Study to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Sitagliptin in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy Alone

Study Overview
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Brief Summary
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Study will evaluate if a combination of saxagliptin and dapagliflozin added concurrently to metformin in combination with diet and exercise is superior to sitagliptin added to metformin in combination with diet and exercise in reducing mean HbA1c over a treatment period of 26 weeks.

Official Title
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A 26-week International, Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group, Phase 3bTrial With a Blinded 26-week Long -Term Extension Period to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Sitagliptin in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy Alone

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Saxagliptin
* Drug: Dapagliflozin
* Drug: Sitagliptin
* Drug: Placebo matching with Saxagliptin
* Drug: Placebo matching with Dapagliflozin
* Drug: Placebo matching with Sitagliptin


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Patients with Type 2 diabetes mellitus (T2DM) with inadequate glycemic control, defined as a central laboratory glycosylated hemoglobin (HbA1c) ≥8.0% and ≤ 10.5 % obtained at the screening visit Subjects should have been taking the same daily dose of metformin ≥ 1500 mg for at least 8 weeks prior to the enrollment visit and with no intake of other antihyperglycemic therapy for more than 14 days (consecutive or not) during 12 weeks prior to screening BMI > 20.0 kg/m2 at the enrollment visit Males and Females, age ≥18 years old at time of screening visit Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug Women must not be breastfeeding Exclusion Criteria: Clinically diagnosed with Type I diabetes, known diagnosis of Maturity Onset Diabetes of Young (MODY), secondary diabetes mellitus or diabetes insipidus History of diabetic ketoacidosis Any of the following cardiovascular (CV)/Vascular Diseases within 3 months of the enrollment visit Myocardial infarction Cardiac surgery or revascularization (coronary artery bypass surgery Coronary Artery Bypass Graft [(CABG)]/percutaneous transluminal coronary angioplasty percutaneous transluminal coronary angioplasty [(PTCA)]) Unstable angina Unstable congestive heart failure (CHF) Transient ischemic attack (TIA) or significant cerebrovascular disease Unstable or previously undiagnosed arrhythmia Congestive heart failure, defined as New York Heart Association (NYHA) Class III and IV, unstable or acute congestive heart failure and/or known left ventricular ejection fraction of ≤ 40% Renal Disease Hepatic Diseases Hematological and Oncological Disease/Conditions Hemoglobin ≤ 11.0 g/dL (110 g/L) for men; hemoglobin ≤ 10.0 g/dL (100 g/L) for women Abnormal Free T4

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1:Saxagliptin / Placebo + Dapagliflozin / Placebo<br>Saxagliptin 5 mg and matching placebo 0 mg (once daily) plus Dapagliflozin 10 mg and matching placebo 0 mg (once daily) | Drug: Saxagliptin<br>* administered orally once daily<br>Drug: Dapagliflozin<br>* administered orally once daily<br>Drug: Placebo matching with Saxagliptin<br>* administered orally once daily<br>Drug: Placebo matching with Dapagliflozin<br>* administered orally once daily<br>|
| Experimental: A2: Sitagliptin / placebo<br>Sitagliptin 100 mg and matching placebo 0 mg (once daily) | Drug: Sitagliptin<br>* administered orally once daily<br>Drug: Placebo matching with Sitagliptin<br>* administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in HbA1c |  | Baseline (randomization) to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects Achieving a Therapeutic Glycemic Response, Defined as HbA1c < 7.0% |  | week 26 | 
| Mean Change in Total Body Weight |  | Baseline (randomization) to Week 26 | 
| Mean Change in Fasting Plasma Glucose (FPG) |  | Baseline (randomization) to Week 26 |