Drug Interaction Study of Apixaban With Cyclosporine and Tacrolimus

Exclusion Criteria

• •1. Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures), dermatologic or psychiatric abnormalities or diseases
• •2. Has history of cancer (excluding treated cutaneous squamous or basal cell carcinoma of \>3 years previous)
• •3. Has history of venous or arterial thromboembolic disease
• •4. Has a history of a major bleeding event (defined as: (i) symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or (ii) a fall in hemoglobin level of 2 g/dL or more, or leading to transfusion of two or more units of whole blood or red cells) within 6 months prior to screening visit
• •5. Has had major surgery within 6 months prior to screening visit
• •6. Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies for 2 weeks prior to trial start date until the post-trial visit
• •7. Is unable to refrain from using any drugs or substance known to be inhibitors or inducers of cytochrome P450 (CYP) enzymes including grapefruit products for 2 weeks prior to dosing and throughout the study, until the post-trial visit
• •8. Has a history of illicit drug abuse within six months prior to screening visit
• •9. Pregnant or lactating
• •10. Consumes greater than 3 glasses of alcoholic beverages per day and cannot refrain from alcohol for the duration of the trial
• •11. Has a history of significant multiple and/or severe allergies (e.g. food, drug), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• •12. Has known anaphylactic or severe systemic reactions to any components of study drugs (including apixaban, cyclosporine or tacrolimus) or contraindication to the administration of study drugs
• •13. Has moderate or severe hepatic disease or other clinically relevant bleeding risk
• •14. Has positive history for hepatitis B surface antigen, hepatitis C or HIV
• •15. Use of any drugs or products which at the discretion of the investigator would increase bleeding risk
• •16. Is considered inappropriate for participation by the investigator for any reason