Trial Outcomes & Findings for Safety and Efficacy Study of Losmapimod (GW856553) in Frequently Exacerbating Participants With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT02299375)

Last Updated: 2018-08-06

Results Overview

An exacerbation of COPD, is defined as the worsening of 2 or more major symptoms (dyspnea, sputum volume, sputum purulence) or the worsening of any 1 major symptom together with any 1 of the minor symptoms (sore throat, cold, fever without other cause, increased cough and wheeze), for at least 2 consecutive days. Moderate-severe exacerbations were defined as use of antibiotics and/or oral steroids and/or hospitalization. Summary only included exacerbations for which a date of resolution or death was provided. Analysis was performed by using Bayesian inference assuming non-informative priors. The mean exacerbation rate was adjusted for treatment group, smoking status, ICS use and region. The adjusted posterior median was summarized per treatment group. The number of exacerbation events per participant was assumed to follow a negative binomial distribution. Modified Intent-to-Treat (mITT) Population comprised of all randomized par. who received at least one dose of study treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

184 participants

Primary outcome timeframe

From the start of the study treatment up to 53 Weeks

Results posted on

2018-08-06

Participant Flow

This was a randomized, double-blind (sponsor unblinded), parallel-group, multi-center study evaluating 15 milligrams (mg) twice daily (BID) of losmapimod versus placebo in addition to standard of care in male and female participants (par.) \>=40 years of age having chronic obstructive pulmonary disease (COPD).

This study consisted of a 28 day screening period followed by treatment period (TP) of minimum 26 weeks. Total duration of TP was variable from 26 weeks to 52 weeks, and safety follow-up after 1 week. Total 365 par. were screened (175 par. failed), of which 190 par. passed screening and 184 par. were randomized in a TP.

Participant milestones

Participant milestones
Measure	Placebo Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Overall Study STARTED	94	90
Overall Study COMPLETED	14	10
Overall Study NOT COMPLETED	80	80

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Overall Study Adverse Event, serious fatal	1	3
Overall Study Adverse Event, non-fatal	8	9
Overall Study Lack of Efficacy	1	3
Overall Study Protocol Violation	1	3
Overall Study Other: Met stopping criteria	1	0
Overall Study Other: Study closed/terminated	66	55
Overall Study Lost to Follow-up	0	2
Overall Study Physician Decision	1	1
Overall Study Withdrawal by Subject	1	4

Baseline Characteristics

Safety and Efficacy Study of Losmapimod (GW856553) in Frequently Exacerbating Participants With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.	Total n=184 Participants Total of all reporting groups
Age, Continuous	64.6 Years STANDARD_DEVIATION 8.27 • n=5 Participants	66.4 Years STANDARD_DEVIATION 6.66 • n=7 Participants	65.5 Years STANDARD_DEVIATION 7.55 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	26 Participants n=7 Participants	59 Participants n=5 Participants
Sex: Female, Male Male	61 Participants n=5 Participants	64 Participants n=7 Participants	125 Participants n=5 Participants
Race/Ethnicity, Customized Race/ Ethnicity · Japanese/East Asian /South East Asian Heritage	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Race/ Ethnicity · White	84 Participants n=5 Participants	81 Participants n=7 Participants	165 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the start of the study treatment up to 53 Weeks

Population: mITT Population

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Annual Rate of Moderate and Severe Exacerbations of COPD	0.84 Exacerbations per participant per year Standard Deviation 0.19	0.88 Exacerbations per participant per year Standard Deviation 0.22

SECONDARY outcome

Timeframe: From the start of the study treatment up to 53 Weeks

Population: mITT Population

The time to first moderate-severe COPD exacerbation in par. treated with losmapimod compared to placebo treated par. was evaluated. The time to the first on-treatment moderate-severe exacerbation was calculated as exacerbation onset date of first on-treatment exacerbation minus exposure start date plus 1. No statistical analysis was conducted. Data was summarized statistically only.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Time to First Occurrence of Moderate or Severe COPD Exacerbation	168.01 Days Standard Deviation 106.222	160.18 Days Standard Deviation 117.142

SECONDARY outcome

Timeframe: From the start of the study treatment up to 53 Weeks

Population: mITT Population

An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. AEs were considered as on-treatment If AE onset date is on or after treatment start date \& on or before treatment stop date. par. having any AE or SAE were included in analysis.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Number of Participants Having Any Adverse Events (AEs), Serious Adverse Events (SAEs) Non-serious AEs	34 Participants	38 Participants
Number of Participants Having Any Adverse Events (AEs), Serious Adverse Events (SAEs) SAEs	8 Participants	19 Participants

SECONDARY outcome

Timeframe: Baseline and up to Week 52

Population: mITT Population

Pre and post FEV1, FVC and FEV6 were performed at Screening, Day 1 pre-dose and Weeks 2, 4, 8, 12, 18, 26, 39 and 52. Par. were asked to withheld all bronchodilator therapy included ipratropiumn bromide and salbutamol/albuterol for at least 4 hours prior to prebronchodilator spirometric test. Post-bronchodilator spirometric assessment was performed after inhalation of 400/360 micograms (µg) of salbutamol/albuterol in 10-15 minutes. Day 1 (pre-dose) values were considered as Baseline values. Change from Baseline was calculated as value at the indicated time point minus Baseline value. The maximum value of the 3 replicate assessments were used. Analysis performed using a mixed-effects repeated measures model. The adjusted mean values were summarized per treatment group. Par. were included in the analysis if they had at least one post-baseline measurement. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 pre-dose, Week 2, n = 90, 83	0.002 Liters Standard Error 0.0241	0.028 Liters Standard Error 0.0258
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 Pre-dose, Week 4, n=88, 82	-0.010 Liters Standard Error 0.0242	0.025 Liters Standard Error 0.0259
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 Pre-dose, Week 8, n=81, 79	-0.031 Liters Standard Error 0.0247	0.028 Liters Standard Error 0.0261
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 Pre-dose, Week 12, n=78, 71	-0.011 Liters Standard Error 0.0250	-0.014 Liters Standard Error 0.0267
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 Pre-dose, Week 18, n=67, 61	-0.037 Liters Standard Error 0.0260	0.013 Liters Standard Error 0.0277
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 Pre-dose, Week 26, n=53, 52	-0.059 Liters Standard Error 0.0278	0.020 Liters Standard Error 0.0289
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 Pre-dose, Week 39, n=28, 28	-0.085 Liters Standard Error 0.0342	0.001 Liters Standard Error 0.0353
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 Pre-dose, Week 52, n=14, 11	-0.034 Liters Standard Error 0.0485	0.016 Liters Standard Error 0.0513
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 post-dose, Week 2, n=89, 82	0.012 Liters Standard Error 0.0188	0.026 Liters Standard Error 0.0203
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 post-dose, Week 4, n=87, 81	-0.022 Liters Standard Error 0.0193	0.019 Liters Standard Error 0.0207
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 post-dose, Week 8, n=80, 78	-0.010 Liters Standard Error 0.0232	0.023 Liters Standard Error 0.0242
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 post-dose, Week 12, n=76, 69	-0.008 Liters Standard Error 0.0217	-0.020 Liters Standard Error 0.0231
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 post-dose, Week 18, n=66, 60	-0.035 Liters Standard Error 0.0256	-0.012 Liters Standard Error 0.0271
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 post-dose, Week 26, n=52, 51	-0.070 Liters Standard Error 0.0273	0.030 Liters Standard Error 0.0282
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 post-dose, Week 39, n=27, 27	-0.086 Liters Standard Error 0.0346	-0.031 Liters Standard Error 0.0356
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV1 post-dose, Week 52, n=13, 10	-0.018 Liters Standard Error 0.0419	0.024 Liters Standard Error 0.0472
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 pre-dose, Week 2, n = 90,82	-0.007 Liters Standard Error 0.0353	0.045 Liters Standard Error 0.0381
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 Pre-dose, Week 4, n=87, 81	-0.034 Liters Standard Error 0.0353	0.012 Liters Standard Error 0.0380
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 Pre-dose, Week 8, n=81, 78	-0.043 Liters Standard Error 0.0400	0.032 Liters Standard Error 0.0424
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 Pre-dose, Week 12, n=78, 71	-0.036 Liters Standard Error 0.0366	-0.034 Liters Standard Error 0.0392
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 Pre-dose, Week 18, n=67, 60	-0.073 Liters Standard Error 0.0413	-0.014 Liters Standard Error 0.0441
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 Pre-dose, Week 26, n=53, 52	-0.076 Liters Standard Error 0.0405	-0.003 Liters Standard Error 0.0425
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 Pre-dose, Week 39, n=28, 28	-0.102 Liters Standard Error 0.0486	0.013 Liters Standard Error 0.0507
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 Pre-dose, Week 52, n=14, 11	-0.101 Liters Standard Error 0.0731	0.071 Liters Standard Error 0.0745
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 post-dose, Week 2, n=89, 81	-0.003 Liters Standard Error 0.0296	0.023 Liters Standard Error 0.0319
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 post-dose, Week 4, n=86, 80	-0.027 Liters Standard Error 0.0273	0.010 Liters Standard Error 0.0295
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 post-dose, Week 8, n=80, 76	-0.039 Liters Standard Error 0.0313	0.012 Liters Standard Error 0.0331
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 post-dose, Week 12, n=76, 69	-0.028 Liters Standard Error 0.0308	-0.029 Liters Standard Error 0.0330
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 post-dose, Week 18, n=66, 59	-0.060 Liters Standard Error 0.0367	-0.035 Liters Standard Error 0.0392
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 post-dose, Week 26, n=51, 51	-0.081 Liters Standard Error 0.0360	0.003 Liters Standard Error 0.0373
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 post-dose, Week 39, n=27, 27	-0.095 Liters Standard Error 0.0428	-0.067 Liters Standard Error 0.0443
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FEV6 post-dose, Week 52, n=13, 10	-0.119 Liters Standard Error 0.0607	-0.017 Liters Standard Error 0.0674
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Pre-dose, Week 2, n =90, 83	-0.018 Liters Standard Error 0.0389	0.038 Liters Standard Error 0.0417
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Pre-dose, Week 4, n =88, 82	-0.039 Liters Standard Error 0.0392	0.006 Liters Standard Error 0.0418
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Pre-dose Week 8, n = 81, 79	-0.061 Liters Standard Error 0.0401	0.011 Liters Standard Error 0.0422
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Pre-dose, Week 12, n =78, 71	-0.046 Liters Standard Error 0.0405	-0.058 Liters Standard Error 0.0430
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Pre-dose Week 18, n =67, 61	-0.093 Liters Standard Error 0.0422	-0.021 Liters Standard Error 0.0447
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Pre-dose Week 26, n=53, 52	-0.095 Liters Standard Error 0.0451	-0.028 Liters Standard Error 0.0468
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Pre-dose Week 39, n =28, 28	-0.115 Liters Standard Error 0.0558	-0.033 Liters Standard Error 0.0574
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Pre-dose Week 52, n =14, 11	-0.052 Liters Standard Error 0.0806	0.031 Liters Standard Error 0.0837
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Post-dose Week 2, n =89, 82	-0.007 Liters Standard Error 0.0359	0.037 Liters Standard Error 0.0385
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Post-dose Week 4, n =87, 81	-0.021 Liters Standard Error 0.0316	0.033 Liters Standard Error 0.0341
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Post-dose Week 8, n =80, 78	-0.052 Liters Standard Error 0.0366	0.019 Liters Standard Error 0.0385
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC,Post-dose Week 12, n =76, 69	-0.020 Liters Standard Error 0.0361	-0.008 Liters Standard Error 0.0385
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Post-dose Week 18, n =66, 60	-0.075 Liters Standard Error 0.0422	-0.016 Liters Standard Error 0.0449
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Post-dose Week 26, n=52, 51	-0.135 Liters Standard Error 0.0495	0.003 Liters Standard Error 0.0513
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Post-dose Week 39, n =27, 27	-0.092 Liters Standard Error 0.0499	-0.043 Liters Standard Error 0.0518
Change From Baseline in Spirometry Parameters in Pre and Post Forced Expiratory Volume in 1 Second (FEV1); Pre and Post Forced Vital Capacity (FVC); Pre and Post Forced Expiratory Volume in 6 Seconds (FEV6). FVC, Post-dose Week 52, n =13, 10	-0.081 Liters Standard Error 0.0612	-0.039 Liters Standard Error 0.0671

SECONDARY outcome

Timeframe: Baseline and up to Week 52

Population: mITT Population.

Pre and post FEV1/FVC, PP FEV1, PP FEV6 and PP FVC were assessed at Screening, Day 1 pre-dose and Weeks 2, 4, 8, 12, 18, 26, 39 and 52. Par. were asked to withheld all bronchodilator therapy included ipratropiumn bromide and salbutamol/albuterol for at least 4 hours prior to the prebronchodilator spirometric test. Post-bronchodilator spirometric assessment was performed after inhalation of 400/360 µg of salbutamol/albuterol in 10-15 minutes. Day 1 (pre-dose) values were considered as Baseline values. Change from Baseline was calculated as value at indicated time point minus Baseline value. The maximum value of the 3 replicate assessments were used. Analysis performed using a mixed-effects repeated measures model. The adjusted mean values were summarized per treatment group. Par. were included in the analysis if they had at least one post-baseline measurement. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FVC, Week 2, n =90, 82	0.72 Percentage Standard Error 1.156	1.31 Percentage Standard Error 1.228
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FVC, Week 4, n =88, 81	-0.73 Percentage Standard Error 1.160	1.72 Percentage Standard Error 1.228
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FVC, Week 8, n =81, 78	-2.05 Percentage Standard Error 1.556	0.47 Percentage Standard Error 1.604
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FVC, Week 12 , n =78, 70	-0.64 Percentage Standard Error 1.324	-0.78 Percentage Standard Error 1.399
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FVC, Week 18, n =67, 60	-1.58 Percentage Standard Error 1.286	1.12 Percentage Standard Error 1.356
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FVC, Week 26, n =53, 51	-2.81 Percentage Standard Error 1.518	1.88 Percentage Standard Error 1.575
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FVC, Week 39, n =28, 27	-2.06 Percentage Standard Error 1.548	1.24 Percentage Standard Error 1.604
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FVC, Week 52, n =14, 11	-1.24 Percentage Standard Error 2.017	0.92 Percentage Standard Error 2.137
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV1, Week 2, n =90, 82	0.28 Percentage Standard Error 0.858	2.03 Percentage Standard Error 0.932
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV1, Week 4, n =88, 81	-0.24 Percentage Standard Error 0.877	1.52 Percentage Standard Error 0.950
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV1, Week 8, n =81, 78	-1.14 Percentage Standard Error 0.979	1.04 Percentage Standard Error 1.037
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV1, Week 12 , n =78, 70	-0.10 Percentage Standard Error 0.940	0.12 Percentage Standard Error 1.013
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV1, Week 18, n =67, 60	-0.79 Percentage Standard Error 1.094	0.58 Percentage Standard Error 1.172
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV1, Week 26, n =53, 51	-2.07 Percentage Standard Error 1.075	1.26 Percentage Standard Error 1.134
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV1, Week 39, n =28, 27	-2.33 Percentage Standard Error 1.307	0.79 Percentage Standard Error 1.370
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV1, Week 52, n =14, 11	-0.32 Percentage Standard Error 1.714	2.03 Percentage Standard Error 1.901
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV6, Week 2, n =87, 75	0.63 Percentage Standard Error 1.163	3.45 Percentage Standard Error 1.252
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV6, Week 4, n =84, 75	-0.72 Percentage Standard Error 1.135	2.15 Percentage Standard Error 1.212
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV6, Week 8, n =79, 74	-1.71 Percentage Standard Error 1.332	2.04 Percentage Standard Error 1.395
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV6, Week 12 , n =76, 67	-0.42 Percentage Standard Error 1.214	-0.02 Percentage Standard Error 1.284
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV6, Week 18, n =65, 56	-1.47 Percentage Standard Error 1.347	1.87 Percentage Standard Error 1.438
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV6, Week 26, n =51, 48	-1.69 Percentage Standard Error 1.359	1.84 Percentage Standard Error 1.436
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV6, Week 39, n =26, 24	-2.10 Percentage Standard Error 1.543	2.09 Percentage Standard Error 1.652
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC PP FEV6, Week 52, n =13, 11	0.99 Percentage Standard Error 2.936	3.66 Percentage Standard Error 3.209
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Pre-dose, Week 2, n =90, 83	0.22 Percentage Standard Error 0.571	0.43 Percentage Standard Error 0.611
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Pre-dose, Week 4, n =88, 82	0.30 Percentage Standard Error 0.674	0.43 Percentage Standard Error 0.716
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Pre-dose Week 8, n = 81, 79	0.10 Percentage Standard Error 0.632	0.46 Percentage Standard Error 0.663
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Pre-dose, Week 12, n =78, 71	0.31 Percentage Standard Error 0.649	0.02 Percentage Standard Error 0.688
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Pre-dose Week 18, n =67, 61	0.11 Percentage Standard Error 0.735	0.34 Percentage Standard Error 0.780
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Pre dose Week 26, n=53, 52	-0.48 Percentage Standard Error 0.767	0.84 Percentage Standard Error 0.803
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Pre-dose Week 39, n =28, 28	-1.36 Percentage Standard Error 0.932	0.70 Percentage Standard Error 0.963
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Pre-dose Week 52, n =14, 11	-0.18 Percentage Standard Error 1.177	1.26 Percentage Standard Error 1.270
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Post-dose Week 2, n =89, 82	0.09 Percentage Standard Error 0.682	0.51 Percentage Standard Error 0.726
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Post-dose Week 4, n =87, 81	-0.90 Percentage Standard Error 0.619	-0.23 Percentage Standard Error 0.662
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Post-dose Week 8, n =80, 78	0.12 Percentage Standard Error 0.646	0.28 Percentage Standard Error 0.679
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC,Post-dose Week 12, n =76, 69	-0.51 Percentage Standard Error 0.693	-0.97 Percentage Standard Error 0.736
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Post-dose Week 18, n =66, 60	-0.65 Percentage Standard Error 0.643	-0.23 Percentage Standard Error 0.682
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Post-dose Week 26, n=52, 51	-0.60 Percentage Standard Error 2.272	3.23 Percentage Standard Error 2.292
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Post-dose Week 39, n =27, 27	-1.27 Percentage Standard Error 0.939	0.18 Percentage Standard Error 0.961
Change From Baseline in Spirometry Parameters in Pre and Post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC FEV1/FVC, Post-dose Week 52, n =13, 10	0.34 Percentage Standard Error 1.280	1.51 Percentage Standard Error 1.397

SECONDARY outcome

Timeframe: Up to 53 Weeks

Population: mITT Population

12-lead ECGs were obtained in triplicate at Screening then singly at Baseline (day 1, pre-dose) and post dose at Weeks 2, 4, 8, 12, 26, 39, 52 and at follow up (Week 53) using an ECG machine that automatically calculates the heart rate (HR) and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) or QT duration corrected for heart rate by Bazett's formula (QTcB) intervals. Change in ECG findings were categorized as normal and abnormal. Abnormal ECG values could be clinically significant (CS) or not clinically significant (NCS), as determined by the investigator. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Number of Participants With Electrocardiogram (ECG) Findings Normal-SCREENING, (n=94,90)	49 Participants	51 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-NCS-SCREENING, (n=94,90)	39 Participants	36 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-CS-SCREENING, (n=94,90)	9 Participants	5 Participants
Number of Participants With Electrocardiogram (ECG) Findings Normal-Baseline, (n=94,90)	44 Participants	54 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-NCS-Baseline, (n=94,90)	46 Participants	31 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-CS-Baseline, (n=94,90)	4 Participants	5 Participants
Number of Participants With Electrocardiogram (ECG) Findings Normal-Week 2, (n=90,84)	40 Participants	52 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-NCS-Week 2, (n=90,84)	45 Participants	29 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-CS-Week 2, (n=90,84)	5 Participants	3 Participants
Number of Participants With Electrocardiogram (ECG) Findings Normal-Week 4, (n=89,82)	45 Participants	53 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-NCS-Week 4, (n=89,82)	40 Participants	27 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-CS-Week 4, (n=89,82)	4 Participants	2 Participants
Number of Participants With Electrocardiogram (ECG) Findings Normal-Week 8, (n=80,80)	42 Participants	50 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-NCS-Week 8, (n=80,80)	35 Participants	28 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-CS-Week 8, (n=80,80)	3 Participants	2 Participants
Number of Participants With Electrocardiogram (ECG) Findings Normal-Week 12, (n=78,72)	45 Participants	42 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-NCS-Week 12, (n=78,72)	29 Participants	29 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-CS-Week 12, (n=78,72)	4 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Findings Normal-Week 26, (n=53,52)	31 Participants	35 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-NCS-Week 26, (n=53,52)	21 Participants	16 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-CS-Week 26, (n=53,52)	1 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Findings Normal-Week 39, (n=28,29)	18 Participants	20 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-NCS-Week 39, (n=28,29)	9 Participants	8 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-CS-Week 39, (n=28,29)	1 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Findings Normal-Week 52, (n=14,11)	11 Participants	7 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-NCS-Week 52, (n=14,11)	2 Participants	4 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-CS-Week 52, (n=14,11)	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Findings Normal-Follow up, (n=83,68)	37 Participants	42 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-NCS-Follow up, (n=83,68)	40 Participants	25 Participants
Number of Participants With Electrocardiogram (ECG) Findings Abnormal-CS-Follow up, (n=83,68)	6 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

SBP and DBP were taken at Screening, Baseline (day 1, pre-dose) and post dose at Weeks 2, 4, 8, 12, 26, 39, 52 and at follow up (Week 53). Measurements were taken in a semi-recumbent position after 5 minutes rest. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the value at day 1, pre-dose. Par. were included in the analysis if they had at least one post-baseline measurement. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

HR was assessed at Screening, Baseline (day 1, pre-dose) and post dose at Weeks 2, 4, 8, 12, 26, 39, 52 and at follow up (Week 53). Measurements were taken in a semi-recumbent position after 5 minutes rest. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the value at day 1, pre-dose. Par. were included in the analysis if they had at least one post-baseline measurement. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points HR, Follow up, (n=83,68)	3.6 Beats per minute (bpm) Standard Deviation 6.72	4.2 Beats per minute (bpm) Standard Deviation 10.99
Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points HR, Week 2, (n=90,84)	1.2 Beats per minute (bpm) Standard Deviation 7.99	1.5 Beats per minute (bpm) Standard Deviation 9.92
Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points HR, Week 4, (n=89,82)	1.4 Beats per minute (bpm) Standard Deviation 7.18	0.6 Beats per minute (bpm) Standard Deviation 8.72
Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points HR, Week 8, (n=81,80)	1.0 Beats per minute (bpm) Standard Deviation 8.39	1.6 Beats per minute (bpm) Standard Deviation 9.50
Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points HR, Week 12, (n=78,72)	3.3 Beats per minute (bpm) Standard Deviation 8.80	2.2 Beats per minute (bpm) Standard Deviation 8.89
Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points HR, Week 26, (n=53,53)	4.1 Beats per minute (bpm) Standard Deviation 10.99	1.8 Beats per minute (bpm) Standard Deviation 8.32
Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points HR, Week 39, (n=28,29)	3.3 Beats per minute (bpm) Standard Deviation 9.48	4.4 Beats per minute (bpm) Standard Deviation 12.64
Change From Baseline in Heart Rate (HR) Values at the Indicated Time Points HR, Week 52, (n=14,11)	4.3 Beats per minute (bpm) Standard Deviation 9.55	1.3 Beats per minute (bpm) Standard Deviation 8.72

SECONDARY outcome

Timeframe: Pre-dose at Weeks 2 and 12; pre-dose and at 2 hours post-dose at Week 26

Population: PK Population.

Pharmacokinetics (PK) of losmapimod was evaluated in participants with COPD using PK samples collected at pre-dose at Week 2 and Week 12. At Week 26, a sample was collected at pre-dose and a second sample was collected at 2 hours post-dose. Par. of mITT population that provided at least one observed concentration data in this study were considered for PK analysis. Drug plasma concentration-time data were modelled by nonlinear mixed effects modelling. AUC\[0-tau\] (tau=12 hours) was estimated from the model.

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Plasma Losmapimod Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the End of Dosing Interval (AUC[0-tau])	668.5 hour (h)*nanogram (ng)/milliliter (mL) Interval 361.7 to 1235.6	—

SECONDARY outcome

Timeframe: Pre-dose at Weeks 2 and 12; pre-dose and at 2 hours post-dose at Week 26

Population: PK Population.

Pharmacokinetics of losmapimod was evaluated in participants with COPD using PK samples collected at pre-dose at Week 2 and Week 12. At Week 26, a sample was collected at pre-dose and a second sample was collected at 2 hours post-dose. Par. of mITT population that provided at least one observed concentration data in this study were considered for PK analysis (represented by n=X, X in the category titles). Drug plasma concentration-time data were modelled by nonlinear mixed effects modelling to develop a Population PK model. Cmax and Ctrough were estimated from the PK model.

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Plasma Losmapimod Maximum Concentration (Cmax) and Lowest Concentration (Ctrough) at Steady State Cmax	49.7 ng/ mL Interval 17.6 to 140.5	—
Plasma Losmapimod Maximum Concentration (Cmax) and Lowest Concentration (Ctrough) at Steady State Ctrough	23.7 ng/ mL Interval 12.9 to 43.3	—

SECONDARY outcome

Timeframe: Baseline and up to Week 52

Population: mITT Population

Use of short acting bronchodilators (short-acting beta2-agonists or short-acting anti-cholinergic) was allowed and was recorded in daily patient diary. It included inhaled short-acting beta2-agonists (e.g. Ipratropium bromide, salbutamol, Ipratropium/salbutamol (albuterol) combination product) and short-acting anti-cholinergics (e.g., ipratropium bromide3). Use of these medications was allowed throughout the study except 4 hours prior to and during each clinic visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use Week 8; n=79, 79	0.1143 Average number of puffs per 24 hours Standard Deviation 0.77946	-0.1473 Average number of puffs per 24 hours Standard Deviation 1.26462
Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use Week 4; n=85, 82	-0.0029 Average number of puffs per 24 hours Standard Deviation 0.73616	-0.0400 Average number of puffs per 24 hours Standard Deviation 0.93329
Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use Week 12; n=76, 70	0.0904 Average number of puffs per 24 hours Standard Deviation 1.06920	0.0022 Average number of puffs per 24 hours Standard Deviation 1.10426
Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use Week 18; n=65, 61	0.3163 Average number of puffs per 24 hours Standard Deviation 1.26883	0.1489 Average number of puffs per 24 hours Standard Deviation 0.97966
Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use Week 26; n=51, 53	0.2725 Average number of puffs per 24 hours Standard Deviation 1.43462	0.2098 Average number of puffs per 24 hours Standard Deviation 1.25768
Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use Week 39; n=27, 27	0.7109 Average number of puffs per 24 hours Standard Deviation 1.61447	0.3418 Average number of puffs per 24 hours Standard Deviation 1.39346
Change From Baseline in Frequency of Short Acting Beta-agonist or Anti-cholinergic Use Week 52; n=14, 10	0.4368 Average number of puffs per 24 hours Standard Deviation 1.22619	-0.2881 Average number of puffs per 24 hours Standard Deviation 0.98057

SECONDARY outcome

Timeframe: Baseline and up to Week 52

Population: mITT Population

SGRQ-C is a health related quality of life questionnaire consisting of 14 questions. SGRQ-C total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. Components (Activity, Symptoms, Impacts) were calculated as 100 multiplied by summed weights from all positive items in that component divided by sum of weights for all items in that component. Score range for SGRQ-C total is 0-100. Maximum weights for Activity, Symptoms and Impacts component is 982.9, 566.2 and 1652.8 respectively. SGRQ-C was transformed to SGRQ for reporting. Higher scores indicate greater disease impact. Score at Day 1, pre-dose (Week 0) was considered as Baseline. Change from Baseline was calculated as score at indicated time point minus Baseline value. Only those par. with analyzable data at the given time points (represented by n=X, X in category titles) were included in analysis.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Total, Week 12, (n=74, 71)	-0.75 Scores on a scale Standard Error 1.541	-1.42 Scores on a scale Standard Error 1.638
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Total, Week 26, (n=50, 49)	-2.20 Scores on a scale Standard Error 1.833	-1.31 Scores on a scale Standard Error 1.904
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Total, Week 39, (n=28, 28)	-0.37 Scores on a scale Standard Error 2.451	-3.19 Scores on a scale Standard Error 2.502
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Total, Week 52, (n=14, 11)	-2.95 Scores on a scale Standard Error 2.769	-3.43 Scores on a scale Standard Error 3.098
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Symptoms, Week 12, (n=78, 72)	-2.41 Scores on a scale Standard Error 1.999	-4.08 Scores on a scale Standard Error 2.115
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Symptoms, Week 26, (n=52, 52)	-5.04 Scores on a scale Standard Error 2.264	-4.30 Scores on a scale Standard Error 2.335
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Symptoms, Week 39, (n=28, 29)	-4.61 Scores on a scale Standard Error 3.411	-8.21 Scores on a scale Standard Error 3.370
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Symptoms, Week 52, (n=14, 11)	-3.69 Scores on a scale Standard Error 3.990	-11.67 Scores on a scale Standard Error 4.296
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Activity, Week 12, (n=77, 71)	-0.08 Scores on a scale Standard Error 1.968	1.15 Scores on a scale Standard Error 2.097
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Activity, Week 26, (n=50, 49)	-0.33 Scores on a scale Standard Error 2.217	0.70 Scores on a scale Standard Error 2.303
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Activity, Week 39, (n=28, 28)	1.41 Scores on a scale Standard Error 3.027	-1.00 Scores on a scale Standard Error 3.095
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Activity, Week 52, (n=14, 11)	-1.80 Scores on a scale Standard Error 3.308	2.59 Scores on a scale Standard Error 3.650
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Impact, Week 12, (n=75, 71)	-0.53 Scores on a scale Standard Error 1.780	-2.22 Scores on a scale Standard Error 1.893
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Impact, Week 26, (n=52, 50)	-1.84 Scores on a scale Standard Error 2.169	-2.19 Scores on a scale Standard Error 2.255
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Impact, Week 39, (n=28, 28)	-0.59 Scores on a scale Standard Error 2.868	-2.80 Scores on a scale Standard Error 2.931
Change From Baseline in St Georges Respiratory Questionnaire (SGRQ) Total, SGRQ Symptoms Score, SGRQ Activity Score and SGRQ Impact Score Over Time SGRQ Impact, Week 52, (n=14, 11)	-2.01 Scores on a scale Standard Error 3.693	-3.31 Scores on a scale Standard Error 4.099

SECONDARY outcome

Timeframe: Up to Week 53

Population: mITT Population

Various liver chemistry parameters were monitored periodically to ensure the safety and tolerability of Losmapimod as compared to placebo. Study treatments were discontinued for par. if alanine aminotransferase (ALT) absolute \>= 5xupper limit of normal (ULN) or; ALT \>= 3xULN persists for \>=4 Weeks or; ALT\>=3x ULN and bilirubin \>=2xULN or; ALT\>=3x ULN and International normalized ratio (INR) \>=1.5 or; ALT\>=3x ULN and cannot be monitored weekly for 4 Weeks or; ALT\>=3x ULN symptomatic.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Number of Participants With Abnormal Liver Events During the Treatment Period	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate hemoglobin, total protein, albumin and MCHC. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate hematocrit. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Hematocrit at the Indicated Time Points Hematocrit, Week 2 (n=85,82)	-0.001 L Standard Deviation 0.0238	-0.002 L Standard Deviation 0.0169
Change From Baseline in Hematocrit at the Indicated Time Points Hematocrit, Week 4 (n=87,80)	-0.002 L Standard Deviation 0.0236	-0.002 L Standard Deviation 0.0218
Change From Baseline in Hematocrit at the Indicated Time Points Hematocrit, Week 8 (n=80,77)	-0.001 L Standard Deviation 0.0274	-0.006 L Standard Deviation 0.0229
Change From Baseline in Hematocrit at the Indicated Time Points Hematocrit, Week 12 (n=76,70)	0.002 L Standard Deviation 0.0251	0.000 L Standard Deviation 0.0361
Change From Baseline in Hematocrit at the Indicated Time Points Hematocrit, Week 18 (n=66,61)	0.007 L Standard Deviation 0.0296	-0.000 L Standard Deviation 0.0337
Change From Baseline in Hematocrit at the Indicated Time Points Hematocrit, Week 26 (n=52,50)	0.003 L Standard Deviation 0.0302	-0.000 L Standard Deviation 0.0318
Change From Baseline in Hematocrit at the Indicated Time Points Hematocrit, Week 39 (n=28,29)	0.003 L Standard Deviation 0.0373	0.001 L Standard Deviation 0.0329
Change From Baseline in Hematocrit at the Indicated Time Points Hematocrit, Week 52 (n=14,11)	0.014 L Standard Deviation 0.0231	-0.001 L Standard Deviation 0.0255
Change From Baseline in Hematocrit at the Indicated Time Points Hematocrit, Follow up (n=80,67)	-0.003 L Standard Deviation 0.0305	-0.015 L Standard Deviation 0.0302

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate absolute WBC count, total neutrophil, total lymphocyte, basophil, absolute eosinophil, percentage eosinophil, monocyte and platelet count. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate eosinophil percentage. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Eosinophil Percentage at the Indicated Time Points Eosinophil percentage, Week 2 (n=85,82)	0.09 Percent change Standard Deviation 0.969	0.30 Percent change Standard Deviation 0.995
Change From Baseline in Eosinophil Percentage at the Indicated Time Points Eosinophil percentage, Week 4 (n=86,80)	0.03 Percent change Standard Deviation 1.583	0.16 Percent change Standard Deviation 0.930
Change From Baseline in Eosinophil Percentage at the Indicated Time Points Eosinophil percentage, Week 8 (n=80,77)	0.14 Percent change Standard Deviation 1.419	0.11 Percent change Standard Deviation 1.248
Change From Baseline in Eosinophil Percentage at the Indicated Time Points Eosinophil percentage, Week 12 (n=76,70)	0.08 Percent change Standard Deviation 1.087	0.08 Percent change Standard Deviation 1.517
Change From Baseline in Eosinophil Percentage at the Indicated Time Points Eosinophil percentage, Week 18 (n=66,60)	0.30 Percent change Standard Deviation 1.513	0.60 Percent change Standard Deviation 2.387
Change From Baseline in Eosinophil Percentage at the Indicated Time Points Eosinophil percentage, Week 26 (n=52,50)	0.58 Percent change Standard Deviation 2.390	0.58 Percent change Standard Deviation 2.082
Change From Baseline in Eosinophil Percentage at the Indicated Time Points Eosinophil percentage, Week 39 (n=28,29)	0.39 Percent change Standard Deviation 0.865	0.21 Percent change Standard Deviation 1.434
Change From Baseline in Eosinophil Percentage at the Indicated Time Points Eosinophil percentage, Week 52 (n=14,11)	-0.11 Percent change Standard Deviation 0.805	0.05 Percent change Standard Deviation 2.819
Change From Baseline in Eosinophil Percentage at the Indicated Time Points Eosinophil percentage, Follow up (n=79,67)	-0.01 Percent change Standard Deviation 1.245	0.29 Percent change Standard Deviation 1.215

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate total bilirubin, direct bilirubin, urice acid and creatinine. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma glutamyl transferase at the indicated time point. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate calcium, chloride, glucose, potassium, sodium and blood urea nitrogenat the indicated time point. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate Red blood cell count. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Red Blood Cell Count at the Indicated Time Points Red blood cell count, Week 2 (n=85,82)	-0.01 Trillion cells per liter (TI/L) Standard Deviation 0.248	-0.00 Trillion cells per liter (TI/L) Standard Deviation 0.183
Change From Baseline in Red Blood Cell Count at the Indicated Time Points Red blood cell count, Week 4 (n=87,80)	-0.03 Trillion cells per liter (TI/L) Standard Deviation 0.242	-0.02 Trillion cells per liter (TI/L) Standard Deviation 0.219
Change From Baseline in Red Blood Cell Count at the Indicated Time Points Red blood cell count, Week 8 (n=80,77)	-0.03 Trillion cells per liter (TI/L) Standard Deviation 0.281	-0.05 Trillion cells per liter (TI/L) Standard Deviation 0.205
Change From Baseline in Red Blood Cell Count at the Indicated Time Points Red blood cell count, Week 12 (n=76,70)	0.02 Trillion cells per liter (TI/L) Standard Deviation 0.278	0.02 Trillion cells per liter (TI/L) Standard Deviation 0.328
Change From Baseline in Red Blood Cell Count at the Indicated Time Points Red blood cell count, Week 18 (n=66,61)	0.04 Trillion cells per liter (TI/L) Standard Deviation 0.341	0.00 Trillion cells per liter (TI/L) Standard Deviation 0.287
Change From Baseline in Red Blood Cell Count at the Indicated Time Points Red blood cell count, Week 26 (n=52,50)	0.01 Trillion cells per liter (TI/L) Standard Deviation 0.318	-0.02 Trillion cells per liter (TI/L) Standard Deviation 0.268
Change From Baseline in Red Blood Cell Count at the Indicated Time Points Red blood cell count, Week 39 (n=28,29)	0.08 Trillion cells per liter (TI/L) Standard Deviation 0.352	0.09 Trillion cells per liter (TI/L) Standard Deviation 0.265
Change From Baseline in Red Blood Cell Count at the Indicated Time Points Red blood cell count, Week 52 (n=14,11)	0.23 Trillion cells per liter (TI/L) Standard Deviation 0.320	0.01 Trillion cells per liter (TI/L) Standard Deviation 0.230
Change From Baseline in Red Blood Cell Count at the Indicated Time Points Red blood cell count, Follow up (n=80,67)	0.06 Trillion cells per liter (TI/L) Standard Deviation 0.354	-0.04 Trillion cells per liter (TI/L) Standard Deviation 0.280

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate mean corpuscle hemoglobin. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points Mean corpuscle hemoglobin, Week 4 (n=87,80)	0.09 Picograms Standard Deviation 0.516	-0.04 Picograms Standard Deviation 0.480
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points Mean corpuscle hemoglobin, Week 8 (n=80,77)	0.02 Picograms Standard Deviation 0.801	-0.20 Picograms Standard Deviation 0.700
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points Mean corpuscle hemoglobin, Week 12 (n=76,70)	-0.22 Picograms Standard Deviation 0.773	-0.46 Picograms Standard Deviation 0.964
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points Mean corpuscle hemoglobin, Week 2 (n=85,82)	0.02 Picograms Standard Deviation 0.551	0.03 Picograms Standard Deviation 0.701
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points Mean corpuscle hemoglobin, Week 18 (n=66,61)	-0.27 Picograms Standard Deviation 1.167	-0.52 Picograms Standard Deviation 0.944
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points Mean corpuscle hemoglobin, Week 26 (n=52,50)	-0.25 Picograms Standard Deviation 0.692	-0.48 Picograms Standard Deviation 0.983
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points Mean corpuscle hemoglobin, Week 39 (n=28,29)	-0.55 Picograms Standard Deviation 1.121	-0.60 Picograms Standard Deviation 1.100
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points Mean corpuscle hemoglobin, Week 52 (n=14,11)	-0.72 Picograms Standard Deviation 1.022	-0.32 Picograms Standard Deviation 0.676
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points Mean corpuscle hemoglobin, Follow up (n=80,67)	-0.46 Picograms Standard Deviation 1.130	-0.73 Picograms Standard Deviation 1.279

SECONDARY outcome

Timeframe: Baseline and up to Week 53

Population: mITT Population

Blood samples were collected at Baseline (Day 1, pre-dose) and at Weeks 2, 4, 8, 12, 18, 26, 39, 52 (or at early withdrawal) and follow up (Week 53) to evaluate mean corpuscle volume. Values obtained at Day 1, pre-dose (Week 0) were considered as Baseline values. Change from Baseline was calculated as laboratory test value obtained at the indicated time point minus Baseline value. If post-dose value was missing for a particular assessment visit, then no derivation were performed and the change from Baseline were set to missing for that visit. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points Mean corpuscle volume, Week 2 (n=85,82)	0.0 Femtoliters Standard Deviation 1.72	-0.4 Femtoliters Standard Deviation 1.97
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points Mean corpuscle volume, Week 4 (n=87,80)	0.1 Femtoliters Standard Deviation 1.66	0.1 Femtoliters Standard Deviation 1.88
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points Mean corpuscle volume, Week 8 (n=80,77)	0.2 Femtoliters Standard Deviation 2.49	-0.4 Femtoliters Standard Deviation 2.11
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points Mean corpuscle volume, Week 12 (n=76,70)	0.3 Femtoliters Standard Deviation 2.29	-0.4 Femtoliters Standard Deviation 2.45
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points Mean corpuscle volume, Week 18 (n=66,61)	0.6 Femtoliters Standard Deviation 2.85	-0.1 Femtoliters Standard Deviation 3.12
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points Mean corpuscle volume, Week 26 (n=52,50)	0.5 Femtoliters Standard Deviation 2.34	0.2 Femtoliters Standard Deviation 3.07
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points Mean corpuscle volume, Week 39 (n=28,29)	-1.0 Femtoliters Standard Deviation 3.50	-1.4 Femtoliters Standard Deviation 3.82
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points Mean corpuscle volume, Week 52 (n=14,11)	-1.4 Femtoliters Standard Deviation 3.15	0.0 Femtoliters Standard Deviation 2.05
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points Mean corpuscle volume, Follow up (n=80,67)	-1.9 Femtoliters Standard Deviation 2.73	-2.4 Femtoliters Standard Deviation 3.36

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 9 other events

Deaths: 1 deaths

Losmapimod 15mg

Serious events: 19 serious events

Other events: 13 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=94 participants at risk Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15mg n=90 participants at risk Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Infections and infestations Nasopharyngitis	9.6% 9/94 • Number of events 13 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	14.4% 13/90 • Number of events 20 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

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

Restriction type: OTHER

Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, Week 2, (n=90,84)	0.2 Millimeter of mercury (mmHg) Standard Deviation 12.00	-2.9 Millimeter of mercury (mmHg) Standard Deviation 11.85
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, Week 4, (n=89,82)	-0.8 Millimeter of mercury (mmHg) Standard Deviation 11.49	-0.4 Millimeter of mercury (mmHg) Standard Deviation 12.49
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, Week 8, (n=81,80)	-1.9 Millimeter of mercury (mmHg) Standard Deviation 14.53	-0.3 Millimeter of mercury (mmHg) Standard Deviation 11.48
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, Week 12, (n=78,72)	0.5 Millimeter of mercury (mmHg) Standard Deviation 12.97	-1.6 Millimeter of mercury (mmHg) Standard Deviation 13.84
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, Week 26, (n=53,53)	-1.5 Millimeter of mercury (mmHg) Standard Deviation 15.39	-1.3 Millimeter of mercury (mmHg) Standard Deviation 13.25
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, Week 39, (n=28,29)	0.3 Millimeter of mercury (mmHg) Standard Deviation 16.30	-3.4 Millimeter of mercury (mmHg) Standard Deviation 10.99
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, Week 52, (n=14,11)	6.1 Millimeter of mercury (mmHg) Standard Deviation 17.81	-7.6 Millimeter of mercury (mmHg) Standard Deviation 12.89
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points SBP, Follow up, (n=83,68)	1.8 Millimeter of mercury (mmHg) Standard Deviation 14.46	0.2 Millimeter of mercury (mmHg) Standard Deviation 13.41
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, Week 2, (n=90,84)	-0.0 Millimeter of mercury (mmHg) Standard Deviation 7.18	-3.8 Millimeter of mercury (mmHg) Standard Deviation 9.81
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, Week 4, (n=89,82)	-0.3 Millimeter of mercury (mmHg) Standard Deviation 8.57	-2.2 Millimeter of mercury (mmHg) Standard Deviation 9.32
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, Week 8, (n=81,80)	-1.4 Millimeter of mercury (mmHg) Standard Deviation 8.75	-1.5 Millimeter of mercury (mmHg) Standard Deviation 7.92
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, Week 12, (n=78,72)	1.5 Millimeter of mercury (mmHg) Standard Deviation 9.79	-1.5 Millimeter of mercury (mmHg) Standard Deviation 9.59
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, Week 26, (n=53,53)	0.9 Millimeter of mercury (mmHg) Standard Deviation 8.33	-1.2 Millimeter of mercury (mmHg) Standard Deviation 7.87
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, Week 39, (n=28,29)	-0.5 Millimeter of mercury (mmHg) Standard Deviation 10.40	-1.9 Millimeter of mercury (mmHg) Standard Deviation 9.58
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, Week 52, (n=14,11)	3.4 Millimeter of mercury (mmHg) Standard Deviation 8.08	-0.2 Millimeter of mercury (mmHg) Standard Deviation 8.46
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points DBP, Follow up, (n=83,68)	1.5 Millimeter of mercury (mmHg) Standard Deviation 10.57	-1.7 Millimeter of mercury (mmHg) Standard Deviation 9.94

Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Hemoglobin, Week 2 (n=85,82)	-0.3 Gram (G)/Liter (L) Standard Deviation 7.12	0.0 Gram (G)/Liter (L) Standard Deviation 4.86
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Hemoglobin, Week 4 (n=87,80)	-0.6 Gram (G)/Liter (L) Standard Deviation 7.01	-1.0 Gram (G)/Liter (L) Standard Deviation 6.34
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Hemoglobin, Week 8 (n=80,77)	-0.9 Gram (G)/Liter (L) Standard Deviation 8.38	-2.5 Gram (G)/Liter (L) Standard Deviation 6.93
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Hemoglobin, Week 12 (n=76,70)	-0.5 Gram (G)/Liter (L) Standard Deviation 7.61	-1.4 Gram (G)/Liter (L) Standard Deviation 9.90
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Hemoglobin, Week 18 (n=66,61)	0.1 Gram (G)/Liter (L) Standard Deviation 9.24	-2.3 Gram (G)/Liter (L) Standard Deviation 9.66
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Hemoglobin, Week 26 (n=52,50)	-0.7 Gram (G)/Liter (L) Standard Deviation 9.27	-2.9 Gram (G)/Liter (L) Standard Deviation 8.86
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Hemoglobin, Week 39 (n=28,29)	0.0 Gram (G)/Liter (L) Standard Deviation 11.71	-0.1 Gram (G)/Liter (L) Standard Deviation 10.09
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Hemoglobin, Week 52 (n=14,11)	2.9 Gram (G)/Liter (L) Standard Deviation 8.43	-1.8 Gram (G)/Liter (L) Standard Deviation 7.90
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Hemoglobin, Follow up (n=80,67)	-0.2 Gram (G)/Liter (L) Standard Deviation 9.30	-4.5 Gram (G)/Liter (L) Standard Deviation 9.42
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Albumin, Week 2 (n=90,84)	-0.3 Gram (G)/Liter (L) Standard Deviation 2.23	-0.6 Gram (G)/Liter (L) Standard Deviation 2.55
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Albumin, Week 4 (n=88,81)	-0.5 Gram (G)/Liter (L) Standard Deviation 2.35	-0.3 Gram (G)/Liter (L) Standard Deviation 2.28
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Albumin, Week 8 (n=81,79)	-1.1 Gram (G)/Liter (L) Standard Deviation 2.43	-1.2 Gram (G)/Liter (L) Standard Deviation 2.38
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Albumin, Week 12 (n=78,72)	-0.4 Gram (G)/Liter (L) Standard Deviation 2.62	-0.8 Gram (G)/Liter (L) Standard Deviation 2.64
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Albumin, Week 18 (n=67,60)	-1.1 Gram (G)/Liter (L) Standard Deviation 2.53	-1.1 Gram (G)/Liter (L) Standard Deviation 2.32
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Albumin, Week 26 (n=53,50)	-0.9 Gram (G)/Liter (L) Standard Deviation 2.89	-1.1 Gram (G)/Liter (L) Standard Deviation 2.25
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Albumin, Week 39 (n=28,29)	-0.8 Gram (G)/Liter (L) Standard Deviation 2.76	-1.2 Gram (G)/Liter (L) Standard Deviation 2.35
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Albumin, Week 52 (n=14,11)	-0.4 Gram (G)/Liter (L) Standard Deviation 2.95	-1.5 Gram (G)/Liter (L) Standard Deviation 2.07
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Albumin, Follow up (n=80,68)	-0.8 Gram (G)/Liter (L) Standard Deviation 2.49	-1.6 Gram (G)/Liter (L) Standard Deviation 2.71
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Total protein, Week 2 (n=90,84)	-0.4 Gram (G)/Liter (L) Standard Deviation 3.68	-1.6 Gram (G)/Liter (L) Standard Deviation 2.96
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Total protein, Week 4 (n=88,81)	-0.8 Gram (G)/Liter (L) Standard Deviation 3.93	-1.2 Gram (G)/Liter (L) Standard Deviation 3.18
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Total protein, Week 8 (n=81,79)	-1.8 Gram (G)/Liter (L) Standard Deviation 3.67	-2.0 Gram (G)/Liter (L) Standard Deviation 3.01
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Total protein, Week 12 (n=78,72)	-0.6 Gram (G)/Liter (L) Standard Deviation 4.14	-0.8 Gram (G)/Liter (L) Standard Deviation 3.45
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Total protein, Week 18 (n=67,60)	-0.8 Gram (G)/Liter (L) Standard Deviation 4.00	-1.5 Gram (G)/Liter (L) Standard Deviation 2.66
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Total protein, Week 26 (n=53,50)	-0.5 Gram (G)/Liter (L) Standard Deviation 4.59	-1.5 Gram (G)/Liter (L) Standard Deviation 3.70
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Total protein, Week 39 (n=28,29)	-0.6 Gram (G)/Liter (L) Standard Deviation 4.50	-2.2 Gram (G)/Liter (L) Standard Deviation 3.51
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Total protein, Week 52 (n=14,11)	-0.8 Gram (G)/Liter (L) Standard Deviation 4.66	-3.0 Gram (G)/Liter (L) Standard Deviation 3.66
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points Total protein, Follow up (n=80,68)	-1.6 Gram (G)/Liter (L) Standard Deviation 4.05	-2.0 Gram (G)/Liter (L) Standard Deviation 3.87
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points MCHC, Week 2 (n=85,82)	0.1 Gram (G)/Liter (L) Standard Deviation 6.94	1.7 Gram (G)/Liter (L) Standard Deviation 6.40
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points MCHC, Week 4 (n=87,80)	0.3 Gram (G)/Liter (L) Standard Deviation 6.31	-0.6 Gram (G)/Liter (L) Standard Deviation 6.80
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points MCHC, Week 8 (n=80,77)	-1.0 Gram (G)/Liter (L) Standard Deviation 7.63	-0.9 Gram (G)/Liter (L) Standard Deviation 6.88
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points MCHC, Week 12 (n=76,70)	-3.1 Gram (G)/Liter (L) Standard Deviation 8.45	-3.3 Gram (G)/Liter (L) Standard Deviation 10.70
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points MCHC, Week 18 (n=66,61)	-5.0 Gram (G)/Liter (L) Standard Deviation 10.38	-4.8 Gram (G)/Liter (L) Standard Deviation 8.75
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points MCHC, Week 26 (n=52,50)	-4.4 Gram (G)/Liter (L) Standard Deviation 7.06	-5.3 Gram (G)/Liter (L) Standard Deviation 8.48
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points MCHC, Week 39 (n=28,29)	-2.8 Gram (G)/Liter (L) Standard Deviation 5.19	-1.5 Gram (G)/Liter (L) Standard Deviation 5.35
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points MCHC, Week 52 (n=14,11)	-3.9 Gram (G)/Liter (L) Standard Deviation 5.55	-3.3 Gram (G)/Liter (L) Standard Deviation 6.15
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points MCHC, Follow up (n=80,67)	1.5 Gram (G)/Liter (L) Standard Deviation 9.77	0.6 Gram (G)/Liter (L) Standard Deviation 8.73

Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Direct bilirubin, Week 52 (n=14,11)	-0.1 Micromole (UMOL)/ L Standard Deviation 1.14	0.1 Micromole (UMOL)/ L Standard Deviation 0.70
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Direct bilirubin, Follow up (n=80,68)	0.1 Micromole (UMOL)/ L Standard Deviation 1.09	0.0 Micromole (UMOL)/ L Standard Deviation 0.96
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Total bilirubin, Week 2 (n=90,84)	-0.5 Micromole (UMOL)/ L Standard Deviation 3.12	0.2 Micromole (UMOL)/ L Standard Deviation 3.62
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Total bilirubin, Week 4 (n=88,81)	0.2 Micromole (UMOL)/ L Standard Deviation 3.07	-0.1 Micromole (UMOL)/ L Standard Deviation 2.97
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Total bilirubin, Week 8 (n=81,79)	-0.4 Micromole (UMOL)/ L Standard Deviation 3.03	-0.7 Micromole (UMOL)/ L Standard Deviation 3.28
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Total bilirubin, Week 12 (n=78,72)	-0.2 Micromole (UMOL)/ L Standard Deviation 3.33	-0.1 Micromole (UMOL)/ L Standard Deviation 3.56
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Total bilirubin, Week 18 (n=67,60)	0.0 Micromole (UMOL)/ L Standard Deviation 3.84	0.2 Micromole (UMOL)/ L Standard Deviation 2.66
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Total bilirubin, Week 26 (n=53,50)	0.0 Micromole (UMOL)/ L Standard Deviation 3.03	-0.5 Micromole (UMOL)/ L Standard Deviation 3.05
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Total bilirubin, Week 39 (n=28,29)	-0.0 Micromole (UMOL)/ L Standard Deviation 2.06	0.2 Micromole (UMOL)/ L Standard Deviation 3.55
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Total bilirubin, Week 52 (n=14,11)	1.1 Micromole (UMOL)/ L Standard Deviation 3.38	0.9 Micromole (UMOL)/ L Standard Deviation 2.91
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Total bilirubin, Follow up (n=80,68)	0.2 Micromole (UMOL)/ L Standard Deviation 3.62	-0.4 Micromole (UMOL)/ L Standard Deviation 2.67
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Direct bilirubin, Week 2 (n=90,84)	-0.1 Micromole (UMOL)/ L Standard Deviation 1.09	0.2 Micromole (UMOL)/ L Standard Deviation 1.04
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Direct bilirubin, Week 4 (n=88,81)	0.1 Micromole (UMOL)/ L Standard Deviation 0.89	0.0 Micromole (UMOL)/ L Standard Deviation 0.94
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Direct bilirubin, Week 8 (n=81,79)	-0.0 Micromole (UMOL)/ L Standard Deviation 0.92	-0.1 Micromole (UMOL)/ L Standard Deviation 0.98
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Direct bilirubin, Week 12 (n=78,72)	0.1 Micromole (UMOL)/ L Standard Deviation 0.92	0.3 Micromole (UMOL)/ L Standard Deviation 1.17
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Direct bilirubin, Week 18 (n=67,60)	0.1 Micromole (UMOL)/ L Standard Deviation 1.00	0.2 Micromole (UMOL)/ L Standard Deviation 0.98
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Direct bilirubin, Week 26 (n=53,50)	-0.1 Micromole (UMOL)/ L Standard Deviation 0.79	0.0 Micromole (UMOL)/ L Standard Deviation 1.14
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Direct bilirubin, Week 39 (n=28,29)	-0.1 Micromole (UMOL)/ L Standard Deviation 0.72	0.1 Micromole (UMOL)/ L Standard Deviation 0.88
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Uric acid, Week 2 (n=90,83)	1.7 Micromole (UMOL)/ L Standard Deviation 44.47	-7.0 Micromole (UMOL)/ L Standard Deviation 45.87
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Uric acid, Week 4 (n=88,80)	-3.8 Micromole (UMOL)/ L Standard Deviation 53.43	-14.0 Micromole (UMOL)/ L Standard Deviation 44.47
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Uric acid, Week 8 (n=81,78)	2.1 Micromole (UMOL)/ L Standard Deviation 47.41	-12.1 Micromole (UMOL)/ L Standard Deviation 52.91
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Uric acid, Week 12 (n=78,71)	7.5 Micromole (UMOL)/ L Standard Deviation 54.68	-10.2 Micromole (UMOL)/ L Standard Deviation 62.09
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Uric acid, Week 18 (n=67,60)	6.7 Micromole (UMOL)/ L Standard Deviation 49.87	-5.9 Micromole (UMOL)/ L Standard Deviation 54.33
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Uric acid, Week 26 (n=53,50)	0.6 Micromole (UMOL)/ L Standard Deviation 54.09	-3.7 Micromole (UMOL)/ L Standard Deviation 61.19
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Uric acid, Week 39 (n=28,29)	13.7 Micromole (UMOL)/ L Standard Deviation 50.99	16.6 Micromole (UMOL)/ L Standard Deviation 87.59
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Uric acid, Week 52 (n=14,11)	7.9 Micromole (UMOL)/ L Standard Deviation 48.23	8.3 Micromole (UMOL)/ L Standard Deviation 57.49
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Uric acid, Follow up (n=80,67)	-2.6 Micromole (UMOL)/ L Standard Deviation 62.22	1.7 Micromole (UMOL)/ L Standard Deviation 63.56
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Creatinine, Week 2 (n=90,84)	0.20 Micromole (UMOL)/ L Standard Deviation 7.974	3.22 Micromole (UMOL)/ L Standard Deviation 9.140
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Creatinine, Week 4 (n=88,81)	0.04 Micromole (UMOL)/ L Standard Deviation 7.224	1.78 Micromole (UMOL)/ L Standard Deviation 9.899
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Creatinine, Week 8 (n=81,79)	0.53 Micromole (UMOL)/ L Standard Deviation 11.111	2.23 Micromole (UMOL)/ L Standard Deviation 10.424
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Creatinine, Week 12 (n=78,72)	-0.11 Micromole (UMOL)/ L Standard Deviation 9.917	3.46 Micromole (UMOL)/ L Standard Deviation 17.547
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Creatinine, Week 18 (n=67,60)	0.41 Micromole (UMOL)/ L Standard Deviation 11.973	5.32 Micromole (UMOL)/ L Standard Deviation 18.863
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Creatinine, Week 26 (n=53,50)	1.61 Micromole (UMOL)/ L Standard Deviation 8.018	1.30 Micromole (UMOL)/ L Standard Deviation 8.927
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Creatinine, Week 39 (n=28,29)	2.16 Micromole (UMOL)/ L Standard Deviation 6.164	5.64 Micromole (UMOL)/ L Standard Deviation 12.546
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Creatinine, Week 52 (n=14,11)	2.94 Micromole (UMOL)/ L Standard Deviation 6.757	0.33 Micromole (UMOL)/ L Standard Deviation 5.150
Change From Baseline in Total Bilirubin, Direct Bilirubin, Uric Acid and Creatinine at the Indicated Time Point Creatinine, Follow up (n=80,68)	0.62 Micromole (UMOL)/ L Standard Deviation 12.075	0.23 Micromole (UMOL)/ L Standard Deviation 9.463

Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alanine aminotransferase, Week 2 (n=90,84)	-0.3 International units (IU)/ L Standard Deviation 3.78	1.2 International units (IU)/ L Standard Deviation 5.52
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alanine aminotransferase, Week 4 (n=88,81)	1.8 International units (IU)/ L Standard Deviation 8.22	0.3 International units (IU)/ L Standard Deviation 6.56
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alanine aminotransferase, Week 8 (n=81,79)	-0.3 International units (IU)/ L Standard Deviation 6.00	-0.1 International units (IU)/ L Standard Deviation 6.53
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alanine aminotransferase, Week 12 (n=78,72)	1.3 International units (IU)/ L Standard Deviation 9.61	1.7 International units (IU)/ L Standard Deviation 7.48
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alanine aminotransferase, Week 18 (n=67,60)	0.3 International units (IU)/ L Standard Deviation 8.03	2.4 International units (IU)/ L Standard Deviation 7.67
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alanine aminotransferase, Week 26 (n=53,50)	-0.2 International units (IU)/ L Standard Deviation 7.88	3.0 International units (IU)/ L Standard Deviation 10.79
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alanine aminotransferase, Week 39 (n=28,29)	3.0 International units (IU)/ L Standard Deviation 14.98	1.9 International units (IU)/ L Standard Deviation 9.74
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alanine aminotransferase, Week 52 (n=14,11)	-1.1 International units (IU)/ L Standard Deviation 5.79	1.9 International units (IU)/ L Standard Deviation 3.24
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alanine aminotransferase, Follow up (n=80,68)	0.7 International units (IU)/ L Standard Deviation 12.02	0.7 International units (IU)/ L Standard Deviation 6.86
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Aspartate aminotransferase, Week 2 (n=90,84)	-0.5 International units (IU)/ L Standard Deviation 3.68	1.4 International units (IU)/ L Standard Deviation 4.25
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Aspartate aminotransferase, Week 4 (n=88,80)	2.0 International units (IU)/ L Standard Deviation 7.65	0.5 International units (IU)/ L Standard Deviation 5.16
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Aspartate aminotransferase, Week 8 (n=81,79)	-0.4 International units (IU)/ L Standard Deviation 6.54	0.5 International units (IU)/ L Standard Deviation 5.13
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Aspartate aminotransferase, Week 12 (n=78,72)	2.2 International units (IU)/ L Standard Deviation 11.91	2.0 International units (IU)/ L Standard Deviation 7.73
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Aspartate aminotransferase, Week 18 (n=67,60)	0.9 International units (IU)/ L Standard Deviation 5.72	2.9 International units (IU)/ L Standard Deviation 6.25
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Aspartate aminotransferase, Week 26 (n=53,49)	0.3 International units (IU)/ L Standard Deviation 5.75	4.7 International units (IU)/ L Standard Deviation 9.94
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Aspartate aminotransferase, Week 39 (n=28,29)	1.3 International units (IU)/ L Standard Deviation 6.50	2.4 International units (IU)/ L Standard Deviation 9.79
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Aspartate aminotransferase, Week 52 (n=14,11)	-1.1 International units (IU)/ L Standard Deviation 9.22	1.7 International units (IU)/ L Standard Deviation 3.23
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Aspartate aminotransferase, Follow up (n=80,67)	0.3 International units (IU)/ L Standard Deviation 6.55	0.1 International units (IU)/ L Standard Deviation 4.56
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alkaline phosphatase, Week 2 (n=90,84)	0.3 International units (IU)/ L Standard Deviation 9.14	-2.0 International units (IU)/ L Standard Deviation 11.62
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alkaline phosphatase, Week 4 (n=88,81)	0.0 International units (IU)/ L Standard Deviation 10.43	-2.8 International units (IU)/ L Standard Deviation 10.32
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alkaline phosphatase, Week 8 (n=81,79)	-2.5 International units (IU)/ L Standard Deviation 10.46	-5.3 International units (IU)/ L Standard Deviation 12.71
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alkaline phosphatase, Week 12 (n=78,72)	-2.9 International units (IU)/ L Standard Deviation 12.67	-4.7 International units (IU)/ L Standard Deviation 12.64
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alkaline phosphatase, Week 18 (n=67,60)	1.0 International units (IU)/ L Standard Deviation 9.87	-4.9 International units (IU)/ L Standard Deviation 13.57
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alkaline phosphatase, Week 26 (n=53,50)	0.2 International units (IU)/ L Standard Deviation 13.06	-4.4 International units (IU)/ L Standard Deviation 16.89
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alkaline phosphatase, Week 39 (n=28,29)	0.9 International units (IU)/ L Standard Deviation 9.77	-4.1 International units (IU)/ L Standard Deviation 22.29
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alkaline phosphatase, Week 52 (n=14,11)	0.1 International units (IU)/ L Standard Deviation 6.39	-9.5 International units (IU)/ L Standard Deviation 9.37
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Alkaline phosphatase, Follow up (n=80,68)	-4.2 International units (IU)/ L Standard Deviation 15.26	-4.4 International units (IU)/ L Standard Deviation 13.57
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Gamma glutamyl transferase, Week 2 (n=90,84)	-0.3 International units (IU)/ L Standard Deviation 11.45	-1.5 International units (IU)/ L Standard Deviation 16.55
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Gamma glutamyl transferase, Week 4 (n=88,81)	1.4 International units (IU)/ L Standard Deviation 19.82	-3.7 International units (IU)/ L Standard Deviation 19.85
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Gamma glutamyl transferase, Week 8 (n=81,79)	-1.8 International units (IU)/ L Standard Deviation 17.32	-5.3 International units (IU)/ L Standard Deviation 20.20
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Gamma glutamyl transferase, Week 12 (n=78,72)	-0.1 International units (IU)/ L Standard Deviation 17.11	-1.1 International units (IU)/ L Standard Deviation 24.97
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Gamma glutamyl transferase, Week 18 (n=67,60)	0.6 International units (IU)/ L Standard Deviation 15.42	-1.7 International units (IU)/ L Standard Deviation 21.15
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Gamma glutamyl transferase, Week 26 (n=53,50)	-1.8 International units (IU)/ L Standard Deviation 13.53	2.5 International units (IU)/ L Standard Deviation 19.87
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Gamma glutamyl transferase, Week 39 (n=28,29)	-1.7 International units (IU)/ L Standard Deviation 10.4	1.4 International units (IU)/ L Standard Deviation 25.46
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Gamma glutamyl transferase, Week 52 (n=14,11)	-0.5 International units (IU)/ L Standard Deviation 13.39	0.1 International units (IU)/ L Standard Deviation 9.06
Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma Glutamyl Transferase at the Indicated Time Points Gamma glutamyl transferase, Follow up (n=80,68)	-2.5 International units (IU)/ L Standard Deviation 17.16	0.1 International units (IU)/ L Standard Deviation 14.92

Measure	Placebo n=94 Participants Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15 mg n=90 Participants Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Chloride, Week 2 (n=90,84)	0.3 Millimole (MMOL)/L Standard Deviation 2.59	0.5 Millimole (MMOL)/L Standard Deviation 2.40
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Chloride, Week 4 (n=88,81)	-0.2 Millimole (MMOL)/L Standard Deviation 2.42	1.1 Millimole (MMOL)/L Standard Deviation 2.51
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Chloride, Week 8 (n=81,79)	0.3 Millimole (MMOL)/L Standard Deviation 2.88	0.7 Millimole (MMOL)/L Standard Deviation 2.85
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Chloride, Week 12 (n=77,72)	0.0 Millimole (MMOL)/L Standard Deviation 2.48	0.2 Millimole (MMOL)/L Standard Deviation 2.93
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Chloride, Week 18 (n=67,60)	0.2 Millimole (MMOL)/L Standard Deviation 2.73	0.3 Millimole (MMOL)/L Standard Deviation 2.66
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Chloride, Week 26 (n=53,50)	-0.3 Millimole (MMOL)/L Standard Deviation 3.35	0.5 Millimole (MMOL)/L Standard Deviation 2.57
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Chloride, Week 39 (n=28,29)	-0.8 Millimole (MMOL)/L Standard Deviation 2.45	0.1 Millimole (MMOL)/L Standard Deviation 2.15
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Chloride, Week 52 (n=14,11)	-1.8 Millimole (MMOL)/L Standard Deviation 2.12	-1.4 Millimole (MMOL)/L Standard Deviation 2.66
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Chloride, Follow up (n=80,68)	-0.2 Millimole (MMOL)/L Standard Deviation 2.87	-0.5 Millimole (MMOL)/L Standard Deviation 2.24
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Calcium, Week 2 (n=90,84)	-0.002 Millimole (MMOL)/L Standard Deviation 0.1031	-0.042 Millimole (MMOL)/L Standard Deviation 0.0774
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Calcium, Week 4 (n=88,80)	-0.024 Millimole (MMOL)/L Standard Deviation 0.1007	-0.31 Millimole (MMOL)/L Standard Deviation 0.0908
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Calcium, Week 8 (n=81,79)	-0.017 Millimole (MMOL)/L Standard Deviation 0.0934	-0.039 Millimole (MMOL)/L Standard Deviation 0.0843
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Calcium, Week 12 (n=78,72)	-0.008 Millimole (MMOL)/L Standard Deviation 0.1106	-0.029 Millimole (MMOL)/L Standard Deviation 0.0982
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Calcium, Week 18 (n=67,60)	-0.017 Millimole (MMOL)/L Standard Deviation 0.0891	-0.033 Millimole (MMOL)/L Standard Deviation 0.0928
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Calcium, Week 26 (n=53,49)	-0.024 Millimole (MMOL)/L Standard Deviation 0.0855	-0.023 Millimole (MMOL)/L Standard Deviation 0.1014
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Calcium, Week 39 (n=28,29)	-0.017 Millimole (MMOL)/L Standard Deviation 0.0922	-0.032 Millimole (MMOL)/L Standard Deviation 0.0927
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Calcium, Week 52 (n=14,11)	0.002 Millimole (MMOL)/L Standard Deviation 0.1004	-0.061 Millimole (MMOL)/L Standard Deviation 0.0791
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Calcium, Follow up (n=80,67)	-0.018 Millimole (MMOL)/L Standard Deviation 0.1042	-0.010 Millimole (MMOL)/L Standard Deviation 0.0959
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Glucose, Week 2 (n=90,84)	-0.13 Millimole (MMOL)/L Standard Deviation 1.456	0.22 Millimole (MMOL)/L Standard Deviation 1.619
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Glucose, Week 4 (n=88,81)	-0.01 Millimole (MMOL)/L Standard Deviation 1.500	0.04 Millimole (MMOL)/L Standard Deviation 1.204
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Glucose, Week 8 (n=81,79)	0.01 Millimole (MMOL)/L Standard Deviation 1.330	0.28 Millimole (MMOL)/L Standard Deviation 1.272
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Glucose, Week 12 (n=78,72)	-0.08 Millimole (MMOL)/L Standard Deviation 1.661	0.24 Millimole (MMOL)/L Standard Deviation 1.439
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Glucose, Week 18 (n=67,60)	0.22 Millimole (MMOL)/L Standard Deviation 1.607	0.50 Millimole (MMOL)/L Standard Deviation 1.974
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Glucose, Week 26 (n=53,50)	-0.08 Millimole (MMOL)/L Standard Deviation 1.518	0.00 Millimole (MMOL)/L Standard Deviation 1.117
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Glucose, Week 39 (n=28,29)	-0.11 Millimole (MMOL)/L Standard Deviation 1.553	-0.16 Millimole (MMOL)/L Standard Deviation 1.202
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Glucose, Week 52 (n=14,11)	0.31 Millimole (MMOL)/L Standard Deviation 1.075	-0.09 Millimole (MMOL)/L Standard Deviation 0.896
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Glucose, Follow up (n=80,68)	0.20 Millimole (MMOL)/L Standard Deviation 1.645	0.34 Millimole (MMOL)/L Standard Deviation 2.104
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Potassium, Week 2 (n=90,84)	0.02 Millimole (MMOL)/L Standard Deviation 0.349	-0.01 Millimole (MMOL)/L Standard Deviation 0.391
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Potassium, Week 4 (n=88,80)	0.01 Millimole (MMOL)/L Standard Deviation 0.498	0.06 Millimole (MMOL)/L Standard Deviation 0.393
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Potassium, Week 8 (n=81,79)	0.05 Millimole (MMOL)/L Standard Deviation 0.406	-0.03 Millimole (MMOL)/L Standard Deviation 0.306
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Potassium, Week 12 (n=77,72)	0.02 Millimole (MMOL)/L Standard Deviation 0.352	-0.06 Millimole (MMOL)/L Standard Deviation 0.354
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Potassium, Week 18 (n=67,60)	0.02 Millimole (MMOL)/L Standard Deviation 0.390	0.14 Millimole (MMOL)/L Standard Deviation 0.525
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Potassium, Week 26 (n=53,49)	0.02 Millimole (MMOL)/L Standard Deviation 0.309	-0.02 Millimole (MMOL)/L Standard Deviation 0.381
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Potassium, Week 39 (n=28,29)	0.13 Millimole (MMOL)/L Standard Deviation 0.395	-0.03 Millimole (MMOL)/L Standard Deviation 0.415
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Potassium, Week 52 (n=14,11)	0.10 Millimole (MMOL)/L Standard Deviation 0.390	-0.13 Millimole (MMOL)/L Standard Deviation 0.422
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Potassium, Follow up (n=80,67)	0.01 Millimole (MMOL)/L Standard Deviation 0.385	-0.02 Millimole (MMOL)/L Standard Deviation 0.395
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Sodium, Week 2 (n=90,84)	0.1 Millimole (MMOL)/L Standard Deviation 2.16	-0.2 Millimole (MMOL)/L Standard Deviation 2.06
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Sodium, Week 4 (n=88,81)	-0.1 Millimole (MMOL)/L Standard Deviation 2.18	0.3 Millimole (MMOL)/L Standard Deviation 2.37
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Sodium, Week 8 (n=81,79)	0.0 Millimole (MMOL)/L Standard Deviation 2.33	-0.1 Millimole (MMOL)/L Standard Deviation 2.50
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Sodium, Week 12 (n=77,72)	-0.1 Millimole (MMOL)/L Standard Deviation 1.96	-0.4 Millimole (MMOL)/L Standard Deviation 2.39
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Sodium, Week 18 (n=67,60)	0.1 Millimole (MMOL)/L Standard Deviation 2.80	-0.7 Millimole (MMOL)/L Standard Deviation 2.49
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Sodium, Week 26 (n=53,50)	0.1 Millimole (MMOL)/L Standard Deviation 2.92	-0.2 Millimole (MMOL)/L Standard Deviation 1.83
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Sodium, Week 39 (n=28,29)	-0.4 Millimole (MMOL)/L Standard Deviation 2.33	-0.3 Millimole (MMOL)/L Standard Deviation 2.18
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Sodium, Week 52 (n=14,11)	-0.6 Millimole (MMOL)/L Standard Deviation 1.28	-0.9 Millimole (MMOL)/L Standard Deviation 1.45
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Sodium, Follow up (n=80,68)	-0.2 Millimole (MMOL)/L Standard Deviation 2.40	-0.1 Millimole (MMOL)/L Standard Deviation 2.14
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Blood urea nitrogen, Week 2 (n=90,84)	-0.04 Millimole (MMOL)/L Standard Deviation 1.368	0.46 Millimole (MMOL)/L Standard Deviation 1.474
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Blood urea nitrogen, Week 4 (n=88,81)	-0.21 Millimole (MMOL)/L Standard Deviation 1.399	0.14 Millimole (MMOL)/L Standard Deviation 1.392
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Blood urea nitrogen, Week 8 (n=81,79)	-0.11 Millimole (MMOL)/L Standard Deviation 1.635	0.15 Millimole (MMOL)/L Standard Deviation 1.464
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Blood urea nitrogen, Week 12 (n=78,72)	-0.12 Millimole (MMOL)/L Standard Deviation 1.511	0.62 Millimole (MMOL)/L Standard Deviation 1.993
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Blood urea nitrogen, Week 18 (n=67,60)	-0.41 Millimole (MMOL)/L Standard Deviation 1.332	0.72 Millimole (MMOL)/L Standard Deviation 2.310
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Blood urea nitrogen, Week 26 (n=53,50)	-0.34 Millimole (MMOL)/L Standard Deviation 1.267	0.24 Millimole (MMOL)/L Standard Deviation 1.636
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Blood urea nitrogen, Week 39 (n=28,29)	-0.26 Millimole (MMOL)/L Standard Deviation 1.385	0.62 Millimole (MMOL)/L Standard Deviation 1.680
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Blood urea nitrogen, Week 52 (n=14,11)	0.01 Millimole (MMOL)/L Standard Deviation 0.975	1.07 Millimole (MMOL)/L Standard Deviation 1.209
Change From Baseline in Chloride, Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen at the Indicated Time Points Blood urea nitrogen, Follow up (n=80,68)	0.07 Millimole (MMOL)/L Standard Deviation 1.577	0.11 Millimole (MMOL)/L Standard Deviation 1.545

Measure	Placebo n=94 participants at risk Participants with COPD received placebo orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of inhaled corticosteroid (ICS). Salbutamol metered dose inhaler (MDI) was provided as a rescue medication.	Losmapimod 15mg n=90 participants at risk Participants with COPD received losmapimod 15 mg tablets orally, twice daily, approximately 12 hours apart and within 30 minutes after meals with a full glass of water for the duration of the treatment period in addition to standard of care, stratified according to whether a center collects sputum or not and current use of ICS. Salbutamol MDI was provided as a rescue medication.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.1% 2/94 • Number of events 2 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	7.8% 7/90 • Number of events 9 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Infections and infestations Pneumonia	1.1% 1/94 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	4.4% 4/90 • Number of events 4 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Cardiac disorders Coronary artery disease	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	2.2% 2/90 • Number of events 2 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Cardiac disorders Acute myocardial infarction	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Blood and lymphatic system disorders Anaemia	1.1% 1/94 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	0.00% 0/90 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Cardiac disorders Angina unstable	1.1% 1/94 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	0.00% 0/90 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Vascular disorders Aortic aneurysm rupture	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Cardiac disorders Atrial fibrillation	1.1% 1/94 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	0.00% 0/90 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bile duct cancer	1.1% 1/94 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	0.00% 0/90 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchial carcinoma	1.1% 1/94 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	0.00% 0/90 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Cardiac disorders Cardiac failure	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Cardiac disorders Cardiopulmonary failure	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Infections and infestations Cellulitis	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Renal and urinary disorders Chronic kidney disease	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Injury, poisoning and procedural complications Contusion	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Ear and labyrinth disorders Deafness unilateral	1.1% 1/94 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	0.00% 0/90 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Gastrointestinal disorders Ileal ulcer	1.1% 1/94 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	0.00% 0/90 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Cardiac disorders Myocardial infarction	1.1% 1/94 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	0.00% 0/90 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Infections and infestations Oesophageal candidiasis	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Injury, poisoning and procedural complications Pelvic fracture	1.1% 1/94 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	0.00% 0/90 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.
Infections and infestations Respiratory tract infection	0.00% 0/94 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.	1.1% 1/90 • Number of events 1 • On-treatment SAEs and non-serious AEs were collected from start of Investigational Medicinal Product (Week 0) until Week 53 including 1 Week of follow up. On-treatment SAEs and non-serious AEs are reported for mITT Population, comprised of all par. who were randomized to treatment and who received at least one dose of study medication.