A Multiple-Ascending Dose Study in Type 2 Diabetes Mellitus Patients

Inclusion criteria

• Diagnosis of type 2 diabetes mellitus
• Must be on a stable treatment regimen (maintained on diet/exercise therapy with or without metformin) for at least 4 weeks prior to study entry
• Have a glycated haemoglobin (HbA1c) value greater than or equal to 6.5% and less than or equal to 10.0% on a stable treatment regimen
• Weigh 45.0 kg or more
• Have a Body Mass Index (BMI) greater than or equal to 18.5 and less than or equal to 40.0 kg/m2
• Are willing and able to conduct self-blood glucose monitoring tests

Exclusion criteria

• Are currently enrolled in, or discontinued within the last 30 days from a clinical trial involving use of an investigational drug or device other than the study drug used in this study, or are concurrently enrolled in any other type of medical research judged not to be compatible with this study
• Use of insulin for diabetic control for more than 6 consecutive days within 1 year prior to study entry
• Use of thiazolidinediones within 3 months, or other oral anti-diabetics (OADs), apart from metformin, within 1 month prior to study entry. Metformin is acceptable for this study
• Previous myocardial infarction, stroke or transient ischaemic event ('TIA'), or clinically significant coronary events or symptoms within 6 months prior to study entry
• Subjects who have any evidence of heart insufficiency, hypokalaemia, family history of long-QT-syndrome or are receiving other drugs which extend the QT interval
• Clinically significant peripheral vascular disease
• Clinical evidence of active diabetic proliferative retinopathy
• Known significant autonomic neuropathy
• Any patient having experienced a keto-acidotic episode requiring hospitalisation in the last 6 months
• Symptomatic hyperglycemia exhibited by significant osmotic symptoms (polyuria or polydipsia), unanticipated weight loss or dehydration
• Evidence of hepatitis B and/or positive hepatitis B surface antigen, at screening
• Subjects who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females)
• Subjects who are heavy smokers (> 10 cigarettes, or equivalent, per day) or are unable or unwilling to refrain from nicotine during CRU admissions

Exclusion criteria

for EU Site only --

• Regular use of known drugs of abuse and/or positive findings on urinary drug screening
• Evidence of human immunodeficiency virus (HIV) and/or positive HIV antibodies
• Evidence of hepatitis C and/or positive hepatitis C antibodies