E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-cardioembolic ischemic stroke |
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E.1.1.1 | Medical condition in easily understood language |
Stroke which occurs when a blood clot has formed somewhere in the human body (but not in the heart) travelled to the brain |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055221 |
E.1.2 | Term | Ischemic stroke |
E.1.2 | System Organ Class | 100000004852 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067625 |
E.1.2 | Term | Secondary prevention |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the dose response of 3 different doses of BAY 2433334 compared to placebo in reducing the composite of symptomatic ischemic strokes and covert brain infarcts detected by MRI as well as other cerebro- and cardiovascular endpoints in participants with an acute non-cardioembolic ischemic stroke and who are treated with antiplatelet therapy.
• To evaluate whether the incidence of bleeding is similar for BAY 2433334 compared to placebo in participants with an acute non-cardioembolic ischemic stroke and who are treated with antiplatelet therapy. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participant must be 45 years of age and older at the time of signing the informed consent
2. Non-cardioembolic ischemic stroke with
a. persistent signs and symptoms of stroke lasting for ≥ 24 hours OR
b. acute brain infarction documented by computed tomography (CT) or MRI AND
c. with the intention to be treated with antiplatelet therapy during the study conduct
3. Imaging of brain (CT or MRI) ruling out hemorrhagic stroke or another pathology that could explain symptoms (e.g. brain tumor, abscess, vascular malformation)
4. Severity of index event nearest the time of randomization:
a. Part A: minor stroke (defined as NIHSS ≤ 7) can be enrolled
b. Part B: participants with minor or moderate stroke and NIHSS ≤ 15 can be enrolled. Participants undergoing thrombolysis or endovascular therapy (mechanical thrombectomy) can be enrolled but at the earliest 24 hours after the intervention
5. Randomization within 48 hours after the onset of symptoms of the index event (or after patients were last known to be without symptoms in case of wake-up stroke)
6. Ability to conduct an MRI either before randomization or within 72 hours after randomization |
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E.4 | Principal exclusion criteria |
1. Prior ischemic stroke within last 30 days of index event
2. History of atrial fibrillation or suspicion of cardioembolic source of stroke
3. Dysphagia with inability to safely swallow study medication at time of randomization
4. Contraindication to perform brain MRI
5. Part A only: thrombolysis or endovascular therapy (mechanical thrombectomy) performed for index event
7. Active bleeding; known bleeding disorder, history of major bleeding (intracranial, retroperitoneal, intraocular) or clinically significant gastrointestinal bleeding within last 6 months of randomization |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint:
Number of participants with symptomatic ischemic stroke or covert brain infarcts detected by MRI
Primary Safety Endpoint:
Time from randomization to first occurrence of International Society on Thrombosis and Hemostasis (ISTH) major bleeding and clinically relevant non-major (CRNM) bleeding |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Efficacy Endpoint: From baseline up to 6 months
Primary Safety Endpoint: From baseline up to 12 months |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints:
1.Number of participants with composite of symptomatic ischemic stroke and covert brain infarcts detected by MRI, CV death, myocardial infarction and systemic embolism
2.Number of participants with covert brain infarcts detected by MRI
3.Time from randomization to first occurrence of symptomatic ischemic stroke
4.Time from randomization to first occurrence of symptomatic ischemic stroke, CV death, myocardial infarction
5.Time from randomization to first occurrence of symptomatic ischemic and hemorrhagic stroke
6.Time from randomization to first occurrence of disabling stroke (mRS≥4)
7.Time from randomization to all-cause mortality
Secondary Safety Endpoints
1. Time from randomization to first occurrence of all bleeding
2. Time from randomization to first occurrence of ISTH major bleeding
3. Time from randomization to first occurrence of ISTH CRNM bleeding
4. Time from randomization to first occurrence of ISTH minor bleeding
5. Time from randomization to first occurrence of Intracerebral hemorrhage (non-traumatic) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline up to 12 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 166 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Bulgaria |
Canada |
China |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hungary |
Italy |
Japan |
Netherlands |
Poland |
Portugal |
Russian Federation |
Slovakia |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 29 |