Resumen

The primary objective of this study is to determine if there will be a greater mean reduction from baseline in glycated hemoglobin (HbA1c) achieved after 26 weeks of oral double-blind add-on therapy of dapagliflozin or saxagliptin compared to placebo in paediatric T2DM patients with HbA1c levels of 6.5 to 10.5% on diet and exercise and metformin, insulin, or metformin plus insulin.

Elegibilidad

Edad mínima: 10 YearsEdad máxima: 18 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

Target Disease Exceptions
Presence of Type 1 diabetes, as demonstrated by Preexisting diagnosis of Type 1 diabetes,
Previous diagnosis of monogenic etiology of Type 2 diabetes
Diabetes ketoacidosis (DKA) within 6 months of screening
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.
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)
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
Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical trials, or breastfeeding
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)
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
Physical and Laboratory Test Findings
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.
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
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.
Anemia of any etiology
Volume-depleted subjects.
Allergies and Adverse Drug Reaction
Known allergy, sensitivity or contraindication to any study drug or its excipient/vehicle
Subject is currently abusing alcohol or other drugs or has done so within the last 6 months prior to the screening visit.
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.
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

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Dapagliflozin

Saxagliptin

Placebo

Ubicaciones

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Patrocinadores