Efficacy and Safety in Patients With Type 2 Diabetes Mellitus and Cardiovascular Disease

Study Overview
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Brief Summary
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This study is carried out to assess whether dapagliflozin improves glycemic control, decreases fasting plasma glucose levels, body weight and blood pressure when added to patient's existing medications and how it compares with their usual treatment without added dapagliflozin. Safety data will be collected and analysed to confirm that treatment with dapagliflozin is safe and well tolerated in patients who have diabetes and cardiovascular disease

Official Title
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A 24-week, Multicentre, Randomised, Double-blind,Age-stratified, Placebo Controlled Phase III Study With an 80-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin 10 mg Once Daily in Patients With T2DM and Cardiovascular Disease, Who Exhibit Inadequate Glycaemic Control on Usual Care

Conditions
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Type 2 Diabetes Mellitus, Cardiovascular Disease, Inadequate Glycaemic Control

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus. Cardiovascular disease Uninterrupted anti-diabetic treatment for at least 8 weeks before enrolment Exclusion Criteria: Patients with type 1 diabetes or diabetes insipidus Patients with 3 or more oral anti-hyperglycaemic drugs with or without insulin and/or poorly controlled diabetes Any clinically significant illness, which would compromise the patient's safety and their participation in the study

Ages Eligible for Study
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Minimum Age: 45 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 10 mg tablet | Drug: Dapagliflozin<br>* 10 mg tablet, oral, once daily, 24- week treatment and 80-week extension period<br>|
| Placebo Comparator: 2<br>matching placebo tablet | Drug: Placebo<br>* matching placebo tablet, oral, once daily, 24- week treatment and 80-week extension period<br>|

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 compare the glycemic efficacy of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease, measured as the mean change in HbA1c from baseline to week 24. | Baseline to Week 24 | 
| Proportion of Responders Meeting All Criteria of a 3-item Endpoint of Clinical Benefit | To compare the clinical benefit of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease at week 24, measured as the proportion of responders for a 3-item endpoint of clinical benefit, defined as an absolute drop of 0.5% or more from baseline HbA1c, and a relative drop of 3% or more from baseline for total body weight, and an absolute drop of 3 mmHg or more from baseline in seated systolic blood pressure. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Percent Change in Body Weight | To compare the mean percent change in body weight from baseline to week 24 between dapagliflozin 10 mg versus placebo. | Baseline to Week 24 | 
| Proportion of Participants With a Reduction From Baseline of 5% or More in Body Weight in Participants With Baseline BMI ≥27 kg/m² | To compare the proportion of participants with BMI baseline ≥27 kg/m2 with a reduction from baseline of 5% or more in body weight with dapagliflozin 10 mg versus placebo from baseline to week 24. Least Squares Mean represents the percent of participants adjusted for baseline body weight and age stratum. | Baseline to Week 24 | 
| Adjusted Mean Change in Systolic Blood Pressure at Week 8 (LOCF) | To compare the mean change in seated systolic blood pressure from baseline to week 8 between dapagliflozin 10 mg versus placebo. | Baseline to Week 8 | 
| Adjusted Mean Change in Seated Systolic Blood Pressure at Week 24 (LOCF) | To compare the mean change in seated systolic blood pressure from baseline to week 24 between dapagliflozin 10 mg versus placebo. | Baseline to Week 24 | 
| Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) at Week 8 (LOCF) in Participants With Baseline SBP>=130 mmHg | To compare the mean change in seated systolic blood pressure (SBP) in participants with baseline seated SBP ≥130 mmHg achieved with dapagliflozin versus placebo from baseline to week 8. | Baseline to Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dapagliflozin, diabetes, cardiovascular disease