Ranolazine Monotherapy in Subjects With Type 2 Diabetes Mellitus

Key Inclusion Criteria:

• Written informed consent
• Males and females, 18 to 75 years old, inclusive
• Documented history of T2DM
• Treatment naïve to antihyperglycemic therapy or having received no prior treatment with antihyperglycemic therapy for at least 90 days prior to Screening
• Body mass index (BMI) 27-45 inclusive at Screening
• HbA1c 7% - 10%, inclusive at Screening and at the end of Period One (Day 14 +2 days)
• FSG of ≥130 mg/dL (7.2 mmol/L) and ≤240 mg/dL (13.3 mmol/L) at Screening and at the end of Period One (Day 14 +2 days)
• C-peptide > 1.0 ng/mL at Screening

Key Exclusion Criteria:

• History of type 1 diabetes mellitus
• History of acute or chronic ketoacidosis, ketosis-prone diabetes, or hyperosmolar hyperglycemic coma
• History of a severe episode of hypoglycemia (eg, requiring assistance of another person or active intervention of any kind) < 3 months before Screening
• Any clinically significant cardiovascular or cerebrovascular event (eg, myocardial infarction [MI], acute coronary syndrome [ACS], recent revascularization [including coronary artery bypass graft procedures or percutaneous coronary intervention], transient ischemic attack or ischemic stroke) ≤ 3 months prior to Screening
• Inadequately controlled or unstable hypertension as defined by systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg at Screening and Period Two Day 1
• Prolonged QTc interval > 500 msec by ECG at Screening, a personal or family history of QTc prolongation, congenital long QT syndrome, or subjects who are receiving drugs that prolong the QTc interval, such as Class Ia or Class III antiarrhythmic agents, erythromycin, and certain antipsychotics (eg, ziprasidone)
• Hemoglobin < 12 g/dL for males; or < 11g/dL for females, at Screening
• History of bariatric surgery at any time in the past or any other surgery < 2 months before Screening, or any planned surgery that, in the opinion of the investigator, might have an effect on glucose homeostasis
• Any other hospitalization in the 14 days prior to Screening or planned hospitalization at any time during the study
• Significant weight change (± 5%) < 2 months prior to Screening
• Undergoing any type of dialysis at Screening or planning to undergo any type of dialysis during the course of the study
• History of liver cirrhosis
• Treatment with strong or moderate CYP3A inhibitors within 14 days prior to Period Two Day 1
• Treatment with CYP3A inducers or P-gp inducers within 14 days prior to Period Two Day 1
• Treatment with CYP3A4 substrates with a narrow therapeutic range (eg, cyclosporine, tacrolimus, sirolimus) within 14 days prior to Period Two Day 1
• Treatment with simvastatin at a daily dose of > 20 mg, within 14 days prior to Period Two Day 1
• Treatment with a thiazolidinedione (TZD) (eg, rosiglitazone or pioglitazone) within 6 months of Screening
• Weight-loss medication or anti-obesity medication (prescription or non-prescription) < 3 months prior to Screening
• Treatment with niacin > 200 mg daily; if receiving ≤ 200 mg daily, should be on stable doses 90 days prior to Screening and for the duration of the for study
• Expected or current treatment with systemic corticosteroids (oral or injectable) for > 14 days from Screening through the end of the Treatment Period. Topical or inhaled corticosteroid formulations are permitted at any time during the study
• If receiving thyroid replacement therapy, should be on stable doses for at least 6 weeks prior to Period Two Day 1