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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by GlaxoSmithKline
Sponsor:
Collaborator:
The TIMI Study Group
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02145468
First received: May 15, 2014
Last updated: September 25, 2014
Last verified: September 2014
  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
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • The primary efficacy endpoint is the composite measure of adjudicated MACE that includes the time to first occurrence of CV death, MI, or SRI-UR. [ Time Frame: Through 12 weeks ] [ Designated as safety issue: No ]
    The primary efficacy endpoint is the composite measure of adjudicated Major Adverse Cardiovascular Events (MACE) that includes the time to first occurrence of 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:
  • Principal Secondary Endpoint: The principal secondary endpoint is the time to first occurrence of the composite of adjudicated CV death or MI [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks. ] [ Designated as safety issue: No ]
  • The composite of CV death, MI, or hospitalization for Heart Failure (HF) [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks. ] [ Designated as safety issue: No ]
  • The expanded composite of arterial CV events, defined as CV death, MI, SRI-UR, or stroke [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks ] [ Designated as safety issue: No ]
  • The composite of coronary events (defined as CHD death, MI, SRI-UR, or any unplanned coronary artery revascularization). [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks. ] [ Designated as safety issue: No ]
    Planned coronary artery revascularizations are those initial or staged interventions performed based on the initial qualifying ACS.

  • The composite of CV death or hospitalization for HF [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks. ] [ Designated as safety issue: No ]
  • The composite of CV death, MI or stroke. [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks. ] [ Designated as safety issue: No ]
  • The composite of CV death, MI, SRI-UR, stroke or hospitalisation for HF [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks. ] [ Designated as safety issue: No ]
  • The primary and principal secondary endpoints will be evaluated replacing CV death separately with CHD death ("Coronary MACE") and all-cause death [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks. ] [ Designated as safety issue: No ]
  • The primary and principal secondary endpoints will be evaluated replacing all MI with Type 1 (spontaneous) MI [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks ] [ Designated as safety issue: No ]
  • Individual components of the composite endpoints (including all-cause mortality). [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks. ] [ Designated as safety issue: No ]
  • Definite or probable stent thrombosis. [ Time Frame: Through 12 weeks with additional analyses through 4 and 24 weeks. ] [ Designated as safety issue: No ]
  • Any re-hospitalization within 30 days of discharge [ Time Frame: Through 30 days after discharge ] [ Designated as safety issue: No ]
  • The composite measure of adjudicated MACE that includes the time to first occurrence of CV death, MI, or SRI-UR. [ Time Frame: Through 4 and 24 weeks ] [ Designated as safety issue: No ]
    The composite measure of adjudicated Major Adverse Cardiovascular Events (MACE) that includes the time to first occurrence of CV death (death due to a cardiovascular cause), MI (Myocardial Infarction) or SRI-UR (Severe Recurrent Ischemia requiring Urgent coronary artery Revascularization)


Estimated Enrollment: 25500
Study Start Date: June 2014
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (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
Losmapimod P38 MAPK inhibitor administered in addition to standard therapy.Other Name: GW856553
Placebo Comparator: Placebo
Placebo twice daily oral tablet
Drug: Placebo twice daily
Placebo administered in addition to standard therapy

  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Both
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

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 182 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
The TIMI Study Group
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02145468     History of Changes
Other Study ID Numbers: 116197
Study First Received: May 15, 2014
Last Updated: September 25, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Agence Fédérale des Medicaments et des Produits de la Santé

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:
Acute Coronary Syndrome
Syndrome
Angina Pectoris
Cardiovascular Diseases
Chest Pain
Disease
Heart Diseases
Myocardial Ischemia
Pain
Pathologic Processes
Signs and Symptoms
Vascular Diseases

ClinicalTrials.gov processed this record on October 22, 2014