Trial Outcomes & Findings for 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) (NCT NCT02145468)

Last Updated: 2017-06-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

3503 participants

Primary outcome timeframe

Up to 12 weeks

Results posted on

2017-06-02

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received losmapimod matching placebo tablets via oral route, twice daily (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.	Losmapimod 7.5 Mllligrms BID Participants received losmapimod 7.5 milligrams (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.
Overall Study STARTED	1758	1731
Overall Study COMPLETED	1753	1723
Overall Study NOT COMPLETED	5	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received losmapimod matching placebo tablets via oral route, twice daily (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.	Losmapimod 7.5 Mllligrms BID Participants received losmapimod 7.5 milligrams (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.
Overall Study Withdrawal by Subject	5	8

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.	Total n=3489 Participants Total of all reporting groups
Age, Continuous	66.5 Years STANDARD_DEVIATION 9.72 • n=99 Participants	66.7 Years STANDARD_DEVIATION 10.00 • n=107 Participants	66.6 Years STANDARD_DEVIATION 9.86 • n=206 Participants
Sex: Female, Male Female	532 Participants n=99 Participants	500 Participants n=107 Participants	1032 Participants n=206 Participants
Sex: Female, Male Male	1226 Participants n=99 Participants	1231 Participants n=107 Participants	2457 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	8 Participants n=99 Participants	8 Participants n=107 Participants	16 Participants n=206 Participants
Race (NIH/OMB) Asian	99 Participants n=99 Participants	105 Participants n=107 Participants	204 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	5 Participants n=99 Participants	10 Participants n=107 Participants	15 Participants n=206 Participants
Race (NIH/OMB) Black or African American	25 Participants n=99 Participants	20 Participants n=107 Participants	45 Participants n=206 Participants
Race (NIH/OMB) White	1616 Participants n=99 Participants	1585 Participants n=107 Participants	3201 Participants n=206 Participants
Race (NIH/OMB) More than one race	2 Participants n=99 Participants	3 Participants n=107 Participants	5 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=99 Participants	0 Participants n=107 Participants	3 Participants n=206 Participants

PRIMARY outcome

Timeframe: Up to 12 weeks

Population: Intent-To-Treat (ITT) Population. ITT population comprised of all randomized participants.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 First occurence of MACE	123 Participants	139 Participants
Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 CV Death	34 Participants	31 Participants
Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 MI	74 Participants	90 Participants
Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12 SRI-UR	15 Participants	18 Participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: ITT Population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
Number of Participants With First Occurrence of MACE Through Week 24 First occurrence of MACE	162 Participants	176 Participants
Number of Participants With First Occurrence of MACE Through Week 24 CV Death	45 Participants	38 Participants
Number of Participants With First Occurrence of MACE Through Week 24 MI	98 Participants	117 Participants
Number of Participants With First Occurrence of MACE Through Week 24 SRI-UR	19 Participants	21 Participants

SECONDARY outcome

Timeframe: Week 12 and Week 24

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	122 Participants
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	156 Participants

SECONDARY outcome

Timeframe: Week 12 and Week 24

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	140 Participants
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	178 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	151 Participants
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	190 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	152 Participants
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	194 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	64 Participants
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	86 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with first occurrence of the composite of CV death, MI or stroke through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	134 Participants
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	170 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	169 Participants
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	212 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	133 Participants
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	167 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with first occurrence of the composite of CHD death or MI through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	116 Participants
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	147 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	142 Participants
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	185 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with first occurrence of the composite of all-cause death or MI through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	125 Participants
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	165 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	94 Participants
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	127 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	77 Participants
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	106 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	11 Participants
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	12 Participants

SECONDARY outcome

Timeframe: Within up to 30 days of post discharge

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
Number of Participants Re-hospitalized Within 30 Days of Discharge	210 Participants	213 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with all-cause mortality through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
Number of Participants With All-cause Mortality Through to Week 12 and Week 24 Week 12	49 Participants	39 Participants
Number of Participants With All-cause Mortality Through to Week 12 and Week 24 Week 24	68 Participants	57 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with CV death events through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
Number of Participants With CV Death Events Through to Week 12 and Week 24 Week 24	59 Participants	47 Participants
Number of Participants With CV Death Events Through to Week 12 and Week 24 Week 12	44 Participants	36 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with CHD death events through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
Number of Participants With CHD Death Events Through to Week 12 and Week 24 Week 12	40 Participants	30 Participants
Number of Participants With CHD Death Events Through to Week 12 and Week 24 Week 24	49 Participants	37 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with first occurrence of myocardial infarction (fatal and non-fatal) events through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
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	90 Participants
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	117 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with first occurrence of type I (spontaneous) MI events through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
Number of Participants With First Occurrence of Type I (Spontaneous) MI Events Through to Week 12 and Week 24 Week 12	32 Participants	42 Participants
Number of Participants With First Occurrence of Type I (Spontaneous) MI Events Through to Week 12 and Week 24 Week 24	51 Participants	62 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with first occurrence of SRI-UR events through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
Number of Participants With First Occurrence of SRI-UR Events Through to Week 12 and Week 24 Week 12	16 Participants	18 Participants
Number of Participants With First Occurrence of SRI-UR Events Through to Week 12 and Week 24 Week 24	22 Participants	22 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with first occurrence of stroke (fatal and non-fatal) events through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
Number of Participants With First Occurrence of Stroke (Fatal and Non-fatal) Events Through to Week 12 and Week 24 Week 12	15 Participants	14 Participants
Number of Participants With First Occurrence of Stroke (Fatal and Non-fatal) Events Through to Week 12 and Week 24 Week 24	19 Participants	18 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with first occurrence of hospitalization for HF through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
Number of Participants With First Occurrence of Hospitalization for HF Through to Week 12 and Week 24 Week 12	42 Participants	35 Participants
Number of Participants With First Occurrence of Hospitalization for HF Through to Week 12 and Week 24 Week 24	53 Participants	49 Participants

SECONDARY outcome

Timeframe: Week 12, Week 24

Population: ITT Population

Number of participants with first occurrence of any unplanned coronary revascularization through to Week 12 and Week 24 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=1758 Participants 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.	Losmapimod 7.5 mg BID n=1731 Participants 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.
Number of Participants With First Occurrence of Any Unplanned Coronary Revascularization Through to Week 12 and Week 24 Week 12	57 Participants	62 Participants
Number of Participants With First Occurrence of Any Unplanned Coronary Revascularization Through to Week 12 and Week 24 Week 24	75 Participants	87 Participants

Adverse Events

Placebo

Serious events: 323 serious events

Other events: 370 other events

Deaths: 68 deaths

Losmapimod 7.5 mg BID

Serious events: 363 serious events

Other events: 376 other events

Deaths: 57 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=1752 participants at risk 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.	Losmapimod 7.5 mg BID n=1724 participants at risk 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.
Vascular disorders Hypertension	2.8% 49/1752 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.	1.9% 33/1724 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.
Vascular disorders Hypotension	1.7% 29/1752 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.	2.1% 36/1724 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.
Investigations Troponin increased	2.2% 39/1752 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.	1.3% 23/1724 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.
Cardiac disorders Angina pectoris	1.8% 32/1752 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.	2.3% 40/1724 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.
Cardiac disorders Atrial fibrillation	3.7% 65/1752 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.	4.2% 72/1724 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.
Respiratory, thoracic and mediastinal disorders Cough	2.2% 38/1752 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.	2.7% 47/1724 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.5% 61/1752 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.	2.8% 48/1724 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.
Blood and lymphatic system disorders Anemia	2.0% 35/1752 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.	2.3% 39/1724 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.
Nervous system disorders Dizziness	2.1% 37/1752 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.	2.3% 39/1724 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.
General disorders Non-cardiac chest pain	2.3% 41/1752 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.	2.6% 44/1724 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.
Gastrointestinal disorders Diarrhoea	2.3% 41/1752 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.	2.8% 49/1724 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Week 24) SAEs and AEs are reported for the Safety population which comprised of all randomized participants who had received at least one dose of investigational product (IP). The SAEs are all SAEs excluding positively CEC-adjudicated CV events.

Additional Information

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