Study to Evaluate Safety and Efficacy of Dapagliflozin and Saxagliptin in Patients With Type 2 Diabetes Mellitus (T2DM) Aged 10 to Below 18 Years Old

Prior treatment

• Previous diagnosis of monogenic etiology of Type 2 diabetes
• Current use of the following medications for the treatment of diabetes, or use within the specified timeframe prior to screening for the main study:
• Eight weeks: sulfonylureas, alpha glucosidase inhibitors, metiglinide, oral or injectable incretins or incretin mimetics, other antidiabetes medications not otherwise specified.
• Initiation or discontinuation of prescription or non-prescription weight loss drugs within 8 weeks of screening. Use of prescription or non-prescription weight loss drugs must be stable during the study.
• Medical History and Concurrent Diseases
• Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for \> 4 weeks within 3 months prior to the Day 1 visit
• Subject is currently abusing alcohol or other drugs or has done so within the last 6 months prior to the screening visit.
• Subjects who have contraindications to therapy as outlined in the saxagliptin and dapagliflozin Investigator Brochure or local package inserts.
• Participation and receiving IP in another clinical study during the prior 3 months

Other illness

• Target Disease Exceptions
• Presence of Type 1 diabetes, as demonstrated by Preexisting diagnosis of Type 1 diabetes,
• Diabetes ketoacidosis (DKA) within 6 months of screening
• History of unstable or rapidly progressive renal disease
• History of unresolved vesico-ureteral reflux
• History of or current, acute or chronic pancreatitis
• History of hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis
• Malignancy within 5 years of the screening visit (with the exception of treated basal cell or treated squamous cell carcinoma)
• Positive serologic evidence of current infectious liver disease including anti hepatitis A virus (HAV) (IgM), hepatitis B surface antigen (HBsAg), or anti hepatitis C virus (HCV). Patients who have isolated positive anti-hepatitis B surface antibodies may be included.
• Allergies and Adverse Drug Reaction
• Known allergy, sensitivity or contraindication to any study drug or its excipient/vehicle
• Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and Sponsor/designee approval is required.)
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
• Psychiatric or cognitive disorder that will, in the opinion of investigators, limit the subject's ability to comply with the study medications and monitoring.

Lab values

• Sixteen weeks: thiazolidinediones, DPP-4 inhibitors (with no reported medication related AEs related to DPP-4 inhibitors), sodium glucose cotransporter-2 (SGLT-2) inhibitors (with no reported medication related AEs related to SGLT-2 inhibitors)
• Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical trials, or breastfeeding
• Physical and Laboratory Test Findings
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2× upper limit of normal (ULN), or clinically significant hepatic disease.
• Serum total bilirubin (TB) \> 2x ULN unless exclusively caused by Gilbert's syndrome

Other

• Abnormal renal function,
• An abnormal thyroid-stimulating hormone (TSH) value at enrollment will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded.
• Hematuria (confirmed by microscopy at screening) with no explanation as judged by the Investigator up to randomization.
• Anemia of any etiology
• Volume-depleted subjects.
• Other Exclusion Criteria

• Signed Written Informed Consent
• Target Population
• Previously diagnosed with Type 2 Diabetes Mellitus by World Health Organization/ADA criteria
• HbA1c between 6.5% and 10.5% obtained at screening.
• Currently on diet and exercise and stable dose of at least 1000 mg metformin (IR or XR) for a minimum of 8 weeks, or stable dose of insulin for a minimum of 8 weeks, or a stable combination of at least 1000 mg metformin (IR or XR) and insulin for a minimum of 8 weeks prior to randomization. For those children on insulin, investigators will confirm that attempts at removing insulin from the subject's therapeutic regimen had been previously made but had not been successful.
• Age and Reproductive Status
• Male and female patients eligible if 10 years of age, up to but not including 18 years of age at the time of enrollment/screening. At least 30% of total subjects will be between the ages of 10 and 14 years and at least one third, but no more than two thirds, female subjects.
• Women of childbearing potential must have a negative pregnancy test within 24 hours prior to the start of study drug.
• Women must not be breastfeeding.
• Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs: saxagliptin, and dapagliflozin, plus 5 half-lives of study drugs or 30 days (whichever is longer), plus 30 days (duration of ovulatory cycle) for a total of 60 days post treatment completion.