A Study to Test How Well BAY 3670549 Works and How Safe it is in Patients With Atrial Fibrillation

Official title

A Placebo-controlled, Parallel-group, Double Blind, Randomized, Multi-cohort Phase 2 Study to Investigate Efficacy, Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of BAY 3670549 in Adult Participants With Atrial Fibrillation.

Overview

The main goal of this study is to find out how well BAY 3670549 works, how safe it is, how well people can tolerate it, and how the body handles the medicine. The study will compare BAY 3670549 to a placebo (a dummy treatment with no active medicine) in people with AF who need a treatment called electrical cardioversion. Electrical cardioversion is a procedure that helps the heart return to a normal rhythm. In this study, each participant will get a single intravenous (IV) infusion of either BAY 3670549 or a placebo. Participants will then be observed to see whether the heart rhythm returns to a normal rhythm. If it does not, electrical cardioversion can still be performed as planned. The study will look at how many participants return from AF to a normal rhythm, without needing electrical cardioversion and how long it takes. It will also show how many participants experience medical problems after treatment and how BAY 3670549 move into, through and out of the participants' body. The total duration of the study for an individual participant may be up two months. The findings from this study may contribute to the development of a new treatment option for people with AF.

Interventions

• Drug BAY 3670549
  intravenous (IV) treatment
• Other Placebo
  intravenous (IV) treatment

Primary outcome measures

• Number of Participants with conversion from atrial fibrillation (AF) to sinus rhythm (SR), sustained for ≥1 minute, within 3 hours after start of study intervention administration, and prior to use of rescue therapy or other SoC for cardioversion [Time frame: Up to 3 hours after start of administration of study intervention]

Secondary outcome measures (4)

• Number of Participants who experienced Treatment Emergent Adverse Events (TEAE)s [Time frame: From pre-dose* up to 48 hours after start of administration of study intervention]
• Time to conversion from AF to SR as defined in the primary endpoint [Time frame: Up to 3 hours after start of administration of study intervention]
• Number of Participants in SR, at 3 hours after start of study intervention administration without prior use of rescue therapy or other SoC for cardioversion [Time frame: Up to 3 hours after start of administration of study intervention]
• Plasma concentration of BAY 3670549 at the end of the infusion [Time frame: From pre-dose* up to 8 hours after start of administration of study intervention]

Eligibility criteria

Inclusion criteria

• Participant must be 18 to 85 years of age inclusive, at the time of signing the informed consent.
• Participant is hemodynamically stable and does not require emergency cardioversion, as determined by the investigator.
• Participant has a current episode of atrial fibrillation (AF) ongoing for at least 3 hours and no more than 30 days at the time of randomization.
• Participant has an indication for electrical cardioversion of AF, as determined by the investigator according to standard clinical practice and national/institutional guidelines.
• At randomization, successful initiation and achievement of therapeutic levels of anticoagulation therapy, as well as completion of imaging evaluation for left atrial thrombi, as appropriate for the duration of the AF episode and risk for the participant according to national guideline and institution-specific routine practice.
• BMI within range \[18 - 39.9\] kg/m2.
• Contraceptive use by participants or participant partners should be consistent with the study protocol and local regulations regarding the methods of contraception for those participating in clinical studies.
• Signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• Willing and able to comply with the receipt, home use, and return of the continuous ECG recording device, as well as with the participation in scheduled telephone follow-up assessments.

Exclusion criteria

• Current atrial flutter (AFL) or combined AF/AFL
• Contraindication for electrical cardioversion on planned treatment day
• Documented severely dilated left atrium (left atrial diameter, LAD >5 cm) measured by any modality within the 6 months prior to screening; if several values are available, the most recent one shall be reported. If left atrium diameter was not measured in the last 6 months or a major cardiovascular event occurred within the last 6 months, a new measurement must be done at screening
• Unsuccessful conversion of current AF episode (pharmacologically or electrically)
• Known severe valvular heart disease (e.g., severe mitral regurgitation, severe aortic stenosis)
• Patients with NYHA Class ≥ III heart failure, or with active management of acute heart failure decompensation on treatment day.
• History within the preceding 3 months prior to randomization of any of the following events, or any other significant cardiovascular event as judged by the investigator:

• Stroke
• Myocardial infarction
• Unstable angina pectoris or other signs of myocardial ischemia
• Cardiac surgery
• Transcatheter valve replacement
• Percutaneous coronary intervention (PCI)
• Coronary artery bypass graft (CABG) or other revascularization procedure
• Severe renal impairment, i.e., estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² (using CKD-EPI formula) or requiring dialysis
• Severe hepatic impairment, i.e. Child Pugh Class C
• Use of anti-arrhythmic class I or III drugs within 5 half-lives before study drug administration (oral amiodarone in the previous 3 months)
• Hypertension with SBP ≥ 180 mmHg or hypotension (SBP < 90 mmHg) at randomization (based on the second BP measurement)
• Stressor-associated AF, i.e., in the setting of an acute and reversible stressor (e.g., cardiac surgery, myocarditis, endocarditis, sepsis, pneumonia, etc.). This includes ablation procedure within the preceding one month prior to randomization.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 5 centers

• UCSF Advanced Heart Failure Comprehensive Care Center — San Francisco
• UCHealth University of Colorado Hospital - Cardiology — Aurora
• Massachusetts General Hospital - Cardiology — Boston
• Henry Ford Hospital - Cardiology — Detroit
• Duke University Hospital - Cardiology — Durham

Bulgaria · 4 centers

• University Multiprofile Hospital For Active Treatment Sveti Georgi' - EAD Department of In — Plovdiv
• Multiprofile Hospital for Active Treatment Knyaginya Klementina Sofia EAD | Cardiology Dep — Sofia
• University Hospital for Active Treatment Tsaritsa Joanna - ISUL | Cardiology Clinic — Sofia
• Multiprofile Hospital for Active Treatment Dr. Stefan Cherkezov | Base 1 - Cardiology Depa — Veliko Tarnovo

Italy · 4 centers

• Ente Ecclesiastico Ospedale Generale Regionale Miulli - Cardiologia e UTIC — Acquaviva delle Fonti
• Centro Cardiologico Monzino S.p.A. - UO Scompenso e Cardiologia Clinica — Milan
• Azienda Ospedaliero-Universitaria Policlinico Umberto I - Malattie Cardiovascolari — Roma
• Azienda Ospedaliero Universitaria Delle Marche - Clinica di Cardiologia e Aritmologia — Torrette

Poland · 4 centers

• American Heart of Poland S.A. - PAKS Centrum Kardiologii i Kardiochirurgii w Bielsku-Białe — Bielsko-Biala
• American Heart of Poland S.A. - MCSN, PAKS w Chrzanowie - Oddział Intensywnej Opieki Kardi — Chrzanów
• Samodzielny Publiczny Specjalistyczny Szpital Zachodni im. sw. Jana Pawla II — Grodzisk Mazowiecki
• USK nr 4 w Lublinie - Kliniczny Odd. Kardiologii, Reh. Kardio., Ch. Wew. z Pododdzialem In — Lublin

Belgium · 3 centers

• UZ Leuven Gasthuisberg - Cardiology diseases department — Leuven
• Jessa Ziekenhuis | Hartcentrum Hasselt — Hasselt
• AZ Delta | Clinical Trial Center - Cardiology — Roeselare

Germany · 3 centers

• Medizinische Hochschule Hannover|Kardiologie und Angiologie — Hanover
• Herz-und Diabeteszentrum NRW|Elektrophysiologie/Rhythmologie — Bad Oeynhausen
• Klinikum Altenburger Land GmbH-Klinik für Kardiologie, Pneumologie und Internistische Inte — Altenburg

Hungary · 2 centers

• Tolna Vármegyei Balassa János Kórház - I. Belgyógyászati Osztály: Kardiológia, Nefrológia — Szekszárd
• Semmelweis Egyetem, Varosmajori Sziv- és Ergyogyaszati Klinika — Budapest

Netherlands · 2 centers

• Maastricht UMC — Maastricht
• Universitair Medisch Centrum Groningen — Groningen

Identifiers

NCT: NCT07625215 · 22961 · 2025-523807-31-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗