Type II diabetes mellitus MedDRA version: 14.0 Level: LLT Classification code 10012613 Term: Diabetes mellitus non-insulin-dependent System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: Dapagliflozin
Product Code: BMS-512148
Pharmaceutical Form: Film-coated tablet
CAS Number: 960404-48-2
Current Sponsor code: BMS-512148-05
Other descriptive name: Dapagliflozin
Concentra
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The following criteria apply to the enrolment, placebo lead-in and randomisation visits (Visits 1, 2, 3, and 4). 1. Provision of informed consent prior to any study specific procedures. 2. Diagnosis of type 2 diabetes mellitus. 3. Men or women age =18 years old, the upper age limit should be based on local metformin label restrictions. 4. Stable dose combination therapy of metformin =1500mg/day and at least half the maximum dose of a sulfonylurea for at least 8 weeks prior to enrolment. 5. HbA1c inclusion criteria: · At enrolment (Visit 1) – laboratory values from screening visit: =7.7% and =11.0%. · At the randomisation visit (Visit 4) – laboratory values from visit 3: =7.0% and =10.5%. 6. For women only: Women not of childbearing potential, or women of childbearing potential who comply with the following: - Use a highly effective method of birth control (see below) to avoid pregnancy throughout the study and for up to 4 weeks after the study. - Have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication and at each visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: The following criteria apply to the enrolment, placebo lead-in and randomisation visits (Visits 1, 2, 3, and 4) Endocrine and metabolic disorders Diagnosis of Type 1 diabetes mellitus, known diagnosis of MODY or secondary diabetes mellitus History of diabetic ketoacidosis 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 FPG >270 mg/dL (>15 mmol/L) – assessed based on laboratory results from Visits 1, 2 and 3 BMI >45 kg/m2 History of bariatric surgery (ie, any surgery to treat obesity; for example, gastric banding or procedures that involve bypassing or transposing sections of the small intestine). History of liposuction is allowed Diabetes insipidus Thyroid-stimulating hormone (TSH) and free T4 values outside normal range; an abnormal TSH value needs to be followed up with a free T4 test. Patients with abnormal free T4 values will be excluded Cardiovascular disorders Recent Cardiovascular Events in a patient: Acute Coronary Syndrome (ACS) within 2 months prior to enrolment Hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrolment Acute Stroke or TIA within 2 months prior to enrolment Less than 2 months post coronary artery revascularization prior to enrolment Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure. Blood pressure: At enrolment (V1), V2 or V3: Syst. BP =170 mmHg and/or diast. BP =110 mmHg. (Pat. with a BP over 170/110 mmHg during the plac. lead-in phase will be excluded from study) At randomisation (V4): Syst. BP =160 mmHg and/or diast. BP =100 mmHg Kidney or urological disorders Measured serum creatinine value of =1.5 mg/dL (133 µmol/L) for male patients and =1.4 mg/dL (124 µmol/L) for female patients or renal function that would preclude treatment with metformin according to local guidance History of unstable or rapidly progressing renal disease Familial renal glucosuria. This condition is diagnosed as glucosuria (>1.0 mmol/L urine) in the presence of normoglycaemia in patients without the diagnosis of diabetes mellitus History of unexplained microscopic or gross hematuria, or microscopic hematuria at visit 1, confirmed by a follow-up sample at next scheduled visit, where according to the investigator a satisfactory evaluation of hematuria has not been conducted based on guidance in section 6.4.9.3 Hepatic disorders Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN Total bilirubin >2.0 mg/dL (34.2 µmol/L) Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody History of drug-induced liver enzyme elevations History of severe hepatobiliary disease or hepatotoxicity with any medication Hematologic/oncologic disorders/conditions Haemoglobin <10 g/dL (<100 g/L) or 6.2 mmol/L for men; haemoglobin <9.0 g/dL (<90 g/L) or 5.9 mmol/L for women History of chronic haemolytic anaemia or haemoglobinopathies (for example, sickle cell anaemia, thalassemia, sideroblastic anaemia). Mild haemolysis due to artificial heart valves or due to sickle cell trait is not an exclusion criterion except when haemoglobin levels are t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare the change from baseline in haemoglobin A1c (HbA1c) to week 24 between dapagliflozin 10 mg in combination with metformin and sulfonylurea and placebo in combination with metformin and sulfonylurea.;Secondary Objective: Key Secondary Objectives · To compare the change from baseline in fasting plasma glucose (FPG) to week 24 between dapagliflozin and placebo. · To compare the change from baseline in total body weight to week 24 between dapagliflozin and placebo. · To compare the proportion of patients achieving a therapeutic glycaemic response, defined as HbA1c < 7.0%, at week 24 between dapagliflozin and placebo. · To compare the change from baseline in seated systolic blood pressure (SBP) to week 8 between dapagliflozin and placebo.;Primary end point(s): Efficacy Primary outcome variable: · Change in HbA1c from baseline to week 24.;Timepoint(s) of evaluation of this end point: see E.5.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary outcome variables: · Change in fasting plasma glucose (FPG) from baseline to week 24. · Change in total body weight from baseline to week 24. · Proportion of patients achieving a therapeutic glycaemic response, defined as HbA1c <7.0% at week 24. · Change in seated systolic blood pressure (SBP) from baseline to week 8. Other secondary outcome variables: · Proportion of patients discontinued for lack of efficacy or rescued for failing to maintain FPG below pre-specified rescue criteria at weeks 4, 8, 16 and 24. · Change in HbA1c in patients with baseline HbA1c =8.0% from baseline to week 24. · Change in HbA1c in patients with baseline HbA1c =9.0% from baseline to week 24. · Change in FPG from baseline to week 8. · Change in seated SBP from baseline to week 24. · Proportion of patients with seated blood pressure of <130/80 mmHg at week 24 in patients with baseline elevated blood pressure (baseline SBP =130 mmHg and/or baseline diastolic blood pressure (DBP) =80 mmHg). · Percent change in fasting lipids (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) from baseline to week 24. · Change in HOMA-2, HOMA-IR from baseline to week 24. · Change in insulin, proinsulin and C-peptide values from baseline to week 24. · Change in waist circumference from baseline to week 24. · Effect of dapagliflozin versus placebo from baseline to week 24 on health-related quality of life (HRQL) as measured by Euro quality of life 5 Dimensions 3 levels (EQ-5D-3L). · Scores of treatment satisfaction, individual satisfaction and perceived frequency of hyper/hypoglycaemia as measured by Diabetes Treatment Satisfaction Questionnaire status (DTSQs) at baseline, week 24 and at week 52. · Scores of change of treatment satisfaction, individual satisfaction and perceived frequency of hyper/hypoglycaemia using the Diabetes Treatment Satisfaction Questionnaire change (DTSQc) observed with | — |
Countries
Canada, Czech Republic, Germany, Poland, Slovakia, Spain
Contacts
Public ContactClinical Study Information
AstraZeneca
Outcome results
None listed