Safety and Efficacy of Combination Saxagliptin & Dapagliflozin Added to Metformin to Treat Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to learn if a combination of BMS-477118 (Saxagliptin) and BMS -512148 (Dapagliflozin) added to Metformin can improve (decrease) Glycosylated Hemoglobin (Hemoglobin A1c) in patients with type 2 diabetes after 24 weeks of treatment. The safety of this treatment will also be studied.

Official Title
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A Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Add-On Therapy With Saxagliptin and Dapagliflozin Added to Metformin Compared to Add-On Therapy With Saxagliptin in Combination With Metformin or Dapagliflozin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone.

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Saxagliptin
* Drug: Metformin XR
* Drug: Dapagliflozin
* Drug: Placebo matching with Dapagliflozin
* Drug: Placebo matching with Saxagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with Type 2 diabetes mellitus (T2DM) with HbA1c ≥ 8.0% and ≤ 12.0% Stable metformin therapy dose of ≥ 1500mg for at least 8 weeks prior to screening Body mass index (BMI) ≤ 45.0kg/m2 Exclusion Criteria: Estimated glomerular filtration rate (eGFR) < 60mL/min/1,73m2 and Serum Creatinine (Scr) ≥ 1.5 mg/dL in males or ≥ 1.4 mg/dL in females Uncontrolled hypertension Systolic Blood Pressure (SBP) ≥ 160mmHg and/or Diastolic Blood Pressure (DBP) ≥ 100mmHg Hepatic disease Cardiovascular disease within 3 months

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: Arm 1: Saxagliptin+Metformin XR+Placebo<br> | Drug: Saxagliptin<br>* Tablets, Oral, 5mg , Once daily, 24 weeks<br>* Other names: Onglyza;Drug: Metformin XR<br>* Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks<br>* Other names: Glucophage XR;Drug: Placebo matching with Dapagliflozin<br>* Tablets, Oral, 0mg, Once daily, 24 weeks<br>|
| Active Comparator: Arm 2: Dapagliflozin+Metformin XR+Placebo<br> | Drug: Metformin XR<br>* Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks<br>* Other names: Glucophage XR;Drug: Dapagliflozin<br>* Tablets, Oral, 10mg , Once daily, 24 weeks<br>* Other names: BMS-512148;Drug: Placebo matching with Saxagliptin<br>* Tablets, Oral, 0mg, Once daily, 24 weeks<br>|
| Experimental: Arm 3: Saxagliptin+Dapagliflozin+Metformin XR<br> | Drug: Saxagliptin<br>* Tablets, Oral, 5mg , Once daily, 24 weeks<br>* Other names: Onglyza;Drug: Metformin XR<br>* Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks<br>* Other names: Glucophage XR;Drug: Dapagliflozin<br>* Tablets, Oral, 10mg , Once daily, 24 weeks<br>* Other names: BMS-512148;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 | HbA1c was measured as percent of hemoglobin by a central laboratory. Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained at Week 24 in the double-blind period, including observations prior to rescue. | Baseline (Week 0) and at Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in 2-hour Post Prandial Glucose (PPG) From a Liquid Meal Tolerance Test (MTT) at Week 24 (Last Observation Carried Forward [LOCF]) | Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. PPG measurements were obtained at week 24 in the doubleblind period, including observations prior to rescue. | Baseline (Week 0) and at Week 24 | 
| Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained at Week 24 in the doubleblind period, including observations prior to rescue. | Baseline (Week 0) and at Week 24 | 
| Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF]) | Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. | At Week 24 | 
| Adjusted Mean Change From Baseline in Body Weight at Week 24 | Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained at Week 24 in the doubleblind period, including observations prior to rescue. | Baseline (Week 0) and at Week 24 |