Study to Evaluate the Potential Pharmacokinetic Interaction and Pharmacodynamic Effects on Renal Parameters of Bumetanide (1mg) and Dapagliflozin (10 mg) when Co-administered in Healthy Subjects

Exclusion Criteria

• - WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period
• - Any significant acute or chronic medical illness
• - Current or recent (within 3 months) gastrointestinal disease
• - Current smoker or recent (within 1 month) history of regular tobacco use
• - Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population
• - Abnormal urinalysis at screening
• - Glucosuria at screening
• - Abnormal liver functions tests (ALT, AST or total bilirubin > 10 % ULN)
• - Presence of edema on physical exam
• - History of diabetes mellitus
• - History of heart failure
• - History of renal insufficiency
• - History of chronic or recurrent UTI (defined as 3 occurrences per year) or UTI in the past 3 months
• - Positive urine screen for drugs of abuse either at screening or before dosing
• - Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1, -2 antibody
• - History of allergy to SGLT2 inhibitors, bumetanide (or related compounds)
• - History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)
• - Prior exposure to dapagliflozin within 3 months of Day -1
• - Exposure to any investigational drug or placebo within 4 weeks of Day -1
• - Use of any prescription drugs within 4 weeks or over-the-counter acid controllers within 2 weeks prior to study drug administration
• - Use of any other drugs, including over-the-counter medications within 1 week and herbal preparations, within 2 weeks prior to study drug administration
• - Use of an oral, injectable or implantable hormonal contraceptive agent within 3 months of study drug administration