52-week add-on to Metformin Comparison of Saxagliptin and Sulphonylurea, With a 52-week Extension Period

Study Overview
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Brief Summary
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Saxagliptin is a new investigational medication being developed for treatment of type 2 diabetes. This study is designed to assess the efficacy and tolerability of saxagliptin in addition to metformin and compare to sulphonylurea in addition with metformin.

Official Title
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A 52-Week International, Multi-centre, Randomized, Parallel-group, Double-blind, Active-controlled, Phase III Study With a 52-Week Extension Period to Evaluate the Safety and Efficacy of Saxagliptin in Combination With Metformin Compared With Sulphonylurea in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Therapy Alone.

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Metformin
* Drug: Sulphonylurea
* Drug: Saxagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 2 diabetes, Treatment with metformin alone on stable doses of 1500 mg or higher per day for at least 8 weeks prior to Visit 1, HbA1c >6.5% and ≤10.0% Exclusion Criteria: Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic coma, Insulin therapy within one year of enrolment (with the exception of insulin therapy during a hospitalization or use in gestational diabetes)

Ages Eligible for Study
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Minimum Age: 18 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<br> | Drug: Metformin<br>* open-label metformin<br>Drug: Saxagliptin<br>* Saxagliptin 5 mg tablets<br>* Other names: Onglyza;|
| Experimental: Glipizide<br> | Drug: Metformin<br>* open-label metformin<br>Drug: Sulphonylurea<br>* Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1c (HbA1c) Change From Baseline to Week 52 | Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 52 (Per Protocol Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 52 value minus the baseline value. | Baseline to 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 52 Weeks | Proportion of participants reporting at least one episode of any hypoglycaemic event for saxagliptin added on to metformin versus glipizide added on to metformin over 52 weeks (Safety Analysis Set) | From Baseline to Week 52 | 
| Body Weight Change From Baseline to Week 52 | Adjusted mean change from baseline in Body Weight achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 52 (Safety Analysis Set). Body Weight is a continuous measure, the change from baseline for each participant is calculated as the Week 52 (LOCF) value minus the baseline value. | Baseline, Week 52 (Last Observation Carried Forward) | 
| Mean Slope of the Regressions of Change From Week 24 to Week 52 in HbA1c | Mean slopes of regression of change from Week 24 to Week 52 in HbA1c for saxagliptin added on to metformin versus glipizide added on to metformin (Per Protocol Analysis Set) achieved by fitting a mixed model with subject specific slopes for the time effect (weeks on randomized treatment was utilized). This analysis gives an assessment of the durability of the HbA1c effect. | Week 24 to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DPP-4 Inhibitors, HbA1c, incretins