Andexanet dosing and timing to restart enoxaparin in healthy adults

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

This tests different doses of andexanet to see how well it reverses rivaroxaban and apixaban and when enoxaparin can be safely restarted in healthy adults.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 186 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: AstraZeneca (Industry-sponsored)
• Locations: 2 sites (Berlin and 1 other locations)
• Trial ID: NCT07312851 on ClinicalTrials.gov

What this trial studies

This single-blind, placebo-controlled Phase 1 study enrolls healthy adults to characterize andexanet dosing (posology) and its interaction with subsequent enoxaparin. The protocol is organized into four modules and two parts: Part A refines andexanet dosing and Part B evaluates re‑institution of anticoagulation with enoxaparin. Modules 1, 2 and 4 assess reversal of rivaroxaban, apixaban, or effects in the absence of anticoagulants and identify when andexanet no longer impacts enoxaparin, while Module 3 examines bolus-only andexanet reversal. Participants complete screening, an in-house residential baseline and treatment period, short safety follow-up, and a final visit about 30 days after dosing.

Who should consider this trial

Good fit: Healthy adults who meet study criteria (BMI 18.5–30 kg/m2, weight ≥60 kg), agree to required contraception and testing, and can complete the residential in‑house periods are eligible.

Not a fit: Patients with active bleeding, those on chronic anticoagulation for clinical indications, or people with significant medical comorbidities are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could guide safer dosing and timing for restarting low‑molecular‑weight heparin after andexanet, helping reduce bleeding and clotting risks.

How similar studies have performed: Prior clinical work has shown andexanet alfa can rapidly reverse rivaroxaban and apixaban anticoagulation, but timing for safe re‑anticoagulation with enoxaparin is less well characterized.

Eligibility 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.

Where this trial is running

Berlin and 1 other locations

• Research Site — Berlin, Germany (Recruiting)
• Research Site — Harrow, United Kingdom (Recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions Healthy Participants; Posology; Re-anticoagulation; Pharmacodynamics; Life-threatening or uncontrolled bleeding; Thrombotic events; Factor Xa inhibitors