A 24-week Open-Label, Phase 3b Trial With a 28-week Extension to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin Compared to Insulin Glargine in Subjects withType 2 Diabetes Who Have Glycemic Control on Metformin

Study Overview
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Brief Summary
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This research study of subjects with inadequately controlled type 2 diabetes mellitus (T2DM) will compare the glycemic control (measured by HbA1c) in subjects co-administered saxagliptin and dapagliflozin, in addition to metformin with or without sulfonylurea, to subjects receiving insulin glargine, in addition to metformin with or without sulfonylurea, over a treatment period of 52 weeks.

Detailed Description
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CV181-369; A 24 Week International, Open-Label Trial With a 28 Week Extension to Evaluate the Efficacy of Saxagliptin Co-administered With Dapagliflozin Compared to Insulin Glargine in Subjects With Type 2 Diabetes on Metformin With or Without Sulfonylurea Therapy

Official Title
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A 24-week International, Multicenter, Randomized, Open-Label, Active-Controlled, Parallel Group, Phase 3b Trial With a 28-week Extension to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin Compared to Insulin Glargine in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin With or Without Sulfonylurea Therapy

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Saxagliptin, Onglyza
* Drug: Dapagliflozin, Farxiga
* Drug: Glargine insulin
* Drug: Metformin


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: At least 18 years of age at screening HbA1c ≥ 8% and ≤ 12% at screening Fasting plasma glucose (FPG) ≤ 270 mg/dL (15mmol/L) Stable dose metformin ≥ 1500 mg per day with or without a stable dose of sulfonylurea (defined as at least 50% maximal dose per local label) for at least 8 weeks estimated glomerular filtration rate (eGFR) &lt; 60 ml/ml/1.73m2 Body Mass Index ≤ 45.0 kg/m2 Exclusion Criteria: Clinical diagnosis of Type 1 diabetes History of ketoacidosis Renal, hepatic or pancreatic disease Impairment of renal function (defined as creatinine clearance [CrCl] < 60 mL/min Cardiovascular or vascular diseases identified within 3 months of participationImpairment of renal function (defined as creatinine clearance [CrCl] < 60 mL/min

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saxagliptin/Dapagliflozin/Metformin<br>Oral route. Saxagliptin/Dapa adminsitered once daily for 24 weeks at a dose of 5 mg Saxagliptin and 10 mg Dapagliflozin | Drug: Saxagliptin, Onglyza<br>* Tablets, Oral, 5mg , Once daily, 24 weeks<br>* Other names: Onglyza;Drug: Dapagliflozin, Farxiga<br>* Tablets, Oral, 10mg , Once daily, 24 weeks<br>* Other names: BMS-512148;Drug: Metformin<br>* Tablets, Oral, ≥ 1500mg/≤ 2500mg, Once daily, 24 weeks<br>* Other names: Glucophage;|
| Active Comparator: Insulin Glargine, Lantos/Metformin<br>Insulin glargine administered once a day with starting dose of 0.2 Unit per kg or 10 units. | Drug: Glargine insulin<br>* 100 Units/ml solution for injection in a prefilled SoloStar pen<br>* Other names: Lantus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in HbA1c at Week 24 | To examine whether the mean change from baseline in HbA1c with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior (noninferiority margin of 0.3%) to titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Total Body Weight at Week 24 | To compare the mean change from baseline in total body weight with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU versus titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment | Baseline and Week 24 | 
| Percentage of Subjects With Confirmed Hypoglycaemia at Week 24 | Hypoglycemia defined as plasma glucose ≤70 mg/dL (3.9 mmol/L) | Baseline and Week 24 | 
| Percentage of Subjects Achieving a Therapeutic Glycemic Response, Without Hypoglycaemia, at Week 24 | To compare the percentage of subjects achieving a therapeutic glycemic response, defined as HbA1c <7.0%, without any reported hypoglycemia, with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU versus titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment. | Baseline and Week 24 | 
| Percentage of Subjects Achieving a Therapeutic Glycemic Response at Week 24 | To examine whether the percentage of subjects achieving a therapeutic glycemic response, defined as HbA1c <7.0%, with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior (noninferiority margin of 10%) to titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment. | Baseline and Week 24 | 
| Change From Baseline in the Mean Value of 24-hour Glucose at Week 2 | Change from baseline in the mean value of 24-hour glucose readings measured by Continuous Glucose Monitoring with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior to titrated insulin glargine plus metformin with or without SU after 2 weeks of open-label treatment. | Baseline and Week 2 |