Dose-Ranging Study In Subjects With Type 2 Diabetes Mellitus Who Are Treatment-Naive

Inclusion Criteria

• Subjects with a documented diagnosis of T2DM and HbA1c ≥7.0% and ≤9.5% measured by the central laboratory at Visit 1.
• Note: Subjects with HbA1c 5.5 mIU/L (>5.5 MCIU/mL) at Screening
• BMI of 43 kg/m2
• Significant weight gain or loss (as defined as >5% of total body weight) in the 3 months prior to Screening
• Diabetic Medication
• Has taken insulin, or any oral or injectable anti-diabetic medication within 3 months of screening
• Has taken insulin or any oral or injectable anti-diabetic medication ≥4 weeks at any time in the past
• Cardiovascular Disease

Recent history or presence of clinically significant acute cardiovascular disease including:

• Documented myocardial infarction in the 6 months prior to Screening.
• Coronary revascularization including percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery either planned and/or occurred in the 6 months prior to Screening.
• Unstable angina in the 6 months prior to Screening.
• Clinically significant supraventricular arrhythmias requiring medical therapy, or history of nonsustained or sustained ventricular tachycardia. Symptomatic valvular heart disease or valvular heart disease requiring therapy other than endocarditis prophylaxis.
• Congestive heart failure (CHF, New York Heart Association (NYHA) Class II to IV) requiring pharmacologic treatment or the NYHA Class criteria in accordance with the local prescribing information for pioglitazone.
• Blood pressure (BP) >150/100mmHg. If a subject is receiving permitted antihypertensive therapy, then they must be on stable dose(s) of therapy for at least 4 weeks prior to Screening.
• Based on local readings, the subject has an initial QTc interval (Bazett's)≥450msec at Screening, and after two additional ECGs taken 5 minutes apart, the average of the QTC interval from the three ECGs is ≥450msec.
• Other clinically significant ECG abnormalities which, in the opinion of the Investigator, may affect the interpretation of efficacy or safety data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity.
• Fasting triglycerides ≥400mg/dL (4.56mmol/L) at Screening. If a subject is receiving permitted lipid-lowering therapy, then they must be on a stable dose(s) of therapy for at least 6 weeks prior to Screening. Niacin and bile acid sequestrants are prohibited.
• Hepatic Disease

Has a diagnosis of active hepatitis (hepatitis B surface antigen or hepatitis C antibody), or clinically significant hepatic enzyme elevation including:

Any one of the following enzymes greater than 2 times the upper limit of the reference range (ULRR) value at Screening.

• alanine aminotransferase (ALT)
• aspartate aminotransferase (AST)
• alkaline phosphatase (AP) Has a total bilirubin level that is >1.5 times the ULRR at Screening with the exception of suspected or confirmed Gilbert's disease.
• Pancreatic Disease
• Secondary causes of diabetes:
• history of chronic or acute pancreatitis
• Renal Disease

Significant renal disease at Screening as manifested by:

• Glomerular filtration rate (GFR) 21 units or an average daily intake of >3 units (males) or an average weekly intake of >14 units or an average daily intake of >2 units (females). One unit is equivalent to a half pint of beer or 1 measure of spirits or 1 glass of wine
• Has participated in any study with an investigational or marketed drug in the 3 months prior to Screening.
• In the opinion of the investigator has a risk of non-compliance with study procedures, or cannot read, understand, or complete study related materials, particularly the informed consent.
• Known allergy to any of the tablet or capsule excipients, or history of drug or other allergy, which, in the opinion of the responsible study physician, contraindicates participation.