Renal Impairment in Type 2 Diabetic Subjects

Study Overview
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Brief Summary
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The purpose of the study is to assess the effect of dapagliflozin on renal glucose clearance in type 2 diabetic subjects with mild, moderate, and severe renal impairment compared to type 2 diabetic and healthy subjects with normal renal function

Official Title
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The Pharmacodynamics, Pharmacokinetics, and Safety of Dapagliflozin in Type 2 Diabetic Subjects With Mild, Moderate, and Severe Renal Impairment

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Dapagliflozin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects in the following groups: Group A: Healthy Subjects with Normal Renal Function (CLcr > 80 mL/min) Group B: Diabetic Subjects with Normal Renal Function (CLcr > 80 mL/min) Group C: Diabetic Subjects with Mild Renal Impairment (CLcr > 50 - ≤80 mL/min) Group D: Diabetic Subjects with Moderate Renal Impairment (CLcr ≥ 30 - ≤50 mL/min) Group E: Diabetic Subjects with Severe Renal Impairment (CLcr < 30 mL/min) (and not receiving dialysis) Men and WOCBP, ages 18 to 79 years old Standard Exclusion Criteria, plus: History of diabetic ketoacidosis HbA*1c > 10% Serum albumin < 2.0 gm/dL Potassium < 3.0 or > 6.0 mEq/L

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>50 mg single dose | Drug: Dapagliflozin<br>* Tablets, Oral, once daily<br>|
| Experimental: Arm 2<br>20 mg up to 7 days | Drug: Dapagliflozin<br>* Tablets, Oral, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine will be collected over a 24 h period for determination of renal glucose clearance, total protein, and measurement of total glucose excreted in urine |  | on Days -1, 1, 4 and 10 | 
| Blood samples for serum glucose and creatinine will be collected |  | on Days -1, 1, 4 and 10 at selected timepoints | 
| Blood and urine PK samples |  | on Days 1, 4, 10 | 
| Iohexol PK blood & urine samples for GFR assessment |  | on Day -12 to -5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs, vital signs |  | scr, Days -1, 1, 4-11, discharge | 
| physical exams |  | scr, Days -12 to -5, -1, discharge | 
| ECGs |  | scr, Days,-1, 4, 7, discharge | 
| clinical labs |  | scr, Day -1, 1, 4, 6, 8, 10, discharge | 
| The following urine/serum safety parameters will be assessed: sodium, potassium, magnesium, phosphorus, calcium, and total protein (urine only) |  | on Days -1, 1, 4 and 10 |