A Phase 3 Clinical Outcomes Study to Compare the Incidence of Major Adverse Cardiovascular Events in Subjects Presenting With Acute Coronary Syndrome Treated With Losmapimod Compared to Placebo (LATITUDE-TIMI 60)
Condition: Acute Coronary Syndrome
MeSH terms: Acute Coronary Syndrome; Syndrome
Intervention: Losmapimod 7.5 mg twice daily; Placebo twice daily; Standard therapy
Intervention description: Subjects will receive Losmapimod 7.5 mg as film-coated, round, plain faced tablets.; Subjects will receive placebo as film-coated, round, plain faced tablets.; Subjects will receive standard therapy consistent with the appropriate guidelines from professional societies. The standard therapy includes nitrates, morphine sulfate, beta adrenergic blockers, renin-angiotensin aldosterone inhibitors, other anti-ischemic therapies, and analgesic therapy.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 3503.0
Sex: All
Minimum age: 35 Years
Healthy volunteers: No
Keywords: Myocardial infarction; Acute coronary syndrome; Cardiovascular disease; p38 mitogen-activated protein kinase (MAPK) inhibitor; NSTEMI; Losmapimod; STEMI

Summary:

      Losmapimod is a new anti-inflammatory medication which potentially may benefit patients with
      Acute Coronary Syndrome, (ACS), a condition which includes heart attack. There is a growing
      understanding that the inflammatory response to ACS is integral to the subsequent evolution
      of plaque instability. Losmapimod inhibits p38 mitogen activated protein kinase (MAPK), an
      enzyme which may play a central role in inflammation in the setting of heart attack.
      Inhibition of p38 MAPK may stabilize atherosclerotic plaques, reduce the risk of subsequent
      plaque rupture, indirectly improve vascular function and prevent subsequent thrombosis, and
      thus reduce infarct size and the risk of subsequent cardiac events. This study will test
      whether losmapimod can safely reduce the risk of a subsequent cardiovascular event (such as
      death, heart attack, or near heart attack requiring urgent treatment ) when started
      immediately after ACS (specifically, heart attack). Patients who present with heart attack
      and qualify for the study will be randomly assigned to receive 3 months treatment with either
      losmapimod twice daily or placebo, which will be administered in addition to the usual
      standard of care therapies for heart attack. Following the in-hospital period, subjects will
      return for outpatient visits at 4 and 12 weeks, as well as a follow up visit at 24 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed written informed consent

          -  Men or women at least 35 years old. Women must be post-menopausal or using a highly
             effective method for avoidance of pregnancy

          -  Hospitalization for NSTEMI or STEMI (Universal Definition Type 1 MI)

          -  With the following timing of symptoms: NSTEMI: Presence of ischemic symptoms (>=5
             minutes) at rest within 24 hours prior to randomization (may include qualifying
             episode). STEMI: Onset of qualifying ischemic symptoms within 12 hours of
             randomization.

          -  At least one of the following

          -  Age >=60 years at randomization.

          -  Myocardial infarction prior to the qualifying ACS event

          -  CABG prior to qualifying ACS event.

          -  NSTEMI with new ischemic ST-segment depression >= 0.1 mV in >= 2 contiguous leads.

          -  Diabetes mellitus requiring pharmacotherapy.

          -  Coexistent clinically diagnosed arterial disease

        Exclusion Criteria:

          -  Unable to be randomized prior to coronary revascularization or fibrinolysis for the
             qualifying MI.

          -  Current severe heart failure or shock

          -  Ongoing clinical instability

          -  History of chronic liver disease

          -  Known severe renal impairment

          -  Any condition, other than vascular disease, with life expectancy <1 year that might
             prevent the subject from completing the study.

          -  Known active tuberculosis, HIV, active opportunistic or life threatening infections.

          -  Vaccination with a live attenuated vaccine within 6 weeks of randomization.

          -  Concomitant use of cytotoxic chemotherapy for cancer or known ongoing or anticipated
             use of chronic severe immunosuppressive agents

          -  Positive pregnancy test or is known to be pregnant or lactating

          -  Known alcohol or drug abuse within the past 6 months

          -  Any current mental condition, which may affect study compliance or prevent
             understanding of the aims, investigational procedures or possible consequences of the
             study.

          -  Participation in a study of an investigational medication within the past 30 days.

          -  Anticipated inability to comply with any study procedures, including participation in
             study visits according to the visit schedule through 24 weeks.

          -  Use of another investigational product within 30 days or 5 half-lives (whichever is
             longer) or according to local regulations, or currently participating in a study of an
             investigational device. Subjects must be randomized only one time in this
             investigational study

          -  Any other reason the investigator deems the subject to be unsuitable for the study