Safety and Efficacy Study of Subjects That Are Taking Saxagliptin Added Onto Metformin XR Compared to Subjects Taking Metformin XR Alone

Study Overview
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Brief Summary
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This protocol will compare 24 hour glucose control for subject taking saxagliptin and metformin extended release (XR) versus metformin XR alone

Official Title
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A 4-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial To Evaluate The Efficacy And Safety Of Saxagliptin In Comparison To Placebo As Add On Treatment To Metformin XR In Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet And Exercise And A Stable Dose Of Metformin ≥1500 mg/Day

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Saxagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18- and ≤77-years-old Type 2 diabetes Taking metformin immediate release (IR) or XR ≥1500 mg for at least 8 weeks as monotherapy Glycosylated hemoglobin (A1C) ≥7% and ≤10% Body mass index (BMI) ≤40 kg/m2 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: 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 5 mg + Metformin<br> | Drug: Saxagliptin<br>* Tablets, Oral, 5mg, once daily, 4 weeks<br>* Other names: BMS-477118;|
| Placebo Comparator: Placebo + Metformin<br> | Drug: Placebo<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 in 4-Hour Mean Weighted Postprandial Plasma Glucose at Week 4 | Adjusted mean change from baseline in 4-hour mean weighted postprandial (after mealtime) plasma glucose after 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 in 2-Hour Postprandial Plasma Glucose After the Evening Meal at Week 4 | Adjusted mean change from baseline in 2-hour postprandial plasma glucose after 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 in Mean Daily Glucose at Week 4 | Adjusted mean change from baseline in daily glucose at Week 4. Mean daily glucose was calculated based on finger stick glucose measurements collected by the subjects at home in a 3-day period, prior to collection of the 24-hour blood samples at baseline and Week 4. Mean change from baseline was adjusted for baseline value. | Baseline, Week 4 | 
| Change From Baseline in 2-Day Average Fasting Plasma Glucose (FPG) at Week 4 | Adjusted mean change from baseline in 2-day average of FPG at baseline and Week 4. Baseline value=the average of the values at Day -2 and Day 1. Week 4 measurement=average of Day 26 and Day 28 value during the double blind period. At pre-randomization and Day 28 the FPG value was the plasma glucose value collected 30 minutes prior to the morning meal during domicile visits. Mean change from baseline was adjusted for baseline value. | Baseline, Week 4 |