Study of Dapagliflozin in Combination With Metformin XR to Initiate the Treatment of Type 2 Diabetes

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: dapagliflozin matching Placebo; Drug: Dapagliflozin; Drug: Metformin XR; Drug: metformin HCl Modified Release matching Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00859898

MB102-034

Eudract #: 2008-007548-33

Details and patient eligibility

About

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

Enrollment: 1,093 patients

Sex: All

Ages: 18 to 77 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,093 participants in 3 patient groups

Dapagliflozin + Metformin XR

Experimental group

Description:

Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks

Treatment:

Drug: Metformin XR

Drug: Dapagliflozin

Dapagliflozin + Placebo

Experimental group

Description:

Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks. Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.

Treatment:

Drug: metformin HCl Modified Release matching Placebo

Drug: Dapagliflozin

Metformin XR + Placebo

Active Comparator group

Description:

Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Treatment:

Drug: Metformin XR

Drug: dapagliflozin matching Placebo