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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) (LATITUDE)

This study has been completed.
Sponsor:
Collaborator:
The TIMI Study Group
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02145468
First received: May 15, 2014
Last updated: March 30, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention Phase
Acute Coronary Syndrome
Drug: Losmapimod 7.5 mg twice daily
Drug: Placebo twice daily
Drug: Standard therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider
Primary Purpose: Treatment
Official Title: 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) LosmApimod To Inhibit p38 MAP Kinase as a TherapeUtic Target and moDify Outcomes After an Acute Coronary syndromE (LATITUDE)-TIMI 60.

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of participants with first occurrence of Major Adverse Cardiovascular Events (MACE) through Week 12 [ Time Frame: Through 12 weeks ]
    The primary efficacy endpoint is the composite measure of adjudicated MACE that includes the time to first occurrence of cardiovascular (CV) death (death due to a cardiovascular cause), MI (Myocardial Infarction) or SRI-UR (Severe Recurrent Ischemia requiring Urgent coronary artery Revascularization)


Secondary Outcome Measures:
  • Number of participants with first occurrence of MACE through Week 24 [ Time Frame: Upto Week 24 ]
    Number of participants with first occurrence of MACE through Week 24 including CV death, MI or SRI-UR are presented. Death for which the CEC or investigator were unable to establish cause were analyzed as CV deaths.

  • Number of participants with first occurrence of the composite of CV death or MI through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Week 12 results are considered the principal secondary endpoint. Number of participants with first occurrence of the composite of CV death or MI through to Week 12 and Week 24 are summarized.

  • Number of participants with first occurrence of the composite of CV death, MI or hospitalization for heart failure (HF) through to Week 12 and Week 24. [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks ]
    Number of participants with first occurrence of the composite of CV death, MI or hospitalization for HF through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of the expanded composite of arterial CV events defined as CV death, MI, SRI-UR or stroke through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of the expanded composite of arterial CV events defined as CV death, MI, SRI-UR or stroke through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of the composite of coronary events defined as CHD death, MI, SRI-UR or any unplanned coronary artery revascularization through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of the composite of coronary events defined as coronary heart disease (CHD) death, MI, SRI-UR or any unplanned coronary artery revascularization through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of the composite of CV death or hospitalization for HF through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of the composite of CV death or hospitalization for HF through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of the composite of CV death, MI or stroke through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of the composite of CV death, MI or stroke through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of the expanded composite of CV death, MI, SRI-UR, stroke or hospitalization for HF through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of the expanded composite of CV death, MI, SRI-UR, stroke or hospitalization for HF through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of the composite of CHD death, MI or SRI-UR through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of the composite of CHD death, MI or SRI-UR through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of the composite of CHD death or MI through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of the composite of CHD death or MI through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of the composite of all-cause death, MI or SRI-UR through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of the composite of all-cause death, MI or SRI-UR through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of the composite of all-cause death or MI through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of the composite of all-cause death or MI through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of the composite of CV death, type I (spontaneous) MI or SRI-UR through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of the composite of CV death, type I (spontaneous) MI or SRI-UR through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of the composite of CV death or type I (spontaneous) MI through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of the composite of CV death or type I (spontaneous) MI through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of definite or probable stent thrombosis through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of definite or probable stent thrombosis through to Week 12 and Week 24 are presented. Participants receiving stent prior to randomization or during the study prior to Week 12 were included.

  • Number of participants re-hospitalized within 30 days of discharge [ Time Frame: Within up to 30 days of post discharge ]
    Participants who had a death or re-hospitalization within 30 days of discharge, plus participants who were never discharged from the initial hospitalization were included.

  • Number of participants with all-cause mortality through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with all-cause mortality through to Week 12 and Week 24 are presented.

  • Number of participants with CV death events through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with CV death events through to Week 12 and Week 24 are presented.

  • Number of participants with CHD death events through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with CHD death events through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of myocardial infarction (fatal and non-fatal) events through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of myocardial infarction (fatal and non-fatal) events through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of type I (spontaneous) MI events through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of type I (spontaneous) MI events through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of SRI-UR events through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of SRI-UR events through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of stroke (fatal and non-fatal) events through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of stroke (fatal and non-fatal) events through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of hospitalization for HF through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of hospitalization for HF through to Week 12 and Week 24 are presented.

  • Number of participants with first occurrence of any unplanned coronary revascularization through to Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ]
    Number of participants with first occurrence of any unplanned coronary revascularization through to Week 12 and Week 24 are presented.


Enrollment: 3503
Actual Study Start Date: June 3, 2014
Study Completion Date: December 14, 2015
Primary Completion Date: December 14, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Losmapimod
Losmapimod 7.5 mg twice daily oral tablet
Drug: Losmapimod 7.5 mg twice daily
Subjects will receive Losmapimod 7.5 mg as film-coated, round, plain faced tablets.
Other Name: GW856553
Drug: Standard therapy
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.
Placebo Comparator: Placebo
Placebo twice daily oral tablet
Drug: Placebo twice daily
Subjects will receive placebo as film-coated, round, plain faced tablets.
Drug: Standard therapy
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.

  Eligibility

Ages Eligible for Study:   35 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02145468

  Show 342 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
The TIMI Study Group
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 116197
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 116197
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 116197
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 116197
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 116197
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 116197
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 116197
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02145468     History of Changes
Other Study ID Numbers: 116197
Study First Received: May 15, 2014
Last Updated: March 30, 2017
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
Myocardial infarction
Acute coronary syndrome
Cardiovascular disease
p38 mitogen-activated protein kinase (MAPK) inhibitor
NSTEMI
Losmapimod
STEMI

Additional relevant MeSH terms:
Syndrome
Acute Coronary Syndrome
Disease
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on April 28, 2017