The Pharmacodynamics, Pharmacokinetics, and Safety of Dapagliflozin in Type 2 Diabetic Subjects With Mild, Moderate, and Severe Renal Impairment
Overview
- Phase
- Phase 1
- Intervention
- Dapagliflozin
- Conditions
- Diabetes Mellitus, Type 2
- Sponsor
- AstraZeneca
- Enrollment
- 40
- Locations
- 4
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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
Investigators
Eligibility Criteria
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
Exclusion Criteria
- Not provided
Arms & Interventions
Arm 1
50 mg single dose
Intervention: Dapagliflozin
Arm 2
20 mg up to 7 days
Intervention: Dapagliflozin
Outcomes
Primary Outcomes
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
Time Frame: on Days -1, 1, 4 and 10
Blood and urine PK samples
Time Frame: on Days 1, 4, 10
Blood samples for serum glucose and creatinine will be collected
Time Frame: on Days -1, 1, 4 and 10 at selected timepoints
Iohexol PK blood & urine samples for GFR assessment
Time Frame: on Day -12 to -5
Secondary Outcomes
- ECGs(scr, Days,-1, 4, 7, discharge)
- AEs, vital signs(scr, Days -1, 1, 4-11, discharge)
- physical exams(scr, Days -12 to -5, -1, 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)