Diabetes Pump With Predictive Low Glucose Suspend Pivotal Trial

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

A 6-week crossover study will compare PLGS to SAP outcomes in adults and youth > 6 years old with type 1 diabetes (T1D).

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 Continuous Glucose Monitoring (CGM) and pump experience

2. CGM and (Sensor Augmented Pump) 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.

   1. 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.
   2. 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.

Inclusion Criteria:

• 1. Clinical diagnosis, based on investigator assessment, of T1D treated with insulin via an insulin pump or injections for at least 1 year, with no major change in the intensity of insulin therapy in the past 3 months (e.g. switching from injections to pump)
• 2. Age ≥6.0 years old
• 3. 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
• 4. For females, not currently known to be pregnant
• - If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative serum or urine pregnancy test will be required for all females of child-bearing potential. Subjects who become pregnant will be discontinued from the study. Also, subjects who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued.
• 5. Investigator has confidence that the participant can successfully use all study devices and is capable of adhering to the protocol

Exclusion Criteria:

• 1. Anticipated need to use acetaminophen during study participation
• 2. Participation in another pharmaceutical or device trial at the time of enrollment or plan to participate in another study during the time period of participation in this study
• 3. Employed by, or having immediate family members employed by Tandem; or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial
• 4. 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
• - Individuals should not be enrolled with uncontrolled thyroid disease, renal failure (e.g., dialysis or estimated glomerular filtration (eGFR) <30), hemophilia or another major bleeding disorder, or unstable cardiovascular disease.
• - Laboratory testing and other work up needed to determine that an individual is a suitable candidate for the study should be performed as part of usual care.