Combination GRA and SGLT-2i Treatment in Type 1 Diabetes

This is an interventional basic science trial for Type 1 Diabetes Read More

Inclusion Criteria:

1. Men and women between the ages of 18 and 65 years old, inclusive, at the time of screening;
2. Females of non-child bearing potential must be ≥ 1 year post-menopausal or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception during the entire study and for an additional 3 months after the end of dosing with the investigational product;
3. Male subjects must be willing to use clinically acceptable method of contraception during the entire study and for an additional 6 months after the end of the treatment period;
4. Diagnosed with Type 1 diabetes based on clinical history or as defined by the current American Diabetes Association (ADA) criteria for > 5 years;
5. Treatment with a stable insulin regimen (< 1u/kg per day) for at least 8 weeks before screening with continuous subcutaneous insulin infusion (CSII) via an insulin pump;
6. Currently using a Continuous Glucose Monitoring (CGM) system
7. HbA1c ≤ 9 % at screening;
8. A minimum weight of 50kg;
9. eGFR ≥ 60 mL/min/1.73m²
10. Able to provide written informed consent approved by an Institutional Review Board (IRB).

Exclusion Criteria:

1. History of T2DM, maturity onset diabetes of the young (MODY), pancreatic surgery or chronic pancreatitis
2. Pancreas, pancreatic islet cells or renal transplant recipient
3. T1DM treatment with any other antihyperglycemic drug (e.g. metformin, alpha- glucosidase inhibitors, SGLT-2 inhibitors, pramlintide, inhaled insulin, pre-mixed insulins, etc.) within 30 days of run-in (visit 2)
4. Occurrence of severe hypoglycemia involving coma and/or seizure that required hospitalization or hypoglycemia-related treatment by an emergency physician or paramedic within 3 months prior to Visit 1 or Visit 2
5. Occurrence of DKA within 3 months prior to Visit 1 or Visit 2
6. Occurrence of symptomatic hypotension within 3 months prior to Visit 1 (Screen) or Visit 2
7. Occurrence of multiple genital mycotic infections within 6 months prior to Visit 1 (Screen) or Visit 2
8. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or transient ischemic attack (TIA) within 3 months prior to Visit 1 or Visit 2
9. Indication of liver disease, defined by serum levels of either alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase above 3 x upper limit of normal (ULN) at Visit 1
10. Current signs and symptoms of anemia accompanied by a hemoglobin laboratory value at or below 10.0 g/dL at screening.
11. Active eating disorders such as bulimia or anorexia nervosa
12. Body Mass Index (BMI) < 18.5 kg/m2 and/or weight less than 50kg;
13. Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening. Donations of plasma, packed RBCs, platelets or quantities less than 500 mL are allowed at investigator discretion;
14. Treatment with systemic corticosteroids within 30 days of run-in (visit 2), or planned initiation of such therapy at Visit 1 or Visit 2. Inhaled or topical use of corticosteroids (e.g. for asthma/chronic obstructive pulmonary disease) is acceptable.
15. Medical history of bladder cancer or treatment for any cancer in the last five years prior to Visit 1. Resected basal cell carcinoma considered cured is exempted.
16. Women who are pregnant, nursing, or who plan to become pregnant while in the trial
17. Intake of an investigational drug in another trial within 30 days prior to Visit 1
18. Patient not able to understand and comply with study requirements, based on Investigator's judgment
19. Any other clinical condition that, based on Investigator's judgment, would jeopardize patient safety during trial participation or would affect the study outcome (e.g. immunocompromised patients who might be at higher risk of developing genital or mycotic infections, patients with chronic viral infections etc.)