CKM For Safe Use of SGLT2i in Type 1 Diabetes

Utilizing Continuous Ketone Monitors to Enable Safe Use of SGLT Inhibitors in Patients With Type 1 Diabetes

This research study is being conducted to learn if wearing a combination continuous glucose monitor/continuous ketone monitor (CGM/CKM) can reduce the side effects of taking sotagliflozin (study drug) in people with type 1 diabetes.

The study is a phase 3, single-site, double-blind, random-order, cross-over study to evaluate the use of continuous ketone monitoring (CKM) in participants with type 1 diabetes taking sotagliflozin.

There will be 2 main groups in the study, participants on Hybrid Closed Loop insulin pumps (HCL), n=26, and participants on Multiple Daily Injections (MDI), n=26. There will also be 2 doses of sotagliflozin examined in the study, 200 milligram (mg) once daily and 400mg once daily. Therefore, there will be 4 treatment groups in the study:

• MDI participants who receive 200mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 400mg sotagliflozin for 6 weeks;
• MDI participants who receive 400mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 200mg sotagliflozin for 6 weeks;
• HCL participants who receive 200mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 400mg sotagliflozin for 6 weeks;
• HCL participants who receive 400mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 200mg sotagliflozin for 6 weeks.

In addition, there will be an open-label extension study for the HCL group. In the extension study, the 26 participants in the HCL group will remain on their insulin pump, receive a low-dose, open-label, once daily injection of long-acting insulin and complete an additional 6 weeks of dosing with open-label 400 mg sotagliflozin.

For MDI participants there will be a total of 12 visits over approximately 22 weeks. For HCL participants there will be a total of 16 visits over approximately 28 weeks.

Inclusion Criteria:

1. All individuals between the ages of >18 years old, inclusive, at the time of screening;

2. Individuals able to become pregnant must:

   1. be ≥1 year post-menopausal or documented as being surgically sterile, or
   2. agree to use two methods of contraception during the entire study and for an additional 2 weeks after the end of dosing with the investigational product;

3. Individuals able to cause a pregnancy must be willing to use clinically acceptable method of contraception during the entire study and for an additional 2 weeks after the end of the treatment period;

4. Diagnosed with Type 1 diabetes ≥ 1 year prior to screening, based on clinical history or as defined by the current American Diabetes Association (ADA) criteria;

5. Treatment with a stable insulin regimen for at least 8 weeks before screening with:

   1. a continuous subcutaneous insulin infusion (CSII) via a hybrid closed loop system, or
   2. multiple daily insulin injections;

6. Currently using a Continuous Glucose Monitoring (CGM) system;

7. Hemoglobin A1c ≤10% at the time of screening;

8. Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m2;

9. Agrees and is able to wear the investigational device;

10. Able to provide written informed consent approved by an Institutional Review Board (IRB).

Exclusion Criteria:

1. Individuals who are currently pregnant or lactating/breastfeeding, or planning to become pregnant within 10 months after screening;

2. Any concurrent diagnosis of diabetes other than type 1 diabetes;

3. History or evidence of clinically significant disorder or condition that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;

4. Hypotension at screening as defined as, systolic blood pressure < 90 and diastolic blood pressure < 60 with symptoms of low blood pressure (confusion, dizziness, lightheadedness, fainting, heart palpitations);

5. Current or recent (within 1 month prior to screening) use of diabetes medications other than insulin; (examples include, Sodium-Glucose Cotransporter 2 (SGLT-2i), Pramlintide, Metformin);

6. Use of glucagon-like-peptide 1 (GLP-1) analogues if not on a stable dose for > 2 months at screening (participants can be rescreened after being on stable dose for > 2 months). Participants on a stable dose of GLP-1 receptor antagonist (RA) and not experiencing frequent vomiting may be included.

7. Chronic systemic corticosteroids use ( > 4 consecutive weeks) within 6 months prior to screening;

8. History of diabetic ketoacidosis within 3 months prior screening;

9. History of a level 3 hypoglycemic event (as defined by ADA criteria) within 3 months of screening.

   • ADA Level 3 Definition - A severe hypoglycemic event characterized by altered mental or physical status requiring the assistance for treatment of hypoglycemia, irrespective of glucose level;

10. History of multiple (≥3 infections) genital mycotic infections within 6 months of screening;

11. Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits;

12. Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent.