A Study to Evaluate the Effect of Dapagliflozin on Blood Glucose Level and Renal Safety in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this clinical research study is to determine whether dapagliflozin can improve (decrease) blood glucose values in patients with Type 2 diabetes and moderate renal impairment.This study will be conducted at approximately 100 centres from countries across North America and European regions. It is planned to randomize a total of 302 patients.

Official Title
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A Multicenter, Double-Blind, Placebo-Controlled, Parallel Group, Randomized, Phase III Study to Evaluate the Glycemic Efficacy and Renal Safety of Dapagliflozin in Patients With Type 2 Diabetes Mellitus and Moderate Renal Impairment (CKD 3A) Who Have Inadequate Glycemic Control.

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin 10 mg
* Drug: Matching Placebo for Dapagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male aged ≥18 years and <75 years. History of T2DM for more than 12 months. Inadequate glycemic control, defined as HbA1c ≥7.0% and ≤11% Stable anti-diabetic treatment regimen Renal impairment: CKD 3A Exclusion Criteria: Women of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period. History of diabetic ketoacidosis or hyperosmolar nonketotic coma. Severe uncontrolled hypertension defined as SBP ≥180 mmHg and/or Diastolic Blood Pressure (DBP) ≥110 mmHg Any of the following Cardiovascular (CV)/Vascular Diseases within 3 months of prior to signing the consent at visit 1: Myocardial infarction, Cardiac surgery or revascularization(CABG/PTCA), Unstable angina, Unstable heart failure (HF), HF New York Heart Association (NYHA) Class IV,Transient ischemic attack (TIA) or significant cerebrovascular disease, Unstable or previously undiagnosed arrhythmia. History of any biopsy or imaging verifying intercurrent kidney disease (such as glomerular nephritis or sign of renal artery stenosis) other than diabetic nephropathy or diabetic nephropathy with nephrosclerosis. Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency. Ongoing treatment with any SGLT2-inhibitor, GLP-1 analogue, or rapid/short acting insulins at screening. Participation in another clinical study with an Investigational Product (IP) during the last 30 days prior to signing the consent at visit 1.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>10 mg Tablets, Oral, Once daily, 24 weeks | Drug: Dapagliflozin 10 mg<br>* Tablets administered orally once daily for 24 weeks. Randomization will be stratified by pre-enrolment anti-hyperglycemic therapy<br>* Other names: Farxiga™;|
| Placebo Comparator: Placebo<br>Matching placebo to Dapagliflozin 10 mg tablet. Oral, Once daily, 24 weeks | Drug: Matching Placebo for Dapagliflozin<br>* Matching Placebo for Dapagliflozin tablets administered orally once daily for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 | To compare the mean change from baseline in HbA1c between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m^2). The number analyzed (142 dapaglifozin, 134 placebo) represents the number with change from baseline available at Week 24. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24. | To compare the mean percent change from baseline in total body weight between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m^2). The number analyzed represents the number with change from baseline available at Week 24. | Baseline, Week 24 | 
| Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24. | To compare the mean change from baseline in FPG between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m^2). The number analyzed represents the number with change from baseline available at Week 24. | Baseline, Week 24 | 
| Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24. | To compare the mean change from baseline in seated systolic blood pressure (SBP) between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m^2). The number analyzed represents the number with change from baseline available at Week 24. | Baseline, Week 24 |