Ranolazine When Added to Glimepiride in Subjects With Type 2 Diabetes Mellitus

Inclusion Criteria

• Written informed consent
• Males and females, 18 to 75 years old, inclusive
• Documented history of T2DM
• Receiving one of the following sulfonylurea or metformin therapies in addition to diet and exercise for at least 90 days prior to Screening:
• glimepiride at a daily dose of ≥ 2 mg and ≤ 4 mg
• glipizide, glyburide, or glibenclamide (or equivalent) at a daily dose of ≥ 7.5 mg
• gliclazide at a daily dose of > 160 mg (or ≥ 60 mg for the modified release [MR] formulation)
• metformin at a daily dose of ≥ 1500 mg
• Body mass index (BMI) 25 kg/m2 to 45 kg/m2, inclusive, at Screening
• HbA1c 7% to 10%, inclusive, at Screening and the end of the Qualifying Period (Day 14)
• Fasting Serum C-peptide ≥ 0.8 ng/mL at Screening
• Fasting serum glucose (FSG) ≥ 130 mg/dL (7.2 mmol/L) and ≤ 240 mg/dL (13.3 mmol/L) at Screening and at the end of the Qualifying Period (Day 14): A one-time central laboratory re-test of FSG is allowed in subjects with an initial central laboratory FSG ≥ 120 mg/dL (6.7 mmol/L) and 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg at Screening and at Randomization
• Prolonged QT interval corrected for heart rate (QTc) interval > 500 msec by electrocardiogram (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)
• History of bariatric surgery at any time in the past or or any other surgery 3 x upper limit of the normal range (ULN) and/or alanine aminotransferase (ALT) > 3 x ULN and/or serum total bilirubin > 2.0 mg/dL
• History of cancer (except nonmelanomic skin cancers or cervical in situ) within 5 years prior to Screening
• History of alcohol or other drug abuse 20 mg daily or lovastatin at a dose of > 40 mg daily within 14 days prior to Randomization
• Weight loss medication or anti-obesity medication (prescription or non-prescription) 200 mg daily; if receiving ≤ 200 mg daily, should be on stable doses for ≥ 3 months prior to Screening
• 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 randomization
• Hemoglobin < 12 g/dL for males or < 11 g/dL for females at Screening
• Participation in another clinical study involving an investigational drug or device < 30 days prior to Screening; participation in another clinical study involving an oral antihyperglycemic agent (OHA) < 90 days prior to Screening
• Donation of blood < 2 months prior to Screening or plans to donate blood while participating in the study
• Females who are pregnant or are breastfeeding
• Other condition(s) that, in the opinion of the investigator, would compromise the safety of the individual, prevent compliance with the study protocol (including the ability to comply with Mixed Meal Tolerance Test [MMTT]), or compromise the quality of the clinical study