The purpose of this study is to determine the safety and tolerability of multiple doses of TAK-442once daily, (QD) or twice daily (BID), in subjects with acute coronary syndrome (unstable angina, myocardial infarction).
Acute coronary syndrome, including myocardial infarction with or without ST-segment elevation and stable or unstable angina, is acknowledged to represent collectively a major global healthcare problem. Despite existing treatments, the rates of patient mortality, myocardial infarction and hospital readmissions during follow-up remain very high. Due to its critical role in propagating the blood coagulation cascade, activated factor X now is considered to be a major therapeutic target in the development of novel antithrombotic therapy by blocking thrombin generation and attenuating the formation of fibrin. Therefore, activated factor X inhibitors, exhibiting either indirect or direct modes of action, are among the novel agents under investigation in the treatment of acute coronary syndrome. This study will evaluate the safety and tolerability of TAK-442 compared with placebo in post-acute coronary syndrome subjects who are also receiving standard antiplatelet and other cardiovascular therapy. Individuals who want to participate in this study will be required to provide written informed consent. Study participation is anticipated to be approximately 3.5 months. Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations, electrocardiograms and bilateral venogram.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
2,753
Stage I: TAK-442 10 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.
Stage I: TAK-442 20 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.
Stage I: TAK-442 40 mg, capsules, orally, once daily and standard care for recurrent ischemic events for up to 24 weeks.
Incidence of Major Bleeding Events defined by the Thrombolysis in Myocardial Infarction Scale.
Time frame: On Occurrence (Up to 24 weeks)
Composite of Cardiovascular Mortality, non-fatal Myocardial Infarction, non-fatal Stroke, or Myocardial Ischemia requiring hospitalization.
Time frame: Week 24
Cardiovascular Mortality.
Time frame: Week 24.
Non-fatal Myocardial Infarction.
Time frame: Week 24.
Non-fatal Stroke.
Time frame: Week 24.
Myocardial Ischemia requiring hospitalization.
Time frame: Week 24.
All-cause Mortality.
Time frame: Week 24.
Hemorrhagic Mortality.
Time frame: Week 24.
Composite of Cardiovascular death, non-fatal Myocardial Infarction, or Myocardial Ischemia requiring hospitalization.
Time frame: Week 24.
Composite of Cardiovascular death, non-fatal Myocardial Infarction, or non-fatal Stroke.
Time frame: Week 24.
Hospitalization for Heart Failure.
Time frame: Week 24.
Incidence of minor bleeding events defined by the Thrombolysis in Myocardial Infarction Scale.
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Stage II: TAK-442 40 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.
Stage II: TAK-442 80 mg, capsules, orally, once daily and standard care for recurrent ischemic events for up to 24 weeks.
Stage II: TAK-442 80 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.
Stage III: TAK-442 160 mg, capsules, orally, once daily and standard care for recurrent ischemic events for up to 24 weeks.
Stage III: TAK-442 120 mg, capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.
Stages I, II \& III: TAK-442 placebo-matching capsules, orally, twice daily and standard care for recurrent ischemic events for up to 24 weeks.
Unnamed facility
Birmingham, Alabama, United States
Unnamed facility
Tucson, Arizona, United States
Unnamed facility
Newark, Delaware, United States
Unnamed facility
Washington D.C., District of Columbia, United States
Unnamed facility
Pensecola, Florida, United States
Unnamed facility
West Des Moines, Iowa, United States
Unnamed facility
Salisbury, Maryland, United States
Unnamed facility
Minneapolis, Minnesota, United States
Unnamed facility
Cherry Hill, New Jersey, United States
Unnamed facility
Toledo, Ohio, United States
...and 93 more locations
Time frame: On Occurrence (Up to 24 weeks).
Incidence of minimal bleeding events defined by the Thrombolysis in Myocardial Infarction Scale.
Time frame: On Occurrence (Up to 24 weeks).
Incidence of major, clinically significant non-major bleeding AND minor bleeding events as defined by the Secondary Bleeding Scale
Time frame: On Occurrence (Up to 24 weeks)