Glycemic Efficacy and Renal Safety Study of Dapagliflozin in Subjects With Type 2 Diabetes Mellitus and Moderate Renal Impairment

Study Overview
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Brief Summary
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The purpose of this study is to determine whether dapagliflozin is effective in the treatment of type 2 diabetes in subjects with poor blood sugar control and moderate renal impairment

Detailed Description
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All eligible subjects will receive a single-blind placebo medication during a 1-week lead-in period prior to randomization. All arms may include the addition of open label medication described (as needed for rescue based on protocol specific criteria). Rescue medication is defined as the addition of an approved, appropriate antihyperglycemic agent, except metformin, used according to conventional standards of care, to treat hyperglycemia, which may therefore allow the subject to remain in the trial

Official Title
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A Multicenter, Double-Blind, Placebo-Controlled, Parallel Group, Randomized, Phase 2/3 Trial to Evaluate the Glycemic Efficacy, Renal Safety, Pharmacokinetics, and Pharmacodynamics of Dapagliflozin in Subjects With Type 2 Diabetes Mellitus and Moderate Renal Impairment Who Have Inadequate Glycemic Control

Conditions
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Diabetes Mellitus, Type 2

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, ≥18 years old, with type 2 diabetes and with inadequate glycemic control Clinical diagnosis of moderate renal impairment Exclusion Criteria: AST and /or ALT > 3.0 times the upper limit of normal Serum total bilirubin > 1.5 times ULN Symptoms of severely uncontrolled diabetes Currently unstable or serious cardiovascular, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dapagliflozin (10 mg)<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 10 mg, Once Daily, 104 weeks<br>* Other names: BMS-512148;|
| Active Comparator: Dapagliflozin (5 mg)<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 5 mg, Once Daily, 104 weeks<br>* Other names: BMS-512148;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Tablets, Oral, 0 mg, Once Daily, 104 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 (Last Observation Carried Forward [LOCF] | HbA1c was measured as percent of hemoglobin by a central laboratory. 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. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 in the double-blind period. | From Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF]) | Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. 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. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 in the double-blind period | From Baseline to Week 24 | 
| Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF]) | Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. 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. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period. | From Baseline to Week 24 |