A Study to Investigate Andexanet Dosing and the Interaction Between Andexanet and Subsequent Enoxaparin in Healthy Participants

Study identifier:D9609C00001

ClinicalTrials.gov identifier:NCT07312851

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

Official Title

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

Medical condition

Healthy Participants

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Andexanet alfa, Rivaroxaban, Apixaban, Enoxaparin

Sex

All

Estimated Enrollment

186

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 19 Jan 2026

Estimated Primary Completion Date: 19 Jun 2026

Estimated Study Completion Date: 19 Jun 2026

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2026 by AstraZeneca

Collaborators

PAREXEL

Inclusion and exclusion criteria

Inclusion Criteria

Main Inclusion Criteria:
• 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.
Main Exclusion Criteria:
• 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 × 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.

Sort by status

No locations available

Arms	Assigned Interventions
Experimental: Module 1: Rivaroxaban + Andexanet (dose A) Participants 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.	Drug: Andexanet alfa Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given. Drug: Rivaroxaban Rivaroxaban will be administered as an oral tablet. Drug: Enoxaparin Enoxaparin will be administered as a subcutaneous injection.
Experimental: Module 1: Rivaroxaban + Andexanet (dose B) Participants 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.	Drug: Andexanet alfa Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given. Drug: Rivaroxaban Rivaroxaban will be administered as an oral tablet.
Experimental: Module 1: Rivaroxaban + Andexanet (dose C) Participants 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.	Drug: Andexanet alfa Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given. Drug: Rivaroxaban Rivaroxaban will be administered as an oral tablet.
Experimental: Module 1: Rivaroxaban + Placebo Participants 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.	Drug: Rivaroxaban Rivaroxaban will be administered as an oral tablet. Drug: Enoxaparin Enoxaparin will be administered as a subcutaneous injection. Other: Placebo 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.
Experimental: Module 2: Apixaban + Andexanet (dose B) Participants 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.	Drug: Andexanet alfa Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given. Drug: Apixaban Apixaban will be administered as an oral tablet. Drug: Enoxaparin Enoxaparin will be administered as a subcutaneous injection.
Experimental: Module 2: Apixaban + Andexanet (dose C) Participants 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.	Drug: Andexanet alfa Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given. Drug: Apixaban Apixaban will be administered as an oral tablet.
Experimental: Module 2: Apixaban + Andexanet (dose D) Participants 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.	Drug: Andexanet alfa Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given. Drug: Apixaban Apixaban will be administered as an oral tablet.
Experimental: Module 2: Apixaban + Placebo Participants 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.	Drug: Apixaban Apixaban will be administered as an oral tablet. Drug: Enoxaparin Enoxaparin will be administered as a subcutaneous injection. Other: Placebo 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.
Experimental: Module 3: Rivaroxaban + Andexanet (Dose A) Participants 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.	Drug: Andexanet alfa Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given. Drug: Rivaroxaban Rivaroxaban will be administered as an oral tablet.
Experimental: Module 3: Apixaban + Andexanet (Dose B) Participants 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.	Drug: Andexanet alfa Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given. Drug: Apixaban Apixaban will be administered as an oral tablet.
Experimental: Module 3: Rivaroxaban + Placebo Participants 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.	Drug: Rivaroxaban Rivaroxaban will be administered as an oral tablet. Other: Placebo 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.
Experimental: Module 3: Apixaban + Placebo Participants 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.	Drug: Apixaban Apixaban will be administered as an oral tablet. Other: Placebo 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.
Experimental: Module 4: Placebo + Andexanet (dose C) Participants 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.	Drug: Andexanet alfa Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given. Other: Placebo 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.
Experimental: Module 4: Placebo + Andexanet (dose B) Participants 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.	Drug: Andexanet alfa Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given. Drug: Enoxaparin Enoxaparin will be administered as a subcutaneous injection. Other: Placebo 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.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]