Trial Outcomes & Findings for A Study to Evaluate the Safety of 12 Weeks of Dosing With GW856553 and Its Effects on Inflammatory Markers, Infarct Size, and Cardiac Function in Subjects With Myocardial Infarction Without ST-segment Elevation (NCT NCT00910962)

Last Updated: 2017-12-07

Results Overview

AE was any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

526 participants

Primary outcome timeframe

Up to Week 14

Results posted on

2017-12-07

Participant Flow

A total of 535 participants, with myocardial infarction without ST segment elevation, were randomized to the study of which 526 participants received at least one dose of study drug. The study was conducted at 83 centers, from 08 October 2009 to 06 March 2012.

Participant milestones

Participant milestones
Measure	Placebo (P) Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) Eligible participants received oral losmapimod 7.5 milligrams (mg) starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).
Overall Study STARTED	135	199	192
Overall Study COMPLETED	92	121	116
Overall Study NOT COMPLETED	43	78	76

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (P) Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) Eligible participants received oral losmapimod 7.5 milligrams (mg) starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).
Overall Study Adverse Event	5	20	17
Overall Study Protocol Violation	1	3	3
Overall Study Lost to Follow-up	0	3	1
Overall Study Physician Decision	0	6	6
Overall Study Withdrawal by Subject	25	32	32
Overall Study Reached defined stopping criteria	12	14	17

Baseline Characteristics

A Study to Evaluate the Safety of 12 Weeks of Dosing With GW856553 and Its Effects on Inflammatory Markers, Infarct Size, and Cardiac Function in Subjects With Myocardial Infarction Without ST-segment Elevation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (P) n=135 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=199 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=192 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	Total n=526 Participants Total of all reporting groups
Age, Continuous	63.4 Years STANDARD_DEVIATION 10.29 • n=5 Participants	62.6 Years STANDARD_DEVIATION 11.03 • n=7 Participants	64.6 Years STANDARD_DEVIATION 10.50 • n=5 Participants	63.5 Years STANDARD_DEVIATION 10.66 • n=4 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	52 Participants n=7 Participants	57 Participants n=5 Participants	149 Participants n=4 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	147 Participants n=7 Participants	135 Participants n=5 Participants	377 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants	17 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) White	128 Participants n=5 Participants	183 Participants n=7 Participants	174 Participants n=5 Participants	485 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to Week 14

Population: Safety Population consisted of all participants randomized to treatment, who had taken at least one dose of study medication.

Outcome measures

Outcome measures
Measure	Placebo (P) n=135 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=199 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=192 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=391 Participants A combined data for eligible participants from arm A and arm B were presented.
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	97 Participants	138 Participants	131 Participants	269 Participants
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE	32 Participants	51 Participants	43 Participants	94 Participants

PRIMARY outcome

Timeframe: Up to Week 14

Population: Safety Population

MACE was defined as all-cause death, adjudicated myocardial infarction, stroke/transient ischemic attack, heart failure or recurrent ischemia requiring urgent revascularization.

Outcome measures

Outcome measures
Measure	Placebo (P) n=135 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=199 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=192 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=391 Participants A combined data for eligible participants from arm A and arm B were presented.
Number of Participants With Any Major Adverse Cardiovascular Events (MACE)	23 Participants	28 Participants	34 Participants	62 Participants

PRIMARY outcome

Timeframe: Up to Week 14

Population: Safety Population.

Pure MACE was defined as all-cause death, adjudicated myocardial infarction or stroke/transient ischemic attack.

Outcome measures

Outcome measures
Measure	Placebo (P) n=135 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=199 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=192 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=391 Participants A combined data for eligible participants from arm A and arm B were presented.
Number of Participants With Any Pure MACE	19 Participants	21 Participants	29 Participants	50 Participants

PRIMARY outcome

Timeframe: Up to Week 14

Population: Safety Population. Number of participants with analyzable samples at the time of analysis were included.

Hematology parameters (PCI range): Eosinophils (\<0.045 or \>0.605 Giga cells per liter \[GI/L\]), Hematocrit (\<0.297 or \>0.506 ratio), Hemoglobin (\<85 or \>200 grams per liter \[g/L\]), Lymphocytes (\<0.765 or \>4.51GI/L), Mean Corpuscle Hemoglobin (MCH) (\<24.3 or \>38.5 picograms \[PG\]), Mean Corpuscle Hemoglobin Concentration (MCHC) (\<256 or \>432 g/L), Mean Corpuscle Volume (MCV) (\<70 or \>115 femtoliter \[FL\]), Monocytes (\<0.18 or \>1.21 GI/L), Platelet count (\<104 or \>480 GI/L), Red Cell Distribution Width (RDW) (\<7.2 or \>18%), Red Blood Cell (RBC) count (\<2.88 or \>6.12 trillion per liter \[TI/L\] for females and \<3.52 or \>6.96 TI/L for males) , Reticulocytes (\<22.5 or \>93.5 10\^9/L), Total Absolute Neutrophil Count (ANC) (\<1.62 or \>8.8 GI/L), White Blood Cell (WBC) count (\<3.04 or \>12 GI/L) were analyzed. The data was presented as High and low, at any visit post-Baseline. Only parameters with observed abnormal values were presented.

Outcome measures

Outcome measures
Measure	Placebo (P) n=120 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=173 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=166 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=339 Participants A combined data for eligible participants from arm A and arm B were presented.
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Eosinophils, high	2 Participants	7 Participants	11 Participants	18 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Eosinophils, low	14 Participants	20 Participants	16 Participants	36 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Hematocrit, high	2 Participants	5 Participants	5 Participants	10 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Hematocrit, low	2 Participants	8 Participants	8 Participants	16 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Hemoglobin, low	0 Participants	1 Participants	2 Participants	3 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Lymphocytes, low	2 Participants	7 Participants	5 Participants	12 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline MCH, low	0 Participants	1 Participants	2 Participants	3 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Monocytes, low	14 Participants	15 Participants	19 Participants	34 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Platelet count, low	2 Participants	1 Participants	2 Participants	3 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline RDW, high	3 Participants	3 Participants	7 Participants	10 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline RBC count, low	10 Participants	10 Participants	11 Participants	21 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Hemoglobin, high	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Lymphocytes, high	0 Participants	1 Participants	2 Participants	3 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Monocytes, high	1 Participants	1 Participants	3 Participants	4 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Platelet count, high	0 Participants	4 Participants	3 Participants	7 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline RBC count, high	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Reticulocytes, high	30 Participants	49 Participants	36 Participants	85 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline Reticulocytes, low	5 Participants	4 Participants	4 Participants	8 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline ANC, high	4 Participants	12 Participants	19 Participants	31 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline ANC, low	1 Participants	2 Participants	0 Participants	2 Participants
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline WBC count, high	5 Participants	11 Participants	15 Participants	26 Participants

PRIMARY outcome

Timeframe: Up to Week 14

Population: Safety Population. Number of participants with analyzable samples at the time of analysis were included.

Clinical chemistry parameters (PCI range): Alanine Amino Transferase (ALT) (\>=3x upper limit normal \[ULN\] units per liter \[U/L\]), Albumin (\<25.6 or \>60 g/L), Alkaline Phosphatase (\>=2x ULN U/L), Aspartate Amino Transferase (AST) (\>=3x ULN U/L), Calcium (\<2.0776 or \>2.6112 millimoles per liter \[mmol/L\]), Carbon dioxide content/Bicarbonate (CO2/HCO3) (\<19.6 or \>32.64 mmol/L), Chloride (\<93.1 or \>110.16 mmol/L), Creatinine (\<39.6 or \>136.4 micromole per liter \[µmol/L\]) , Glucose (\<3.51 or \>6.05 mmol/L), Potassium (\<3.43 or \>5.406 mmol/L), Sodium (\<132.3 or \>148.92 mmol/L), Total Bilirubin (T. bilirubin) (\>=1.5xULN µmol/L) , Total Protein (\<50 or \>95 g/L), Urea/Blood urea nitrogen (BUN) (\<2.25 or \>11.55 mmol/L) and Uric acid (\<135 or \>495 µmol/L) were analyzed. The data was presented as High and low, at any visit post-Baseline. Only parameters with observed abnormal values were presented.

Outcome measures

Outcome measures
Measure	Placebo (P) n=135 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=199 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=192 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=391 Participants A combined data for eligible participants from arm A and arm B were presented.
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Chloride, low	0 Participants	3 Participants	1 Participants	4 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Creatinine, high	6 Participants	10 Participants	17 Participants	27 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Creatinine, low	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Total protein, low	0 Participants	2 Participants	3 Participants	5 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Uric acid, low	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline ALT, high	1 Participants	4 Participants	2 Participants	6 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Albumin, low	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Alkaline phosphatase, high	0 Participants	2 Participants	0 Participants	2 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline AST, high	0 Participants	2 Participants	2 Participants	4 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Calcium, high	4 Participants	3 Participants	5 Participants	8 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Calcium, low	9 Participants	17 Participants	15 Participants	32 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline CO2/HCO3, high	1 Participants	1 Participants	3 Participants	4 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline CO2/HCO3, low	39 Participants	61 Participants	76 Participants	137 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Chloride, high	1 Participants	5 Participants	6 Participants	11 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Glucose, high	90 Participants	132 Participants	113 Participants	245 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Glucose, low	3 Participants	0 Participants	2 Participants	2 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Potassium, high	0 Participants	6 Participants	4 Participants	10 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Potassium, low	3 Participants	1 Participants	4 Participants	5 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Sodium, high	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Sodium, low	1 Participants	6 Participants	2 Participants	8 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline T. Bilirubin, high	0 Participants	3 Participants	0 Participants	3 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Urea/BUN, high	4 Participants	8 Participants	15 Participants	23 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Urea/BUN, low	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline Uric acid, high	19 Participants	29 Participants	29 Participants	58 Participants

PRIMARY outcome

Timeframe: Up to Week 14

Population: Safety Population. Number of participants with analyzable samples at the time of analysis were included.

Liver function test parameters: Alanine aminotransferase (ALT), Total Bilirubin (T. Bilirubin), Aspartate aminotransferase (AST), Alkaline Phosphatase, Gamma glutamyl transferase (GGT) and Creatine Kinase were analyzed and presented as elevated test values at any time post-Baseline. The elevations were presented as \>=2xULN, \>=3xULN, \>=5xULN, \>=10xULN, and \>=20xULN. n= number of participants with at least one non-missing result of the particular lab test post-Baseline.

Outcome measures

Outcome measures
Measure	Placebo (P) n=135 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=199 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=192 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=391 Participants A combined data for eligible participants from arm A and arm B were presented.
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline ALT, >=5xULN	0 Participants	3 Participants	0 Participants	3 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline AST, >=2xULN	3 Participants	10 Participants	3 Participants	13 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline Alkaline phosphatase, >=1.5xULN	0 Participants	3 Participants	2 Participants	5 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline GGT, >=3xULN	5 Participants	5 Participants	4 Participants	9 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline GGT, >=5xULN	1 Participants	2 Participants	2 Participants	4 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline AST, >=3xULN	0 Participants	2 Participants	2 Participants	4 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline ALT, >=2xULN	4 Participants	7 Participants	4 Participants	11 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline ALT, >=3xULN	1 Participants	4 Participants	2 Participants	6 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline T. Bilirubin, >=1.5xULN	0 Participants	3 Participants	0 Participants	3 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline AST, >=5xULN	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline Alkaline phosphatase, >=2xULN	0 Participants	2 Participants	1 Participants	3 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline Alkaline phosphatase, >=3xULN	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline Alkaline phosphatase, >=5xULN	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline GGT, >=2xULN	11 Participants	13 Participants	12 Participants	25 Participants
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline Creatine kinase, >=2xULN	0 Participants	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to Week 14

Population: Safety Population. Only those participants with data available at the indicated time points were analyzed.

A single 12-lead ECG was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT corrected (QTc) intervals. ECG findings were presented as Normal, Abnormal - Not clinically significant and Abnormal - Clinically significant at any time post-Baseline.

Outcome measures

Outcome measures
Measure	Placebo (P) n=125 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=182 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=180 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=362 Participants A combined data for eligible participants from arm A and arm B were presented.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline Abnormal - Not clinically significant	77 Participants	115 Participants	118 Participants	233 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline Normal	34 Participants	41 Participants	40 Participants	81 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline Abnormal - clinically significant	14 Participants	26 Participants	22 Participants	48 Participants

PRIMARY outcome

Timeframe: Up to Week 14

Population: Safety Population. Number of participants with analyzable samples at the time of analysis were included.

Vital signs (PCI range): Systolic blood pressure (SBP) (\<75 and \>200 millimeter of mercury \[mmHg\]), Diastolic blood pressure (DBP) (\<40 and \>120 mmHg) and Heart rate (\<30 and \>200 beats per minute \[bpm\]) were analyzed and were presented at any visit post-Baseline. Participants with both Normal and Low values were counted once under their worst case (Low). Participants with both Normal and High values were counted once under their worst case (High). Participants with both High and Low values were counted under both categories. All heart rate values were within normal range, hence not presented.

Outcome measures

Outcome measures
Measure	Placebo (P) n=132 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=192 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=189 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=381 Participants A combined data for eligible participants from arm A and arm B were presented.
Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline DBP, high	0 Participants	0 Participants	2 Participants	2 Participants
Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline DBP, low	1 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline SBP, high	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline SBP, low	0 Participants	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: At Week 12

Population: Intent-to-treat (ITT) Population comprised all randomized participants who received at least one dose of study medication and at least one on treatment assessment. Only those participants with data available at Week 12 were analyzed.

Analysis of hsCRP included all participants who provided data at Baseline and at least one post-Baseline measure. Statistical analyses was performed to compare hsCRP levels between study drug and placebo. Log transformed ratio to Baseline hsCRP was analyzed using repeated measures analysis of covariance (ANCOVA) including a term for treatment, adjusting for Baseline hsCRP as a covariate, and accounting for other covariates as appropriate to the study design.

Outcome measures

Outcome measures
Measure	Placebo (P) n=87 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=105 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=109 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=214 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean High-sensitive C-Reactive Protein (hsCRP) Value at Week 12	1.52 mg per liter (mg/L) Geometric Coefficient of Variation 153.7	1.30 mg per liter (mg/L) Geometric Coefficient of Variation 183.5	1.46 mg per liter (mg/L) Geometric Coefficient of Variation 164.4	1.38 mg per liter (mg/L) Geometric Coefficient of Variation 173.3

PRIMARY outcome

Timeframe: At pre-dose and at 8, 16, 24, 32, 40, 48, 56, 64 and 72 hours

Population: ITT Population. Only those participants available at 72 hours were analyzed.

cTnI AUC was the average concentration of cTnI during hospital stay. Statistical analyses was performed to compare cTnI levels between study drug and placebo, via ANCOVA.

Outcome measures

Outcome measures
Measure	Placebo (P) n=48 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=75 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=74 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=149 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean Cardiac Troponin I (cTnI) Area Under Concentration-time Curve (AUC) Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First)	1.7 nonogramshour per milliliter (nghr/mL) Geometric Coefficient of Variation 469.3	1.1 nonogramshour per milliliter (nghr/mL) Geometric Coefficient of Variation 397.6	1.3 nonogramshour per milliliter (nghr/mL) Geometric Coefficient of Variation 586.6	1.2 nonogramshour per milliliter (nghr/mL) Geometric Coefficient of Variation 478.9

SECONDARY outcome

Timeframe: Up to Week 14

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Analysis of hsCRP included all participants who provided data at Baseline and at least one post-Baseline measure. The sample had a collection window of +/- 8 hours. Statistical analyses was performed to compare hsCRP levels between study drug and placebo. Log transformed ratio to Baseline hsCRP was analyzed using ANCOVA including a term for treatment, adjusting for Baseline hsCRP as a covariate, and accounting for other covariates as appropriate to the study design.

Outcome measures

Outcome measures
Measure	Placebo (P) n=138 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=196 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=192 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=388 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean hsCRP Over Hospitalization Period and Through Week 14 Predose	4.03 mg/L Geometric Coefficient of Variation 232.4	4.26 mg/L Geometric Coefficient of Variation 263.8	4.31 mg/L Geometric Coefficient of Variation 210.1	4.29 mg/L Geometric Coefficient of Variation 235.7
Mean hsCRP Over Hospitalization Period and Through Week 14 24 hours	9.10 mg/L Geometric Coefficient of Variation 241.8	6.76 mg/L Geometric Coefficient of Variation 325.1	6.07 mg/L Geometric Coefficient of Variation 259.9	6.41 mg/L Geometric Coefficient of Variation 291.3
Mean hsCRP Over Hospitalization Period and Through Week 14 48 hours	14.82 mg/L Geometric Coefficient of Variation 236.8	7.53 mg/L Geometric Coefficient of Variation 306.3	6.69 mg/L Geometric Coefficient of Variation 335.6	7.11 mg/L Geometric Coefficient of Variation 318.7
Mean hsCRP Over Hospitalization Period and Through Week 14 72 hours	15.34 mg/L Geometric Coefficient of Variation 300.8	7.92 mg/L Geometric Coefficient of Variation 314.6	6.91 mg/L Geometric Coefficient of Variation 337.6	7.40 mg/L Geometric Coefficient of Variation 323.8
Mean hsCRP Over Hospitalization Period and Through Week 14 Discharge/Early withdrawal	8.95 mg/L Geometric Coefficient of Variation 171.3	6.46 mg/L Geometric Coefficient of Variation 292.5	4.82 mg/L Geometric Coefficient of Variation 214.5	5.59 mg/L Geometric Coefficient of Variation 253.9
Mean hsCRP Over Hospitalization Period and Through Week 14 Week 2	3.30 mg/L Geometric Coefficient of Variation 232.6	2.30 mg/L Geometric Coefficient of Variation 302.9	2.18 mg/L Geometric Coefficient of Variation 319.3	2.24 mg/L Geometric Coefficient of Variation 309.6
Mean hsCRP Over Hospitalization Period and Through Week 14 Week 4	1.85 mg/L Geometric Coefficient of Variation 203.0	1.42 mg/L Geometric Coefficient of Variation 227.0	1.66 mg/L Geometric Coefficient of Variation 214.8	1.54 mg/L Geometric Coefficient of Variation 220.7
Mean hsCRP Over Hospitalization Period and Through Week 14 Week 8	1.65 mg/L Geometric Coefficient of Variation 160.7	1.36 mg/L Geometric Coefficient of Variation 198.0	1.50 mg/L Geometric Coefficient of Variation 193.1	1.43 mg/L Geometric Coefficient of Variation 195.0
Mean hsCRP Over Hospitalization Period and Through Week 14 Week 14	1.60 mg/L Geometric Coefficient of Variation 172.5	2.47 mg/L Geometric Coefficient of Variation 187.0	2.59 mg/L Geometric Coefficient of Variation 168.9	2.53 mg/L Geometric Coefficient of Variation 177.0

SECONDARY outcome

Timeframe: 24 hours post-randomization and at Weeks 2 and 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Statistical analyses was performed to compare IL-6 levels between study drug and placebo. Log transformed ratio to Baseline IL-6 was analyzed using repeated measures ANCOVA including a term for treatment, adjusting for Baseline IL-6 as a covariate, and accounting for other covariates as appropriate to the study design.

Outcome measures

Outcome measures
Measure	Placebo (P) n=138 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=196 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=192 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=388 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 24 hours	10.59 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 147.8	6.08 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 144.6	7.11 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 148.6	6.57 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 146.8
Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 Week 2	3.50 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 140.6	2.75 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 116.1	3.14 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 111.6	2.94 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 114.0
Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 Week 12	2.62 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 102.8	2.29 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 96.0	2.61 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 88.4	2.45 picograms per milliliter (pg/mL) Geometric Coefficient of Variation 92.3

SECONDARY outcome

Timeframe: At pre-dose and at hours 8, 16, 24, 32, 40, 48, 56, 64 and 72

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Statistical analyses was performed to compare CK-MB levels between study drug and placebo. Log transformed ratio to Baseline CK-MB was analyzed using repeated measures ANCOVA including a term for treatment, adjusting for Baseline CK-MB as a covariate, and accounting for other covariates as appropriate to the study design.

Outcome measures

Outcome measures
Measure	Placebo (P) n=138 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=196 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=192 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=388 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) 24 hours	6.2 ng*hr/mL Geometric Coefficient of Variation 151.1	5.2 ng*hr/mL Geometric Coefficient of Variation 147.2	6.1 ng*hr/mL Geometric Coefficient of Variation 171.8	5.6 ng*hr/mL Geometric Coefficient of Variation 159.3
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) Predose	11.5 ng*hr/mL Geometric Coefficient of Variation 247.9	10.5 ng*hr/mL Geometric Coefficient of Variation 196.4	9.8 ng*hr/mL Geometric Coefficient of Variation 233.5	10.2 ng*hr/mL Geometric Coefficient of Variation 213.5
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) 8 hours	9.0 ng*hr/mL Geometric Coefficient of Variation 234.5	7.8 ng*hr/mL Geometric Coefficient of Variation 185.0	8.4 ng*hr/mL Geometric Coefficient of Variation 242.2	8.1 ng*hr/mL Geometric Coefficient of Variation 210.4
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) 16 hours	7.1 ng*hr/mL Geometric Coefficient of Variation 194.2	6.5 ng*hr/mL Geometric Coefficient of Variation 170.9	7.0 ng*hr/mL Geometric Coefficient of Variation 213.7	6.8 ng*hr/mL Geometric Coefficient of Variation 190.4
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) 32 hours	4.1 ng*hr/mL Geometric Coefficient of Variation 139.5	4.5 ng*hr/mL Geometric Coefficient of Variation 129.5	5.1 ng*hr/mL Geometric Coefficient of Variation 130.4	4.8 ng*hr/mL Geometric Coefficient of Variation 129.9
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) 40 hours	3.2 ng*hr/mL Geometric Coefficient of Variation 119.3	3.6 ng*hr/mL Geometric Coefficient of Variation 110.1	4.0 ng*hr/mL Geometric Coefficient of Variation 118.9	3.8 ng*hr/mL Geometric Coefficient of Variation 114.3
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) 48 hours	3.0 ng*hr/mL Geometric Coefficient of Variation 103.1	3.2 ng*hr/mL Geometric Coefficient of Variation 110.0	3.3 ng*hr/mL Geometric Coefficient of Variation 103.3	3.3 ng*hr/mL Geometric Coefficient of Variation 106.3
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) 56 hours	2.5 ng*hr/mL Geometric Coefficient of Variation 81.5	2.8 ng*hr/mL Geometric Coefficient of Variation 98.3	3.1 ng*hr/mL Geometric Coefficient of Variation 91.9	2.9 ng*hr/mL Geometric Coefficient of Variation 95.2
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) 64 hours	2.2 ng*hr/mL Geometric Coefficient of Variation 75.5	2.6 ng*hr/mL Geometric Coefficient of Variation 97.8	3.0 ng*hr/mL Geometric Coefficient of Variation 87.5	2.8 ng*hr/mL Geometric Coefficient of Variation 93.0
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) 72 hours	2.4 ng*hr/mL Geometric Coefficient of Variation 117.7	2.6 ng*hr/mL Geometric Coefficient of Variation 94.3	2.8 ng*hr/mL Geometric Coefficient of Variation 84.3	2.7 ng*hr/mL Geometric Coefficient of Variation 89.1
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) DIS/EW	2.9 ng*hr/mL Geometric Coefficient of Variation 117.4	2.6 ng*hr/mL Geometric Coefficient of Variation 96.4	2.9 ng*hr/mL Geometric Coefficient of Variation 105.6	2.8 ng*hr/mL Geometric Coefficient of Variation 100.8

SECONDARY outcome

Timeframe: Up to 72 hours

Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.

Statistical analyses was performed to compare cTnI levels between study drug and placebo. Log transformed ratio to Baseline cTnI was analyzed using repeated measures ANCOVA including a term for treatment, adjusting for Baseline cTnI as a covariate, and accounting for other covariates as appropriate to the study design.

Outcome measures

Outcome measures
Measure	Placebo (P) n=129 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=187 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=181 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=368 Participants A combined data for eligible participants from arm A and arm B were presented.
Peak cTnI Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First)	4.02 ng/mL Geometric Coefficient of Variation 482.0	3.49 ng/mL Geometric Coefficient of Variation 575.3	3.54 ng/mL Geometric Coefficient of Variation 867.8	3.52 ng/mL Geometric Coefficient of Variation 701.0

SECONDARY outcome

Timeframe: At discharge and Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Statistical analyses was performed to compare BNP levels between study drug and placebo. Log transformed ratio to Baseline BNP was analyzed using repeated measures ANCOVA including a term for treatment, adjusting for Baseline BNP as a covariate, and accounting for other covariates as appropriate to the study design.

Outcome measures

Outcome measures
Measure	Placebo (P) n=138 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=196 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=192 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=388 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12 Week 12	49.41 pg/mL Geometric Coefficient of Variation 167.1	37.41 pg/mL Geometric Coefficient of Variation 141.8	37.02 pg/mL Geometric Coefficient of Variation 159.8	37.22 pg/mL Geometric Coefficient of Variation 150.1
Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12 Discharge/Early withdrawal	72.56 pg/mL Geometric Coefficient of Variation 208.2	65.84 pg/mL Geometric Coefficient of Variation 174.8	73.24 pg/mL Geometric Coefficient of Variation 193.9	69.49 pg/mL Geometric Coefficient of Variation 183.9

SECONDARY outcome

Timeframe: Prior to discharge (visit 1) and at Week 12

Population: MRI ITT Population was subset of participants in the ITT Population who had at least one MRI scan. Only those participants available at the specified time points were analyzed.

Statistical analyses was performed to compare the infarct size (via MRI) at Week 12 via repeated measures ANOVA between study drug and placebo using Bayesian methods for inference. Myocardial infarct size was measured by delayed enhancement magnetic resonance imaging (MRI) as: Infarct size (% of left ventricular myocardium \[% of LV\]) for infarct 1. The infarct region 1 was the infarct region which the MRI interpretation process identified as the primary infarct region of the index hospitalization. Participants were included in the analyses, provided they have data for derivation of the measures of interest (MR infarct size). A total of 15 participants out of 93 MRI ITT participants were excluded from the analysis due to missing Baseline cTnI (10 participants) and onset chest pain duration (9 participants). Four participants had both covariate values missing.

Outcome measures

Outcome measures
Measure	Placebo (P) n=26 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=37 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=30 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=67 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12 Day 3-5 (Visit 1)	7.804 Percent of left ventricle Standard Deviation 7.4066	5.575 Percent of left ventricle Standard Deviation 6.0525	5.848 Percent of left ventricle Standard Deviation 7.6326	5.697 Percent of left ventricle Standard Deviation 6.7483
Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12 Week 12	5.620 Percent of left ventricle Standard Deviation 5.4493	4.783 Percent of left ventricle Standard Deviation 5.2992	4.335 Percent of left ventricle Standard Deviation 5.9772	4.550 Percent of left ventricle Standard Deviation 5.6090

SECONDARY outcome

Timeframe: At Week 12

Population: MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.

Statistical analyses of the treatment differences was performed to compare the LVEF (via MRI) at Week 12, and for the change from Day 3 to Week 12 via repeated measures ANCOVA between study drug and placebo. Cardiac MRIs were performed at qualified sites on participants who agree to participate in the MRI sub-study. A total of 15 participants out of 93 MRI ITT participants were excluded from the analysis due to missing Baseline cTnI (10 participants) and onset chest pain duration (9 participants). Four participants had both covariate values missing.

Outcome measures

Outcome measures
Measure	Placebo (P) n=20 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=24 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=26 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=50 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean Percent Left Ventricular Ejection Fraction (LVEF) at Week 12	56.615 Percent Standard Deviation 11.1103	59.571 Percent Standard Deviation 7.2745	59.738 Percent Standard Deviation 9.5443	59.658 Percent Standard Deviation 8.4453

SECONDARY outcome

Timeframe: At Week 12

Population: MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.

Statistical analyses of the treatment differences was performed to compare the LVEDV and LVESV (via MRI) at Week 12, and for the change from Day 3 to Week 12 via repeated measures ANCOVA between study drug and placebo. Cardiac MRIs were performed at qualified sites on participants who agree to participate in the MRI sub-study. A total of 15 participants out of 93 MRI ITT participants were excluded from the analysis due to missing Baseline cTnI (10 participants) and onset chest pain duration (9 participants). Four participants had both covariate values missing.

Outcome measures

Outcome measures
Measure	Placebo (P) n=20 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=24 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=26 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=50 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12 LVEDV	132.895 mL Standard Deviation 35.5648	125.942 mL Standard Deviation 30.2434	130.642 mL Standard Deviation 27.1760	128.386 mL Standard Deviation 28.4914
Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12 LVESV	58.660 mL Standard Deviation 24.8018	52.115 mL Standard Deviation 19.4760	53.710 mL Standard Deviation 20.8387	52.944 mL Standard Deviation 20.0063

SECONDARY outcome

Timeframe: At Week 12

Population: MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.

Statistical analyses of the treatment differences was performed to compare the left ventricular mass (via MRI) at Week 12, and for the change from Day 3 to Week 12 via repeated measures ANCOVA between study drug and placebo.Cardiac MRIs were performed at qualified sites on participants who agree to participate in the MRI sub-study. A total of 15 participants out of 93 MRI ITT participants were excluded from the analysis due to missing Baseline cTnI (10 participants) and onset chest pain duration (9 participants). Four participants had both covariate values missing.

Outcome measures

Outcome measures
Measure	Placebo (P) n=20 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=24 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=26 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=50 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean Left Ventricular Mass at Week 12	145.463 grams (gm) Standard Deviation 36.9074	141.449 grams (gm) Standard Deviation 40.5956	154.194 grams (gm) Standard Deviation 42.3668	148.076 grams (gm) Standard Deviation 41.6018

SECONDARY outcome

Timeframe: At Week 12

Population: MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.

Wall motion score index is a semi-quantitative analysis of regional systolic function. Each segment is analyzed individually and scored on the basis of its motion and systolic thickening. This score is a 5-level score defines as: 1=normokinesis or hyperkinesis, 2=hypokinesi, 3=akinesis, 4=dyskinesis, 5=aneurysm. Wall motion score index is derived as a sum of all scores divided by the number of segments visualized. Larger score index indicates higher degree of abnormalities. Cardiac MRIs were performed at qualified sites on participants who agree to participate in the MRI sub-study. A total of 15 participants out of 93 MRI ITT participants were excluded from the analysis due to missing Baseline cTnI (10 participants) and onset chest pain duration (9 participants). Four participants had both covariate values missing.

Outcome measures

Outcome measures
Measure	Placebo (P) n=20 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=23 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=26 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=49 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean Regional Wall Motion Score Index at Week 12	0.306 Scores on a scale Standard Deviation 0.4096	0.179 Scores on a scale Standard Deviation 0.2704	0.186 Scores on a scale Standard Deviation 0.3326	0.182 Scores on a scale Standard Deviation 0.3019

SECONDARY outcome

Timeframe: At week 12

Population: MRI ITT Population. Only those participants with data available at week 12 were analyzed.

The myocardium was divided into 17 segments. A score ranging from 0 to 4 was visually attributed to each of the 17 segments according to the transmural extent of the hyperenhancement: score 0=0%, 1=\>0-25%, 2=\>25-50%, 3=\>50-75% and 4=\>75-100%. All these 17 scores were summed. The resulting summed score ranged in theory from 0 to 68 and was thereafter expressed as a percentage of the maximum possible score of 68, with higher percentages indicating hyper-enhancement in a greater percentage of the tissue in a greater number of segments. Cardiac MRIs were performed at qualified sites on participants who agree to participate in the MRI sub-study. A total of 15 participants out of 93 MRI ITT participants were excluded from the analysis due to missing Baseline cTnI (10 participants) and onset chest pain duration (9 participants). Four participants had both covariate values missing. Statistical analysis was performed on LS mean value using repeated measures ANCOVA.

Outcome measures

Outcome measures
Measure	Placebo (P) n=20 Participants Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=24 Participants Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=26 Participants Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Combined (C) n=50 Participants A combined data for eligible participants from arm A and arm B were presented.
Mean Hyperenhancement Score Index at Week 12	0.350 Scores on a scale Standard Deviation 0.2648	0.282 Scores on a scale Standard Deviation 0.3117	0.249 Scores on a scale Standard Deviation 0.3096	0.265 Scores on a scale Standard Deviation 0.3079

Adverse Events

Placebo (P)

Serious events: 32 serious events

Other events: 52 other events

Deaths: 4 deaths

Losmapimod 7.5 mg (A)

Serious events: 51 serious events

Other events: 55 other events

Deaths: 4 deaths

Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)

Serious events: 43 serious events

Other events: 49 other events

Deaths: 10 deaths

A and B Comb (C)

Serious events: 94 serious events

Other events: 104 other events

Deaths: 14 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo (P) n=135 participants at risk Eligible participants received matching placebo, orally twice daily for 12 weeks.	Losmapimod 7.5 mg (A) n=199 participants at risk Eligible participants received oral losmapimod 7.5 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as non-loading dose group).	Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) n=192 participants at risk Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group).	A and B Comb (C) n=391 participants at risk A combined data for eligible participants from arm A and arm B were presented.
Nervous system disorders Headache	8.1% 11/135 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	7.5% 15/199 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	6.8% 13/192 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	7.2% 28/391 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.
Nervous system disorders Dizziness	7.4% 10/135 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	5.5% 11/199 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	3.6% 7/192 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	4.6% 18/391 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.
General disorders Chest pain	5.2% 7/135 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	6.5% 13/199 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	4.7% 9/192 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	5.6% 22/391 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.
General disorders Fatigue	7.4% 10/135 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.0% 4/199 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.6% 5/192 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.3% 9/391 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.
Gastrointestinal disorders Nausea	5.9% 8/135 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	3.5% 7/199 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.1% 4/192 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.8% 11/391 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.
Gastrointestinal disorders Diarrhoea	5.2% 7/135 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.0% 4/199 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	3.1% 6/192 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.6% 10/391 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.
Vascular disorders Haematoma	5.9% 8/135 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	5.5% 11/199 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	3.1% 6/192 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	4.3% 17/391 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.
Infections and infestations Nasopharyngitis	5.2% 7/135 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	0.50% 1/199 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	4.7% 9/192 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.6% 10/391 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.2% 7/135 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.5% 5/199 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.1% 4/192 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.3% 9/391 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.
Cardiac disorders Atrial fibrillation	5.2% 7/135 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	1.5% 3/199 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.6% 5/192 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.	2.0% 8/391 • SAEs and nSAEs were collected from start of study medication up to Week 14. SAEs and nSAEs were reported for safety Population which consisted of all participants randomized to treatment, who had taken at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER