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. (PACIFIC-AF)

Bayer

Status and phase: Completed; Phase 2

Conditions: Atrial Fibrillation (AF)

Treatments: Other: Apixaban matching placebo; Drug: BAY2433334; Drug: Apixaban; Other: BAY2433334 matching placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04218266

19765

2019-002365-35 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 755 patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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755 participants in 3 patient groups

BAY2433334 50mg+Apixaban matching placebo

Experimental group

Treatment:

Other: Apixaban matching placebo

Drug: BAY2433334

BAY2433334 20mg+Apixaban matching placebo

Experimental group

Treatment:

Other: Apixaban matching placebo

Drug: BAY2433334

BAY2433334 matching placebo+Apixaban

Active Comparator group

Description:

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.

Treatment:

Drug: Apixaban

Other: BAY2433334 matching placebo