ot applicable.

• Conditions: type 2 diabetes mellitus; MedDRA version: 15.1Level: LLTClassification code 10012613Term: Diabetes mellitus non-insulin-dependentSystem Organ Class: 100000004861; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2009-017061-28-DE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-02-02
• Last Update Posted: 17 June 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 940

Inclusion Criteria

Inclusion criteria at enrolment (Visit 1) and start of placebo lead-in (Visits 2)
1.Provision of informed consent prior to any study specific procedures
2.Prior diagnosis of type 2 diabetes
3.Age at enrolment visit
-Men =45 years old
-Women =50 years old
4.Anti-hyperglycaemic treatment should have been used uninterrupted on a daily basis for 8 weeks and stable for at least 4 weeks before enrolment and identical to one of the following:
-Monotherapy or dual combination therapy with oral anti-diabetic drug(s) for example metformin, pioglitazone, sulfonylurea, acarbose, or a DPP-4 inhibitor (saxagliptin, sitagliptin, vildagliptin), except rosiglitazone which is not allowed for at least 8 weeks before enrolment (refer to Section 4.2, exclusion criteria 29), or
-Insulin therapy in combination with oral anti-hyperglycaemic therapy, or
-Insulin monotherapy
5.At enrolment: 7.2% =HbA1c =10.5% (value from blood sample obtained at screening)
6.Cardiovascular disease, defined as:
-Prior documented Coronary Heart Disease
-History of myocardial infarction or
-History of revascularization, or coronary artery stenosis >50%, confirmed with angiography or
-Abnormal imaging at stress test, compatible with ischemia or prior myocardial infarction or
-Prior documented Stroke or TIA, or
-Prior documented Peripheral Artery Disease (PAD) treated with revascularization (amputation is not accepted)
7.Patients who use anti-hypertensive medication (diuretics, beta blockers, ace-inhibitors, angiotensin receptor blockers, or calcium channel antagonists, and drugs that are known to have a blood pressure lowering effect, for example, medication used in treatment of congestive heart failure), should have used their medication uninterrupted on a daily basis in the last 4 weeks before the enrolment.
8.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

Inclusion criteria at randomisation (visit 4, laboratory values from visit 3):
Patients should fulfil inclusion criteria 1 to 8(listed above) and the following criteria at randomisation:
9.HbA1c =7.0% and =10.0% at randomisation (value from blood sample obtained at Visit 3).
10.Uninterrupted monotherapy or dual combination therapy of oral diabetes drugs (with or without insulin) for at least 12 weeks before randomisation.
11.Insulin treatment for at least 12 weeks before randomisation, if administered.
12.The dose of anti-hyperglycaemic drugs and the insulin regimen should be stable for 8 weeks before randomisation.
13.The use of anti-hypertensive medication in patients - including diuretics and drugs that are known to have a blood pressure lowering effect, for example, medication used in treatment of congestive heart failure - should be uninterrupted for 8 weeks before randomisation and the dose should be stable for 4 weeks before randomisation.
14.Lipid lowering and/ or anti-platelet treatment should be uninterrupted for 4 weeks before randomisation, if administered.
For inclusion in the optional genetic research, patients must fulfil the following criterion:
15.

Exclusion Criteria

The following criteria apply to the enrolment, placebo lead in and randomisation visits (Visits 1, 2, and 4).

Endocrine and metabolic disorders
1.Diagnosis of Type 1 diabetes mellitus, known diagnosis of MODY or secondary diabetes mellitus
2.Use of 3 or more oral anti-hyperglycaemic drugs with or without insulin
3.History of diabetic ketoacidosis
4.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
5.FPG >270 mg/dl (>15 mmol/L) at randomisation (sample will be taken at visit 3)
6.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.
7.Diabetes insipidus
8.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
9.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 two months prior to enrolment
-Less than two months post coronary artery revascularization
10.Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure. Note: eligible patients with congestive heart failure, especially those who are on diuretic therapy, should have careful monitoring of their volume status throughout the study.
11.Blood pressure:
-At enrolment (Visit 1):
Systolic BP =165 mmHg and/or diastolic BP =100 mmHg
-At randomisation (Visit 4):
Systolic BP =160 mmHg and/or diastolic BP =100 mmHg

Kidney disorders
12.Calculated creatinine clearance <60 mL/min
13.Urine albumin: creatinine ratio (UACR) >1800 mg/g (>203.4 mg/mmol/L)
14.History of unstable or rapidly progressing renal disease
15.Familial renal glucosuria. This condition is diagnosed as glucosuria (>1.0 mmol/L urine) in the presence of normoglycaemia in a patients without the diagnosis of diabetes mellitus

Hepatic disorders
16.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
17.Total bilirubin >2.0 mg/dL (34.2 µmol/L)
18.Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody
19.History of drug-induced liver enzyme elevations
20.History of severe hepatobiliary disease or hepatotoxicity with any medication

Hematologic/oncologic disorders/conditions
21.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
22.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).
23.Donation or transfusion of blood, plasma, or platelets within the past 3 months prior to Visit 1
24.History of mal

Study & Design

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