Type 2 Diabetes Mellitus MedDRA version: 9.1 Level: LLT Classification code 10012613 Term: Diabetes mellitus non-insulin-dependent
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures 2. Females aged =55 and =75 years who are post menopausal (or have had hysterectomy) for a period of at least 5 years at time of consenting or males aged =30 and =75 years at time of consenting 3. Diagnosed with type 2 diabetes 4. HbA1c =6.5% and =8.5% 5. Body mass index (BMI) =25 kg/m2 6. Body weight =120 kg (due to limitations imposed by DXA equipment) 7. Ongoing treatment with metformin on a stable dose of =1500 mg/day for at least 12 weeks prior to enrolment before lead-in period: 8. HbA1c =6.5% and =8.5% 9. FPG =13.2 mmol/L (=240 mg/dL) at randomization: 10. HbA1c =6.5% and =8.5% 11. FPG =13.2 mmol/L (=240 mg/dL) 12. Body mass index (BMI) =25 kg/m2 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to dapagliflozin or metformin. Intolerance to metformin 2. Type 1 diabetes, diabetes insipidus, corticosteroid-induced type 2 diabetes, history of diabetic ketoacidosis or hypersmolar non-ketonic coma or known condition of congenital renal glucosuria 3. Symptoms of poorly controlled diabetes that would preclude participation in this trial 4. Any ongoing oral anti-diabetic treatment apart from metformin or treatment with chronic insulin, within 24 weeks prior to Visit 1 Administration of weight loss medication, including but not limited to sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, and/or phendimetrazine, within 30 days prior to enrolment 5. Administration of treatment known to significantly influence bone metabolism, including, but not limited to bisphosphonate, calcitonin, replacement or chronic systemic treatment with corticosteroids, hormone replacement therapy (HRT) within 6 months prior to enrolment 6. Treatment for Human immunodeficiency virus (HIV)/use of antiviral drugs and/or known immunocompromised status, including subjects who have undergone organ transplantation 7. Body weight change >5% within 3 months prior to enrolment 8. Severe uncontrolled hypertension defined as systolic BP =180 mmHg and/or diastolic BP =110 mmHg 9. Subjects who, in the judgment of the investigator, may be at risk for dehydration 10. T-score 3 x ULN, ALT >3 x ULN or serum total bilirubin (TB) >34.2 µmol/L (2 mg/dL) 13. Creatine kinase (CK) >3 x ULN 14. Haemoglobin =105 g/L (=10.5 g/dL) for men; haemoglobin =95 g/L (=9.5 g/dL) for women 15. Urine albumin: creatinine ratio (UACR) >1800 mg/g (>203.4 mg/mmol) 16. Renal failure or renal dysfunction (Creatinine-Clearance using Cockroft Gault formula <60 ml/min) or serum creatinine =133 mmol/L (1.5 mg/dL) for male subjects and =124 mmol/L (1.4 mg/dL) for female subjects 17. Thyroid-stimulating hormone (TSH) values outside normal range, to be further confirmed by abnormal free T4 values. Subjects with abnormal free T4 values will be excluded 18. Significant cardiovascular history within the past 6 months prior to the enrolment visit (myocardial infarction, unstable angina, transient ischemic attack (TIA), unstable or previously undiagnosed arrhythmia, unstable chronic heart failure, cardiac surgery or revascularization (CABG/PTCA)) 19. History of bariatric surgery
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin on total body weight after 24 weeks of oral administration of double-blind treatment.;Secondary Objective: To assess effect on: - Waist circumference - Total Body Fat Mass measured by Dual Energy X-ray Absorptiometry - Additional weight and glycaemic variables - Lean tissue mass as measured by Dual Energy X-ray Absorptiometry - Blood pressure - Adipose tissue markers - Patient reported outcomes To assess, in a sub-population, the effect on: - Visceral adipose tissue mass - Hepatic lipid content -To evaluate the safety and tolerability by assessment of adverse events, laboratory values, electrocardiogram, pulse, blood pressure, hypoglycaemic events, calculated creatinine clearance and physical examination findings (eg, oedema) after 24 weeks and 102 weeks To assess the same objectives as for the 24-week treatment after 102 weeks To assess after 50 and 102 weeks the effect on: - Bone Mineral Density - Biochemical markers of bone formation and bone resorption ;Primary end point(s): Primary outcome variable: 1. Change in body weight from baseline to week 24 | — |
Countries
Bulgaria, Czech Republic, Hungary, Sweden
Outcome results
None listed