Evaluation of Safety and Efficacy of Dapagliflozin in subjects with Type 2 Diabetes who have Inadequate Glycaemic Control on background combination of Metformin and Sulfonylurea

• Conditions: Type II diabetes mellitus; MedDRA version: 14.1Level: LLTClassification code 10012613Term: Diabetes mellitus non-insulin-dependentSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2011-002231-26-CZ
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-08-01
• Last Update Posted: 11 April 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 216

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 ³1500mg/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) 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

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 (Visit 1): Systolic BP =170 mmHg and/or diastolic BP =110 mmHg
At randomisation (Visit 4): Systolic BP =160 mmHg and/or diastolic 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 too low (as defined in haemoglobin criteria above)
Iron deficiency anaemia with iron

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified