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)

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Acute Coronary Syndrome

Treatments: Drug: Standard therapy; Drug: Placebo twice daily; Drug: Losmapimod 7.5 mg twice daily

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02145468

116197

Details and patient eligibility

About

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.

Enrollment: 3,503 patients

Sex: All

Ages: 35+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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3,503 participants in 2 patient groups, including a placebo group

Losmapimod

Experimental group

Description:

Losmapimod 7.5 mg twice daily oral tablet

Treatment:

Drug: Losmapimod 7.5 mg twice daily

Drug: Standard therapy

Placebo

Placebo Comparator group

Description:

Placebo twice daily oral tablet

Treatment:

Drug: Placebo twice daily

Drug: Standard therapy