Randomised, Double-Blind, Placebo-Controlled, Parallel-Gr... | NCT01218126

Label	Type	Description	Intervention Names
losmapimod 2.5 mg	Experimental	losmapimod 2.5 mg	Drug: losmapimod
placebo	Placebo Comparator		Drug: placebo
losmapimod 7.5 mg	Experimental	losmapimod 7.5 mg	Drug: losmapimod
losmapimod 15 mg	Experimental	losmapimod 15 mg	Drug: losmapimod

Name	Type	Description	Arm Group Labels	Other Names
losmapimod	Drug	comparison of different dosages of drug 2.5 mg, 7.5 mg or 15 mg	losmapimod 15 mg losmapimod 2.5 mg losmapimod 7.5 mg

Measure	Description	Time Frame
Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24	Exercise tolerance was assessed using the 6MWD. If a participant was recorded as having used supplemental oxygen or a walking aid (including sitting down then continuing walking) or a technical problem during a 6MWD then that walk was considered as invalid; otherwise the 6MWD was considered as valid. The baseline 6MWD value was defined as the longest distance walked, for a valid walk, at Visit 2. Variability between the distances walked during the first six-minute walk test (6MWD1) and the second six-minute walk test (6MWD2) being compared was defined as: Variability = [100 x (6MWD2 - 6MWD1)]/6MWD1. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0).	Baseline (Week 0) and Week 4, 12, 24

Measure	Description	Time Frame
Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Pre and post-bronchodilator spirometry was performed by the investigator. For post-bronchodilator measurements, spirometry was performed 10-15 minutes after inhalation of 400/360 microgram (mcg) of salbutamol/albuterol. Participants were asked to withhold all bronchodilator therapy (regularly used ipratropium bromide and salbutamol/albuterol used as required) for at least 4 hours prior to spirometric testing. The change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization values.Baseline visit was Visit 2 (Week 0).

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Birmingham	Alabama	35294	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
31197640	Derived	Largajolli A, Beerahee M, Yang S. Bayesian approach to investigate a two-state mixed model of COPD exacerbations. J Pharmacokinet Pharmacodyn. 2019 Aug;46(4):371-384. doi: 10.1007/s10928-019-09643-6. Epub 2019 Jun 13.
24461903	Derived	Watz H, Barnacle H, Hartley BF, Chan R. Efficacy and safety of the p38 MAPK inhibitor losmapimod for patients with chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2014 Jan;2(1):63-72. doi: 10.1016/S2213-2600(13)70200-5. Epub 2013 Dec 5.

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
113006	Clinical Study Report	View IPD

ID	Title	Description
FG000	Placebo	Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24

Exercise tolerance was assessed using the 6MWD. If a participant was recorded as having used supplemental oxygen or a walking aid (including sitting down then continuing walking) or a technical problem during a 6MWD then that walk was considered as invalid; otherwise the 6MWD was considered as valid. The baseline 6MWD value was defined as the longest distance walked, for a valid walk, at Visit 2. Variability between the distances walked during the first six-minute walk test (6MWD1) and the second six-minute walk test (6MWD2) being compared was defined as: Variability = [100 x (6MWD2 - 6MWD1)]/6MWD1. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0).

Intent-to-treat (ITT) population consisted of all participants randomized to treatment and who received at least one dose of study drug. Only those participants with data available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Meter (m)

Baseline (Week 0) and Week 4, 12, 24

ID	Title	Description
OG000	Placebo	Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG001	Losmapimod 2.5 mg	Participants received Losmapimod 2.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG002	Losmapimod 7.5 mg	Participants received Losmapimod 7.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG003	Losmapimod 15 mg	Participants received Losmapimod 7.5 mg tablet twice daily orally for 4 weeks followed by Losmapimod 15 mg for a total period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.

Units	Counts
Participants	OG000153 OG001149 OG002151 OG003

Title	Denominators	Categories
Week 4	ParticipantsOG000145 ParticipantsOG001140 ParticipantsOG002145 ParticipantsOG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Placebo versus Losmapimod 2.5 mg at Week 4.	mixed model repeated measures		0.517		Mean Difference (Net)	-2.6			2-Sided	95	-10.4	5.2			Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.		Superiority or Other

Secondary

Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24

Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Pre and post-bronchodilator spirometry was performed by the investigator. For post-bronchodilator measurements, spirometry was performed 10-15 minutes after inhalation of 400/360 microgram (mcg) of salbutamol/albuterol. Participants were asked to withhold all bronchodilator therapy (regularly used ipratropium bromide and salbutamol/albuterol used as required) for at least 4 hours prior to spirometric testing. The change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization values.Baseline visit was Visit 2 (Week 0).

ITT population. Only those participants with data available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Millilitre(mL)

Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24

ID	Title	Description
OG000	Placebo	Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG001	Losmapimod 2.5 mg

Secondary

Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24

FVC is the total amount of air exhaled during the lung function test. and post-bronchodilator spirometry was performed by the investigator. For post-bronchodilator measurements, spirometry was performed 10-15 minutes after inhalation of 400/360 microgram (mcg) of salbutamol/albuterol. Participants were asked to withhold all bronchodilator therapy (regularly used ipratropium bromide and salbutamol/albuterol used as required) for at least 4 hours prior to spirometric testing. The change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization values.. Baseline visit was Visit 2 (Week 0).

ITT population. Only those participants with data available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24

ID	Title	Description
OG000	Placebo	Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG001	Losmapimod 2.5 mg	Participants received Losmapimod 2.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.

Secondary

Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24

The SGRQ-C questionnaire had 14 questions of COPD and participant had to rate each question. These 14 questions were separated to evaluate the three components of SGRQ-C. These three components were symptom component (question 1 to 7), activity component (question 9 and 12) and impact component (question 8, 10, 11, 13 and 14). The total score is 0 to 100 with a higher score indicating greater impairment of health status. Change from Baseline was calculated as the specified time point value minus the Baseline value. Baseline visit was Visit 2 (Week 0).

ITT population. Only those participants with data available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Score on scale

Baseline (Week 0) and Week 12, 24

ID	Title	Description
OG000	Placebo	Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG001	Losmapimod 2.5 mg	Participants received Losmapimod 2.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.

Secondary

Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24

A plethysmograph is an instrument for measuring changes in volume within an organ or whole body (usually resulting from fluctuations in the amount of blood or air it contains). Plethysmography was used to assess IC, RV, TGV at FRC, SLV, and TLC. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0).

ITT population. Only those participants with data available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Baseline(Week 0) and Week 12, 24

ID	Title	Description
OG000	Placebo	Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG001	Losmapimod 2.5 mg	Participants received Losmapimod 2.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.

Secondary

Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks

Least square mean ratio to Baseline of plasma fibrinogen was assessed at Week 4, 8, 12, 24. Blood samples for biomarker analysis were taken at selected visits.

ITT population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Standard Error

Ratio

Baseline (Week 0) and Week 4, 8, 12, 24

ID	Title	Description
OG000	Placebo	Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG001	Losmapimod 2.5 mg	Participants received Losmapimod 2.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG002

Secondary

Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks

Least square mean ratio to Baseline of HsCRP was assessed at Week 4, 8, 12, 24. Blood samples for biomarker analysis were taken at selected visits.

ITT population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Standard Error

Ratio

Baseline (Week 0) and Week 4, 8, 12, 24

ID	Title	Description
OG000	Placebo	Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG001	Losmapimod 2.5 mg	Participants received Losmapimod 2.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG002

Secondary

Total Number of Exacerbations Over 24 Weeks

An exacerbation of COPD is defined as a worsening of COPD symptoms requiring changes to normal treatment (other than increased use of relief salbutamol/albuterol) including antimicrobial therapy, short courses of oral steroids, other bronchodilator therapy and/or emergency treatment or hospitalization.

ITT population.

Posted

Number

Number of exacerbations

Up to 24 weeks

ID	Title	Description
OG000	Placebo	Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG001	Losmapimod 2.5 mg	Participants received Losmapimod 2.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
OG002

Serious Adverse Events

Term	Organ System	Statistical Information
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	EG0008 affected153 at risk EG0016 affected149 at risk EG0022 affected151 at risk EG0033 affected149 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	EG0001 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	EG0001 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Pneumonia	Infections and infestations	EG0004 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Sinobronchitis	Infections and infestations	EG0001 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Urinary tract infection	Infections and infestations	EG0000 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Angina pectoris	Cardiac disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0022 affected151 at risk EG003
Acute myocardial infarction	Cardiac disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Atrial fibrillation	Cardiac disorders	EG0001 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Atrioventricular block second degree	Cardiac disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Myocardial infarction	Cardiac disorders	EG0000 affected153 at risk EG0011 affected149 at risk EG0020 affected151 at risk EG003
Stress cardiomyopathy	Cardiac disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	EG0000 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Lower limb fracture	Injury, poisoning and procedural complications	EG0000 affected153 at risk EG0011 affected149 at risk EG0020 affected151 at risk EG003
Spinal fracture	Injury, poisoning and procedural complications	EG0000 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Ulna fracture	Injury, poisoning and procedural complications	EG0000 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Spinal column stenosis	Musculoskeletal and connective tissue disorders	EG0001 affected153 at risk EG0011 affected149 at risk EG0020 affected151 at risk EG003
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	EG0001 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	EG0001 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Leukoplakia	Skin and subcutaneous tissue disorders	EG0001 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Pemphigoid	Skin and subcutaneous tissue disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Gastritis	Gastrointestinal disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Pancreatitis	Gastrointestinal disorders	EG0001 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Peptic ulcer	Gastrointestinal disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Chest pain	General disorders	EG0001 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Polyp	General disorders	EG0000 affected153 at risk EG0011 affected149 at risk EG0020 affected151 at risk EG003
Pyrexia	General disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	EG0000 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	EG0001 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Anxiety	Psychiatric disorders	EG0001 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Psychotic disorder	Psychiatric disorders	EG0000 affected153 at risk EG0011 affected149 at risk EG0020 affected151 at risk EG003
Deep vein thrombosis	Vascular disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003
Peripheral arterial occlusive disease	Vascular disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Cholecystitis	Hepatobiliary disorders	EG0000 affected153 at risk EG0010 affected149 at risk EG0021 affected151 at risk EG003
Anaphylactic reaction	Immune system disorders	EG0000 affected153 at risk EG0011 affected149 at risk EG0020 affected151 at risk EG003
Nephrolithiasis	Renal and urinary disorders	EG0001 affected153 at risk EG0010 affected149 at risk EG0020 affected151 at risk EG003

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Non-Inferiority Type
OG000 OG001	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 4	mixed model repeated measures	0.968	Mean Difference (Net)	-1	2-Sided	95	-39	38	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Pre-Bronchodilator FEV1 Placebo versus Losmapimod 7.5 mg at Week 4	mixed model repeated measures	0.715	Mean Difference (Net)	-7	2-Sided	95	-45	31	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 4	mixed model repeated measures	0.152	Mean Difference (Net)	28	2-Sided	95	-10	66	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG001	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 8	mixed model repeated measures	0.922	Mean Difference (Net)	-2	2-Sided	95	-45	40	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 8	mixed model repeated measures	0.694	Mean Difference (Net)	8	2-Sided	95	-34	50	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 8	mixed model repeated measures	0.094	Mean Difference (Net)	37	2-Sided	95	-6.3	79	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG001	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 12	mixed model repeated measures	0.456	Mean Difference (Net)	16	2-Sided	95	-26	58	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 12	mixed model repeated measures	0.355	Mean Difference (Net)	20	2-Sided	95	-22	61	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 12	mixed model repeated measures	0.023	Mean Difference (Net)	49	2-Sided	95	6.7	91	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG001	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 16	mixed model repeated measures	0.320	Mean Difference (Net)	22	2-Sided	95	-21	65	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 16	mixed model repeated measures	0.267	Mean Difference (Net)	24	2-Sided	95	-19	67	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 16	mixed model repeated measures	0.289	Mean Difference (Net)	24	2-Sided	95	-20	67	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG001	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 20	mixed model repeated measures	0.786	Mean Difference (Net)	6	2-Sided	95	-37	49	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 20	mixed model repeated measures	0.134	Mean Difference (Net)	33	2-Sided	95	-10	76	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 20	mixed model repeated measures	0.191	Mean Difference (Net)	29	2-Sided	95	-15	74	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG001	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 24	mixed model repeated measures	0.852	Mean Difference (Net)	4	2-Sided	95	-38	46	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 24	mixed model repeated measures	0.397	Mean Difference (Net)	18	2-Sided	95	-24	60	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 24	mixed model repeated measures	0.494	Mean Difference (Net)	15	2-Sided	95	-28	58	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG001	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 4	mixed model repeated measures	0.807	Mean Difference (Net)	4	2-Sided	95	-31	40	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 4	mixed model repeated measures	0.386	Mean Difference (Net)	16	2-Sided	95	-20	51	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 4	mixed model repeated measures	0.089	Mean Difference (Net)	31	2-Sided	95	-4.8	67	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG001	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 8	mixed model repeated measures	0.958	Mean Difference (Net)	-1	2-Sided	95	-45	43	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 8	mixed model repeated measures	0.766	Mean Difference (Net)	7	2-Sided	95	-37	50	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 8	mixed model repeated measures	0.060	Mean Difference (Net)	43		95	-1.7	87	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG001	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 12	mixed model repeated measures	0.678	Mean Difference (Net)	-9	2-Sided	95	-53	35	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 12	mixed model repeated measures	0.636	Mean Difference (Net)	11	2-Sided	95	-33	54	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 12	mixed model repeated measures	0.094	Mean Difference (Net)	38	2-Sided	95	-6.5	83	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG001	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 16	mixed model repeated measures	0.772	Mean Difference (Net)	-6	2-Sided	95	-49	37	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 16	mixed model repeated measures	0.387	Mean Difference (Net)	19	2-Sided	95	-24	61	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 16	mixed model repeated measures	0.243	Mean Difference (Net)	26	2-Sided	95	-18	69	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG001	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 20	mixed model repeated measures	0.398	Mean Difference (Net)	-19	2-Sided	95	-62	25	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 20	mixed model repeated measures	0.214	Mean Difference (Net)	27	2-Sided	95	-16	70	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 20	mixed model repeated measures	0.526	Mean Difference (Net)	14	2-Sided	95	-30	58	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG001	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 24	mixed model repeated measures	0.671	Mean Difference (Net)	-9	2-Sided	95	-53	34	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG002	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 24	mixed model repeated measures	0.355	Mean Difference (Net)	20	2-Sided	95	-23	64	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other
OG000 OG003	Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 24	mixed model repeated measures	0.781	Mean Difference (Net)	6	2-Sided	95	-38	50	Analysis performed using a repeated measures model with covariates of treatment, region, smoking status at screening (stratum), history of exacerbations, baseline, visit, visit by baseline and visit by treatment interactions.	Superiority or Other

Term	Organ System	Assessment Type	Statistical Information
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00035 events30 affected153 at risk EG00141 events30 affected149 at risk EG00243 events36 affected151 at risk EG00332 events24 affected149 at risk
Headache	Nervous system disorders	Systematic Assessment	EG00024 events13 affected153 at risk EG00121 events15 affected149 at risk EG00213 events11 affected151 at risk EG003
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG00012 events12 affected153 at risk EG0019 events8 affected149 at risk EG0026 events5 affected151 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00011 events10 affected153 at risk EG0017 events7 affected149 at risk EG0026 events5 affected151 at risk EG003

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Placebo	Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
BG001	Losmapimod 2.5 mg	Participants received Losmapimod 2.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
BG002	Losmapimod 7.5 mg	Participants received Losmapimod 7.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
BG003	Losmapimod 15 mg	Participants received Losmapimod 7.5 mg tablet twice daily orally for 4 weeks followed by Losmapimod 15 mg for a total period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.	3	153	17	153	51	153
EG001	Losmapimod 2.5 mg	Participants received Losmapimod 2.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.	0	149	12	149	49	149
EG002	Losmapimod 7.5 mg	Participants received Losmapimod 7.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.	1	151	14	151	51	151
EG003	Losmapimod 15 mg	Participants received Losmapimod 7.5 mg tablet twice daily orally for 4 weeks followed by Losmapimod 15 mg for a total period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug.	2	149	15	149	48	149