A Study Assessing Saxagliptin Treatment 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 clinical research study is to learn whether Saxagliptin can improve the body's ability to make its own insulin and lower blood sugar in people with type 2 diabetes

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 who have an elevated blood sugar that requires additional medication for blood sugar control will be eligible to receive open-label metformin added onto their blinded study medication

Official Title
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Mechanism of Action and Efficacy of Saxagliptin (BMS-477118) in the Treatment of Type 2 Diabetic Patients

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Saxagliptin
* Drug: Placebo
* Drug: Metformin (blinded)
* Drug: Metformin (open-label)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus Drug naive Hemoglobin A1c (HbA1c) ≥6.0% and ≤8.0% Fasting C-peptide ≥1.0 ng/mL Body mass index ≤40 kg/m² Exclusion Criteria: Recent cardiac or cerebrovascular event Elevated serum creatinine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 (A)<br>Metformin 500-1500 mg (open-label, as needed for rescue in LT) | Drug: Saxagliptin<br>* Tablet, Oral, 5 mg, Once daily, (up to 12 weeks ST, up to 104 weeks LT)<br>* Other names: BMS-477118;|
| Placebo Comparator: Placebo (ST) / Metformin (LT) (B)<br>Metformin 500-1500 mg (open-label, as needed for rescue in LT) | Drug: Placebo<br>* Tablet, Oral, 0 mg, Once daily (up to 12 weeks ST)<br>Drug: Metformin (blinded)<br>* Tablet, Oral, 500 mg titrated to 1000 mg, Once daily (up to 104 weeks LT, starting at Week 12)<br>Drug: Metformin (open-label)<br>* Tablets, Oral, 500-1500 mg, as needed (starting in LT)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Secretion Rate Area Under the Curve (AUC) During Intravenous (IV)-Oral Hyperglycemic Clamp - Percent Change From Baseline at Week 12 | Adjusted percent change in the insulin secretion rate AUC during a hyperglycemic clamp with an enteral glucose load [intravenous-oral hyperglycemic clamp (180-480 minutes)] at Week 12. The method used for calculating the insulin secretion rate was C-peptide deconvolution. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Secretion Rate AUC During IV Hyperglycemic Clamp - Percent Change From Baseline at Week 12 | Adjusted percent change in the insulin secretion rate AUC during an intravenous hyperglycemic clamp (120-180 minutes) at Week 12. The method used for calculating the insulin secretion rate was C-peptide deconvolution. | Baseline, Week 12 |