Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    201496: A Study to Evaluate the Efficacy and Safety of 15mg BID Losmapimod (GW856553) Compared to Placebo in Frequently Exacerbating Subjects with Chronic Obstructive Pulmonary Disease (COPD).

    Summary
    EudraCT number
    		 2014-002992-27
    Trial protocol
    		 SK   DE   BG   ES  
    Global end of trial date
    30 Jun 2016

    Results information
    Results version number
    		 v3(current)
    This version publication date
    12 Jul 2018
    First version publication date
    08 Mar 2017
    Other versions
    		 v1 , v2
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    201496
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Sep 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Jun 2016
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the yearly rate of moderate-severe COPD exacerbations in losmapimod compared to placebo treated subjects.
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Dec 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 59
    Country: Number of subjects enrolled
    Bulgaria: 25
    Country: Number of subjects enrolled
    Chile: 9
    Country: Number of subjects enrolled
    Germany: 48
    Country: Number of subjects enrolled
    Korea, Republic of: 19
    Country: Number of subjects enrolled
    Slovakia: 22
    Country: Number of subjects enrolled
    Spain: 8
    Worldwide total number of subjects
    190
    EEA total number of subjects
    103
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    90
    From 65 to 84 years
    100
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 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).

    Pre-assignment
    Screening details
    		 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.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Carer, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 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.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo tablet was administered 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.

    Arm title
    		 Losmapimod 15 mg
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Losmapimod
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Losmapimod 15 mg tablet was administered 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.

    Number of subjects in period 1 [1]
    		Placebo Losmapimod 15 mg
    Started
    94
    90
    Completed
    14
    10
    Not completed
    80
    80
         Physician decision
    1
    1
         Consent withdrawn by subject
    1
    4
         Other: Study closed/terminated
    66
    55
         Adverse Event, non-fatal
    8
    9
         Other: Met stopping criteria
    1
    -
         Lost to follow-up
    -
    2
         Adverse Event, serious fatal
    1
    3
         Lack of efficacy
    1
    3
         Protocol deviation
    1
    3
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of 190 enrolled participants, 184 were randomized in a TP.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 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.

    Reporting group title
    Losmapimod 15 mg
    Reporting group description
    		 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.

    Reporting group values
    		 Placebo Losmapimod 15 mg Total
    Number of subjects
    		 94 90
    Age categorical
    Units: Subjects
    Age continuous
    Age continuous description
    Units: years
        arithmetic mean (standard deviation)
    		 64.6 ( 8.27 ) 66.4 ( 6.66 ) -
    Gender categorical
    Gender categorical description
    Units: Subjects
        Female
    		 33 26 59
        Male
    		 61 64 125
    Race/Ethnicity, Customized
    Race/ Ethnicity details were collected.
    Units: Subjects
        Japanese/East Asian /South East Asian Heritage
    		 10 9 19
        White
    		 84 81 165

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 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.

    Reporting group title
    Losmapimod 15 mg
    Reporting group description
    		 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.

    Primary: Annual rate of moderate and severe exacerbations of COPD

    		 Close Top of page
    End point title
    		 Annual rate of moderate and severe exacerbations of COPD
    End point description
    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.
    End point type
    Primary
    End point timeframe
    From the start of the study treatment up to 53 Weeks
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [1]
    90 [2]
    Units: Exacerbations per participant per year
        median (standard deviation)
    0.84 ( 0.19 )
    0.88 ( 0.22 )
    Notes
    [1] - mITT Population
    [2] - mITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Data presented above are for 95% equal-tailed credible intervals. The estimated posterior probability that the true ratio losmapimod/placebo is <1 assuming noninformative priors is 0.44.
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Adjusted median
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.73
    Variability estimate
    Standard deviation
    Dispersion value
    0.28

    Secondary: Time to first occurrence of moderate or severe COPD exacerbation

    		 Close Top of page
    End point title
    		 Time to first occurrence of moderate or severe COPD exacerbation
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    From the start of the study treatment up to 53 Weeks
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [3]
    90 [4]
    Units: Days
        arithmetic mean (standard deviation)
    168.01 ( 106.222 )
    160.18 ( 117.142 )
    Notes
    [3] - mITT Population
    [4] - mITT Population
    No statistical analyses for this end point

    Secondary: Number of participants having any adverse events (AEs), Serious adverse events (SAEs)

    		 Close Top of page
    End point title
    		 Number of participants having any adverse events (AEs), Serious adverse events (SAEs)
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    From the start of the study treatment up to 53 Weeks
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [5]
    90 [6]
    Units: Participants
        Non-serious AEs
    34
    38
        SAEs
    8
    19
    Notes
    [5] - mITT Population
    [6] - mITT Population
    No statistical analyses for this end point

    Secondary: 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).

    		 Close Top of page
    End point title
    		 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).
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 52
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [7]
    90 [8]
    Units: Liters
    arithmetic mean (standard error)
        FEV1 pre-dose, Week 2, n = 90, 83
    0.002 ( 0.0241 )
    0.028 ( 0.0258 )
        FEV1 Pre-dose, Week 4, n=88, 82
    -0.010 ( 0.0242 )
    0.025 ( 0.0259 )
        FEV1 Pre-dose, Week 8, n=81, 79
    -0.031 ( 0.0247 )
    0.028 ( 0.0261 )
        FEV1 Pre-dose, Week 12, n=78, 71
    -0.011 ( 0.0250 )
    -0.014 ( 0.0267 )
        FEV1 Pre-dose, Week 18, n=67, 61
    -0.037 ( 0.0260 )
    0.013 ( 0.0277 )
        FEV1 Pre-dose, Week 26, n=53, 52
    -0.059 ( 0.0278 )
    0.020 ( 0.0289 )
        FEV1 Pre-dose, Week 39, n=28, 28
    -0.085 ( 0.0342 )
    0.001 ( 0.0353 )
        FEV1 Pre-dose, Week 52, n=14, 11
    -0.034 ( 0.0485 )
    0.016 ( 0.0513 )
        FEV1 post-dose, Week 2, n=89, 82
    0.012 ( 0.0188 )
    0.026 ( 0.0203 )
        FEV1 post-dose, Week 4, n=87, 81
    -0.022 ( 0.0193 )
    0.019 ( 0.0207 )
        FEV1 post-dose, Week 8, n=80, 78
    -0.010 ( 0.0232 )
    0.023 ( 0.0242 )
        FEV1 post-dose, Week 12, n=76, 69
    -0.008 ( 0.0217 )
    -0.020 ( 0.0231 )
        FEV1 post-dose, Week 18, n=66, 60
    -0.035 ( 0.0256 )
    -0.012 ( 0.0271 )
        FEV1 post-dose, Week 26, n=52, 51
    -0.070 ( 0.0273 )
    0.030 ( 0.0282 )
        FEV1 post-dose, Week 39, n=27, 27
    -0.086 ( 0.0346 )
    -0.031 ( 0.0356 )
        FEV1 post-dose, Week 52, n=13, 10
    -0.018 ( 0.0419 )
    0.024 ( 0.0472 )
        FEV6 pre-dose, Week 2, n = 90,82
    -0.007 ( 0.0353 )
    0.045 ( 0.0381 )
        FEV6 Pre-dose, Week 4, n=87, 81
    -0.034 ( 0.0353 )
    0.012 ( 0.0380 )
        FEV6 Pre-dose, Week 8, n=81, 78
    -0.043 ( 0.0400 )
    0.032 ( 0.0424 )
        FEV6 Pre-dose, Week 12, n=78, 71
    -0.036 ( 0.0366 )
    -0.034 ( 0.0392 )
        FEV6 Pre-dose, Week 18, n=67, 60
    -0.073 ( 0.0413 )
    -0.014 ( 0.0441 )
        FEV6 Pre-dose, Week 26, n=53, 52
    -0.076 ( 0.0405 )
    -0.003 ( 0.0425 )
        FEV6 Pre-dose, Week 39, n=28, 28
    -0.102 ( 0.0486 )
    0.013 ( 0.0507 )
        FEV6 Pre-dose, Week 52, n=14, 11
    -0.101 ( 0.0731 )
    0.071 ( 0.0745 )
        FEV6 post-dose, Week 2, n=89, 81
    -0.003 ( 0.0296 )
    0.023 ( 0.0319 )
        FEV6 post-dose, Week 4, n=86, 80
    -0.027 ( 0.0273 )
    0.010 ( 0.0295 )
        FEV6 post-dose, Week 8, n=80, 76
    -0.039 ( 0.0313 )
    0.012 ( 0.0331 )
        FEV6 post-dose, Week 12, n=76, 69
    -0.028 ( 0.0308 )
    -0.029 ( 0.0330 )
        FEV6 post-dose, Week 18, n=66, 59
    -0.060 ( 0.0367 )
    -0.035 ( 0.0392 )
        FEV6 post-dose, Week 26, n=51, 51
    -0.081 ( 0.0360 )
    0.003 ( 0.0373 )
        FEV6 post-dose, Week 39, n=27, 27
    -0.095 ( 0.0428 )
    -0.067 ( 0.0443 )
        FEV6 post-dose, Week 52, n=13, 10
    -0.119 ( 0.0607 )
    -0.017 ( 0.0674 )
        FVC, Pre-dose, Week 2, n =90, 83
    -0.018 ( 0.0389 )
    0.038 ( 0.0417 )
        FVC, Pre-dose, Week 4, n =88, 82
    -0.039 ( 0.0392 )
    0.006 ( 0.0418 )
        FVC, Pre-dose Week 8, n = 81, 79
    -0.061 ( 0.0401 )
    0.011 ( 0.0422 )
        FVC, Pre-dose, Week 12, n =78, 71
    -0.046 ( 0.0405 )
    -0.058 ( 0.0430 )
        FVC, Pre-dose Week 18, n =67, 61
    -0.093 ( 0.0422 )
    -0.021 ( 0.0447 )
        FVC, Week 26, n=53, 52
    -0.095 ( 0.0451 )
    -0.028 ( 0.0468 )
        FVC, Pre-dose Week 39, n =28, 28
    -0.115 ( 0.0558 )
    -0.033 ( 0.0574 )
        FVC, Pre-dose Week 52, n =14, 11
    -0.052 ( 0.0806 )
    0.031 ( 0.0837 )
        FVC, Post-dose Week 2, n =89, 82
    -0.007 ( 0.0359 )
    0.037 ( 0.0385 )
        FVC, Post-dose Week 4, n =87, 81
    -0.021 ( 0.0316 )
    0.033 ( 0.0341 )
        FVC, Post-dose Week 8, n =80, 78
    -0.052 ( 0.0366 )
    0.019 ( 0.0385 )
        FVC,Post-dose Week 12, n =76, 69
    -0.020 ( 0.0361 )
    -0.008 ( 0.0385 )
        FVC, Post-dose Week 18, n =66, 60
    -0.075 ( 0.0422 )
    -0.016 ( 0.0449 )
        FVC, Post-dose Week 26, n=52, 51
    -0.135 ( 0.0495 )
    0.003 ( 0.0513 )
        FVC, Post-dose Week 39, n =27, 27
    -0.092 ( 0.0499 )
    -0.043 ( 0.0518 )
        FVC, Post-dose Week 52, n =13, 10
    -0.081 ( 0.0612 )
    -0.039 ( 0.0671 )
    Notes
    [7] - mITT Population
    [8] - mITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    FEV1 pre-dose, Week 2
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.371 [9]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.026
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.031
         upper limit
    		 0.084
    Notes
    [9] - Analysis performed using a Mixed-effect Model Repeated Measures (MMRM) with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    FEV1 pre-dose, Week 4
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.244 [10]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.035
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.024
         upper limit
    		 0.093
    Notes
    [10] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    FEV1 pre-dose, Week 8
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.05 [11]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.059
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.119
    Notes
    [11] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    FEV1 pre-dose, Week 12
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.942 [12]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.002
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.063
         upper limit
    		 0.058
    Notes
    [12] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    FEV1 pre-dose, Week 18
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.127 [13]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.014
         upper limit
    		 0.114
    Notes
    [13] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    FEV1 pre-dose, Week 26
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.024 [14]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.079
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.011
         upper limit
    		 0.148
    Notes
    [14] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    FEV1 pre-dose, Week 39
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.057 [15]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.086
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.003
         upper limit
    		 0.174
    Notes
    [15] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    FEV1 pre-dose, Week 52
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.481 [16]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.09
         upper limit
    		 0.191
    Notes
    [16] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    FEV1 post-dose, Week 2
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.521 [17]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.014
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 0.059
    Notes
    [17] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    FEV1 post-dose, Week 4
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.084 [18]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.005
         upper limit
    		 0.086
    Notes
    [18] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    FEV1 post-dose, Week 8
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.266 [19]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.033
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.025
         upper limit
    		 0.09
    Notes
    [19] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    FEV1 post-dose, Week 12
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.665 [20]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.012
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.066
         upper limit
    		 0.042
    Notes
    [20] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 13
    Statistical analysis description
    FEV1 post-dose, Week 18
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.489 [21]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.023
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.043
         upper limit
    		 0.09
    Notes
    [21] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 14
    Statistical analysis description
    FEV1 post-dose, Week 26
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.007 [22]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.099
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.028
         upper limit
    		 0.17
    Notes
    [22] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 15
    Statistical analysis description
    FEV1 post-dose, Week 39
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.248 [23]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.055
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.039
         upper limit
    		 0.148
    Notes
    [23] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 16
    Statistical analysis description
    FEV1 post-dose, Week 52
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.506 [24]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.043
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.087
         upper limit
    		 0.172
    Notes
    [24] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 17
    Statistical analysis description
    FEV6 pre-dose, Week 2
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.223 [25]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.051
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.032
         upper limit
    		 0.134
    Notes
    [25] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 18
    Statistical analysis description
    FEV6 pre-dose, Week 4
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.276 [26]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.046
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.037
         upper limit
    		 0.129
    Notes
    [26] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 19
    Statistical analysis description
    FEV6 pre-dose, Week 8
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.131 [27]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.075
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.023
         upper limit
    		 0.173
    Notes
    [27] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 20
    Statistical analysis description
    FEV6 pre-dose, Week 12
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.949 [28]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.003
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.084
         upper limit
    		 0.09
    Notes
    [28] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 21
    Statistical analysis description
    FEV6 pre-dose, Week 18
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.259 [29]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.059
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.044
         upper limit
    		 0.163
    Notes
    [29] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 22
    Statistical analysis description
    FEV6 pre-dose, Week 26
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.152 [30]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.073
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.027
         upper limit
    		 0.172
    Notes
    [30] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 23
    Statistical analysis description
    FEV6 pre-dose, Week 39
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.076 [31]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.114
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.012
         upper limit
    		 0.241
    Notes
    [31] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 24
    Statistical analysis description
    FEV6 pre-dose, Week 52
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.107 [32]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.171
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.038
         upper limit
    		 0.381
    Notes
    [32] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 25
    Statistical analysis description
    FEV6 post-dose, Week 2
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.484 [33]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.025
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.046
         upper limit
    		 0.097
    Notes
    [33] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 26
    Statistical analysis description
    FEV6 post-dose, Week 4
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.256 [34]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.037
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.027
         upper limit
    		 0.1
    Notes
    [34] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 27
    Statistical analysis description
    FEV6 post-dose, Week 8
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.184 [35]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.052
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.025
         upper limit
    		 0.128
    Notes
    [35] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 28
    Statistical analysis description
    FEV6 post-dose, Week 12
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.97 [36]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.001
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.077
         upper limit
    		 0.074
    Notes
    [36] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 29
    Statistical analysis description
    FEV6 post-dose, Week 18
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.608 [37]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.025
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.07
         upper limit
    		 0.12
    Notes
    [37] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 30
    Statistical analysis description
    FEV6 post-dose, Week 26
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.071 [38]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.084
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.007
         upper limit
    		 0.175
    Notes
    [38] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 31
    Statistical analysis description
    FEV6 post-dose, Week 39
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.622 [39]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.028
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.085
         upper limit
    		 0.141
    Notes
    [39] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 32
    Statistical analysis description
    FEV6 post-dose, Week 52
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.277 [40]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.102
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.086
         upper limit
    		 0.291
    Notes
    [40] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 33
    Statistical analysis description
    FVC Pre-dose, Week 2
    Comparison groups
    Losmapimod 15 mg v Placebo
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.241 [41]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.056
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.038
         upper limit
    		 0.15
    Notes
    [41] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 34
    Statistical analysis description
    FVC Pre-dose, Week 4
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.348 [42]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.045
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.049
         upper limit
    		 0.14
    Notes
    [42] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 35
    Statistical analysis description
    FVC Pre-dose, Week 8
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.138 [43]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.073
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.024
         upper limit
    		 0.169
    Notes
    [43] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 36
    Statistical analysis description
    FVC Pre-dose, Week 12
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.813 [44]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.012
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.111
         upper limit
    		 0.087
    Notes
    [44] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 37
    Statistical analysis description
    FVC Pre-dose, Week 18
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.172 [45]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.073
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.032
         upper limit
    		 0.177
    Notes
    [45] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 38
    Statistical analysis description
    FVC Pre-dose, Week 26
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.242 [46]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.067
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.045
         upper limit
    		 0.18
    Notes
    [46] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 39
    Statistical analysis description
    FVC Pre-dose, Week 39
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.267 [47]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.082
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.063
         upper limit
    		 0.228
    Notes
    [47] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 40
    Statistical analysis description
    FVC Pre-dose, Week 52
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.471 [48]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.083
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.143
         upper limit
    		 0.309
    Notes
    [48] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 41
    Statistical analysis description
    FVC Post-dose, Week 2
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.315 [49]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.045
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.043
         upper limit
    		 0.132
    Notes
    [49] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 42
    Statistical analysis description
    FVC Post-dose, Week 4
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.143 [50]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.054
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.018
         upper limit
    		 0.126
    Notes
    [50] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 43
    Statistical analysis description
    FVC Post-dose, Week 8
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.111 [51]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.072
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.017
         upper limit
    		 0.16
    Notes
    [51] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 44
    Statistical analysis description
    FVC Post-dose, Week 12
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.783 [52]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.012
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.075
         upper limit
    		 0.1
    Notes
    [52] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 45
    Statistical analysis description
    FVC Post-dose, Week 18
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.283 [53]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.059
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.049
         upper limit
    		 0.167
    Notes
    [53] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 46
    Statistical analysis description
    FVC Post-dose, Week 26
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.038 [54]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.138
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.008
         upper limit
    		 0.267
    Notes
    [54] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 47
    Statistical analysis description
    FVC Post-dose, Week 39
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.467 [55]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.048
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.083
         upper limit
    		 0.18
    Notes
    [55] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 48
    Statistical analysis description
    FVC Post-dose, Week 52
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.64 [56]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.042
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.138
         upper limit
    		 0.222
    Notes
    [56] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.

    Secondary: Change from Baseline in spirometry parameters in pre and post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC

    		 Close Top of page
    End point title
    		 Change from Baseline in spirometry parameters in pre and post FEV1/FVC, Percent Predicted (PP) FEV1, PP FEV6 and PP FVC
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 52
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [57]
    90 [58]
    Units: Percentage
    arithmetic mean (standard error)
        PP FVC, Week 2, n =90, 82
    0.72 ( 1.156 )
    1.31 ( 1.228 )
        PP FVC, Week 4, n =88, 81
    -0.73 ( 1.160 )
    1.72 ( 1.228 )
        PP FVC, Week 8, n =81, 78
    -2.05 ( 1.556 )
    0.47 ( 1.604 )
        PP FVC, Week 12 , n =78, 70
    -0.64 ( 1.324 )
    -0.78 ( 1.399 )
        PP FVC, Week 18, n =67, 60
    -1.58 ( 1.286 )
    1.12 ( 1.356 )
        PP FVC, Week 26, n =53, 51
    -2.81 ( 1.518 )
    1.88 ( 1.575 )
        PP FVC, Week 39, n =28, 27
    -2.06 ( 1.548 )
    1.24 ( 1.604 )
        PP FVC, Week 52, n =14, 11
    -1.24 ( 2.017 )
    0.92 ( 2.137 )
        PP FEV1, Week 2, n =90, 82
    0.28 ( 0.858 )
    2.03 ( 0.932 )
        PP FEV1, Week 4, n =88, 81
    -0.24 ( 0.877 )
    1.52 ( 0.950 )
        PP FEV1, Week 8, n =81, 78
    -1.14 ( 0.979 )
    1.04 ( 1.037 )
        PP FEV1, Week 12 , n =78, 70
    -0.10 ( 0.940 )
    0.12 ( 1.013 )
        PP FEV1, Week 18, n =67, 60
    -0.79 ( 1.094 )
    0.58 ( 1.172 )
        PP FEV1, Week 26, n =53, 51
    -2.07 ( 1.075 )
    1.26 ( 1.134 )
        PP FEV1, Week 39, n =28, 27
    -2.33 ( 1.307 )
    0.79 ( 1.370 )
        PP FEV1, Week 52, n =14, 11
    -0.32 ( 1.714 )
    2.03 ( 1.901 )
        PP FEV6, Week 2, n =87, 75
    0.63 ( 1.163 )
    3.45 ( 1.252 )
        PP FEV6, Week 4, n =84, 75
    -0.72 ( 1.135 )
    2.15 ( 1.212 )
        PP FEV6, Week 8, n =79, 74
    -1.71 ( 1.332 )
    2.04 ( 1.395 )
        PP FEV6, Week 12 , n =76, 67
    -0.42 ( 1.214 )
    -0.02 ( 1.284 )
        PP FEV6, Week 18, n =65, 56
    -1.47 ( 1.347 )
    1.87 ( 1.438 )
        PP FEV6, Week 26, n =51, 48
    -1.69 ( 1.359 )
    1.84 ( 1.436 )
        PP FEV6, Week 39, n =26, 24
    -2.10 ( 1.543 )
    2.09 ( 1.652 )
        PP FEV6, Week 52, n =13, 11
    0.99 ( 2.936 )
    3.66 ( 3.209 )
        FEV1/FVC, Pre-dose, Week 2, n =90, 83
    0.22 ( 0.571 )
    0.43 ( 0.611 )
        FEV1/FVC, Pre-dose, Week 4, n =88, 82
    0.30 ( 0.674 )
    0.43 ( 0.716 )
        FEV1/FVC, Pre-dose Week 8, n = 81, 79
    0.10 ( 0.632 )
    0.46 ( 0.663 )
        FVC, Pre-dose, Week 12, n =78, 71
    0.31 ( 0.649 )
    0.02 ( 0.688 )
        FEV1/FVC, Pre-dose Week 18, n =67, 61
    0.11 ( 0.735 )
    0.34 ( 0.780 )
        FEV1/FVC, Week 26, n=53, 52
    -0.48 ( 0.767 )
    0.84 ( 0.803 )
        FEV1/FVC, Pre-dose Week 39, n =28, 28
    -1.36 ( 0.932 )
    0.70 ( 0.963 )
        FEV1/FVC, Pre-dose Week 52, n =14, 11
    -0.18 ( 1.177 )
    1.26 ( 1.270 )
        FEV1/FVC, Post-dose Week 2, n =89, 82
    0.09 ( 0.682 )
    0.51 ( 0.726 )
        FEV1/FVC, Post-dose Week 4, n =87, 81
    -0.90 ( 0.619 )
    -0.23 ( 0.662 )
        FEV1/FVC, Post-dose Week 8, n =80, 78
    0.12 ( 0.646 )
    0.28 ( 0.679 )
        FEV1/FVC,Post-dose Week 12, n =76, 69
    -0.51 ( 0.693 )
    -0.97 ( 0.736 )
        FEV1/FVC, Post-dose Week 18, n =66, 60
    -0.65 ( 0.643 )
    -0.23 ( 0.682 )
        FEV1/FEV1/FVC, Post-dose Week 26, n=52, 51
    -0.60 ( 2.272 )
    3.23 ( 2.292 )
        FEV1/FVC, Post-dose Week 39, n =27, 27
    -1.27 ( 0.939 )
    0.18 ( 0.961 )
        FEV1/FVC, Post-dose Week 52, n =13, 10
    0.34 ( 1.280 )
    1.51 ( 1.397 )
    Notes
    [57] - mITT Population
    [58] - mITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    PP FVC, Week 2
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.661 [59]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.08
         upper limit
    		 3.27
    Notes
    [59] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    PP FVC, Week 6
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.074 [60]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.24
         upper limit
    		 5.12
    Notes
    [60] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    PP FVC, Week 8
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.21 [61]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.43
         upper limit
    		 6.46
    Notes
    [61] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    PP FVC, Week 12
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.933 [62]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 3.12
    Notes
    [62] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    PP FVC, Week 18
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.091 [63]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.43
         upper limit
    		 5.82
    Notes
    [63] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    PP FVC, Week 26
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.018 [64]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    4.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 8.56
    Notes
    [64] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    PP FVC, Week 39
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.103 [65]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.69
         upper limit
    		 7.29
    Notes
    [65] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    PP FVC, Week 52
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.448 [66]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.5
         upper limit
    		 7.82
    Notes
    [66] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    PP FEV1, Week 2
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.089 [67]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.27
         upper limit
    		 3.77
    Notes
    [67] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    PP FEV1, Week 4
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.095 [68]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.31
         upper limit
    		 3.84
    Notes
    [68] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    PP FEV1, Week 8
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.073 [69]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 4.58
    Notes
    [69] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    PP FEV1, Week 12
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.853 [70]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.08
         upper limit
    		 2.51
    Notes
    [70] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 13
    Statistical analysis description
    PP FEV1, Week 18
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.334 [71]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.43
         upper limit
    		 4.17
    Notes
    [71] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 14
    Statistical analysis description
    PP FEV1, Week 26
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.017 [72]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 6.05
    Notes
    [72] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 15
    Statistical analysis description
    PP FEV1, Week 39
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.077 [73]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.34
         upper limit
    		 6.59
    Notes
    [73] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 16
    Statistical analysis description
    PP FEV1, Week 52
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.355 [74]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 7.38
    Notes
    [74] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 17
    Statistical analysis description
    PP FEV6, Week 2
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.044 [75]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.08
         upper limit
    		 5.55
    Notes
    [75] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 18
    Statistical analysis description
    PP FEV6, Week 4
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.032 [76]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.25
         upper limit
    		 5.49
    Notes
    [76] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 19
    Statistical analysis description
    PP FEV6, Week 8
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.025 [77]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.49
         upper limit
    		 7.01
    Notes
    [77] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 20
    Statistical analysis description
    PP FEV6, Week 12
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.785 [78]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.5
         upper limit
    		 3.29
    Notes
    [78] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 21
    Statistical analysis description
    PP FEV6, Week 18
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.052 [79]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 6.7
    Notes
    [79] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 22
    Statistical analysis description
    PP FEV6, Week 26
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.041 [80]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.14
         upper limit
    		 6.92
    Notes
    [80] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 23
    Statistical analysis description
    PP FEV6, Week 39
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.043 [81]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    4.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.13
         upper limit
    		 8.25
    Notes
    [81] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 24
    Statistical analysis description
    PP FEV6, Week 52
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.562 [82]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.58
         upper limit
    		 11.92
    Notes
    [82] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 25
    Statistical analysis description
    Pre-dose FEV1/FVC, Week 2
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.746 [83]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.09
         upper limit
    		 1.52
    Notes
    [83] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 26
    Statistical analysis description
    Pre-dose FEV1/FVC, Week 4
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.878 [84]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.53
         upper limit
    		 1.79
    Notes
    [84] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 27
    Statistical analysis description
    Pre-dose FEV1/FVC, Week 8
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.644 [85]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.15
         upper limit
    		 1.85
    Notes
    [85] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 28
    Statistical analysis description
    Pre-dose FEV1/FVC, Week 12
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.715 [86]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.86
         upper limit
    		 1.28
    Notes
    [86] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 29
    Statistical analysis description
    Pre-dose FEV1/FVC, Week 18
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.803 [87]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.62
         upper limit
    		 2.1
    Notes
    [87] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 30
    Statistical analysis description
    Pre-dose FEV1/FVC, Week 26
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.184 [88]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.63
         upper limit
    		 3.27
    Notes
    [88] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 31
    Statistical analysis description
    Pre-dose FEV1/FVC, Week 39
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.102 [89]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.42
         upper limit
    		 4.52
    Notes
    [89] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 32
    Statistical analysis description
    Pre-dose FEV1/FVC, Week 52
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.383 [90]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.85
         upper limit
    		 4.73
    Notes
    [90] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 33
    Statistical analysis description
    Post-dose FEV1/FVC, Week 2
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.607 [91]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 2.06
    Notes
    [91] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 34
    Statistical analysis description
    Post-dose FEV1/FVC, Week 4
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.348 [92]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.74
         upper limit
    		 2.08
    Notes
    [92] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 35
    Statistical analysis description
    Post-dose FEV1/FVC, Week 8
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.826 [93]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.32
         upper limit
    		 1.65
    Notes
    [93] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 36
    Statistical analysis description
    Post-dose FEV1/FVC, Week 12
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.588 [94]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.13
         upper limit
    		 1.21
    Notes
    [94] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 37
    Statistical analysis description
    Post-dose FEV1/FVC, Week 18
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.585 [95]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.08
         upper limit
    		 1.91
    Notes
    [95] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 38
    Statistical analysis description
    Post-dose FEV1/FVC, Week 26
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.231 [96]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.48
         upper limit
    		 10.12
    Notes
    [96] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 39
    Statistical analysis description
    Post-dose FEV1/FVC, Week 39
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.24 [97]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.99
         upper limit
    		 3.89
    Notes
    [97] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.
    Statistical analysis title
    		 Statistical analysis 40
    Statistical analysis description
    Post-dose FEV1/FVC, Week 52
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.517 [98]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.49
         upper limit
    		 4.84
    Notes
    [98] - Analysis performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment and Baseline by visit interactions. Toeplitz structure was used.

    Secondary: Number of participants with electrocardiogram (ECG) findings

    		 Close Top of page
    End point title
    		 Number of participants with electrocardiogram (ECG) findings
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Up to 53 Weeks
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [99]
    90 [100]
    Units: Participants
        Normal-SCREENING, (n=94,90)
    49
    51
        Abnormal-NCS-SCREENING, (n=94,90)
    39
    36
        Abnormal-CS-SCREENING, (n=94,90)
    9
    5
        Normal-Baseline, (n=94,90)
    44
    54
        Abnormal-NCS-Baseline, (n=94,90)
    46
    31
        Abnormal-CS-Baseline, (n=94,90)
    4
    5
        Normal-Week 2, (n=90,84)
    40
    52
        Abnormal-NCS-Week 2, (n=90,84)
    45
    29
        Abnormal-CS-Week 2, (n=90,84)
    5
    3
        Normal-Week 4, (n=89,82)
    45
    53
        Abnormal-NCS-Week 4, (n=89,82)
    40
    27
        Abnormal-CS-Week 4, (n=89,82)
    4
    2
        Normal-Week 8, (n=80,80)
    42
    50
        Abnormal-NCS-Week 8, (n=80,80)
    35
    28
        Abnormal-CS-Week 8, (n=80,80)
    3
    2
        Normal-Week 12, (n=78,72)
    45
    42
        Abnormal-NCS-Week 12, (n=78,72)
    29
    29
        Abnormal-CS-Week 12, (n=78,72)
    4
    1
        Normal-Week 26, (n=53,52)
    31
    35
        Abnormal-NCS-Week 26, (n=53,52)
    21
    16
        Abnormal-CS-Week 26, (n=53,52)
    1
    1
        Normal-Week 39, (n=28,29)
    18
    20
        Abnormal-NCS-Week 39, (n=28,29)
    9
    8
        Abnormal-CS-Week 39, (n=28,29)
    1
    1
        Normal-Week 52, (n=14,11)
    11
    7
        Abnormal-NCS-Week 52, (n=14,11)
    2
    4
        Abnormal-CS-Week 52, (n=14,11)
    1
    0
        Normal-Follow up, (n=83,68)
    37
    42
        Abnormal-NCS-Follow up, (n=83,68)
    40
    25
        Abnormal-CS-Follow up, (n=83,68)
    6
    1
    Notes
    [99] - mITT Population
    [100] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the indicated time points

    		 Close Top of page
    End point title
    		 Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the indicated time points
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [101]
    90 [102]
    Units: Millimeter of mercury (mmHg)
    arithmetic mean (standard deviation)
        SBP, Week 2, (n=90,84)
    0.2 ( 12.00 )
    -2.9 ( 11.85 )
        SBP, Week 4, (n=89,82)
    -0.8 ( 11.49 )
    -0.4 ( 12.49 )
        SBP, Week 8, (n=81,80)
    -1.9 ( 14.53 )
    -0.3 ( 11.48 )
        SBP, Week 12, (n=78,72)
    0.5 ( 12.97 )
    -1.6 ( 13.84 )
        SBP, Week 26, (n=53,53)
    -1.5 ( 15.39 )
    -1.3 ( 13.25 )
        SBP, Week 39, (n=28,29)
    0.3 ( 16.30 )
    -3.4 ( 10.99 )
        SBP, Week 52, (n=14,11)
    6.1 ( 17.81 )
    -7.6 ( 12.89 )
        SBP, Follow up, (n=83,68)
    1.8 ( 14.46 )
    0.2 ( 13.41 )
        DBP, Week 2, (n=90,84)
    0.0 ( 7.18 )
    -3.8 ( 9.81 )
        DBP, Week 4, (n=89,82)
    -0.3 ( 8.57 )
    -2.2 ( 9.32 )
        DBP, Week 8, (n=81,80)
    -1.4 ( 8.75 )
    -1.5 ( 7.92 )
        DBP, Week 12, (n=78,72)
    1.5 ( 9.79 )
    -1.5 ( 9.59 )
        DBP, Week 26, (n=53,53)
    0.9 ( 8.33 )
    -1.2 ( 7.87 )
        DBP, Week 39, (n=28,29)
    -0.5 ( 10.40 )
    -1.9 ( 9.58 )
        DBP, Week 52, (n=14,11)
    3.4 ( 8.08 )
    -0.2 ( 8.46 )
        DBP, Follow up, (n=83,68)
    1.5 ( 10.57 )
    -1.7 ( 9.94 )
    Notes
    [101] - mITT Population
    [102] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in heart rate (HR) values at the indicated time points

    		 Close Top of page
    End point title
    		 Change from Baseline in heart rate (HR) values at the indicated time points
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [103]
    90 [104]
    Units: Beats per minute (bpm)
    arithmetic mean (standard deviation)
        HR, Week 2, (n=90,84)
    1.2 ( 7.99 )
    1.5 ( 9.92 )
        HR, Week 4, (n=89,82)
    1.4 ( 7.18 )
    0.6 ( 8.72 )
        HR, Week 8, (n=81,80)
    1.0 ( 8.39 )
    1.6 ( 9.50 )
        HR, Week 12, (n=78,72)
    3.3 ( 8.80 )
    2.2 ( 8.89 )
        HR, Week 26, (n=53,53)
    4.1 ( 10.99 )
    1.8 ( 8.32 )
        HR, Week 39, (n=28,29)
    3.3 ( 9.48 )
    4.4 ( 12.64 )
        HR, Week 52, (n=14,11)
    4.3 ( 9.55 )
    1.3 ( 8.72 )
        HR, Follow up, (n=83,68)
    3.6 ( 6.72 )
    4.2 ( 10.99 )
    Notes
    [103] - mITT Population
    [104] - mITT Population
    No statistical analyses for this end point

    Secondary: Plasma Losmapimod area under the plasma concentration time curve (AUC) from time zero to the end of dosing interval (AUC[0-tau])

    		 Close Top of page
    End point title
    		 Plasma Losmapimod area under the plasma concentration time curve (AUC) from time zero to the end of dosing interval (AUC[0-tau]) [105]
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Pre-dose at Weeks 2 and 12; pre-dose and at 2 hours post-dose at Week 26
    Notes
    [105] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Losmapimod 15 mg
    Number of subjects analysed
    85 [106]
    Units: hour (h)*nanogram (ng)/milliliter (mL)
        geometric mean (confidence interval 95%)
    668.5 (361.7 to 1235.6)
    Notes
    [106] - PK Population
    No statistical analyses for this end point

    Secondary: Plasma losmapimod maximum concentration (Cmax) and lowest concentration (Ctrough) at steady state

    		 Close Top of page
    End point title
    		 Plasma losmapimod maximum concentration (Cmax) and lowest concentration (Ctrough) at steady state [107]
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Pre-dose at Weeks 2 and 12; pre-dose and at 2 hours post-dose at Week 26
    Notes
    [107] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Losmapimod 15 mg
    Number of subjects analysed
    85 [108]
    Units: ng/ mL
    geometric mean (confidence interval 95%)
        Cmax
    49.7 (17.6 to 140.5)
        Ctrough
    23.7 (12.9 to 43.3)
    Notes
    [108] - PK Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in frequency of short acting beta-agonist or anti-cholinergic use

    		 Close Top of page
    End point title
    		 Change from Baseline in frequency of short acting beta-agonist or anti-cholinergic use
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 52
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [109]
    90 [110]
    Units: Average number of puffs per 24 hours
    arithmetic mean (standard deviation)
        Week 4; n=85, 82
    -0.0029 ( 0.73616 )
    -0.0400 ( 0.93329 )
        Week 8; n=79, 79
    0.1143 ( 0.77946 )
    -0.1473 ( 1.26462 )
        Week 12; n=76, 70
    0.0904 ( 1.06920 )
    0.0022 ( 1.10426 )
        Week 18; n=65, 61
    0.3163 ( 1.26883 )
    0.1489 ( 0.97966 )
        Week 26; n=51, 53
    0.2725 ( 1.43462 )
    0.2098 ( 1.25768 )
        Week 39; n=27, 27
    0.7109 ( 1.61447 )
    0.3418 ( 1.39346 )
        Week 52; n=14, 10
    0.4368 ( 1.22619 )
    -0.2881 ( 0.98057 )
    Notes
    [109] - mITT Population
    [110] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in St Georges Respiratory Questionnaire (SGRQ) total, SGRQ symptoms score, SGRQ activity score and SGRQ impact score over time

    		 Close Top of page
    End point title
    		 Change from Baseline in St Georges Respiratory Questionnaire (SGRQ) total, SGRQ symptoms score, SGRQ activity score and SGRQ impact score over time
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 52
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [111]
    90 [112]
    Units: Scores on a scale
    least squares mean (standard error)
        SGRQ Total, Week 12, (n=74, 71)
    -0.75 ( 1.541 )
    -1.42 ( 1.638 )
        SGRQ Total, Week 26, (n=50, 49)
    -2.20 ( 1.833 )
    -1.31 ( 1.904 )
        SGRQ Total, Week 39, (n=28, 28)
    -0.37 ( 2.451 )
    -3.19 ( 2.502 )
        SGRQ Total, Week 52, (n=14, 11)
    -2.95 ( 2.769 )
    -3.43 ( 3.098 )
        SGRQ Symptoms, Week 12, (n=78, 72)
    -2.41 ( 1.999 )
    -4.08 ( 2.115 )
        SGRQ Symptoms, Week 26, (n=52, 52)
    -5.04 ( 2.264 )
    -4.30 ( 2.335 )
        SGRQ Symptoms, Week 39, (n=28, 29)
    -4.61 ( 3.411 )
    -8.21 ( 3.370 )
        SGRQ Symptoms, Week 52, (n=14, 11)
    -3.69 ( 3.990 )
    -11.67 ( 4.296 )
        SGRQ Activity, Week 12, (n=77, 71)
    -0.08 ( 1.968 )
    1.15 ( 2.097 )
        SGRQ Activity, Week 26, (n=50, 49)
    -0.33 ( 2.217 )
    0.70 ( 2.303 )
        SGRQ Activity, Week 39, (n=28, 28)
    1.41 ( 3.027 )
    -1.00 ( 3.095 )
        SGRQ Activity, Week 52, (n=14, 11)
    -1.80 ( 3.308 )
    2.59 ( 3.650 )
        SGRQ Impact, Week 12, (n=75, 71)
    -0.53 ( 1.780 )
    -2.22 ( 1.893 )
        SGRQ Impact, Week 26, (n=52, 50)
    -1.84 ( 2.169 )
    -2.19 ( 2.255 )
        SGRQ Impact, Week 39, (n=28, 28)
    -0.59 ( 2.868 )
    -2.80 ( 2.931 )
        SGRQ Impact, Week 52, (n=14, 11)
    -2.01 ( 3.693 )
    -3.31 ( 4.099 )
    Notes
    [111] - mITT Population
    [112] - mITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    SGRQ Total, Week 12
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.706 [113]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.2
         upper limit
    		 2.85
    Notes
    [113] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    SGRQ Total, Week 26
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.694 [114]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.58
         upper limit
    		 5.36
    Notes
    [114] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    SGRQ Total, Week 39
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.382 [115]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.23
         upper limit
    		 3.58
    Notes
    [115] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    SGRQ Total, Week 52
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.903 [116]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.54
         upper limit
    		 7.57
    Notes
    [116] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    SGRQ Symptoms, Week 12
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.481 [117]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.33
         upper limit
    		 2.99
    Notes
    [117] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    SGRQ Symptoms, Week 26
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.793 [118]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.79
         upper limit
    		 6.25
    Notes
    [118] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    SGRQ Symptoms, Week 39
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.421 [119]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.45
         upper limit
    		 5.26
    Notes
    [119] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    SGRQ Symptoms, Week 52
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.162 [120]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -7.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.35
         upper limit
    		 3.4
    Notes
    [120] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    SGRQ Activity, Week 12
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.592 [121]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.31
         upper limit
    		 5.78
    Notes
    [121] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    SGRQ Activity, Week 26
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.704 [122]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.31
         upper limit
    		 6.36
    Notes
    [122] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    SGRQ Activity, Week 39
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.546 [123]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.32
         upper limit
    		 5.5
    Notes
    [123] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    SGRQ Activity, Week 52
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.35 [124]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    4.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.06
         upper limit
    		 13.84
    Notes
    [124] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 13
    Statistical analysis description
    SGRQ Impact, Week 12
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.411 [125]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.75
         upper limit
    		 2.37
    Notes
    [125] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 14
    Statistical analysis description
    SGRQ Impact, Week 26
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.896 [126]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.67
         upper limit
    		 4.97
    Notes
    [126] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 15
    Statistical analysis description
    SGRQ Impact, Week 39
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.559 [127]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.73
         upper limit
    		 5.3
    Notes
    [127] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.
    Statistical analysis title
    		 Statistical analysis 16
    Statistical analysis description
    SGRQ Impact, Week 52
    Comparison groups
    Placebo v Losmapimod 15 mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.809 [128]
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.19
         upper limit
    		 9.6
    Notes
    [128] - Analysis was performed using a mixed-effects repeated measures model with covariates of treatment, smoking status at Screening, ICS use, region, Baseline, visit, treatment by visit and Baseline by visit interactions.

    Secondary: Number of participants with abnormal liver events during the treatment period

    		 Close Top of page
    End point title
    		 Number of participants with abnormal liver events during the treatment period
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [129]
    90 [130]
    Units: Participants
    0
    0
    Notes
    [129] - mITT Population
    [130] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hemoglobin, total protein, albumin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points

    		 Close Top of page
    End point title
    		 Change from Baseline in hemoglobin, total protein, albumin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [131]
    90 [132]
    Units: Gram (G)/Liter (L)
    arithmetic mean (standard deviation)
        Hemoglobin, Week 2 (n=85,82)
    -0.3 ( 7.12 )
    0.0 ( 4.86 )
        Hemoglobin, Week 4 (n=87,80)
    -0.6 ( 7.01 )
    -1.0 ( 6.34 )
        Hemoglobin, Week 8 (n=80,77)
    -0.9 ( 8.38 )
    -2.5 ( 6.93 )
        Hemoglobin, Week 12 (n=76,70)
    -0.5 ( 7.61 )
    -1.4 ( 9.90 )
        Hemoglobin, Week 18 (n=66,61)
    0.1 ( 9.24 )
    -2.3 ( 9.66 )
        Hemoglobin, Week 26 (n=52,50)
    -0.7 ( 9.27 )
    -2.9 ( 8.86 )
        Hemoglobin, Week 39 (n=28,29)
    0.0 ( 11.71 )
    -0.1 ( 10.09 )
        Hemoglobin, Week 52 (n=14,11)
    2.9 ( 8.43 )
    -1.8 ( 7.90 )
        Hemoglobin, Follow up (n=80,67)
    -0.2 ( 9.30 )
    -4.5 ( 9.42 )
        Albumin, Week 2 (n=90,84)
    -0.3 ( 2.23 )
    -0.6 ( 2.55 )
        Albumin, Week 4 (n=88,81)
    -0.5 ( 2.35 )
    -0.3 ( 2.28 )
        Albumin, Week 8 (n=81,79)
    -1.1 ( 2.43 )
    -1.2 ( 2.38 )
        Albumin, Week 12 (n=78,72)
    -0.4 ( 2.62 )
    -0.8 ( 2.64 )
        Albumin, Week 18 (n=67,60)
    -1.1 ( 2.53 )
    -1.1 ( 2.32 )
        Albumin, Week 26 (n=53,50)
    -0.9 ( 2.89 )
    -1.1 ( 2.25 )
        Albumin, Week 39 (n=28,29)
    -0.8 ( 2.76 )
    -1.2 ( 2.35 )
        Albumin, Week 52 (n=14,11)
    -0.4 ( 2.95 )
    -1.5 ( 2.07 )
        Albumin, Follow up (n=80,68)
    -0.8 ( 2.49 )
    -1.6 ( 2.71 )
        Total protein, Week 2 (n=90,84)
    -0.4 ( 3.68 )
    -1.6 ( 2.96 )
        Total protein, Week 4 (n=88,81)
    -0.8 ( 3.93 )
    -1.2 ( 3.18 )
        Total protein, Week 8 (n=81,79)
    -1.8 ( 3.67 )
    -2.0 ( 3.01 )
        Total protein, Week 12 (n=78,72)
    -0.6 ( 4.14 )
    -0.8 ( 3.45 )
        Total protein, Week 18 (n=67,60)
    -0.8 ( 4.00 )
    -1.5 ( 2.66 )
        Total protein, Week 26 (n=53,50)
    -0.5 ( 4.59 )
    -1.5 ( 3.70 )
        Total protein, Week 39 (n=28,29)
    -0.6 ( 4.50 )
    -2.2 ( 3.51 )
        Total protein, Week 52 (n=14,11)
    -0.8 ( 4.66 )
    -3.0 ( 3.66 )
        Total protein, Follow up (n=80,68)
    -1.6 ( 4.05 )
    -2.0 ( 3.87 )
        MCHC, Week 2 (n=85,82)
    0.1 ( 6.94 )
    1.7 ( 6.40 )
        MCHC, Week 4 (n=87,80)
    0.3 ( 6.31 )
    -0.6 ( 6.80 )
        MCHC, Week 8 (n=80,77)
    -1.0 ( 7.63 )
    -0.9 ( 6.88 )
        MCHC, Week 12 (n=76,70)
    -3.1 ( 8.45 )
    -3.3 ( 10.70 )
        MCHC, Week 18 (n=66,61)
    -5.0 ( 10.38 )
    -4.8 ( 8.75 )
        MCHC, Week 26 (n=52,50)
    -4.4 ( 7.06 )
    -5.3 ( 8.48 )
        MCHC, Week 39 (n=28,29)
    -2.8 ( 5.19 )
    -1.5 ( 5.35 )
        MCHC, Week 52 (n=14,11)
    -3.9 ( 5.55 )
    -3.3 ( 6.15 )
        MCHC, Follow up (n=80,67)
    1.5 ( 9.77 )
    0.6 ( 8.73 )
    Notes
    [131] - mITT Population
    [132] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematocrit at the indicated time points

    		 Close Top of page
    End point title
    		 Change from Baseline in hematocrit at the indicated time points
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [133]
    90 [134]
    Units: Liter
    arithmetic mean (standard deviation)
        Hematocrit, Week 2 (n=85,82)
    -0.001 ( 0.0238 )
    -0.002 ( 0.0169 )
        Hematocrit, Week 4 (n=87,80)
    -0.002 ( 0.0236 )
    -0.002 ( 0.0218 )
        Hematocrit, Week 8 (n=80,77)
    -0.001 ( 0.0274 )
    -0.006 ( 0.0229 )
        Hematocrit, Week 12 (n=76,70)
    0.002 ( 0.0251 )
    0.000 ( 0.0361 )
        Hematocrit, Week 18 (n=66,61)
    0.007 ( 0.0296 )
    0.000 ( 0.0337 )
        Hematocrit, Week 26 (n=52,50)
    0.003 ( 0.0302 )
    0.000 ( 0.0318 )
        Hematocrit, Week 39 (n=28,29)
    0.003 ( 0.0373 )
    0.001 ( 0.0329 )
        Hematocrit, Week 52 (n=14,11)
    0.014 ( 0.0231 )
    -0.001 ( 0.0255 )
        Hematocrit, Follow up (n=80,67)
    -0.003 ( 0.0305 )
    -0.015 ( 0.0302 )
    Notes
    [133] - mITT Population
    [134] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in absolute white blood cell (WBC) count, total neutrophil, total lymphocyte, basophil, eosinophil, monocyte and platelet count at the indicated time point

    		 Close Top of page
    End point title
    		 Change from Baseline in absolute white blood cell (WBC) count, total neutrophil, total lymphocyte, basophil, eosinophil, monocyte and platelet count at the indicated time point
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [135]
    90 [136]
    Units: Giga cells per liter (GI/L)
    arithmetic mean (standard deviation)
        Absolute WBC count, Week 2 (n=85,82)
    -0.04 ( 1.586 )
    0.21 ( 1.710 )
        Absolute WBC count, Week 4 (n=86,80)
    0.03 ( 1.742 )
    0.12 ( 2.116 )
        Absolute WBC count, Week 8 (n=80,77)
    0.04 ( 1.474 )
    0.32 ( 1.939 )
        Absolute WBC count, Week 12 (n=76,70)
    -0.07 ( 1.628 )
    0.51 ( 1.905 )
        Absolute WBC count, Week 18 (n=66,60)
    0.29 ( 1.921 )
    0.17 ( 1.842 )
        Absolute WBC count, Week 26 (n=52,50)
    -0.07 ( 1.625 )
    0.09 ( 1.876 )
        Absolute WBC count, Week 39 (n=28,29)
    0.29 ( 1.777 )
    1.08 ( 2.857 )
        Absolute WBC count, Week 52 (n=14,11)
    0.86 ( 1.687 )
    0.75 ( 1.637 )
        Absolute WBC count, Follow up (n=79,67)
    0.73 ( 1.691 )
    0.50 ( 2.195 )
        Total neutrophils, Week 2 (n=85,82)
    -0.038 ( 1.5980 )
    -0.080 ( 1.7982 )
        Total neutrophils, Week 4 (n=86,80)
    -0.014 ( 1.7572 )
    -0.012 ( 2.0753 )
        Total neutrophils, Week 8 (n=80,77)
    -0.052 ( 1.6060 )
    0.060 ( 2.0525 )
        Total neutrophils, Week 12 (n=76,70)
    0.023 ( 1.7039 )
    0.316 ( 2.0173 )
        Total neutrophils, Week 18 (n=66,60)
    0.189 ( 1.9556 )
    -0.161 ( 1.7378 )
        Total neutrophils, Week 26 (n=52,50)
    -0.067 ( 1.4529 )
    -0.190 ( 1.8779 )
        Total neutrophils, Week 39 (n=28,29)
    0.240 ( 1.7846 )
    0.689 ( 2.9389 )
        Total neutrophils, Week 52 (n=14,11)
    1.001 ( 1.8753 )
    0.248 ( 1.4497 )
        Total neutrophils, Follow up (n=79,67)
    0.555 ( 1.7317 )
    0.309 ( 2.3168 )
        Total lymphocyte, Week 2 (n=85,82)
    0.022 ( 0.4739 )
    0.282 ( 0.7058 )
        Total lymphocyte, Week 4 (n=86,80)
    0.043 ( 0.6599 )
    0.161 ( 0.5497 )
        Total lymphocyte, Week 8 (n=80,77)
    0.089 ( 0.5532 )
    0.263 ( 0.7366 )
        Total lymphocyte, Week 12 (n=76,70)
    -0.083 ( 0.5983 )
    0.210 ( 0.6986 )
        Total lymphocyte, Week 18 (n=66,60)
    0.076 ( 0.4751 )
    0.321 ( 0.6855 )
        Total lymphocyte, Week 26 (n=52,50)
    -0.042 ( 0.6673 )
    0.296 ( 0.7236 )
        Total lymphocyte, Week 39 (n=28,29)
    0.019 ( 0.4731 )
    0.387 ( 0.6355 )
        Total lymphocyte, Week 52 (n=14,11)
    -0.107 ( 0.4707 )
    0.449 ( 0.5762 )
        Total lymphocyte, Follow up (n=79,67)
    0.100 ( 0.5969 )
    0.090 ( 0.6346 )
        Basophils, Week 2 (n=85,82)
    0.000 ( 0.0194 )
    0.002 ( 0.0290 )
        Basophils, Week 4 (n=86,80)
    -0.001 ( 0.0332 )
    -0.002 ( 0.0231 )
        Basophils, Week 8 (n=80,77)
    -0.003 ( 0.0288 )
    0.003 ( 0.0254 )
        Basophils, Week 12 (n=76,70)
    0.001 ( 0.0328 )
    0.000 ( 0.0212 )
        Basophils, Week 18 (n=66,60)
    -0.002 ( 0.0249 )
    -0.002 ( 0.0191 )
        Basophils, Week 26 (n=52,50)
    0.001 ( 0.0241 )
    -0.006 ( 0.0173 )
        Basophils, Week 39 (n=28,29)
    -0.001 ( 0.0180 )
    -0.005 ( 0.0190 )
        Basophils, Week 52 (n=14,11)
    -0.006 ( 0.0109 )
    0.000 ( 0.0184 )
        Basophils, Follow up (n=79,67)
    -0.004 ( 0.0305 )
    0.000 ( 0.0234 )
        Eosinophil, Week 2 (n=85,82)
    0.000 ( 0.0660 )
    0.025 ( 0.0941 )
        Eosinophil, Week 4 (n=86,80)
    -0.002 ( 0.1092 )
    0.013 ( 0.0713 )
        Eosinophil, Week 8 (n=80,77)
    0.008 ( 0.0948 )
    0.014 ( 0.0918 )
        Eosinophil, Week 12 (n=76,70)
    -0.001 ( 0.0817 )
    0.013 ( 0.1173 )
        Eosinophil, Week 18 (n=66,60)
    0.030 ( 0.1287 )
    0.046 ( 0.1926 )
        Eosinophil, Week 26 (n=52,50)
    0.037 ( 0.1554 )
    0.051 ( 0.1646 )
        Eosinophil, Week 39 (n=28,29)
    0.037 ( 0.0628 )
    0.028 ( 0.1035 )
        Eosinophil, Week 52 (n=14,11)
    -0.001 ( 0.0539 )
    0.006 ( 0.1688 )
        Eosinophil, Follow up (n=79,67)
    0.011 ( 0.0935 )
    0.025 ( 0.0903 )
        Monocytes, Week 2 (n=85,82)
    -0.029 ( 0.1598 )
    -0.024 ( 0.1898 )
        Monocytes, Week 4 (n=86,80)
    0.002 ( 0.1404 )
    -0.029 ( 0.1975 )
        Monocytes, Week 8 (n=80,77)
    0.001 ( 0.1785 )
    -0.014 ( 0.1653 )
        Monocytes, Week 12 (n=76,70)
    -0.007 ( 0.1709 )
    -0.026 ( 0.2145 )
        Monocytes, Week 18 (n=66,60)
    -0.010 ( 0.2023 )
    -0.025 ( 0.2235 )
        Monocytes, Week 26 (n=52,50)
    0.001 ( 0.2093 )
    -0.057 ( 0.1790 )
        Monocytes, Week 39 (n=28,29)
    -0.005 ( 0.1210 )
    -0.020 ( 0.2376 )
        Monocytes, Week 52 (n=14,11)
    -0.034 ( 0.1075 )
    0.020 ( 0.1511 )
        Monocytes, Follow up (n=79,67)
    0.071 ( 0.2319 )
    0.083 ( 0.2190 )
        Platelet count, Week 2 (n=85,82)
    -3.3 ( 45.84 )
    -2.3 ( 47.94 )
        Platelet count, Week 4 (n=87,80)
    -6.4 ( 41.43 )
    -0.4 ( 35.50 )
        Platelet count, Week 8 (n=79,77)
    -2.2 ( 40.51 )
    6.3 ( 53.31 )
        Platelet count, Week 12 (n=75,70)
    -10.0 ( 44.01 )
    5.1 ( 55.82 )
        Platelet count, Week 18 (n=66,59)
    5.3 ( 53.14 )
    3.2 ( 50.43 )
        Platelet count, Week 26 (n=52,50)
    -2.7 ( 48.66 )
    -0.4 ( 42.21 )
        Platelet count, Week 39 (n=28,29)
    -3.4 ( 35.47 )
    0.0 ( 45.29 )
        Platelet count, Week 52 (n=14,11)
    -13.6 ( 34.98 )
    -0.5 ( 30.06 )
        Platelet count, Follow up (n=80,67)
    9.7 ( 58.86 )
    10.5 ( 50.76 )
    Notes
    [135] - mITT Population
    [136] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in eosinophil percentage at the indicated time points

    		 Close Top of page
    End point title
    		 Change from Baseline in eosinophil percentage at the indicated time points
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [137]
    90 [138]
    Units: Percent change
    arithmetic mean (standard deviation)
        Eosinophil percentage, Week 2 (n=85,82)
    0.09 ( 0.969 )
    0.30 ( 0.995 )
        Eosinophil percentage, Week 4 (n=86,80)
    0.03 ( 1.583 )
    0.16 ( 0.930 )
        Eosinophil percentage, Week 8 (n=80,77)
    0.14 ( 1.419 )
    0.11 ( 1.248 )
        Eosinophil percentage, Week 12 (n=76,70)
    0.08 ( 1.087 )
    0.08 ( 1.517 )
        Eosinophil percentage, Week 18 (n=66,60)
    0.30 ( 1.513 )
    0.60 ( 2.387 )
        Eosinophil percentage, Week 26 (n=52,50)
    0.58 ( 2.390 )
    0.58 ( 2.082 )
        Eosinophil percentage, Week 39 (n=28,29)
    0.39 ( 0.865 )
    0.21 ( 1.434 )
        Eosinophil percentage, Week 52 (n=14,11)
    -0.11 ( 0.805 )
    0.05 ( 2.819 )
        Eosinophil percentage, Follow up (n=79,67)
    -0.01 ( 1.245 )
    0.29 ( 1.215 )
    Notes
    [137] - mITT Population
    [138] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in total bilirubin, direct bilirubin, uric acid and creatinine at the indicated time point

    		 Close Top of page
    End point title
    		 Change from Baseline in total bilirubin, direct bilirubin, uric acid and creatinine at the indicated time point
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [139]
    90 [140]
    Units: Micromole (UMOL)/ L
    arithmetic mean (standard deviation)
        Total bilirubin, Week 2 (n=90,84)
    -0.5 ( 3.12 )
    0.2 ( 3.62 )
        Total bilirubin, Week 4 (n=88,81)
    0.2 ( 3.07 )
    -0.1 ( 2.97 )
        Total bilirubin, Week 8 (n=81,79)
    -0.4 ( 3.03 )
    -0.7 ( 3.28 )
        Total bilirubin, Week 12 (n=78,72)
    -0.2 ( 3.33 )
    -0.1 ( 3.56 )
        Total bilirubin, Week 18 (n=67,60)
    0.0 ( 3.84 )
    0.2 ( 2.66 )
        Total bilirubin, Week 26 (n=53,50)
    0.0 ( 3.03 )
    -0.5 ( 3.05 )
        Total bilirubin, Week 39 (n=28,29)
    0.0 ( 2.06 )
    0.2 ( 3.55 )
        Total bilirubin, Week 52 (n=14,11)
    1.1 ( 3.38 )
    0.9 ( 2.91 )
        Total bilirubin, Follow up (n=80,68)
    0.2 ( 3.62 )
    -0.4 ( 2.67 )
        Direct bilirubin, Week 2 (n=90,84)
    -0.1 ( 1.09 )
    0.2 ( 1.04 )
        Direct bilirubin, Week 4 (n=88,81)
    0.1 ( 0.89 )
    0.0 ( 0.94 )
        Direct bilirubin, Week 8 (n=81,79)
    0.0 ( 0.92 )
    -0.1 ( 0.98 )
        Direct bilirubin, Week 12 (n=78,72)
    0.1 ( 0.92 )
    0.3 ( 1.17 )
        Direct bilirubin, Week 18 (n=67,60)
    0.1 ( 1.00 )
    0.2 ( 0.98 )
        Direct bilirubin, Week 26 (n=53,50)
    -0.1 ( 0.79 )
    0.0 ( 1.14 )
        Direct bilirubin, Week 39 (n=28,29)
    -0.1 ( 0.72 )
    0.1 ( 0.88 )
        Direct bilirubin, Week 52 (n=14,11)
    -0.1 ( 1.14 )
    0.1 ( 0.70 )
        Direct bilirubin, Follow up (n=80,68)
    0.1 ( 1.09 )
    0.0 ( 0.96 )
        Uric acid, Week 2 (n=90,83)
    1.7 ( 44.47 )
    -7.0 ( 45.87 )
        Uric acid, Week 4 (n=88,80)
    -3.8 ( 53.43 )
    -14.0 ( 44.47 )
        Uric acid, Week 8 (n=81,78)
    2.1 ( 47.41 )
    -12.1 ( 52.91 )
        Uric acid, Week 12 (n=78,71)
    7.5 ( 54.68 )
    -10.2 ( 62.09 )
        Uric acid, Week 18 (n=67,60)
    6.7 ( 49.87 )
    -5.9 ( 54.33 )
        Uric acid, Week 26 (n=53,50)
    0.6 ( 54.09 )
    -3.7 ( 61.19 )
        Uric acid, Week 39 (n=28,29)
    13.7 ( 50.99 )
    16.6 ( 87.59 )
        Uric acid, Week 52 (n=14,11)
    7.9 ( 48.23 )
    8.3 ( 57.49 )
        Uric acid, Follow up (n=80,67)
    -2.6 ( 62.22 )
    1.7 ( 63.56 )
        Creatinine, Week 2 (n=90,84)
    0.20 ( 7.974 )
    3.22 ( 9.140 )
        Creatinine, Week 4 (n=88,81)
    0.04 ( 7.224 )
    1.78 ( 9.899 )
        Creatinine, Week 8 (n=81,79)
    0.53 ( 11.111 )
    2.23 ( 10.424 )
        Creatinine, Week 12 (n=78,72)
    -0.11 ( 9.917 )
    3.46 ( 17.547 )
        Creatinine, Week 18 (n=67,60)
    0.41 ( 11.973 )
    5.32 ( 18.863 )
        Creatinine, Week 26 (n=53,50)
    1.61 ( 8.018 )
    1.30 ( 8.927 )
        Creatinine, Week 39 (n=28,29)
    2.16 ( 6.164 )
    5.64 ( 12.546 )
        Creatinine, Week 52 (n=14,11)
    2.94 ( 6.757 )
    0.33 ( 5.150 )
        Creatinine, Follow up (n=80,68)
    0.62 ( 12.075 )
    0.23 ( 9.463 )
    Notes
    [139] - mITT Population
    [140] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma glutamyl transferase at the indicated time points

    		 Close Top of page
    End point title
    		 Change from Baseline in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma glutamyl transferase at the indicated time points
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [141]
    90 [142]
    Units: International units (IU)/ L
    arithmetic mean (standard deviation)
        Alanine aminotransferase, Week 2 (n=90,84)
    -0.3 ( 3.78 )
    1.2 ( 5.52 )
        Alanine aminotransferase, Week 4 (n=88,81)
    1.8 ( 8.22 )
    0.3 ( 6.56 )
        Alanine aminotransferase, Week 8 (n=81,79)
    -0.3 ( 6.00 )
    -0.1 ( 6.53 )
        Alanine aminotransferase, Week 12 (n=78,72)
    1.3 ( 9.61 )
    1.7 ( 7.48 )
        Alanine aminotransferase, Week 18 (n=67,60)
    0.3 ( 8.03 )
    2.4 ( 7.67 )
        Alanine aminotransferase, Week 26 (n=53,50)
    -0.2 ( 7.88 )
    3.0 ( 10.79 )
        Alanine aminotransferase, Week 39 (n=28,29)
    3.0 ( 14.98 )
    1.9 ( 9.74 )
        Alanine aminotransferase, Week 52 (n=14,11)
    -1.1 ( 5.79 )
    1.9 ( 3.24 )
        Alanine aminotransferase, Follow up (n=80,68)
    0.7 ( 12.02 )
    0.7 ( 6.86 )
        Aspartate aminotransferase, Week 2 (n=90,84)
    -0.5 ( 3.68 )
    1.4 ( 4.25 )
        Aspartate aminotransferase, Week 4 (n=88,80)
    2.0 ( 7.65 )
    0.5 ( 5.16 )
        Aspartate aminotransferase, Week 8 (n=81,79)
    -0.4 ( 6.54 )
    0.5 ( 5.13 )
        Aspartate aminotransferase, Week 12 (n=78,72)
    2.2 ( 11.91 )
    2.0 ( 7.73 )
        Aspartate aminotransferase, Week 18 (n=67,60)
    0.9 ( 5.72 )
    2.9 ( 6.25 )
        Aspartate aminotransferase, Week 26 (n=53,49)
    0.3 ( 5.75 )
    4.7 ( 9.94 )
        Aspartate aminotransferase, Week 39 (n=28,29)
    1.3 ( 6.50 )
    2.4 ( 9.79 )
        Aspartate aminotransferase, Week 52 (n=14,11)
    -1.1 ( 9.22 )
    1.7 ( 3.23 )
        Aspartate aminotransferase, Follow up (n=80,67)
    0.3 ( 6.55 )
    0.1 ( 4.56 )
        Alkaline phosphatase, Week 2 (n=90,84)
    0.3 ( 9.14 )
    -2.0 ( 11.62 )
        Alkaline phosphatase, Week 4 (n=88,81)
    0.0 ( 10.43 )
    -2.8 ( 10.32 )
        Alkaline phosphatase, Week 8 (n=81,79)
    -2.5 ( 10.46 )
    -5.3 ( 12.71 )
        Alkaline phosphatase, Week 12 (n=78,72)
    -2.9 ( 12.67 )
    -4.7 ( 12.64 )
        Alkaline phosphatase, Week 18 (n=67,60)
    1.0 ( 9.87 )
    -4.9 ( 13.57 )
        Alkaline phosphatase, Week 26 (n=53,50)
    0.2 ( 13.06 )
    -4.4 ( 16.89 )
        Alkaline phosphatase, Week 39 (n=28,29)
    0.9 ( 9.77 )
    -4.1 ( 22.29 )
        Alkaline phosphatase, Week 52 (n=14,11)
    0.1 ( 6.39 )
    -9.5 ( 9.37 )
        Alkaline phosphatase, Follow up (n=80,68)
    -4.2 ( 15.26 )
    -4.4 ( 13.57 )
        Gamma glutamyl transferase, Week 2 (n=90,84)
    -0.3 ( 11.45 )
    -1.5 ( 16.55 )
        Gamma glutamyl transferase, Week 4 (n=88,81)
    1.4 ( 19.82 )
    -3.7 ( 19.85 )
        Gamma glutamyl transferase, Week 8 (n=81,79)
    -1.8 ( 17.32 )
    -5.3 ( 20.20 )
        Gamma glutamyl transferase, Week 12 (n=78,72)
    -0.1 ( 17.11 )
    -1.1 ( 24.97 )
        Gamma glutamyl transferase, Week 18 (n=67,60)
    0.6 ( 15.42 )
    -1.7 ( 21.15 )
        Gamma glutamyl transferase, Week 26 (n=53,50)
    -1.8 ( 13.53 )
    2.5 ( 19.87 )
        Gamma glutamyl transferase, Week 39 (n=28,29)
    -1.7 ( 10.4 )
    1.4 ( 25.46 )
        Gamma glutamyl transferase, Week 52 (n=14,11)
    -0.5 ( 13.39 )
    0.1 ( 9.06 )
        Gamma glutamyl transferase, Follow up (n=80,68)
    -2.5 ( 17.16 )
    0.1 ( 14.92 )
    Notes
    [141] - mITT Population
    [142] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in chloride, calcium, glucose, potassium, sodium and blood urea nitrogen at the indicated time points

    		 Close Top of page
    End point title
    		 Change from Baseline in chloride, calcium, glucose, potassium, sodium and blood urea nitrogen at the indicated time points
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [143]
    90 [144]
    Units: Millimole (MMOL)/L
    arithmetic mean (standard deviation)
        Chloride, Week 2 (n=90,84)
    0.3 ( 2.59 )
    0.5 ( 2.40 )
        Chloride, Week 4 (n=88,81)
    -0.2 ( 2.42 )
    1.1 ( 2.51 )
        Chloride, Week 8 (n=81,79)
    0.3 ( 2.88 )
    0.7 ( 2.85 )
        Chloride, Week 12 (n=77,72)
    0.0 ( 2.48 )
    0.2 ( 2.93 )
        Chloride, Week 18 (n=67,60)
    0.2 ( 2.73 )
    0.3 ( 2.66 )
        Chloride, Week 26 (n=53,50)
    -0.3 ( 3.35 )
    0.5 ( 2.57 )
        Chloride, Week 39 (n=28,29)
    -0.8 ( 2.45 )
    0.1 ( 2.15 )
        Chloride, Week 52 (n=14,11)
    -1.8 ( 2.12 )
    -1.4 ( 2.66 )
        Chloride, Follow up (n=80,68)
    -0.2 ( 2.87 )
    -0.5 ( 2.24 )
        Calcium, Week 2 (n=90,84)
    -0.002 ( 0.1031 )
    -0.042 ( 0.0774 )
        Calcium, Week 4 (n=88,80)
    -0.024 ( 0.1007 )
    -0.31 ( 0.0908 )
        Calcium, Week 8 (n=81,79)
    -0.017 ( 0.0934 )
    -0.039 ( 0.0843 )
        Calcium, Week 12 (n=78,72)
    -0.008 ( 0.1106 )
    -0.029 ( 0.0982 )
        Calcium, Week 18 (n=67,60)
    -0.017 ( 0.0891 )
    -0.033 ( 0.0928 )
        Calcium, Week 26 (n=53,49)
    -0.024 ( 0.0855 )
    -0.023 ( 0.1014 )
        Calcium, Week 39 (n=28,29)
    -0.017 ( 0.0922 )
    -0.032 ( 0.0927 )
        Calcium, Week 52 (n=14,11)
    0.002 ( 0.1004 )
    -0.061 ( 0.0791 )
        Calcium, Follow up (n=80,67)
    -0.018 ( 0.1042 )
    -0.010 ( 0.0959 )
        Glucose, Week 2 (n=90,84)
    -0.13 ( 1.456 )
    0.22 ( 1.619 )
        Glucose, Week 4 (n=88,81)
    -0.01 ( 1.500 )
    0.04 ( 1.204 )
        Glucose, Week 8 (n=81,79)
    0.01 ( 1.330 )
    0.28 ( 1.272 )
        Glucose, Week 12 (n=78,72)
    -0.08 ( 1.661 )
    0.24 ( 1.439 )
        Glucose, Week 18 (n=67,60)
    0.22 ( 1.607 )
    0.50 ( 1.974 )
        Glucose, Week 26 (n=53,50)
    -0.08 ( 1.518 )
    0.00 ( 1.117 )
        Glucose, Week 39 (n=28,29)
    -0.11 ( 1.553 )
    -0.16 ( 1.202 )
        Glucose, Week 52 (n=14,11)
    0.31 ( 1.075 )
    -0.09 ( 0.896 )
        Glucose, Follow up (n=80,68)
    0.20 ( 1.645 )
    0.34 ( 2.104 )
        Potassium, Week 2 (n=90,84)
    0.02 ( 0.349 )
    -0.01 ( 0.391 )
        Potassium, Week 4 (n=88,80)
    0.01 ( 0.498 )
    0.06 ( 0.393 )
        Potassium, Week 8 (n=81,79)
    0.05 ( 0.406 )
    -0.03 ( 0.306 )
        Potassium, Week 12 (n=77,72)
    0.02 ( 0.352 )
    -0.06 ( 0.354 )
        Potassium, Week 18 (n=67,60)
    0.02 ( 0.390 )
    0.14 ( 0.525 )
        Potassium, Week 26 (n=53,49)
    0.02 ( 0.309 )
    -0.02 ( 0.381 )
        Potassium, Week 39 (n=28,29)
    0.13 ( 0.395 )
    -0.03 ( 0.415 )
        Potassium, Week 52 (n=14,11)
    0.10 ( 0.390 )
    -0.13 ( 0.422 )
        Potassium, Follow up (n=80,67)
    0.01 ( 0.385 )
    -0.02 ( 0.395 )
        Sodium, Week 2 (n=90,84)
    0.1 ( 2.16 )
    -0.2 ( 2.06 )
        Sodium, Week 4 (n=88,81)
    -0.1 ( 2.18 )
    0.3 ( 2.37 )
        Sodium, Week 8 (n=81,79)
    0.0 ( 2.33 )
    -0.1 ( 2.50 )
        Sodium, Week 12 (n=77,72)
    -0.1 ( 1.96 )
    -0.4 ( 2.39 )
        Sodium, Week 18 (n=67,60)
    0.1 ( 2.80 )
    -0.7 ( 2.49 )
        Sodium, Week 26 (n=53,50)
    0.1 ( 2.92 )
    -0.2 ( 1.83 )
        Sodium, Week 39 (n=28,29)
    -0.4 ( 2.33 )
    -0.3 ( 2.18 )
        Sodium, Week 52 (n=14,11)
    -0.6 ( 1.28 )
    -0.9 ( 1.45 )
        Sodium, Follow up (n=80,68)
    -0.2 ( 2.40 )
    -0.1 ( 2.14 )
        Blood urea nitrogen, Week 2 (n=90,84)
    -0.04 ( 1.368 )
    0.46 ( 1.474 )
        Blood urea nitrogen, Week 4 (n=88,81)
    -0.21 ( 1.399 )
    0.14 ( 1.392 )
        Blood urea nitrogen, Week 8 (n=81,79)
    -0.11 ( 1.635 )
    0.15 ( 1.464 )
        Blood urea nitrogen, Week 12 (n=78,72)
    -0.12 ( 1.511 )
    0.62 ( 1.993 )
        Blood urea nitrogen, Week 18 (n=67,60)
    -0.41 ( 1.332 )
    0.72 ( 2.310 )
        Blood urea nitrogen, Week 26 (n=53,50)
    -0.34 ( 1.267 )
    0.24 ( 1.636 )
        Blood urea nitrogen, Week 39 (n=28,29)
    -0.26 ( 1.385 )
    0.62 ( 1.680 )
        Blood urea nitrogen, Week 52 (n=14,11)
    0.01 ( 0.975 )
    1.07 ( 1.209 )
        Blood urea nitrogen, Follow up (n=80,68)
    0.07 ( 1.577 )
    0.11 ( 1.545 )
    Notes
    [143] - mITT Population
    [144] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in Red blood cell count at the indicated time points

    		 Close Top of page
    End point title
    		 Change from Baseline in Red blood cell count at the indicated time points
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [145]
    90 [146]
    Units: Trillion cells per liter (TI/L)
    arithmetic mean (standard deviation)
        Red blood cell count, Week 2 (n=85,82)
    -0.01 ( 0.248 )
    0.00 ( 0.183 )
        Red blood cell count, Week 4 (n=87,80)
    -0.03 ( 0.242 )
    -0.02 ( 0.219 )
        Red blood cell count, Week 8 (n=80,77)
    -0.03 ( 0.281 )
    -0.05 ( 0.205 )
        Red blood cell count, Week 12 (n=76,70)
    0.02 ( 0.278 )
    0.02 ( 0.328 )
        Red blood cell count, Week 18 (n=66,61)
    0.04 ( 0.341 )
    0.00 ( 0.287 )
        Red blood cell count, Week 26 (n=52,50)
    0.01 ( 0.318 )
    -0.02 ( 0.268 )
        Red blood cell count, Week 39 (n=28,29)
    0.08 ( 0.352 )
    0.09 ( 0.265 )
        Red blood cell count, Week 52 (n=14,11)
    0.23 ( 0.320 )
    0.01 ( 0.230 )
        Red blood cell count, Follow up (n=80,67)
    0.06 ( 0.354 )
    -0.04 ( 0.280 )
    Notes
    [145] - mITT Population
    [146] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in mean corpuscle hemoglobin at the indicated time points

    		 Close Top of page
    End point title
    		 Change from Baseline in mean corpuscle hemoglobin at the indicated time points
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [147]
    90 [148]
    Units: Picograms
    arithmetic mean (standard deviation)
        Mean corpuscle hemoglobin, Week 2 (n=85,82)
    0.02 ( 0.551 )
    0.03 ( 0.701 )
        Mean corpuscle hemoglobin, Week 4 (n=87,80)
    0.09 ( 0.516 )
    -0.04 ( 0.480 )
        Mean corpuscle hemoglobin, Week 8 (n=80,77)
    0.02 ( 0.801 )
    -0.20 ( 0.700 )
        Mean corpuscle hemoglobin, Week 12 (n=76,70)
    -0.22 ( 0.773 )
    -0.46 ( 0.964 )
        Mean corpuscle hemoglobin, Week 18 (n=66,61)
    -0.27 ( 1.167 )
    -0.52 ( 0.944 )
        Mean corpuscle hemoglobin, Week 26 (n=52,50)
    -0.25 ( 0.692 )
    -0.48 ( 0.983 )
        Mean corpuscle hemoglobin, Week 39 (n=28,29)
    -0.55 ( 1.121 )
    -0.60 ( 1.100 )
        Mean corpuscle hemoglobin, Week 52 (n=14,11)
    -0.72 ( 1.022 )
    -0.32 ( 0.676 )
        Mean corpuscle hemoglobin, Follow up (n=80,67)
    -0.46 ( 1.130 )
    -0.73 ( 1.279 )
    Notes
    [147] - mITT Population
    [148] - mITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in mean corpuscle volume at the indicated time points

    		 Close Top of page
    End point title
    		 Change from Baseline in mean corpuscle volume at the indicated time points
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 53
    End point values
    		 Placebo Losmapimod 15 mg
    Number of subjects analysed
    94 [149]
    90 [150]
    Units: Femtoliters
    arithmetic mean (standard deviation)
        Mean corpuscle volume, Week 2 (n=85,82)
    0.0 ( 1.72 )
    -0.4 ( 1.97 )
        Mean corpuscle volume, Week 4 (n=87,80)
    0.1 ( 1.66 )
    0.1 ( 1.88 )
        Mean corpuscle volume, Week 8 (n=80,77)
    0.2 ( 2.49 )
    -0.4 ( 2.11 )
        Mean corpuscle volume, Week 12 (n=76,70)
    0.3 ( 2.29 )
    -0.4 ( 2.45 )
        Mean corpuscle volume, Week 18 (n=66,61)
    0.6 ( 2.85 )
    -0.1 ( 3.12 )
        Mean corpuscle volume, Week 26 (n=52,50)
    0.5 ( 2.34 )
    0.2 ( 3.07 )
        Mean corpuscle volume, Week 39 (n=28,29)
    -1.0 ( 3.50 )
    -1.4 ( 3.82 )
        Mean corpuscle volume, Week 52 (n=14,11)
    -1.4 ( 3.15 )
    0.0 ( 2.05 )
        Mean corpuscle volume, Follow up (n=80,67)
    -1.9 ( 2.73 )
    -2.4 ( 3.36 )
    Notes
    [149] - mITT Population
    [150] - mITT Population
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    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.
    Adverse event reporting additional description
    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.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 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.

    Reporting group title
    Losmapimod 15mg
    Reporting group description
    		 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.

    Serious adverse events
    		 Placebo Losmapimod 15mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 94 (8.51%)
    19 / 90 (21.11%)
         number of deaths (all causes)
    1
    3
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bile duct cancer
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastric cancer
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm rupture
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac disorders
    Coronary artery disease
         subjects affected / exposed
    0 / 94 (0.00%)
    2 / 90 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Myocardial infarction
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness unilateral
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ileal ulcer
         subjects affected / exposed
    1 / 94 (1.06%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 94 (2.13%)
    7 / 90 (7.78%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Psoriasis
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 94 (1.06%)
    4 / 90 (4.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 94 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Losmapimod 15mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 94 (9.57%)
    13 / 90 (14.44%)
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    9 / 94 (9.57%)
    13 / 90 (14.44%)
         occurrences all number
    13
    20

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 02 21:27:25 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA