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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 (Solstice)

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ClinicalTrials.gov Identifier: NCT00910962
Recruitment Status : Completed
First Posted : June 1, 2009
Results First Posted : October 27, 2017
Last Update Posted : December 7, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Coronary Syndrome
Interventions Drug: GW856553
Drug: Placebo
Enrollment 526
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Hide Arm/Group Description Eligible participants received matching placebo, orally twice daily for 12 weeks. 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). 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).
Period Title: Overall Study
Started 135 199 192
Completed 92 121 116
Not Completed 43 78 76
Reason Not Completed
Adverse Event             5             20             17
Protocol Violation             1             3             3
Lost to Follow-up             0             3             1
Physician Decision             0             6             6
Withdrawal by Subject             25             32             32
Reached defined stopping criteria             12             14             17
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) Total
Hide Arm/Group Description Eligible participants received matching placebo, orally twice daily for 12 weeks. 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). 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 of all reporting groups
Overall Number of Baseline Participants 135 199 192 526
Hide Baseline Analysis Population Description
The race of one participant each in treatment A and treatment B were unknown.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 135 participants 199 participants 192 participants 526 participants
63.4  (10.29) 62.6  (11.03) 64.6  (10.50) 63.5  (10.66)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 199 participants 192 participants 526 participants
Female
40
  29.6%
52
  26.1%
57
  29.7%
149
  28.3%
Male
95
  70.4%
147
  73.9%
135
  70.3%
377
  71.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 199 participants 192 participants 526 participants
American Indian or Alaska Native
0
   0.0%
3
   1.5%
0
   0.0%
3
   0.6%
Asian
4
   3.0%
4
   2.0%
9
   4.7%
17
   3.2%
Native Hawaiian or Other Pacific Islander
1
   0.7%
2
   1.0%
3
   1.6%
6
   1.1%
Black or African American
2
   1.5%
6
   3.0%
5
   2.6%
13
   2.5%
White
128
  94.8%
183
  92.0%
174
  90.6%
485
  92.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   0.5%
1
   0.5%
2
   0.4%
1.Primary Outcome
Title Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description 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.
Time Frame Up to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population consisted of all participants randomized to treatment, who had taken at least one dose of study medication.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 135 199 192 391
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
97
  71.9%
138
  69.3%
131
  68.2%
269
  68.8%
Any SAE
32
  23.7%
51
  25.6%
43
  22.4%
94
  24.0%
2.Primary Outcome
Title Number of Participants With Any Major Adverse Cardiovascular Events (MACE)
Hide Description MACE was defined as all-cause death, adjudicated myocardial infarction, stroke/transient ischemic attack, heart failure or recurrent ischemia requiring urgent revascularization.
Time Frame Up to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 135 199 192 391
Measure Type: Count of Participants
Unit of Measure: Participants
23
  17.0%
28
  14.1%
34
  17.7%
62
  15.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4110
Comments [Not Specified]
Method Cox' proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.46 to 1.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9318
Comments [Not Specified]
Method Cox' proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.60 to 1.74
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6805
Comments [Not Specified]
Method Cox' proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.56 to 1.46
Estimation Comments [Not Specified]
3.Primary Outcome
Title Number of Participants With Any Pure MACE
Hide Description Pure MACE was defined as all-cause death, adjudicated myocardial infarction or stroke/transient ischemic attack.
Time Frame Up to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 135 199 192 391
Measure Type: Count of Participants
Unit of Measure: Participants
19
  14.1%
21
  10.6%
29
  15.1%
50
  12.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2990
Comments [Not Specified]
Method Cox' proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.39 to 1.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8235
Comments [Not Specified]
Method Cox' proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.60 to 1.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6590
Comments [Not Specified]
Method Cox' proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.52 to 1.51
Estimation Comments [Not Specified]
4.Primary Outcome
Title Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline
Hide Description 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.
Time Frame Up to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Number of participants with analyzable samples at the time of analysis were included.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 120 173 166 339
Measure Type: Count of Participants
Unit of Measure: Participants
Eosinophils, high
2
   1.7%
7
   4.0%
11
   6.6%
18
   5.3%
Eosinophils, low
14
  11.7%
20
  11.6%
16
   9.6%
36
  10.6%
Hematocrit, high
2
   1.7%
5
   2.9%
5
   3.0%
10
   2.9%
Hematocrit, low
2
   1.7%
8
   4.6%
8
   4.8%
16
   4.7%
Hemoglobin, high
0
   0.0%
1
   0.6%
0
   0.0%
1
   0.3%
Hemoglobin, low
0
   0.0%
1
   0.6%
2
   1.2%
3
   0.9%
Lymphocytes, high
0
   0.0%
1
   0.6%
2
   1.2%
3
   0.9%
Lymphocytes, low
2
   1.7%
7
   4.0%
5
   3.0%
12
   3.5%
MCH, low
0
   0.0%
1
   0.6%
2
   1.2%
3
   0.9%
Monocytes, high
1
   0.8%
1
   0.6%
3
   1.8%
4
   1.2%
Monocytes, low
14
  11.7%
15
   8.7%
19
  11.4%
34
  10.0%
Platelet count, high
0
   0.0%
4
   2.3%
3
   1.8%
7
   2.1%
Platelet count, low
2
   1.7%
1
   0.6%
2
   1.2%
3
   0.9%
RDW, high
3
   2.5%
3
   1.7%
7
   4.2%
10
   2.9%
RBC count, high
0
   0.0%
1
   0.6%
0
   0.0%
1
   0.3%
RBC count, low
10
   8.3%
10
   5.8%
11
   6.6%
21
   6.2%
Reticulocytes, high
30
  25.0%
49
  28.3%
36
  21.7%
85
  25.1%
Reticulocytes, low
5
   4.2%
4
   2.3%
4
   2.4%
8
   2.4%
ANC, high
4
   3.3%
12
   6.9%
19
  11.4%
31
   9.1%
ANC, low
1
   0.8%
2
   1.2%
0
   0.0%
2
   0.6%
WBC count, high
5
   4.2%
11
   6.4%
15
   9.0%
26
   7.7%
5.Primary Outcome
Title Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline
Hide Description 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.
Time Frame Up to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Number of participants with analyzable samples at the time of analysis were included.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 135 199 192 391
Measure Type: Count of Participants
Unit of Measure: Participants
ALT, high Number Analyzed 124 participants 177 participants 173 participants 350 participants
1
   0.8%
4
   2.3%
2
   1.2%
6
   1.7%
Albumin, low Number Analyzed 122 participants 175 participants 170 participants 345 participants
0
   0.0%
0
   0.0%
1
   0.6%
1
   0.3%
Alkaline phosphatase, high Number Analyzed 127 participants 183 participants 185 participants 368 participants
0
   0.0%
2
   1.1%
0
   0.0%
2
   0.5%
AST, high Number Analyzed 124 participants 177 participants 173 participants 350 participants
0
   0.0%
2
   1.1%
2
   1.2%
4
   1.1%
Calcium, high Number Analyzed 121 participants 175 participants 170 participants 345 participants
4
   3.3%
3
   1.7%
5
   2.9%
8
   2.3%
Calcium, low Number Analyzed 121 participants 175 participants 170 participants 345 participants
9
   7.4%
17
   9.7%
15
   8.8%
32
   9.3%
CO2/HCO3, high Number Analyzed 121 participants 175 participants 170 participants 345 participants
1
   0.8%
1
   0.6%
3
   1.8%
4
   1.2%
CO2/HCO3, low Number Analyzed 121 participants 175 participants 170 participants 345 participants
39
  32.2%
61
  34.9%
76
  44.7%
137
  39.7%
Chloride, high Number Analyzed 122 participants 175 participants 170 participants 345 participants
1
   0.8%
5
   2.9%
6
   3.5%
11
   3.2%
Chloride, low Number Analyzed 122 participants 175 participants 170 participants 345 participants
0
   0.0%
3
   1.7%
1
   0.6%
4
   1.2%
Creatinine, high Number Analyzed 122 participants 175 participants 170 participants 345 participants
6
   4.9%
10
   5.7%
17
  10.0%
27
   7.8%
Creatinine, low Number Analyzed 122 participants 175 participants 170 participants 345 participants
0
   0.0%
1
   0.6%
0
   0.0%
1
   0.3%
Glucose, high Number Analyzed 122 participants 175 participants 169 participants 344 participants
90
  73.8%
132
  75.4%
113
  66.9%
245
  71.2%
Glucose, low Number Analyzed 122 participants 175 participants 169 participants 344 participants
3
   2.5%
0
   0.0%
2
   1.2%
2
   0.6%
Potassium, high Number Analyzed 120 participants 175 participants 170 participants 345 participants
0
   0.0%
6
   3.4%
4
   2.4%
10
   2.9%
Potassium, low Number Analyzed 120 participants 175 participants 170 participants 345 participants
3
   2.5%
1
   0.6%
4
   2.4%
5
   1.4%
Sodium, high Number Analyzed 122 participants 175 participants 169 participants 344 participants
0
   0.0%
1
   0.6%
1
   0.6%
2
   0.6%
Sodium, low Number Analyzed 122 participants 175 participants 169 participants 344 participants
1
   0.8%
6
   3.4%
2
   1.2%
8
   2.3%
T. Bilirubin, high Number Analyzed 124 participants 177 participants 173 participants 350 participants
0
   0.0%
3
   1.7%
0
   0.0%
3
   0.9%
Total protein, low Number Analyzed 122 participants 175 participants 170 participants 345 participants
0
   0.0%
2
   1.1%
3
   1.8%
5
   1.4%
Urea/BUN, high Number Analyzed 122 participants 175 participants 170 participants 345 participants
4
   3.3%
8
   4.6%
15
   8.8%
23
   6.7%
Urea/BUN, low Number Analyzed 122 participants 175 participants 170 participants 345 participants
0
   0.0%
0
   0.0%
1
   0.6%
1
   0.3%
Uric acid, high Number Analyzed 122 participants 175 participants 170 participants 345 participants
19
  15.6%
29
  16.6%
29
  17.1%
58
  16.8%
Uric acid, low Number Analyzed 122 participants 175 participants 170 participants 345 participants
0
   0.0%
1
   0.6%
0
   0.0%
1
   0.3%
6.Primary Outcome
Title Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline
Hide Description 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.
Time Frame Up to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Number of participants with analyzable samples at the time of analysis were included.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 135 199 192 391
Measure Type: Count of Participants
Unit of Measure: Participants
ALT, >=2xULN Number Analyzed 124 participants 177 participants 173 participants 350 participants
4
   3.2%
7
   4.0%
4
   2.3%
11
   3.1%
ALT, >=3xULN Number Analyzed 124 participants 177 participants 173 participants 350 participants
1
   0.8%
4
   2.3%
2
   1.2%
6
   1.7%
ALT, >=5xULN Number Analyzed 124 participants 177 participants 173 participants 350 participants
0
   0.0%
3
   1.7%
0
   0.0%
3
   0.9%
T. Bilirubin, >=1.5xULN Number Analyzed 124 participants 177 participants 173 participants 350 participants
0
   0.0%
3
   1.7%
0
   0.0%
3
   0.9%
AST, >=2xULN Number Analyzed 124 participants 177 participants 173 participants 350 participants
3
   2.4%
10
   5.6%
3
   1.7%
13
   3.7%
AST, >=3xULN Number Analyzed 124 participants 177 participants 173 participants 350 participants
0
   0.0%
2
   1.1%
2
   1.2%
4
   1.1%
AST, >=5xULN Number Analyzed 124 participants 177 participants 173 participants 350 participants
0
   0.0%
1
   0.6%
0
   0.0%
1
   0.3%
Alkaline phosphatase, >=1.5xULN Number Analyzed 122 participants 176 participants 170 participants 346 participants
0
   0.0%
3
   1.7%
2
   1.2%
5
   1.4%
Alkaline phosphatase, >=2xULN Number Analyzed 122 participants 176 participants 170 participants 346 participants
0
   0.0%
2
   1.1%
1
   0.6%
3
   0.9%
Alkaline phosphatase, >=3xULN Number Analyzed 122 participants 176 participants 170 participants 346 participants
0
   0.0%
1
   0.6%
0
   0.0%
1
   0.3%
Alkaline phosphatase, >=5xULN Number Analyzed 122 participants 176 participants 170 participants 346 participants
0
   0.0%
1
   0.6%
0
   0.0%
1
   0.3%
GGT, >=2xULN Number Analyzed 122 participants 175 participants 170 participants 345 participants
11
   9.0%
13
   7.4%
12
   7.1%
25
   7.2%
GGT, >=3xULN Number Analyzed 122 participants 175 participants 170 participants 345 participants
5
   4.1%
5
   2.9%
4
   2.4%
9
   2.6%
GGT, >=5xULN Number Analyzed 122 participants 175 participants 170 participants 345 participants
1
   0.8%
2
   1.1%
2
   1.2%
4
   1.2%
Creatine kinase, >=2xULN Number Analyzed 1 participants 5 participants 3 participants 8 participants
0
   0.0%
1
  20.0%
0
   0.0%
1
  12.5%
7.Primary Outcome
Title Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline
Hide Description 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.
Time Frame Up to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 125 182 180 362
Measure Type: Count of Participants
Unit of Measure: Participants
Normal
34
  27.2%
41
  22.5%
40
  22.2%
81
  22.4%
Abnormal - Not clinically significant
77
  61.6%
115
  63.2%
118
  65.6%
233
  64.4%
Abnormal - clinically significant
14
  11.2%
26
  14.3%
22
  12.2%
48
  13.3%
8.Primary Outcome
Title Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline
Hide Description 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.
Time Frame Up to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Number of participants with analyzable samples at the time of analysis were included.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 132 192 189 381
Measure Type: Count of Participants
Unit of Measure: Participants
DBP, high
0
   0.0%
0
   0.0%
2
   1.1%
2
   0.5%
DBP, low
1
   0.8%
1
   0.5%
1
   0.5%
2
   0.5%
SBP, high
0
   0.0%
1
   0.5%
0
   0.0%
1
   0.3%
SBP, low
0
   0.0%
1
   0.5%
0
   0.0%
1
   0.3%
9.Primary Outcome
Title Mean High-sensitive C-Reactive Protein (hsCRP) Value at Week 12
Hide Description 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.
Time Frame At Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 87 105 109 214
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mg per liter (mg/L)
1.52
(153.7%)
1.30
(183.5%)
1.46
(164.4%)
1.38
(173.3%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.151
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.59 to 1.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.744
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.70 to 1.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.317
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to treatment ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.66 to 1.14
Estimation Comments [Not Specified]
10.Primary Outcome
Title Mean Cardiac Troponin I (cTnI) Area Under Concentration-time Curve (AUC) Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First)
Hide Description 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.
Time Frame At pre-dose and at 8, 16, 24, 32, 40, 48, 56, 64 and 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at 72 hours were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 48 75 74 149
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nonograms*hour per milliliter (ng*hr/mL)
1.7
(469.3%)
1.1
(397.6%)
1.3
(586.6%)
1.2
(478.9%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.83
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.80 to 1.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.84 to 1.39
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.84 to 1.32
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Mean hsCRP Over Hospitalization Period and Through Week 14
Hide Description 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.
Time Frame Up to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 138 196 192 388
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mg/L
Predose Number Analyzed 131 participants 186 participants 178 participants 364 participants
4.03
(232.4%)
4.26
(263.8%)
4.31
(210.1%)
4.29
(235.7%)
24 hours Number Analyzed 104 participants 148 participants 139 participants 287 participants
9.10
(241.8%)
6.76
(325.1%)
6.07
(259.9%)
6.41
(291.3%)
48 hours Number Analyzed 73 participants 104 participants 98 participants 202 participants
14.82
(236.8%)
7.53
(306.3%)
6.69
(335.6%)
7.11
(318.7%)
72 hours Number Analyzed 52 participants 77 participants 76 participants 153 participants
15.34
(300.8%)
7.92
(314.6%)
6.91
(337.6%)
7.40
(323.8%)
Discharge/Early withdrawal Number Analyzed 89 participants 127 participants 123 participants 250 participants
8.95
(171.3%)
6.46
(292.5%)
4.82
(214.5%)
5.59
(253.9%)
Week 2 Number Analyzed 96 participants 128 participants 130 participants 258 participants
3.30
(232.6%)
2.30
(302.9%)
2.18
(319.3%)
2.24
(309.6%)
Week 4 Number Analyzed 95 participants 112 participants 109 participants 221 participants
1.85
(203.0%)
1.42
(227.0%)
1.66
(214.8%)
1.54
(220.7%)
Week 8 Number Analyzed 90 participants 109 participants 109 participants 218 participants
1.65
(160.7%)
1.36
(198.0%)
1.50
(193.1%)
1.43
(195.0%)
Week 14 Number Analyzed 87 participants 107 participants 111 participants 218 participants
1.60
(172.5%)
2.47
(187.0%)
2.59
(168.9%)
2.53
(177.0%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For 24 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Test to reference ratio
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.60 to 0.99
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For 24 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.52 to 0.85
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For 24 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.57 to 0.89
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For 48 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.56
Confidence Interval (2-Sided) 95%
0.40 to 0.78
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For 48 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.33 to 0.65
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For 48 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.38 to 0.69
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For 72 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.059
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.45 to 1.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For 72 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.40 to 0.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For 72 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.45 to 0.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.48 to 1.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.48 to 1.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.50 to 0.99
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.157
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.55 to 1.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.548
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.63 to 1.28
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.253
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.61 to 1.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.204
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.58 to 1.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.965
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.71 to 1.39
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.457
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.66 to 1.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For Week 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 1.58
Confidence Interval (2-Sided) 95%
1.13 to 2.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 1.69
Confidence Interval (2-Sided) 95%
1.21 to 2.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For Week 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 1.64
Confidence Interval (2-Sided) 95%
1.21 to 2.21
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12
Hide Description 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.
Time Frame 24 hours post-randomization and at Weeks 2 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 138 196 192 388
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: picograms per milliliter (pg/mL)
24 hours Number Analyzed 102 participants 147 participants 142 participants 289 participants
10.59
(147.8%)
6.08
(144.6%)
7.11
(148.6%)
6.57
(146.8%)
Week 2 Number Analyzed 101 participants 134 participants 134 participants 268 participants
3.50
(140.6%)
2.75
(116.1%)
3.14
(111.6%)
2.94
(114.0%)
Week 12 Number Analyzed 93 participants 110 participants 113 participants 223 participants
2.62
(102.8%)
2.29
(96.0%)
2.61
(88.4%)
2.45
(92.3%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For 24 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
0.43 to 0.69
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For 24 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.50 to 0.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For 24 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.48 to 0.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.031
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.59 to 0.98
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.315
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.68 to 1.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.65 to 1.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.068
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.65 to 1.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.824
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.78 to 1.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.246
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.73 to 1.09
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First)
Hide Description 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.
Time Frame At pre-dose and at hours 8, 16, 24, 32, 40, 48, 56, 64 and 72
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 138 196 192 388
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Predose Number Analyzed 128 participants 176 participants 167 participants 343 participants
11.5
(247.9%)
10.5
(196.4%)
9.8
(233.5%)
10.2
(213.5%)
8 hours Number Analyzed 107 participants 172 participants 155 participants 327 participants
9.0
(234.5%)
7.8
(185.0%)
8.4
(242.2%)
8.1
(210.4%)
16 hours Number Analyzed 105 participants 162 participants 151 participants 313 participants
7.1
(194.2%)
6.5
(170.9%)
7.0
(213.7%)
6.8
(190.4%)
24 hours Number Analyzed 97 participants 138 participants 134 participants 272 participants
6.2
(151.1%)
5.2
(147.2%)
6.1
(171.8%)
5.6
(159.3%)
32 hours Number Analyzed 84 participants 127 participants 124 participants 251 participants
4.1
(139.5%)
4.5
(129.5%)
5.1
(130.4%)
4.8
(129.9%)
40 hours Number Analyzed 78 participants 117 participants 113 participants 230 participants
3.2
(119.3%)
3.6
(110.1%)
4.0
(118.9%)
3.8
(114.3%)
48 hours Number Analyzed 63 participants 96 participants 92 participants 188 participants
3.0
(103.1%)
3.2
(110.0%)
3.3
(103.3%)
3.3
(106.3%)
56 hours Number Analyzed 52 participants 84 participants 72 participants 156 participants
2.5
(81.5%)
2.8
(98.3%)
3.1
(91.9%)
2.9
(95.2%)
64 hours Number Analyzed 46 participants 81 participants 71 participants 152 participants
2.2
(75.5%)
2.6
(97.8%)
3.0
(87.5%)
2.8
(93.0%)
72 hours Number Analyzed 46 participants 70 participants 70 participants 140 participants
2.4
(117.7%)
2.6
(94.3%)
2.8
(84.3%)
2.7
(89.1%)
DIS/EW Number Analyzed 75 participants 119 participants 112 participants 231 participants
2.9
(117.4%)
2.6
(96.4%)
2.9
(105.6%)
2.8
(100.8%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For 72 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.66
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.89 to 1.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For 72 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.92 to 1.25
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For 72 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.92 to 1.21
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Peak cTnI Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First)
Hide Description 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.
Time Frame Up to 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 129 187 181 368
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
4.02
(482.0%)
3.49
(575.3%)
3.54
(867.8%)
3.52
(701.0%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.92
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.78 to 1.25
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.52
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.85 to 1.36
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.84 to 1.27
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12
Hide Description 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.
Time Frame At discharge and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 138 196 192 388
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: pg/mL
Discharge/Early withdrawal Number Analyzed 83 participants 122 participants 125 participants 247 participants
72.56
(208.2%)
65.84
(174.8%)
73.24
(193.9%)
69.49
(183.9%)
Week 12 Number Analyzed 89 participants 112 participants 112 participants 224 participants
49.41
(167.1%)
37.41
(141.8%)
37.02
(159.8%)
37.22
(150.1%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For discharge/early withdrawal
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.72 to 1.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For discharge/early withdrawal
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.52
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.72 to 1.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For discharge/early withdrawal
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.74 to 1.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.55 to 0.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.61 to 1.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter test to reference ratio
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.60 to 0.98
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12
Hide Description 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.
Time Frame Prior to discharge (visit 1) and at Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 26 37 30 67
Mean (Standard Deviation)
Unit of Measure: Percent of left ventricle
Day 3-5 (Visit 1) Number Analyzed 24 participants 36 participants 29 participants 65 participants
7.804  (7.4066) 5.575  (6.0525) 5.848  (7.6326) 5.697  (6.7483)
Week 12 Number Analyzed 20 participants 24 participants 26 participants 50 participants
5.620  (5.4493) 4.783  (5.2992) 4.335  (5.9772) 4.550  (5.6090)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For Day 3-5 (visit 1)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.254
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.92
Confidence Interval (2-Sided) 95%
-5.25 to 1.41
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Day 3-5 (visit 1)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.106
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.84
Confidence Interval (2-Sided) 95%
-6.29 to 0.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For Day 3-5 (visit 1)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.126
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.38
Confidence Interval (2-Sided) 95%
-5.44 to 0.69
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.184
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.91
Confidence Interval (2-Sided) 95%
-4.74 to 0.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.093
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.47
Confidence Interval (2-Sided) 95%
-5.37 to 0.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.096
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.19
Confidence Interval (2-Sided) 95%
-4.78 to 0.40
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Mean Percent Left Ventricular Ejection Fraction (LVEF) at Week 12
Hide Description 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.
Time Frame At Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 20 24 26 50
Mean (Standard Deviation)
Unit of Measure: Percent
56.615  (11.1103) 59.571  (7.2745) 59.738  (9.5443) 59.658  (8.4453)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.124
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.22
Confidence Interval (2-Sided) 95%
-1.18 to 9.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.05
Confidence Interval (2-Sided) 95%
0.63 to 11.47
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.14
Confidence Interval (2-Sided) 95%
0.28 to 10.00
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12
Hide Description 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.
Time Frame At Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 20 24 26 50
Mean (Standard Deviation)
Unit of Measure: mL
LVEDV 132.895  (35.5648) 125.942  (30.2434) 130.642  (27.1760) 128.386  (28.4914)
LVESV 58.660  (24.8018) 52.115  (19.4760) 53.710  (20.8387) 52.944  (20.0063)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For LVEDV
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -21.53
Confidence Interval (2-Sided) 95%
-40.27 to -2.79
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For LVEDV
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.053
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -18.65
Confidence Interval (2-Sided) 95%
-37.58 to 0.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For LVEDV
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -20.09
Confidence Interval (2-Sided) 95%
-37.01 to -3.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments Placebo (P) vs Losmapimod 7.5 mg (A): For LVESV
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -15.82
Confidence Interval (2-Sided) 95%
-29.51 to -2.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For LVESV
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.22
Confidence Interval (2-Sided) 95%
-31.14 to -3.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments Placebo (P) vs A and B Combined (C): For LVESV
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.52
Confidence Interval (2-Sided) 95%
-28.91 to -4.13
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Mean Left Ventricular Mass at Week 12
Hide Description 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.
Time Frame At Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 20 24 26 50
Mean (Standard Deviation)
Unit of Measure: grams (gm)
145.463  (36.9074) 141.449  (40.5956) 154.194  (42.3668) 148.076  (41.6018)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -22.21
Confidence Interval (2-Sided) 95%
-49.51 to 5.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.614
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.13
Confidence Interval (2-Sided) 95%
-35.22 to 20.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.243
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -14.67
Confidence Interval (2-Sided) 95%
-39.52 to 10.18
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Mean Regional Wall Motion Score Index at Week 12
Hide Description 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.
Time Frame At Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 20 23 26 49
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
0.306  (0.4096) 0.179  (0.2704) 0.186  (0.3326) 0.182  (0.3019)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.44 to -0.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.45 to -0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.42 to -0.06
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Mean Hyperenhancement Score Index at Week 12
Hide Description 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.
Time Frame At week 12
Hide Outcome Measure Data
Hide Analysis Population Description
MRI ITT Population. Only those participants with data available at week 12 were analyzed.
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Combined (C)
Hide Arm/Group Description:
Eligible participants received matching placebo, orally twice daily for 12 weeks.
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).
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 combined data for eligible participants from arm A and arm B were presented.
Overall Number of Participants Analyzed 20 24 26 50
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
0.350  (0.2648) 0.282  (0.3117) 0.249  (0.3096) 0.265  (0.3079)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (P), Losmapimod 7.5 mg (A)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.137
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.26 to 0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Losmapimod 7.5 mg (A), Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.32 to -0.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (P), A and B Combined (C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.047
Comments [Not Specified]
Method Repeated measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.28 to -0.00
Estimation Comments [Not Specified]
Time Frame SAEs and nSAEs were collected from start of study medication up to Week 14.
Adverse Event Reporting Description 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.
 
Arm/Group Title Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Comb (C)
Hide Arm/Group Description Eligible participants received matching placebo, orally twice daily for 12 weeks. 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). 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 combined data for eligible participants from arm A and arm B were presented.
All-Cause Mortality
Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Comb (C)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/135 (2.96%)   4/199 (2.01%)   10/192 (5.21%)   14/391 (3.58%) 
Hide Serious Adverse Events
Placebo (P) Losmapimod 7.5 mg (A) Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) A and B Comb (C)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   32/135 (23.70%)   51/199 (25.63%)   43/192 (22.40%)   94/391 (24.04%) 
Blood and lymphatic system disorders         
Anaemia  1  0/135 (0.00%)  1/199 (0.50%)  1/192 (0.52%)  2/391 (0.51%) 
Cardiac disorders         
Acute myocardial infarction  1  2/135 (1.48%)  4/199 (2.01%)  6/192 (3.13%)  10/391 (2.56%) 
Angina unstable  1  3/135 (2.22%)  4/199 (2.01%)  5/192 (2.60%)  9/391 (2.30%) 
Myocardial infarction  1  7/135 (5.19%)  4/199 (2.01%)  1/192 (0.52%)  5/391 (1.28%) 
Angina pectoris  1  4/135 (2.96%)  1/199 (0.50%)  3/192 (1.56%)  4/391 (1.02%) 
Atrial fibrillation  1  1/135 (0.74%)  2/199 (1.01%)  3/192 (1.56%)  5/391 (1.28%) 
Cardiac failure  1  0/135 (0.00%)  2/199 (1.01%)  4/192 (2.08%)  6/391 (1.53%) 
Cardiogenic shock  1  1/135 (0.74%)  2/199 (1.01%)  2/192 (1.04%)  4/391 (1.02%) 
Arrhythmia  1  1/135 (0.74%)  0/199 (0.00%)  2/192 (1.04%)  2/391 (0.51%) 
Cardiac failure congestive  1