Trial Outcomes & Findings for Study to Gather Information About Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following a Recent Non Cardioembolic Ischemic Stroke Which Occurs When a Blood Clot Has Formed Somewhere in the Human Body (But Not in the Heart) Travelled to the Brain. (NCT NCT04304508)

Last Updated: 2023-04-19

Results Overview

Ischemic stroke was defined as either of : 1) Rapid onset (or present on awakening) of a new focal neurological deficit with clinical (\>24 hours symptoms/signs) or imaging evidence of infarction that was not attributable to a non-ischemic cause; 2) Acute worsening of an existing focal neurological deficit that was judged to be attributable to a new infarction or extension of the previous infarction in the same vascular territory, based on persisting symptoms/signs or imaging evidence of infarction and no evidence of a non-ischemic etiology. If imaging was inconclusive, persistent symptoms/signs must be significant (worsening of NIHSS score of 4 or more) and sustained (duration of ≥24 hours or until death). Covert brain infarcts were defined as incident infarcts detected by serial MRI in the absence of an adjudicated stroke consistent with the location of the infarct. MRI criteria for brain infarction were available in the MRI procedures manual.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

1808 participants

Primary outcome timeframe

From baseline up to 26 weeks

Results posted on

2023-04-19

Participant Flow

Study was conducted at 197 centers in 23 countries or regions, between 15-Jun-2020 (first participant first visit) and 18-Feb-2022 (last participant last visit)

1880 participants were screened. 72 participants were screening failures. 1808 participants were randomized in a 1:1:1:1 ratio to 4 treatment groups: 455, 450, and 447 participants to asundexian 10 mg, 20 mg and 50 mg groups, 456 participants to placebo group. 22 participants (10, 4, 4 and 4 in the asundexian 10 mg, 20 mg and 50 mg, and placebo groups) never administered.

Participant milestones

Participant milestones
Measure	Asundexian 10 mg Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Overall Study STARTED	455	450	447	456
Overall Study Treated	445	446	443	452
Overall Study COMPLETED	335	329	313	314
Overall Study NOT COMPLETED	120	121	134	142

Reasons for withdrawal

Reasons for withdrawal
Measure	Asundexian 10 mg Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Overall Study Subject Decision	29	39	37	48
Overall Study Death	6	1	8	5
Overall Study Non-compliance With Study Drug	3	1	2	0
Overall Study Switching To Other Therapy	1	1	1	2
Overall Study Subject Decision: COVID-19 Pandemic Related	0	1	0	2
Overall Study Withdrawal by Subject	7	5	11	6
Overall Study Logistical Difficulties	2	2	3	2
Overall Study Missing Information	1	2	1	3
Overall Study Other	7	6	5	4
Overall Study Physician Decision: COVID-19 Pandemic Related	1	0	0	0
Overall Study Physician Decision	3	4	9	7
Overall Study Study drug never administered	10	4	4	4
Overall Study Adverse Event	49	50	51	56
Overall Study Lost to Follow-up	1	5	2	3

Baseline Characteristics

Study to Gather Information About Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following a Recent Non Cardioembolic Ischemic Stroke Which Occurs When a Blood Clot Has Formed Somewhere in the Human Body (But Not in the Heart) Travelled to the Brain.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Asundexian 10 mg n=455 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=450 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=447 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=456 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Total n=1808 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	186 Participants n=5 Participants	154 Participants n=7 Participants	174 Participants n=5 Participants	195 Participants n=4 Participants	709 Participants n=21 Participants
Age, Categorical >=65 years	269 Participants n=5 Participants	296 Participants n=7 Participants	273 Participants n=5 Participants	261 Participants n=4 Participants	1099 Participants n=21 Participants
Sex: Female, Male Female	161 Participants n=5 Participants	150 Participants n=7 Participants	154 Participants n=5 Participants	150 Participants n=4 Participants	615 Participants n=21 Participants
Sex: Female, Male Male	294 Participants n=5 Participants	300 Participants n=7 Participants	293 Participants n=5 Participants	306 Participants n=4 Participants	1193 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	67 Participants n=5 Participants	67 Participants n=7 Participants	68 Participants n=5 Participants	66 Participants n=4 Participants	268 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants	3 Participants n=4 Participants	18 Participants n=21 Participants
Race (NIH/OMB) White	381 Participants n=5 Participants	377 Participants n=7 Participants	367 Participants n=5 Participants	380 Participants n=4 Participants	1505 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	14 Participants n=21 Participants

PRIMARY outcome

Timeframe: From baseline up to 26 weeks

Population: FAS

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=455 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=450 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=447 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=456 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke or Covert Brain Infarcts Detected by Magnetic Resonance Imaging (MRI) Symptomatic ischemic stroke	24 Participants	25 Participants	17 Participants	23 Participants	—
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke or Covert Brain Infarcts Detected by Magnetic Resonance Imaging (MRI) Covert brain infarct	56 Participants	57 Participants	56 Participants	55 Participants	—
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke or Covert Brain Infarcts Detected by Magnetic Resonance Imaging (MRI) Imputed infarcts seen in participants with incomplete MRI follow-up	6 Participants	11 Participants	7 Participants	5 Participants	—
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke or Covert Brain Infarcts Detected by Magnetic Resonance Imaging (MRI) Imputed infarcts with the rule of Quan	11 Participants	14 Participants	16 Participants	15 Participants	—

PRIMARY outcome

Timeframe: From baseline up to 52 weeks

Population: SAF

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.

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=445 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=446 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=443 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=1334 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo n=452 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Safety-Number of Participants With Composite of International Society on Thrombosis and Hemostasis (ISTH) Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding	19 Participants	14 Participants	19 Participants	52 Participants	11 Participants

SECONDARY outcome

Timeframe: From baseline up to 26 weeks

Population: FAS

CV death included death due to stroke, MI, heart failure or cardiogenic shock, sudden death or any other death due to other cardiovascular causes. Death due to non-traumatic hemorrhage was included. Acute MI was used when there was evidence of myocardial necrosis in a clinical setting consistent with acute myocardial ischemia. According to MI Universal Definition from 2018 the diagnosis of MI required the combination of: 1) Presence of acute myocardial injury, and 2) Evidence of acute myocardial ischemia derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging, or in case of post-mortem pathological findings irrespective of biomarker values. Systemic embolism was defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms (this did not include thromboembolism of the pulmonary vasculature or venous thrombosis).

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=455 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=450 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=447 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=456 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke and Covert Brain Infarcts Detected by MRI, Cardiovascular (CV) Death, Myocardial Infarction (MI) and Systemic Embolism. Ischemic Stroke	24 Participants	25 Participants	17 Participants	23 Participants	—
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke and Covert Brain Infarcts Detected by MRI, Cardiovascular (CV) Death, Myocardial Infarction (MI) and Systemic Embolism. CV death	3 Participants	2 Participants	6 Participants	6 Participants	—
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke and Covert Brain Infarcts Detected by MRI, Cardiovascular (CV) Death, Myocardial Infarction (MI) and Systemic Embolism. MI	3 Participants	0 Participants	3 Participants	3 Participants	—
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke and Covert Brain Infarcts Detected by MRI, Cardiovascular (CV) Death, Myocardial Infarction (MI) and Systemic Embolism. Systemic embolism	1 Participants	0 Participants	0 Participants	0 Participants	—
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke and Covert Brain Infarcts Detected by MRI, Cardiovascular (CV) Death, Myocardial Infarction (MI) and Systemic Embolism. Covert brain infarct	56 Participants	57 Participants	56 Participants	55 Participants	—
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke and Covert Brain Infarcts Detected by MRI, Cardiovascular (CV) Death, Myocardial Infarction (MI) and Systemic Embolism. Imputed infarcts seen in participants with incomplete MRI follow-up	6 Participants	11 Participants	7 Participants	5 Participants	—

SECONDARY outcome

Timeframe: From baseline up to 52 weeks

Population: FAS

Definition of symptomatic ischemic stroke can be referred to first Primary endpoint.

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=455 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=450 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=447 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=456 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Efficacy-Number of Participants With Symptomatic Ischemic Stroke	26 Participants	26 Participants	22 Participants	28 Participants	—

SECONDARY outcome

Timeframe: From baseline up to 26 weeks

Population: FAS

Definition of covert brain infarcts can be referred to first Primary endpoint.

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=455 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=450 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=447 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=456 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Efficacy-Number of Participants With Covert Brain Infarcts Detected by MRI	62 Participants	68 Participants	63 Participants	60 Participants	—

SECONDARY outcome

Timeframe: From baseline up to 52 weeks

Population: FAS

Definition of symptomatic ischemic stroke can be referred to first Primary endpoint. Definition of CV death and MI can be referred to first Second endpoint.

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=455 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=450 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=447 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=456 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Efficacy-Number of Participants With Symptomatic Ischemic Stroke, CV Death, MI	33 Participants	30 Participants	33 Participants	35 Participants	—

SECONDARY outcome

Timeframe: From baseline up to 52 weeks

Population: FAS

Definition of symptomatic ischemic can be referred to fourth secondary endpoint. Hemorrhagic stroke was defined as an acute, atraumatic extravasation of blood into the brain parenchyma, intraventricular or subarachnoid space with associated neurological symptoms. This did not include microbleeds or hemorrhagic transformation of an ischemic stroke.

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=455 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=450 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=447 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=456 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Efficacy-Number of Participants With Symptomatic Ischemic and Hemorrhagic Stroke	26 Participants	26 Participants	25 Participants	30 Participants	—

SECONDARY outcome

Timeframe: From baseline up to 52 weeks

Population: FAS

Modified ranking score (mRS): 0-No symptoms at all; 1-No significant disability despite symptoms; despite symptoms, able to carry out all usual duties and activities; 2-Slight disability; unable to carry out all previous activities but able to look after own affairs without assistance; 3-Moderate disability; requiring some help, but able to walk without assistance; 4-Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5-Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6-Death.

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=455 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=450 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=447 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=456 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Efficacy-Number of Participants With Disabling Stroke (mRS≥4)	5 Participants	5 Participants	1 Participants	3 Participants	—

SECONDARY outcome

Timeframe: From baseline up to 52 weeks

Population: FAS

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=455 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=450 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=447 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=456 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Efficacy-Number of Participants With All-cause Mortality	10 Participants	6 Participants	17 Participants	10 Participants	—

SECONDARY outcome

Timeframe: From baseline up to 52 weeks

Population: SAF

All bleeding events occurred from first intake of study intervention until 2 days after the last intake of study intervention.

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=445 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=446 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=443 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=452 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Safety-Number of Participants With All Bleeding	37 Participants	48 Participants	48 Participants	44 Participants	—

SECONDARY outcome

Timeframe: From baseline up to 52 weeks

Population: SAF

Definition of ISTH major bleeding can be referred to second Primary endpoint.

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=445 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=446 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=443 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=452 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Safety-Number of Participants With ISTH Major Bleeding	4 Participants	3 Participants	7 Participants	4 Participants	—

SECONDARY outcome

Timeframe: From baseline up to 52 weeks

Population: SAF

Definition of ISTH CRNM bleeding can be referred to second Primary endpoint.

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=445 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=446 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=443 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=452 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Safety-Number of Participants With ISTH CRNM Bleeding	15 Participants	12 Participants	12 Participants	7 Participants	—

SECONDARY outcome

Timeframe: From baseline up to 52 weeks

Population: SAF

All other overt bleeding episodes not meeting the above criteria for ISTH major or CRNM bleeding were classified as minor bleeding (e.g. bleeding from a minor wound that does not prompt a face-to-face evaluation for a physical examination or laboratory testing).

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=445 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=446 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=443 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=452 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Safety-Number of Participants With ISTH Minor Bleeding	21 Participants	39 Participants	34 Participants	34 Participants	—

SECONDARY outcome

Timeframe: From baseline up to 52 weeks

Population: SAF

Non-traumatic intracerebral hemorrhage was defined as a hemorrhagic stroke on the "recurrent stroke" CRF page that is in addition classified as a bleeding with bleeding site intracranial (-subarachnoid, -intraparenchymal \[excluding microbleeds\], or -intraventricular) and spontaneous causality of bleeding, excluding all symptomatic and hemorrhagic transformation (defined by the PT "hemorrhagic transformation").

Outcome measures

Outcome measures
Measure	Asundexian 10 mg n=445 Participants Participants received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=446 Participants Participants received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=443 Participants Participants received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=452 Participants Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks	Placebo Participants received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Safety-Number of Participants With Intracerebral Hemorrhage (Non-traumatic)	0 Participants	0 Participants	3 Participants	1 Participants	—

Adverse Events

Asundexian 10 mg

Serious events: 90 serious events

Other events: 126 other events

Deaths: 10 deaths

Asundexian 20 mg

Serious events: 83 serious events

Other events: 127 other events

Deaths: 6 deaths

Asundexian 50 mg

Serious events: 93 serious events

Other events: 136 other events

Deaths: 17 deaths

Placebo

Serious events: 98 serious events

Other events: 136 other events

Deaths: 10 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Asundexian 10 mg n=445 participants at risk Subjects received Asundexian (BAY2433334) 10 mg for 26 weeks at least and up to 52 weeks	Asundexian 20 mg n=446 participants at risk Subjects received Asundexian (BAY2433334) 20 mg for 26 weeks at least and up to 52 weeks	Asundexian 50 mg n=443 participants at risk Subjects received Asundexian (BAY2433334) 50 mg for 26 weeks at least and up to 52 weeks	Placebo n=452 participants at risk Subjects received Asundexian (BAY2433334) placebo for 26 weeks at least and up to 52 weeks
Cardiac disorders Atrial fibrillation	4.0% 18/445 • Number of events 18 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	4.7% 21/446 • Number of events 21 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	3.6% 16/443 • Number of events 16 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	4.9% 22/452 • Number of events 22 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.
Gastrointestinal disorders Constipation	6.3% 28/445 • Number of events 29 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	4.0% 18/446 • Number of events 20 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	6.3% 28/443 • Number of events 29 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	7.5% 34/452 • Number of events 35 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.
Gastrointestinal disorders Diarrhoea	2.7% 12/445 • Number of events 12 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	3.1% 14/446 • Number of events 15 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	3.4% 15/443 • Number of events 18 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	2.7% 12/452 • Number of events 12 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.
Infections and infestations Urinary tract infection	2.9% 13/445 • Number of events 15 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	2.5% 11/446 • Number of events 11 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	2.9% 13/443 • Number of events 14 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	3.1% 14/452 • Number of events 18 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.
Infections and infestations COVID-19	4.9% 22/445 • Number of events 22 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	3.1% 14/446 • Number of events 14 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	3.2% 14/443 • Number of events 14 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	2.7% 12/452 • Number of events 12 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	2.5% 11/445 • Number of events 11 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	2.5% 11/446 • Number of events 13 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	3.6% 16/443 • Number of events 16 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	2.7% 12/452 • Number of events 12 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.
Nervous system disorders Dizziness	1.6% 7/445 • Number of events 7 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	3.6% 16/446 • Number of events 18 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	3.8% 17/443 • Number of events 17 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	3.1% 14/452 • Number of events 14 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.
Nervous system disorders Headache	4.3% 19/445 • Number of events 20 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	4.3% 19/446 • Number of events 38 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	4.7% 21/443 • Number of events 31 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	4.0% 18/452 • Number of events 19 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.
Psychiatric disorders Insomnia	1.3% 6/445 • Number of events 6 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	3.6% 16/446 • Number of events 16 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	2.5% 11/443 • Number of events 12 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	2.7% 12/452 • Number of events 13 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.
Vascular disorders Hypertension	5.2% 23/445 • Number of events 24 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	4.3% 19/446 • Number of events 19 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	5.6% 25/443 • Number of events 25 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.	5.3% 24/452 • Number of events 25 • After the first administration of study intervention for up to 52 weeks (but not starting after more than 2 days after the last administration). Reporting for the the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, for up to 54 weeks.

Additional Information

Therapeutic Area Head

Bayer AG

Phone: (+) 1-888-8422937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI prohibited from publishing results for 18 months following completion of the study at all sites. Sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review.
Publication restrictions are in place

Restriction type: OTHER