Efficacy and Safety Study of Saxagliptin + Metformin Immediate Release (IR) Versus Metformin IR Alone in Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study is to compare the reduction in hemoglobin A1C (A1C) for participants taking saxagliptin in combination with metformin immediate release (IR) versus metformin IR alone.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Trial to Evaluate the Efficacy and Safety of 2.5 mg Saxagliptin, Twice Daily, in Combination With Metformin IR in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin IR Alone

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Saxagliptin plus metformin IR
* Drug: Placebo plus metformin IR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes 18-78 years of age Taking stable twice daily (BID) dosing of metformin IR (at least 1500 mg) for at least 8 weeks A1C: 7-10% C-peptide: ≥ 0.8 ng/mL Body mass index (BMI): ≤45 kg/m^2 Exclusion Criteria: Women of childbearing potential unable or unwilling to use acceptable birth control Women who are pregnant or breastfeeding Fasting plasma glucose (FPG) >270 mg/dL Significant cardiovascular history Symptoms of poorly controlled diabetes History of diabetic ketoacidosis or hyperosmolar nonketotic coma Insulin therapy within one year of screening Cardiovascular even within the prior 6 months New York Heart Association Stage III/IV congestive heart failure and/or known left ventricular ejection fraction <=40% Significant history of renal or hepatic disease History of a psychiatric disorder, alcohol or drug abuse within the previous year Treatment with potent CYP3A4 inhibitors or inducers Immunocompromised participants Active liver disease or clinically significant abnormal hepatic, renal , endocrine, metabolic, or hematological screening tests

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 |
| --- | --- |
| Active Comparator: Saxagliptin plus metformin IR<br> | Drug: Saxagliptin plus metformin IR<br>* Tablets, Oral, 2.5 mg, Twice daily, 12 weeks<br>* Other names: Onglyza;|
| Placebo Comparator: Placebo plus metformin IR<br> | Drug: Placebo plus metformin IR<br>* Tablets, Oral, Placebo, Twice daily, 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Hemoglobin A1C (A1c) and Change From Baseline to Week 12 | Mean change was adjusted for baseline. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Baseline and Change From Baseline in Fasting Plasma Glucose (FPG) | Mean change was adjusted for baseline. | Baseline, Week 12 | 
| Percentage of Participants Achieving a Therapeutic Glycemic Response (A1C < 7.0%) at Week 12 | Adjusted for baseline. Calculated using the method by Zhang et al. (Zhang M, Tsiatis A, Davidian M. Improving efficiency of inference in randomized clinical trials using auxiliary covariates. Biometrics. Published online on January 11, 2008; Digital Object Identifier: 10.1111/j.1541-0420.2007.00976.x.) | Week 12 | 
| Percentage of Participants Achieving a Therapeutic Glycemic Response (A1C <= 6.5%) at Week 12 | Adjusted for baseline. Calculated using the method by Zhang et al. (Zhang M, Tsiatis A, Davidian M. Improving efficiency of inference in randomized clinical trials using auxiliary covariates. Biometrics. Published online on January 11, 2008; Digital Object Identifier: 10.1111/j.1541-0420.2007.00976.x.) | Week 12 |