of the 
482 
major features of the pump. For participants who are already pump users, differences 
483 
from their personal pump will be reviewed. 
484 
• Training topics will include calculation of insulin-on-board (IOB) and correction boluses, 
485 
infusion site initiation, cartridge/priming procedures, setting up the pump, navigation 
486 
through menus, bolus procedures including stopping a bolus, etc. 
487 
• The study team will assist the participant in study pump infusion site insertion and 
488 
initiation of the pump. The Tandem SAP pump will be programmed with the participant’s 
489 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 20 of 47 
 
 
usual basal rates and pump parameters, if available. The participant will be observed 
490 
using the Tandem SAP pump during at least one meal or snack bolus. 
491 
 
492 
Participants will be provided with an insulin pump, cartridges, and infusion sets and insulin if 
493 
they are not already using an insulin that can be used in the Tandem pump. Participants will also 
494 
be given the appropriate CGM supplies for the SAP Training Period. 
495 
 
496 
 SAP Training Contact and Visit Schedule 
497 
Participants will be contacted via email, phone, or text after 7±1 day (preceded by an upload of 
498 
the pump and sensor data if possible) and have a visit after 14+3 days to review use of the study 
499 
CGM and Tandem SAP pump. Adjustments may be made to optimize pump settings during the 
500 
SAP Training Period per investigator discretion. 
501 
 
502 
If the investigator deems it necessary, an additional two-week SAP Training Period may occur, 
503 
with the same contact and visit schedule as above. 
504 
 
505 
 Assessment of SAP Training Period 
506 
The CGM data will be downloaded and reviewed to assess whether the participant had used the 
507 
CGM on at least 85% of possible days and the Tandem SAP pump was used every day unless 
508 
extenuating circumstances existed. 
509 
 
510 
Participants who do not meet these criteria after an additional two-week SAP Training Period 
511 
will be withdrawn from the study, unless the investigator believes that there were extenuating 
512 
circumstances that prevented successful completion. 
513 
 
514 
Participants will continue to use the study CGM and Tandem SAP pump until the 10-Day Pilot 
515 
Period initiation visit or crossover trial randomization visit, unless the visit is concomitant with 
516 
an SAP Training Assessment visit. 
517 
 
518 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 21 of 47 
 
 
 PLGS PILOT PERIOD 
519 
 
520 
 PLGS Pilot Period Overview 
521 
Prior to the initiation of the crossover trial, 10 adult participants will use the study CGM and 
522 
Tandem’s t:slim X2 with Basal-IQ Technology system that includes the predictive low glucose 
523 
suspend function (referred to subsequently as “Tandem PLGS pump”) in a 10-day Pilot Period. 
524 
Data will be evaluated for system usability and predetermined safety metrics before participants 
525 
≥12 years old may be randomized into the crossover trial. 
526 
 
 
527 
 Initiation of PLGS 
528 
Participants will be trained on the use of the PLGS feature of the pump and instructed to use the 
529 
Tandem PLGS pump and study CGM daily until returning to the clinic. Participants will be 
530 
provided with all CGM and pump supplies, including insulin if needed. 
531 
 
532 
 Visit and Contact Schedule 
533 
Contact via phone, email, or text will occur on days 1, 2, and 5 (±1 day) to assess for adverse 
534 
events and system issues.  
535 
 
536 
Participants will use the PLGS system for at least 10 days and then return to the clinic after 10+4 
537 
days. Participants may use commercially available features of the study CGM system related to 
538 
mobile data access or remote monitoring, but will be instructed not to use any third-party 
539 
components for this purpose. 
540 
 
541 
Device data will be downloaded at the day 10 clinic visit. Participants will be transitioned to a 
542 
study Tandem SAP pump (no PLGS feature) and may continue study CGM use until data review 
543 
from all Pilot Period participants has been completed. Participants will then return to the clinic to 
544 
participate in the crossover trial as described below when that part of the study begins. 
545 
 
546 
 PLGS Pilot Period Data Review 
547 
After the 10th participant completes the Pilot Period, data from approximately 100 participant-
548 
days will be evaluated for system usability and predetermined safety metrics. 
549 
 
550 
Predetermined safety metrics are the following: 
551 
• No PLGS-related DKA 
552 
• No severe hypoglycemia related to system malfunction 
553 
 
554 
All instances of DKA or severe hypoglycemia will be adjudicated by the Medical Monitor to 
555 
determine whether the events were related to system performance. If the predetermined safety 
556 
metrics are not satisfied, the study will be stopped for system evaluation as described in Section 
557 
8.6. 
558 
 
559 
Usability will be assessed on participant and investigator feedback. If system changes are 
560 
required due to safety or usability issues, any necessary regulatory or IRB reviews will be 
561 
performed. Then the Pilot Period will be repeated, and the results will again be evaluated for 
562 
safety and usability prior to the crossover trial.
563 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 22 of 47 
 
 
 CROSSOVER TRIAL 
564 
 
565 
 Crossover Trial Overview 
566 
The main part of the study, a six-week crossover trial, consists of two arms which will receive different 
567 
treatments. Participants will be randomly assigned to one treatment option, then cross over to the other 
568 
treatment option after three weeks. The two treatment options are: 
569 
• Intervention (PLGS Group): Use of the Dexcom G5 CGM with an insulin pump that has 
570 
a PLGS feature (t:slim X2 with Basal-IQ Technology) 
571 
• Control (SAP Group): Use of the Dexcom G5 CGM with an insulin pump that does not 
572 
have a PLGS feature (t:slim X2 Dexcom G5 Mobile CGM Enabled) 
573 
The two Tandem pumps, referred to as the Tandem PLGS and the Tandem SAP pumps, respectively, 
574 
are identical in functionality and user interface (UI) with the exception of the PLGS feature and 
575 
associated UI component. 
576 
 
577 
 Crossover Trial Initiation 
578 
The crossover trial will begin after successful completion of the Pilot Period (see Chapter 4). 
579 
 
580 
Initially, participants >12 years old can be entered into the crossover trial. Initiation of the crossover 
581 
trial by participants 6 to 11 years old will be deferred until data from 100 post-randomization PLGS 
582 
participant-days have been evaluated from participants 12 to 17 years old (of which at least 50 
583 
participant-days will come from participants 12 to <15 years old) and the same predetermined safety 
584 
metrics used to evaluate the Pilot Period have been satisfied. 
585 
• If the safety criteria to proceed to the younger age group are not met, then there will be a hold 
586 
on initiating the crossover trial in this age group until either additional data are collected from 
587 
the active participants or a revision is made to the risk mitigation plan and approved by FDA 
588 
before proceeding 
589 
 
590 
Randomization into the crossover trial may be restricted to participants with at least 3% of sensor 
591 
glucose values <70 mg/dL during an approximately two-week period prior to randomization if the 
592 
crossover trial is projected to include fewer than 75% of such participants.  
593 
 
594 
 Crossover Study Periods 
595 
• Study Period 1: 3-week period of PLGS (Group A) or SAP (Group B) 
596 
• Study Period 2: 3-week period of PLGS (Group B) or SAP (Group A) 
597 
 
598 
 Home Procedures during the Study Periods 
599 
During the two study periods, participants will be asked to: 
600 
• Use the study pump and study CGM every day  
601 
• Keep the PLGS feature activated if using the Tandem PLGS pump 
602 
• Not change pump settings related to insulin delivery (such as basal rate, correction factor, and 
603 
carb ratio) without first discussing with study staff 
604 
• Ensure proper calibration of the CGM at all times, using the study-provided glucose meter 
605 
• Measure blood ketones with the study-provided ketone meter when CGM glucose is >300 
606 
mg/dL on awakening or for at least one hour at other times, or >400 mg/dL at any time. CGM 
607 
glucose >300 mg/dL should be confirmed by self-monitoring of blood glucose (SMBG) 
608 
readings 
609 
• Participants may use commercially available features of the study CGM system related to 
610 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 23 of 47 
 
 
mobile data access or remote monitoring, but will be instructed not to use any third-party 
611 
components for this purpose. Participants will be encouraged to be consistent with their use of 
612 
any such features between the two periods of the crossover study. 
613 
• Contact the study staff if: 
614 
o Blood ketone readings are ≥1.5 mmol/L 
615 
o There are any technical issues with the system 
616 
o There are any symptoms or occurrences of DKA, severe hypoglycemia, or development 
617 
of other medical problems 
618 
o Pregnancy is possible 
619 
o Discontinuation of study participation is desired 
620 
 
621 
Participants will also receive study staff contact information to ask any questions they may have during 
622 
the study. 
623 
 
624 
 Prohibited Medications, Treatments, and Procedures 
625 
Participants will be instructed that acetaminophen must be avoided during the study. If acetaminophen 
626 
is inadvertently taken, the participant will be instructed to disable the PLGS feature for 4 hours and to 
627 
not use the CGM measurements for diabetes management during this time. 
628 
 
629 
Participants will be instructed not to add any new glucose-lowering agents during the study. 
630 
 
631 
 Study Visits and Contacts 
632 
The schedule for follow-up visits and contacts is the same during both periods of the crossover trial.  
633 
• 2±1 day: Contact via phone, email, or text 
634 
• 7±2 days: Visit 
635 
• 14±3 days: Contact via phone, email, or text 
636 
• 21+7 days: Visit  
637 
 
638 
At each contact and visit, the occurrence of device issues and adverse events will be solicited. Device 
639 
data will be uploaded at the day 7 visit (and from home if possible) and are needed to assess issues that 
640 
may arise. 
641 
 
642 
Additional visits and contacts may occur at investigator discretion. 
643 
 
644 
 Crossover Trial Randomization Visit (Beginning of Study Period 1) 
645 
The following procedures will be completed at the crossover trial randomization visit: 
646 
• Eligibility criteria will be reviewed to verify that there have been no changes that could affect 
647 
eligibility since enrollment 
648 
• The individual’s understanding of the protocol and willingness to participate in the crossover 
649 
trial will be reviewed 
650 
• HbA1c will be measured using the DCA Vantage or similar point-of-care (POC) device or local 
651 
lab if not already measured on the same day during the screening visit 
652 
• A pregnancy test will be performed if not already performed on the same day during the 
653 
screening visit 
654 
• All needed study supplies will be given to the participant 
655 
 
 
656 
Study personnel will enter data on the study website to verify eligibility and obtain random assignment 
657 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 24 of 47 
 
 
to Group A or Group B 
658 
• Group A: intervention period first (PLGS), control period second (SAP) 
659 
• Group B: control period first (SAP), intervention period second (PLGS) 
660 
 
661 
Group A participants will receive PLGS training (if not previously received through participation in 
662 
the Pilot Period). 
663 
 
664 
 End of Study Period 1 Follow-up Clinic Visit and Beginning of Study Period 2 
665 
The following procedures will occur during this visit: 
666 
• Data will be reviewed for potential safety issues, and if none pump settings will not be adjusted 
667 
prior to initiation of Study Period 2 
668 
• HbA1c level will be measured using the DCA Vantage or similar point-of-care device or local 
669 
lab 
670 
• Group A participants will complete the PLGS usability survey (see Chapter 7) 
671 
• Initiation of Study Period 2 
672 
o 
Group A participants will return the Tandem PLGS pump and receive the Tandem SAP 
673 
pump with all needed supplies. 
674 
o 
Group B participants will return the Tandem SAP pump and receive the Tandem PLGS 
675 
pump with all needed supplies, and will receive training (or refresher training if applicable) 
676 
on the PLGS feature of the pump. 
677 
 
678 
 End of Study Period 2 and Final Visit  
679 
The following procedures will occur at the end of Study Period 2: 
680 
• Data will be reviewed for potential safety issues 
681 
• HbA1c level will be measured using the DCA Vantage or similar point-of-care device or local 
682 
lab 
683 
• Group B participants will complete the PLGS usability survey (see Chapter 7) 
684 
• All applicable study supplies will be returned to the clinic 
685 
 
686 
 
687 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 25 of 47 
 
 
 STUDY DEVICES 
688 
 
689 
 Description of the Investigational Device 
690 
 Insulin Pump 
691 
The Tandem Diabetes ambulatory infusion pump with PLGS (t:slim X2 with Basal-IQ Technology) is 
692 
intended for the subcutaneous delivery of insulin for the management of diabetes mellitus in persons 
693 
requiring insulin. A touch sensitive Liquid Crystal Display (LCD) provides both the pump information 
694 
to the user as well as the interface for the user to program insulin delivery timing and quantity, both 
695 
basal and bolus delivery of insulin at set and variable rates.  
696 
 
697 
Additionally these pumps are integrated with and display continuous glucose data (CGM) and contain 
698 
a Predictive Low Glucose Suspend (PLGS) algorithm which allows the user to set the system to 
699 
automatically suspend delivery of insulin when the predicted glucose value falls below a predefined 
700 
threshold.  
701 
 
702 
The device system components include an insulin pump and cartridge, infusion catheter, CGM sensor 
703 
and transmitter, and a blood glucose meter for CGM calibrations. 
704 
 
705 
Figure 3 - Tandem Pump Showing Labeled Components 
706 
 
707 
 
708 
 Continuous Glucose Monitoring 
709 
The study CGM will included an unmodified Dexcom G5 Mobile transmitter and sensors. This is an 
710 
FDA-approved device system with no changes to its hardware or firmware components. The CGM 
711 
sensor will be replaced at least once every seven days. 
712 
 
713 
 Blood Glucose Meter and Strips 
714 
Blood glucose levels will be measured and the CGM device will be calibrated using the Accu-Chek 
715 
Guide Blood Glucose Monitoring System in accordance with the manufacturer labeling. 
716 
 
717 
 Ketone Meter and Strips 
718 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 26 of 47 
 
 
Blood ketone levels will be measured using the Abbott Precision Xtra meter and strips in accordance 
719 
with the manufacturer’s labeling. The blood glucose meter component of the Precision Xtra device will 
720 
not be used. 
721 
 
722 
 Study Device Accountability Procedures 
723 
Device accountability procedures will be detailed in the study procedures manual. 
724 
 
725 
 Blood Glucose Meter Testing 
726 
• Participants will be provided with instructions to perform QC testing per manufacturer 
727 
guidelines.  
728 
• All study blood glucose meters will be QC tested with at least two different concentrations of 
729 
control solution if available during all office visits. A tested meter will not be used in a study if 
730 
it does not read within the target range at each concentration per manufacturer labeling. The 
731 
Participant will be instructed to contact study staff for a replacement of the meter, test strips, 
732 
and control solution if a meter fails QC testing at home. 
733 
• Participants will be reminded to use the study blood glucose meter for all fingerstick blood 
734 
glucose measurements  
735 
• Participants will be asked to perform fingerstick blood glucose measurements in accordance 
736 
with the labelling of the study CGM device. 
737 
 
738 
 Blood Ketone Testing 
739 
• Participants to perform QC testing at home per manufacturer guidelines. 
740 
• All study blood ketone meters will be QC tested with at least two different concentrations of 
741 
control solution if available during all office visits. A tested meter will not be used in a study if 
742 
it does not read within the target range at each concentration per manufacturer labeling. The 
743 
Participant will be instructed to contact study staff for a replacement of the meter, test strips, 
744 
and control solution if a meter fails QC testing at home.  
745 
• Participants will be instructed on how to perform blood ketone testing 
746 
• Participants will be given guidelines for treatment of elevated blood ketones 
747 
 
748 
 Safety Measures  
749 
 CGM Calibration 
750 
Throughout the study, participants will be instructed to calibrate the study CGM in accordance with 
751 
manufacturer labelling. 
752 
 
753 
 PLGS Suspend and Resume Alerts 
754 
By default, the Tandem PLGS pump’s audible PLGS suspend and resume alerts will be disabled when 
755 
the participant receives the pump. The participant will be permitted to enable these audible alerts if 
756 
desired during system use. 
757 
 
758 
 Low Glucose Alert and Safety Protocol 
759 
Participants will be required to set the CGM low glucose alert level between 60 mg/dL and 70 mg/dL 
760 
during the course of the study, and not to change this setting during the crossover trial. 
761 
 
762 
If a participant receives a CGM low glucose alert or notes that the CGM glucose is below the low 
763 
glucose threshold alert value, confirmatory fingerstick testing will be performed if required by CGM 
764 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 27 of 47 
 
 
labelling and the participant will be instructed to treat hypoglycemia with ~16 grams of fast-acting oral 
765 
glucose. 
766 
 
767 
 High Glucose Alert and Safety Protocol 
768 
Participants will be required to set the CGM high glucose alert level between 200 mg/dL and 300 
769 
mg/dL during the course of the study, and not to change this setting during the crossover trial. 
770 
 
771 
If a participant receives a CGM hyperglycemia threshold alert or notes that the CGM glucose is above 
772 
the hyperglycemia threshold alert value, confirmatory fingerstick testing will be performed if required 
773 
by CGM labelling.  
774 
 
775 
If a participant’s CGM reading is ≥300 mg/dL when fasting in the morning upon awakening, >300 
776 
mg/dL for over 1 hour during the day, or ≥400 mg/dL at any point, the participant will be instructed to 
777 
take the following steps: 
778 
• Perform a blood glucose meter check. 
779 
• If the blood glucose is >300 mg/dL, then blood ketones should be measured with the study 
780 
ketone meter.  
781 
• Correction insulin may be taken per the participant’s usual routine.  
782 
• Participants will be instructed to change their pump site and administer correction insulin via 
783 
insulin syringe or pen for ketones ≥0.6 mmol/L and to additionally notify study staff for 
784 
ketones ≥1.5 mmol/L. 
785 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 28 of 47 
 
 
 TESTING PROCEDURES AND QUESTIONNAIRES 
786 
 
787 
 Testing Procedures 
788 
The following tests and test procedures will be performed during the study: 
789 
1) Hemoglobin A1c (HbA1c) will be tested using a DCA Vantage or similar point-of-care device 
790 
or local lab 
791 
2) Pregnancy tests will be performed using a urine or serum pregnancy test 
792 
 
793 
 Questionnaire 
794 
The following questionnaire will be completed by each participant after the crossover study period 
795 
during which the PLGS system was used. The procedures for administration are described in the study 
796 
procedures manual. 
797 
 
798 
 Usability Questionnaire 
799 
The System Usability Scale (SUS) is a 10-item questionnaire that measures the overall usability of a 
800 
system that will be administered to all participants. It is a valid and reliable measure of the perceived 
801 
usability of a system and is technology-agnostic. The questionnaire presents statements with five 
802 
response options (anchoring the options from strongly disagree to strongly agree) and asks users to rate 
803 
their agreement to the statements.  User scores are transformed into a composite score, from 0 to 100, 
804 
and this score is taken as an overall measure of the system’s usability; higher scores indicate better 
805 
perceived usability. 
806 
 
807 
Administration time is approximately 5 minutes. 
808 
 
809 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 29 of 47 
 
 
 ADVERSE EVENTS, REPORTING, AND STOPPING RULES  
810 
 
811 
 Definitions 
812 
Adverse Event (AE): Any untoward medical occurrence in a study participant, irrespective of the 
813 
relationship between the adverse event and the device(s) under investigation. 
814 
 
815 
Serious Adverse Event (SAE): Any untoward medical occurrence that: 
816 
• Results in death. 
817 
• Is life-threatening; (a non-life-threatening event which, had it been more severe, might have 
818 
become life-threatening, is not necessarily considered a serious adverse event). 
819 
• Requires inpatient hospitalization or prolongation of existing hospitalization. 
820 
• Results in persistent or significant disability/incapacity or substantial disruption of the ability to 
821 
conduct normal life functions (sight threatening). 
822 
• Is a congenital anomaly or birth defect. 
823 
• Is considered a significant medical event by the investigator based on medical judgment (e.g., 
824 
may jeopardize the participant or may require medical/surgical intervention to prevent one of 
825 
the outcomes listed above). 
826 
 
827 
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety or any 
828 
life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or 
829 
death was not previously identified in nature, severity, or degree of incidence in the investigational 
830 
plan or application (including a supplementary plan or application), or any other unanticipated serious  
831 
problem associated with a device that relates to the rights, safety, or welfare of participants (21 CFR 
832 
812.3(s)). 
833 
 
834 
Adverse Device Effect (ADE): Any untoward medical occurrence in a study participant which the 
835 
device may have caused or to which the device may have contributed. (Note that an Adverse Event 
836 
Form is to be completed in addition to a Device Deficiency or Issue Form). 
837 
 
838 
Device Complaints: A device complication or complaint is something that happens to a device or is 
839 
related to device performance, whereas an adverse event happens to a participant. A device complaint 
840 
may occur independently from an AE, or along with an AE. An AE may occur without a device 
841 
complaint or there may be an AE related to a device complaint. 
842 
 
843 
Device Malfunction: Any failure of a device to meet its performance specifications or otherwise 
844 
perform as intended. Performance specifications include all claims made in the labeling for the device. 
845 
The intended performance of a device refers to the intended use for which the device is labeled or 
846 
marketed. (21 CFR 803.3) 
847 
 
848 
 Reportable Adverse Events 
849 
For this protocol, a reportable adverse event includes any untoward medical occurrence that meets one 
850 
of the following criteria:   
851 
1) A serious adverse event 
852 
2) An Adverse Device Effect as defined in Section 8.1, unless excluded from reporting in Section 8.3 
853 
3) An Adverse Event occurring in association with a study procedure  
854 
4) Hypoglycemia meeting the definition of severe hypoglycemia as defined below  
855 
5) Diabetic ketoacidosis (DKA) as defined below 
856 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 30 of 47 
 
 
Hypoglycemia and hyperglycemia not meeting the criteria below will not be recorded as adverse 
857 
events unless associated with an Adverse Device Effect.  Skin reactions from sensor placement are 
858 
only reportable if severe and/or required treatment.   
859 
 
860 
Pregnancy occurring during the study will be recorded. 
861 
 
862 
 Hypoglycemic Events 
863 
Hypoglycemia not associated with an Adverse Device Effect is only reportable as an adverse event 
864 
when the following definition for severe hypoglycemia is met:  the event required assistance of another 
865 
person due to altered consciousness, and required another person to actively administer carbohydrate, 
866 
glucagon, or other resuscitative actions. This means that the participant was impaired cognitively to the 
867 
point that he/she was unable to treat himself/herself, was unable to verbalize his/ her needs, was 
868 
incoherent, disoriented, and/or combative, or experienced seizure or coma. These episodes may be 
869 
associated with sufficient neuroglycopenia to induce seizure or coma.  If plasma glucose measurements 
870 
are not available during such an event, neurological recovery attributable to the restoration of plasma 
871 
glucose to normal is considered sufficient evidence that the event was induced by a low plasma 
872 
glucose concentration. 
873 
 
874 
 Hyperglycemic Events/Diabetic Ketoacidosis 
875 
Hyperglycemia not associated with an Adverse Device Effect is only reportable as an adverse event 
876 
when one of the following criteria is met:  (1) the event involved DKA, as defined by the Diabetes 
877 
Control and Complications Trial (DCCT) and described below, or (2) in the absence of DKA if 
878 
evaluation or treatment was obtained at a health care provider facility for an acute event involving 
879 
hyperglycemia or ketosis.  
880 
 
881 
Hyperglycemic events are classified as DKA if the following are present:  
882 
• 
Symptoms such as polyuria, polydipsia, nausea, or vomiting;  
883 
• 
Serum ketones >1.5 mmol/L or large/moderate urine ketones;  
884 
• 
Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate <15; and 
885 
• 
Treatment provided in a health care facility     
886 
 
887 
All reportable Adverse Events whether volunteered by the participant, discovered by study personnel 
888 
during questioning, or detected through physical examination, laboratory test, or other means will be 
889 
reported on an adverse event form online. Each adverse event form is reviewed by the Medical 
890 
Monitor to verify the coding and the reporting that is required.  
891 
 
892 
 Relationship of Adverse Event to Study Device 
893 
The study investigator will assess the relationship of any adverse event to be related or unrelated by 
894 
determining if there is a reasonable possibility that the adverse event may have been caused by the 
895 
study device. 
896 
 
897 
To ensure consistency of adverse event causality assessments, investigators should apply the following 
898 
general guideline when determining whether an adverse event is related: 
899 
 
900 
Yes 
901 
There is a plausible temporal relationship between the onset of the adverse event and the study 
902 
intervention, and the adverse event cannot be readily explained by the participant’s clinical state, 
903 
intercurrent illness, or concomitant therapies; and/or the adverse event follows a known pattern of 
904 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 31 of 47 
 
 
response to the study intervention; and/or the adverse event abates or resolves upon discontinuation of 
905 
the study intervention or dose reduction and, if applicable, reappears upon re-challenge. 
906 
 
907 
No 
908 
Evidence exists that the adverse event has an etiology other than the study intervention (e.g., 
909 
preexisting medical condition, underlying disease, intercurrent illness, or concomitant medication); 
910 
and/or the adverse event has no plausible temporal relationship to study intervention.    
911 
 
912 
 Intensity of Adverse Event 
913 
The intensity of an adverse event will be rated on a three point scale: (1) mild, (2) moderate, or (3) 
914 
severe. It is emphasized that the term severe is a measure of intensity: thus a severe adverse event is 
915 
not necessarily serious. For example, itching for several days may be rated as severe, but may not be 
916 
clinically serious. 
917 
• MILD: Usually transient, requires no special treatment, and does not interfere with the 
918 
participant’s daily activities. 
919 
• MODERATE: Usually causes a low level of inconvenience or concern to the participant and 
920 
may interfere with daily activities, but is usually ameliorated by simple therapeutic measures. 
921 
• SEVERE: Interrupts a participant’s usual daily activities and generally requires systemic drug 
922 
therapy or other treatment. 
923 
 
924 
 Coding of Adverse Events 
925 
Adverse events will be coded using the MedDRA dictionary. The Medical Monitor will review the 
926 
investigator’s assessment of causality and may agree or disagree. Both the investigator’s and Medical 
927 
Monitor’s assessments will be recorded. The Medical Monitor will have the final say in determining 
928 
the causality. 
929 
 
930 
Adverse events that continue after the participant’s discontinuation or completion of the study will be 
931 
followed until their medical outcome is determined or until no further change in the condition is 
932 
expected. 
933 
 
934 
 Outcome of Adverse Event 
935 
The outcome of each reportable adverse event will be classified by the investigator as follows: 
936 
• RESOLVED – The participant recovered from the AE/SAE without sequelae. Record the 
937 
AE/SAE stop date. 
938 
• RESOLVED WITH SEQUELAE – The event persisted and had stabilized without change in 
939 
the event anticipated. Record the AE/SAE stop date. 
940 
• FATAL – A fatal outcome is defined as the SAE that resulted in death. Only the event that was 
941 
the cause of death should be reported as fatal. AEs/SAEs that were ongoing at the time of 
942 
death; however, were not the cause of death, will be recorded as “resolved” at the time of death. 
943 
• UNKNOWN – An unknown outcome is defined as an inability to access the participant or the 
944 
participant’s records to determine the outcome (for example, a participant that was lost to 
945 
follow-up).  
946 
• ONGOING – An ongoing AE/SAE is defined as the event was ongoing with an undetermined 
947 
outcome.  
948 
o An ongoing outcome will require follow-up by the site in order to determine the final 
949 
outcome of the AE/SAE. 
950 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 32 of 47 
 
 
o The outcome of an ongoing event at the time of death that was not the cause of death, 
951 
will be updated and recorded as “resolved” with the date of death recorded as the stop 
952 
date.  
953 
 
954 
All clinically significant abnormalities of clinical laboratory measurements or adverse events occurring 
955 
during the study and continuing at study termination should be followed by the participant’s physician 
956 
and evaluated with additional tests (if necessary) until diagnosis of the underlying cause, or resolution. 
957 
Follow-up information should be recorded on source documents.  
958 
 
959 
If any reported adverse events are present when a participant completes the study, or if a participant is 
960 
withdrawn from the study due to an adverse event, the participant will be contacted for re-evaluation 
961 
within 2 weeks. If the adverse event has not resolved, additional follow-up will be performed as 
962 
appropriate. Every effort should be made by the Investigator or delegate to contact the participant until 
963 
the adverse event has resolved or stabilized. 
964 
 
965 
 Reportable Device Issues 
966 
All UADEs, ADEs, device complaints, and device malfunctions will be reported irrespective of 
967 
whether an adverse event occurred, except in the following circumstances.  
968 
 
969 
The following device issues are anticipated and will not be reported on a Device Issue Form but will 
970 
reported as an Adverse Event if the criteria for AE reporting described above are met:  
971 
• Component disconnections 
972 
• CGM sensors lasting fewer than 7 days  
973 
• CGM tape adherence issues 
974 
• Pump infusion set occlusion not leading to ketosis 
975 
• Battery lifespan deficiency due to inadequate charging or extensive wireless communication 
976 
• Intermittent device component disconnections/communication failures not leading to system 
977 
replacement 
978 
• Device issues clearly addressed in the user guide manual that do not require additional 
979 
troubleshooting 
980 
• Skin reactions from CGM sensor placement or pump infusion set placement that don’t meet 
981 
criteria for AE reporting 
982 
 
983 
 Pregnancy Reporting 
984 
If pregnancy occurs, the participant will be discontinued from the study and a final visit will be 
985 
conducted. The occurrence of pregnancy will be reported on an AE Form. 
986 
 
987 
 Timing of Event Reporting 
988 
Serious or unexpected device-related adverse events must be reported to the Coordinating Center 
989 
within 24 hours via completion of the online serious adverse event form.  
990 
 
991 
Other reportable adverse events and device malfunctions (with or without an adverse event) will be 
992 
reported within 3 days of the investigator becoming aware of the event by completion of an electronic 
993 
case report form. 
994 
 
995 
Device complaints not associated with device malfunction or an adverse event must be reported within 
996 
7 days of the investigator becoming aware of the event. 
997 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 33 of 47 
 
 
 
998 
The Coordinating Center will notify all participating investigators of any adverse event that is serious, 
999 
related, and unexpected. Notification will be made within 10 days after the Coordinating Center 
1000 
becomes aware of the event.  
1001 
 
 
1002 
Each principal investigator is responsible for reporting serious study-related adverse events and 
1003 
abiding by any other reporting requirements specific to his/her Institutional Review Board or Ethics 
1004 
Committee. 
1005 
 
1006 
Upon receipt of a UADE report, the Sponsor will investigate the UADE and if indicated, report the 
1007 
results of the investigation to the sites’ IRBs, and the FDA within ten working days of the Sponsor 
1008 
becoming aware of the UADE per 21CFR 812.46(b) (2). The Medical Monitor must determine if the 
1009 
UADE presents an unreasonable risk to participants. If so, the Medical Monitor must ensure that all 
1010 
investigations, or parts of investigations presenting that risk, are terminated as soon as possible but no 
1011 
later than 5 working days after the Medical Monitor makes this determination and no later than 15 
1012 
working days after first receipt notice of the UADE.  
1013 
 
1014 
Device malfunctions will be handled by the Sponsor or designee as described below. In the case of a 
1015 
CGM transmitter or sensor device malfunction, the Coordinating Center will be contacted and the 
1016 
Sponsor will be notified accordingly. 
1017 
 
1018 
 Stopping Criteria 
1019 
 Participant Discontinuation of Study Device 
1020 
Rules for discontinuing study device use are described below.  
1021 
 
1022 
1. The investigator believes it is unsafe for the participant to continue on the intervention. This 
1023 
could be due to the development of a new medical condition or worsening of an existing 
1024 
condition; or participant behavior contrary to the indications for use of the device that imposes 
1025 
on the participant’s safety  
1026 
2. The participant requests that the treatment be stopped  
1027 
3. Two distinct episodes of DKA 
1028 
4. Two distinct severe hypoglycemia events as defined in Section 8.2 
1029 
 
1030 
Even if the study device system is discontinued, the participant will be encouraged to remain in the 
1031 
study through the final study visit. 
1032 
 
1033 
Participants who become pregnant will be discontinued from the study with a final clinic visit and no 
1034 
subsequent use of study device components. 
1035 
 
1036 
 Criteria for Suspending or Stopping Overall Study 
1037 
In the case of a system malfunction resulting in a severe hypoglycemia or severe hyperglycemia event 
1038 
(as defined in Section 8.2), use of the study device system will be suspended while the problem is 
1039 
diagnosed.   
1040 
 
1041 
In addition, study activities could be similarly suspended if the manufacturer of any constituent study 
1042 
device requires stoppage of device use for safety reasons (e.g. product recall). The affected study 
1043 
activities may resume if the underlying problem can be corrected by a protocol or system modification 
1044 
that will not invalidate the results obtained prior to suspension. 
1045 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 34 of 47 
 
 
 
1046 
The study Medical Monitor will be informed of all serious adverse events and any unanticipated 
1047 
adverse device events that occur during the study and will review compiled safety data at periodic 
1048 
intervals. The medical monitor may request suspension of study activities or stoppage of the study if 
1049 
deemed necessary based on the totality of safety data available. 
1050 
 
1051 
 Risks 
1052 
The potential risks associated with use of the study device are described in Section 1.4. 
1053 
 
1054 
Additional risks are minor and/or infrequent and include 
1055 
• Pain, bruising, redness, or infection from blood draws  
1056 
• Loss of confidentiality 
1057 
• Stress from completing quality of life questionnaires 
1058 
• Skin irritation, infection, or bleeding from CGM sensor or pump infusion set or adhesive 
1059 
tap 
1060 
• Breaking of CGM sensor with small portion retained under skin causing redness, swelling, 
1061 
or pain 
1062 
 
1063 
The risk of hypoglycemia should be no greater and possibly less than it is in everyday living for 
1064 
someone with T1D. 
1065 
 
1066 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 35 of 47 
 
 
 MISCELLANEOUS CONSIDERATIONS 
1067 
 
1068 
 Participant Compensation 
1069 
Participants will be compensated $50 for each protocol-specified clinic visit during the study. 
1070 
Participants will typically receive these amounts at the end of each clinic visit. For completing all 
1071 
required study visits, participants will be compensated a minimum of $300 and a maximum of $600 
1072 
due to additional study visits that may be required for some participants. 
1073 
 
1074 
 Participant Withdrawal 
1075 
Participation in the study is voluntary, and a participant may withdraw at any time. For participants 
1076 
who withdraw, their data will be used up until the time of withdrawal. 
1077 
 
1078 
 Confidentiality 
1079 
For security and confidentiality purposes, participants will be assigned an identifier that will be used 
1080 
instead of their name. Protected health information gathered for this study will be shared with the 
1081 
coordinating center, the Jaeb Center for Health Research in Tampa, FL. De-identified participant 
1082 
information may be provided to research sites involved in the study.
1083 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 36 of 47 
 
 
 STATISTICAL CONSIDERATIONS 
1084 
 
1085 
 Statistical and Analytical Plans 
1086 
The approach to sample size and statistical analyses are summarized below.  A detailed statistical 
1087 
analysis plan will be written and finalized prior to the completion of the study.  The analysis plan 
1088 
synopsis in this chapter contains the framework of the anticipated final analysis plan. 
1089 
 
1090 
 Statistical Hypotheses 
1091 
• Null hypothesis: There will be no difference in percentage of CGM-measured glucose values 
1092 
<70 mg/dL between PLGS and SAP 
1093 
• Alternate hypothesis: PLGS will improve the percentage of CGM-measured glucose values <70 
1094 
mg/dL over SAP. 
1095 
 
1096 
 Sample Size 
1097 
Data from the JDRF Continuous Glucose Monitoring Randomized Clinical Trial was used to estimate 
1098 
SD and the frequency of time <70 mg/dL for the pump or MDI population. Assuming a crossover 
1099 
design with two 3 weeks periods, a 2-tailed test, a 33% relative reduction in 24-hour time <70 mg/dL, 
1100 
standard deviation of the paired differences = 3%, a type I error = 5%, and 90% power; a sample of 52 
1101 
participants is required. 
1102 
 
1103 
With a sample size of 90 participants, the primary analysis will have 99% power. The larger sample 
1104 
size will provide increased precision for safety analyses and subgroup analyses. 
1105 
 
1106 
 Outcome Measures 
1107 
Primary Efficacy Endpoint: 
1108 
• Percentage of sensor glucose values <70 mg/dL 
1109 
 
1110 
Secondary Efficacy Endpoints: 
1111 
 
1112 
Hypoglycemia 
1113 
• Percentage of values <60 mg/dL  
1114 
• Percentage of values <50 mg/dL  
1115 
• AUC <70 mg/dL 
1116 
• Low blood glucose index 
1117 
• Frequency of CGM-measured hypoglycemic events (see below):  
1118 
Glucose Control 
1119 
• Mean glucose 
1120 
• Percentage of values 70 to 180 mg/dL 
1121 
Hyperglycemia 
1122 
• Percentage of values >250 mg/dL 
1123 
• Percentage of values >180 mg/dL 
1124 
• AUC glucose >180 mg/dL 
1125 
• High blood glucose index 
1126 
 
1127 
Each of the metrics listed will be calculated over 24 hours and separately for daytime (6am – 10pm) 
1128 
and nighttime (10pm – 6am).  Secondary outcomes will also include the percentage of sensor glucose 
1129 
values <70 mg/dL calculated separately for daytime and nighttime. 
1130 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 37 of 47 
 
 
 
1131 
A CGM-measured hypoglycemic event will be defined as at least 2 sensor values <54 mg/dl that are 15 
1132 
or more minutes apart plus no intervening values >54 mg/dl; at least 2 sensor values >70 mg/dl that are 
1133 
30 or more minutes apart with no intervening values <70 mg/dl, are required to define the end of an 
1134 
event, at which point the study participant becomes eligible for a new event.. 
1135 
 
1136 
 Description of Statistical Methods 
1137 
 General Approach 
1138 
This is a crossover study where each participant is randomized to treatment order. All analyses will 
1139 
compare the 3-week period of PLGS to the 3 week period of SAP and will follow the intention-to-treat 
1140 
principle with each period analyzed according to the treatment assigned by randomization regardless of 
1141 
actual PLGS utilization. All participants who have at least one CGM reading in each 3-week period 
1142 
will be analyzed. All p-values will be two-sided. 
1143 
 
1144 
 Analysis Cohorts 
1145 
• All randomized participants who have at least one CGM reading in each 3-week period will 
1146 
be analyzed for the Intention-to-Treat (ITT) Analysis. 
1147 
• Safety outcomes will be reported for all enrolled participants, irrespective of whether the 
1148 
study was completed. 
1149 
• A per-protocol analysis restricted to participants with at least 200 hours of CGM data in 
1150 
each 3 week period will also be conducted provided that there are at least 5 participants 
1151 
with less than 200 hours of CGM data in both treatment periods. 
1152 
 
1153 
 Analysis of the Primary Efficacy Endpoint 
1154 
The percentage of sensor glucose values <70 mg/dL will be calculated for each participant in each 3-
1155 
week treatment period by pooling all sensor glucose readings that occur within each 3-week period. All 
1156 
sensor glucose readings will be weighted equally in the pooled percentages regardless of how they 
1157 
distribute across weeks. The percentage in the PLGS period will then be compared to the percentage in 
1158 
the SAP period for the same participant.  
1159 
 
1160 
Summary statistics appropriate to the distribution will be calculated for % time below <70 mg/dL 
1161 
separately by treatment arm. A repeated measures regression model with an unstructured covariance 
1162 
structure will be fit for percent time below below <70 mg/dL to compare the two treatments. The 
1163 
model will adjust for period as a covariate. If residual values from the regression model have a skewed 
1164 
distribution then an appropriate transformation or a nonparametric analysis based on ranks will be 
1165 
performed.  
1166 
 
1167 
There will be no imputation of missing CGM data. 
1168 
 
1169 
 Analysis of the Secondary Endpoints 
1170 
Analysis of the secondary endpoints and additional CGM metrics will parallel the analysis of the 
1171 
primary endpoint above.  
1172 
 
1173 
 Safety Analyses 
1174 
The following safety outcomes will be tabulated by participant within each 3-week treatment period. 
1175 
The summary statistics will include start date, stop date, severity, relationship, resolution, and duration. 
1176 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 38 of 47 
 
 
• Diabetic ketoacidosis (DKA), as defined by the Diabetes Control and Complications Trial 
1177 
(DCCT).  
1178 
• Severe clinical hypoglycemic events such that the participant required assistance from 
1179 
another person to actively administer carbohydrate, glucagon, or engage in other resuscitative 
1180 
actions; note severe hypoglycemia could be considered both and efficacy and safety outcome 
1181 
• Ketosis events (blood ketone level >1.0 mmol/L) 
1182 
• All other reported adverse events 
1183 
• Unanticipated adverse device effects 
1184 
 
1185 
 Other Analyses 
1186 
The following outcomes will be tabulated separately over 24-hour period, daytime, and nighttime 
1187 
where applicable: 
1188 
• Insulin delivery including total insulin, basal insulin, and bolus insulin  
1189 
• Frequency of insulin suspension events and duration of events, including individual 
1190 
suspensions and cumulative suspension time 
1191 
• CGM glucose nadir during suspension events and peak within 2 hours after events 
1192 
• The amount of CGM use in both 3-week periods. 
1193 
• Percentage of time PLGS is active. 
1194 
 
1195 
 Baseline Descriptive Statistics 
1196 
Baseline demographic and clinical characteristics of the study cohort including CGM metrics will be 
1197 
tabulated.  For continuous variables, summary statistics appropriate to the distribution will be given. 
1198 
For discrete variables, number and percentage will be reported for each category.  
1199 
  
1200 
 
1201 
 Planned Interim Analyses 
1202 
An interim analysis to re-estimate sample size will be conducted approximately when the 90th subject 
1203 
is enrolled into the screening phase of the study.  The objective is to assess whether the observed rate 
1204 
of hypoglycemia in the control arm matches the value assumed in the original sample size calculation. 
1205 
 
1206 
A longitudinal regression model will be fit using CGM data from SAP use during run-in and available 
1207 
outcome data from the control arm during Period 1 (for subjects randomized to control-first) and 
1208 
during Period 2 (for subjects randomized to control-second).  The dependent variable will be CGM 
1209 
measured hypoglycemia to match the primary outcome described above.  This model will be used to 
1210 
estimate the amount of hypoglycemia in the control arm. 
1211 
 
1212 
The required sample size is roughly proportional to the amount of hypoglycemia in the control arm.  
1213 
The adjusted sample size will therefore be calculated as: 
1214 
 
1215 
52*4% / estimated hypoglycemia rate in control arm 
1216 
 
1217 
where the estimated rate in the denominator is calculated from the regression model described above.  
1218 
This new sample size would be restricted to be a minimum of N=90 and a maximum of N=150 
1219 
subjects completing the crossover trial with sufficient data to include in the primary analysis.  If 
1220 
conditional power is <20% even with a sample size of N=150, the study may be stopped and limited to 
1221 
the subjects who have already been randomized (N not to be less than approximately 100). 
1222 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 39 of 47 
 
 
 
1223 
Simulations show that basing the sample size on the estimated control arm rate in this manner does not 
1224 
materially inflate the type 1 error rate. 
1225 
 
1226 
 Sub-Group Analyses 
1227 
The primary outcome will be tabulated by: 
1228 
• age 
1229 
• diabetes duration 
1230 
• baseline HbA1c  
1231 
• baseline CGM hypoglycemia 
1232 
 
1233 
These analyses are considered exploratory and are not being evaluated as independent hypothesis tests. 
1234 
 
1235 
 Multiple Comparison/Multiplicity 
1236 
The primary analysis involves a simple treatment arm comparison for a single outcome measure so no 
1237 
correction for multiple comparisons will be performed. 
1238 
 
1239 
For the secondary analyses described above, the false discovery rate will be controlled using the 
1240 
adaptive Benjamini-Hochberg procedure for multiple comparisons.  Note that this procedure can 
1241 
handle correlated outcome metrics and does not assume independent hypothesis tests. 
1242 
 
1243 
 Exploratory Analyses 
1244 
No additional exploratory analyses are planned.
1245 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 40 of 47 
 
 
 DATA COLLECTION AND MONITORING 
1246 
 
1247 
 Case Report Forms and Device Data 
1248 
The main study data are collected through a combination of electronic case report forms (CRFs) and 
1249 
electronic device data files obtained from the study software and individual hardware components. 
1250 
These electronic device files and electronic CRFs from the study website are considered the primary 
1251 
source documentation. 
1252 
 
1253 
When data are directly collected in electronic case report forms, this will be considered the source data. 
1254 
Each participating site will maintain appropriate medical and research records for this trial, in 
1255 
compliance with ICH E6 and regulatory and institutional requirements for the protection of 
1256 
confidentiality of participants. 
1257 
 
1258 
 Study Records Retention 
1259 
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
1260 
application in an ICH region and until there are no pending or contemplated marketing applications in 
1261 
an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical 
1262 
development of the investigational product. These documents should be retained for a longer period, 
1263 
however, if required by local regulations. No records will be destroyed without the written consent of 
1264 
the sponsor, if applicable. It is the responsibility of the sponsor to inform the investigator when these 
1265 
documents no longer need to be retained. 
1266 
 
1267 
 Quality Assurance and Monitoring 
1268 
Designated personnel from the Coordinating Center will be responsible for maintaining quality 
1269 
assurance (QA) and quality control (QC) systems to ensure that the clinical portion of the trial is 
1270 
conducted and data are generated, documented and reported in compliance with the protocol, Good 
1271 
Clinical Practice (GCP) and the applicable regulatory requirements. Adverse events will be prioritized 
1272 
for monitoring. 
1273 
 
1274 
A risk-based monitoring (RBM) plan will be developed and revised as needed during the course of the 
1275 
study, consistent with the FDA “Guidance for Industry Oversight of Clinical Investigations — A Risk-
1276 
Based Approach to Monitoring” (August 2013). Study conduct and monitoring will conform with 21 
1277 
Code of Federal Regulations (CFR) 812. 
1278 
 
1279 
The data of most importance for monitoring at the site are participant eligibility and adverse events. 
1280 
Therefore, the RBM plan will focus on these areas. As much as possible, remote monitoring will be 
1281 
performed in real-time with on-site monitoring performed to evaluate the verity and completeness of 
1282 
the key site data. Elements of the RBM may include: 
1283 
 
1284 
• Qualification assessment, training, and certification for sites and site personnel 
1285 
• Oversight of Institutional Review Board (IRB) coverage and informed consent procedures 
1286 
• Central (remote) data monitoring: validation of data entry, data edits/audit trail, protocol review 
1287 
of entered data and edits, statistical monitoring, study closeout 
1288 
• On-site monitoring (site visits): source data verification, site visit report 
1289 
• Agent/Device accountability 
1290 
• Communications with site staff 
1291 
• Patient retention and visit completion 
1292 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 41 of 47 
 
 
• Quality control reports 
1293 
• Management of noncompliance 
1294 
• Documenting monitoring activities 
1295 
• Adverse event reporting and monitoring 
1296 
 
1297 
Coordinating Center representatives or their designees may visit the study facilities at any time in order 
1298 
to maintain current and personal knowledge of the study through review of the records, comparison 
1299 
with source documents, observation and discussion of the conduct and progress of the study.  
1300 
 
1301 
 Protocol Deviations 
1302 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or procedure 
1303 
requirements. The noncompliance may be either on the part of the participant, the investigator, or the 
1304 
study site staff. As a result of deviations, corrective actions are to be developed by the site and 
1305 
implemented promptly. 
1306 
 
1307 
The site PI/study staff is responsible for knowing and adhering to their IRB requirements. Further 
1308 
details about the handling of protocol deviations will be included in the monitoring plan.
1309 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 42 of 47 
 
 
 ETHICS AND PROTECTION OF HUMAN PARTICIPANTS 
1310 
 
1311 
 Ethical Standard 
1312 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
1313 
the Protection of Human Participants of Research codified in 45 CFR Part 46, 21 CFR Part 50, 
1314 
21 CFR Part 56, and/or the ICH E6. 
1315 
 
1316 
 Institutional Review Boards 
1317 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
1318 
be submitted to the IRB for review and approval. Approval of both the protocol and the consent 
1319 
form must be obtained before any participant is enrolled. Any amendment to the protocol will 
1320 
require review and may require approval by the IRB before the changes are implemented to the 
1321 
study. All changes to the consent form will be IRB approved; a determination will be made 
1322 
regarding whether previously consented participants need to be re-consented. 
1323 
 
1324 
 Informed Consent Process 
1325 
 Consent Procedures and Documentation 
1326 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
1327 
the study and continues throughout the individual’s study participation. Extensive discussion of 
1328 
risks and possible benefits of participation will be provided to the participants and their families. 
1329 
Consent forms will be IRB-approved and the participant will be asked to read and review the 
1330 
document. The investigator will explain the research study to the participant and answer any 
1331 
questions that may arise. All participants will receive a verbal explanation in terms suited to their 
1332 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
1333 
research participants. Participants will have the opportunity to carefully review the written 
1334 
consent form and ask questions prior to signing. 
1335 
 
1336 
The participants should have the opportunity to discuss the study with their surrogates or think 
1337 
about it prior to agreeing to participate. The participant will sign the informed consent document 
1338 
prior to any procedures being done specifically for the study. The participants may withdraw 
1339 
consent at any time throughout the course of the trial. A copy of the informed consent document 
1340 
will be given to the participants for their records. The rights and welfare of the participants will 
1341 
be protected by emphasizing to them that the quality of their medical care will not be adversely 
1342 
affected if they decline to participate in this study. 
1343 
 
1344 
 Participant and Data Confidentiality 
1345 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, 
1346 
and the sponsor(s) and their agents. This confidentiality is extended to cover testing of biological 
1347 
samples in addition to the clinical information relating to participants. Therefore, the study 
1348 
protocol, documentation, data, and all other information generated will be held in strict 
1349 
confidence. No information concerning the study or the data will be released to any unauthorized 
1350 
third party without prior written approval of the sponsor. 
1351 
 
1352 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or 
1353 
device company supplying study product may inspect all documents and records required to be 
1354 
maintained by the investigator, including but not limited to, medical records (office, clinic, or 
1355 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 43 of 47 
 
 
hospital) and pharmacy records for the participants in this study. The clinical study site will 
1356 
permit access to such records. 
1357 
 
1358 
The study participant’s contact information will be securely stored at each clinical site for 
1359 
internal use during the study. At the end of the study, all records will continue to be kept in a 
1360 
secure location for as long a period as dictated by local IRB and Institutional regulations. 
1361 
 
1362 
Study participant research data, which is for purposes of statistical analysis and scientific 
1363 
reporting, will be transmitted to and stored at the Jaeb Center for Health Research. This will not 
1364 
include the participant’s contact or identifying information. Rather, individual participants and 
1365 
their research data will be identified by a unique study identification number. The study data 
1366 
entry and study management systems used by clinical sites and by Jaeb Center for Health 
1367 
Research staff will be secured and password protected. At the end of the study, all study 
1368 
databases will be de-identified and archived at the Jaeb Center for Health Research. 
1369 
 
1370 
 Future Use of Stored Specimens 
1371 
Not applicable 
1372 
 
1373 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 44 of 47 
 
 
 INVESTIGATOR AND SPONSOR OBLIGATIONS 
1374 
 
1375 
 Role of Sponsor 
 
1376 
As the study sponsor of this clinical trial, Tandem Diabetes Care, Inc. has the overall responsibility for 
1377 
the conduct of the study, including the assurance that the study meets regulatory requirements and is 
1378 
conducted according to Good Clinical Practice. 
1379 
 
1380 
 Medical Supervision and Investigator Responsibility 
1381 
Medical supervision is the responsibility of the investigator named on the Investigator Agreement. The 
1382 
investigator may delegate day-to-day activities to a sub-investigator or study staff member, but retains 
1383 
overall responsibility for ensuring that the study is conducted properly and in accordance with the 
1384 
study protocol. A delegation list is to be maintained that includes all qualified persons to whom the 
1385 
investigator may delegate significant study-related duties. The investigator is responsible for ensuring 
1386 
that drugs and devices are available for treating possible medical emergencies, or that emergency 
1387 
medical facilities are available and accessible. The investigator is responsible for ensuring that the 
1388 
study is conducted according to Good Clinical Practice (GCP), other applicable regulatory guidelines, 
1389 
and sound medical practices. 
1390 
 
1391 
 Study Initiation and Sponsor Discontinuation 
1392 
Prior to initiation of the study, the investigator must provide the Sponsor or designee with the 
1393 
following documents (copies of which must be maintained by the investigator): 
1394 
• 
Completed and signed original Investigator Agreement 
1395 
• 
Current curriculum vitae, signed and dated; also required is a state license for the investigator 
1396 
and for other medically qualified sub-investigators 
1397 
• 
Completed Financial Disclosure information 
1398 
• 
Signed copy of the Institutional Review Board (IRB) approval letter that lists the approved 
1399 
items 
1400 
• 
List of the IRB members who voted on the approval, including their specialty and affiliation, or 
1401 
the IRB assurance numbers if the roster cannot be obtained 
1402 
• 
Copy of the IRB-approved informed consent 
1403 
• 
Copy of the IRB-approved Authorization to Use and Disclose Protected Health Information 
1404 
form, consistent with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) 
1405 
legislation (if separate from the informed consent form) 
1406 
 
1407 
Upon receipt of all necessary paperwork, the Sponsor or designee will arrange for all study material to 
1408 
be delivered to the clinical study site. The Sponsor or designee will conduct an initiation conference 
1409 
call or visit to orient and provide in-depth training for all personnel expected to be involved in the 
1410 
study. Study protocol procedures, instruction for data capture, and overall responsibilities, including 
1411 
device accountability and study file maintenance, will be reviewed.  
1412 
 
1413 
The Sponsor has the right to terminate the study for any of the following reasons: 
1414 
• 
Non-adherence to the protocol 
1415 
• 
Unavailability of the investigator or the study personnel to the sponsor’s monitoring personnel 
1416 
(or their designee) 
1417 
• 
Inability to recruit the expected participant population 
1418 
• 
Other administrative reasons 
1419 
 
1420 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 45 of 47 
 
 
Throughout the course of the study, the investigator is to make a reasonable effort to maintain the 
1421 
enrollment rate that was agreed upon with the Sponsor. The investigator will also make a reasonable 
1422 
effort to enroll appropriate participants. The sponsor may elect to terminate the study at a given site if 
1423 
the enrollment rate lags or if significant numbers of non-evaluable participants are enrolled. 
1424 
  
1425 
 
1426 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 46 of 47 
 
 
 APPENDIX A – EXTENSION PHASE 
1427 
 
1428 
Introduction 
1429 
The Tandem PLGS Pivotal Trial is being extended to allow interested trial participants to continue to 
1430 
use the Tandem PLGS pump system after completion of the main trial. 
1431 
 
1432 
Study Design 
1433 
All participants will be assigned the Tandem PLGS pump and will return to the clinic approximately 
1434 
every 13 weeks (±2 weeks). The Extension Phase will continue until the system is commercially 
1435 
available or two years after the initial regulatory approval date, whichever comes first. 
1436 
 
1437 
Participant Eligibility and Informed Consent 
1438 
Participants who completed the PLGS Pivotal Trial within the previous 6 months will be eligible for 
1439 
the Extension Phase. 
1440 
 
1441 
Study sites will inform the participants regarding the Extension Phase. Interested participants, 
1442 
parents/guardians, or both will sign new consent/assent forms. 
1443 
 
1444 
Extension Phase Procedures 
1445 
At the initial visit after the consent (and assent if applicable) is signed, the participant will be provided 
1446 
with study supplies and device training as needed. Study supplies include: study pump and related 
1447 
supplies, study CGM and related supplies, and study blood glucose and ketone meters and test strips. 
1448 
 
1449 
The home procedures will be the same as described in sections 5.3 and 5.4. Device use will be as 
1450 
described in Chapter 6. 
1451 
 
1452 
At each 13-week (±2 weeks) follow-up visit and for the final visit, device data will be uploaded. The 
1453 
occurrence of adverse events and device issues will be solicited, as well as any new medications or 
1454 
medical conditions since the previous visit. Other testing and changes in diabetes management will be 
1455 
performed as part of usual care. Additional supplies will be distributed as needed. The System 
1456 
Usability Scale (SUS) will also be completed by each participant at each visit. Administration time is 
1457 
approximately 5 minutes. 
1458 
There will be no compensation to participants for completion of visits. 
1459 
 
1460 
Statistical Analyses 
1461 
CGM data will be compiled across visits and the metrics listed in section 10.4 will be descriptively 
1462 
reported.  Frequency of pump use, CGM use, adverse events, and device issues will be tabulated. 
1463 
 
1464 

 
TAND2_Tandem PLGS Pivotal Trial Protocol v6.0 02-21-2018 
Page 47 of 47 
 
 
 REFERENCES 
1465 
 
1466 
1. Davis E, Keating B, Byrne G, Russell M, Jones T: Hypoglycemia: incidence and clinical predictors 
1467 
in a large population-based sample of children and adolescents with IDDM. Diabetes Care 20:22-25, 
1468 
1997 
1469 
 
1470 
2. The Diabetes Control and Complications Trial Research Group. Hypoglycemia in the diabetes 
1471 
control and complications trial. Diabetes 46:271-286, 1997 
1472 
 
1473 
3. Buckingham B, Block J, Burdick J, Kalajian A, Kollman C, Choy M, Wilson DM, Chase P, for the 
1474 
Diabetes Research in Children Network. Response to nocturnal alarms using a real-time glucose 
1475 
sensor. Diabetes Technol Ther 7:440-447, 2005 
1476 
 
1477 
4. Buckingham BA, Cameron F, Calhoun P, Maahs DM, Wilson DM, Chase HP, Bequette BW, Lum J, 
1478 
Sibayan J, Beck RW, Kollman C. Outpatient safety assessment of an in-home predictive low-glucose 
1479 
suspend system with type 1 diabetes participants at elevated risk of nocturnal hypoglycemia. Diabetes 
1480 
Technol Ther 15:622-627, 2013 
1481 
 
1482 
5. Buckingham BA, Raghinaru D, Cameron F, Bequette BW, Chase HP, Maahs DM, Slover R, Wadwa 
1483 
RP, Wilson DM, Ly T, Aye T, Hramiak I, Clarson C, Stein R, Gallego PH, Lum J, Sibayan J, Kollman 
1484 
C, Beck RW. Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal 
1485 
Hypoglycemia in Children Without Increasing Ketosis. Diabetes Care 38:1197-1204, 2015 
1486 
 
1487 
6. Maahs DM, Calhoun P, Buckingham BA, Chase HP, Hramiak I, Lum J, Cameron F, Bequette BW, 
1488 
Aye T, Paul T, Slover R, Wadwa RP, Wilson DM, Kollman C, Beck RW. A randomized trial of a 
1489 
home system to reduce nocturnal hypoglycemia in type 1 diabetes. Diabetes Care 37:1885-1891, 2014 
1490 
 
1491 
7. Beck, RW, Raghinaru D, Wadwa RP, Chase HP, Maahs DM, Buckingham BA. Frequency of 
1492 
morning ketosis after overnight insulin suspension using an automated nocturnal predictive low 
1493 
glucose suspend system. Diabetes Care 37:1224-1229, 2014 
1494 
 
1495 
8. Wadwa RP, Chase HP, Raghinaru D, Buckingham BA, Hramiak I, Maahs DM, Messer L, Ly T, Aye 
1496 
T, Clinton P, Kollman C, Beck RW, Lum J. Ketone production in children with type 1 diabetes, ages 
1497 
4-14 years, with and without nocturnal insulin pump suspension. Pediatric Diabetes. doi: 
1498 
10.1111/pedi.12410. 2016 
1499 
 
1500 
 
1501