A Study of Saxagliptin in Subjects With Type 2 Diabetes Who Have Inadequate Blood Sugar Control With Sulfonylureas

Study Overview
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Brief Summary
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The purpose of this trial is to understand if adding saxagliptin to a sulfonylurea is safe and works better than increasing the amount of sulfonylurea a patient takes

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 (defined as rescue) will be eligible to enter the long-term treatment extension period where they will receive metformin.Rescue treatment with metformin is also available during the long-term extension period for subjects who meet glycemic criteria.

Official Title
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A Multicenter, Randomized, Double-Blind Placebo-Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination With Glyburide in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Glyburide Alone

Conditions
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Diabetes

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetes. Treated with a sulfonylurea for at least 2 months. Inadequate blood sugar control. Are not on any other medications to lower blood sugar. No major heart, liver or kidney problems. Women not 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 2.5 mg + Glyburide 7.5 mg (A)<br>Metformin 500-2500 mg (as needed) | Drug: Saxagliptin<br>* Tablets, Oral, 2.5 mg, Daily AM, (24 weeks short-term [ST], 12 months long-term [LT])<br>* Other names: BMS-477118;Drug: Glyburide<br>* Capsules, Oral, OL, 7.5 mg, Daily, AM (24 weeks ST, 12 months LT)<br>Drug: Metformin<br>* Tablets, Oral, OL, 500 - 2500 mg, 1 or 2 times per day (12 months LT)<br>|
| Experimental: Saxagliptin 5 mg + Glyburide 7.5 mg (B)<br>Metformin 500-2500 mg (as needed) | Drug: Saxagliptin<br>* Tablets, Oral, 5 mg, Daily AM (24 weeks ST, 12 months LT).<br>* Other names: BMS-477118;Drug: Glyburide<br>* Capsules, Oral, OL, 7.5 mg, Daily, AM (24 weeks ST, 12 months LT)<br>Drug: Metformin<br>* Tablets, Oral, OL, 500 - 2500 mg, 1 or 2 times per day (12 months LT)<br>|
| Placebo Comparator: Placebo + Glyburide 7.5 mg (C)<br>Metformin 500-2500 mg (as needed) | Drug: Placebo<br>* Tablets, Oral, 0 mg, Daily AM/PM, (24 weeks ST, 12 months LT)<br>Drug: Glyburide<br>* Capsules, Oral, DB Glyburide, 2.5 mg titrated to 7.5 mg + 7.5 mg OL, Daily AM/PM (24 weeks ST, 12 months LT)<br>Drug: Metformin<br>* Tablets, Oral, OL, 500 - 2500 mg, 1 or 2 times per day (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 | 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 | 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 | Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus glyburide versus placebo plus upward titrated glyburide 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 | Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjusted for baseline values. | Baseline, Week 24 |