Type 2 Diabetes Mellitus MedDRA version: 12.0 Level: LLT Classification code 10012613 Term: Diabetes mellitus non-insulin-dependent
Conditions
Interventions
Product Name: Dapagliflozin
Product Code: BMS-512148
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: BMS-512148-05
Other descriptive name: dapagliflozin
Concentration unit: mg milligram(
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures 2. Diagnosis of type 2 diabetes 3. Men or women age =18 years old (for patients taking metformin, the upper age limit should be based on local metformin label restrictions) 4. Current antihyperglycaemic treatment: - Drug naïve (defined as no antihyperglycaemic therapy for at least 10 weeks prior to enrolment), or - Ongoing treatment with sitagliptin monotherapy 100 mg QD for at least 10 weeks prior to enrolment, or - Ongoing treatment with vildagliptin monotherapy 50 mg BID for at least 10 weeks prior to enrolment, or - Ongoing treatment with metformin IR or XR monotherapy =1500 mg/day for at least 10 weeks prior to enrolment, or - Ongoing treatment with metformin IR or XR =1500 mg/day plus sitagliptin 100 mg/day for at least 10 weeks prior to enrolment, or - Ongoing treatment with metformin IR or XR =1500 mg/day plus vildagliptin 50 mg BID for at least 10 weeks prior to enrolment. 5. HbA1c: At enrolment (Visit 1) - =7.2% and =10.0% for patients entering the study on sitagliptin100 mg QD or vildagliptin 50 mg BID monotherapy, sitagliptin 100 mg QD plus metformin =1500 mg/day or vildagliptin 50 mg BID plus metformin =1500 mg/day - =7.7% and =10.5% for patients who are drug naïve or who are treated with metformin =1500 mg/day monotherapy 6. Women of childbearing potential who comply with defined criteria. 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. Diagnosis of Type 1 diabetes mellitus, known diagnosis of MODY or secondary diabetes mellitus 2. History of diabetic ketoacidosis; history of severe diabetic retinopathy or severe diabetic foot complications 3. Symptoms of poorly controlled diabetes including, but not limited to, marked polyuria, polydipsia, and/or greater than 10% weight loss during the 3 months prior to enrolment 4. FPG >270 mg/dL (>15 mmol/L) 5. History of bariatric surgery 6. Diabetes insipidus 7. Thyroid-stimulating hormone (TSH) values outside normal range 8. Renal failure or renal dysfunction (Calculated Creatinine Clearance 1800 mg/g (>203.4 mg/mmol)) 9. Known condition of familial renal glucosuria 10. AST >3 xULN and/or ALT >3 x ULN, total bilirubin >2.0 mg/dL (>34.2 µmol/L) 11. Congestive heart failure NYHA class IV, unstable or acute congestive heart failure 12. Significant cardiovascular history within the past 3 months prior to the screening visit (myocardial infarction, unstable angina pectoris, transient ischemic attack, unstable or previously undiagnosed arrhythmia, cardiac surgery or revascularization, cerebrovascular accident), unstable cardiovascular disease at enrolment as judged by investigator 13. Systolic BP =170 mmHg and/or diastolic BP =110 mmHg 14. Haemoglobin =10 g/dL (=100 g/L) for men; haemoglobin =9.0 g/dL (=90 g/L) for women 15. Creatinine Kinase >3X ULN, history of drug-induced myopathy or drug-induced CK elevation 16. Use of: antihyperglycaemic medications other than DPP-4 inhibitors or metformin during the 10 weeks prior to enrolment, insulin within 24 weeks of enrolment (with exceptions), weight loss medication (including but not limited to sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylproprion, methamphetamine, and/or phendimetrazine) within 30 days prior to enrolment, glucocorticoids equivalent to oral prednisolone =10 mg (betametasone =1.2 mg, dexamethasone =1.5 mg, hydrocortisone =40 mg) per day within 30 days prior to enrolment, unstable doses of teriparatide, bisphosphonates and/or calcitonin, antiviral drugs 17. Patients at risk of dehydration 18. Acute or chronic metabolic acidosis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the change from baseline in haemoglobin A1c at 24 weeks between dapagliflozin 10 mg and placebo in patients with type 2 diabetes who are inadequately controlled on sitagliptin alone or on sitagliptin plus metformin.;Secondary Objective: To assess effect on: total body weight – fasting plasma glucose – 2-hour post liquid meal glucose – blood pressure - glycaemic control – lipid metabolism; To assess, in a sub-population, the effect on: seated systolic blood pressure – haemoglobin A1c; To evaluate the safety and tolerability by assessment of adverse events, laboratory values, electrocardiogram, pulse, blood pressure, hypoglycaemic events, calculated creatinine clearance, estimated glomerular filtration rate and physical examination findings over 24 weeks of treatment; To collect and store DNA for future exploratory genetic research studies; Objectives of the 24-week extension period: - to assess the maintenance of efficacy of dapagliflozin versus placebo over 48 weeks of treatment - to assess the safety and tolerability of dapagliflozin over 48 weeks of treatment.;Primary end point(s): Primary outcome variable: Change in haemoglobin A1c from baseline to week 24 | — |
Countries
Germany, Poland, United Kingdom
Outcome results
None listed