E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012613 |
E.1.2 | Term | Diabetes mellitus non-insulin-dependent |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The MR sub study is a part of main study and therefore there is no special title, date and version for this sub study. The objectives related to this MR substudy are: To assess, in a sub-population, the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin on energy depots after 24 and 102 weeks of double-blind treatment on: - visceral adipose tissue mass - hepatic lipid content
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E.3 | Principal 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 |
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E.4 | Principal 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 <-2.0 for BMD at lumbar spine, femoral neck, or total hip at baseline DXA measurement. The Medical DXA Core Lab will inform the recruiting investigator whether the subject is eligible or not for randomization based on this criterion. 11. Vitamin D deficiency (25-hydroxyvitamin D level <12 ng per millilitre (30 nmol per liter) 12. AST >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
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome variable: 1. Change in body weight from baseline to week 24
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |