Comparison of Two Doses of Edoxaban Using Different Tests (Assays) and Clinical Outcomes

Not Applicable

Completed

Brief Summary: Atrial fibrillation is when the heart's two upper chambers (called atria) beat chaotically and irregularly, out of coordination with the two lower chambers (called ventricles) of the heart. This can lead to blood clots forming in the heart chamber.

Patients with atrial fibrillation will be treated with either 60 mg or 75 mg of edoxaban for up to 12 months, with a 2-4 week follow-up, after which their participation is complete.

Blood samples will be collected before the first dose of study drug (Day 0), and on Days 30, 90 and 360 (at pre dose, 1-2 hours post dose and 4-8 hours post-dose).

Recruitment & Eligibility

Inclusion Criteria

Meets protocol-specified criteria for qualification
Is able to follow the protocol specified contraception methods
Is willing and able to comply with any restrictions related to food, drink and medications
Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures

Exclusion Criteria

Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters
Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:
1. the safety or well-being of the participant or study staff
2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding)
3. the analysis of results

Arm && Interventions

Group	Intervention	Description
Edoxaban 75 mg	Edoxaban	Edoxaban 60 mg + edoxaban 15 mg orally, once daily, at the same time (preferably morning) for up to 12 months, with a 2-4 week follow-up period. If needed when the patient completes or discontinues the study, an open-label transition dose of 30 mg and 15 mg edoxaban tablets will be provided.
Edoxaban 60 mg	Edoxaban	Edoxaban 60 mg + placebo 15 mg orally, once daily, at the same time (preferably morning) for up to 12 months, with a 2-4 week follow-up period. If needed when the patient completes or discontinues the study, an open-label transition dose of 30 mg and 15 mg edoxaban tablets will be provided.

Primary Outcome Measures

Name	Time	Method
Pharmacodynamics: Mean exposure with anti-Factor Xa (FXa) assay	Pre-dose and after initiation of dosing on Days 30, 90, and 360 (at pre dose, 1-2 hours post dose and 4-8 hours post-dose)	Exposure analysis performed with anti-FXa assay, using sodium citrate plasma samples Categories: Edoxaban and D21-2393
Pharmacokinetics: Average Concentration of Edoxaban at Steady State (Cav)	After initiation of dosing on Days 30, 90, and 360 (at pre dose, 1-2 hours post dose and 4-8 hours post-dose)	In pharmacokinetics, steady state means the overall intake of a drug is about equal to its elimination
Pharmacokinetics: Minimum Concentration of Edoxaban in Plasma (Cmin)	After initiation of dosing on Days 30, 90, and 360 (at pre dose, 1-2 hours post dose and 4-8 hours post-dose)	Cmin is a term used in pharmacokinetics that usually refers to the minimum blood plasma concentration that a drug achieves after the drug has been administered and prior to the administration of a second dose
Pharmacodynamics: Mean exposure using validated assays	Pre-dose and after initiation of dosing on Days 30, 90, and 360 (at pre dose, 1-2 hours post dose and 4-8 hours post-dose)	Exposure analysis performed with validated Liquid Chromatography/Tandem Mass Spectrometry/Mass Spectrometry (LC/MS/MS) assay with lithium heparin plasma. Categories: Edoxaban and its metabolite (D21-2393)

Secondary Outcome Measures

Name	Time	Method
Efficacy: Number of participants with composite event 1	within 3 years	Composite event 1 includes ischemic or hemorrhagic stroke/transient ischemic attack (TIA) and systemic embolic events (SEE)
Safety: Number of participants with major bleeding (including intracranial)	within 3 years	Major bleeding is defined per the International Society on Thrombosis and Haemostasis (ISTH) definition
Safety: Number of participants with any bleeding	within 3 years	Count of participants who experienced any bleeding event
Safety: Number of participants with clinically relevant bleeding	within 3 years	Clinically relevant bleeding is a combination of major bleeding and clinically relevant non-major (CRNM) bleeding
Efficacy: Number of participants with composite event 2	within 3 years	Composite event 2 includes stroke/TIA, SEE, myocardial infarction, cardiovascular death, and major bleeding

Locations (230): O L V Ziekenhuis
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Aalst, Belgium
ZNA Middelheim
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Antwerpen, Belgium
AZ Sint-Jan Brugge
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Brugge, Belgium
C H U Brugmann - Site Victor Horta
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Bruxelles, Belgium
Jessa Ziekenhuis - Campus Virga Jesse
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Hasselt, Belgium
St-Franciskus Ziekenhuis
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Heusden-Zolder, Belgium
Universitairsitaire Ziekenhuizen Leuven
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Leuven, Belgium
C H R de la Citadelle
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Liege, Belgium
AZ Sint-Maarten
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Mechelen, Belgium
AZ Turnhout - Campus Sint-Elisabeth
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Turnhout, Belgium
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O L V Ziekenhuis
🇧🇪Aalst, Belgium