Study of the Effect of Dapagliflozin on the Pharmacokinetics of Warfarin or Digoxin in Healthy Subjects

Inclusion criteria

• Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations
• Body Mass Index (BMI) of 18 to 32 kg/m², inclusive. BMI = weight (kg)/ [height (m)]²
• Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) and men, ages 18 to 45

Exclusion criteria

• WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal
• Any significant acute or chronic medical illness or relevant trauma (e.g. history of chronic hypertension, bacterial endocarditis, hemorrhagic stroke, motor vehicle accident resulting in significant head trauma or internal injuries)
• History of important arrhythmias as determined by the Investigator, including but not limited to ventricular fibrillation, ventricular tachycardia, A-V block, Wolff-Parkinson-White Syndrome, and sinus bradycardia (defined in this study as heart rate < 50 bpm based on vital signs and ECG performed within 21 days of Study Day 1)
• History or evidence of abnormal bleeding or coagulation disorder (e.g., history of prolonged bleeding during dental procedures, pregnancy delivery, previous surgery or injury) and/or having a first degree relative under 50 years of age with a history of abnormal bleeding or coagulation disorder per patient's report
• History of unexplained syncope
• Presence of external hemorrhoids with signs of rectal bleeding on physical exam
• Positive fecal occult blood (FOB), using the Hemoccult Sensa® assay (or equivalent), or hematuria (more than trace), unless deemed not clinically significant by the Investigator and Medical Monitor at screening or dosing
• Platelet count < 150,000 cells/µL at screening or dosing
• INR or aPTT values above the upper limit of normal (ULN) at screening or dosing
• Hemoglobin or hematocrit < LLN at screening or dosing
• Abnormal urinalysis at screening or dosing (repeat urinalysis may be allowed for positive hematuria in women)
• Glucosuria at screening or dosing
• Abnormal liver functions tests (ALT, AST or total bilirubin > 10% above ULN) at screening or dosing
• History of diabetes mellitus
• History of heart failure
• History of renal insufficiency
• History of recurrent (defined as 3 occurrences per year) or recent vulvovaginal mycotic infections
• 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
• Protein C or Protein S deficiency
• History of allergy to SGLT2 inhibitors or related compounds
• History of allergy to warfarin or related compounds
• History of allergy to digoxin or related compounds
• 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 or over-the-counter acid controllers or vitamin K containing products within 4 weeks prior to study drug administration