Effects of Dapagliflozin on Kidney Function (Glomerular Filtration Rate) in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of dapagliflozin on kidney function, as assessed by glomerular filtration rate.

Official Title
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An Exploratory Phase 2 Study to Assess the Effect of Dapagliflozin on Glomerular Filtration Rate (GFR) in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic and Blood Pressure (BP) Control

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebo
* Drug: Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes and inadequate glycemic control, defined as A1C ≥ 6.6 and ≤ 9.5% Stable dose of metformin AND/OR a sulfonylurea, for at least 4 weeks prior to the enrollment visit Inadequate blood pressure (BP) control, defined as systolic BP (SBP) ≥ 130 and < 165 mmHg, AND/OR diastolic BP (DBP) ≥ 80 and < 105 mmHg C-peptide ≥ 0.8 ng/mL Estimated GFR by the Modification of Diet in Renal Disease (MDRD) formula > 60 mL/min/1.73m² and < 150 mL/min/1.73m² Urine albumin:creatinine ratio (UACR) < 300 mg/g BMI ≤ 45.0 kg/m2 Exclusion Criteria: Administration of diuretics or other medication approved for the treatment of hypertension (with the exception of either ACEI or ARB), at any dose during the 12 weeks prior to the enrollment visit History of adverse reaction to radio-contrast dye Allergy or contraindication to use of thiazide diuretics Aspartate Aminotransferase (AST) > 3X Upper limit of normal (ULN) Alanine aminotransferase (ALT) > 3X ULN Serum Total Bilirubin > 1.5X ULN Serum Creatinine (Scr) ≥ 1.50 mg/dL (133 μmol/l) for men; SCr ≥ 1.40 mg/dL (124 μmol/l) for women Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncologic, endocrine, psychiatric, or rheumatic diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 10 mg, once daily, 12 weeks<br>* Other names: BMS-512148;Drug: Placebo<br>* Tablets, Oral, 0 mg, once daily, 12 weeks<br>|
| Active Comparator: Hydrochlorothiazide<br> | Drug: Hydrochlorothiazide<br>* Tablets, Oral, 25 mg, once daily, 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Percent Change From Baseline in Glomerular Filtration Rate (GFR) at Week 12 (Modified Last Observation Carried Forward [MLOCF]) | Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. If no Week 12 measurement was available, the last available post-baseline measurement obtained on or after Day 23 was used regardless of rescue medication. Measurements were obtained during radomization visit, and Week 12 in the double-blind period by a central laboratory. | From Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in 24-Hour Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF]) | Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during lead-in, and Week 12 in the double-blind period. | From Baseline to Week 12 | 
| Adjusted Mean Change From Baseline in Daytime (0900 to 2100 Hours) Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF]) | Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during lead-in, and Week 12 in the double-blind period. | From Baseline to Week 12 | 
| Adjusted Mean Change From Baseline in Nighttime (0100 to 0600 Hours) Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF]) | Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during lead-in, and Week 12 in the double-blind period. | From Baseline to Week 12 |