Acute Coronary Syndrome
Conditions
Keywords
NSTEMI, acute coronary syndrome, p38 MAPK inhibitor, GW856553, percutaneous coronary intervention
Brief summary
This is a randomized, double-blind, placebo-controlled, parallel group, multi-center study to evaluate initial safety and efficacy of GW856553 in subjects with NSTEMI. Up to approximately 525 subjects will be randomized to meet the MRI recruitment target (90 subjects in substudy.) All subjects will continue to receive the local standard of care for the duration of the study.
Interventions
DRUGGW856553
7.5 mg GW856553 starting dose, followed 12 hours later by 7.5mg BID
DRUGPlacebo
Placebo
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with a NSTEMI, defined as: symptoms (e.g. chest pain, dyspnea) consistent with acute coronary syndrome, lasting at least 10 minutes, with most recent symptoms occurring within the 24 hours prior to presentation, without persistent ST-segment elevation on admission 12-lead ECG, and with Troponin (T or I) above the upper limit of normal (ULN) for the local institution within 18 hours of presentation. * Subject able to be randomized within 18 hours of presentation. * Subjects to be managed with an early invasive strategy, with PCI likely to occur at least 2 hours after the start of dosing \[subjects who do not undergo PCI will not be withdrawn from the study\]. * Male or female subject who is 45 years of age or older. * A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) greater than 40 MlU/ml and estradiol less than 40 pg/ml (less than 140 pmol/L) is confirmatory), or child-bearing potential and agrees to use one of the contraception methods listed in the protocol for the duration of dosing and until the first follow-up visit (approximately 2 weeks post last-dose). * Negative urine or serum pregnancy test (in women of child-bearing potential only). * Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the first follow-up visit (approximately 2 weeks post last-dose). * QTcB or QTcF greater than 530 msec. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion criteria
* History of severe heart failure defined as NYHA class III or IV or those with known severe LV dysfunction \[ejection fraction less than 30%\] regardless of symptomatic status. * Suspected aortic dissection. * Severe aortic stenosis or other severe valvular disease. * Current known life-threatening condition other than vascular disease (e.g. severe chronic airways disease) that may prevent a subject from completing the study. * Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic or acute inflammation (e.g. inflammatory bowel disease, osteomyelitis, pneumonia, etc.). Intermittent conditions treated with short-term oral antibiotics (e.g. typical URI) or conditions that are not currently exacerbated (e.g. gout with no current flair) may be included. * History of myopathy or rhabdomyolysis. * Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Known to be Hepatitis B or Hepatitis C positive. * Current or anticipated use of systemic steroids (oral or IV). Inhaled, intranasal and topical steroids are allowed. A single prophylactic dose of systemic steroid is allowed at time of PCI for subjects with contrast allergy. * Current or anticipated use of BCRP substrates with a narrow therapeutic index (e.g. daunorubicin, doxorubicin, topotecan, mitoxantrone). * Previously diagnosed cancer that has not been in complete remission for at least 5 years. Localized carcinomas of the skin and carcinoma in situ of the cervix that have been resected or ablated for cure are not exclusionary.. * Known alcohol or drug abuse within the past 6 months. * Previous exposure to GW856553. * Use of another investigational product within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of IP in the current study. * Any other subject whom the Investigator deems unsuitable for the study (e.g., due to either medical reasons, laboratory abnormalities, expected study medication non-compliance). * Unwillingness or inability to follow the procedures outlined in the protocol. * Previous MI or coronary artery bypass graft (CABG) surgery. * History of kidney transplant or a history of contrast nephropathy. * Contraindication to MRI scanning (as assessed by local MRI safety questionnaire) which includes but is not limited to: intracranial aneurysm clips or other metallic objects; history of intra-orbital metal fragments that have not been removed by an MD; pacemakers and non-MR compatible heart valves; inner ear implants; history of claustrophobia in MR. * Allergy to MRI contrast enhancement agent (gadolinium). * Estimated creatinine clearance by Cockcroft-Gault formula \< 30 mL/min.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Week 14 | 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. |
| Number of Participants With Any Major Adverse Cardiovascular Events (MACE) | Up to Week 14 | MACE was defined as all-cause death, adjudicated myocardial infarction, stroke/transient ischemic attack, heart failure or recurrent ischemia requiring urgent revascularization. |
| Number of Participants With Any Pure MACE | Up to Week 14 | Pure MACE was defined as all-cause death, adjudicated myocardial infarction or stroke/transient ischemic attack. |
| Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Up to Week 14 | 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. |
| Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Up to Week 14 | 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. |
| Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Up to Week 14 | 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. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Up to Week 14 | 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. |
| Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | Up to Week 14 | 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. |
| Mean High-sensitive C-Reactive Protein (hsCRP) Value at Week 12 | At Week 12 | 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. |
| Mean Cardiac Troponin I (cTnI) Area Under Concentration-time Curve (AUC) Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | At pre-dose and at 8, 16, 24, 32, 40, 48, 56, 64 and 72 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean hsCRP Over Hospitalization Period and Through Week 14 | Up to Week 14 | 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. |
| Mean Hyperenhancement Score Index at Week 12 | At week 12 | 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. |
| Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | 24 hours post-randomization and at Weeks 2 and 12 | 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. |
| Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | At pre-dose and at hours 8, 16, 24, 32, 40, 48, 56, 64 and 72 | 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. |
| Peak cTnI Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | Up to 72 hours | 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. |
| Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12 | At discharge and Week 12 | 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. |
| Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12 | Prior to discharge (visit 1) and at Week 12 | 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. |
| Mean Percent Left Ventricular Ejection Fraction (LVEF) at Week 12 | At Week 12 | 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. |
| Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12 | At Week 12 | 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. |
| Mean Left Ventricular Mass at Week 12 | At Week 12 | 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. |
| Mean Regional Wall Motion Score Index at Week 12 | At Week 12 | 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. |
Countries
Australia, Canada, Germany, India, Netherlands, Poland, Spain, United Kingdom, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (P) Eligible participants received matching placebo, orally twice daily for 12 weeks. | 135 |
| Losmapimod 7.5 mg (A) 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). | 199 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) Eligible participants received oral losmapimod 15 mg starting dose, followed 12+/-4 hours, later by losmapimod 7.5 mg twice daily maintenance dose for 12 weeks (referred to as loading dose group). | 192 |
| Total | 526 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 20 | 17 |
| Overall Study | Lost to Follow-up | 0 | 3 | 1 |
| Overall Study | Physician Decision | 0 | 6 | 6 |
| Overall Study | Protocol Violation | 1 | 3 | 3 |
| Overall Study | Reached defined stopping criteria | 12 | 14 | 17 |
| Overall Study | Withdrawal by Subject | 25 | 32 | 32 |
Baseline characteristics
| Characteristic | Placebo (P) | Losmapimod 7.5 mg (A) | Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Total |
|---|---|---|---|---|
| Age, Continuous | 63.4 Years STANDARD_DEVIATION 10.29 | 62.6 Years STANDARD_DEVIATION 11.03 | 64.6 Years STANDARD_DEVIATION 10.5 | 63.5 Years STANDARD_DEVIATION 10.66 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 9 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 128 Participants | 183 Participants | 174 Participants | 485 Participants |
| Sex: Female, Male Female | 40 Participants | 52 Participants | 57 Participants | 149 Participants |
| Sex: Female, Male Male | 95 Participants | 147 Participants | 135 Participants | 377 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 135 | 4 / 199 | 10 / 192 | 14 / 391 |
| other Total, other adverse events | 52 / 135 | 55 / 199 | 49 / 192 | 104 / 391 |
| serious Total, serious adverse events | 32 / 135 | 51 / 199 | 43 / 192 | 94 / 391 |
Outcome results
Primary
Mean Cardiac Troponin I (cTnI) Area Under Concentration-time Curve (AUC) Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First)
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
Population: ITT Population. Only those participants available at 72 hours were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (P) | Mean Cardiac Troponin I (cTnI) Area Under Concentration-time Curve (AUC) Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 1.7 nonograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 469.3 |
| Losmapimod 7.5 mg (A) | Mean Cardiac Troponin I (cTnI) Area Under Concentration-time Curve (AUC) Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 1.1 nonograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 397.6 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Cardiac Troponin I (cTnI) Area Under Concentration-time Curve (AUC) Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 1.3 nonograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 586.6 |
| A and B Combined (C) | Mean Cardiac Troponin I (cTnI) Area Under Concentration-time Curve (AUC) Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 1.2 nonograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 478.9 |
p-value: 0.8395% CI: [0.8, 1.32]ANCOVA
p-value: 0.5695% CI: [0.84, 1.39]ANCOVA
p-value: 0.6595% CI: [0.84, 1.32]ANCOVA
Primary
Mean High-sensitive C-Reactive Protein (hsCRP) Value at Week 12
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
Population: Intent-to-treat (ITT) Population comprised all randomized participants who received at least one dose of study medication and at least one on treatment assessment. Only those participants with data available at Week 12 were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (P) | Mean High-sensitive C-Reactive Protein (hsCRP) Value at Week 12 | 1.52 mg per liter (mg/L) | Geometric Coefficient of Variation 153.7 |
| Losmapimod 7.5 mg (A) | Mean High-sensitive C-Reactive Protein (hsCRP) Value at Week 12 | 1.30 mg per liter (mg/L) | Geometric Coefficient of Variation 183.5 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean High-sensitive C-Reactive Protein (hsCRP) Value at Week 12 | 1.46 mg per liter (mg/L) | Geometric Coefficient of Variation 164.4 |
| A and B Combined (C) | Mean High-sensitive C-Reactive Protein (hsCRP) Value at Week 12 | 1.38 mg per liter (mg/L) | Geometric Coefficient of Variation 173.3 |
p-value: 0.15195% CI: [0.59, 1.09]Repeated measures ANCOVA
p-value: 0.74495% CI: [0.7, 1.29]Repeated measures ANCOVA
p-value: 0.31795% CI: [0.66, 1.14]Repeated measures ANCOVA
Primary
Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline
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
Population: Safety Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (P) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Abnormal - clinically significant | 14 Participants |
| Placebo (P) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Abnormal - Not clinically significant | 77 Participants |
| Placebo (P) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Normal | 34 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Abnormal - Not clinically significant | 115 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Normal | 41 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Abnormal - clinically significant | 26 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Normal | 40 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Abnormal - Not clinically significant | 118 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Abnormal - clinically significant | 22 Participants |
| A and B Combined (C) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Abnormal - Not clinically significant | 233 Participants |
| A and B Combined (C) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Abnormal - clinically significant | 48 Participants |
| A and B Combined (C) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline | Normal | 81 Participants |
Primary
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
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
Population: Safety Population consisted of all participants randomized to treatment, who had taken at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (P) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 97 Participants |
| Placebo (P) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 32 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 51 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 138 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 43 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 131 Participants |
| A and B Combined (C) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 269 Participants |
| A and B Combined (C) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 94 Participants |
Primary
Number of Participants With Any Major Adverse Cardiovascular Events (MACE)
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
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (P) | Number of Participants With Any Major Adverse Cardiovascular Events (MACE) | 23 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Any Major Adverse Cardiovascular Events (MACE) | 28 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Any Major Adverse Cardiovascular Events (MACE) | 34 Participants |
| A and B Combined (C) | Number of Participants With Any Major Adverse Cardiovascular Events (MACE) | 62 Participants |
p-value: 0.41195% CI: [0.46, 1.38]Cox' proportional hazards model
p-value: 0.931895% CI: [0.6, 1.74]Cox' proportional hazards model
p-value: 0.680595% CI: [0.56, 1.46]Cox' proportional hazards model
Primary
Number of Participants With Any Pure MACE
Pure MACE was defined as all-cause death, adjudicated myocardial infarction or stroke/transient ischemic attack.
Time frame: Up to Week 14
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (P) | Number of Participants With Any Pure MACE | 19 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Any Pure MACE | 21 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Any Pure MACE | 29 Participants |
| A and B Combined (C) | Number of Participants With Any Pure MACE | 50 Participants |
p-value: 0.29995% CI: [0.39, 1.34]Cox' proportional hazards model
p-value: 0.823595% CI: [0.6, 1.9]Cox' proportional hazards model
p-value: 0.65995% CI: [0.52, 1.51]Cox' proportional hazards model
Primary
Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline
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
Population: Safety Population. Number of participants with analyzable samples at the time of analysis were included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Calcium, high | 4 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | AST, high | 0 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Calcium, low | 9 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | CO2/HCO3, high | 1 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Chloride, low | 0 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | CO2/HCO3, low | 39 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Albumin, low | 0 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Chloride, high | 1 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Uric acid, high | 19 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Creatinine, high | 6 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Creatinine, low | 0 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | ALT, high | 1 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Urea/BUN, low | 0 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Glucose, high | 90 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Uric acid, low | 0 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Glucose, low | 3 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Sodium, high | 0 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Alkaline phosphatase, high | 0 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Urea/BUN, high | 4 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Potassium, high | 0 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Potassium, low | 3 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Total protein, low | 0 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Sodium, low | 1 Participants |
| Placebo (P) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | T. Bilirubin, high | 0 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Alkaline phosphatase, high | 2 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Total protein, low | 2 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Sodium, low | 6 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Glucose, high | 132 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Calcium, low | 17 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | AST, high | 2 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Chloride, low | 3 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | T. Bilirubin, high | 3 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | CO2/HCO3, high | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Uric acid, low | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Urea/BUN, high | 8 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Potassium, low | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | CO2/HCO3, low | 61 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | ALT, high | 4 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Chloride, high | 5 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Glucose, low | 0 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Calcium, high | 3 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Sodium, high | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Creatinine, high | 10 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Albumin, low | 0 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Urea/BUN, low | 0 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Uric acid, high | 29 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Creatinine, low | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Potassium, high | 6 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | ALT, high | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Albumin, low | 1 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Alkaline phosphatase, high | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | AST, high | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Chloride, low | 1 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Creatinine, high | 17 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Creatinine, low | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Glucose, high | 113 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Glucose, low | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Potassium, high | 4 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Potassium, low | 4 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Sodium, high | 1 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Calcium, high | 5 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Calcium, low | 15 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | CO2/HCO3, high | 3 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | CO2/HCO3, low | 76 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Chloride, high | 6 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Sodium, low | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | T. Bilirubin, high | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Total protein, low | 3 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Urea/BUN, high | 15 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Urea/BUN, low | 1 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Uric acid, high | 29 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Uric acid, low | 0 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | AST, high | 4 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Sodium, high | 2 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Uric acid, low | 1 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | T. Bilirubin, high | 3 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Potassium, low | 5 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Potassium, high | 10 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Uric acid, high | 58 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Total protein, low | 5 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Glucose, low | 2 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Glucose, high | 245 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Albumin, low | 1 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Urea/BUN, high | 23 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Creatinine, low | 1 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Creatinine, high | 27 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | ALT, high | 6 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Urea/BUN, low | 1 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | CO2/HCO3, low | 137 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Chloride, low | 4 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Chloride, high | 11 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | CO2/HCO3, high | 4 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Calcium, low | 32 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Calcium, high | 8 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Alkaline phosphatase, high | 2 Participants |
| A and B Combined (C) | Number of Participants With Clinical Chemistry Data of PCI at Any Visit Post-Baseline | Sodium, low | 8 Participants |
Primary
Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline
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
Population: Safety Population. Number of participants with analyzable samples at the time of analysis were included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Eosinophils, high | 2 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Eosinophils, low | 14 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hematocrit, high | 2 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hematocrit, low | 2 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hemoglobin, high | 0 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hemoglobin, low | 0 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Lymphocytes, high | 0 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Lymphocytes, low | 2 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | MCH, low | 0 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Monocytes, high | 1 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Monocytes, low | 14 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Platelet count, high | 0 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Platelet count, low | 2 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RDW, high | 3 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RBC count, high | 0 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RBC count, low | 10 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Reticulocytes, high | 30 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Reticulocytes, low | 5 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | ANC, high | 4 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | ANC, low | 1 Participants |
| Placebo (P) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | WBC count, high | 5 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Reticulocytes, low | 4 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Eosinophils, high | 7 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Lymphocytes, low | 7 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Platelet count, high | 4 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Lymphocytes, high | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RBC count, low | 10 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RBC count, high | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Platelet count, low | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hematocrit, high | 5 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | ANC, low | 2 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Reticulocytes, high | 49 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RDW, high | 3 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | MCH, low | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hemoglobin, high | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hemoglobin, low | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | WBC count, high | 11 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Monocytes, high | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hematocrit, low | 8 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Eosinophils, low | 20 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | ANC, high | 12 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Monocytes, low | 15 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Eosinophils, low | 16 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hemoglobin, low | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Lymphocytes, high | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Reticulocytes, low | 4 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Lymphocytes, low | 5 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | MCH, low | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Monocytes, high | 3 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Monocytes, low | 19 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | ANC, high | 19 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Platelet count, high | 3 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Platelet count, low | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | WBC count, high | 15 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RDW, high | 7 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RBC count, high | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | ANC, low | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RBC count, low | 11 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Eosinophils, high | 11 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hematocrit, high | 5 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Reticulocytes, high | 36 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hematocrit, low | 8 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hemoglobin, high | 0 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RBC count, low | 21 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Monocytes, low | 34 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Reticulocytes, high | 85 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Eosinophils, high | 18 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | ANC, low | 2 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Monocytes, high | 4 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | MCH, low | 3 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Eosinophils, low | 36 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Reticulocytes, low | 8 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Lymphocytes, low | 12 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hemoglobin, low | 3 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hematocrit, high | 10 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | WBC count, high | 26 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RDW, high | 10 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Platelet count, low | 3 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | ANC, high | 31 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Lymphocytes, high | 3 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | RBC count, high | 1 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hemoglobin, high | 1 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Platelet count, high | 7 Participants |
| A and B Combined (C) | Number of Participants With Hematology Data of Potential Clinical Importance (PCI) at Any Visit Post-Baseline | Hematocrit, low | 16 Participants |
Primary
Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline
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
Population: Safety Population. Number of participants with analyzable samples at the time of analysis were included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=2xULN | 4 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=2xULN | 11 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=2xULN | 0 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=5xULN | 0 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=3xULN | 0 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=5xULN | 0 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | T. Bilirubin, >=1.5xULN | 0 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=3xULN | 1 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=5xULN | 1 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=2xULN | 3 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=3xULN | 0 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=3xULN | 5 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=5xULN | 0 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Creatine kinase, >=2xULN | 0 Participants |
| Placebo (P) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=1.5xULN | 0 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=1.5xULN | 3 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=2xULN | 13 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=2xULN | 10 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=2xULN | 2 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=3xULN | 4 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=5xULN | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=3xULN | 5 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=3xULN | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=5xULN | 3 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=5xULN | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Creatine kinase, >=2xULN | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=5xULN | 2 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=3xULN | 2 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | T. Bilirubin, >=1.5xULN | 3 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=2xULN | 7 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=1.5xULN | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=2xULN | 4 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=3xULN | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=5xULN | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | T. Bilirubin, >=1.5xULN | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=2xULN | 3 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=3xULN | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=5xULN | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=2xULN | 1 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=3xULN | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=5xULN | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=2xULN | 12 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=3xULN | 4 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=5xULN | 2 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Creatine kinase, >=2xULN | 0 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=5xULN | 1 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=3xULN | 6 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=2xULN | 25 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=3xULN | 4 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | AST, >=2xULN | 13 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=2xULN | 11 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=3xULN | 9 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | T. Bilirubin, >=1.5xULN | 3 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | ALT, >=5xULN | 3 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Creatine kinase, >=2xULN | 1 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=3xULN | 1 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=2xULN | 3 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | GGT, >=5xULN | 4 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=5xULN | 1 Participants |
| A and B Combined (C) | Number of Participants With Liver Function Test Elevations at Any Time Post-Baseline | Alkaline phosphatase, >=1.5xULN | 5 Participants |
Primary
Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline
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
Population: Safety Population. Number of participants with analyzable samples at the time of analysis were included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (P) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | DBP, high | 0 Participants |
| Placebo (P) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | DBP, low | 1 Participants |
| Placebo (P) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | SBP, high | 0 Participants |
| Placebo (P) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | SBP, low | 0 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | DBP, low | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | SBP, high | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | SBP, low | 1 Participants |
| Losmapimod 7.5 mg (A) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | DBP, high | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | SBP, high | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | DBP, low | 1 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | SBP, low | 0 Participants |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | DBP, high | 2 Participants |
| A and B Combined (C) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | SBP, low | 1 Participants |
| A and B Combined (C) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | DBP, low | 2 Participants |
| A and B Combined (C) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | DBP, high | 2 Participants |
| A and B Combined (C) | Number of Participants With Vital Signs of PCI at Any Visit Post-Baseline | SBP, high | 1 Participants |
Secondary
Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12
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
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (P) | Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12 | Discharge/Early withdrawal | 72.56 pg/mL | Geometric Coefficient of Variation 208.2 |
| Placebo (P) | Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12 | Week 12 | 49.41 pg/mL | Geometric Coefficient of Variation 167.1 |
| Losmapimod 7.5 mg (A) | Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12 | Week 12 | 37.41 pg/mL | Geometric Coefficient of Variation 141.8 |
| Losmapimod 7.5 mg (A) | Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12 | Discharge/Early withdrawal | 65.84 pg/mL | Geometric Coefficient of Variation 174.8 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12 | Week 12 | 37.02 pg/mL | Geometric Coefficient of Variation 159.8 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12 | Discharge/Early withdrawal | 73.24 pg/mL | Geometric Coefficient of Variation 193.9 |
| A and B Combined (C) | Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12 | Discharge/Early withdrawal | 69.49 pg/mL | Geometric Coefficient of Variation 183.9 |
| A and B Combined (C) | Mean Brain Natriuretic Peptide (BNP) at Discharge and Week 12 | Week 12 | 37.22 pg/mL | Geometric Coefficient of Variation 150.1 |
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For discharge/early withdrawalp-value: 0.5795% CI: [0.72, 1.2]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For discharge/early withdrawalp-value: 0.5295% CI: [0.72, 1.18]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For discharge/early withdrawalp-value: 0.595% CI: [0.74, 1.16]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For Week 12p-value: 0.0395% CI: [0.55, 0.96]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 12p-value: 0.1495% CI: [0.61, 1.07]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For Week 12p-value: 0.0495% CI: [0.6, 0.98]Repeated measures ANCOVA
Secondary
Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First)
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
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (P) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | Predose | 11.5 ng*hr/mL | Geometric Coefficient of Variation 247.9 |
| Placebo (P) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 24 hours | 6.2 ng*hr/mL | Geometric Coefficient of Variation 151.1 |
| Placebo (P) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 56 hours | 2.5 ng*hr/mL | Geometric Coefficient of Variation 81.5 |
| Placebo (P) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 8 hours | 9.0 ng*hr/mL | Geometric Coefficient of Variation 234.5 |
| Placebo (P) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 48 hours | 3.0 ng*hr/mL | Geometric Coefficient of Variation 103.1 |
| Placebo (P) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 32 hours | 4.1 ng*hr/mL | Geometric Coefficient of Variation 139.5 |
| Placebo (P) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 16 hours | 7.1 ng*hr/mL | Geometric Coefficient of Variation 194.2 |
| Placebo (P) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | DIS/EW | 2.9 ng*hr/mL | Geometric Coefficient of Variation 117.4 |
| Placebo (P) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 72 hours | 2.4 ng*hr/mL | Geometric Coefficient of Variation 117.7 |
| Placebo (P) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 40 hours | 3.2 ng*hr/mL | Geometric Coefficient of Variation 119.3 |
| Placebo (P) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 64 hours | 2.2 ng*hr/mL | Geometric Coefficient of Variation 75.5 |
| Losmapimod 7.5 mg (A) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 40 hours | 3.6 ng*hr/mL | Geometric Coefficient of Variation 110.1 |
| Losmapimod 7.5 mg (A) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 64 hours | 2.6 ng*hr/mL | Geometric Coefficient of Variation 97.8 |
| Losmapimod 7.5 mg (A) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 48 hours | 3.2 ng*hr/mL | Geometric Coefficient of Variation 110 |
| Losmapimod 7.5 mg (A) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 56 hours | 2.8 ng*hr/mL | Geometric Coefficient of Variation 98.3 |
| Losmapimod 7.5 mg (A) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 16 hours | 6.5 ng*hr/mL | Geometric Coefficient of Variation 170.9 |
| Losmapimod 7.5 mg (A) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | DIS/EW | 2.6 ng*hr/mL | Geometric Coefficient of Variation 96.4 |
| Losmapimod 7.5 mg (A) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 24 hours | 5.2 ng*hr/mL | Geometric Coefficient of Variation 147.2 |
| Losmapimod 7.5 mg (A) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 72 hours | 2.6 ng*hr/mL | Geometric Coefficient of Variation 94.3 |
| Losmapimod 7.5 mg (A) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 32 hours | 4.5 ng*hr/mL | Geometric Coefficient of Variation 129.5 |
| Losmapimod 7.5 mg (A) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 8 hours | 7.8 ng*hr/mL | Geometric Coefficient of Variation 185 |
| Losmapimod 7.5 mg (A) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | Predose | 10.5 ng*hr/mL | Geometric Coefficient of Variation 196.4 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 72 hours | 2.8 ng*hr/mL | Geometric Coefficient of Variation 84.3 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | Predose | 9.8 ng*hr/mL | Geometric Coefficient of Variation 233.5 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 8 hours | 8.4 ng*hr/mL | Geometric Coefficient of Variation 242.2 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 16 hours | 7.0 ng*hr/mL | Geometric Coefficient of Variation 213.7 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 24 hours | 6.1 ng*hr/mL | Geometric Coefficient of Variation 171.8 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 32 hours | 5.1 ng*hr/mL | Geometric Coefficient of Variation 130.4 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 40 hours | 4.0 ng*hr/mL | Geometric Coefficient of Variation 118.9 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 48 hours | 3.3 ng*hr/mL | Geometric Coefficient of Variation 103.3 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 56 hours | 3.1 ng*hr/mL | Geometric Coefficient of Variation 91.9 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 64 hours | 3.0 ng*hr/mL | Geometric Coefficient of Variation 87.5 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | DIS/EW | 2.9 ng*hr/mL | Geometric Coefficient of Variation 105.6 |
| A and B Combined (C) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 40 hours | 3.8 ng*hr/mL | Geometric Coefficient of Variation 114.3 |
| A and B Combined (C) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | DIS/EW | 2.8 ng*hr/mL | Geometric Coefficient of Variation 100.8 |
| A and B Combined (C) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 64 hours | 2.8 ng*hr/mL | Geometric Coefficient of Variation 93 |
| A and B Combined (C) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 32 hours | 4.8 ng*hr/mL | Geometric Coefficient of Variation 129.9 |
| A and B Combined (C) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 24 hours | 5.6 ng*hr/mL | Geometric Coefficient of Variation 159.3 |
| A and B Combined (C) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 16 hours | 6.8 ng*hr/mL | Geometric Coefficient of Variation 190.4 |
| A and B Combined (C) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 72 hours | 2.7 ng*hr/mL | Geometric Coefficient of Variation 89.1 |
| A and B Combined (C) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 8 hours | 8.1 ng*hr/mL | Geometric Coefficient of Variation 210.4 |
| A and B Combined (C) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | Predose | 10.2 ng*hr/mL | Geometric Coefficient of Variation 213.5 |
| A and B Combined (C) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 56 hours | 2.9 ng*hr/mL | Geometric Coefficient of Variation 95.2 |
| A and B Combined (C) | Mean Creatine Kinase (MB Isoenzyme) (CK-MB) AUC Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 48 hours | 3.3 ng*hr/mL | Geometric Coefficient of Variation 106.3 |
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For 72 hoursp-value: 0.6695% CI: [0.89, 1.21]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For 72 hoursp-value: 0.3995% CI: [0.92, 1.25]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For 72 hoursp-value: 0.4795% CI: [0.92, 1.21]Repeated measures ANCOVA
Secondary
Mean hsCRP Over Hospitalization Period and Through Week 14
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
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (P) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Discharge/Early withdrawal | 8.95 mg/L | Geometric Coefficient of Variation 171.3 |
| Placebo (P) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 24 hours | 9.10 mg/L | Geometric Coefficient of Variation 241.8 |
| Placebo (P) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 2 | 3.30 mg/L | Geometric Coefficient of Variation 232.6 |
| Placebo (P) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 4 | 1.85 mg/L | Geometric Coefficient of Variation 203 |
| Placebo (P) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 14 | 1.60 mg/L | Geometric Coefficient of Variation 172.5 |
| Placebo (P) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 48 hours | 14.82 mg/L | Geometric Coefficient of Variation 236.8 |
| Placebo (P) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Predose | 4.03 mg/L | Geometric Coefficient of Variation 232.4 |
| Placebo (P) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 72 hours | 15.34 mg/L | Geometric Coefficient of Variation 300.8 |
| Placebo (P) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 8 | 1.65 mg/L | Geometric Coefficient of Variation 160.7 |
| Losmapimod 7.5 mg (A) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 72 hours | 7.92 mg/L | Geometric Coefficient of Variation 314.6 |
| Losmapimod 7.5 mg (A) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 48 hours | 7.53 mg/L | Geometric Coefficient of Variation 306.3 |
| Losmapimod 7.5 mg (A) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 4 | 1.42 mg/L | Geometric Coefficient of Variation 227 |
| Losmapimod 7.5 mg (A) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 14 | 2.47 mg/L | Geometric Coefficient of Variation 187 |
| Losmapimod 7.5 mg (A) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 2 | 2.30 mg/L | Geometric Coefficient of Variation 302.9 |
| Losmapimod 7.5 mg (A) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 24 hours | 6.76 mg/L | Geometric Coefficient of Variation 325.1 |
| Losmapimod 7.5 mg (A) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 8 | 1.36 mg/L | Geometric Coefficient of Variation 198 |
| Losmapimod 7.5 mg (A) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Predose | 4.26 mg/L | Geometric Coefficient of Variation 263.8 |
| Losmapimod 7.5 mg (A) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Discharge/Early withdrawal | 6.46 mg/L | Geometric Coefficient of Variation 292.5 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 14 | 2.59 mg/L | Geometric Coefficient of Variation 168.9 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Predose | 4.31 mg/L | Geometric Coefficient of Variation 210.1 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 24 hours | 6.07 mg/L | Geometric Coefficient of Variation 259.9 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 48 hours | 6.69 mg/L | Geometric Coefficient of Variation 335.6 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 72 hours | 6.91 mg/L | Geometric Coefficient of Variation 337.6 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Discharge/Early withdrawal | 4.82 mg/L | Geometric Coefficient of Variation 214.5 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 2 | 2.18 mg/L | Geometric Coefficient of Variation 319.3 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 4 | 1.66 mg/L | Geometric Coefficient of Variation 214.8 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 8 | 1.50 mg/L | Geometric Coefficient of Variation 193.1 |
| A and B Combined (C) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Predose | 4.29 mg/L | Geometric Coefficient of Variation 235.7 |
| A and B Combined (C) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 4 | 1.54 mg/L | Geometric Coefficient of Variation 220.7 |
| A and B Combined (C) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 72 hours | 7.40 mg/L | Geometric Coefficient of Variation 323.8 |
| A and B Combined (C) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 48 hours | 7.11 mg/L | Geometric Coefficient of Variation 318.7 |
| A and B Combined (C) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 14 | 2.53 mg/L | Geometric Coefficient of Variation 177 |
| A and B Combined (C) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 8 | 1.43 mg/L | Geometric Coefficient of Variation 195 |
| A and B Combined (C) | Mean hsCRP Over Hospitalization Period and Through Week 14 | 24 hours | 6.41 mg/L | Geometric Coefficient of Variation 291.3 |
| A and B Combined (C) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Week 2 | 2.24 mg/L | Geometric Coefficient of Variation 309.6 |
| A and B Combined (C) | Mean hsCRP Over Hospitalization Period and Through Week 14 | Discharge/Early withdrawal | 5.59 mg/L | Geometric Coefficient of Variation 253.9 |
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For 24 hoursp-value: 0.0495% CI: [0.6, 0.99]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For 24 hoursp-value: 0.00195% CI: [0.52, 0.85]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For 24 hoursp-value: 0.00395% CI: [0.57, 0.89]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For 48 hoursp-value: <0.00195% CI: [0.4, 0.78]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For 48 hoursp-value: <0.00195% CI: [0.33, 0.65]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For 48 hoursp-value: <0.00195% CI: [0.38, 0.69]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For 72 hoursp-value: 0.05995% CI: [0.45, 1.01]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For 72 hoursp-value: 0.01395% CI: [0.4, 0.9]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For 72 hoursp-value: 0.01595% CI: [0.45, 0.92]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For Week 2p-value: 0.07395% CI: [0.48, 1.03]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 2p-value: 0.07595% CI: [0.48, 1.04]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For Week 2p-value: 0.04495% CI: [0.5, 0.99]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For Week 4p-value: 0.15795% CI: [0.55, 1.1]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 4p-value: 0.54895% CI: [0.63, 1.28]ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For Week 4p-value: 0.25395% CI: [0.61, 1.14]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For Week 8p-value: 0.20495% CI: [0.58, 1.13]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 8p-value: 0.96595% CI: [0.71, 1.39]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For Week 8p-value: 0.45795% CI: [0.66, 1.2]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For Week 14p-value: 0.00895% CI: [1.13, 2.22]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 14p-value: 0.00295% CI: [1.21, 2.38]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For Week 14p-value: 0.00195% CI: [1.21, 2.21]Repeated measures ANCOVA
Secondary
Mean Hyperenhancement Score Index at Week 12
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
Population: MRI ITT Population. Only those participants with data available at week 12 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (P) | Mean Hyperenhancement Score Index at Week 12 | 0.350 Scores on a scale | Standard Deviation 0.2648 |
| Losmapimod 7.5 mg (A) | Mean Hyperenhancement Score Index at Week 12 | 0.282 Scores on a scale | Standard Deviation 0.3117 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Hyperenhancement Score Index at Week 12 | 0.249 Scores on a scale | Standard Deviation 0.3096 |
| A and B Combined (C) | Mean Hyperenhancement Score Index at Week 12 | 0.265 Scores on a scale | Standard Deviation 0.3079 |
p-value: 0.13795% CI: [-0.26, 0.04]Repeated measures ANCOVA
p-value: 0.03695% CI: [-0.32, -0.01]Repeated measures ANCOVA
p-value: 0.04795% CI: [-0.28, 0]Repeated measures ANCOVA
Secondary
Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12
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
Population: MRI ITT Population was subset of participants in the ITT Population who had at least one MRI scan. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (P) | Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12 | Day 3-5 (Visit 1) | 7.804 Percent of left ventricle | Standard Deviation 7.4066 |
| Placebo (P) | Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12 | Week 12 | 5.620 Percent of left ventricle | Standard Deviation 5.4493 |
| Losmapimod 7.5 mg (A) | Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12 | Week 12 | 4.783 Percent of left ventricle | Standard Deviation 5.2992 |
| Losmapimod 7.5 mg (A) | Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12 | Day 3-5 (Visit 1) | 5.575 Percent of left ventricle | Standard Deviation 6.0525 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12 | Day 3-5 (Visit 1) | 5.848 Percent of left ventricle | Standard Deviation 7.6326 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12 | Week 12 | 4.335 Percent of left ventricle | Standard Deviation 5.9772 |
| A and B Combined (C) | Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12 | Day 3-5 (Visit 1) | 5.697 Percent of left ventricle | Standard Deviation 6.7483 |
| A and B Combined (C) | Mean Infarct Size Prior to Discharge From Hospital (Approximately Day 3) and at Week 12 | Week 12 | 4.550 Percent of left ventricle | Standard Deviation 5.609 |
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For Day 3-5 (visit 1)p-value: 0.25495% CI: [-5.25, 1.41]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Day 3-5 (visit 1)p-value: 0.10695% CI: [-6.29, 0.62]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For Day 3-5 (visit 1)p-value: 0.12695% CI: [-5.44, 0.69]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For Week 12p-value: 0.18495% CI: [-4.74, 0.92]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 12p-value: 0.09395% CI: [-5.37, 0.43]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For Week 12p-value: 0.09695% CI: [-4.78, 0.4]Repeated measures ANCOVA
Secondary
Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12
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
Population: ITT Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (P) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | 24 hours | 10.59 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 147.8 |
| Placebo (P) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | Week 12 | 2.62 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 102.8 |
| Placebo (P) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | Week 2 | 3.50 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 140.6 |
| Losmapimod 7.5 mg (A) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | 24 hours | 6.08 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 144.6 |
| Losmapimod 7.5 mg (A) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | Week 12 | 2.29 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 96 |
| Losmapimod 7.5 mg (A) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | Week 2 | 2.75 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 116.1 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | Week 2 | 3.14 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 111.6 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | 24 hours | 7.11 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 148.6 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | Week 12 | 2.61 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 88.4 |
| A and B Combined (C) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | 24 hours | 6.57 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 146.8 |
| A and B Combined (C) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | Week 12 | 2.45 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 92.3 |
| A and B Combined (C) | Mean Interleukin-6 (IL-6) Value at 24 Hours Post-randomization and at Weeks 2 and 12 | Week 2 | 2.94 picograms per milliliter (pg/mL) | Geometric Coefficient of Variation 114 |
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For 24 hoursp-value: <0.00195% CI: [0.43, 0.69]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For 24 hoursp-value: <0.00195% CI: [0.5, 0.82]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For 24 hoursp-value: <0.00195% CI: [0.48, 0.73]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For Week 2p-value: 0.03195% CI: [0.59, 0.98]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 2p-value: 0.31595% CI: [0.68, 1.13]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For Week 2p-value: 0.07595% CI: [0.65, 1.02]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For Week 12p-value: 0.06895% CI: [0.65, 1.02]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For Week 12p-value: 0.82495% CI: [0.78, 1.22]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For Week 12p-value: 0.24695% CI: [0.73, 1.09]Repeated measures ANCOVA
Secondary
Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12
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
Population: MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (P) | Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12 | LVEDV | 132.895 mL | Standard Deviation 35.5648 |
| Placebo (P) | Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12 | LVESV | 58.660 mL | Standard Deviation 24.8018 |
| Losmapimod 7.5 mg (A) | Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12 | LVESV | 52.115 mL | Standard Deviation 19.476 |
| Losmapimod 7.5 mg (A) | Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12 | LVEDV | 125.942 mL | Standard Deviation 30.2434 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12 | LVEDV | 130.642 mL | Standard Deviation 27.176 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12 | LVESV | 53.710 mL | Standard Deviation 20.8387 |
| A and B Combined (C) | Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12 | LVEDV | 128.386 mL | Standard Deviation 28.4914 |
| A and B Combined (C) | Mean Left Ventricular End-diastolic Volume (LVEDV) and Left Ventricular End-systolic Volume (LVESV) at Week 12 | LVESV | 52.944 mL | Standard Deviation 20.0063 |
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For LVEDVp-value: 0.02595% CI: [-40.27, -2.79]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For LVEDVp-value: 0.05395% CI: [-37.58, 0.29]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For LVEDVp-value: 0.02195% CI: [-37.01, -3.18]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 7.5 mg (A): For LVESVp-value: 0.02495% CI: [-29.51, -2.14]Repeated measures ANCOVA
Comparison: Placebo (P) vs Losmapimod 15 mg followed by Losmapimod 7.5 mg (B): For LVESVp-value: 0.01695% CI: [-31.14, -3.29]Repeated measures ANCOVA
Comparison: Placebo (P) vs A and B Combined (C): For LVESVp-value: 0.0195% CI: [-28.91, -4.13]Repeated measures ANCOVA
Secondary
Mean Left Ventricular Mass at Week 12
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
Population: MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (P) | Mean Left Ventricular Mass at Week 12 | 145.463 grams (gm) | Standard Deviation 36.9074 |
| Losmapimod 7.5 mg (A) | Mean Left Ventricular Mass at Week 12 | 141.449 grams (gm) | Standard Deviation 40.5956 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Left Ventricular Mass at Week 12 | 154.194 grams (gm) | Standard Deviation 42.3668 |
| A and B Combined (C) | Mean Left Ventricular Mass at Week 12 | 148.076 grams (gm) | Standard Deviation 41.6018 |
p-value: 0.10995% CI: [-49.51, 5.09]Repeated measures ANCOVA
p-value: 0.61495% CI: [-35.22, 20.96]Repeated measures ANCOVA
p-value: 0.24395% CI: [-39.52, 10.18]Repeated measures ANCOVA
Secondary
Mean Percent Left Ventricular Ejection Fraction (LVEF) at Week 12
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
Population: MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (P) | Mean Percent Left Ventricular Ejection Fraction (LVEF) at Week 12 | 56.615 Percent | Standard Deviation 11.1103 |
| Losmapimod 7.5 mg (A) | Mean Percent Left Ventricular Ejection Fraction (LVEF) at Week 12 | 59.571 Percent | Standard Deviation 7.2745 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Percent Left Ventricular Ejection Fraction (LVEF) at Week 12 | 59.738 Percent | Standard Deviation 9.5443 |
| A and B Combined (C) | Mean Percent Left Ventricular Ejection Fraction (LVEF) at Week 12 | 59.658 Percent | Standard Deviation 8.4453 |
p-value: 0.12495% CI: [-1.18, 9.62]Repeated measures ANCOVA
p-value: 0.02995% CI: [0.63, 11.47]Repeated measures ANCOVA
p-value: 0.03995% CI: [0.28, 10]Repeated measures ANCOVA
Secondary
Mean Regional Wall Motion Score Index at Week 12
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
Population: MRI ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (P) | Mean Regional Wall Motion Score Index at Week 12 | 0.306 Scores on a scale | Standard Deviation 0.4096 |
| Losmapimod 7.5 mg (A) | Mean Regional Wall Motion Score Index at Week 12 | 0.179 Scores on a scale | Standard Deviation 0.2704 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Mean Regional Wall Motion Score Index at Week 12 | 0.186 Scores on a scale | Standard Deviation 0.3326 |
| A and B Combined (C) | Mean Regional Wall Motion Score Index at Week 12 | 0.182 Scores on a scale | Standard Deviation 0.3019 |
p-value: 0.02395% CI: [-0.44, -0.03]Repeated measures ANCOVA
p-value: 0.02195% CI: [-0.45, -0.04]Repeated measures ANCOVA
p-value: 0.01195% CI: [-0.42, -0.06]Repeated measures ANCOVA
Secondary
Peak cTnI Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First)
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
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (P) | Peak cTnI Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 4.02 ng/mL | Geometric Coefficient of Variation 482 |
| Losmapimod 7.5 mg (A) | Peak cTnI Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 3.49 ng/mL | Geometric Coefficient of Variation 575.3 |
| Losmapimod 15 mg Followed by Losmapimod 7.5 mg (B) | Peak cTnI Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 3.54 ng/mL | Geometric Coefficient of Variation 867.8 |
| A and B Combined (C) | Peak cTnI Over 72 Hours Post-randomization or Until Hospital Discharge (Whichever Comes First) | 3.52 ng/mL | Geometric Coefficient of Variation 701 |
p-value: 0.9295% CI: [0.78, 1.25]Repeated measures ANCOVA
p-value: 0.5295% CI: [0.85, 1.36]Repeated measures ANCOVA
p-value: 0.7695% CI: [0.84, 1.27]Repeated measures ANCOVA