Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of Ultra Low Doses of Dapagliflozin in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), safety and tolerability following single oral doses of 0.001 mg to 2.5 mg dapagliflozin in healthy subjects.

Official Title
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Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of Ultra Low Doses of Dapagliflozin in Healthy Subjects

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: dapagliflozin
* Drug: dapagliflozin
* Drug: dapagliflozin
* Drug: dapagliflozin
* Drug: dapagliflozin
* Drug: dapagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women WOCBP who are using acceptable method of contraception Women who are not nursing Exclusion Criteria: History of GI disease Any GI surgery that could impact study drug absorption Glucosuria at screening or Day -2 Abnormal liver function tests (ALT, AST or total bilirubin > 10% above ULN) History of current or recurrent UTI History of Diabetes Mellitus History of chronic or recurrent vulvovaginal mycotic infections Estimated creatinine clearance (ClCr) < 80 mL/min using Cockroft-Gault formula History of allergy to SGLT2 inhibitors or related compounds

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dapagliflozin (0.001 mg)<br>Cohort 1 | Drug: dapagliflozin<br>* Oral Solution, Oral, 0.001 mg, once on Day 1 only, 2 days<br>* Other names: BMS-512148;|
| Experimental: dapagliflozin (0.01 mg)<br>Cohort 2 | Drug: dapagliflozin<br>* Oral Solution, Oral, 0.01 mg, once on Day 1 only, 2 days<br>* Other names: BMS-512148;|
| Experimental: dapagliflozin (0.1 mg)<br>Cohort 3 | Drug: dapagliflozin<br>* Oral Solution, Oral, 0.1 mg, once on Day 1 only, 2 days<br>* Other names: BMS-512148;|
| Experimental: dapagliflozin (0.3 mg)<br>Cohort 4 | Drug: dapagliflozin<br>* Tablets, Oral, 0.3 mg, once on Day 1 only, 2 days<br>* Other names: BMS-512148;|
| Experimental: dapagliflozin (1 mg)<br>Cohort 5 | Drug: dapagliflozin<br>* Tablets, Oral, 1 mg, once on Day 1 only, 2 days<br>* Other names: BMS-512148;|
| Experimental: dapagliflozin (2.5 mg)<br>Cohort 6 | Drug: dapagliflozin<br>* Tablets, Oral, 2.5 mg, once on Day 1 only, 2 days<br>* Other names: BMS-512148;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total 24-hour Urinary Glucose Excretion as a Measure of Pharmacodynamic Effect |  | 24 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability |  | 24 hours after dosing | 
| Dapagliflozin and Dapagliflozin 3-O-glucuronide (Metabolite of Dapagliflozin) Concentrations to Characterize Dapagliflozin Pharmacokinetics |  | 2 days after dosing |