PM1116197 is a Clinical Study to Compare the Incidence of Major Adverse Cardiovascular Events in Subjects Presenting with Acute Coronary Syndrome Treated with Losmapimod Compared to Placebo
- Conditions
- MedDRA version: 17.1Level: LLTClassification code 10003723Term: Attack coronarySystem Organ Class: 10007541 - Cardiac disordersMedDRA version: 17.1Level: PTClassification code 10051592Term: Acute coronary syndromeSystem Organ Class: 10007541 - Cardiac disordersMedDRA version: 17.1Level: LLTClassification code 10071111Term: Non ST segment elevation acute coronary syndromeSystem Organ Class: 10007541 - Cardiac disordersMedDRA version: 17.1Level: LLTClassification code 10041894Term: ST segment elevationSystem Organ Class: 100000004848Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2013-000657-50-EE
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 3489
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).
STEMI: Onset of qualifying ischemic symptoms within 12 hours of randomization.
5.All subjects must also have at least one of the following additional predictors of cardiovascular risk:
a.Age =60 years at randomization.
b.History of documented MI (known or presumed Type 1 MI) prior to qualifying ACS event.
c.History of CABG prior to qualifying ACS event.
d.NSTEMI with new ischemic ST-segment depression =0.1 mV in =2 contiguous leads.
e.Diabetes mellitus requiring pharmacotherapy.
f.Coexistent clinically diagnosed arterial disease in at least 1 peripheral arterial territory, defined as:
•History of non-cardioembolic (known or presumed), ischemic stroke (confirmed by medical records or history) or
•Current or history of peripheral arterial disease: current intermittent claudication with an ankle-brachial index =0.85 or history of peripheral arterial stenting or surgery (including amputation due to vascular causes).
French subjects: In France, a subject will be eligible for inclusion in this study
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.
8.Vaccination with a live attenuated vaccine (see SPM) within 6 weeks of randomization.
9.Concomitant use of cytotoxic chemotherapy for cancer or known ongoing or anticipated use of chronic severe immunosuppressive agents as listed below:
•Chronic prednisone use >10 mg/day for >14 consecutive days.
•Currently receiving any systemic immunosuppressive therapy (See SPM for details).
10.Positive pregnancy test or is known to be pregnant or lactating.
All female subjects of childbearing potential must have a urine or serum ß-human chorionic gonadotropin [hCG] pregnancy test performed prior to randomization.
11.Known alcohol or drug abuse within the past 6 months.
12.Any current mental condition (psychiatric disorder, senility or dementia), which may affect study compliance or prevent understanding of the aims, investigational procedures or possible consequences of the study.
13.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.
14.Anticipated inability to comply with any study procedures, including participation in study visits according to the visit schedule through 24 weeks.
15.Any other reason the investigator deems the subject to be unsuitable for the study.
French subjects: In France, a subject will be excluded if he/she has participated in any study using an investigational drug during the previous 30 days.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method