Efficacy and Safety of Dapagliflozin and Dapagliflozin Plus Saxagliptin in Combination With Metformin in Type 2 Diabetes Patients Compared With Sulphonylurea

Study Overview
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Brief Summary
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This study is being carried out to see if dapagliflozin and dapagliflozin plus saxagliptin as an addition to metformin is effective and safe in treating patients with type 2 diabetes when compared to glimepiride (sulphonylurea) as an addition to metformin treatment.

Official Title
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A 52-Week, Multi-Centre, Randomised, Parallel-Group, Double-Blind, Active Controlled, Phase IV Study to Evaluate the Safety and Efficacy of Dapagliflozin or Dapagliflozin Plus Saxagliptin Compared With Sulphonylurea All Given as Add-on Therapy to Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Monotherapy

Conditions
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Inadequate Glycaemic Control, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Saxagliptin
* Drug: Glimepiride
* Drug: Placebo for dapagliflozin
* Drug: Placebo for saxagliptin
* Drug: Placebo for glimepiride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Main Inclusion Criteria: Is male or female and ≥18 and <75 years old at time of informed consent. Has a HbA1c of ≥7.5% and ≤10.5% based on central laboratory results from Visit 1, with individual need for therapy escalation. Currently treated with a stable maximum tolarated dose (MTD) (≥1500 mg/day) of metformin therapy for at least 8 weeks prior to Enrolment visit. Has a BMI of ≤45 kg/m2 at Enrolment visit. Has a C-peptide laboratory value of ≥1.0 ng/mL (0.33 nmol/L; 333.3 pmol/L) based on central laboratory results from Visit 1. Main, Exclusion Criteria: Clinically diagnosed with Type I diabetes, known diagnosis of maturity onset diabetes of the young (MODY), or secondary diabetes mellitus or known presence of glutamate decarboxylase 65 (GAD65) antibodies. Patients who, in the judgment of the Investigator, may be at risk for dehydration or volume depletion that may affect the patient's safety and/or the interpretation of efficacy or safety data. Clinically significant cardiovascular disease or procedure within 3 months prior to Enrolment or expected to require coronary revascularization procedure during the course of the study. Concomitant treatment with loop diuretics

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dapagliflozin+metformin<br>Dapagliflozin + saxagliptin placebo + glimepiride placebo + metformin | Drug: Dapagliflozin<br>* 10 mg, orally Green, plain, diamond-shaped, film-coated tablet<br>* Other names: Forxiga;Drug: Placebo for saxagliptin<br>* Does not contain active ingredient, orally Plain, yellow, biconvex, round, film-coated tablet<br>Drug: Placebo for glimepiride<br>* Does not contain active ingredient, orally. Opaque gray capsule<br>|
| Active Comparator: Dapagliflozin+saxagliptin+metformin<br>Dapagliflozin + saxagliptin + glimepiride placebo+ metformin | Drug: Dapagliflozin<br>* 10 mg, orally Green, plain, diamond-shaped, film-coated tablet<br>* Other names: Forxiga;Drug: Saxagliptin<br>* 5 mg, orally Plain, yellow, biconvex, round, film-coated tablet<br>* Other names: Onglyza™;Drug: Placebo for glimepiride<br>* Does not contain active ingredient, orally. Opaque gray capsule<br>|
| Active Comparator: Glimepiride+metformin<br>Glimepiride + dapagliflozin placebo + saxagliptin placebo + metformin | Drug: Glimepiride<br>* 1, 2, or 4 mg, orally Opaque gray capsule<br>* Other names: Amaryl;Drug: Placebo for dapagliflozin<br>* Does not contain active ingredient, orally Green, plain, diamond-shaped, film-coated tablet<br>Drug: Placebo for saxagliptin<br>* Does not contain active ingredient, orally Plain, yellow, biconvex, round, film-coated tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Haemoglobin A1c (HbA1c) From Baseline to Week 52 | Change in HbA1c from baseline (week 0) to week 52. | Baseline, week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients With at Least One Episode of Confirmed Hypoglycaemia | Percentage of patients reporting at least 1 episode of hypoglycaemia (symptomatic + blood glucose <=50 mg/dL) during the double-blind treatment period | Up to Week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis | 
| Change in Total Body Weight From Baseline at Week 52 | Change in body weight from baseline (week 0) to week 52 | Baseline, week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis | 
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52 | Change in FPG from baseline (week 0) to week 52 | Baseline, week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis | 
| Time to Rescue | The time to rescue (from first dose date after randomisation to start of rescue medication or discontinuation due to lack of glycaemic control) during the 52 week double blind treatment period | Over the 52 week treatment period | 
| Number of Patients Rescued | Number (%) of patients rescued. | Over the 52 week treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inadequate glycaemic control, Diabetes Mellitus Type 2,, metformin,, saxagliptin,, dapagliflozin,, glimepiride,