A Multi-Center, Randomized, Double-Blind, Phase III Trial to Evaluate the Safety and Efficacy of Saxagliptin Co-administered With Dapagliflozin Compared to Saxagliptin or Dapagliflozin All Given as add-on Therapy to Metformin in Subject With Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus; Inadequate Glycaemic Control
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Dapagliflozin; Placebo for Dapagliflozin; Saxagliptin; Placebo for Saxagliptin
Intervention description: 5mg, orally, Green, plain, diamond-shaped, film-coated tablet; Does not contain active ingredient, orally, Green, plain, diamond-shaped, film-coated tablet; 5mg, orally, Plain, yellow, biconvex, round, film-coated tablet; Does not contain active ingredient, orally, Plain, yellow, biconvex, round, film-coated tablet
Intervention MeSH terms: Dapagliflozin; Saxagliptin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 905.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus Type 2,; saxagliptin,; dapagliflozin,; metformin

Summary:

      The aim of this study is to evaluate safety and efficacy of therapy with saxagliptin 5mg
      co-administered with dapagliflozin 5mg, compared to therapy with saxagliptin 5mg or
      dapagliflozin 5mg in patients who are inadequately controlled on ≥1500mg/day of metformin
      monotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients aged ≥18 years old at time of informed consent;

          2. Patients with Type 2 diabetes mellitus (T2DM) defined as HbA1C≥7.5% to ≤10.0% at
             screening visit;

          3. Stable metformin therapy for at least 8 weeks prior to enrolment at a dose of ≥1500mg
             per day;

          4. BMI ≤45.0kg/m2 at Enrolment visit;

          5. Fasting Plasma Glucose (FPG) ≤ 270mg/dl(15.0mmol/L) at the enrolment visit;

          6. For Females Only: Women of childbearing potential (WOCBP) must be using an acceptable
             method of contraception to avoid pregnancy throughout the study and for at least 4
             weeks after the last dose of study medication in such a manner that the risk of
             pregnancy is minimized.

        Exclusion Criteria:

          1. History of diabetes insipidus, Type 1 diabetes or Latent Autoimmune Diabetes of
             Adults, diabetic ketoacidosis or hyperosmolar nonketotic coma and Symptoms of poorly
             controlled diabetes that would preclude participation in this trial including but not
             limited to marked polyuria and polydipsia with greater than 10% weight loss during the
             3 months prior to Enrolment (Visit 1), or other signs and symptoms.

          2. History of pancreatitis.

          3. Administration of any antihyperglycaemic therapy, other than metformin, for more than
             14 days (consecutive or not) during the 8 weeks prior to enrolment

          4. Any use of DPP-4 inhibitor or SGLT-2 inhibitor within 8 weeks prior to enrolment.

          5. Significant hepatic disease, including, but not limited to, chronic active hepatitis
             and/or severe hepatic insufficiency and/or significant abnormal liver function,
             including patients with Alanine transaminase (ALT) and/or Aspartate transaminase (AST)
             ≥3x ULN (Upper Limit of Normal)and/or Total Bilirubin ≥2.0x ULN. History of severe
             hepatobiliary disease or hepatotoxicity with any medication. Positive serologic
             evidence of current infectious liver disease, including patients who are known to be
             positive for Hepatitis viral antibody ImmunoglobulinM (IgM), Hepatitis B surface
             antigen, and Hepatitis C virus antibody.

          6. Moderate or severe impairment of renal function [defined as Estimated Glomerular
             Filtration Rate (eGFR) <60milliLitre/min/1.73 m2 (estimated by Modification in Diet
             and Renal Disease (MDRD)) or serum creatinine ≥1.5mg/dL in males or ≥1.4mg/dL in
             females]. Conditions of congenital renal glucosuria, history of unstable or rapidly
             progressing renal disease.

          7. History of any clinically significant disease or disorder which, in the opinion of the
             investigator, may put the patient at risk because of participation in the study, may
             influence the results, or may limit the patient's ability to participate in or
             complete the study.