A Study to Investigate Andexanet Dosing and the Interaction Between Andexanet and Subsequent Enoxaparin in Healthy Participants
A Phase I, Randomized, Single-blind, Placebo-controlled Study to Further Characterize Andexanet Posology and Assess the Interaction Between Andexanet and Subsequent Enoxaparin in Healthy Participants
2 other identifiers
interventional
186
2 countries
2
Brief Summary
The purpose of this study is to characterize andexanet posology and interaction between andexanet and enoxaparin post infusion in healthy participants.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2026
Shorter than P25 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 27, 2025
CompletedFirst Posted
Study publicly available on registry
December 31, 2025
CompletedStudy Start
First participant enrolled
January 19, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 19, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 19, 2026
April 24, 2026
April 1, 2026
5 months
November 27, 2025
April 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (10)
Anti-Factor (F) Xa activity
To determine the pharmacodynamic (PD) effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured by chromogenic enzymatic anti-FXa activity assays.
Day 1 post dose
Change from baseline in anti-FXa activity
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured by chromogenic enzymatic anti-FXa activity assays.
Day 1 post dose
Thrombin generation potential
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as thrombin generation potential (including Endogenous Thrombin Potential \[ETP\]).
Day 1 post dose
Change from pre-direct oral anticoagulants (DOAC) in thrombin generation potential
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as thrombin generation potential (including ETP).
Day 1 post dose
Change from baseline in thrombin generation potential
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as thrombin generation potential (including ETP).
Day 1 post dose
Time to onset of coagulation
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as time to onset of coagulation.
Day 1 post dose
Change from pre-DOAC in time to onset of coagulation
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as time to onset of coagulation.
Day 1 post dose
Change from baseline in time to onset of coagulation
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as time to onset of coagulation.
Day 1 post dose
Anti-FXa activity following enoxaparin dosing
To determine anticoagulation by enoxaparin at different time points after andexanet treatment measured by chromogenic enzymatic anti-FXa activity assays.
From Day 1 to Day 2
Thrombin generation potential following enoxaparin dosing
To determine anticoagulation by enoxaparin at different time points after andexanet treatment measured as thrombin generation potential (including ETP).
From Day 1 to Day 2
Secondary Outcomes (13)
Module 3: Anti-FXa activity
Day 1 post dose
Module 3: Change from baseline in anti-FXa activity
Day 1 post dose
Module 3: Thrombin generation potential
Day 1 post dose
Module 3: Change from baseline in thrombin generation potential
Day 1 post dose
Module 3: Change from pre-DOAC in thrombin generation potential
Day 1 post dose
- +8 more secondary outcomes
Study Arms (14)
Module 1: Rivaroxaban + Andexanet (dose A)
EXPERIMENTALParticipants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose A) dosing, the participants will receive an additional dose of rivaroxaban. Participants will be further allocated to groups to receive doses of enoxaparin at different time points after the end of andexanet bolus.
Module 1: Rivaroxaban + Andexanet (dose B)
EXPERIMENTALParticipants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose B) dosing, the participants will receive an additional dose of rivaroxaban.
Module 1: Rivaroxaban + Andexanet (dose C)
EXPERIMENTALParticipants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose C) dosing, the participants will receive an additional dose of rivaroxaban.
Module 1: Rivaroxaban + Placebo
EXPERIMENTALParticipants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before placebo (equivalent to dose B of andexanet) dosing, the participants will receive an additional dose of rivaroxaban. Participants will be further allocated to groups to receive doses of enoxaparin at different time points after placebo administration.
Module 2: Apixaban + Andexanet (dose B)
EXPERIMENTALParticipants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose B) dosing, the participants will receive an additional dose of apixaban. Participants will be further allocated to groups to receive doses of enoxaparin at different time points after the end of andexanet bolus.
Module 2: Apixaban + Andexanet (dose C)
EXPERIMENTALParticipants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose C) dosing, the participants will receive an additional dose of apixaban.
Module 2: Apixaban + Andexanet (dose D)
EXPERIMENTALParticipants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose D) dosing, the participants will receive an additional dose of apixaban.
Module 2: Apixaban + Placebo
EXPERIMENTALParticipants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before placebo (equivalent to dose B of andexanet) dosing, the participants will receive an additional dose of apixaban. Participants will be further allocated to groups to receive doses of enoxaparin at different time points after placebo administration.
Module 3: Rivaroxaban + Andexanet (Dose A)
EXPERIMENTALParticipants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose A) dosing, the participants will receive an additional dose of rivaroxaban.
Module 3: Apixaban + Andexanet (Dose B)
EXPERIMENTALParticipants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose B) dosing, the participants will receive an additional dose of apixaban.
Module 3: Rivaroxaban + Placebo
EXPERIMENTALParticipants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before placebo (equivalent to dose A of andexanet) dosing, the participants will receive an additional dose of rivaroxaban.
Module 3: Apixaban + Placebo
EXPERIMENTALParticipants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before placebo (equivalent to dose B of andexanet) dosing, the participants will receive an additional dose of apixaban.
Module 4: Placebo + Andexanet (dose C)
EXPERIMENTALParticipants will receive daily dose of one placebo tablet from Day -3 to Day -1. On Day 1, approximately 3 hours before andexanet (dose C) dosing, the participants will receive an additional placebo tablet.
Module 4: Placebo + Andexanet (dose B)
EXPERIMENTALParticipants will receive daily dose of one placebo tablet from Day -3 to Day -1. On Day 1, approximately 3 hours before andexanet (dose B) dosing, the participants will receive an additional placebo tablet. Participants will be further allocated to groups to receive doses of enoxaparin at different time points after the end of andexanet bolus.
Interventions
Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given.
Rivaroxaban will be administered as an oral tablet.
Apixaban will be administered as an oral tablet.
Enoxaparin will be administered as a subcutaneous injection.
Placebo will replace andexanet and be given as an IV bolus plus infusion in Modules 1 and 2; in Module 3, placebo will be IV bolus only. In Module 4, an oral placebo tablet will replace rivaroxaban and apixaban.
Eligibility Criteria
You may qualify if:
- All females must have a negative pregnancy test at the Screening Visit.
- Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception.
- Sexually active fertile male participants with partners of childbearing potential must adhere to the study specific contraception methods.
- Have a Body Mass Index (BMI) between 18.5 and 30.0 kg/m2 (both inclusive) and weigh at least 60 kg.
- Agree to abstain from alcohol consumption or smoking for the duration of the residential period, and from the use of drugs of abuse for the duration of the study.
- Be in good health and agree to have any dietary or nutritional supplements, if needed.
You may not qualify if:
- History of any clinically significant disease or disorder which may either put the participant at risk because of participation in the study or influence the results or the participant's ability to participate in the study.
- History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- History of abnormal bleeding or bleeding disorders (eg, hemophilia, von Willebrand disease), signs or symptoms of active bleeding, or risk factors for bleeding.
- History of adult asthma or chronic obstructive pulmonary disease or current regular or as needed use of inhaled medications.
- Family history of or known risk factors for a hypercoagulable or thrombotic condition or thrombotic event, such as anti-phospholipid syndrome; Factor V Leiden carrier or homozygote; Protein C, S, or AT3 activity below the normal range.
- Past or current medical history of thrombosis, any sign or symptom that suggests an increased risk of a systemic thrombotic condition, or recent events that may increase risk of thrombosis.
- Any medical or surgical conditions which may impair drug (anticoagulant or andexanet) uptake, metabolism, or excretion.
- An absolute or relative contraindication to anticoagulation or treatment with apixaban, rivaroxaban or enoxaparin.
- Any clinically significant illness or medical procedure within 4 weeks of the first administration of study intervention.
- Any clinically significant abnormalities in clinical chemistry, hematology, coagulation or urinalysis results
- Any positive result on Screening for serum hepatitis B surface antigen (HBsAg) OR anti-hepatitis B core (HBc) antibody, indicative of active hepatitis B (ie, participants with positive anti-HBc antibody result are acceptable if anti-HBc IgM antibodies are negative), anti- hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
- History of severe allergy/hypersensitivity or ongoing clinically significant allergy/hypersensitivity, including heparin-induced thrombocytopenia, or history of hypersensitivity to drugs with a similar chemical structure or class to andexanet, apixaban, rivaroxaban, or enoxaparin or any of the vehicle ingredients.
- Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, intake of \> 3 Ă— daily recommended levels of vitamins and minerals during the 2 weeks prior to the first administration of study intervention or longer (\> 5 half-lives) if the medication has a long half-life. The participant has taken (by any route) one or more doses of aspirin (including baby aspirin), salicylate or subsalicylate, other antiplatelet drugs (eg, ticagrelor, clopidogrel, ticlopidine), non-steroidal anti-inflammatory drugs, fibrinolytic, or any anticoagulant within 7 days prior to Admission or is anticipated to require such drugs during the study. The participant has been receiving (by any route) hormonal contraception, postmenopausal HRT (including over-the-counter products), or testosterone during the 4 weeks prior to Admission or is anticipated to require such drugs during the study.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days or 5 half-lives (whichever is longest) of Admission.
- Participants who have previously received andexanet.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Parexelcollaborator
Study Sites (2)
Research Site
Berlin, 14050, Germany
Research Site
Harrow, HA1 3UJ, United Kingdom
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Masking Details
- Single blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 27, 2025
First Posted
December 31, 2025
Study Start
January 19, 2026
Primary Completion (Estimated)
June 19, 2026
Study Completion (Estimated)
June 19, 2026
Last Updated
April 24, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.