Study to Gather Information About the Proper Dosing of the Oral FXIa Inhibitor BAY 2433334 and to Compare the Safety of the Study Drug to Apixaban, a Non-vitamin K Oral Anticoagulant (NOAC) in Patients With Irregular Heartbeat (Atrial Fibrillation) That Can Lead to Heart-related Complications.

NCT04218266 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 197652019-002365-35
• Study Type: interventional
• Target: 755
• Locations: 14 countries
• Sites: 93

Brief Summary

The purpose of this study is to try to find the best dose of the new drug BAY 2433334 to give to participants and to look at how well BAY 2433334 works in patients with irregular heartbeat (atrial fibrillation) that can lead to blood clots, stroke and other heart-related complications. In addition researchers want to compare the safety of the study drug to apixaban, a non-vitamin K oral anticoagulant (NOAC) in patients with atrial fibrillation. This study is also done to learn how the drug in this study moves into, through and out of the body. BAY 2433334, works by blocking a step of the blood clotting process in our body and thins the blood and is a so called oral FXIa inhibitor. Apixaban, works by reducing the production of blood clotting factors in our body and thins the blood and is a so called non-vitamin K oral anticoagulant (NOAC). Thinning the blood can prevent you from blood clots which can cause a stroke.

Conditions

Atrial Fibrillation (AF)

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Composite of International Society on Thrombosis and Hemostasis (ISTH) Major Bleeding or Clinically Relevant Non-major (CRNM) Bleeding

  ISTH Major Bleeding criteria: 1. Fatal bleeding, and/or 2. Symptomatic bleeding in a critical area or organ (intracranial, intraocular, intraspinal, pericardial, retroperitoneal, intraarticular, or intramuscular with compartment syndrome), and/or 3. Clinically overt bleeding associated with a recent decrease in the hemoglobin level of ≥ 2 g/dL (20 g/L; 1.24 mmol/L) compared to the most recent hemoglobin value available before the event, and/or 4. Clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. ISTH Clinically Relevant Non-Major Bleeding is considered any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding, but does meet at least one of the following criteria 1. requiring medical intervention by a healthcare professional. 2. leading to hospitalization or increased level of care. 3. prompting a face to face (i.e. not just a telephone or electronic communication) evaluation.

  After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration)

Secondary Outcomes (4)

• Number of Participants With All Bleeding

  After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration)

• Number of Participants With ISTH Major Bleeding

  After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration)

• Number of Participants of ISTH Clinically Relevant Non-major (CRNM) Bleeding

  After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration)

• Number of Participants With ISTH Minor Bleeding

  After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration)

Study Arms (3)

BAY2433334 50mg+Apixaban matching placebo

EXPERIMENTAL

Drug: BAY2433334; Other: Apixaban matching placebo

BAY2433334 20mg+Apixaban matching placebo

EXPERIMENTAL

Drug: BAY2433334; Other: Apixaban matching placebo

BAY2433334 matching placebo+Apixaban

ACTIVE COMPARATOR

Apixaban usual dose is 5 mg, reduced to 2.5 mg for participants with any 2 of the following criteria: age 80 years or older, body weight less than 60 kg, or serum creatinine level of 1.5 mg per dL or more.

Drug: Apixaban; Other: BAY2433334 matching placebo

Interventions

BAY2433334 DRUG

Tablet, taken orally once a day.

BAY2433334 20mg+Apixaban matching placebo; BAY2433334 50mg+Apixaban matching placebo

Apixaban DRUG

Capsule, taken orally twice a day.

BAY2433334 matching placebo+Apixaban

BAY2433334 matching placebo OTHER

Tablet, taken orally once a day.

BAY2433334 matching placebo+Apixaban

Apixaban matching placebo OTHER

Capsule, taken orally twice a day.

BAY2433334 20mg+Apixaban matching placebo; BAY2433334 50mg+Apixaban matching placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 45 years of age or older at the time of signing the informed consent.
• 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 Acetylsalicylic acid(ASA) ≤ 100 mg)
• Written informed consent

You may not qualify if:

• Mechanical heart valve prosthesis
• Any degree of rheumatic mitral stenosis or moderate-to-severe, non-rheumatic mitral stenosis
• Atrial fibrillation due to a reversible cause, participants in sinus rhythm after successful ablation, or plan for cardioversion or ablation during study conduct
• Requirement for chronic anticoagulation (for a different indication than AF) or antiplatelet therapy (up to 100 mg ASA is allowed). Anticipated need for chronic therapy with Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Treated with a Vitamin K antagonist in the 30 days prior to screening

Sponsors & Collaborators

• Bayer: lead

Study Sites (93)

Medizinische Universität Graz

Graz, Styria, 8036, Austria

Location

Medizinische Universität Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Krankenhaus St. Josef Braunau

Braunau am Inn, Upper Austria, 5280, Austria

Location

Ordensklinikum Linz GmbH Elisabethinen

Linz, Upper Austria, 4020, Austria

Location

Landeskrankenhaus Feldkirch

Feldkirch, Vorarlberg, 6807, Austria

Location

Uniklinikum Salzburg - Landeskrankenhaus

Salzburg, 5020, Austria

Location

Universitätsklinikum AKH Wien

Vienna, 1090, Austria

Location

Klinik Floridsdorf - Krankenhaus Nord

Vienna, 1210, Austria

Location

UZ Leuven Gasthuisberg

Leuven, Vlaams Brabant, 3000, Belgium

Location

Imeldaziekenhuis - St-Elisabethkliniek

Bonheiden, 2820, Belgium

Location

AZ St-Jan Brugge Oostende AV

Bruges, 8000, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Jessa Ziekenhuis

Hasselt, 3500, Belgium

Location

VZW Emmaus

Mechelen, 2800, Belgium

Location

AZ Delta

Roeselare, 8800, Belgium

Location

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Clinique Sante Cardio MC

Montreal, Quebec, H1T 3Y7, Canada

Location

Institut universitaire de cardiologie et de pneumologie

Ste-Foy, Quebec, G1V 4G5, Canada

Location

Fakultni nemocnice Plzen - Lochotin

Pilsen, 304 60, Czechia

Location

Fakultni nemocnice Kralovske Vinohrady

Prague, 100 34, Czechia

Location

Institut Klinicke a Experimentalni Mediciny

Prague, 140 21, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Nemocnice Slany

Slaný, 274 01, Czechia

Location

Krajska nemocnice T. Bati, a.s.

Zlín, 762 75, Czechia

Location

Hôpital Henri Mondor

Créteil, 94010, France

Location

Centre Hospitalier Départemental Vendée

La Roche-sur-Yon, 85025, France

Location

Centre Hospitalier Louis Pasteur

Le Coudray, 28630, France

Location

Hopital Bichat - Paris

Paris, 75018, France

Location

Centre Hospitalier Régional - Saint Brieuc

Saint-Brieuc, 22000, France

Location

Hôpital de Rangueil - Toulouse

Toulouse, 31403, France

Location

Centre Hospitalier - Valenciennes Cedex

Valenciennes, 59322, France

Location

Tagore Medical Center

Balatonfüred, 8230, Hungary

Location

University of Semmelweis/ Semmelweis Egyetem

Budapest, 1122, Hungary

Location

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, Hungary

Location

Kanizsai Dorottya Hospital

Nagykanizsa, 8800, Hungary

Location

Medifarma-98 Egeszsegugyi, Kereskedelmi es Szolgaltato Kft.

Nyíregyháza, 4400, Hungary

Location

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, 7624, Hungary

Location

Tolna Megyei Balassa Janos Korhaz

Szekszárd, 7100, Hungary

Location

Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz

Szentes, 6600, Hungary

Location

A.O.U. Policlinico Umberto I

Rome, Lazio, 00161, Italy

Location

IRCCS Ospedale Policlinico San Martino

Genoa, Liguria, 16132, Italy

Location

ASST Spedali Civili di Brescia

Brescia, Lombardy, 25123, Italy

Location

ASUR Marche - Area Vasta 5

Ascoli Piceno, The Marches, 63074, Italy

Location

AUSL Toscana Sud-Est

Arezzo, Tuscany, 52044, Italy

Location

AUSL Toscana Sud-Est

Arezzo, Tuscany, 52100, Italy

Location

A.O. di Perugia

Perugia, Umbria, 06129, Italy

Location

Nakamura Cardiovascular Clinic

Itoshima, Fukuoka, 819-1104, Japan

Location

Hyogo Prefectural Harima-Himeji General Medical Center

Himeji, Hyōgo, 670-8560, Japan

Location

Hayama Heart Center

Miura-gun, Kanagawa, 240-0116, Japan

Location

Kishiwada Tokushukai Hospital

Kishiwada, Osaka, 596-0042, Japan

Location

Yao Tokushukai General Hospital

Yao, Osaka, 581-0011, Japan

Location

Nishiarai Heart Central Clinic

Adachi-ku, Tokyo, 123-0845, Japan

Location

Minamino Cardiovascular Hospital

Hachiōji, Tokyo, 192-0918, Japan

Location

Tokyo Angel Hospital

Hachiōji, Tokyo, 193-0811, Japan

Location

Koto Hospital

Koto-ku, Tokyo, 136-0072, Japan

Location

Doctor's Practice in Cardiology

Daugavpils, LV-5401, Latvia

Location

Daugavpils Regional Hospital

Daugavpils, LV-5417, Latvia

Location

Liepaja Regional Hospital

Liepāja, LV-3414, Latvia

Location

1st Riga Clinical Hospital

Riga, LV-1001, Latvia

Location

P. Stradins Clinical University Hospital

Riga, LV-1002, Latvia

Location

Riga East Clinical University Hospital "Gailezers"

Riga, LV-1038, Latvia

Location

Academisch Medisch Centrum (AMC)

Amsterdam, 1105 AZ, Netherlands

Location

Ziekenhuis Rijnstate

Arnhem, 6815 AD, Netherlands

Location

Amphia Ziekenhuis, locatie Molengracht

Breda, 4818 CK, Netherlands

Location

Albert Schweitzer Ziekenhuis, Dordwijk

Dordrecht, 3318 AT, Netherlands

Location

Medisch Spectrum Twente

Enschede, 7511 JX, Netherlands

Location

Martini Ziekenhuis, Locatie van Swieten

Groningen, 9728 NT, Netherlands

Location

Spaarne Gasthuis - locatie Zuid

Haarlem, 2035 RC, Netherlands

Location

Maastricht UMC

Maastricht, 6229 HX, Netherlands

Location

Ciutat Sanitària i Universitària de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Ciutat Sanitària i Universitaria de la Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i de Sant Pau | Cardiología

Barcelona, 08041, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Virgen de la Victoria

Málaga, 29010, Spain

Location

Falu Lasarett

Falun, 791 82, Sweden

Location

Clemenstorget Hjärtmottagning

Lund, 222 21, Sweden

Location

Avdelningen för kliniska prövningar AKP

Örebro, 703 62, Sweden

Location

Östersunds Sjukhus

Östersund, 831 83, Sweden

Location

Skellefteå Lasarett

Skellefteå, 931 86, Sweden

Location

Södersjukhuset AB

Stockholm, 118 83, Sweden

Location

Danderyds sjukhus

Stockholm, 182 88, Sweden

Location

Kantonsspital Aarau

Aarau, Canton of Aargau, 5001, Switzerland

Location

Universitätsspital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

Inselspital Universitätsspital Bern

Bern, 3010, Switzerland

Location

Hôpital Cantonal Universitaire de Genève

Geneva, 1211, Switzerland

Location

Ospedale regionale di Lugano

Lugano, 6900, Switzerland

Location

Staploe Medical Centre

Ely, Cambridgeshire, CB7 5SQ, United Kingdom

Location

Queen Elizabeth II Hospital

Welwyn Garden City, Hertfordshire, AL7 4HQ, United Kingdom

Location

Northwick Park Hospital

Harrow, London, HA1 3UJ, United Kingdom

Location

St Richard's Hospital

Chichester, West Sussex, PO19 6SE, United Kingdom

Location

Heart and Chest Hospital

Liverpool, L14 3PE, United Kingdom

Location

Related Publications (1)

• Piccini JP, Caso V, Connolly SJ, Fox KAA, Oldgren J, Jones WS, Gorog DA, Durdil V, Viethen T, Neumann C, Mundl H, Patel MR; PACIFIC-AF Investigators. Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study. Lancet. 2022 Apr 9;399(10333):1383-1390. doi: 10.1016/S0140-6736(22)00456-1. Epub 2022 Apr 3.

  PMID: 35385695 DERIVED

Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe
• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

apixaban

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer AG

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2020
• First Posted: January 6, 2020
• Study Start: January 30, 2020
• Primary Completion: October 8, 2021
• Study Completion: October 8, 2021
• Last Updated: October 27, 2022
• Results First Posted: October 27, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); SE (7); IT (7); BE (7); AU (8); CZ (6); LA (6); JP (9); FR (7); GB (5); CA (4); NL (8); CH (6); HU (8)