Characterization of the Kinetics of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus (T2DM)

Study Overview
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Brief Summary
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It is anticipated that 7 days of oral administration of 10 mg dapagliflozin will reduce the renal glucose reabsorption similarly in healthy subjects and in subjects with T2DM.

Official Title
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Characterization of the Kinetics of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for T2DM Diagnosis of T2DM Must be on one of the following therapies: diet therapy alone, diet plus a sulfonylurea, diet plus metformin, or diet plus sulfonylurea plus metformin Subjects taking metformin, and/or sulfonylurea must be on a stable dose for at least 2 months prior to study drug administration Must have a fasting plasma glucose concentration ≤ 200 mg/dl, and HbA1C ≤ 10% Inclusion criteria for healthy subjects: Healthy subjects (as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations) Inclusion criteria for all subjects: Subjects with (eGFR ≥ 60 and ≤ 160 mL/min/1.73m² and urinary albumin excretion < 300 mg/g creatinine) Body Mass Index (BMI) of 18 to 38 kg/m² Men and women, ages 18 to 65 years, inclusive Exclusion criteria for all subjects: Subjects with Type 1 Diabetes or uncontrolled Type 2 Diabetes Mellitus Subjects with T2DM with fasting plasma glucose > 200 mg/dL, healthy subjects with fasting plasma glucose > 105 mg/dL Subjects with T2DM with HbA1C > 10.0%, healthy subjects with HbA1C > 6.8%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dapagliflozin (T2DM)<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 10 mg, Once daily, 7 days<br>|
| Active Comparator: Dapagliflozin (Healthy Subjects)<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 10 mg, Once daily, 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The reduction in TmG after 7 days of oral administration of 10 mg of dapagliflozin |  | Before 7 days of oral administration of 10 mg of dapagliflozin | 
| The reduction in TmG after 7 days of oral administration of 10 mg of dapagliflozin |  | After 7 days of oral administration of 10 mg of dapagliflozin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Splay of the glucose titration curve |  | Before 7 days of oral administration of 10 mg of dapagliflozin | 
| Splay of the glucose titration curve |  | After 7 days of oral administration of 10 mg of dapagliflozin | 
| Pharmacokinetics (Cmin, Cmax, Tmax, and AUC (TAU)) of dapagliflozin |  | Study Day 7 | 
| Pharmacokinetics (Cmin, Cmax, Tmax, and AUC (TAU)) of dapagliflozin |  | Study Day 8 |