Saxagliptin Triple Oral Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the addition of saxagliptin to a patient's combination treatment of metformin and sulfonylurea for a 24 week period will provide better control of the patient's type 2 diabetes and will be well tolerated.

Detailed Description
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A 24-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase IIIb Study to Evaluate Efficacy and Safety of Saxagliptin in Combination with Metformin and Sulfonylurea in Subjects with Type 2 Diabetes who have Inadequate Glycaemic Control with Combination of Metformin and Sulfonylurea

Official Title
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A 24-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase IIIb Study to Evaluate Efficacy and Safety of Saxagliptin in Combination With Metformin and Sulfonylurea in Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control With Combination of Metformin and Sulfonylurea

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: Written Informed Consent Males or females with type 2 diabetes with inadequate glycaemic control (HbA1c > or = 7% and < or = 10%) despite being on combination of metformin and sulfonylurea for at least 8 weeks prior to Visit 1 BMI < or = 40 kg/m2 Exclusion Criteria: Symptoms of poorly controlled diabetes including but not limited to marked polyuria and marked polydipsia with > 10% weight loss in 3 months prior to entry, or other signs and symptoms History of diabetic ketoacidosis or hyperosmolar non-ketotic coma Current or prior use within 3 months of Visit 1 of insulin, DDP4 inhibitor, GLP-1 analogues, and/or other oral anti-diabetic agents (other than metformin or sulfonylurea) Treatment with CYP3A4 inducers and/or potent CYP3A4/5 inhibitor Estimated CrCl < 60 ml/min at Visit 2 CHF (NYHA class III or IV) and/or LVEF <40% Active liver disease and/or significant abnormal liver function defined as AST and/or ALT > 3 x ULN and/or bilirubin > 2.0 mg/dL at Visit 2. Creatine kinase > or = 10 x ULN at Visit 2

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 5 mg once daily<br> | Drug: Saxagliptin<br>* 5 mg tablet once daily for 24 weeks to be taken orally<br>* Other names: Onglyza;|
| Placebo Comparator: Placebo once daily<br> | Drug: Placebo<br>* tablet once daily for 24 weeks to be taken orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline to Week 24, Last Observation Carried Forward (LOCF) | Adjusted Mean Change in HbA1c from baseline to Week 24 using analysis of covariance model | From Baseline to Week 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 2-hour Postprandial Glucose (PPG) From Baseline to Week 24, Last Observation Carried Forward (LOCF) Measured as [mg/dL] | Adjusted Mean Change in 2-hour PPG from baseline to Week 24 using analysis of covariance model | From Baseline to Week 24 | 
| Change in 2-hour Postprandial Glucose (PPG) From Baseline to Week 24, Last Observation Carried Forward (LOCF) Measured as [mmol/L] | Adjusted Mean Change in 2-hour PPG from baseline to Week 24 using analysis of covariance model | From Baseline to Week 24 | 
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24, Last Observation Carried Forward (LOCF) Measured as [mg/dL] | Adjusted Mean Change in fasting plasma glucose from baseline to Week 24 using analysis of covariance | From Baseline to Week 24 | 
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24, Last Observation Carried Forward (LOCF) Measured as [mmol/L] | Adjusted Mean Change in FPG from baseline to Week 24 using analysis of covariance model | From Baseline to Week 24 | 
| Proportion of Participants Achieving a Therapeutic Response: HbA1c Less Than 7% at Week 24, Last Observation Carried Forward (LOCF) | Number of participants achieving a glycaemic response defined as HbA1c less than 7% at Week 24 | From Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes, Inadequate Glycaemic Control, Saxagliptin, Metformin, Sulfonylurea, Triple Oral Therapy