Study Assessing Saxagliptin Treatment In Type 2 Diabetic Subjects Who Are Not Controlled With Metformin Alone

Study Overview
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Brief Summary
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The purpose of this clinical research study is to learn whether Saxagliptin added to Metformin therapy is more effective than Metformin alone as a treatment for type 2 diabetic subjects who are not sufficiently controlled with 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 pioglitizone added onto their blinded study medication

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial to Evaluate the Efficacy and Safety of BMS-477118 in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Saxagliptin + Metformin
* Drug: Saxagliptin + Metformin
* Drug: Saxagliptin + Metformin
* Drug: Placebo + Metformin
* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus requiring treatment with at least 1500 mg but not greater than 2550 mg of a maximum tolerated dose of Metformin therapy for at least 8 weeks prior to screening. HbA1c >= 7.0% and <= 10.0 % Body mass index <= 40 kg/m2 Fasting C-peptide >= 1 ng/dL Exclusion Criteria: Symptomatic poorly controlled diabetes Recent cardiac or cerebrovascular event Serum creatinine >= 1.5 mg/dL for males and >= 1.4 mg/dL for females

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 + Metformin (A)<br>Pioglitazone 15-45 mg (as needed for rescue) | Drug: Saxagliptin + Metformin<br>* Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)<br>* Other names: BMS-477118;Drug: Pioglitazone<br>* Tablets, Oral, 15 - 45 mg (as needed for rescue)<br>|
| Experimental: Saxagliptin + Metformin (B)<br>Pioglitazone 15-45 mg (as needed for rescue) | Drug: Saxagliptin + Metformin<br>* Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)<br>* Other names: BMS-477118;Drug: Pioglitazone<br>* Tablets, Oral, 15 - 45 mg (as needed for rescue)<br>|
| Experimental: Saxagliptin + Metformin (C)<br>Pioglitazone 15-45 mg (as needed for rescue) | Drug: Saxagliptin + Metformin<br>* Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)<br>* Other names: BMS-477118;Drug: Pioglitazone<br>* Tablets, Oral, 15 - 45 mg (as needed for rescue)<br>|
| Placebo Comparator: Placebo+ Metformin (D)<br>Pioglitazone 15-45 mg (as needed for rescue) | Drug: Placebo + Metformin<br>* Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT)<br>Drug: Pioglitazone<br>* Tablets, Oral, 15 - 45 mg (as needed for rescue)<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline and Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Mean change from baseline is adjusted for baseline value. | Baseline, Week 24 | 
| Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24 |  | Week 24 | 
| Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC) | Mean change from baseline is adjusted for baseline value. | Baseline, Week 24 |