Bleeding
Conditions
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.
Interventions
DRUGEdoxaban
factor Xa inhibitor
DRUGPlacebo
Placebo
BIOLOGICALAndexanet alfa
fXa inhibitor antidote
DRUGApixaban
factor Xa inhibitor
DRUGRivaroxaban
factor Xa inhibitor
Sponsors
Portola Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double Blind (Participant, Care Provider, Investigator, Sponsor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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. 6. Systolic blood pressure \< 160 mmHg and diastolic blood pressure \< 90 mmHg at Screening and Day -1. 7. The following laboratory values must be within the normal laboratory reference range within 45 days of Day -1: Prothrombin Time (PT), Activated Partial Thromboplastin Time (aPTT), and Activated Clotting Time (ACT); hemoglobin, hematocrit, and platelet count. 8. The following laboratory values must be equal to or below 2 times the upper limit of normal (ULN) range within 45 days of Day -1: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and total bilirubin. 9. The Screening serum creatinine must be below 1.5 mg/dL within 45 days of Day -1. 10. Body mass index of less than 30 kg/m2, inclusive, and body weight between 50 kg and 80 kg, inclusive. In addition, subjects must be greater than 60 kg for Cohorts 3, 4, and 10. 11. Agrees to abstain from alcohol consumption for the duration of the domicile period, and from the use of drugs of abuse for the duration of the study. 12. Able to read and give written informed consent and has signed a consent form approved by the Investigator's Institutional Review Board (IRB) or Independent Ethics Committee (IEC).
Exclusion criteria
1. Previous use of andexanet or previous participation in the current study (even if the subject received placebo). 2. History of abnormal bleeding, signs or symptoms of active bleeding, or risk factors for bleeding. 3. Has a stool specimen that was positive for occult blood within 6 months of study Screening or during the Screening Period. 4. Past or current medical history of thrombosis, any sign or symptom that suggests an increased risk of a systemic thrombotic condition or thrombotic event, or recent events that may increase risk of thrombosis. a. For example, subjects with a known or suspected hypercoagulable state, history of Venous Thromboembolism(VTE), Deep Venous Thrombosis (DVT), stroke, myocardial infarction (MI), cancer (other than non-melanoma skin cancer), atrial fibrillation, heart failure, cardiomyopathy, phlebitis, lower extremity edema, major surgery, or trauma within 2 months of Study Day -1, airplane travel with a planned flight time for any single flight segment ≥ 6 hours during the 4 weeks prior to Study Day -1, or general immobility are excluded. 5. Absolute or relative contraindication to anticoagulation or treatment with apixaban, rivaroxaban, and/or edoxaban. 6. Prior consumption of (by any route) one or more doses of aspirin (including baby aspirin), salicylate or subsalicylate, other antiplatelet drugs (e.g., ticlopidine, clopidogrel), non-steroidal anti-inflammatory drugs, fibrinolytic, or any anticoagulant within 7 days prior to Day -1 or is anticipated to require such drugs during the study. 7. Receipt of (by any route) hormonal contraception, post- menopausal hormone replacement therapy (HRT) (including over-the-counter products), or testosterone during the 4 weeks prior to Study Day -1 or is anticipated to require such drugs during the study. 8. Family history of or risk factors for a hypercoagulable or thrombotic condition, including one of the following: 1. Factor V Leiden carrier or homozygote. 2. Protein C, S, or ATIII activity below the normal range. 9. History of adult asthma or chronic obstructive pulmonary disease or current regular or as needed use of inhaled medications. 10. Active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV-1/2 infection. 11. Use of any drugs that are strong dual inhibitors or inducers of CYP3A4 (apixaban and rivaroxaban cohorts only) and P-gp (all cohorts) within 7 days prior to Study Day -1 or anticipated need for such drugs during the study. 12. Participation in an investigational drug study within 45 days of Day -1 or Day -1 is within 5 half-lives of the investigational compound. 13. Positive screen for drugs of abuse at Day -1 that is not explained by a prescription medication that the subject is known to be taking. 14. A medical or surgical condition that may impair drug (anticoagulant or andexanet) metabolism. 15. Allergy to any of the vehicle ingredients: Tris, arginine, sucrose, hydrochloric acid, mannitol, and polysorbate 80. 16. Allergy to soy or soy products. 17. Current breastfeeding or a positive pregnancy test at Screening or Day -1. 18. Any condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would in the opinion of the Investigator increase the risk of the subject's participation in the study. This would include but is not limited to alcoholism, drug dependency or abuse, psychiatric disease, epilepsy, or any unexplained blackouts. 19. The subject is not judged by the study staff to have adequate bilateral venous access. 20. Unwillingness to adhere to the activity requirements of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
Healthy Subjects
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet Andexanet 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Japanese Subjects | 6 |
| Cohort 1 Apixaban 5 mg BID/Placebo Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Japanese Subjects | 3 |
| Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet Andexanet 800 mg bolus+ 8 mg/min 120 minute infusion (dosing at 4 hours post-rivaroxaban); Japanese Subjects | 6 |
| Cohort 2 Rivaroxaban 15 mg BID/Placebo Placebo 800 mg bolus+ 8 mg/min 120 minute infusion placebo (dosing at 4 hours post-rivaroxaban); Japanese Subjects | 3 |
| Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects | 8 |
| Cohort 3 Edooxaban 60 mg QD/Placebo Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 3 hours post-edoxaban); Japanese Subjects | 4 |
| Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet Andexanet 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects | 8 |
| Cohort 4 Edooxaban 60 mg QD/Placebo Placebo 800 mg bolus+8 mg/min 120 minutes infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects | 4 |
| Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet 400 mg bolus+4 mg/min 120 minute Andexanet infusion (dosing at 3 hours post-apixaban); Caucasian Subjects | 6 |
| Cohort 5 Apixaban 5 mg BID/Placebo Placebo 400 mg bolus+4 mg/min 120 minute infusion (placebo dosing at 3 hours post-apixaban); Caucasian Subjects | 3 |
| Cohort 6 Apixaban 10 mg BID/High Dose Andexanet Andexanet 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects | 6 |
| Cohort 6 Apixaban 10 mg BID/Placebo Placebo 800 mg bolus+8 mg/min 120 minute infusion (dosing at 3 hours post-apixaban); Japanese Subjects | 3 |
| Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects | 8 |
| Cohort 7 Edoxaban 30 mg QD/Placebo Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 90 minutes post-edoxaban); Japanese Subjects | 4 |
| Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects | 6 |
| Cohort 8 Apixaban 10 mg BID/Placebo Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-apixaban); Japanese Subjects | 3 |
| Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects | 10 |
| Cohort 9 Rivaroxaban 15 mg BID/Placebo Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-rivaroxaban); Japanese Subjects | 5 |
| Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet Andexanet 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects | 8 |
| Cohort 10 Edoxaban 60 mg QD/Placebo Placebo 400 mg bolus+4 mg/min 120 minute infusion (dosing at 8 hours post-edoxaban); Japanese Subjects | 3 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 7 Edoxaban 30 mg QD/Placebo | 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 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.00 years | 44.50 years | 51.00 years | 47.50 years | 58.00 years | 45.00 years | 35.50 years | 33.0 years | 31.50 years | 31.50 years | 31.00 years | 46.50 years | 36.00 years | 34.50 years | 41.00 years | 53.00 years | 51.00 years | 35.00 years | 28.50 years | 41.00 years | 38.00 years |
| Race/Ethnicity, Customized Asian | 4 Participants | 6 Participants | 3 Participants | 6 Participants | 3 Participants | 8 Participants | 4 Participants | 8 Participants | 4 Participants | 0 Participants | 0 Participants | 6 Participants | 3 Participants | 8 Participants | 6 Participants | 3 Participants | 10 Participants | 5 Participants | 8 Participants | 3 Participants | 98 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 4 Participants | 3 Participants | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 1 Participants | 36 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 8 Participants | 4 Participants | 7 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 6 Participants | 4 Participants | 6 Participants | 2 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 8 | 0 / 4 | 0 / 8 | 0 / 4 | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 8 | 0 / 4 | 0 / 6 | 0 / 3 | 0 / 10 | 0 / 5 | 0 / 8 | 0 / 3 |
| other Total, other adverse events | 1 / 6 | 2 / 3 | 3 / 6 | 1 / 3 | 1 / 8 | 1 / 4 | 3 / 8 | 1 / 4 | 4 / 6 | 0 / 3 | 2 / 6 | 1 / 3 | 2 / 8 | 0 / 4 | 3 / 6 | 0 / 3 | 2 / 10 | 0 / 5 | 1 / 8 | 0 / 3 |
| serious Total, serious adverse events | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 8 | 0 / 4 | 0 / 8 | 0 / 4 | 1 / 6 | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 8 | 0 / 4 | 0 / 6 | 0 / 3 | 0 / 10 | 0 / 5 | 0 / 8 | 0 / 3 |
Outcome results
Primary
Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir.
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -94.50 percent change |
| Cohort 1 Apixaban 5 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -29.00 percent change |
| Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -98.00 percent change |
| Cohort 2 Rivaroxaban 15 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -37.00 percent change |
| Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -81.00 percent change |
| Cohort 3 Edooxaban 60 mg QD/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -47.50 percent change |
| Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -75.50 percent change |
| Cohort 4 Edooxaban 60 mg QD/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -37.00 percent change |
| Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -93.00 percent change |
| Cohort 5 Apixaban 5 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -34.00 percent change |
| Cohort 6 Apixaban 10 mg BID/High Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -97.00 percent change |
| Cohort 6 Apixaban 10 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -31.00 percent change |
| Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -52.50 percent change |
| Cohort 7 Edoxaban 30 mg QD/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -37.00 percent change |
| Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -92.00 percent change |
| Cohort 8 Apixaban 10 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -24.00 percent change |
| Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -93.50 percent change |
| Cohort 9 Rivaroxaban 15 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -37.00 percent change |
| Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -63.50 percent change |
| Cohort 10 Edoxaban 60 mg QD/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. | -27.00 percent change |
p-value: 0.027595% CI: [-78, -58]2-sided Wilcoxon Rank Sum
p-value: 0.02595% CI: [-65, -44]2-sided Wilcoxon Rank Sum
p-value: 0.013695% CI: [-47, -9]2-sided Wilcoxon Rank Sum
p-value: 0.013695% CI: [-62, -9]2-sided Wilcoxon Rank Sum
p-value: 0.02595% CI: [-70, -38]2-sided Wilcoxon Rank Sum
p-value: 0.011995% CI: [-68, -61]2-sided Wilcoxon Rank Sum
p-value: 0.266795% CI: [-38, 17]2-sided Wilcoxon Rank Sum
p-value: 0.023895% CI: [-74, -59]2-sided Wilcoxon Rank Sum
p-value: 0.000795% CI: [-65, -39]2-sided Wilcoxon Rank Sum
p-value: 0.012195% CI: [-53, -24]2-sided Wilcoxon Rank Sum
Secondary
Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir.
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 1145.03 nM.min |
| Cohort 1 Apixaban 5 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 179.94 nM.min |
| Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 1337.28 nM.min |
| Cohort 2 Rivaroxaban 15 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 209.99 nM.min |
| Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 758.92 nM.min |
| Cohort 3 Edooxaban 60 mg QD/Placebo | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 215.71 nM.min |
| Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 815.07 nM.min |
| Cohort 4 Edooxaban 60 mg QD/Placebo | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 48.59 nM.min |
| Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 1244.30 nM.min |
| Cohort 5 Apixaban 5 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 103.13 nM.min |
| Cohort 6 Apixaban 10 mg BID/High Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 1177.47 nM.min |
| Cohort 6 Apixaban 10 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 0.16 nM.min |
| Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 781.42 nM.min |
| Cohort 7 Edoxaban 30 mg QD/Placebo | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 67.97 nM.min |
| Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 1184.62 nM.min |
| Cohort 8 Apixaban 10 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 2.69 nM.min |
| Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 1306.23 nM.min |
| Cohort 9 Rivaroxaban 15 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 117.50 nM.min |
| Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | 902.17 nM.min |
| Cohort 10 Edoxaban 60 mg QD/Placebo | Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. | -92.82 nM.min |
p-value: 0.028295% CI: [474.48, 1377.35]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [769.46, 1575.02]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [307.65, 1175.28]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [535.38, 836.4]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [964.03, 1736.78]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [988.82, 1670.3]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [585.92, 1108.92]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [1001.72, 1471.45]2-sided Wilcoxon Rank Sum
p-value: 0.002795% CI: [857.21, 1296.02]2-sided Wilcoxon Rank Sum
p-value: 0.018995% CI: [585.99, 1498.37]2-sided Wilcoxon Rank Sum
Secondary
Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir.
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 1000.630 nM.min |
| Cohort 1 Apixaban 5 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 171.220 nM.min |
| Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 1329.580 nM.min |
| Cohort 2 Rivaroxaban 15 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 207.590 nM.min |
| Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 804.405 nM.min |
| Cohort 3 Edooxaban 60 mg QD/Placebo | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 347.535 nM.min |
| Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 910.935 nM.min |
| Cohort 4 Edooxaban 60 mg QD/Placebo | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 236.610 nM.min |
| Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 1130.575 nM.min |
| Cohort 5 Apixaban 5 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 118.130 nM.min |
| Cohort 6 Apixaban 10 mg BID/High Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 1119.41 nM.min |
| Cohort 6 Apixaban 10 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 108.67 nM.min |
| Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 833.46 nM.min |
| Cohort 7 Edoxaban 30 mg QD/Placebo | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 175.72 nM.min |
| Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 1058.09 nM.min |
| Cohort 8 Apixaban 10 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 138.14 nM.min |
| Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 1173.38 nM.min |
| Cohort 9 Rivaroxaban 15 mg BID/Placebo | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 293.15 nM.min |
| Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | 793.44 nM.min |
| Cohort 10 Edoxaban 60 mg QD/Placebo | Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. | -72.69 nM.min |
p-value: 0.028295% CI: [505.4, 1362.11]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [873.87, 1552.77]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [291.2, 1077.46]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [500.92, 902.73]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [859.08, 1352.05]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [818.96, 1634.3]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [421.78, 1124.28]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [663.74, 1216.28]2-sided Wilcoxon Rank Sum
p-value: 0.002795% CI: [631.67, 1051.06]2-sided Wilcoxon Rank Sum
p-value: 0.018995% CI: [637.25, 1412.21]2-sided Wilcoxon Rank Sum
Secondary
Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir.
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -94.50 percent change |
| Cohort 1 Apixaban 5 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -14.00 percent change |
| Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -97.50 percent change |
| Cohort 2 Rivaroxaban 15 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -18.00 percent change |
| Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -65.50 percent change |
| Cohort 3 Edooxaban 60 mg QD/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -16.00 percent change |
| Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -22.50 percent change |
| Cohort 4 Edooxaban 60 mg QD/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -15.00 percent change |
| Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -94.00 percent change |
| Cohort 5 Apixaban 5 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -10.00 percent change |
| Cohort 6 Apixaban 10 mg BID/High Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -96.00 percent change |
| Cohort 6 Apixaban 10 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -18.00 percent change |
| Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -58.00 percent change |
| Cohort 7 Edoxaban 30 mg QD/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -8.00 percent change |
| Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -94.50 percent change |
| Cohort 8 Apixaban 10 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -5.00 percent change |
| Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -95.00 percent change |
| Cohort 9 Rivaroxaban 15 mg BID/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -11.00 percent change |
| Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -73.00 percent change |
| Cohort 10 Edoxaban 60 mg QD/Placebo | Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. | -4.00 percent change |
p-value: 0.025695% CI: [-83, -77]2-sided Wilcoxon Rank Sum
p-value: 0.02595% CI: [-97, -67]2-sided Wilcoxon Rank Sum
p-value: 0.07495% CI: [-66, 5]2-sided Wilcoxon Rank Sum
p-value: 0.106695% CI: [-59, 10]2-sided Wilcoxon Rank Sum
p-value: 0.021995% CI: [-87, -71]2-sided Wilcoxon Rank Sum
p-value: 0.026295% CI: [-83, -74]2-sided Wilcoxon Rank Sum
p-value: 0.041295% CI: [-65, 0]2-sided Wilcoxon Rank Sum
p-value: 0.026995% CI: [-93, -77]2-sided Wilcoxon Rank Sum
p-value: 0.002695% CI: [-86, -69]2-sided Wilcoxon Rank Sum
p-value: 0.018195% CI: [-76, -57]2-sided Wilcoxon Rank Sum
Secondary
Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir.
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -93.00 percent change |
| Cohort 1 Apixaban 5 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -11.94 percent change |
| Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -97.72 percent change |
| Cohort 2 Rivaroxaban 15 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -28.57 percent change |
| Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -78.20 percent change |
| Cohort 3 Edooxaban 60 mg QD/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -17.60 percent change |
| Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -56.05 percent change |
| Cohort 4 Edooxaban 60 mg QD/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -2.49 percent change |
| Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -94.45 percent change |
| Cohort 5 Apixaban 5 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | 5.80 percent change |
| Cohort 6 Apixaban 10 mg BID/High Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -93.57 percent change |
| Cohort 6 Apixaban 10 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -12.94 percent change |
| Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -70.88 percent change |
| Cohort 7 Edoxaban 30 mg QD/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -5.48 percent change |
| Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -91.61 percent change |
| Cohort 8 Apixaban 10 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -0.32 percent change |
| Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -95.51 percent change |
| Cohort 9 Rivaroxaban 15 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -14.02 percent change |
| Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -75.80 percent change |
| Cohort 10 Edoxaban 60 mg QD/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. | -17.91 percent change |
p-value: 0.028295% CI: [-92.99, -71.96]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [-96.91, -48.64]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [-72.07, -40.03]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [-80.42, -25.5]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [-133.08, -84.48]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [-86.36, -65.74]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [-89.54, -39.17]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [-128.88, -60.83]2-sided Wilcoxon Rank Sum
p-value: 0.003495% CI: [-91.05, -65.96]2-sided Wilcoxon Rank Sum
p-value: 0.018995% CI: [-110.86, -46.12]2-sided Wilcoxon Rank Sum
Secondary
Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir.
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -92.940 percent change |
| Cohort 1 Apixaban 5 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -33.550 percent change |
| Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -98.650 percent change |
| Cohort 2 Rivaroxaban 15 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -39.390 percent change |
| Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -85.005 percent change |
| Cohort 3 Edooxaban 60 mg QD/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -48.710 percent change |
| Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -81.040 percent change |
| Cohort 4 Edooxaban 60 mg QD/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -42.755 percent change |
| Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -93.495 percent change |
| Cohort 5 Apixaban 5 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -31.830 percent change |
| Cohort 6 Apixaban 10 mg BID/High Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -96.65 percent change |
| Cohort 6 Apixaban 10 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -29.02 percent change |
| Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -62.72 percent change |
| Cohort 7 Edoxaban 30 mg QD/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -24.34 percent change |
| Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -90.63 percent change |
| Cohort 8 Apixaban 10 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -31.45 percent change |
| Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -94.89 percent change |
| Cohort 9 Rivaroxaban 15 mg BID/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -37.82 percent change |
| Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -67.10 percent change |
| Cohort 10 Edoxaban 60 mg QD/Placebo | Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. | -34.25 percent change |
p-value: 0.028295% CI: [-66.48, -52.62]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [-70.34, -26.94]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [-46.14, -29.76]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [-55.81, -20.46]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [-75.82, -43.78]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [-77.4, -61.99]2-sided Wilcoxon Rank Sum
p-value: 0.008595% CI: [-59.77, -11.17]2-sided Wilcoxon Rank Sum
p-value: 0.028295% CI: [-101.02, -48.14]2-sided Wilcoxon Rank Sum
p-value: 0.002795% CI: [-59.14, -41.19]2-sided Wilcoxon Rank Sum
p-value: 0.018995% CI: [-65.78, -15.37]2-sided Wilcoxon Rank Sum