Study To Evaluate 24 Hour Blood Sugar Control (24-hour Mean Weighted Glucose) In Subjects That Are Taking Saxagliptin 5 mg Added Onto Metformin XR 1500 XR mg Compared To Subjects Taking Metformin XR 1500 mg Up-titrated To Metformin XR 2000 mg

Study Overview
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Brief Summary
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The purpose of this study was to compare effect of Saxagliptin as add-on to Metformin on 24-hour mean weighted glucose (MWG) to the effect of uptitrating Metformin in subjects with T2DM inadequately controlled on metformin alone.

Official Title
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A 4-Week, Multicenter, Randomized, Double-Blind, Phase 3b Trial to Evaluate the Efficacy of Saxagliptin in Combination With Metformin XR 1500 mg Versus Up-titrated Metformin XR to 2000 mg in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise and a Stable Dose of Metformin XR 1500 mg

Conditions
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Type 2 Diabetes

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes 18-78 years of age Taking stable dose of metformin immediate release (IR) or XR ≥850 mg and ≤1500 mg as monotherapy for at least 8 weeks prior to screening Glycosylated hemoglobin A1C (A1C) 7.5-11.5% at screening Fasting C-peptide: ≥1.0 ng/mL FPG≥126 mg/dl obtained at the Day -7 visit Body mass index (BMI): ≤ 40kg/m² A1C ≥ 7.0% and ≤ 11.0% obtained at the Day -7 visit for randomization Exclusion Criteria: Women of childbearing potential unable or unwilling to use acceptable birth control Women who are pregnant or breastfeeding Significant cardiovascular history Active liver disease Renal impairment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 78 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saxagliptin + Metformin XR + matching Metformin XR placebo<br>(Saxagliptin 5 mg plus Metformin XR 1500 plus matching Metformin XR 500 mg placebo) | Drug: Saxagliptin<br>* Tablets, Oral, 5 mg, once daily, 4 weeks<br>* Other names: Onglyza;Drug: Metformin XR<br>* Tablets, Oral, 1500 mg, once daily, 4 weeks<br>* Other names: Glucophage XR®;Drug: Placebo matching Metformin XR<br>* Tablets, Oral, 0 mg, once daily, 4 weeks<br>|
| Active Comparator: Metformin XR + Metformin XR + matching Saxagliptin placebo<br>(Metformin XR 500 mg plus Metformin XR 1500 mg plus matching Saxagliptin 5 mg placebo) | Drug: Metformin XR<br>* Tablets, Oral, 1500 mg, once daily, 4 weeks<br>* Other names: Glucophage XR®;Drug: Metformin XR<br>* Tablets, Oral, 500 mg, once daily, 4 weeks<br>* Other names: Glucophage XR®;Drug: Placebo matching Saxagliptin<br>* Tablets, Oral, 0 mg, once daily, 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4 | Adjusted mean change from baseline in MWG achieved with saxagliptin 5 mg plus metformin XR versus placebo plus metformin XR at Week 24. MWG was calculated as the area under the curve (AUC) for the full 24 hours expressed as average mg/dL. Glucose measurements were collected 30 minutes before and just prior to each meal (0 minutes) and 30, 60, 120, and 180 minutes after each meal (with 1 additional measurement at 240 minutes after the evening meal), midnight, 3 AM, and at end-of-domicile visit 24 hours after the first measurement. Mean change from baseline was adjusted for baseline value. | Baseline, Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 4 in 2-hour Postprandial Glucose (PPG) (2 Hours After the Evening Meal) | Adjusted mean change from baseline in 2-hour postprandial (after mealtime) plasma glucose two hours after start of the evening meal during 24-hour domicile visits evaluated both at pre-randomization (baseline) and at Week 4. Mean change from baseline was adjusted for baseline value. | Baseline, Week 4 | 
| Change From Baseline Fasting Plasma Glucose (FPG) at Week 4, Obtained Immediately Before the Morning Meal | FPG measurements were done at baseline, day 14 and 28. At baseline and day 28, the FPG value=plasma glucose value collected 30 minutes prior to the morning meal during the domicile visit. | Baseline, Week 4 |