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    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
    		 v2
    This version publication date
    03 Mar 2018
    First version publication date
    08 Mar 2017
    Other versions
    		 v1 , v3
    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

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    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. were enrolled in study. 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
    		 Subject, Investigator, Carer

    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
         Consent withdrawn by subject
    1
    4
         Physician decision
    1
    1
         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

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    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
    Units: Subjects
        Japanese/East Asian /South East Asian Heritage
    		 10 9 19
        White
    		 84 81 165

    End points

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    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

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    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

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    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)

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    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).

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    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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-effects repeated measures (MERM) 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
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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

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    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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
    		 MERM Model
    Parameter type
    		 Mean difference (final values)
    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

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    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 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=90,90)
    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

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    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. 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

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    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. 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])

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    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
    Weeks 2, 12 and 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

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    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
    Weeks 2, 12 and 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

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    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

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    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
    The total and component SGRQ-C Scores (Activity, Symptoms, Impacts) were calculated at Weeks 0, 12, 26, 39 and 52. 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 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. SGRQ-C was transformed to SGRQ for reporting. 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. Analysis performed using a mixed-effects repeated measures model. Par. were included in the analysis if they had at least one post-baseline measurement. 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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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 (final values)
    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

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    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

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    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

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    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

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    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 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

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    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 of eosinophil percentage
    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

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    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

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    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

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    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

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    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 (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

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    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

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    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: Picograms
    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

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    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

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    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.

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