BleedingPhase 2NCT03310021

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

A Phase 2 study testing Andexanet alfa, Apixaban and Rivaroxaban in people with Bleeding, run by Portola Pharmaceuticals at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Bleeding
What is being tested?: Andexanet alfa, Apixaban and Rivaroxaban
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 108 participants
Where: 1 siteUnited States
Study dates: 28 Aug 2017to 13 Aug 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Show all 18Show fewer

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.
Systolic blood pressure < 160 mmHg and diastolic blood pressure < 90 mmHg at Screening and Day -1.
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.
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.
The Screening serum creatinine must be below 1.5 mg/dL within 45 days of Day -1.
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.
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.
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)."

Who cannot join

Previous use of andexanet or previous participation in the current study (even if the subject received placebo).
History of abnormal bleeding, signs or symptoms of active bleeding, or risk factors for bleeding.
Has a stool specimen that was positive for occult blood within 6 months of study Screening or during the Screening Period.
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.
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.
Absolute or relative contraindication to anticoagulation or treatment with apixaban, rivaroxaban, and/or edoxaban.

Show all 23Show fewer

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.
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.
Family history of or risk factors for a hypercoagulable or thrombotic condition, including one of the following:
Factor V Leiden carrier or homozygote.
Protein C, S, or ATIII activity below the normal range.
History of adult asthma or chronic obstructive pulmonary disease or current regular or as needed use of inhaled medications.
Active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV-1/2 infection.
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.
Participation in an investigational drug study within 45 days of Day -1 or Day -1 is within 5 half-lives of the investigational compound.
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.
A medical or surgical condition that may impair drug (anticoagulant or andexanet) metabolism.
Allergy to any of the vehicle ingredients: Tris, arginine, sucrose, hydrochloric acid, mannitol, and polysorbate 80.
Allergy to soy or soy products.
Current breastfeeding or a positive pregnancy test at Screening or Day -1.
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.
The subject is not judged by the study staff to have adequate bilateral venous access.
Unwillingness to adhere to the activity requirements of the study."

Trial locations and contacts

1 site in 1 country.

United States1 site

WCCT Global
Cypress, California, 90630

Other trials in United States

About this study

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

Conditions: Bleeding
Being tested: Andexanet alfa, Apixaban, Rivaroxaban, Edoxaban, Placebo
Medical subject headings: Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Andexanet alfaBiological
Also called 200 mg/vial for IV injection
fXa inhibitor antidote
ApixabanDrug
Also called Eliquis
factor Xa inhibitor
RivaroxabanDrug
Also called Xarelto
factor Xa inhibitor
EdoxabanDrug
Also called Savaysa, Lixiana
factor Xa inhibitor
PlaceboDrug
Placebo

Study groups in NCT03310021
Study group	Role	What they receive
Cohort 1	Experimental	Apixaban + low dose andexanet Receives: Biological: Andexanet alfa; Drug: Apixaban; Drug: Placebo
Cohort 2	Experimental	Rivaroxaban + high dose andexanet Receives: Biological: Andexanet alfa; Drug: Rivaroxaban; Drug: Placebo
Cohort 3	Experimental	Edoxaban + high dose andexanet Receives: Biological: Andexanet alfa; Drug: Edoxaban; Drug: Placebo
Cohort 4	Experimental	Edoxaban + high dose andexanet Receives: Biological: Andexanet alfa; Drug: Edoxaban; Drug: Placebo
Cohort 5	Experimental	Apixaban + low dose andexanet Receives: Biological: Andexanet alfa; Drug: Apixaban; Drug: Placebo
Cohort 6	Experimental	Apixaban + high dose andexanet Receives: Biological: Andexanet alfa; Drug: Apixaban; Drug: Placebo
Cohort 7	Experimental	Edoxaban + low dose andexanet Receives: Biological: Andexanet alfa; Drug: Edoxaban; Drug: Placebo
Cohort 8	Experimental	Apixaban + low dose andexanet Receives: Biological: Andexanet alfa; Drug: Apixaban; Drug: Placebo
Cohort 9	Experimental	Rivaroxaban + low dose andexanet Receives: Biological: Andexanet alfa; Drug: Rivaroxaban; Drug: Placebo
Cohort 10	Experimental	Edoxaban + low dose andexanet Receives: Biological: Andexanet alfa; Drug: Edoxaban; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours

Secondary outcomes (5)

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.
Measured: Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours
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.
Measured: Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours
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.
Measured: Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours
Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir.
The change in thrombin generation from baseline to its EOB peak.
Measured: Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours
Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir.
The change in thrombin generation from baseline to its EOI peak.
Measured: Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Aug 201713 Aug 2019

First posted16 Oct 2017
Study start28 Aug 2017
Primary completion13 Aug 2019
Study completion13 Aug 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for BleedingStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 108 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03310021
Sponsor's protocol ID: 16-508
Status last verified: Feb 2023
First submitted: 7 Sep 2017
Last updated: 24 Feb 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Not yet recruiting
BrainGate2: Feasibility Study of an Intracortical Neural Interface System for Persons With Aphasia (BG-Aphasia-01)
Expressive Aphasia, Aphasia Following Cerebral Infarction
RecruitingObservational study
A Study in Children and, Adults With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Treated With Adzynma
Thrombotic Thrombocytopenic Purpura (TTP)
Not yet recruitingPhase 3
TicAgreLor Versus Placebo to Prevent Cerebral ISCHemia in anEuRysmal Low Grade SAH A Double Blinded Randomised Controlled Study
Subarachnoid Hemorrhage, Aneurysmal, Brain Ischemia
Not yet recruitingObservational study
Systematic Intraoperative Cell Salvage in On-Pump Cardiac Surgery Within a Mature Patient Blood Management Programme
Cardiac Surgical Procedures, Blood Transfusion

All Bleeding trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03310021
Acronym / sponsor ID: 16-508
Conditions: Bleeding
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 108 participants (actual)
Lead sponsor: Portola PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 28 Aug 2017 (actual)
Primary completion: 13 Aug 2019 (actual)
Study completion: 13 Aug 2019 (actual)
First posted: 16 Oct 2017 (actual)
Results: Posted 14 Aug 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 10

Arm	Type	Receives
Cohort 1	Experimental	Biological: Andexanet alfa, Drug: Apixaban, Drug: PlaceboApixaban + low dose andexanet
Cohort 2	Experimental	Biological: Andexanet alfa, Drug: Rivaroxaban, Drug: PlaceboRivaroxaban + high dose andexanet
Cohort 3	Experimental	Biological: Andexanet alfa, Drug: Edoxaban, Drug: PlaceboEdoxaban + high dose andexanet
Cohort 4	Experimental	Biological: Andexanet alfa, Drug: Edoxaban, Drug: PlaceboEdoxaban + high dose andexanet
Cohort 5	Experimental	Biological: Andexanet alfa, Drug: Apixaban, Drug: PlaceboApixaban + low dose andexanet
Cohort 6	Experimental	Biological: Andexanet alfa, Drug: Apixaban, Drug: PlaceboApixaban + high dose andexanet
Cohort 7	Experimental	Biological: Andexanet alfa, Drug: Edoxaban, Drug: PlaceboEdoxaban + low dose andexanet
Cohort 8	Experimental	Biological: Andexanet alfa, Drug: Apixaban, Drug: PlaceboApixaban + low dose andexanet
Cohort 9	Experimental	Biological: Andexanet alfa, Drug: Rivaroxaban, Drug: PlaceboRivaroxaban + low dose andexanet
Cohort 10	Experimental	Biological: Andexanet alfa, Drug: Edoxaban, Drug: PlaceboEdoxaban + low dose andexanet

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (18 listed)

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.
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.
Must be between the ages of 18 and 75 years, inclusive, at the time of signing of the Inform Consent Form (ICF).
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.
Agrees to comply with the contraception and reproduction restrictions of the study:

Key exclusion criteria (23 listed)

Previous use of andexanet or previous participation in the current study (even if the subject received placebo).
History of abnormal bleeding, signs or symptoms of active bleeding, or risk factors for bleeding.
Has a stool specimen that was positive for occult blood within 6 months of study Screening or during the Screening Period.
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.
Absolute or relative contraindication to anticoagulation or treatment with apixaban, rivaroxaban, and/or edoxaban.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Andexanet alfaAlso: 200 mg/vial for IV injectionfXa inhibitor antidote	Biological	Cohort 1, Cohort 10, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6, Cohort 7, Cohort 8, Cohort 9
ApixabanAlso: Eliquisfactor Xa inhibitor	Drug	Cohort 1, Cohort 5, Cohort 6, Cohort 8
RivaroxabanAlso: Xareltofactor Xa inhibitor	Drug	Cohort 2, Cohort 9
EdoxabanAlso: Savaysa, Lixianafactor Xa inhibitor	Drug	Cohort 10, Cohort 3, Cohort 4, Cohort 7
PlaceboPlacebo	Drug	Cohort 1, Cohort 10, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6, Cohort 7, Cohort 8, Cohort 9

Primary outcome

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

5 secondary outcomes

Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir.
Time frame: Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours
Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir.
Time frame: Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours
Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir.
Time frame: Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours
Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir.
Time frame: Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours
Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir.
Time frame: Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours

Results and safety

Results posted to the registry on 14 Aug 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet	6	6
Cohort 1 Apixaban 5 mg BID/Placebo	3	3
Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet	6	6
Cohort 2 Rivaroxaban 15 mg BID/Placebo	3	3
Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet	8	8
Cohort 3 Edooxaban 60 mg QD/Placebo	4	4
Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet	8	7
Cohort 4 Edooxaban 60 mg QD/Placebo	4	4
Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet	6	6
Cohort 5 Apixaban 5 mg BID/Placebo	3	3
Cohort 6 Apixaban 10 mg BID/High Dose Andexanet	6	5
Cohort 6 Apixaban 10 mg BID/Placebo	3	3
Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet	8	8
Cohort 7 Edoxaban 30 mg QD/Placebo	4	4
Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet	6	6
Cohort 8 Apixaban 10 mg BID/Placebo	3	3
Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet	10	10
Cohort 9 Rivaroxaban 15 mg BID/Placebo	5	5
Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet	8	8
Cohort 10 Edoxaban 60 mg QD/Placebo	3	3

Primary outcome: Percent Change in 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. Median (Full Range). Unit: percent change

Measure	Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet n = 6	Cohort 1 Apixaban 5 mg BID/Placebo n = 3	Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet n = 6	Cohort 2 Rivaroxaban 15 mg BID/Placebo n = 3	Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet n = 8	Cohort 3 Edooxaban 60 mg QD/Placebo n = 4	Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet n = 8	Cohort 4 Edooxaban 60 mg QD/Placebo n = 4	Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet n = 6	Cohort 5 Apixaban 5 mg BID/Placebo n = 3	Cohort 6 Apixaban 10 mg BID/High Dose Andexanet n = 6	Cohort 6 Apixaban 10 mg BID/Placebo n = 3	Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet n = 8	Cohort 7 Edoxaban 30 mg QD/Placebo n = 4	Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet n = 6	Cohort 8 Apixaban 10 mg BID/Placebo n = 3	Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet n = 10	Cohort 9 Rivaroxaban 15 mg BID/Placebo n = 5	Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet n = 8	Cohort 10 Edoxaban 60 mg QD/Placebo n = 3
Value	-94.50 (-96.00 to -90.00)	-29.00 (-32.00 to -18.00)	-98.00 (-99.00 to -97.00)	-37.00 (-53.00 to -34.00)	-81.00 (-89.00 to -51.00)	-47.50 (-62.00 to -34.00)	-75.50 (-82.00 to -45.00)	-37.00 (-46.00 to -16.00)	-93.00 (-94.00 to -91.00)	-34.00 (-53.00 to -24.00)	-97.00 (-98.00 to -96.00)	-31.00 (-35.00 to -30.00)	-52.50 (-69.00 to -34.00)	-37.00 (-67.00 to -17.00)	-92.00 (-95.00 to -90.00)	-24.00 (-31.00 to -21.00)	-93.50 (-98.00 to -89.00)

Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet vs Cohort 1 Apixaban 5 mg BID/Placebo: Hodges lehman Location shift: -65.5 (95% CI -78.00 to -58.00), p = 0.0275, 2-sided Wilcoxon Rank Sum
Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet vs Cohort 2 Rivaroxaban 15 mg BID/Placebo: Hodges lehman Location shift: -61 (95% CI -65.00 to -44.00), p = 0.025, 2-sided Wilcoxon Rank Sum
Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet vs Cohort 3 Edooxaban 60 mg QD/Placebo: Hodges lehman Location shift: -32.5 (95% CI -47.00 to -9.00), p = 0.0136, 2-sided Wilcoxon Rank Sum

Population analysed: 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.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Study day 1 to 39. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Cohort 1 Apixaban 5 mg BID/Placebo	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Cohort 2 Rivaroxaban 15 mg BID/Placebo	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
Cohort 3 Edooxaban 60 mg QD/Placebo	0 of 4 (0%)	1 of 4 (25%)	0 of 4
Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8
Cohort 4 Edooxaban 60 mg QD/Placebo	0 of 4 (0%)	1 of 4 (25%)	0 of 4
Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet	1 of 6 (16.7%)	4 of 6 (66.7%)	0 of 6
Cohort 5 Apixaban 5 mg BID/Placebo	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Cohort 6 Apixaban 10 mg BID/High Dose Andexanet	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Cohort 6 Apixaban 10 mg BID/Placebo	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Cohort 7 Edoxaban 30 mg QD/Placebo	0 of 4 (0%)	0 of 4 (0%)	0 of 4
Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Cohort 8 Apixaban 10 mg BID/Placebo	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet	0 of 10 (0%)	2 of 10 (20%)	0 of 10
Cohort 9 Rivaroxaban 15 mg BID/Placebo	0 of 5 (0%)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Bleeding

Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Not yet recruiting
BrainGate2: Feasibility Study of an Intracortical Neural Interface System for Persons With Aphasia (BG-Aphasia-01)
Expressive Aphasia, Aphasia Following Cerebral Infarction
RecruitingObservational study
A Study in Children and, Adults With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Treated With Adzynma
Thrombotic Thrombocytopenic Purpura (TTP)
Not yet recruitingPhase 3
TicAgreLor Versus Placebo to Prevent Cerebral ISCHemia in anEuRysmal Low Grade SAH A Double Blinded Randomised Controlled Study
Subarachnoid Hemorrhage, Aneurysmal, Brain Ischemia
Not yet recruitingObservational study
Systematic Intraoperative Cell Salvage in On-Pump Cardiac Surgery Within a Mature Patient Blood Management Programme
Cardiac Surgical Procedures, Blood Transfusion

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Andexanet alfa, Apixaban and Rivaroxaban in people with Bleeding, run by Portola Pharmaceuticals at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change in 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03310021.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2023; AzTrials last refreshed its copy on 8 Nov 2026.