"This is a single-center, randomized, double-blind, and placebo-controlled trial designed to: 1) demonstrate the degree to which administered andexanet doses can reverse Factor Ten A (FXa)-inhibitor induced anticoagulation; and 2) evaluate the safety and PK/PD of andexanet in healthy Japanese subjects taking direct FXa inhibitors at therapeutic doses."

Inclusion Criteria:

1. Must be in reasonably good health as determined by the Investigator based on medical history, full physical examination (including blood pressure and pulse rate measurement), 12-lead ECG, and clinical laboratory tests. Subjects with well-controlled, chronic, stable conditions (e.g., controlled hypertension, non-insulin dependent diabetes, osteoarthritis, hypothyroidism) may be enrolled based on the clinical judgment of the Investigator.

2. For all cohorts except Cohort 5, subjects must be of Japanese ethnicity, defined as having four ethnic Japanese grandparents. Subjects may not have lived outside of Japan for more than 10 years. For Cohort 5, subjects must be of Caucasian race.

3. Must be between the ages of 18 and 75 years, inclusive, at the time of signing of the Inform Consent Form (ICF).

4. Agrees to have any dietary or nutritional supplements reviewed by the Investigator and potentially held during the study if advised by the Investigator. Standard multivitamin and mineral supplementation will be permitted.

5. Agrees to comply with the contraception and reproduction restrictions of the study:

   • Men whose sexual partner is of childbearing potential and/or who are not monogamous must be using two acceptable methods of contraception, at least one of which must be a barrier method (e.g., spermicidal gel plus condom), for the entire duration of the study and for at least 1 month following study-drug administration; and men must refrain from attempting to father a child or donating sperm in the 1 month following the study-drug administration. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
   • Men who report surgical sterilization (e.g., bilateral vasectomy) must have had the procedure at least 6 months before study drug administration.
   • Surgical sterilization procedures should be supported with clinical documentation and noted in the Relevant Medical History/Current Medical Conditions section of the case report forms (CRFs).
   • Women of childbearing potential must be using two medically acceptable methods of contraception, at least one of which must be a barrier method (e.g., non-hormone containing intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom), from the time of Screening and for the duration of the study, through at least 1 month following study drug administration. Note: Oral and topical hormonal contraceptive use, as well as the use of hormone-containing intra-uterine devices, is not permitted due to their increased risk of thromboembolism. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post- ovulation methods) and withdrawal are not acceptable methods of contraception; OR
   • Postmenopausal women must have had no regular menstrual bleeding for at least 1 year before initial dosing and either be over the age of 60 years or have an elevated plasma follicle-stimulating hormone (FSH) level (i.e., > 40 milli-international units (mIU)/mL) at Screening;
   • Women who report surgical sterilization (i.e., hysterectomy, tubal ligation, and/or bilateral oophorectomy) must have had the procedure at least 6 months before study drug administration. Surgical sterilization procedures should be supported with clinical documentation and noted in the Relevant Medical History/Current Medical Conditions section of the CRF; AND All female subjects must have a documented negative pregnancy test result at Screening and on Study Day -1.

6. Systolic blood pressure < 160 mmHg and diastolic blood pressure < 90 mmHg at Screening and Day -1.

7. The following laboratory values must be within the normal laboratory reference range within 45 days of Day -1: Prothrombin Time (PT), Activated Partial Thromboplastin Time (aPTT), and Activated Clotting Time (ACT); hemoglobin, hematocrit, and platelet count.

8. The following laboratory values must be equal to or below 2 times the upper limit of normal (ULN) range within 45 days of Day -1: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and total bilirubin.

9. The Screening serum creatinine must be below 1.5 mg/dL within 45 days of Day -1.

10. Body mass index of less than 30 kg/m2, inclusive, and body weight between 50 kg and 80 kg, inclusive. In addition, subjects must be greater than 60 kg for Cohorts 3, 4, and 10.

11. Agrees to abstain from alcohol consumption for the duration of the domicile period, and from the use of drugs of abuse for the duration of the study.

12. Able to read and give written informed consent and has signed a consent form approved by the Investigator's Institutional Review Board (IRB) or Independent Ethics Committee (IEC)."

Exclusion Criteria:

1. Previous use of andexanet or previous participation in the current study (even if the subject received placebo).

2. History of abnormal bleeding, signs or symptoms of active bleeding, or risk factors for bleeding.

3. Has a stool specimen that was positive for occult blood within 6 months of study Screening or during the Screening Period.

4. Past or current medical history of thrombosis, any sign or symptom that suggests an increased risk of a systemic thrombotic condition or thrombotic event, or recent events that may increase risk of thrombosis.

   a. For example, subjects with a known or suspected hypercoagulable state, history of Venous Thromboembolism(VTE), Deep Venous Thrombosis (DVT), stroke, myocardial infarction (MI), cancer (other than non-melanoma skin cancer), atrial fibrillation, heart failure, cardiomyopathy, phlebitis, lower extremity edema, major surgery, or trauma within 2 months of Study Day -1, airplane travel with a planned flight time for any single flight segment ≥ 6 hours during the 4 weeks prior to Study Day -1, or general immobility are excluded.

5. Absolute or relative contraindication to anticoagulation or treatment with apixaban, rivaroxaban, and/or edoxaban.

6. Prior consumption of (by any route) one or more doses of aspirin (including baby aspirin), salicylate or subsalicylate, other antiplatelet drugs (e.g., ticlopidine, clopidogrel), non-steroidal anti-inflammatory drugs, fibrinolytic, or any anticoagulant within 7 days prior to Day -1 or is anticipated to require such drugs during the study.

7. Receipt of (by any route) hormonal contraception, post- menopausal hormone replacement therapy (HRT) (including over-the-counter products), or testosterone during the 4 weeks prior to Study Day -1 or is anticipated to require such drugs during the study.

8. Family history of or risk factors for a hypercoagulable or thrombotic condition, including one of the following:

   1. Factor V Leiden carrier or homozygote.
   2. Protein C, S, or ATIII activity below the normal range.

9. History of adult asthma or chronic obstructive pulmonary disease or current regular or as needed use of inhaled medications.

10. Active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV-1/2 infection.

11. Use of any drugs that are strong dual inhibitors or inducers of CYP3A4 (apixaban and rivaroxaban cohorts only) and P-gp (all cohorts) within 7 days prior to Study Day -1 or anticipated need for such drugs during the study.

12. Participation in an investigational drug study within 45 days of Day -1 or Day -1 is within 5 half-lives of the investigational compound.

13. Positive screen for drugs of abuse at Day -1 that is not explained by a prescription medication that the subject is known to be taking.

14. A medical or surgical condition that may impair drug (anticoagulant or andexanet) metabolism.

15. Allergy to any of the vehicle ingredients: Tris, arginine, sucrose, hydrochloric acid, mannitol, and polysorbate 80.

16. Allergy to soy or soy products.

17. Current breastfeeding or a positive pregnancy test at Screening or Day -1.

18. Any condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would in the opinion of the Investigator increase the risk of the subject's participation in the study. This would include but is not limited to alcoholism, drug dependency or abuse, psychiatric disease, epilepsy, or any unexplained blackouts.

19. The subject is not judged by the study staff to have adequate bilateral venous access.

20. Unwillingness to adhere to the activity requirements of the study."

Double Blind (Participant, Care Provider, Investigator, Sponsor)