ESR-15-11293 - Saxa/Dapa, Safety and Efficacy Study

Inclusion Criteria

• Provision of informed consent prior to any study-specific procedures.
• Is able to read, understand, and sign the Informed Consent Forms (ICFs) and, if applicable, an Authorization to Use and Disclose Protected Health Information form (consistent with Health Insurance Portability and Accountability Act of 1996 legislation), communicate with the Investigator, and understand and comply with protocol requirements, including the use of diary and glucose meter measurements.
• Age = 18-70 years.
• Has a diagnosis of T2DM.
• Has HbA1c ≥7.5% and ≤11.0% obtained at Screening.
• Treated with a stable dose of metformin ≥1000 mg/day or stable dose of metformin (≥ 1000 mg/day) plus sulfonylurea (glipizide, ≥ 5 mg/day; glyburide, ≥ 5 mg/day; glimepiride, ≥ 4 mg/day) for at least 8 weeks prior to Screening.
• Has a BMI of 20 to 45 kg/m2 (inclusive) at Screening.
• Is male, or is female, and meets all the following criteria:
• Not pregnant or breastfeeding.
• Negative pregnancy test result at Visit 1 (Screening).
• Women of childbearing potential (WOCBP; [including perimenopausal women who have had a menstrual period within 1 year]) must practice and be willing to continue to practice appropriate birth control (defined as a method that results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as implants, injectables, hormonal contraceptives [pills, vaginal rings, or patches], some intrauterine contraceptive devices [levonorgestrel-releasing or copper-T], tubal ligation or occlusion, or a vasectomized partner) during the entire duration of the study. As applicable, all methods must be in effect prior to receiving the first dose of study medication.

Exclusion Criteria

Target Disease Exceptions

• Clinically diagnosed with Type I diabetes .
• History of diabetic ketoacidosis, hyperosmolar nonketotic coma, or corticosteroid induced Type 2 diabetes.

Medical History and Concurrent Diseases

• History of bariatric surgery or lap-band surgery, or either procedure is planned during the time period of the study.
• History of any unstable endocrine, psychiatric, rapidly progressing, or unstable renal disease, or rheumatic disorder, as judged by the Investigator.
• Patients who, in the judgment of the Investigator, may be at risk for dehydration or volume depletion that may affect the patient's safety and/or the interpretation of efficacy or safety data.
• Has evidence of current abuse of drugs or alcohol or a history of abuse within the past 52 weeks that, in the Investigator's opinion, would cause the individual to be noncompliant.

Cardiovascular Conditions

• Cardiovascular disease within 3 months of Screening (i.e., MI, cardiac surgery, revascularization, unstable angina, stroke, transient ischemic attack, or arrhythmia).
• Presence or history of severe congestive heart failure (New York Heart Association Class III and IV [CCNYHA 1994]), unstable or acute congestive heart failure, and/or known left ventricular ejection fraction of ≤40%.

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.

Kidney Conditions

• Estimated (eGFR) 1.4 mg/dL for female patients and >1.5 mg/dL for male patients. If the serum creatinine is ≤ 1.4 (female) or ≤ 1.5 (male) and the eGFR is ≥ 60±5 ml/min/1.73m2, the subject is eligible to participate in the study.
• Congenital renal glucosuria. Hepatic Conditions
• Significant hepatic disease, including, but not limited to, severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) of >3x upper limit of normal (ULN).
• Serum total bilirubin (TB) >2 mg/dL.
• History of, or currently have, acute or chronic pancreatitis or have triglyceride concentrations ≥500 mg/dL at Visit 1 (Screening).
• Suspicion that the patient