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CompletedNCT05419635Updated Aug 29, 2023

A Study to Learn How the Study Treatment Asundexian Moves Into, Through and Out of the Body, How it Works, How Safe it is, and How it Affects the Body in Participants With Mild or Moderate Reduction of Liver Function Compared to Participants With Normal Liver Function

A Phase 1 interventional study of Asundexian (BAY2433334) in Prevention of Thromboembolic Events, Atrial Fibrillation and Acute Myocardial Infarction, sponsored by Bayer. Completed at 1 site in Germany. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-08-29.

Sponsored by Bayer · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
27
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

Researchers are looking for a better way to prevent the formation of blood clots in people who have or have had:

  • an irregular and often rapid heartbeat
  • a blocked blood flow to the heart
  • a blocked or reduced blood flow to a part of the brain. When a blood clot forms in the body in patients with the above conditions, it may block vessels of the heart, the brain and/or other parts of the body. This may lead to heart attack, stroke and other serious complications.

Blood clots are formed in a process known as coagulation. This is a complex series of steps that must occur in a specific sequence. Medications are already available to prevent the formation of blood clots. They work by interrupting one or more of the coagulation steps and are therefore known as anticoagulants. They decrease the risk of the above-mentioned complications.

The study treatment asundexian works by blocking a very specific step in the blood clotting process, the activation of a protein called Factor XIa. Due to its very specific action that is not thought to be involved in the main blood clotting steps needed to stop bleeding (e.g. like from a cut finger), asundexian is expected to reduce the risk of bleeding that is still seen with existing anticoagulants. Since people who need an anticoagulant may also have liver problems, information on asundexian use in this group is needed.

The main purpose of this study is to learn how asundexian moves into, through and out of the body in participants with a mild or moderate reduction in liver function compared to participants with normal liver function who are similar in age, weight, and gender.

To answer this question, researchers will measure

  • the average highest level of asundexian in the blood (also referred to as Cmax)
  • the average total level of asundexian in the blood (also referred to as AUC). that were reached after intake of a single tablet of asundexian.

The researchers will compare these data between participants with reduced liver function and matched participants with normal liver function to look for differences.

Each participant will be in the study for up to 4 weeks. Participants will stay in-house for 6 days, starting the day before taking asundexian. In addition, two visits to the study site are planned.

During the study, the doctors and their study team will:

  • do physical examinations
  • check vital signs
  • take blood and urine samples
  • examine heart health using an electrocardiogram (ECG)
  • ask the participants questions about how they are feeling and what adverse events they are having.

An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

02

Conditions studied

  • Prevention of Thromboembolic Events
  • Atrial Fibrillation
  • Acute Myocardial Infarction
  • Non-cardioembolic Ischemic Stroke
  • Hepatic Impairment
03

In context

Ischemic Stroke

2,593 studies on the registry are indexed under Ischemic Stroke; 930 are open to participants now.

This study's enrollment of 27 is below the median of 120 across 1,752 interventional studies indexed under Ischemic Stroke.

Browse Ischemic Stroke studies →

Lead sponsor

Bayer is the lead sponsor of 1,643 studies on the registry; 57 are open to participants now.

Of its 209 completed or terminated interventional studies of FDA-regulated products, 129 (62%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

All participants:

  • Participant must be more than 18 years of age inclusive, at the time of signing the informed consent.
  • Body mass index (BMI) within the range 18.0 and 35.0 kg2 (inclusive).
  • Race: White (Note: Clinical Data Interchange Standards Consortium definition of White: Denotes a person with European, Middle Eastern, or North African ancestral origin who identifies, or is identified, as White [FDA]).
  • Male and/or female participants.
  • Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Participants With Hepatic Impairment:

  • Participants with documented liver cirrhosis confirmed by histopathology (e.g., previous liver biopsy), laparoscopy, or by ultrasound, or fibroscan.
  • Participants with hepatic impairment (Child Pugh A or B).
  • Participants with stable liver disease in the last 2 months prior to screening.

Participants of age-, weight-, and gender-matched group :

  • Participants with normal hepatic function.
  • Mean age and body weight in the control group and in the two groups with hepatic impairment (Child Pugh A and B) should not vary by more than ±10 years and ±10 kg.
  • Gender-matched (the gender distribution in the control group should be as similar as possible to the groups with hepatic impairment).

Exclusion criteria

Exclusion Criteria:

All participants:

  • Pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study intervention will not be normal except for hepatic impairment in participants with hepatic impairment.
  • Known severe allergies e.g., allergies to more than 3 allergens, allergies affecting the lower respiratory tract - allergic asthma, allergies requiring therapy with corticosteroids (except for topical use), urticaria or significant non-allergic drug reactions.
  • History of known or suspected malignant tumors except completely resected basal cell cancer of the skin (excision >6 months before screening).
  • Tendency for vasovagal reactions (e.g. after venipuncture) or history of syncope after venipuncture.
  • Participants with untreated, unstable thyroid disorders as evidenced by clinically relevant deviation from normal ranges of thyroid stimulating hormone (TSH) and signs/symptoms of a thyroid disorder at screening.

Participants With Hepatic Impairment:

  • Evidence of hepatic encephalopathy related to chronic liver disease > grade 2
  • Congestive heart failure of New York Heart Association grade III or IV.
  • Participants with percutaneous transluminal coronary angioplasty or coronary artery bypass graft less than 6 months prior to administration of study intervention.
  • History of conspicuous bleeding within the past 3 months.
  • Severe ascites of more than 6 L (estimated by ultrasound).
  • Participants with primary and secondary biliary cirrhosis.
  • Participants with sclerosing cholangitis.
  • Clinically relevant findings in the electrocardiogram (ECG) such as a second- or third-degree atrioventricular (AV) block or a prolongation of the QTcF-interval (Fridericia's correction) over 480 ms (males and females).
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) in conjunction with gamma glutamyl transpeptidase (GGT) equal or above 4 times the upper limit of normal (ULN) (an isolated elevation of GGT above 4 times ULN will not exclude the participant).
  • Serum albumin below 2 g/dL.
  • Prothrombin time (Quick test) below 40%
  • Participants with diabetes mellitus with a glycated hemoglobin (HbA1c) above 10%.
  • Chronic kidney disease with an estimated glomerular filtration rate (eGFR) equal or below 40 mL/min/1.73 m\^2 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).

Participants of age-, weight-, and gender-matched group:

  • A history of relevant diseases with the exception of mild, well controlled hypertension, dyslipoproteinemia and thyroid disorders.
  • History of Morbus Meulengracht (Gilbert´s syndrome) and impairment of bile secretion/flow (cholestasis, also history of it).
  • Relevant history of liver disorders which could increase the individual risk for the participant.
  • Hepatic impairment or active liver disease, which may include unexplained persistent transaminase elevations.
  • Renal impairment with an eGFR below age-appropriate values (CKD-EPI).
  • Clinically relevant findings in the ECG, such as relevant arrhythmic or conduction disturbances (e.g., AV block grad II or III, QRS complex ≥120 ms), QTcF interval (Fridericia's correction) >450 ms (males) or >470 ms (females) at screening.
  • Liver markers (e.g., ALT, AST, alkaline phosphatase, gamma glutamyl transpeptidase or total bilirubin) above 1.5 x ULN at screening.
  • HbA1c above 6.7%.
05

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
27 participants (actual)

Study arms

  • Experimental
    Arm A: Child-Pugh A

    Participants with mildly impaired hepatic function (Child-Pugh A)

    Drug: Asundexian (BAY2433334)

  • Experimental
    Arm B: Child-Pugh B

    Participants with moderately impaired hepatic function (Child-Pugh B)

    Drug: Asundexian (BAY2433334)

  • Experimental
    Arm C: Normal hepatic (Matched A and B)

    Participants with normal hepatic function matched to Arm A and B

    Drug: Asundexian (BAY2433334)

Interventions

  • DrugAsundexian (BAY2433334)

    Study intervention BAY2433334 will be administered as tablet taken orally.

06

What researchers measure

Primary outcomes

  1. Area under the concentration vs. time curve from zero to infinity after single dose (AUC)*of BAY2433334

    \*AUC(0-tlast) and AUC(0 tlast)/D will be used as main parameter, respectively, if mean AUC cannot be reliably determined in all participants. In case of dose adaptation for Child Pugh B patients, AUC/D\*will be evaluated instead of AUC.

    Time frame: 0 - 96 hours post dose

  2. Area under the concentration vs. time curve in plasma from zero to infinity (AUCu)* (unbound) after a single dose of BAY2433334.

    \* AUC(0-tlast)u and AUC(0-tlast)u/D will be used as main parameter, respectively, if mean AUC cannot be reliably determined in all participants. In case of dose adaptation for Child Pugh B patients, AUCu/D\*, will be evaluated instead of AUCu.

    Time frame: 0 - 96 hours post dose

  3. Maximum observed drug concentration (Cmax) after single dose administration of BAY2433334.

    In case of dose adaptation for Child Pugh B patients, Cmax/D will be evaluated instead of Cmax.

    Time frame: 0 - 96 hours post dose

  4. Maximum observed drug concentration (Cmax,u) (unbound) after a single dose of BAY2433334.

    In case of dose adaptation for Child Pugh B patients, Cmax,u/D will be evaluated instead of Cmax,u.

    Time frame: 0 - 96 hours post dose

Secondary outcomes

  1. Number of participants with treatment-emergent adverse events (TEAEs)

    Time frame: From first administration of study drug up to 4 days after end of treatment with study medication.

07

Study locations

1 site
  • CRS-Kiel
    Kiel, Schleswig-Holstein 24105, Germany
08

References and documents

Individual participant data

Plan to share: No — Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 29, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05419635
Lead sponsor
Bayer
Responsible party
Sponsor
First posted
Jun 15, 2022
Start date
Jun 14, 2022
Primary completion
May 24, 2023
Completion
Aug 21, 2023
Last update
Aug 29, 2023

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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