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 (BMS-477118) is more effective than placebo as a treatment for type 2 diabetic subjects who are not sufficiently controlled with diet and exercise

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 metformin added onto their blinded study medication. Subjects with screening hemoglobin A1c (A1C) > 10.0% and ≤ 12.0%, who otherwise meet all inclusion/exclusion criteria, were eligible to enroll directly into Open-Label Treatment Cohort (Direct Enrollees) and receive open-label saxagliptin 10 mg. Those who completed the short-term period were eligible to enter into the long-term treatment extension period.Saxagliptin dose titration was not permitted.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin (BMS-477118) as Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise

Conditions
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Diabetes Mellitus, Type 2

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus Drug naive Hemoglobin (Hb) A1c >= 7.0% and <= 10.0% (>10% and <= 12% for open label arm) Fasting C-peptide >= 1 ng/mL Body mass index <= 40 kg/m2 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 Women of Child Bearing Potential

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 (A)<br>Metformin 500-2000 mg (as needed for rescue) | Drug: Saxagliptin<br>* Tablets, Oral, 2.5 mg, Once daily (24 weeks short term [ST], 42 months long term [LT])<br>* Other names: BMS-477118;Drug: Placebo matching Metformin<br>* Tablets, Oral, 0 mg, daily (42 months LT)<br>Drug: Metformin<br>* Tablets, Oral, 500-2000 mg (as needed for rescue)<br>|
| Experimental: Saxagliptin 5 mg (B)<br>Metformin 500-2000 mg (as needed for rescue) | Drug: Saxagliptin<br>* Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT)<br>* Other names: BMS-477118;Drug: Placebo matching Metformin<br>* Tablets, Oral, 0 mg, daily (42 months LT)<br>Drug: Metformin<br>* Tablets, Oral, 500-2000 mg (as needed for rescue)<br>|
| Experimental: Saxagliptin 10 mg (C)<br>Metformin 500-2000 mg (as needed for rescue) | Drug: Saxagliptin<br>* Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT)<br>* Other names: BMS-477118;Drug: Placebo matching Metformin<br>* Tablets, Oral, 0 mg, daily (42 months LT)<br>Drug: Metformin<br>* Tablets, Oral, 500-2000 mg (as needed for rescue)<br>|
| Placebo Comparator: Placebo (D)<br>Metformin 500-2000 mg (as needed for rescue) | Drug: Placebo matching Saxagliptin<br>* Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT)<br>Drug: Metformin<br>* Tablets, Oral, 500 mg, daily (42 months LT)<br>Drug: Metformin<br>* Tablets, Oral, 500-2000 mg (as needed for rescue)<br>|
| Experimental: Open-Label Treatment Cohort (Direct Enrollees) (E)<br>Saxagliptin 10 mg Metformin 500-2000 mg (as needed for rescue) | Drug: Saxagliptin<br>* Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT) Open Label<br>* Other names: BMS-477118;Drug: Metformin<br>* Tablets, Oral, 500-2000 mg (as needed for rescue)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1c (A1C) Changes From Baseline at Week 24 | To compare the change from baseline in HbA1c achieved with each dose of saxagliptin versus placebo in treatment naive subjects with type 2 diabetes who have inadequate glycemic control defined as A1C ≥7.0% and ≤10.0%. | Baseline, Week 24 | 
| A1C Changes From Baseline at Week 24 - Open Label Cohort | To compare the change from baseline in HbA1c achieved with each dose of saxagliptin versus placebo in treatment naive subjects with type 2 diabetes who have inadequate glycemic control defined as A1C ≥7.0% and ≤10.0%. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline and Change From Baseline at Week 24 in Fasting Plasma Glucose (FPG) |  | 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) |  | Baseline, Week 24 | 
| Baseline and Change From Baseline at Week 24 in Fasting Plasma Glucose (FPG) - Open Label Cohort |  | Baseline, Week 24 | 
| Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24 - Open Label Cohort |  | Week 24 | 
| Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC) - Open Label Cohort |  | Baseline, Week 24 |