Overview
Sponsor-declared trial summary
Prevention of stroke or systemic embolism in atrial fibrillation
To demonstrate that asundexian is superior (at least non-inferior) when compared with apixaban for prevention of stroke and systemic embolism in participants with atrial fibrillation at risk for stroke. To demonstrate that asundexian is superior to apixaban as assessed by International Society on Thrombosis and Hemosta…
Key facts
- Sponsor
- Bayer AG
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 24 Nov 2022 → 31 Jan 2024
- Decision date (initial)
- 2023-09-13
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Bayer AG
External identifiers
- EU CT number
- 2023-503794-38-00
- EudraCT number
- 2022-000758-28
- ClinicalTrials.gov
- NCT05643573
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Others, Pharmacodynamic, Therapy, Efficacy, Pharmacogenetic, Pharmacokinetic, Safety
To demonstrate that asundexian is superior (at least non-inferior) when compared with apixaban for prevention of stroke and systemic embolism in participants with atrial fibrillation at risk for stroke.
To demonstrate that asundexian is superior to apixaban as assessed by International Society on Thrombosis and Hemostasis (ISTH) major bleeding in participants with atrial fibrillation at risk for stroke.
To demonstrate that asundexian is superior to apixaban with respect to benefit and risk.
Secondary objectives 3
- To compare the effects of asundexian and apixaban with respect to composite and individual efficacy endpoints
- To compare asundexian and apixaban with respect to composite and individual bleeding endpoints
- To compare the benefit and risk of asundexian and apixaban with respect to a composite of efficacy and safety endpoints
Conditions and MedDRA coding
Prevention of stroke or systemic embolism in atrial fibrillation
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10049165 | Cerebrovascular accident prophylaxis | 100000004865 |
| 21.1 | LLT | 10049910 | Thromboembolism prophylaxis | 10042613 |
| 20.0 | PT | 10003658 | Atrial fibrillation | 100000004849 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Overall This study is a multicenter, randomized, active comparator-controlled, double-blind, double-dummy, parallel-group, 2-arm, Phase 3 study.
|
Randomised Controlled | Double | [{"id":23785,"code":2,"name":"Investigator"},{"id":23782,"code":3,"name":"Monitor"},{"id":23781,"code":4,"name":"Analyst"},{"id":23784,"code":1,"name":"Subject"},{"id":23783,"code":5,"name":"Carer"}] | Asundexian: Participants will receive asundexian and apixaban matching placebo. Apixaban: Participants will receive apixaban and asundexian matching placebo. |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency, Pharmaceuticals And Medical Devices Agency
- EMA paediatric investigation plan (PIP)
- EMEA-003144-PIP01-21
| EU CT number | Title | Sponsor |
|---|---|---|
| 2022-001067-27 | A multicenter, international, randomized, placebo controlled, double-blind, parallel group and event driven Phase 3 study of the oral FXIa inhibitor asundexian (BAY 2433334) for the prevention of ischemic stroke in male and female participants aged 18 years and older after an acute non-cardioembolic ischemic stroke or high-risk TIA, Ensayo fase III multicéntrico, internacional, aleatorizado, controlado con placebo, doble ciego, de grupos paralelos y determinado por eventos, del inhibidor oral del FXIa -Asundexian (BAY 2433334), para la prevención de ictus isquémicos en pacientes de ambos sexos mayores de edad, tras un ictus isquémico no cardioembólico agudo o AIT de alto riesgo., Multicentrické, mezinárodní, randomizované, placebem kontrolované, dvojitě zaslepené, paralelně uspořádané a událostmi řízené klinické hodnocení fáze III perorálního inhibitoru FXIa asundexianu (BAY 2433334) v prevenci ischemické mozkové příhody u mužů a žen od 18 let a starších po akutní nekardioembolické ischemické cévní mozkové příhodě nebo vysoce rizikové TIA, Ensaio de fase 3, multicêntrico, internacional, aleatorizado, controlado com placebo, em dupla ocultação, de grupos paralelos e orientado por eventos do inibidor oral do FXIa asundexiano (BAY 2433334) para a prevenção de AVC isquémico em participantes do sexo masculino e do sexo feminino com idade igual ou superior a 18 anos após um AVC isquémico não cardioembólico agudo ou AIT de alto risco, „Многоцентрово, международно, рандомизирано, плацебо контролирано, двойно сляпо, с паралелни групи и зависимо от събития изпитване 3та фаза на пероралния инхибитор на фактор XIa, асундексиан (BAY 2433334), за превенция на исхемични инсулти при мъже и жени пациенти на възраст 18 или повече години след остър не-кардиоемболичен исхемичен инсулт или високо рискови транзиторни исхемични атаки (TIA) “ OCEANIC-STROKE |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- 18 years of age or older (at legal age of consent according to local legislation) at the time of signing the informed consent
- Atrial fibrillation documented by ECG evidence with an indication for indefinite treatment with an oral anticoagulant
- CHA2DS2-VASc score >=3 if male or >= 4 if female, OR CHA2DS2-VASc score of 2 if male or 3 if female and enrichment criteria.
Exclusion criteria 4
- Mechanical heart valve prosthesis
- Moderate-to-severe mitral stenosis at the time of inclusion into the study
- Atrial fibrillation only due to reversible cause
- Requirement for chronic anticoagulation for a different indication than atrial fibrillation
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 3
- Time to first occurrence of composite of stroke or systemic embolism
- Time to first occurrence of ISTH major bleeding
- Time to first occurrence of composite of stroke, systemic embolism, or ISTH major bleeding
Secondary endpoints 13
- Time to first occurrence of composite of ischemic stroke or systemic embolism
- Time to first occurrence of all-cause mortality
- Time to first occurrence of ischemic stroke
- Time to first occurrence of cardiovascular (CV) death
- Time to first occurrence of composite of CV death, stroke, or myocardial infarction
- Time to first occurrence of composite of ISTH major or clinically relevant non-major bleeding
- Time to first occurrence of clinically relevant non-major bleeding
- Time to first occurrence of hemorrhagic stroke
- Time to first occurrence of intracranial hemorrhage
- Time to first occurrence of fatal bleeding
- Time to first occurrence of minor bleeding
- Time to first occurrence of composite of stroke, systemic embolism, ISTH major bleeding, or all-cause mortality
- Time to first occurrence of composite of disabling stroke (modified Rankin Scale (mRS) >=3), critical bleeding, or all-cause mortality
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD7514744 · Product
- Active substance
- Asundexian
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 50000 mg milligram(s)
- Max treatment duration
- 33 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- BAYER AG
- Paediatric formulation
- No
- Orphan designation
- No
Comparator 2
Eliquis 2.5 mg film-coated tablets
PRD1722226 · Product
- Active substance
- Apixaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 5000 mg milligram(s)
- Max treatment duration
- 33 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AF02 — -
- Marketing authorisation
- EU/1/11/691/015
- MA holder
- BRISTOL-MYERS SQUIBB/PFIZER EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Repackaged and relabelled.
Eliquis 5 mg film-coated tablets
PRD734387 · Product
- Active substance
- Apixaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10000 mg milligram(s)
- Max treatment duration
- 33 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AF02 — -
- Marketing authorisation
- EU/1/11/691/012
- MA holder
- BRISTOL-MYERS SQUIBB/PFIZER EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- repackaged and relabelled
Placebo 3
Placebo for comparator product Apixaban 2.5mg
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Placebo for comparator product Apixaban 5mg
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Placebo for test product BAY 2433334
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Bayer AG
- Sponsor organisation
- Bayer AG
- Address
- Kaiser-Wilhelm-Allee 1, Wiesdorf Wiesdorf
- City
- Leverkusen
- Postcode
- 51373
- Country
- Germany
Scientific contact point
- Organisation
- Bayer AG
- Contact name
- Therapeutic Area Head
Public contact point
- Organisation
- Bayer AG
- Contact name
- Therapeutic Area Head
Third parties 7
| Organisation | City, country | Duties |
|---|---|---|
| Labcorp Central Laboratory Services LP ORG-100032236
|
Indianapolis, United States | Other |
| Illingworth Research Group Limited ORG-100042356
|
Macclesfield, United Kingdom | Other |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | Other |
| Nuvisan GmbH ORG-100011873
|
Neu-Ulm, Germany | Other |
| Suvoda LLC ORG-100043523
|
Conshohocken, United States | Interactive response technologies (IRT) |
| Labcorp Central Laboratory Services LP ORG-100032236
|
Indianapolis, United States | Laboratory analysis |
| Mlm Medical Labs GmbH ORG-100043721
|
Mönchengladbach, Germany | Other |
Locations
22 EU/EEA countries · 455 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ended | 205 | 16 |
| Belgium | Ended | 335 | 24 |
| Bulgaria | Ended | 630 | 23 |
| Czechia | Ended | 280 | 20 |
| Denmark | Ended | 353 | 16 |
| Estonia | Ended | 115 | 7 |
| Finland | Ended | 280 | 8 |
| France | Ended | 1,100 | 34 |
| Germany | Ended | 940 | 31 |
| Greece | Ended | 405 | 26 |
| Hungary | Ended | 435 | 22 |
| Italy | Ended | 630 | 29 |
| Latvia | Ended | 240 | 15 |
| Lithuania | Ended | 280 | 15 |
| Netherlands | Ended | 400 | 24 |
| Norway | Ended | 340 | 17 |
| Poland | Ended | 424 | 26 |
| Portugal | Ended | 464 | 17 |
| Romania | Ended | 695 | 22 |
| Slovakia | Ended | 450 | 21 |
| Spain | Ended | 262 | 23 |
| Sweden | Ended | 315 | 19 |
| Rest of world
Canada, Turkey, Argentina, United States, Japan, Korea, Republic of, Israel, Hong Kong, New Zealand, Colombia, China, Australia, United Kingdom, Brazil, Malaysia, Taiwan, Switzerland, Singapore
|
— | 7,882 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Austria | 2022-12-05 | 2024-01-16 | 2022-12-09 | 2023-11-19 | |
| Belgium | 2022-12-22 | 2024-01-21 | 2022-12-28 | 2023-11-19 | |
| Bulgaria | 2023-02-01 | 2024-01-15 | 2023-02-03 | 2023-11-19 | |
| Czechia | 2023-02-17 | 2024-01-11 | 2023-03-01 | 2023-11-19 | |
| Denmark | 2022-11-24 | 2024-01-12 | 2023-01-11 | 2023-11-19 | |
| Estonia | 2023-03-13 | 2024-01-19 | 2023-04-03 | 2023-11-19 | |
| Finland | 2023-02-03 | 2024-01-16 | 2023-02-21 | 2023-11-19 | |
| France | 2023-02-01 | 2024-01-08 | 2023-02-03 | 2023-11-19 | |
| Germany | 2023-02-28 | 2024-01-12 | 2023-04-05 | 2023-11-19 | |
| Greece | 2023-02-21 | 2024-01-16 | 2023-02-22 | 2023-11-19 | |
| Hungary | 2023-01-17 | 2024-01-12 | 2023-01-18 | 2023-11-19 | |
| Italy | 2023-02-17 | 2024-01-19 | 2023-02-20 | 2023-11-19 | |
| Latvia | 2023-01-26 | 2024-01-11 | 2023-01-30 | 2023-11-19 | |
| Lithuania | 2023-03-07 | 2024-01-02 | 2023-03-09 | 2023-11-19 | |
| Netherlands | 2023-01-16 | 2024-01-23 | 2023-01-24 | 2023-11-19 | |
| Norway | 2023-01-09 | 2024-01-03 | 2023-02-02 | 2023-11-19 | |
| Poland | 2023-01-30 | 2024-01-21 | 2023-02-03 | 2023-11-19 | |
| Portugal | 2023-05-11 | 2024-01-11 | 2023-05-17 | 2023-11-19 | |
| Romania | 2023-02-20 | 2024-01-18 | 2023-02-22 | 2023-11-19 | |
| Slovakia | 2023-01-19 | 2024-01-12 | 2023-01-23 | 2023-11-19 | |
| Spain | 2023-02-14 | 2024-01-18 | 2023-03-02 | 2023-11-19 | |
| Sweden | 2023-02-03 | 2024-01-12 | 2023-02-14 | 2023-11-19 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| Summary of Results_EN_2023-503794-38-00 SUM-60372
|
2024-11-28T11:45:58 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Layperson summary of results | 2024-11-28T11:48:04 | Submitted | Laypersons Summary of Results |
Documents 22 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | Layperson summary of results_BG_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_CZ_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_DE_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_DK_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_EN_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_ES_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_ET_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_FI_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_FR_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_GR_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_HU_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_IT_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_LT_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_LV_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_NL_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_NO_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_PL_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_PT_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_RO_2023-503794-38-00_V1_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_SE_2023-503794-38-00_public | 1 |
| Laypersons summary of results (for publication) | Layperson summary of results_SK_2023-503794-38-00_public | 1 |
| Summary of results (for publication) | Summary of Results_EN_2023-503794-38-00_public | 2 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-08-04 | Sweden | Acceptable 2023-09-07
|
2023-09-08 |