Atrial Fibrillation
Conditions
Keywords
Nonvalvular Atrial Fibrillation, High Creatinine Clearance, Developmental Phase III, Anticoagulant Naïve
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).
Interventions
DRUGEdoxaban
Edoxaban will be provided in blister packs with active and placebo tablets maintaining the blind, i.e., one 60 mg active tablet and a 15 mg placebo or one 60 mg active tablet and a 15 mg active tablet. Transition doses of 30 mg + 15 mg edoxaban are provided in 14-tablet blister packs.
Sponsors
Quintiles, Inc.
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 any bleeding | within 3 years | Count of participants who experienced any bleeding event |
| 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 |
| 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 clinically relevant bleeding | within 3 years | Clinically relevant bleeding is a combination of major bleeding and clinically relevant non-major (CRNM) bleeding |
Countries
Belgium, Bulgaria, Croatia, Czechia, Denmark, Estonia, Hungary, Latvia, Lithuania, Poland, Russia, Serbia, Slovakia, Spain, Ukraine
Outcome results
None listed