Efficacy and Safety of Dapagliflozin in Combination With Glimepiride (a Sulphonylurea) in Type 2 Diabetes Patients

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

Official Title
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A 24-Week,Int.,Rand.,Double-blind,Parallel-group,Multi-centre, Plac.-Controlled Phase III Study With a 24-Wk Ext.Per.to Eval.the Efficacy and Safety of Dapagliflozin in Comb.With Glimepiride (a Sulphonylurea) in Subjects With Type2 Diab.Who Have Inadeq. Glycaemic Control on Glimepiride Therapy Alone

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: dapagliflozin
* Drug: Glimepiride
* Drug: metformin hydrochloride
* Drug: pioglitazone hydrochloride
* Drug: Rosiglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetes Treatment with a stable sulphonylurea monotherapy dose that is at least half the maximal recommended dose for a minimum of 8 weeks prior to study Inadequate glycaemic control, defined as A1C ≥ 7.0 % and ≤ 10% Exclusion Criteria: Type 1 Diabetes Hepatic (liver) impairment Renal (kidney) failure or dysfunction

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: 1<br>dapagliflozin 2.5mg + Glimepiride | Drug: dapagliflozin<br>* tablet oral 2.5, 5, or 10 mg total daily dose once daily 48 weeks<br>Drug: Glimepiride<br>* tablet oral 2.5, 5, or 10 mg total daily dose once daily 48 weeks<br>* Other names: Amaryl;Drug: metformin hydrochloride<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Glucophage;Drug: pioglitazone hydrochloride<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Actos;Drug: Rosiglitazone<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Avandia;|
| Experimental: 2<br>dapagliflozin 5mg + Glimepiride | Drug: dapagliflozin<br>* tablet oral 2.5, 5, or 10 mg total daily dose once daily 48 weeks<br>Drug: Glimepiride<br>* tablet oral 2.5, 5, or 10 mg total daily dose once daily 48 weeks<br>* Other names: Amaryl;Drug: metformin hydrochloride<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Glucophage;Drug: pioglitazone hydrochloride<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Actos;Drug: Rosiglitazone<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Avandia;|
| Experimental: 3<br>dapagliflozin 10mg + Glimepiride | Drug: dapagliflozin<br>* tablet oral 2.5, 5, or 10 mg total daily dose once daily 48 weeks<br>Drug: Glimepiride<br>* tablet oral 2.5, 5, or 10 mg total daily dose once daily 48 weeks<br>* Other names: Amaryl;Drug: metformin hydrochloride<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Glucophage;Drug: pioglitazone hydrochloride<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Actos;Drug: Rosiglitazone<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Avandia;|
| Placebo Comparator: 4<br>Placebo + Glimepiride | Drug: Glimepiride<br>* tablet oral 2.5, 5, or 10 mg total daily dose once daily 48 weeks<br>* Other names: Amaryl;Drug: metformin hydrochloride<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Glucophage;Drug: pioglitazone hydrochloride<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Actos;Drug: Rosiglitazone<br>* rescue medication oral dosing in accordance with the manufacturer's recommendations and clinical practice<br>* Other names: Avandia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change in HbA1c Levels | To assess the efficacy of dapagliflozin compared to placebo as add-on therapy to glimepiride in improving glycemic control in participants with type 2 diabetes, as determined by the change in HbA1C levels from baseline to the end of the 24-week double-blind treatment period. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change in Body Weight | To show that dapagliflozin plus glimepiride results in greater reduction in body weight or less weight gain after 24 weeks of treatment when compared to placebo plus glimepiride. | Baseline to Week 24 | 
| Adjusted Mean Change in 2-h Post-challenge Plasma Glucose Rise | To show that dapagliflozin plus glimepiride results in greater reductions in the 2-h post-challenge plasma glucose rise as a response to an oral glucose tolerance test (OGTT) from baseline to Week 24. | Baseline to Week 24 | 
| Proportion of Participants Achieving Glycemic Response Defined as HbA1c <7% | To show that dapagliflozin plus glimepiride results in a larger proportion of participants achieving a therapeutic glycemic response, defined as HbA1c < 7% after 24 weeks of treatment, compared to placebo plus glimepiride. | At Week 24 | 
| Adjusted Mean Change in Body Weight for Participants With Baseline Body Mass Index (BMI)≥27 kg/m2 | To show that dapagliflozin plus glimepiride results in greater reductions in body weight or less weight gain in participants with baseline BMI ≥27 kg/m2 after 24 weeks of treatment when compared to placebo plus glimepiride. | Baseline to Week 24 | 
| Adjusted Mean Change in Fasting Plasma Glucose (FPG) | To show that dapagliflozin plus glimepiride leads to greater reductions in FPG after 24 weeks of treatment compared to placebo plus glimepiride. | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dapagliflozin, efficacy, safety, sulphonylurea, Type 2 diabetes