Recurrent Brain Infarction in Subjects receiving acetylsalicyl acid (ASA) following Acute Ischemic Stroke or Transient Ischemic Attack MedDRA version: 19.0 Level: PT Classification code 10061256 Term: Ischaemic stroke System Organ Class: 10029205 - Nervous system disorders MedDRA version: 19.0 Level: PT Classification code 10044390 Term: Transient isc
Conditions
Interventions
Product Name: BMS-986141
Pharmaceutical Form: Tablet
INN or Proposed INN: Not applicable yet
CAS Number: 1478711-48-6
Current Sponsor co
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Signed Written Informed Consent a) Subjects or Legally Acceptable Representatives (LAR), must be willing and able to give signed and dated written informed consent. (Note: Consent by a LAR will only be allowed if permitted by local regulations.) Target Population a) Either acute ischemic stroke or high-risk TIA as defined here i) Acute ischemic stroke, defined as: (1) Neurological deficit attributed to the focal brain ischemia, and either of the following: • Persistent signs or symptoms of the ischemic event at the time of randomization • Acute, ischemic brain lesion documented by computed tomography (CT) scan or MRI AND (2) National Institutes of Health Stroke Score (NIHSS) = 7 ii) High-risk TIA, defined as: (1) Neurological deficit of acute onset attributed to focal ischemia of the brain by history or examination with complete resolution of the deficit, and at least one of the following: • ABCD2 score = 4 OR motor or speech symptoms • Symptomatic intracranial arterial occlusive disease documented by transcranial Doppler, ultrasound or vascular imaging, defined as at least 50% narrowing in diameter of a vessel that could account for the clinical presentation • Documented internal carotid arterial occlusive disease, defined as at least 50% narrowing in diameter of a vessel that is presumed to be atherosclerotic and could account for the clinical presentation • Documented stenosis in the vertebral circulation that is presumed to be atherosclerotic and could account for the clinical presentation b) CT or MRI ruling out hemorrhage or other pathology, such as vascular malformation, tumor, or abscess that could explain symptoms or contraindicate therapy c) Randomization occurring within 48 hours after onset of symptoms; if the time of onset of symptoms is unknown, such as when symptoms are first present on awakening, onset should be considered as time last seen normal d) Subject is able to be evaluated by study-specific MRI no later than 24 hours after randomization, does not have contraindications to the performance of the MRI, and has suitable weight and circumference. e) Ability to tolerate ASA at a dose from 75 to 162 mg/day f) Subject Re-enrollment: This study does not permit the re-enrollment of a subject that has discontinued the study as a pre-treatment failure Age and Reproductive Status a) Males and females, minimum age 18 years old or age of majority (if local age of majority is > 18 years of age) at the time of the screening visit b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug c) Women must not be breastfeeding d) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) BMS-986141 plus 5 half-lives of study drug BMS-986141 (6 days) plus 30 days (duration of ovulatory cycle) for a total of 36 days post-treatment c
Exclusion criteria
Exclusion criteria: Target Disease Exceptions a) Any history of atrial fibrillation (AF) other than transient AF related to cardiac surgery, b) Severe left ventricular systolic dysfunction, left ventricular thrombus, or other high-risk cardioembolic source deemed the likely cause of brain ischemia c) TIA symptoms limited to isolated numbness, isolated visual changes, or isolated dizziness/vertigo d) Carotid or vertebral stenosis for which there is a plan for revascularization therapy e) Any condition requiring ongoing treatment with an anticoagulant after discharge. For prophylactic measures to prevent deep vein thrombosis (DVT), pneumatic pressure devices are preferred Medical History and Concurrent Diseases a) Subjects with known bleeding diathesis or coagulation disorder (eg, thrombotic thrombocytopenic purpura) b) History of previous non-traumatic or traumatic intracranial hemorrhage at any time c) Acute gastrointestinal ulcer or history of gastrointestinal (GI) bleed which required medical treatment within the past 3 months d) Planned or anticipated invasive surgery or procedure during study duration e) Persistent, uncontrolled hypertension (systolic BP > 180 mm Hg, or diastolic BP > 100 mm Hg) that does not respond to acute treatment f) Moderate or severe hepatic impairment, defined as Child-Pugh Class B or C; (see Appendix 5) g) Moderate to severe renal impairment, defined as estimated glomerular filtration rate (eGFR) < 45 mL/min; (see Section 5.3.7.1) h) Any other reason, in the opinion of the investigator that the subject may be at undue risk from study participation i) Qualifying ischemic event induced by angiography or surgery j) Any gastrointestinal surgery that could impact upon the absorption of study drug k) Inability to tolerate oral medication or swallow tablets whole l) Inability to undergo venipuncture and/or tolerate venous access m) Subjects in whom MRI procedures cannot be performed. Section 3.4.3 (of the protocol) provides a list of some common conditions that may preclude the subjects from having MRI. However, this should not be used as a substitute for local clinical standards of care. The ultimate decision to perform any of these procedures in an individual subject in this study rests with the site radiologist, the investigator and the standard set by the local ethics committee/institutional review board n) Any other medical, psychiatric and/or social reason including drug or alcohol abuse which in the opinion of the investigator may impact the subject’s ability to comply with study procedures o) Subjects who have received intravenous or intra-arterial thrombolysis or mechanical thrombectomy within the past 48 hours or who are currently eligible and able to receive these treatments for their current stroke Physical and Laboratory Test Findings a) Any of the following on 12-lead electrocardiogram (ECG) prior to study drug administration, confirmed by repeat i) Atrial fibrillation or atrial flutter ii) Complete heart block or Mobitz 2 se
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the dose-response relationship of BMS-986141 on the recurrence of brain infarction at 28 days as assessed by a composite of symptomatic stroke and unrecognized brain infarction as assessed by MRI in subjects with ischemic stroke or TIA treated with ASA.; Secondary Objective: 1. To assess the effect of BMS-986141 on the occurrence of major adverse cardiovascular events (MACE, including all stroke, myocardial infarction, and CV death) by Day 90 2. To assess the effect of BMS-986141 on the occurrence of the composite of ischemic stroke, myocardial infarction, and CV death by Day 90 3. To assess the effect of BMS-986141 on incidence of symptomatic recurrent ischemic stroke up to 28 days of treatment 4. To assess the effect of BMS-986141 on the occurrence of the composite of unrecognized brain infarction assessed by MRI at Day 28 and MACE by Day 90 5. To assess the effect of BMS-986141 on the composite of Major and Clinically Relevant Non-Major (CRNM) Bleeding 6. To assess the effect of BMS-986141 on all reported bleeding 7. To evaluate safety and tolerability of BMS-986141 ; Primary end point(s): 1.The primary efficacy endpoint of the study is the incidence of a composite of symptomatic stroke by Day 28 and unrecognized brain infarction assessed by MRI at Day 28. 2.The primary safety endpoint will be incidence of a composite of adjudicated major bleeding and adjudicated CRNM bleeding during the treatment period. ; Timepoint(s) of evaluation of this end point: 1. Day 28 2. By Day 90 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The incidence of major adverse cardiovascular events (MACE) by Day 90, defined as a composite of adjudicated recurrent stroke, myocardial infarction, or CV death 2. The incidence of a composite of adjudicated recurrent ischemic stroke, myocardial infarction, or CV death 3. The incidence of adjudicated symptomatic recurrent stroke (including fatal and non-fatal) by Day 28 4. The incidence of the composite of unrecognized brain infarction assessed by MRI at Day 28 and MACE by Day 90 ; Timepoint(s) of evaluation of this end point: 1. By Day 90 2. By Day 90 3. By Day 28 4. At Day 28 and by Day 90 | — |
Countries
Argentina, Australia, Canada, Chile, Czech Republic, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Romania, Spain, Sweden, United States
Contacts
Public ContactGCT-SU
Bristol-Myers Squibb International Corporation
Outcome results
None listed