A 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 (PM1116197)Short title: LosmApimod To Inhibit p38 MAP kinase as a TherapeUtic target and moDify outcomes after an acute coronary syndromE (LATITUDE)-TIMI 60

GlaxoSmithKline Research & Development Ltd0 sites3,489 target enrollmentMarch 3, 2015

ConditionsSubjects with ACS on the time to first occurrence of adjudicated MACE (defined as CV death, MI, or severe recurrent ischemia [SRI-UR])MedDRA version: 17.1Level: LLTClassification code 10003723Term: Attack coronarySystem Organ Class: 10007541 - Cardiac disorders MedDRA version: 17.1Level: PTClassification code 10051592Term: Acute coronary syndromeSystem Organ Class: 10007541 - Cardiac disorders MedDRA version: 17.1Level: LLTClassification code 10071111Term: Non ST segment elevation acute coronary syndromeSystem Organ Class: 10007541 - Cardiac disorders MedDRA version: 17.1Level: LLTClassification code 10041894Term: ST segment elevationSystem Organ Class: 100000004848 Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Subjects with ACS on the time to first occurrence of adjudicated MACE (defined as CV death, MI, or severe recurrent ischemia [SRI-UR])
Sponsor: GlaxoSmithKline Research & Development Ltd
Enrollment: 3489
Status: Active, not recruiting
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

March 3, 2015

End Date

December 14, 2015

Last Updated

4 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

GlaxoSmithKline Research & Development Ltd

Eligibility Criteria

Inclusion Criteria

•1\.Signed written informed consent prior to beginning study\-related procedures.
•The subject must understand the aims, investigational procedures and possible consequences of the study
•2\.Male or female aged 35 years or older at randomization.
•A female subject is eligible to participate if she is of non\-child bearing potential defined as pre\-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea or if of child\-bearing potential is using a highly effective method for avoidance of pregnancy (refer to Appendix 1\) for the duration of dosing and until 2 weeks post last\-dose. The decision to include or exclude women of childbearing potential may be made at the discretion of the investigator and in accordance with local practice in relation to adequate contraception.
•3\.Hospitalization for NSTEMI or STEMI (Universal Definition Type 1 MI).
•NSTEMI that is presumed spontaneous (Universal Definition Type 1\) and is defined as ischemic chest discomfort (or equivalent) that occurs or persists at rest with at least 1 episode lasting \=10 minutes and is accompanied by a diagnostic elevation in cardiac troponin above the upper limit of normal (99th percentile decision\-limit) according to the local laboratory without persistent ST segment elevation. If cardiac troponin is not available, then creatine\-kinase MB isoenzyme (CK\-MB) must be above the upper limit of normal. The biomarker should exhibit a rising and/or falling pattern when serial testing is available prior to randomization.
•STEMI is defined as ischemic chest discomfort (or equivalent) that occurs or persists at rest with ST segment elevation of at least 0\.1 mV in 2 or more contiguous leads or new (or presumed new) left bundle branch block (LBBB) and a presumed diagnosis of STEMI.
•NOTE: Subjects with clinical or laboratory manifestations of ACS (e.g., ST\-elevation or increase in cardiac enzymes) that are believed to be secondary to other apparent illness (e.g., sepsis, profound anemia, hypertensive emergency or decompensated heart failure, coronary embolism or dissection; Universal Type 2 MI) or known to be procedurally related (Type 4 \- including stent thrombosis\- or Type 5\) are not considered to meet these criteria for NSTEMI or STEMI.
•4\.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).

Exclusion Criteria

•Subjects meeting any of the following criteria must not be enrolled in the study:
•1\. Unable to be randomized prior to coronary revascularization or fibrinolysis for the qualifying MI.
•2\. Current severe heart failure or shock (New York Heart Association \[NYHA] class III or IV, or Killip class III or IV).
•3\. Ongoing clinical instability (e.g., hypotension requiring vasopressor or inotropic support, new stroke or transient ischemic attack \[TIA], or recurrent sustained ventricular tachycardia).
•4\. History of chronic liver disease (defined below) or known to have current ALT \=2x upper limit of normal or total bilirubin \>1\.5x upper limit of normal or known history of hepatitis B or C.
•Defined as known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones). Such abnormalities include current drug therapy for the treatment of liver disease, unstable liver disease (defined by the presence of any of the following deemed by the investigator to be related to liver disease and not to other disease processes: ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice) or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
•5\.Known severe renal impairment.
•Severe renal impairment is defined as receiving chronic dialysis or known estimated glomerular filtration rate (eGFR) \<30 mL/min/1\.73 m2 at the time of randomization based on serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD\-EPI) equation (see SPM).
•6\.Any condition, other than vascular disease, with life expectancy \<1 year that might prevent the subject from completing the study.
•7\.Known active tuberculosis, HIV, active opportunistic or life threatening infections.