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A Healthy Volunteer Pharmacokinetics (PK)/Pharmacodynamics (PD), Safety and Tolerability Study of Andexanet in Healthy Japanese and Caucasian Subjects

Sponsor
Portola Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03310021
Collaborator
(none)
108
Enrollment
1
Location
10
Arms
23.5
Actual Duration (Months)
4.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

"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."
Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
108 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
Double Blind (Participant, Care Provider, Investigator, Sponsor)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Andexanet Alfa Administered to Healthy Japanese and Caucasian Subjects
Actual Study Start Date :
Aug 28, 2017
Actual Primary Completion Date :
Aug 13, 2019
Actual Study Completion Date :
Aug 13, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1

Apixaban + low dose andexanet

Biological: Andexanet alfa
fXa inhibitor antidote
Other Names:
  • 200 mg/vial for IV injection

    • Drug: Apixaban
    factor Xa inhibitor
    Other Names:
  • Eliquis

    • Drug: Placebo
    Placebo
    Experimental: Cohort 2

    Rivaroxaban + high dose andexanet

    Biological: Andexanet alfa
    fXa inhibitor antidote
    Other Names:
  • 200 mg/vial for IV injection

    • Drug: Rivaroxaban
    factor Xa inhibitor
    Other Names:
  • Xarelto

    • Drug: Placebo
    Placebo
    Experimental: Cohort 3

    Edoxaban + high dose andexanet

    Biological: Andexanet alfa
    fXa inhibitor antidote
    Other Names:
  • 200 mg/vial for IV injection

    • Drug: Edoxaban
    factor Xa inhibitor
    Other Names:
  • Savaysa, Lixiana

    • Drug: Placebo
    Placebo
    Experimental: Cohort 4

    Edoxaban + high dose andexanet

    Biological: Andexanet alfa
    fXa inhibitor antidote
    Other Names:
  • 200 mg/vial for IV injection

    • Drug: Edoxaban
    factor Xa inhibitor
    Other Names:
  • Savaysa, Lixiana

    • Drug: Placebo
    Placebo
    Experimental: Cohort 5

    Apixaban + low dose andexanet

    Biological: Andexanet alfa
    fXa inhibitor antidote
    Other Names:
  • 200 mg/vial for IV injection

    • Drug: Apixaban
    factor Xa inhibitor
    Other Names:
  • Eliquis

    • Drug: Placebo
    Placebo
    Experimental: Cohort 6

    Apixaban + high dose andexanet

    Biological: Andexanet alfa
    fXa inhibitor antidote
    Other Names:
  • 200 mg/vial for IV injection

    • Drug: Apixaban
    factor Xa inhibitor
    Other Names:
  • Eliquis

    • Drug: Placebo
    Placebo
    Experimental: Cohort 7

    Edoxaban + low dose andexanet

    Biological: Andexanet alfa
    fXa inhibitor antidote
    Other Names:
  • 200 mg/vial for IV injection

    • Drug: Edoxaban
    factor Xa inhibitor
    Other Names:
  • Savaysa, Lixiana

    • Drug: Placebo
    Placebo
    Experimental: Cohort 8

    Apixaban + low dose andexanet

    Biological: Andexanet alfa
    fXa inhibitor antidote
    Other Names:
  • 200 mg/vial for IV injection

    • Drug: Apixaban
    factor Xa inhibitor
    Other Names:
  • Eliquis

    • Drug: Placebo
    Placebo
    Experimental: Cohort 9

    Rivaroxaban + low dose andexanet

    Biological: Andexanet alfa
    fXa inhibitor antidote
    Other Names:
  • 200 mg/vial for IV injection

    • Drug: Rivaroxaban
    factor Xa inhibitor
    Other Names:
  • Xarelto

    • Drug: Placebo
    Placebo
    Experimental: Cohort 10

    Edoxaban + low dose andexanet

    Biological: Andexanet alfa
    fXa inhibitor antidote
    Other Names:
  • 200 mg/vial for IV injection

    • Drug: Edoxaban
    factor Xa inhibitor
    Other Names:
  • Savaysa, Lixiana

    • Drug: Placebo
    Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. [Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours]

      The primary efficacy endpoint is the percent change in the anti-FXa activity from baseline to the end of infusion (EOI) nadir.

    Secondary Outcome Measures

    1. Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. [Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours]

      The percent change from baseline in anti-FXa activity at its end of bolus (EOB) nadir.

    2. Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. [Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours]

      The percent change from baseline in free FXa inhibitors concentration (ng/mL) at its EOB nadir.

    3. Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. [Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours]

      The percent change from baseline in free FXa inhibitors concentration (ng/mL) at its EOI nadir.

    4. Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. [Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours]

      The change in thrombin generation from baseline to its EOB peak.

    5. Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. [Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours]

      The change in thrombin generation from baseline to its EOI peak.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.

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

    2. 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.

    3. 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.

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

    5. 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

    7. 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.

    8. 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.

    1. 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.

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

    2. 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.

    3. 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.

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

    5. Factor V Leiden carrier or homozygote.

    6. Protein C, S, or ATIII activity below the normal range.

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

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

    9. 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.

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

    11. 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.

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

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

    14. Allergy to soy or soy products.

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

    16. 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.

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

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 WCCT Global Cypress California United States 90630

    Sponsors and Collaborators

    • Portola Pharmaceuticals

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Portola Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03310021
    Other Study ID Numbers:
    • 16-508
    First Posted:
    Oct 16, 2017
    Last Update Posted:
    Aug 21, 2020
    Last Verified:
    Jul 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Rivaroxaban
    Apixaban
    Edoxaban

    Study Results

    Participant Flow

    Recruitment Details Healthy Subjects
    Pre-assignment Detail One subject in cohort 10 (Edoxaban/Placebo) discontinued due to protocol deviation (mis-enrolled, inclusion criteria #10 not met(weight>80kg). This subject (100003) is not summarized in tables because he/she did not receive any andexanet/Placebo. The safety population (N=107) is defined as having received study drug andexanet/placebo.
    Arm/Group Title Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo
    Arm/Group Description Andexanet 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 800 mg bolus+ 8 mg/min 120 minute infusion (dosing at 4 hours post-rivaroxaban); Japanese Subjects Placebo 800 mg bolus+ 8 mg/min 120 minute infusion placebo (dosing at 4 hours post-rivaroxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Caucasian Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Caucasian Subjects Andexanet 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects
    Period Title: Overall Study
    STARTED 6 3 6 3 8 4 8 4 6 3 6 3 8 4 6 3 10 5 8 3
    COMPLETED 6 3 6 3 8 4 7 4 6 3 5 3 8 4 6 3 10 5 8 3
    NOT COMPLETED 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo Total
    Arm/Group Description Andexanet 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 800 mg bolus+ 8 mg/min 120 minute infusion (dosing at 4 hours post-rivaroxaban); Japanese Subjects Placebo 800 mg bolus+ 8 mg/min 120 minute infusion placebo (dosing at 4 hours post-rivaroxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Caucasian Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Caucasian Subjects Andexanet 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects Total of all reporting groups
    Overall Participants 6 3 6 3 8 4 8 4 6 3 6 3 8 4 6 3 10 5 8 3 107
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    44.00
    (8.99)
    52.00
    (6.56)
    46.83
    (17.50)
    55.33
    (12.22)
    42.38
    (10.45)
    36.75
    (9.32)
    33.13
    (9.26)
    33.00
    (7.30)
    35.00
    (14.53)
    30.33
    (2.08)
    44.17
    (11.02)
    42.33
    (12.74)
    38.13
    (11.04)
    47.75
    (8.96)
    42.17
    (7.70)
    46.33
    (12.42)
    49.70
    (12.88)
    33.60
    (5.13)
    30.13
    (9.91)
    39.00
    (6.24)
    40.69
    (11.97)
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    44.50
    51.00
    47.50
    58.00
    45.00
    35.50
    33.0
    31.50
    31.50
    31.00
    46.50
    36.00
    34.50
    47.00
    41.00
    53.00
    51.00
    35.00
    28.50
    41.00
    38.00
    Sex: Female, Male (Count of Participants)
    Female
    3
    50%
    2
    66.7%
    4
    66.7%
    1
    33.3%
    0
    0%
    0
    0%
    1
    12.5%
    0
    0%
    3
    50%
    1
    33.3%
    2
    33.3%
    1
    33.3%
    4
    50%
    2
    50%
    3
    50%
    1
    33.3%
    4
    40%
    1
    20%
    2
    25%
    1
    33.3%
    36
    33.6%
    Male
    3
    50%
    1
    33.3%
    2
    33.3%
    2
    66.7%
    8
    100%
    4
    100%
    7
    87.5%
    4
    100%
    3
    50%
    2
    66.7%
    4
    66.7%
    2
    66.7%
    4
    50%
    2
    50%
    3
    50%
    2
    66.7%
    6
    60%
    4
    80%
    6
    75%
    2
    66.7%
    71
    66.4%
    Race/Ethnicity, Customized (Count of Participants)
    White
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    6
    100%
    3
    100%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9
    8.4%
    Asian
    6
    100%
    3
    100%
    6
    100%
    3
    100%
    8
    100%
    4
    100%
    8
    100%
    4
    100%
    0
    0%
    0
    0%
    6
    100%
    3
    100%
    8
    100%
    4
    100%
    6
    100%
    3
    100%
    10
    100%
    5
    100%
    8
    100%
    3
    100%
    98
    91.6%

    Outcome Measures

    1. Primary Outcome
    Title Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir.
    Description The primary efficacy endpoint is the percent change in the anti-FXa activity from baseline to the end of infusion (EOI) nadir.
    Time Frame Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours

    Outcome Measure Data

    Analysis Population Description
    Efficacy Population: all randomized subjects who received andexanet or placebo during the double-blind treatment period and had at least one evaluable post-baseline efficacy assessment as well as the required baseline sample assessment.
    Arm/Group Title Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo
    Arm/Group Description Andexanet 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 800 mg bolus+ 8 mg/min 120 minute infusion (dosing at 4 hours post-rivaroxaban); Japanese Subjects Placebo 800 mg bolus+ 8 mg/min 120 minute infusion placebo (dosing at 4 hours post-rivaroxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Caucasian Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Caucasian Subjects Andexanet 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects
    Measure Participants 6 3 6 3 8 4 8 4 6 3 6 3 8 4 6 3 10 5 8 3
    Median (Full Range) [percent change]
    -94.50
    -29.00
    -98.00
    -37.00
    -81.00
    -47.50
    -75.50
    -37.00
    -93.00
    -34.00
    -97.00
    -31.00
    -52.50
    -37.00
    -92.00
    -24.00
    -93.50
    -37.00
    -63.50
    -27.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 1 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0275
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -65.5
    Confidence Interval (2-Sided) 95%
    -78.00 to -58.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet, Cohort 2 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.025
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -61
    Confidence Interval (2-Sided) 95%
    -65.00 to -44.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 3 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0136
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -32.5
    Confidence Interval (2-Sided) 95%
    -47.00 to -9.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 4 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0136
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -36.5
    Confidence Interval (2-Sided) 95%
    -62.00 to -9.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 5 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.025
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -59
    Confidence Interval (2-Sided) 95%
    -70.00 to -38.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 6 Apixaban 10 mg BID/High Dose Andexanet, Cohort 6 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0119
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -66
    Confidence Interval (2-Sided) 95%
    -68.00 to -61.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet, Cohort 7 Edoxaban 30 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2667
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -15.5
    Confidence Interval (2-Sided) 95%
    -38.00 to 17.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet, Cohort 8 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0238
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -68
    Confidence Interval (2-Sided) 95%
    -74.00 to -59.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet, Cohort 9 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0007
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -56.5
    Confidence Interval (2-Sided) 95%
    -65.00 to -39.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet, Cohort 10 Edoxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0121
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -35
    Confidence Interval (2-Sided) 95%
    -53.00 to -24.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir.
    Description The percent change from baseline in anti-FXa activity at its end of bolus (EOB) nadir.
    Time Frame Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours

    Outcome Measure Data

    Analysis Population Description
    Efficacy Population: all randomized subjects who received andexanet or placebo during the double-blind treatment period and had at least one evaluable post-baseline efficacy assessment as well as the required baseline sample assessment.
    Arm/Group Title Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo
    Arm/Group Description Andexanet 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 800 mg bolus+ 8 mg/min 120 minute infusion (dosing at 4 hours post-rivaroxaban); Japanese Subjects Placebo 800 mg bolus+ 8 mg/min 120 minute infusion placebo (dosing at 4 hours post-rivaroxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Caucasian Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Caucasian Subjects Andexanet 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects
    Measure Participants 6 3 6 3 8 4 8 4 6 3 6 3 8 4 6 3 10 5 8 3
    Median (Full Range) [percent change]
    -94.50
    -14.00
    -97.50
    -18.00
    -65.50
    -16.00
    -22.50
    -15.00
    -94.00
    -10.00
    -96.00
    -18.00
    -58.00
    -8.00
    -94.50
    -5.00
    -95.00
    -11.00
    -73.00
    -4.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 1 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0256
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -80
    Confidence Interval (2-Sided) 95%
    -83.00 to -77.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet, Cohort 2 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.025
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -79.5
    Confidence Interval (2-Sided) 95%
    -97.00 to -67.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 3 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.074
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -37
    Confidence Interval (2-Sided) 95%
    -66.00 to 5.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 4 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1066
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -10.5
    Confidence Interval (2-Sided) 95%
    -59.00 to 10.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 5 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0219
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -84
    Confidence Interval (2-Sided) 95%
    -87.00 to -71.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 6 Apixaban 10 mg BID/High Dose Andexanet, Cohort 6 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0262
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -78
    Confidence Interval (2-Sided) 95%
    -83.00 to -74.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet, Cohort 7 Edoxaban 30 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0412
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -50
    Confidence Interval (2-Sided) 95%
    -65.00 to 0.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet, Cohort 8 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0269
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -89.5
    Confidence Interval (2-Sided) 95%
    -93.00 to -77.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet, Cohort 9 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0026
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -84
    Confidence Interval (2-Sided) 95%
    -86.00 to -69.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet, Cohort 10 Edoxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0181
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -65
    Confidence Interval (2-Sided) 95%
    -76.00 to -57.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir.
    Description The percent change from baseline in free FXa inhibitors concentration (ng/mL) at its EOB nadir.
    Time Frame Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours

    Outcome Measure Data

    Analysis Population Description
    Efficacy Population: all randomized subjects who received andexanet or placebo during the double-blind treatment period and had at least one evaluable post-baseline efficacy assessment as well as the required baseline sample assessment.
    Arm/Group Title Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo
    Arm/Group Description Andexanet 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 800 mg bolus+ 8 mg/min 120 minute infusion (dosing at 4 hours post-rivaroxaban); Japanese Subjects Placebo 800 mg bolus+ 8 mg/min 120 minute infusion placebo (dosing at 4 hours post-rivaroxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Caucasian Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Caucasian Subjects Andexanet 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects
    Measure Participants 6 3 6 3 8 4 8 4 6 3 6 3 8 4 6 3 9 5 8 3
    Median (Full Range) [percent change]
    -93.00
    -11.94
    -97.72
    -28.57
    -78.20
    -17.60
    -56.05
    -2.49
    -94.45
    5.80
    -93.57
    -12.94
    -70.88
    -5.48
    -91.61
    -0.32
    -95.51
    -14.02
    -75.80
    -17.91
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 1 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -81.06
    Confidence Interval (2-Sided) 95%
    -92.99 to -71.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet, Cohort 2 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -69.15
    Confidence Interval (2-Sided) 95%
    -96.91 to -48.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 3 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -57.39
    Confidence Interval (2-Sided) 95%
    -72.07 to -40.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 4 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -54.96
    Confidence Interval (2-Sided) 95%
    -80.42 to -25.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 5 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -100.25
    Confidence Interval (2-Sided) 95%
    -133.08 to -84.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 6 Apixaban 10 mg BID/High Dose Andexanet, Cohort 6 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -79.87
    Confidence Interval (2-Sided) 95%
    -86.36 to -65.74
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet, Cohort 7 Edoxaban 30 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -65.02
    Confidence Interval (2-Sided) 95%
    -89.54 to -39.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet, Cohort 8 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -91.29
    Confidence Interval (2-Sided) 95%
    -128.88 to -60.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet, Cohort 9 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0034
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -81.49
    Confidence Interval (2-Sided) 95%
    -91.05 to -65.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet, Cohort 10 Edoxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0189
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -58.47
    Confidence Interval (2-Sided) 95%
    -110.86 to -46.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir.
    Description The percent change from baseline in free FXa inhibitors concentration (ng/mL) at its EOI nadir.
    Time Frame Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours

    Outcome Measure Data

    Analysis Population Description
    Efficacy Population: all randomized subjects who received andexanet or placebo during the double-blind treatment period and had at least one evaluable post-baseline efficacy assessment as well as the required baseline sample assessment.
    Arm/Group Title Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo
    Arm/Group Description Andexanet 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 800 mg bolus+ 8 mg/min 120 minute infusion (dosing at 4 hours post-rivaroxaban); Japanese Subjects Placebo 800 mg bolus+ 8 mg/min 120 minute infusion placebo (dosing at 4 hours post-rivaroxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Caucasian Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Caucasian Subjects Andexanet 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects
    Measure Participants 6 3 6 3 8 4 8 4 6 3 6 3 8 4 6 3 10 5 8 3
    Median (Full Range) [percent change]
    -92.940
    -33.550
    -98.650
    -39.390
    -85.005
    -48.710
    -81.040
    -42.755
    -93.495
    -31.830
    -96.65
    -29.02
    -62.72
    -24.34
    -90.63
    -31.45
    -94.89
    -37.82
    -67.10
    -34.25
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 1 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -59.39
    Confidence Interval (2-Sided) 95%
    -66.48 to -52.62
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet, Cohort 2 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -59.26
    Confidence Interval (2-Sided) 95%
    -70.34 to -26.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 3 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -36.76
    Confidence Interval (2-Sided) 95%
    -46.14 to -29.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 4 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -36.82
    Confidence Interval (2-Sided) 95%
    -55.81 to -20.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 5 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -61.67
    Confidence Interval (2-Sided) 95%
    -75.82 to -43.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 6 Apixaban 10 mg BID/High Dose Andexanet, Cohort 6 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -67.63
    Confidence Interval (2-Sided) 95%
    -77.40 to -61.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet, Cohort 7 Edoxaban 30 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -40.33
    Confidence Interval (2-Sided) 95%
    -59.77 to -11.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet, Cohort 8 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -59.18
    Confidence Interval (2-Sided) 95%
    -101.02 to -48.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet, Cohort 9 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0027
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -54.63
    Confidence Interval (2-Sided) 95%
    -59.14 to -41.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet, Cohort 10 Edoxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0189
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value -38.14
    Confidence Interval (2-Sided) 95%
    -65.78 to -15.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir.
    Description The change in thrombin generation from baseline to its EOB peak.
    Time Frame Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours

    Outcome Measure Data

    Analysis Population Description
    Efficacy Population: all randomized subjects who received andexanet or placebo during the double-blind treatment period and had at least one evaluable post-baseline efficacy assessment as well as the required baseline sample assessment.
    Arm/Group Title Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo
    Arm/Group Description Andexanet 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 800 mg bolus+ 8 mg/min 120 minute infusion (dosing at 4 hours post-rivaroxaban); Japanese Subjects Placebo 800 mg bolus+ 8 mg/min 120 minute infusion placebo (dosing at 4 hours post-rivaroxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Caucasian Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Caucasian Subjects Andexanet 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects
    Measure Participants 6 3 6 3 8 4 8 4 6 3 6 3 8 4 6 3 10 5 8 3
    Median (Full Range) [nM.min]
    1145.03
    179.94
    1337.28
    209.99
    758.92
    215.71
    815.07
    48.59
    1244.30
    103.13
    1177.47
    0.16
    781.42
    67.97
    1184.62
    2.69
    1306.23
    117.50
    902.17
    -92.82
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 1 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 965.09
    Confidence Interval (2-Sided) 95%
    474.48 to 1377.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet, Cohort 2 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 1127.29
    Confidence Interval (2-Sided) 95%
    769.46 to 1575.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 3 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 574.89
    Confidence Interval (2-Sided) 95%
    307.65 to 1175.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 4 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 715.34
    Confidence Interval (2-Sided) 95%
    535.38 to 836.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 5 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 1141.17
    Confidence Interval (2-Sided) 95%
    964.03 to 1736.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 6 Apixaban 10 mg BID/High Dose Andexanet, Cohort 6 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 1198.83
    Confidence Interval (2-Sided) 95%
    988.82 to 1670.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet, Cohort 7 Edoxaban 30 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 721.21
    Confidence Interval (2-Sided) 95%
    585.92 to 1108.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet, Cohort 8 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 1204.62
    Confidence Interval (2-Sided) 95%
    1001.72 to 1471.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet, Cohort 9 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0027
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 1180.5
    Confidence Interval (2-Sided) 95%
    857.21 to 1296.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet, Cohort 10 Edoxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0189
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 976.59
    Confidence Interval (2-Sided) 95%
    585.99 to 1498.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir.
    Description The change in thrombin generation from baseline to its EOI peak.
    Time Frame Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours

    Outcome Measure Data

    Analysis Population Description
    Efficacy Population: all randomized subjects who received andexanet or placebo during the double-blind treatment period and had at least one evaluable post-baseline efficacy assessment as well as the required baseline sample assessment.
    Arm/Group Title Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo
    Arm/Group Description Andexanet 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 800 mg bolus+ 8 mg/min 120 minute infusion (dosing at 4 hours post-rivaroxaban); Japanese Subjects Placebo 800 mg bolus+ 8 mg/min 120 minute infusion placebo (dosing at 4 hours post-rivaroxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Caucasian Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Caucasian Subjects Andexanet 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects
    Measure Participants 6 3 6 3 8 4 8 4 6 3 6 3 8 4 6 3 10 5 8 3
    Median (Full Range) [nM.min]
    1000.630
    171.220
    1329.580
    207.590
    804.405
    347.535
    910.935
    236.610
    1130.575
    118.130
    1119.41
    108.67
    833.46
    175.72
    1058.09
    138.14
    1173.38
    293.15
    793.44
    -72.69
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 1 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 826.9
    Confidence Interval (2-Sided) 95%
    505.40 to 1362.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet, Cohort 2 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 1125.7
    Confidence Interval (2-Sided) 95%
    873.87 to 1552.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 3 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 538.84
    Confidence Interval (2-Sided) 95%
    291.20 to 1077.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet, Cohort 4 Edooxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 687.57
    Confidence Interval (2-Sided) 95%
    500.92 to 902.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet, Cohort 5 Apixaban 5 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 1012.45
    Confidence Interval (2-Sided) 95%
    859.08 to 1352.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 6 Apixaban 10 mg BID/High Dose Andexanet, Cohort 6 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 1057.27
    Confidence Interval (2-Sided) 95%
    818.96 to 1634.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet, Cohort 7 Edoxaban 30 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 630.81
    Confidence Interval (2-Sided) 95%
    421.78 to 1124.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet, Cohort 8 Apixaban 10 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0282
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 925.84
    Confidence Interval (2-Sided) 95%
    663.74 to 1216.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet, Cohort 9 Rivaroxaban 15 mg BID/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0027
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 871.11
    Confidence Interval (2-Sided) 95%
    631.67 to 1051.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet, Cohort 10 Edoxaban 60 mg QD/Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0189
    Comments
    Method 2-sided Wilcoxon Rank Sum
    Comments
    Method of Estimation Estimation Parameter Hodges lehman Location shift
    Estimated Value 874.44
    Confidence Interval (2-Sided) 95%
    637.25 to 1412.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Study day 1 to 39
    Adverse Event Reporting Description Treatment emergent AEs occurring between informed consent and the Termination Visit will be recorded on the e-CRFs. All AEs should be monitored until they are resolved, reach a level of stability and are not expected to improve further, or are clearly determined to be due to a subject's stable or chronic condition or intercurrent illness. Any AE that begins after completion of the study and that the Investigator considers to be related to study medication, must be reported to Portola.
    Arm/Group Title Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo
    Arm/Group Description Andexanet 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 800 mg bolus+ 8 mg/min 120 minute infusion (dosing at 4 hours post-rivaroxaban); Japanese Subjects Placebo 800 mg bolus+ 8 mg/min 120 minute infusion placebo (dosing at 4 hours post-rivaroxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Caucasian Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Caucasian Subjects Andexanet 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Placebo 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects
    All Cause Mortality
    Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Serious Adverse Events
    Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Renal and urinary disorders
    Nephrolithiasis 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%) 1/6 (16.7%) 1/3 (33.3%) 1/8 (12.5%) 1/4 (25%) 1/6 (16.7%) 1/3 (33.3%) 1/10 (10%) 1/5 (20%) 1/8 (12.5%) 1/3 (33.3%)
    Other (Not Including Serious) Adverse Events
    Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Cohort 1 Apixaban 5 mg BID/Placebo Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Cohort 2 Rivaroxaban 15 mg BID/Placebo Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Cohort 3 Edooxaban 60 mg QD/Placebo Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Cohort 4 Edooxaban 60 mg QD/Placebo Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet Cohort 5 Apixaban 5 mg BID/Placebo Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Cohort 6 Apixaban 10 mg BID/Placebo Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Cohort 7 Edoxaban 30 mg QD/Placebo Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Cohort 8 Apixaban 10 mg BID/Placebo Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Cohort 9 Rivaroxaban 15 mg BID/Placebo Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Cohort 10 Edoxaban 60 mg QD/Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/6 (16.7%) 2/3 (66.7%) 3/6 (50%) 1/3 (33.3%) 1/8 (12.5%) 1/4 (25%) 3/8 (37.5%) 1/4 (25%) 4/6 (66.7%) 0/3 (0%) 2/6 (33.3%) 1/3 (33.3%) 2/8 (25%) 0/4 (0%) 3/6 (50%) 0/3 (0%) 2/10 (20%) 0/5 (0%) 1/8 (12.5%) 0/3 (0%)
    Gastrointestinal disorders
    Abdominal Pain Upper 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/6 (16.7%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Aphthous Ulcer 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Diarrhoea 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 2/6 (33.3%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Vomiting 1/6 (16.7%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    General disorders
    Catheter Site Pain 0/6 (0%) 1/3 (33.3%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Infusion Site Pain 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Vessel Puncture Site Haemorrhage 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Infections and infestations
    Nasopharyngitis 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Oral Herpes 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Pharyngitis 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Rash Pustular 0/6 (0%) 0/3 (0%) 1/6 (16.7%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Sinusitis 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Upper Respiratory Tract Infection 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/6 (16.7%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Injury, poisoning and procedural complications
    Foot Fracture 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Muscle Strain 0/6 (0%) 0/3 (0%) 1/6 (16.7%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Costochondritis 0/6 (0%) 0/3 (0%) 1/6 (16.7%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Myalgia 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/10 (10%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Muscle Spasms 0/6 (0%) 0/3 (0%) 1/6 (16.7%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Osteoarthritis 0/6 (0%) 0/3 (0%) 1/6 (16.7%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Pain in Extremity 0/6 (0%) 1/3 (33.3%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Nervous system disorders
    Dizziness 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/6 (16.7%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Headache 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 1/8 (12.5%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 2/6 (33.3%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/10 (10%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Migraine 0/6 (0%) 1/3 (33.3%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Neuropathy Peripheral 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 1/3 (33.3%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal Pain 0/6 (0%) 0/3 (0%) 1/6 (16.7%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis Contact 0/6 (0%) 0/3 (0%) 0/6 (0%) 1/3 (33.3%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Dry Skin 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 1/4 (25%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Eczema 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Petechiae 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 1/8 (12.5%) 0/3 (0%)
    Rash 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)
    Vascular disorders
    Phlebitis 0/6 (0%) 0/3 (0%) 1/6 (16.7%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/6 (0%) 0/3 (0%) 0/8 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/10 (0%) 0/5 (0%) 0/8 (0%) 0/3 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Head of Clinical Development
    Organization Portola Pharmaceuticals
    Phone 6502767153
    Email ClinicalTrials@Portola.com
    Responsible Party:
    Portola Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03310021
    Other Study ID Numbers:
    • 16-508
    First Posted:
    Oct 16, 2017
    Last Update Posted:
    Aug 21, 2020
    Last Verified:
    Jul 1, 2020