Multicenter, randomized, active comparator-controlled, double-blind, double-dummy, parallel group, dose-finding Phase 2 study to compare the safety of the oral FXIa inhibitor BAY 2433334 to apixaban in patients with atrial fibrillatio
- Conditions
- arrhythmiaatrial fibrillation10007521
- Registration Number
- NL-OMON49562
- Lead Sponsor
- Bayer
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 62
1. Participant must be 45 years of age or older at the time of signing the
informed consent.
2. Participant with AF documented by ECG evidence with
* CHA2DS2-VASc score **2 if male or CHA2DS2-VASc score **3 if female
* Indication for treatment with an oral anticoagulant in
* any participant currently not treated with an oral anticoagulant
(e.g. treatment naïve) or alternatively,
* participant on a NOAC in case of at least one bleeding risk feature
(history of a prior bleed within the last 12 months requiring medical
attention and*/*or moderate renal dysfunction with eGFR 30-50 ml/min and*/*or
current clinically indicated antiplatelet therapy with ASA * 100 mg)
1. Mechanical heart valve prosthesis
2. Any degree of rheumatic mitral stenosis or moderate-to-severe, non-rheumatic
mitral stenosis
3. Atrial fibrillation due to a reversible cause, participants in sinus rhythm
after successful ablation, or plan for cardioversion or ablation during study
conduct
4. Stroke within the last 30 days of screening
5. Uncontrolled hypertension (systolic blood pressure **160 mmHg or diastolic
blood pressure **100 mmHg) at randomization
6. Active bleeding; known bleeding disorder
7. Known significant liver disease (e.g. acute hepatitis, chronic active
hepatitis, cirrhosis) or hepatic insufficiency classified as Child-Pugh B or C,
or ALT/AST >*2.5 x the upper limit of normal, measured between screening and
randomization
8. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, calculated
by Modification of Diet in Renal Disease (MDRD) formula, determined between
screening and randomization
9. Major surgery during the last 30 days or planned major surgery or
intervention within study period (e.g. carotid endarterectomy, coronary artery
bypass grafting)
10. Known allergy, intolerance or hypersensitivity to either of the study
interventions (active substance or excipients)
11. Any contraindication for the use of an anticoagulant or listed in the local
labeling for apixaban
12. Requirement for chronic anticoagulation (for a different indication than AF
e.g. mechanical heart valve or cardiac thrombus) or antiplatelet therapy (up to
100 mg ASA is allowed). Anticipated need for chronic (more than 4 weeks)
therapy with NSAIDs
13. Treated with a Vitamin K antagonist in the 30 days prior to screening
14. Concomitant use of any of the following therapies within 14 days (or at
least five half-lives of the active substance whatever is longer) before
randomization and first study intervention administration:
* Strong inhibitors of cytochrome P450 isoenzyme 3A4 (CYP3A4) e.g. human
immunodeficiency virus protease inhibitors, systemically used azole-antimycotic
agents, clarithromycin or telithromycin
* Strong inducers of CYP3A4, e.g. phenytoin, carbamazepine, phenobarbital,
rifampicin or St. John*s wort.
15. Women of childbearing potential (women are considered of childbearing
potential if they are not surgically sterile or postmenopausal, defined as
amenorrhea for >*12 months). Male participants not willing to use condoms
when sexually active with a woman of childbearing potential
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Safety Endpoint:<br /><br>* Composite of International Society on Thrombosis and Hemostasis (ISTH) major<br /><br>and clinically relevant non-major bleeding. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secundary Safety Enpoints<br /><br>* All bleeding<br /><br>* ISTH major bleeding<br /><br>* ISTH clinically relevant non-major bleeding<br /><br>* ISTH minor bleeding</p><br>