A Phase 3 Study of BMS-477118 in Combination With Metformin in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise

Study Overview
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Brief Summary
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The purpose of this trial is to understand if adding saxagliptin to metformin therapy is safe and works better than taking either saxagliptin or metformin alone

Detailed Description
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All subjects will participate in a lead-in period, and qualifying subjects will continue into a short-term randomized treatment period. Subjects who complete the short-term period will be eligible to enter the long term extension period. Also, subjects in the short-term period who have an elevated blood sugar that requires additional medication for blood sugar control will be eligible to enter the long-term treatment extension period where they will receive pioglitazone (rescue medication) added onto their blinded study medication

Official Title
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A Multicenter, Randomized, Double-Blind Active-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR as Initial Therapy Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control

Conditions
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Diabetes

Intervention / Treatment
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* Drug: Saxagliptin
* Drug: Saxagliptin
* Drug: Metformin
* Drug: Placebo
* Drug: pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes Inadequate blood sugar control No current treatment with other medications to lower blood sugar Exclusion Criteria: Major heart, liver or kidney problems Pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 77 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saxagliptin and Metformin (A)<br>PLUS open-label pioglitazone (as needed as rescue medication) | Drug: Saxagliptin<br>* Coated Tablets, Oral, 10 mg, Daily (6 months ST, 12 months LT)<br>* Other names: BMS-477118;Drug: Metformin<br>* Coated tablets, Oral, 500 mg, Daily (6 months ST, 12 months LT)<br>Drug: pioglitazone<br>* Tablets, Oral, 15-45 mg, as needed (12 months LT)<br>|
| Experimental: Saxagliptin and Metformin (B)<br>PLUS open-label pioglitazone (as needed as rescue medication) | Drug: Saxagliptin<br>* Coated tablets, PO, 5 mg, Daily (6 months ST, 12 months LT)<br>* Other names: BMS-477118;Drug: Metformin<br>* Coated tablets, Oral, 500 mg, Daily (6 months ST, 12 months LT)<br>Drug: pioglitazone<br>* Tablets, Oral, 15-45 mg, as needed (12 months LT)<br>|
| Experimental: Saxagliptin and Placebo (C)<br>PLUS open-label pioglitazone (as needed as rescue medication) | Drug: Saxagliptin<br>* Coated Tablets, Oral, 10 mg, Daily (6 months ST, 12 months LT)<br>* Other names: BMS-477118;Drug: Placebo<br>* Coated tablets, Oral, 0 mg, Daily (6 months ST, 12 months LT)<br>Drug: pioglitazone<br>* Tablets, Oral, 15-45 mg, as needed (12 months LT)<br>|
| Active Comparator: Metformin and Placebo (D)<br>PLUS open-label pioglitazone (as needed as rescue medication) | Drug: Metformin<br>* Coated tablets, Oral, 500 mg, Daily (6 months ST, 12 months LT)<br>Drug: Placebo<br>* Coated tablets, Oral, 0 mg, Daily (6 months ST, 12 months LT)<br>Drug: pioglitazone<br>* Tablets, Oral, 15-45 mg, as needed (12 months LT)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (A1C) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy | Mean change from baseline in A1C at Week 24, adjusted for baseline value. | Baseline, Week 24 | 
| Change From Baseline in A1C at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy | Mean change from baseline in A1C at Week 24, adjusted for baseline value. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy | Mean change from baseline in FPG at Week 24, adjusted for baseline value. | Baseline, Week 24 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy | Mean change from baseline in FPG at Week 24, adjusted for baseline value. | Baseline, Week 24 | 
| Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy | Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24. | Week 24 | 
| Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy | Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus metformin alone at Week 24. | Week 24 | 
| Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy | Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjusted for baseline value. | Baseline, Week 24 | 
| Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy | Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjsuted for baseline value. | Baseline, Week 24 | 
| Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy | Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24. | Week 24 | 
| Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy | Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus metformin alone at Week 24. | Week 24 | 
| Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy | Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus saxagliptin alone. | Week 24 | 
| Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy | Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus metformin alone. | Week 24 |