Prevention of Thromboembolic EventsPhase 1NCT05419635
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 study testing Asundexian (BAY2433334) in people with Prevention of Thromboembolic Events and Atrial Fibrillation, run by Bayer at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Prevention of Thromboembolic Events, Atrial Fibrillation, Acute Myocardial Infarction
- What is being tested?
- Asundexian (BAY2433334)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteGermany
- Study dates
- 14 Jun 2022to 21 Aug 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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.
Show all 29Show fewer
- 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%.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Investigation of the Influence of Hepatic Impairment on Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Asundexian in Participants With Mild or Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function.
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.
Read more
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.
- Conditions
- Prevention of Thromboembolic Events, Atrial Fibrillation, Acute Myocardial Infarction, Non-cardioembolic Ischemic Stroke, Hepatic Impairment
- Being tested
- Asundexian (BAY2433334)
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Asundexian (BAY2433334)Drug
Study intervention BAY2433334 will be administered as tablet taken orally.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Child-Pugh A | Experimental | Participants with mildly impaired hepatic function (Child-Pugh A) Receives: Drug: Asundexian (BAY2433334) |
| Arm B: Child-Pugh B | Experimental | Participants with moderately impaired hepatic function (Child-Pugh B) Receives: Drug: Asundexian (BAY2433334) |
| Arm C: Normal hepatic (Matched A and B) | Experimental | Participants with normal hepatic function matched to Arm A and B Receives: Drug: Asundexian (BAY2433334) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 0 - 96 hours post dose
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.
Measured: 0 - 96 hours post dose
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.
Measured: 0 - 96 hours post dose
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.
Measured: 0 - 96 hours post dose
Secondary outcomes (1)
Number of participants with treatment-emergent adverse events (TEAEs)
Measured: From first administration of study drug up to 4 days after end of treatment with study medication.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2022
- Study start14 Jun 2022
- Primary completion24 May 2023
- Study completion21 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prevention of Thromboembolic EventsStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05419635
- Sponsor's protocol ID
- 20462
- Other IDs
- 2022-000196-38
- Status last verified
- Aug 2023
- First submitted
- 3 Jun 2022
- Last updated
- 29 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Influence of Hepatic Impairment on Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Asundexian in Participants With Mild or Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function.
- ClinicalTrials.gov ID
- NCT05419635
- Acronym / sponsor ID
- 20462
- Conditions
- Prevention of Thromboembolic Events, Atrial Fibrillation, Acute Myocardial Infarction, Non-cardioembolic Ischemic Stroke, Hepatic Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 14 Jun 2022 (actual)
- Primary completion
- 24 May 2023 (actual)
- Study completion
- 21 Aug 2023 (actual)
- First posted
- 15 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: Child-Pugh A | Experimental | Drug: Asundexian (BAY2433334)Participants with mildly impaired hepatic function (Child-Pugh A) |
| Arm B: Child-Pugh B | Experimental | Drug: Asundexian (BAY2433334)Participants with moderately impaired hepatic function (Child-Pugh B) |
| Arm C: Normal hepatic (Matched A and B) | Experimental | Drug: Asundexian (BAY2433334)Participants with normal hepatic function matched to Arm A and B |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Asundexian (BAY2433334)Study intervention BAY2433334 will be administered as tablet taken orally. | Drug | Arm A: Child-Pugh A, Arm B: Child-Pugh B, Arm C: Normal hepatic (Matched A and B) |
Primary outcome
Area under the concentration vs. time curve from zero to infinity after single dose (AUC)*of BAY2433334
Time frame: 0 - 96 hours post dose
*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.
Area under the concentration vs. time curve in plasma from zero to infinity (AUCu)* (unbound) after a single dose of BAY2433334.
Time frame: 0 - 96 hours post dose
* 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.
Maximum observed drug concentration (Cmax) after single dose administration of BAY2433334.
Time frame: 0 - 96 hours post dose
In case of dose adaptation for Child Pugh B patients, Cmax/D will be evaluated instead of Cmax.
Maximum observed drug concentration (Cmax,u) (unbound) after a single dose of BAY2433334.
Time frame: 0 - 96 hours post dose
In case of dose adaptation for Child Pugh B patients, Cmax,u/D will be evaluated instead of Cmax,u.
1 secondary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2023.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Asundexian (BAY2433334) in people with Prevention of Thromboembolic Events and Atrial Fibrillation, run by Bayer at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the concentration vs. time curve from zero to infinity after single dose (AUC)*of BAY2433334 (time frame: 0 - 96 hours post dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2023.