To evaluate that the oral FXIa inhibitor BAY 2433334 when compared to apixaban leads to a lower incidence of bleeding in participants with AF
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Safety Endpoint:
* Composite of International Society on Thrombosis and Hemostasis (ISTH) major
and clinically relevant non-major bleeding.
Secondary outcome
Secundary Safety Enpoints
* All bleeding
* ISTH major bleeding
* ISTH clinically relevant non-major bleeding
* ISTH minor bleeding
Background summary
Current guidelines recommend long-term oral anticoagulant therapy such as
non-Vitamin K oral anticoagulants (NOACs).
Patients receiving NOACs continue to have a significant risk for developing
strokes, systemic embolism and CV death. In addition there is still a
significant risk for major bleeding. The inhibition of FXIa is expected to not
lead to a relevant increase in bleeding and especially major bleeding, while
maintaining the efficacy benefit of NOACs.
Study objective
To evaluate that the oral FXIa inhibitor BAY 2433334 when compared to apixaban
leads to a lower incidence of bleeding in participants with AF
Study design
This is a multicenter, randomized, active comparator-controlled, double-blind,
double-dummy, parallel-group dose-finding study
Intervention
BAY 2433334 is the sponsor*s study drug under investigation. Apixaban is the
drug used as comparator. The following intervention groups are included in the
study:
* BAY 2433334 50 mg
* BAY 2433334 20mg
* Apixaban 5 mg or 2.5 mg, according to label
Study duration is between 14 and 16 weeks (max. 2 weeks for screening, 12 weeks
of treatment, safety follow up 2 weeks after end of treatment)
Study burden and risks
The safety profile of BAY 2433334 has not yet been established. The following
safety and risk information is available:
-Risk for bleeding cannot be excluded in participants with atrial fibrillation.
- Increase in liver enzymes has been oberserved in animal testing.
-Strong CYP3A4 inhibitors should not be taken because exposure to BAY 2433334
and the half-life is enhanced.
Energieweg 1
Mijdrecht 3641 RT
NL
Energieweg 1
Mijdrecht 3641 RT
NL
Listed location countries
Age
Inclusion criteria
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)
Exclusion criteria
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-002365-35-NL |
| CCMO | NL71685.018.19 |