Study of Dapagliflozin in Combination With Metformin XR to Initiate the Treatment of Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Dapagliflozin; Metformin XR; Metformin XR; dapagliflozin matching Placebo; metformin HCl Modified Release matching Placebo
Intervention description: Tablets, Oral, 10 mg, once daily, 24 weeks; Tablets, Oral, up to 2000 mg, once daily, 24 weeks; Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks; Tablets; Tablets
Intervention MeSH terms: Metformin; Dapagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1093.0
Sex: All
Minimum age: 18 Years
Maximum age: 77 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus, Type 2; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Metformin; Dapagliflozin; Hypoglycemic Agents; Pharmacologic Actions; Physiological Effects of Drugs

Summary:

      The primary purpose of this study is to compare the change from baseline in hemoglobin A1C
      achieved with dapagliflozin 10 mg in combination with metformin XR as compared with metformin
      XR monotherapy and compared with Dapagliflozin monotherapy, after 24 weeks of oral
      administration of double-blind treatment. The safety of treatment with dapagliflozin will
      also be assessed in this study
    

Eligibility criteria:

        Inclusion Criteria:

          -  Treatment naive males and females, >= 18 years old and

        <= 77 years old, with type 2 diabetes mellitus

          -  Subjects must have central laboratory pre-randomization hemoglobin A1C >= 7.5 and <=
             12.0%

          -  C-peptide >= 1.0 ng/mL (0.34 nmol/L)

          -  Body Mass Index <= 45 kg/m2

          -  Must be able to perform self monitoring of blood glucose

        Exclusion Criteria:

          -  aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3X*upper limit
             of normal (ULN)

          -  Serum Total bilirubin >2 mg/dL (34.2 µmol/L)

          -  Creatinine kinase >3*ULN

          -  Serum creatinine >= 1.50 mg/dL (133 µmol/L) for male subjects, >= 1.40 mg/dL (124
             µmol/L) for female subjects

          -  Calcium value outside of the central laboratory normal reference range

          -  Currently unstable or serious cardiovascular, renal, hepatic, hematological,
             oncological, endocrine, psychiatric, or rheumatic diseases

          -  Urine albumin:creatinine ratio (UACR) >1800 mg/g (203.4 mg/mmol Cr)

          -  Severe uncontrolled hypertension defined as systolic blood pressure (SBP) >=180 mmHg
             and/or diastolic blood pressure (DBP) >=110 mmHg

          -  Hemoglobin >=11.0 g/dL (110 g/L) for men; hemoglobin >=10.0 g/dL (100 g/L) for women

          -  Positive for hepatitis B surface antigen

          -  Positive for anti-hepatitis C virus antibody

          -  History of diabetes insipidus

          -  History of diabetic ketoacidosis or hyperosmolar nonketotic coma

          -  Symptoms of poorly controlled diabetes that would preclude participation in this trial