Acute Coronary Syndrome
Conditions
Keywords
Myocardial infarction, Acute coronary syndrome, Cardiovascular disease, p38 mitogen-activated protein kinase (MAPK) inhibitor, NSTEMI, Losmapimod, STEMI
Brief summary
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.
Interventions
DRUGLosmapimod 7.5 mg twice daily
Subjects will receive Losmapimod 7.5 mg as film-coated, round, plain faced tablets.
Subjects will receive placebo as film-coated, round, plain faced tablets.
DRUGStandard 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.
Sponsors
The TIMI Study Group
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 | Up to 12 weeks | The primary efficacy endpoint is the composite measure of adjudicated MACE that includes the time to first occurrence of CV death (death due to a cardiovascular cause), MI or SRI-UR (Severe Recurrent Ischemia requiring Urgent coronary artery Revascularization). Death for which the Clinical Events Committee (CEC) or investigator were unable to establish cause were analyzed as CV deaths. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Occurrence of the Composite of CV Death or MI up to Week 12 and Week 24 | Week 12 and 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 up 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) up to Week 12 and Week 24. | Week 12 and Week 24 | Number of participants with first occurrence of the composite of CV death, MI or hospitalization for HF up 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 MACE Through Week 24 | Up to 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 Definite or Probable Stent Thrombosis Through to Week 12 and Week 24 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Week 12, Week 24 | Number of participants with first occurrence of any unplanned coronary revascularization 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 | 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. |
Countries
Argentina, Australia, Belgium, Bulgaria, Canada, Chile, Czechia, Denmark, Estonia, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Mexico, Netherlands, New Zealand, Norway, Philippines, Poland, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The study was planned in 2 parts (Part A, N=3500 and Part B, N=22000). Upon completing Part A, a decision was made not to progress to Part B because of lack of efficacy. 3503 participants were randomized to Part A, 14 participants were excluded due to concerns over data integrity. 3489 participants were analyzed.
Pre-assignment details
Eligible: \>=35 years and hospitalized with type1 myocardial infarction (MI) and 1 additional predictor of cardiovascular (CV) risk; Excluded: unstable, known liver disease, life-threatening/opportunistic infection, severe renal impairment, NYHA III/IV or Killip III/IV CHF. All participants were followed until they withdrew consent to participate.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received losmapimod matching placebo tablets via oral route, BID, according to the randomization schedule for 12 weeks in addition to standard of care, and were followed for an additional 12 weeks after completing treatment, for a total study duration of 24 weeks. | 1,758 |
| Losmapimod 7.5 mg BID Participants received losmapimod 7.5 mg tablets via oral route, BID, according to the randomization schedule for 12 weeks in addition to standard of care, and were followed for an additional 12 weeks after completing treatment, for a total study duration of 24 weeks. | 1,731 |
| Total | 3,489 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 5 | 8 |
Baseline characteristics
| Characteristic | Losmapimod 7.5 mg BID | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 66.7 Years STANDARD_DEVIATION 10 | 66.6 Years STANDARD_DEVIATION 9.86 | 66.5 Years STANDARD_DEVIATION 9.72 |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 16 Participants | 8 Participants |
| Race (NIH/OMB) Asian | 105 Participants | 204 Participants | 99 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants | 45 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 10 Participants | 15 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 1585 Participants | 3201 Participants | 1616 Participants |
| Sex: Female, Male Female | 500 Participants | 1032 Participants | 532 Participants |
| Sex: Female, Male Male | 1231 Participants | 2457 Participants | 1226 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 68 / 1,752 | 57 / 1,724 |
| other Total, other adverse events | 370 / 1,752 | 376 / 1,724 |
| serious Total, serious adverse events | 323 / 1,752 | 363 / 1,724 |
Outcome results
Primary
Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12
The primary efficacy endpoint is the composite measure of adjudicated MACE that includes the time to first occurrence of CV death (death due to a cardiovascular cause), MI or SRI-UR (Severe Recurrent Ischemia requiring Urgent coronary artery Revascularization). Death for which the Clinical Events Committee (CEC) or investigator were unable to establish cause were analyzed as CV deaths.
Time frame: Up to 12 weeks
Population: Intent-To-Treat (ITT) Population. ITT population comprised of all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 | First occurence of MACE | 123 Participants |
| Placebo | Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 | CV Death | 34 Participants |
| Placebo | Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 | MI | 74 Participants |
| Placebo | Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 | SRI-UR | 15 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 | SRI-UR | 18 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 | First occurence of MACE | 139 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 | MI | 90 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 | CV Death | 31 Participants |
p-value: 0.23895% CI: [0.91, 1.47]Log Rank
Secondary
Number of Participants Re-hospitalized Within 30 Days of 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.
Time frame: Within up to 30 days of post discharge
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Re-hospitalized Within 30 Days of Discharge | 210 Participants |
| Losmapimod 7.5 mg BID | Number of Participants Re-hospitalized Within 30 Days of Discharge | 213 Participants |
p-value: 0.74495% CI: [0.84, 1.27]Wald chi-squared
Secondary
Number of Participants With All-cause Mortality Through to Week 12 and Week 24
Number of participants with all-cause mortality through to Week 12 and Week 24 are presented.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With All-cause Mortality Through to Week 12 and Week 24 | Week 12 | 49 Participants |
| Placebo | Number of Participants With All-cause Mortality Through to Week 12 and Week 24 | Week 24 | 68 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With All-cause Mortality Through to Week 12 and Week 24 | Week 12 | 39 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With All-cause Mortality Through to Week 12 and Week 24 | Week 24 | 57 Participants |
Comparison: Participants with all-cause mortality, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.30995% CI: [0.53, 1.22]Log Rank
Secondary
Number of Participants With CHD Death Events Through to Week 12 and Week 24
Number of participants with CHD death events through to Week 12 and Week 24 are presented.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With CHD Death Events Through to Week 12 and Week 24 | Week 12 | 40 Participants |
| Placebo | Number of Participants With CHD Death Events Through to Week 12 and Week 24 | Week 24 | 49 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With CHD Death Events Through to Week 12 and Week 24 | Week 12 | 30 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With CHD Death Events Through to Week 12 and Week 24 | Week 24 | 37 Participants |
Comparison: CHD death events, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.25195% CI: [0.47, 1.22]Log Rank
Secondary
Number of Participants With CV Death Events Through to Week 12 and Week 24
Number of participants with CV death events through to Week 12 and Week 24 are presented.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With CV Death Events Through to Week 12 and Week 24 | Week 12 | 44 Participants |
| Placebo | Number of Participants With CV Death Events Through to Week 12 and Week 24 | Week 24 | 59 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With CV Death Events Through to Week 12 and Week 24 | Week 12 | 36 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With CV Death Events Through to Week 12 and Week 24 | Week 24 | 47 Participants |
Comparison: CV death events, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.39895% CI: [0.53, 1.28]Log Rank
Comparison: CV death events, Placebo Vs Losmapimod 7.5 mg BID at Week 24p-value: 0.26495% CI: [0.55, 1.18]Log Rank
Secondary
Number of Participants With First Occurrence of Any Unplanned Coronary Revascularization Through to Week 12 and Week 24
Number of participants with first occurrence of any unplanned coronary revascularization through to Week 12 and Week 24 are presented.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of Any Unplanned Coronary Revascularization Through to Week 12 and Week 24 | Week 12 | 57 Participants |
| Placebo | Number of Participants With First Occurrence of Any Unplanned Coronary Revascularization Through to Week 12 and Week 24 | Week 24 | 75 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Any Unplanned Coronary Revascularization Through to Week 12 and Week 24 | Week 12 | 62 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Any Unplanned Coronary Revascularization Through to Week 12 and Week 24 | Week 24 | 87 Participants |
Comparison: Any unplanned coronary revascularization, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.58195% CI: [0.77, 1.59]Log Rank
Secondary
Number of Participants With First Occurrence of Definite or Probable Stent Thrombosis Through to Week 12 and 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.
Time frame: Week 12, Week 24
Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, in the category titles).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of Definite or Probable Stent Thrombosis Through to Week 12 and Week 24 | Week 12, n=1281, 1306 | 19 Participants |
| Placebo | Number of Participants With First Occurrence of Definite or Probable Stent Thrombosis Through to Week 12 and Week 24 | Week 24, n=1758, 1731 | 21 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Definite or Probable Stent Thrombosis Through to Week 12 and Week 24 | Week 12, n=1281, 1306 | 11 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Definite or Probable Stent Thrombosis Through to Week 12 and Week 24 | Week 24, n=1758, 1731 | 12 Participants |
Comparison: Participants with first occurrence of definite or probable stent thrombosis, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.1395% CI: [0.27, 1.19]Log Rank
Secondary
Number of Participants With First Occurrence of Hospitalization for HF Through to Week 12 and Week 24
Number of participants with first occurrence of hospitalization for HF through to Week 12 and Week 24 are presented.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of Hospitalization for HF Through to Week 12 and Week 24 | Week 12 | 42 Participants |
| Placebo | Number of Participants With First Occurrence of Hospitalization for HF Through to Week 12 and Week 24 | Week 24 | 53 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Hospitalization for HF Through to Week 12 and Week 24 | Week 12 | 35 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Hospitalization for HF Through to Week 12 and Week 24 | Week 24 | 49 Participants |
Comparison: Hospitalization for HF, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.45795% CI: [0.54, 1.32]Log Rank
Comparison: Hospitalization for HF, Placebo Vs Losmapimod 7.5 mg BID at Week 24p-value: 0.73695% CI: [0.63, 1.38]Log Rank
Secondary
Number of Participants With First Occurrence of MACE Through 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.
Time frame: Up to Week 24
Population: ITT Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of MACE Through Week 24 | First occurrence of MACE | 162 Participants |
| Placebo | Number of Participants With First Occurrence of MACE Through Week 24 | CV Death | 45 Participants |
| Placebo | Number of Participants With First Occurrence of MACE Through Week 24 | MI | 98 Participants |
| Placebo | Number of Participants With First Occurrence of MACE Through Week 24 | SRI-UR | 19 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of MACE Through Week 24 | SRI-UR | 21 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of MACE Through Week 24 | First occurrence of MACE | 176 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of MACE Through Week 24 | MI | 117 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of MACE Through Week 24 | CV Death | 38 Participants |
p-value: 0.32995% CI: [0.9, 1.38]Log Rank
Secondary
Number of Participants With First Occurrence of Myocardial Infarction (Fatal and Non-fatal) Events Through to Week 12 and 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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of Myocardial Infarction (Fatal and Non-fatal) Events Through to Week 12 and Week 24 | Week 12 | 75 Participants |
| Placebo | Number of Participants With First Occurrence of Myocardial Infarction (Fatal and Non-fatal) Events Through to Week 12 and Week 24 | Week 24 | 99 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Myocardial Infarction (Fatal and Non-fatal) Events Through to Week 12 and Week 24 | Week 12 | 90 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Myocardial Infarction (Fatal and Non-fatal) Events Through to Week 12 and Week 24 | Week 24 | 117 Participants |
Comparison: Myocardial infarction (fatal and non-fatal) events, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.18295% CI: [0.91, 1.67]Log Rank
Comparison: Myocardial infarction (fatal and non-fatal) events, Placebo Vs Losmapimod 7.5 mg BID at Week 24p-value: 0.15895% CI: [0.93, 1.58]Log Rank
Secondary
Number of Participants With First Occurrence of SRI-UR Events Through to Week 12 and Week 24
Number of participants with first occurrence of SRI-UR events through to Week 12 and Week 24 are presented.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of SRI-UR Events Through to Week 12 and Week 24 | Week 12 | 16 Participants |
| Placebo | Number of Participants With First Occurrence of SRI-UR Events Through to Week 12 and Week 24 | Week 24 | 22 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of SRI-UR Events Through to Week 12 and Week 24 | Week 12 | 18 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of SRI-UR Events Through to Week 12 and Week 24 | Week 24 | 22 Participants |
Comparison: SRI-UR events, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.69795% CI: [0.58, 2.24]Log Rank
Secondary
Number of Participants With First Occurrence of Stroke (Fatal and Non-fatal) Events Through to Week 12 and Week 24
Number of participants with first occurrence of stroke (fatal and non-fatal) events through to Week 12 and Week 24 are presented.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of Stroke (Fatal and Non-fatal) Events Through to Week 12 and Week 24 | Week 12 | 15 Participants |
| Placebo | Number of Participants With First Occurrence of Stroke (Fatal and Non-fatal) Events Through to Week 12 and Week 24 | Week 24 | 19 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Stroke (Fatal and Non-fatal) Events Through to Week 12 and Week 24 | Week 12 | 14 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Stroke (Fatal and Non-fatal) Events Through to Week 12 and Week 24 | Week 24 | 18 Participants |
Comparison: Stroke (fatal and non-fatal) events, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.88395% CI: [0.46, 1.96]Log Rank
Secondary
Number of Participants With First Occurrence of the Composite of All-cause Death, MI or SRI-UR Through to Week 12 and 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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of the Composite of All-cause Death, MI or SRI-UR Through to Week 12 and Week 24 | Week 12 | 128 Participants |
| Placebo | Number of Participants With First Occurrence of the Composite of All-cause Death, MI or SRI-UR Through to Week 12 and Week 24 | Week 24 | 169 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of All-cause Death, MI or SRI-UR Through to Week 12 and Week 24 | Week 12 | 142 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of All-cause Death, MI or SRI-UR Through to Week 12 and Week 24 | Week 24 | 185 Participants |
Comparison: Composite of all-cause death, MI or SRI-UR,Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.29595% CI: [0.89, 1.44]Log Rank
Secondary
Number of Participants With First Occurrence of the Composite of All-cause Death or MI Through to Week 12 and 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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of the Composite of All-cause Death or MI Through to Week 12 and Week 24 | Week 12 | 115 Participants |
| Placebo | Number of Participants With First Occurrence of the Composite of All-cause Death or MI Through to Week 12 and Week 24 | Week 24 | 152 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of All-cause Death or MI Through to Week 12 and Week 24 | Week 12 | 125 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of All-cause Death or MI Through to Week 12 and Week 24 | Week 24 | 165 Participants |
Comparison: Composite of all-cause death or MI, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.41295% CI: [0.86, 1.43]Log Rank
Secondary
Number of Participants With First Occurrence of the Composite of CHD Death, MI or SRI-UR Through to Week 12 and 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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of the Composite of CHD Death, MI or SRI-UR Through to Week 12 and Week 24 | Week 12 | 119 Participants |
| Placebo | Number of Participants With First Occurrence of the Composite of CHD Death, MI or SRI-UR Through to Week 12 and Week 24 | Week 24 | 152 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CHD Death, MI or SRI-UR Through to Week 12 and Week 24 | Week 12 | 133 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CHD Death, MI or SRI-UR Through to Week 12 and Week 24 | Week 24 | 167 Participants |
Comparison: Composite of CHD death, MI or SRI-UR, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.28595% CI: [0.89, 1.47]Log Rank
Secondary
Number of Participants With First Occurrence of the Composite of CHD Death or MI Through to Week 12 and 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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of the Composite of CHD Death or MI Through to Week 12 and Week 24 | Week 12 | 106 Participants |
| Placebo | Number of Participants With First Occurrence of the Composite of CHD Death or MI Through to Week 12 and Week 24 | Week 24 | 135 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CHD Death or MI Through to Week 12 and Week 24 | Week 12 | 116 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CHD Death or MI Through to Week 12 and Week 24 | Week 24 | 147 Participants |
Comparison: Composite of CHD death or MI, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.40195% CI: [0.86, 1.46]Log Rank
Secondary
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
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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 | Week 12 | 144 Participants |
| Placebo | 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 | Week 24 | 186 Participants |
| Losmapimod 7.5 mg BID | 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 | Week 12 | 152 Participants |
| Losmapimod 7.5 mg BID | 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 | Week 24 | 194 Participants |
Comparison: Composite of coronary events (CHD death, MI, SRI-UR or any unplanned coronary artery revascularization), Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.50595% CI: [0.86, 1.36]Log Rank
Secondary
Number of Participants With First Occurrence of the Composite of CV Death, MI or Hospitalization for Heart Failure (HF) up to Week 12 and Week 24.
Number of participants with first occurrence of the composite of CV death, MI or hospitalization for HF up to Week 12 and Week 24 are presented.
Time frame: Week 12 and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of the Composite of CV Death, MI or Hospitalization for Heart Failure (HF) up to Week 12 and Week 24. | Week 12 | 131 Participants |
| Placebo | Number of Participants With First Occurrence of the Composite of CV Death, MI or Hospitalization for Heart Failure (HF) up to Week 12 and Week 24. | Week 24 | 169 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CV Death, MI or Hospitalization for Heart Failure (HF) up to Week 12 and Week 24. | Week 12 | 140 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CV Death, MI or Hospitalization for Heart Failure (HF) up to Week 12 and Week 24. | Week 24 | 178 Participants |
Comparison: CV death, MI or hospitalization for HF, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.47295% CI: [0.86, 1.38]Log Rank
Secondary
Number of Participants With First Occurrence of the Composite of CV Death, MI or Stroke Through to Week 12 and 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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of the Composite of CV Death, MI or Stroke Through to Week 12 and Week 24 | Week 12 | 122 Participants |
| Placebo | Number of Participants With First Occurrence of the Composite of CV Death, MI or Stroke Through to Week 12 and Week 24 | Week 24 | 157 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CV Death, MI or Stroke Through to Week 12 and Week 24 | Week 12 | 134 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CV Death, MI or Stroke Through to Week 12 and Week 24 | Week 24 | 170 Participants |
Comparison: Composite of CV death, MI or stroke, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.35695% CI: [0.88, 1.43]Log Rank
Secondary
Number of Participants With First Occurrence of the Composite of CV Death or Hospitalization for HF Through to Week 12 and 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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of the Composite of CV Death or Hospitalization for HF Through to Week 12 and Week 24 | Week 12 | 72 Participants |
| Placebo | Number of Participants With First Occurrence of the Composite of CV Death or Hospitalization for HF Through to Week 12 and Week 24 | Week 24 | 94 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CV Death or Hospitalization for HF Through to Week 12 and Week 24 | Week 12 | 64 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CV Death or Hospitalization for HF Through to Week 12 and Week 24 | Week 24 | 86 Participants |
Comparison: Composite of CV death or hospitalization for HF, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.53695% CI: [0.64, 1.26]Log Rank
Comparison: Composite of CV death or hospitalization for HF, Placebo Vs Losmapimod 7.5 mg BID at Week 24p-value: 0.695% CI: [0.69, 1.24]Log Rank
Secondary
Number of Participants With First Occurrence of the Composite of CV Death or MI up to Week 12 and 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 up to Week 12 and Week 24 are summarized.
Time frame: Week 12 and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of the Composite of CV Death or MI up to Week 12 and Week 24 | Week 12 | 110 Participants |
| Placebo | Number of Participants With First Occurrence of the Composite of CV Death or MI up to Week 12 and Week 24 | Week 24 | 145 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CV Death or MI up to Week 12 and Week 24 | Week 12 | 122 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CV Death or MI up to Week 12 and Week 24 | Week 24 | 156 Participants |
Comparison: CV death or MI, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.33895% CI: [0.88, 1.47]Log Rank
Comparison: CV death or MI, Placebo Vs Losmapimod 7.5 mg BID at Week 24p-value: 0.4195% CI: [0.88, 1.38]Log Rank
Secondary
Number of Participants With First Occurrence of the Composite of CV Death or Type I (Spontaneous) MI Through to Week 12 and 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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of the Composite of CV Death or Type I (Spontaneous) MI Through to Week 12 and Week 24 | Week 12 | 73 Participants |
| Placebo | Number of Participants With First Occurrence of the Composite of CV Death or Type I (Spontaneous) MI Through to Week 12 and Week 24 | Week 24 | 104 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CV Death or Type I (Spontaneous) MI Through to Week 12 and Week 24 | Week 12 | 77 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of the Composite of CV Death or Type I (Spontaneous) MI Through to Week 12 and Week 24 | Week 24 | 106 Participants |
Comparison: Composite of CV death or type I (spontaneous) MI, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.66495% CI: [0.78, 1.48]Log Rank
Secondary
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
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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 | Week 12 | 86 Participants |
| Placebo | 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 | Week 24 | 122 Participants |
| Losmapimod 7.5 mg BID | 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 | Week 12 | 94 Participants |
| Losmapimod 7.5 mg BID | 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 | Week 24 | 127 Participants |
Comparison: Composite of CV death, type I (spontaneous) MI or SRI-UR, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.46995% CI: [0.83, 1.49]Log Rank
Secondary
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
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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 | Week 12 | 135 Participants |
| Placebo | 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 | Week 24 | 174 Participants |
| Losmapimod 7.5 mg BID | 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 | Week 12 | 151 Participants |
| Losmapimod 7.5 mg BID | 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 | Week 24 | 190 Participants |
Comparison: Composite of arterial CV events (CV death, MI, SRI-UR or stroke), Placebo Vs Losmapimod 7.5 mg BID at Week 1295% CI: [0.91, 1.44]Log Rank
Secondary
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
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.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 | Week 12 | 155 Participants |
| Placebo | 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 | Week 24 | 197 Participants |
| Losmapimod 7.5 mg BID | 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 | Week 12 | 169 Participants |
| Losmapimod 7.5 mg BID | 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 | Week 24 | 212 Participants |
Comparison: Composite of CV death, MI, SRI-UR, stroke or hospitalization for HF, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.32995% CI: [0.9, 1.39]Log Rank
Secondary
Number of Participants With First Occurrence of Type I (Spontaneous) MI Events Through to Week 12 and Week 24
Number of participants with first occurrence of type I (spontaneous) MI events through to Week 12 and Week 24 are presented.
Time frame: Week 12, Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With First Occurrence of Type I (Spontaneous) MI Events Through to Week 12 and Week 24 | Week 12 | 32 Participants |
| Placebo | Number of Participants With First Occurrence of Type I (Spontaneous) MI Events Through to Week 12 and Week 24 | Week 24 | 51 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Type I (Spontaneous) MI Events Through to Week 12 and Week 24 | Week 12 | 42 Participants |
| Losmapimod 7.5 mg BID | Number of Participants With First Occurrence of Type I (Spontaneous) MI Events Through to Week 12 and Week 24 | Week 24 | 62 Participants |
Comparison: Type I (spontaneous) MI events, Placebo Vs Losmapimod 7.5 mg BID at Week 12p-value: 0.2195% CI: [0.85, 2.12]Log Rank