Drug Interaction Study of Apixaban With Cyclosporine and Tacrolimus

Inclusion Criteria:

Be a healthy male or female between ages 18-55 (inclusive) at the screening visit
Have a body mass index (BMI) ≥ 19 and ≤ 33 (inclusive)

Be a female subject, subject

Can be of childbearing potential and must demonstrate a urine β-hCG level consistent with the non-pregnancy state and agree to use an acceptable method of birth control throughout the study.
Can be of non-childbearing potential.
Be a nonsmoker for at least approximately 6 months
Have serum creatinine level < 1.5 mg/dL
Have a prothrombin time (PT) and activated partial thromboplastin time (PTT) level below the upper limit of normal
Have platelet count within normal limits
Be willing to refrain from the use of anticoagulants and antiplatelet medications including aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) during the entire period of study participation
Be willing to comply with trial restrictions

Exclusion Criteria:

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
Has history of cancer (excluding treated cutaneous squamous or basal cell carcinoma of >3 years previous)
Has history of venous or arterial thromboembolic disease
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
Has had major surgery within 6 months prior to screening visit
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
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
Has a history of illicit drug abuse within six months prior to screening visit
Pregnant or lactating
Consumes greater than 3 glasses of alcoholic beverages per day and cannot refrain from alcohol for the duration of the trial
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
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
Has moderate or severe hepatic disease or other clinically relevant bleeding risk
Has positive history for hepatitis B surface antigen, hepatitis C or HIV
Use of any drugs or products which at the discretion of the investigator would increase bleeding risk
Is considered inappropriate for participation by the investigator for any reason