Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A two part, Phase IIa, randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical efficacy of oral danirixin (GSK1325756) in symptomatic COPD subjects with mild to moderate airflow limitation at risk for exacerbations

    Summary
    EudraCT number
    		 2013-003510-41
    Trial protocol
    		 DE  
    Global end of trial date
    29 Aug 2016

    Results information
    Results version number
    		 v2(current)
    This version publication date
    23 Jul 2017
    First version publication date
    20 Apr 2017
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    200163
    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
    14 Feb 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Aug 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Main objective of the trial: Primary-Part A & Part B: To evaluate the safety and tolerability of danirixin compared with placebo in symptomatic COPD subjects with mild to moderate airflow limitation Primary -Part A: To characterize the pharmacokinetics of danirixin in symptomatic COPD subjects with mild to moderate airflow limitation Primary-Part B: To characterize the effect of danirixin compared with placebo on the incidence and severity of respiratory symptoms and COPD exacerbations in symptomatic COPD subjects with mild to moderate airflow limitation
    Protection of trial subjects
    Not Applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Feb 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
    Germany: 90
    Country: Number of subjects enrolled
    United States: 12
    Worldwide total number of subjects
    102
    EEA total number of subjects
    90
    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)
    68
    From 65 to 84 years
    34
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This was a 2 part study. In Part A, an open label, single arm, participants (par.) received danrixin 50 milligrams (mg) twice daily (BID) for 2 weeks. In Part B, a randomized (1:1), double-blind (sponsor unblinded) placebo controlled on top of standard of care study, par. received DNX 75 mg BID in one arm and placebo in the other arm for 52 weeks.

    Pre-assignment
    Screening details
    		 A total of 19 par. in Part A were screened (10 failed) and 9 were randomized in a 2-week treatment period (TP) followed by a follow-up visit (FU) at 7- 14 days after last dose. A total of 127 par. in Part B were screened (34 failed) and 93 were randomized in a 52-week TP followed by a FU at 14- 28 days after last dose of the study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant’s current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
    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
    Participants received one tablet of placebo twice daily for 52 weeks in Part B of the study

    Arm title
    		 DNX 75 mg
    Arm description
    		 Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant’s current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Danirixin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received one immediate release tablet of danirixin 75 mg twice daily for 52 weeks in Part B of the study.

    Number of subjects in period 1 [1]
    		Placebo DNX 75 mg
    Started
    48
    45
    Completed
    38
    37
    Not completed
    10
    8
         Consent withdrawn by subject
    3
    3
         Physician decision
    -
    1
         Adverse event, non-fatal
    5
    3
         Protocol deviation
    2
    1
    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: A total of 19 par. in Part A were screened (10 failed) and 9 were randomized in a 2-week treatment period (TP) followed by a follow-up visit (FU) at 7- 14 days after last dose. A total of 127 par. in Part B were screened (34 failed) and 93 were randomized in a 52-week TP followed by a FU at 14- 28 days after last dose of the study.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant’s current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).

    Reporting group title
    DNX 75 mg
    Reporting group description
    		 Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant’s current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).

    Reporting group values
    		 Placebo DNX 75 mg Total
    Number of subjects
    		 48 45
    Age categorical
    Units: Subjects
    Age continuous
    Data for Part B is presented.
    Units: years
        arithmetic mean (standard deviation)
    		 58.8 ± 7.32 62.4 ± 6.91 -
    Gender categorical
    Gender categorical description
    Units: Subjects
        Female
    		 25 23 48
        Male
    		 23 22 45
    Race/Ethnicity, Customized
    Units: Subjects
        African American/African Heritage
    		 1 0 1
        White - White/Caucasian/European Heritage
    		 47 45 92

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant’s current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).

    Reporting group title
    DNX 75 mg
    Reporting group description
    		 Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant’s current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).

    Subject analysis set title
    DNX 50 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant’s current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).

    Subject analysis set title
    DNX 75 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant’s current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).

    Primary: Number of participants with any adverse event (AE) and, serious adverse event (SAE) in Part A

    		 Close Top of page
    End point title
    		 Number of participants with any adverse event (AE) and, serious adverse event (SAE) in Part A [1]
    End point description
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, 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 that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention, events associated with liver injury and impaired liver function were categorized as SAE. Participants with any AE or SAE were summarized. Participants with AE or SAE occurrences >= 5 percent were summarized. All Subjects Population comprised of all participants who were screened and for whom a record existed on the study database.
    End point type
    Primary
    End point timeframe
    Up to Day 28 in Part A
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [2]
    Units: Participants
        AE
    5
        SAEs
    1
    Notes
    [2] - All Subjects Population
    No statistical analyses for this end point

    Primary: Number of participants with any AE and SAE in Part B

    		 Close Top of page
    End point title
    		 Number of participants with any AE and SAE in Part B [3]
    End point description
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, 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 that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention, events associated with liver injury and impaired liver function were categorized as SAE. Participants with AE or SAE occurrences >= 5 percent were summarized.
    End point type
    Primary
    End point timeframe
    Up to Day 392 in Part B
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [4]
    45 [5]
    Units: Participants
        AE
    25
    25
        SAEs
    10
    10
    Notes
    [4] - All Subjects Population
    [5] - All Subjects Population
    No statistical analyses for this end point

    Primary: Number of participants with systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, respiratory rate and body temperature abnormalities of potential clinical importance in Part A

    		 Close Top of page
    End point title
    		 Number of participants with systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, respiratory rate and body temperature abnormalities of potential clinical importance in Part A [6]
    End point description
    Vital signs including SBP, DBP, pulse rate, respiratory rate and body temperature were taken on Day 1 pre-dose and on Day 14 and at Follow-up (Day 21 to 28) in Part A. Measurements were obtained in a semi-supine/ supine position after 5 minutes rest. The mean of replicate assessments at any given time point was used as the value for that time point. SBP <90 or >160 millimeter of mercury (mmHg); DBP <40 or >110 mmHg, pulse rate <35 or >120 beats per minute (bpm) and respiratory rate <8 or >30 breaths per minute were considered as values of potential clinical importance and were presented as 'High' or 'Low' values. Intent-to-Treat (ITT) Population comprised of all randomized par. who received at least one dose of study medication.
    End point type
    Primary
    End point timeframe
    Up to Day 28 in Part A
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [7]
    Units: Participants
        SBP, Day 14, low
    0
        SBP, Day 14, high
    2
        DBP, Day 14, low
    0
        DBP, Day 14, high
    1
    Notes
    [7] - ITT Population
    No statistical analyses for this end point

    Primary: Number of participants with systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate and respiratory rate abnormalities of potential clinical importance in Part B

    		 Close Top of page
    End point title
    		 Number of participants with systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate and respiratory rate abnormalities of potential clinical importance in Part B [8]
    End point description
    Vital signs including SBP, DBP, pulse rate and respiratory rate were taken on Day 1 pre-dose and on Day 28, 56, 112, 168, 280, 364 and at Follow-up (Day 378 to 392) in Part B. Measurements were obtained in a semi-supine/ supine position after 5 minutes rest. The mean of replicate assessments at any given time point was used as the value for that time point. SBP <90 or >160 mmHg, DBP <40 or >110 mmHg, pulse rate <35 or >120 bpm and respiratory rate <8 or >30 breaths per minute were considered as values of potential clinical importance and were presented as 'High' or 'Low' values. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
    End point type
    Primary
    End point timeframe
    Up to Day 392 in Part B
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [9]
    45 [10]
    Units: Participants
        SBP, Day 1, low, n=48, 45
    0
    0
        SBP, Day 1, high, n=48, 45
    0
    2
        SBP, Day 28, low, n=47, 44
    0
    0
        SBP, Day 28, high, n=47, 44
    0
    3
        SBP, Day 56, low, n=46, 41
    0
    0
        SBP, Day 56, high, n=46, 41
    2
    2
        SBP, Day 112, low, n=46, 40
    0
    0
        SBP, Day 112, high, n=46, 40
    3
    2
        SBP, Day 168, low, n=44, 39
    0
    0
        SBP, Day 168, high, n=44, 39
    2
    3
        SBP, Day 280, low, n=39, 37
    1
    0
        SBP, Day 280, high, n=39, 37
    2
    2
        SBP, Day 364, low, n=39, 37
    0
    0
        SBP, Day 364, high, n=39, 37
    1
    4
        DBP, Day 280, low, n=39, 37
    0
    0
        DBP, Day 280, high, n=39, 37
    1
    0
        Respiratory rate, Day 1, low, n=48, 45
    1
    0
        Respiratory rate, Day 1, high, n=48, 45
    1
    0
        Respiratory rate, Day 56, low, n=46, 41
    0
    0
        Respiratory rate, Day 56, high, n=46, 41
    2
    0
        Respiratory rate, Day 112, low, n=46, 40
    1
    0
        Respiratory rate, Day 112, high, n=46, 40
    0
    0
        Respiratory rate, Day 168, low, n=44, 39
    0
    0
        Respiratory rate, Day 168, high, n=44, 39
    0
    1
    Notes
    [9] - ITT Population
    [10] - ITT Population
    No statistical analyses for this end point

    Primary: Number of participants with abnormal 12-lead electrocardiogram (ECG) in Part A

    		 Close Top of page
    End point title
    		 Number of participants with abnormal 12-lead electrocardiogram (ECG) in Part A [11]
    End point description
    12-lead ECG was taken on Day 1 pre-dose and on Follow-up visit (Day 21 to 28) in Part A using an ECG machine. Triplicate reading were taken on Day 1 pre-dose. Participants with abnormal-clinically not significant (NCS) and abnormal-clinically significant (CS) findings were sumarized.
    End point type
    Primary
    End point timeframe
    Up to Day 28 in Part A
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [12]
    Units: Participants
        Abnormal-NCS, Day 1, pre-dose
    3
        Abnormal-CS, Day 1, pre-dose
    0
        Abnormal-NCS, Day 1, pre-dose 2
    2
        Abnormal-CS, Day 1, pre-dose 2
    0
        Abnormal-NCS, Day 1, pre-dose 3
    2
        Abnormal-CS, Day 1, pre-dose 3
    0
    Notes
    [12] - ITT Population
    No statistical analyses for this end point

    Primary: Number of participants with abnormal 12-lead ECG in Part B

    		 Close Top of page
    End point title
    		 Number of participants with abnormal 12-lead ECG in Part B [13]
    End point description
    12-lead ECG was taken on Day 1 pre-dose and on Day 28, 168 and at Follow-up (Day 378 to 392) in Part B using an ECG machine. Participants with abnormal-NCS and abnormal-CS findings were sumarized. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
    End point type
    Primary
    End point timeframe
    Up to Day 392 in Part B
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [14]
    45 [15]
    Units: Participants
        Abnormal-NCS, Day 28, n=47, 44
    20
    16
        Abnormal-CS, Day 28, n=47, 44
    0
    1
        Abnormal-NCS, Day 168, n=44, 38
    15
    11
        Abnormal-CS, Day 168, n=44, 38
    0
    0
    Notes
    [14] - ITT Population
    [15] - ITT Population
    No statistical analyses for this end point

    Primary: Number of participants with hematology values of potential clinical importance in Part A

    		 Close Top of page
    End point title
    		 Number of participants with hematology values of potential clinical importance in Part A [16]
    End point description
    Blood samples were collected at Screening and Day 14 in Part A to evaluate hematology parameters which included hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), red blood cell (RBC) count, white blood cell (WBC) count, platelet count and reticulocyte count. Hematology values of potential clinical importance were presented as 'High' or 'Low' values based on the reference laboratory standards.
    End point type
    Primary
    End point timeframe
    Up to Day 28 in Part A
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [17]
    Units: Participants
        RBC count, Day 14, low
    1
        Category title 2. RBC count, Day 14, high
    0
    Notes
    [17] - ITT Population
    No statistical analyses for this end point

    Primary: Number of participants with hematology values of potential clinical importance in Part B

    		 Close Top of page
    End point title
    		 Number of participants with hematology values of potential clinical importance in Part B [18]
    End point description
    Blood samples were collected at Screening and on Day 28, 168, and 364 in Part B to evaluate hematology parameters which included hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, MCHC, MCH, MCV, RBC count, WBC count, platelet count and reticulocyte count. Hematology values of potential clinical importance were presented as 'High' or 'Low' values based on the reference laboratory standards. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
    End point type
    Primary
    End point timeframe
    Up to Day 392 in Part B
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [19]
    45 [20]
    Units: Participants
        Platelet count, Day 28, low, n=46, 43
    0
    1
        Platelet count, Day 28, high, n=46, 43
    0
    0
        RBC count, Day 28, low, n=46, 43
    0
    1
        RBC count, Day 28, high, n=46, 43
    0
    0
        Platelet count, Day 168, low, n=43, 38
    0
    1
        Platelet count, Day 168, high, n=43, 38
    1
    0
        RBC count, Day 168, low, n=44, 38
    2
    1
        RBC count, Day 168, high, n=44, 38
    0
    0
        WBC count, Day 168, low, n=44, 38
    0
    0
        WBC count, Day 168, high, n=44, 38
    1
    0
        Platelet count, Day 364, low, n=39, 36
    0
    1
        Platelet count, Day 364, high, n=39, 36
    0
    0
        RBC count, Day 364, low, n=39, 36
    2
    1
        RBC count, Day 364, high, n=39, 36
    0
    0
    Notes
    [19] - ITT Population
    [20] - ITT Population
    No statistical analyses for this end point

    Primary: Number of participants with clinical chemistry values of potential clinical importance in Part A

    		 Close Top of page
    End point title
    		 Number of participants with clinical chemistry values of potential clinical importance in Part A [21]
    End point description
    Blood samples were collected at Screening and Day 14 in Part A to evaluate clinical chemistry parameters which included alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin, calcium, bicarbonate, chloride, creatinine, direct bilirubin, gamma glutamyl transferase (GGT), glucose, potassium, total protein, sodium, blood urea nitrogen (BUN) and uric acid. Additional liver monitoring chemistry (ALT, AST, ALP and total and direct bilirubin) was done on Day 1 pre-dose. Clinical chemistry values of potential clinical importance were presented as 'High' or 'Low' values based on the reference laboratory standards.
    End point type
    Primary
    End point timeframe
    Up to Day 28 in Part A
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [22]
    Units: Participants
        GGT, Day 14, low
    0
        GGT, Day 14, high
    2
        Uric acid, Day 14, low
    0
        Uric acid, Day 14, high
    8
    Notes
    [22] - ITT Population
    No statistical analyses for this end point

    Primary: Number of participants with clinical chemistry values of potential clinical importance in Part B

    		 Close Top of page
    End point title
    		 Number of participants with clinical chemistry values of potential clinical importance in Part B [23]
    End point description
    Blood samples were collected at Screening and on Day 28, 168 and 364 in Part B to evaluate clinical chemistry parameters which included ALT, albumin, ALP, AST, total bilirubin, calcium, bicarbonate, chloride, creatinine, direct bilirubin, GGT, glucose, potassium, total protein, sodium, BUN and uric acid. Additional liver monitoring chemistry (ALT, AST, ALP and total and direct bilirubin) was done on Day 14, 56, 84, 224 and 280. Clinical chemistry values of potential clinical importance were presented as 'High' or 'Low' values based on the reference laboratory standards. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
    End point type
    Primary
    End point timeframe
    Up to Day 392 in Part B
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [24]
    45 [25]
    Units: Participants
        Creatinine, Day 28, low, n=47, 44
    0
    0
        Creatinine, Day 28, high, n=47, 44
    0
    1
        GGT, Day 28, low, n=47, 44
    0
    0
        GGT, Day 28, high, n=47, 44
    7
    3
        Uric acid, Day 28, low, n=47, 44
    0
    0
        Uric acid, Day 28, high, n=47, 44
    47
    44
        ALP, Day 84, low, n=46, 40
    0
    0
        ALP, Day 84, high, n=46, 40
    0
    1
        ALT, Day 84, low, n=46, 40
    0
    0
        ALT, Day 84, high, n=46, 40
    0
    1
        AST, Day 84, low, n=46, 40
    0
    0
        AST, Day 84, high, n=46, 40
    0
    1
        GGT, Day 168, low, n=43, 39
    0
    0
        GGT, Day 168, high, n=43, 39
    5
    1
        Uric acid, Day 168, low, n=43, 39
    0
    0
        Uric acid, Day 168, high, n=43, 39
    43
    39
        Direct bilirubin, Day 364, low, n=39, 37
    0
    0
        Direct bilirubin, Day 364, high, n=39, 37
    1
    0
        Total bilirubin, Day 364, low, n=39, 37
    0
    0
        Total bilirubin, Day 364, high, n=39, 37
    1
    0
        GGT, Day 364, low, n=39, 37
    0
    0
        GGT, Day 364, high, n=39, 37
    5
    1
        Uric acid, Day 364, low, n=39, 37
    0
    0
        Uric acid, Day 364, high, n=39, 37
    39
    37
    Notes
    [24] - ITT Population
    [25] - ITT Population
    No statistical analyses for this end point

    Primary: Number of participants with urinalysis dipstick results in Part A

    		 Close Top of page
    End point title
    		 Number of participants with urinalysis dipstick results in Part A [26]
    End point description
    Test strip urinalysis was done for glucose, ketones, occult blood and protein at Screening and Day 14 in Part A. Results were presented as negative, trace, 1+, 2+ and 3+ for glucose, ketones, occult blood and protein. Urine microscopic examination was done if urine blood or protein was found abnormal. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Primary
    End point timeframe
    Up to Day 28 in Part A
    Notes
    [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [27]
    Units: Participants
        Occult blood, Day 14, negative, n=9
    9
        Glucose, Day 14, negative, n=9
    9
        Ketones, Day 14, negative, n=9
    9
        Protein, Day 14, 1+, n=9
    1
        Protein, Day 14, negative, n=9
    8
        Urine microscopy-RBC, Day 14, not seen, n=1
    1
        Urine microscopy-WBC, Day 14, not seen, n=1
    1
    Notes
    [27] - ITT Population
    No statistical analyses for this end point

    Primary: Number of participants with urinalysis dipstick results in Part B

    		 Close Top of page
    End point title
    		 Number of participants with urinalysis dipstick results in Part B [28]
    End point description
    Test strip urinalysis was done for glucose, ketones, occult blood and protein at Screening and on Day 28, 168, 224 and 364 in Part B. Results were presented as negative, trace, 1+, 2+ and 3+ for glucose, ketones, occult blood and protein. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
    End point type
    Primary
    End point timeframe
    Up to Day 392 in Part B
    Notes
    [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [29]
    45 [30]
    Units: Participants
        Occult blood, Day 28, trace, n=47, 44
    0
    2
        Occult blood, Day 28, 1+, n=47, 44
    3
    0
        Occult blood, Day 28, negative, n=47, 44
    44
    42
        Glucose, Day 28, trace, n=47, 44
    0
    1
        Glucose, Day 28, 1+, n=47, 44
    1
    0
        Glucose, Day 28, 3+, n=47, 44
    0
    2
        Glucose, Day 28, negative, n=47, 44
    46
    41
        Ketones, Day 28, trace, n=47, 44
    3
    2
        Ketones, Day 28, negative, n=47, 44
    44
    42
        Protein, Day 28, trace, n=47, 44
    2
    1
        Protein, Day 28, 1+, n=47, 44
    2
    2
        Protein, Day 28, negative, n=47, 44
    43
    41
        Occult blood, Day 168, trace, n=42, 36
    3
    2
        Occult blood, Day 168, 1+, n=42, 36
    1
    1
        Occult blood, Day 168, 3+, n=42, 36
    1
    0
        Occult blood, Day 168, negative, n=42, 36
    37
    33
        Glucose, Day 168, 2+, n=42, 36
    1
    0
        Glucose, Day 168, negative, n=42, 36
    41
    36
        Ketones, Day 168, trace, n=42, 36
    3
    0
        Ketones, Day 168, negative, n=42, 36
    39
    36
        Protein, Day 168, trace, n=42, 36
    2
    1
        Protein, Day 168, 1+, n=42, 36
    1
    2
        Protein, Day 168, 2+, n=42, 36
    1
    0
        Protein, Day 168, negative, n=42, 36
    38
    33
        Occult blood, Day 224, negative, n=1, 0
    1
    0
        Glucose, Day 224, negative, n=1, 0
    1
    0
        Ketones, Day 224, negative, n=1, 0
    1
    0
        Protein, Day 224, negative, n=1, 0
    1
    0
        Occult blood, Day 364, trace, n=38, 36
    3
    2
        Occult blood, Day 364, 1+, n=38, 36
    2
    1
        Occult blood, Day 364, negative, n=38, 36
    33
    33
        Glucose, Day 364, trace, n=38, 36
    1
    0
        Glucose, Day 364, 2+, n=38, 36
    1
    0
        Glucose, Day 364, negative, n=38, 36
    36
    36
        Ketones, Day 364, trace, n=38, 36
    3
    0
        Ketones, Day 364, negative, n=38, 36
    35
    36
        Protein, Day 364, trace, n=38, 36
    3
    0
        Protein, Day 364, 1+, n=38, 36
    1
    2
        Protein, Day 364, 2+, n=38, 36
    1
    1
        Protein, Day 364, negative, n=38, 36
    33
    33
    Notes
    [29] - ITT Population
    [30] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in urine power of hydrogen (pH) at Day 14 in Part A

    		 Close Top of page
    End point title
    		 Change from Baseline in urine power of hydrogen (pH) at Day 14 in Part A [31]
    End point description
    Urinalysis including urine pH was done at Screening and Day 14 in Part A. Baseline was considered as the measurement obtained at Screening (Day -1). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
    End point type
    Primary
    End point timeframe
    Up to Day 28 in Part A
    Notes
    [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [32]
    Units: pH
        arithmetic mean (standard deviation)
    -0.06 ± 1.488
    Notes
    [32] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in urine pH in Part B

    		 Close Top of page
    End point title
    		 Change from Baseline in urine pH in Part B [33]
    End point description
    Urinalysis including urine pH was done at Screening and on Day 28, 168 and 364 in Part B. Baseline was considered as the measurement obtained at Screening (Day -1). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
    End point type
    Primary
    End point timeframe
    Up to Day 392 in Part B
    Notes
    [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [34]
    45 [35]
    Units: pH
    arithmetic mean (standard deviation)
        Day 28, n=45, 43
    -0.17 ± 0.648
    -0.1 ± 0.552
        Day 168, n=40, 35
    -0.18 ± 0.694
    -0.13 ± 0.751
        Day 364, n=36, 35
    -0.29 ± 0.731
    -0.07 ± 0.768
    Notes
    [34] - ITT Population
    [35] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in urine specific gravity of urine in Part A

    		 Close Top of page
    End point title
    		 Change from Baseline in urine specific gravity of urine in Part A [36]
    End point description
    Urinalysis including urine specific gravity was done at Screening and Day 14 in Part A. Baseline was considered as the measurement obtained at Screening (Day -1). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
    End point type
    Primary
    End point timeframe
    Up to Day 28 in Part A
    Notes
    [36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [37]
    Units: Urine specific gravity
        arithmetic mean (standard deviation)
    -0.0008 ± 0.00817
    Notes
    [37] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in urine specific gravity of urine in Part B

    		 Close Top of page
    End point title
    		 Change from Baseline in urine specific gravity of urine in Part B [38]
    End point description
    Urinalysis including urine specific gravity was done at Screening and on Day 28, 168 and 364 in Part B. Baseline was considered as the measurement obtained at Screening (Day -1). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
    End point type
    Primary
    End point timeframe
    Up to Day 392 in Part B
    Notes
    [38] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [39]
    45 [40]
    Units: Urine specific gravity
    arithmetic mean (standard deviation)
        Day 28, n=45, 43
    -0.0011 ± 0.00643
    -0.0008 ± 0.00536
        Day 168, n=40, 35
    -0.0012 ± 0.00771
    -0.0002 ± 0.00748
        Day 364, n=36, 35
    0.0004 ± 0.00569
    0.0013 ± 0.00561
    Notes
    [39] - ITT Population
    [40] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at the indicated time points in Part A

    		 Close Top of page
    End point title
    		 Change from Baseline in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at the indicated time points in Part A [41]
    End point description
    FEV1 measures how much air a person can exhale during a forced breath in 1 second. FVC is the total amount of air exhaled during the FEV test. FEV1 and FVC were performed at Screening and on Day 1, 14 and at Follow-up visit (Day 21 to 28). FEV1 and FVC assessments at each time point (post-bronchodilator) were taken in triplicate. The maximum of the triplicate assessments were used. Baseline was considered as the measurement obtained at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
    End point type
    Primary
    End point timeframe
    Up to Day 28 in Part A
    Notes
    [41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [42]
    Units: Liter
    arithmetic mean (standard deviation)
        FEV1, Day 14
    0.0978 ± 0.10378
        FVC, Day 14
    0.2233 ± 0.25407
    Notes
    [42] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in FEV1 and FVC at the indicated time points in Part B

    		 Close Top of page
    End point title
    		 Change from Baseline in FEV1 and FVC at the indicated time points in Part B
    End point description
    FEV1 and FVC were performed at Screening and on Day 1, 28, 56, 112, 168, 280, 364 and at Follow-up (Day 378 to 392) in Part B. FEV1 and FVC assessments at each time point (post-bronchodilator) were taken in triplicate. The maximum of the triplicate assessments were used. Baseline was considered as the measurement obtained at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Statistical analysis was performed using a repeated measures mixed effects model in a Bayesian framework. The estimate of the treatment difference and corresponding 95 percent credible interval was constructed for the difference between danirixin and placebo for each visit. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
    End point type
    Primary
    End point timeframe
    Up to Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [43]
    45 [44]
    Units: Liter
    arithmetic mean (standard deviation)
        FEV1, Day 28, n=47, 44
    -0.018 ± 0.2049
    0.048 ± 0.1433
        FEV1, Day 56, n=46, 41
    0.048 ± 0.3377
    0.017 ± 0.1633
        FEV1, Day 112, n=45, 39
    0.011 ± 0.2431
    0.088 ± 0.3044
        FEV1, Day 168, n=44, 39
    0.018 ± 0.2944
    0.015 ± 0.2129
        FEV1, Day 280, n=39, 37
    -0.012 ± 0.33
    0.043 ± 0.231
        FEV1, Day 364, n=39, 37
    -0.009 ± 0.2746
    0.028 ± 0.2988
        FVC, Day 28, n=47, 44
    0.027 ± 0.3407
    0.022 ± 0.2845
        FVC, Day 56, n=46, 41
    0.046 ± 0.4344
    0.036 ± 0.2706
        FVC, Day 112, n=45, 39
    0.024 ± 0.4195
    0.014 ± 0.3714
        FVC, Day 168, n=44, 39
    -0.061 ± 0.3956
    -0.005 ± 0.3301
        FVC, Day 280, n=39, 37
    -0.02 ± 0.5966
    0.041 ± 0.4271
        FVC, Day 364, n=39, 37
    -0.021 ± 0.429
    0.008 ± 0.419
    Notes
    [43] - ITT Population
    [44] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [45]
    P-value
    		 = 0.87 [46]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.05
         upper limit
    		 0.18
    Variability estimate
    Standard deviation
    Dispersion value
    0.06
    Notes
    [45] - P-value is actually a posterior probability.
    [46] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [47]
    P-value
    		 = 0.78 [48]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.05
         upper limit
    		 0.18
    Variability estimate
    Standard deviation
    Dispersion value
    0.06
    Notes
    [47] - P-value is actually a posterior probability.
    [48] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 [49]
    P-value
    		 = 0.67 [50]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.05
         upper limit
    		 0.18
    Variability estimate
    Standard deviation
    Dispersion value
    0.06
    Notes
    [49] - P-value is actually a posterior probability.
    [50] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [51]
    P-value
    		 = 0.52 [52]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.05
         upper limit
    		 0.18
    Variability estimate
    Standard deviation
    Dispersion value
    0.06
    Notes
    [51] - P-value is actually a posterior probability.
    [52] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [53]
    P-value
    		 = 0.39 [54]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.05
         upper limit
    		 0.18
    Variability estimate
    Standard deviation
    Dispersion value
    0.06
    Notes
    [53] - P-value is actually a posterior probability.
    [54] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [55]
    P-value
    		 = 0.26 [56]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.05
         upper limit
    		 0.18
    Variability estimate
    Standard deviation
    Dispersion value
    0.06
    Notes
    [55] - P-value is actually a posterior probability.
    [56] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 [57]
    P-value
    		 = 0.31 [58]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.09
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [57] - P-value is actually a posterior probability.
    [58] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 [59]
    P-value
    		 = 0.22 [60]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.09
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [59] - P-value is actually a posterior probability.
    [60] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 [61]
    P-value
    		 = 0.14 [62]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.09
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [61] - P-value is actually a posterior probability.
    [62] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 [63]
    P-value
    		 = 0.09 [64]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.09
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [63] - P-value is actually a posterior probability.
    [64] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [65]
    P-value
    		 = 0.05 [66]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.09
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [65] - P-value is actually a posterior probability.
    [66] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [67]
    P-value
    		 = 0.03 [68]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.09
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [67] - P-value is actually a posterior probability.
    [68] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
    Statistical analysis title
    		 Statistical analysis 13
    Statistical analysis description
    FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [69]
    P-value
    		 = 0.85 [70]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.06
         upper limit
    		 0.23
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [69] - P-value is actually a posterior probability.
    [70] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 14
    Statistical analysis description
    FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [71]
    P-value
    		 = 0.79 [72]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.06
         upper limit
    		 0.23
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [71] - P-value is actually a posterior probability.
    [72] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 15
    Statistical analysis description
    FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [73]
    P-value
    		 = 0.71 [74]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.06
         upper limit
    		 0.23
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [73] - P-value is actually a posterior probability.
    [74] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 16
    Statistical analysis description
    FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [75]
    P-value
    		 = 0.61 [76]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.06
         upper limit
    		 0.23
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [75] - P-value is actually a posterior probability.
    [76] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 17
    Statistical analysis description
    FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [77]
    P-value
    		 = 0.51 [78]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.06
         upper limit
    		 0.23
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [77] - P-value is actually a posterior probability.
    [78] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 18
    Statistical analysis description
    FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [79]
    P-value
    		 = 0.41 [80]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.06
         upper limit
    		 0.23
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [79] - P-value is actually a posterior probability.
    [80] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
    Statistical analysis title
    		 Statistical analysis 19
    Statistical analysis description
    FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [81]
    P-value
    		 = 0.47 [82]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.14
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [81] - P-value is actually a posterior probability.
    [82] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 20
    Statistical analysis description
    FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [83]
    P-value
    		 = 0.36 [84]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.14
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [83] - P-value is actually a posterior probability.
    [84] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 21
    Statistical analysis description
    FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [85]
    P-value
    		 = 0.26 [86]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.14
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [85] - P-value is actually a posterior probability.
    [86] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 22
    Statistical analysis description
    FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [87]
    P-value
    		 = 0.19 [88]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.14
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [87] - P-value is actually a posterior probability.
    [88] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 23
    Statistical analysis description
    FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [89]
    P-value
    		 = 0.13 [90]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.14
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [89] - P-value is actually a posterior probability.
    [90] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 24
    Statistical analysis description
    FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [91]
    P-value
    		 = 0.09 [92]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.14
    Variability estimate
    Standard deviation
    Dispersion value
    0.07
    Notes
    [91] - P-value is actually a posterior probability.
    [92] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
    Statistical analysis title
    		 Statistical analysis 25
    Statistical analysis description
    FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [93]
    P-value
    		 = 0.78 [94]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [93] - P-value is actually a posterior probability.
    [94] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 26
    Statistical analysis description
    FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [95]
    P-value
    		 = 0.69 [96]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [95] - P-value is actually a posterior probability.
    [96] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 27
    Statistical analysis description
    FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [97]
    P-value
    		 = 0.59 [98]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [97] - P-value is actually a posterior probability.
    [98] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 28
    Statistical analysis description
    FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [99]
    P-value
    		 = 0.5 [100]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [99] - P-value is actually a posterior probability.
    [100] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 29
    Statistical analysis description
    FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [101]
    P-value
    		 = 0.39 [102]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [101] - P-value is actually a posterior probability.
    [102] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 30
    Statistical analysis description
    FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [103]
    P-value
    		 = 0.3 [104]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [103] - P-value is actually a posterior probability.
    [104] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
    Statistical analysis title
    		 Statistical analysis 31
    Statistical analysis description
    FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [105]
    P-value
    		 = 0.68 [106]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [105] - P-value is actually a posterior probability.
    [106] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 32
    Statistical analysis description
    FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [107]
    P-value
    		 = 0.59 [108]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [107] - P-value is actually a posterior probability.
    [108] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 33
    Statistical analysis description
    FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [109]
    P-value
    		 = 0.5 [110]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [109] - P-value is actually a posterior probability.
    [110] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 34
    Statistical analysis description
    FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [111]
    P-value
    		 = 0.4 [112]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [111] - P-value is actually a posterior probability.
    [112] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 35
    Statistical analysis description
    FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [113]
    P-value
    		 = 0.3 [114]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [113] - P-value is actually a posterior probability.
    [114] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 36
    Statistical analysis description
    FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [115]
    P-value
    		 = 0.22 [116]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [115] - P-value is actually a posterior probability.
    [116] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
    Statistical analysis title
    		 Statistical analysis 37
    Statistical analysis description
    FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [117]
    P-value
    		 = 0.41 [118]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.19
         upper limit
    		 0.13
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [117] - P-value is actually a posterior probability.
    [118] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 38
    Statistical analysis description
    FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [119]
    P-value
    		 = 0.32 [120]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.19
         upper limit
    		 0.13
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [119] - P-value is actually a posterior probability.
    [120] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 39
    Statistical analysis description
    FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [121]
    P-value
    		 = 0.24 [122]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.19
         upper limit
    		 0.13
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [121] - P-value is actually a posterior probability.
    [122] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 40
    Statistical analysis description
    FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [123]
    P-value
    		 = 0.16 [124]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.19
         upper limit
    		 0.13
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [123] - P-value is actually a posterior probability.
    [124] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 41
    Statistical analysis description
    FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 [125]
    P-value
    		 = 0.11 [126]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.19
         upper limit
    		 0.13
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [125] - P-value is actually a posterior probability.
    [126] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 42
    Statistical analysis description
    FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [127]
    P-value
    		 = 0.07 [128]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.19
         upper limit
    		 0.13
    Variability estimate
    Standard deviation
    Dispersion value
    0.08
    Notes
    [127] - P-value is actually a posterior probability.
    [128] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
    Statistical analysis title
    		 Statistical analysis 43
    Statistical analysis description
    FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [129]
    P-value
    		 = 0.41 [130]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.15
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [129] - P-value is actually a posterior probability.
    [130] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 44
    Statistical analysis description
    FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [131]
    P-value
    		 = 0.32 [132]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.15
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [131] - P-value is actually a posterior probability.
    [132] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 45
    Statistical analysis description
    FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [133]
    P-value
    		 = 0.25 [134]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.15
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [133] - P-value is actually a posterior probability.
    [134] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 46
    Statistical analysis description
    FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [135]
    P-value
    		 = 0.18 [136]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.15
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [135] - P-value is actually a posterior probability.
    [136] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 47
    Statistical analysis description
    FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [137]
    P-value
    		 = 0.12 [138]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.15
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [137] - P-value is actually a posterior probability.
    [138] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 48
    Statistical analysis description
    FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [139]
    P-value
    		 = 0.07 [140]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.15
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [139] - P-value is actually a posterior probability.
    [140] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
    Statistical analysis title
    		 Statistical analysis 49
    Statistical analysis description
    FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [141]
    P-value
    		 = 0.45 [142]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.17
    Variability estimate
    Standard deviation
    Dispersion value
    0.1
    Notes
    [141] - P-value is actually a posterior probability.
    [142] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 50
    Statistical analysis description
    FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 [143]
    P-value
    		 = 0.37 [144]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.17
    Variability estimate
    Standard deviation
    Dispersion value
    0.1
    Notes
    [143] - P-value is actually a posterior probability.
    [144] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 51
    Statistical analysis description
    FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [145]
    P-value
    		 = 0.3 [146]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.17
    Variability estimate
    Standard deviation
    Dispersion value
    0.1
    Notes
    [145] - P-value is actually a posterior probability.
    [146] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 52
    Statistical analysis description
    FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [147]
    P-value
    		 = 0.22 [148]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.17
    Variability estimate
    Standard deviation
    Dispersion value
    0.1
    Notes
    [147] - P-value is actually a posterior probability.
    [148] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 53
    Statistical analysis description
    FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [149]
    P-value
    		 = 0.17 [150]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.17
    Variability estimate
    Standard deviation
    Dispersion value
    0.1
    Notes
    [149] - P-value is actually a posterior probability.
    [150] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 54
    Statistical analysis description
    FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [151]
    P-value
    		 = 0.12 [152]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.17
    Variability estimate
    Standard deviation
    Dispersion value
    0.1
    Notes
    [151] - P-value is actually a posterior probability.
    [152] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
    Statistical analysis title
    		 Statistical analysis 55
    Statistical analysis description
    FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [153]
    P-value
    		 = 0.72 [154]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.13
         upper limit
    		 0.24
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [153] - P-value is actually a posterior probability.
    [154] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 56
    Statistical analysis description
    FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [155]
    P-value
    		 = 0.65 [156]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.13
         upper limit
    		 0.24
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [155] - P-value is actually a posterior probability.
    [156] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 57
    Statistical analysis description
    FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [157]
    P-value
    		 = 0.57 [158]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.13
         upper limit
    		 0.24
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [157] - P-value is actually a posterior probability.
    [158] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 58
    Statistical analysis description
    FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [159]
    P-value
    		 = 0.48 [160]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.13
         upper limit
    		 0.24
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [159] - P-value is actually a posterior probability.
    [160] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 59
    Statistical analysis description
    FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [161]
    P-value
    		 = 0.39 [162]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.13
         upper limit
    		 0.24
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [161] - P-value is actually a posterior probability.
    [162] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 60
    Statistical analysis description
    FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [163]
    P-value
    		 = 0.3 [164]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.13
         upper limit
    		 0.24
    Variability estimate
    Standard deviation
    Dispersion value
    0.09
    Notes
    [163] - P-value is actually a posterior probability.
    [164] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
    Statistical analysis title
    		 Statistical analysis 61
    Statistical analysis description
    FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [165]
    P-value
    		 = 0.76 [166]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.32
    Variability estimate
    Standard deviation
    Dispersion value
    0.12
    Notes
    [165] - P-value is actually a posterior probability.
    [166] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 62
    Statistical analysis description
    FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [167]
    P-value
    		 = 0.71 [168]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.32
    Variability estimate
    Standard deviation
    Dispersion value
    0.12
    Notes
    [167] - P-value is actually a posterior probability.
    [168] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 63
    Statistical analysis description
    FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [169]
    P-value
    		 = 0.65 [170]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.32
    Variability estimate
    Standard deviation
    Dispersion value
    0.12
    Notes
    [169] - P-value is actually a posterior probability.
    [170] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 64
    Statistical analysis description
    FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [171]
    P-value
    		 = 0.59 [172]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.32
    Variability estimate
    Standard deviation
    Dispersion value
    0.12
    Notes
    [171] - P-value is actually a posterior probability.
    [172] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 65
    Statistical analysis description
    FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [173]
    P-value
    		 = 0.53 [174]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.32
    Variability estimate
    Standard deviation
    Dispersion value
    0.12
    Notes
    [173] - P-value is actually a posterior probability.
    [174] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 66
    Statistical analysis description
    FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [175]
    P-value
    		 = 0.46 [176]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.32
    Variability estimate
    Standard deviation
    Dispersion value
    0.12
    Notes
    [175] - P-value is actually a posterior probability.
    [176] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
    Statistical analysis title
    		 Statistical analysis 67
    Statistical analysis description
    FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [177]
    P-value
    		 = 0.68 [178]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.28
    Variability estimate
    Standard deviation
    Dispersion value
    0.11
    Notes
    [177] - P-value is actually a posterior probability.
    [178] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
    Statistical analysis title
    		 Statistical analysis 68
    Statistical analysis description
    FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [179]
    P-value
    		 = 0.61 [180]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.28
    Variability estimate
    Standard deviation
    Dispersion value
    0.11
    Notes
    [179] - P-value is actually a posterior probability.
    [180] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
    Statistical analysis title
    		 Statistical analysis 69
    Statistical analysis description
    FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [181]
    P-value
    		 = 0.55 [182]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.28
    Variability estimate
    Standard deviation
    Dispersion value
    0.11
    Notes
    [181] - P-value is actually a posterior probability.
    [182] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
    Statistical analysis title
    		 Statistical analysis 70
    Statistical analysis description
    FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [183]
    P-value
    		 = 0.46 [184]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.28
    Variability estimate
    Standard deviation
    Dispersion value
    0.11
    Notes
    [183] - P-value is actually a posterior probability.
    [184] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
    Statistical analysis title
    		 Statistical analysis 71
    Statistical analysis description
    FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [185]
    P-value
    		 = 0.4 [186]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.28
    Variability estimate
    Standard deviation
    Dispersion value
    0.11
    Notes
    [185] - P-value is actually a posterior probability.
    [186] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
    Statistical analysis title
    		 Statistical analysis 72
    Statistical analysis description
    FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [187]
    P-value
    		 = 0.33 [188]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.28
    Variability estimate
    Standard deviation
    Dispersion value
    0.11
    Notes
    [187] - P-value is actually a posterior probability.
    [188] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.

    Primary: Maximum observed plasma concentration (Cmax) of danirixin in Part A

    		 Close Top of page
    End point title
    		 Maximum observed plasma concentration (Cmax) of danirixin in Part A [189]
    End point description
    Cmax of danirixin was derived from the Pharmacokinetics (PK) samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A. PK analysis of danirixin was conducted by non-compartmental methods. PK Concenteration Population comprised of par. in the ITT Population and who had provided at least one on-treatment blood sample for determination of danirixin concentration.
    End point type
    Primary
    End point timeframe
    Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A
    Notes
    [189] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [190]
    Units: Nanogram per milliliter (ng/mL)
    geometric mean (confidence interval 95%)
        Day 1 dose
    397.785 (222.166 to 712.229)
        Day 14 dose
    512.576 (350.162 to 750.324)
    Notes
    [190] - PK Population
    No statistical analyses for this end point

    Primary: Time of occurrence of Cmax (Tmax) of danirixin in Part A

    		 Close Top of page
    End point title
    		 Time of occurrence of Cmax (Tmax) of danirixin in Part A [191]
    End point description
    Tmax of danirixin was derived from the PK samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A. PK analysis of danirixin was conducted by non-compartmental methods.
    End point type
    Primary
    End point timeframe
    Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A
    Notes
    [191] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [192]
    Units: Hour
    median (full range (min-max))
        Day 1 dose
    1.017 (0.98 to 4)
        Day 14 dose
    2 (0.35 to 4.02)
    Notes
    [192] - PK Population
    No statistical analyses for this end point

    Primary: Area under the blood concentration-time curve (AUC) over dosing interval (AUC[0-12]) of danirixin in Part A

    		 Close Top of page
    End point title
    		 Area under the blood concentration-time curve (AUC) over dosing interval (AUC[0-12]) of danirixin in Part A [193]
    End point description
    AUC (0-12) of danirixin was derived from the PK samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A. PK analysis of danirixin was conducted by non-compartmental methods. A Bayesian random effects model was performed adjusting for the trial as a random effect. A non-informative normal prior distribution was used. Point estimates and corresponding 90 percent credible intervals were constructed.
    End point type
    Primary
    End point timeframe
    Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A
    Notes
    [193] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 DNX 50 mg
    Number of subjects analysed
    9 [194]
    Units: Hour*ng/mL
    geometric mean (confidence interval 95%)
        Day 1 dose
    2203.522 (1303.851 to 3723.976)
        Day 14 dose
    2838.526 (1907.863 to 4223.171)
    Notes
    [194] - PK Population
    No statistical analyses for this end point

    Primary: Number of health care resource utilization (HCRU) defined COPD exacerbations per year in Part B

    		 Close Top of page
    End point title
    		 Number of health care resource utilization (HCRU) defined COPD exacerbations per year in Part B
    End point description
    HCRU COPD exacerbations are defined as moderate or severe exacerbations based on requirement of new prescription antibiotics or oral corticosteroids, hospitalization or emergency room visits for management of COPD exacerbation. For par. with less than 364 days on-treatment, the annual exacerbation rate was imputed as the number of recorded on-treatment exacerbations, divided by the number of 4-week treatment period intervals for which the par. was in the study, multiplied by 13. For par. with 364 or more days on-treatment, the annual exacerbation rate was calculated as the number of recorded exacerbations between study days 1 and 364. Statistical analysis was done using a Bayesian Cox model, assuming a negative binomial distribution for the underlying exacerbation rate. The exacerbation rates along with the ratio (danirixin/placebo), were estimated and corresponding 95 percent credible intervals were produced using non-informative priors. 1 par. was excluded from the analysis.
    End point type
    Primary
    End point timeframe
    Up to Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    23 [195]
    20 [196]
    Units: Exacerbations per year
        arithmetic mean (standard deviation)
    2.9 ± 3.13
    3.2 ± 5.82
    Notes
    [195] - ITT Population
    [196] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [197]
    P-value
    		 = 0.013 [198]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    2.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 4.43
    Variability estimate
    Standard deviation
    Dispersion value
    0.977
    Notes
    [197] - P-value is actually a posterior probability.
    [198] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 1.0 is presented.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [199]
    P-value
    		 = 0.006 [200]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    2.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 4.43
    Variability estimate
    Standard deviation
    Dispersion value
    0.977
    Notes
    [199] - P-value is actually a posterior probability.
    [200] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.9 is presented.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [201]
    P-value
    		 = 0.003 [202]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    2.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 4.43
    Variability estimate
    Standard deviation
    Dispersion value
    0.977
    Notes
    [201] - P-value is actually a posterior probability.
    [202] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.8 is presented.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [203]
    P-value
    		 = 0.001 [204]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    2.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 4.43
    Variability estimate
    Standard deviation
    Dispersion value
    0.977
    Notes
    [203] - P-value is actually a posterior probability.
    [204] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    DNX 75 mg v Placebo
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [205]
    P-value
    		 < 0.001 [206]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    2.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 4.43
    Variability estimate
    Standard deviation
    Dispersion value
    0.977
    Notes
    [205] - P-value is actually a posterior probability.
    [206] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.6 is presented.

    Primary: Monthly weighted means of exacerbations of chronic pulmonary disease tool-respiratory symptoms (EXACT-RS) total score in Part B

    		 Close Top of page
    End point title
    		 Monthly weighted means of exacerbations of chronic pulmonary disease tool-respiratory symptoms (EXACT-RS) total score in Part B
    End point description
    EXACT-RS is a tool which consists of 11 items from the 14 item EXACT- patient reported outcomes (EXACT-PRO) instrument, intended to capture information related to the respiratory symptoms of COPD, i.e. breathlessness, cough, sputum production, chest congestion and chest tightness. The EXACT-RS has a scoring range of 0-40, higher scores indicate more severe symptoms. A par. had at least 10 days of diary data in any month to contribute a non-missing weighted mean AUC of daily values; otherwise the weighted mean for that month were considered missing. A mixed effects model in a Bayesian framework with repeated measures were performed on the EXACT-RS monthly weighted mean AUC data. The posterior mean and corresponding 95 percent credible interval were calculated. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
    End point type
    Primary
    End point timeframe
    Up to Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [207]
    45 [208]
    Units: Score on a scale
    arithmetic mean (standard deviation)
        EXACT-RS, 1 month, n=48,45
    12.4 ± 5.86
    11.8 ± 5.87
        EXACT-RS, 2 month, n=47,44
    12.5 ± 6.67
    11.6 ± 6.31
        EXACT-RS, 3 month, n=46,41
    12.5 ± 7.03
    10.5 ± 6.33
        EXACT-RS, 4 month, n=46,41
    12.4 ± 6.97
    10.6 ± 6.61
        EXACT-RS, 5 month, n=46,40
    12 ± 7.12
    10.6 ± 6.65
        EXACT-RS, 6 month, n=44,39
    12.4 ± 7.34
    10.4 ± 6.14
        EXACT-RS, 7 month, n=44,39
    12.3 ± 7.16
    10.3 ± 6.48
        EXACT-RS, 8 month, n=43,39
    12.4 ± 7.3
    10.3 ± 6.93
        EXACT-RS, 9 month, n=40,38
    12.2 ± 6.98
    10.7 ± 7.08
        EXACT-RS, 10 month, n=39,38
    13 ± 7.14
    10.3 ± 7.09
        EXACT-RS, 11 month, n=39,37
    12.2 ± 7.23
    10.5 ± 6.91
        EXACT-RS, 12 month, n=39,37
    12.5 ± 7.08
    10.5 ± 7.12
    Notes
    [207] - ITT Population
    [208] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    EXACT-RS, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [209]
    P-value
    		 = 0.6 [210]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.81
         upper limit
    		 2.17
    Variability estimate
    Standard deviation
    Dispersion value
    1.29
    Notes
    [209] - P-value is actually a posterior probability.
    [210] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    EXACT-RS, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [211]
    P-value
    		 = 0.65 [212]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.11
         upper limit
    		 2.37
    Variability estimate
    Standard deviation
    Dispersion value
    1.42
    Notes
    [211] - P-value is actually a posterior probability.
    [212] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    EXACT-RS, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [213]
    P-value
    		 = 0.83 [214]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.43
         upper limit
    		 1.45
    Variability estimate
    Standard deviation
    Dispersion value
    1.52
    Notes
    [213] - P-value is actually a posterior probability.
    [214] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    EXACT-RS, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [215]
    P-value
    		 = 0.78 [216]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.07
         upper limit
    		 1.9
    Variability estimate
    Standard deviation
    Dispersion value
    1.53
    Notes
    [215] - P-value is actually a posterior probability.
    [216] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    EXACT-RS, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [217]
    P-value
    		 = 0.73 [218]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.82
         upper limit
    		 2.28
    Variability estimate
    Standard deviation
    Dispersion value
    1.56
    Notes
    [217] - P-value is actually a posterior probability.
    [218] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    EXACT-RS, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [219]
    P-value
    		 = 0.72 [220]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.01
         upper limit
    		 2.26
    Variability estimate
    Standard deviation
    Dispersion value
    1.58
    Notes
    [219] - P-value is actually a posterior probability.
    [220] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    EXACT-RS, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [221]
    P-value
    		 = 0.73 [222]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.15
         upper limit
    		 2.09
    Variability estimate
    Standard deviation
    Dispersion value
    1.58
    Notes
    [221] - P-value is actually a posterior probability.
    [222] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    EXACT-RS, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [223]
    P-value
    		 = 0.81 [224]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.71
         upper limit
    		 1.76
    Variability estimate
    Standard deviation
    Dispersion value
    1.69
    Notes
    [223] - P-value is actually a posterior probability.
    [224] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    EXACT-RS, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [225]
    P-value
    		 = 0.76 [226]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.66
         upper limit
    		 2.22
    Variability estimate
    Standard deviation
    Dispersion value
    1.75
    Notes
    [225] - P-value is actually a posterior probability.
    [226] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    EXACT-RS, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [227]
    P-value
    		 = 0.91 [228]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -2.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.66
         upper limit
    		 0.99
    Variability estimate
    Standard deviation
    Dispersion value
    1.74
    Notes
    [227] - P-value is actually a posterior probability.
    [228] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    EXACT-RS, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [229]
    P-value
    		 = 0.71 [230]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.73
         upper limit
    		 2.13
    Variability estimate
    Standard deviation
    Dispersion value
    1.73
    Notes
    [229] - P-value is actually a posterior probability.
    [230] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    EXACT-RS, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [231]
    P-value
    		 = 0.78 [232]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.77
         upper limit
    		 2.04
    Variability estimate
    Standard deviation
    Dispersion value
    1.74
    Notes
    [231] - P-value is actually a posterior probability.
    [232] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.

    Secondary: Cmax of danirixin in Part B

    		 Close Top of page
    End point title
    		 Cmax of danirixin in Part B
    End point description
    Cmax of danirixin was derived from the PK samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B. PK analysis of danirixin was conducted by non-compartmental methods. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B
    End point values
    		 DNX 75 mg
    Number of subjects analysed
    45 [233]
    Units: ng/mL
    geometric mean (confidence interval 95%)
        Day 1 dose, n=44
    517.784 (388.207 to 690.612)
        Day 364 dose, n=36
    756.391 (554.011 to 1032.7)
    Notes
    [233] - PK Population
    No statistical analyses for this end point

    Secondary: Tmax of danirixin in Part B

    		 Close Top of page
    End point title
    		 Tmax of danirixin in Part B
    End point description
    Tmax of danirixin was derived from the PK samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B. PK analysis of danirixin was conducted by non-compartmental methods. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B
    End point values
    		 DNX 75 mg
    Number of subjects analysed
    45 [234]
    Units: Hour
    median (full range (min-max))
        Day 1 dose, n=44
    2 (0.48 to 6)
        Day 364 dose, n=36
    1.1 (0.5 to 10)
    Notes
    [234] - PK Population
    No statistical analyses for this end point

    Secondary: AUC(0-12) of danirixin in Part B

    		 Close Top of page
    End point title
    		 AUC(0-12) of danirixin in Part B
    End point description
    AUC (0-12) of danirixin was derived from the PK samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B. PK analysis of danirixin was conducted by non-compartmental methods. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B
    End point values
    		 DNX 75 mg
    Number of subjects analysed
    45 [235]
    Units: Hour*ng/mL
    geometric mean (confidence interval 95%)
        Day 1 dose, n=44
    2388.303 (1834.42 to 3109.425)
        Day 364 dose, n=36
    4366.995 (3254.122 to 5860.458)
    Notes
    [235] - PK Population
    No statistical analyses for this end point

    Secondary: Number of EXACT-PRO exacerbations per year in Part B

    		 Close Top of page
    End point title
    		 Number of EXACT-PRO exacerbations per year in Part B
    End point description
    EXACT-PRO is a 14 item patient reported outcome instrument designed to capture information on the occurrence, frequency, severity, and duration of COPD exacerbations. The total score for EXACT-PRO ranges from 0-100, higher scores indicate more severe symptoms. For par. with less than 364 days on-treatment, the annual exacerbation rate was imputed as the number of recorded on-treatment exacerbations, divided by the number of 4-week treatment period intervals for which the par. was in the study, multiplied by 13. For par. with 364 or more days on-treatment, the annual exacerbation rate was calculated as the number of recorded exacerbations between study days 1 and 364. Statistical analysis was done using a Bayesian Cox model, assuming a negative binomial distribution for the underlying exacerbation rate. The exacerbation rates and the ratio (danirixin/placebo), were estimated and 95 percent credible intervals were produced using non-informative priors. 1 par. was excluded from analysis.
    End point type
    Secondary
    End point timeframe
    Up to Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    27 [236]
    28 [237]
    Units: Exacerbations per year
        arithmetic mean (standard deviation)
    3.6 ± 2.75
    3.3 ± 3.47
    Notes
    [236] - ITT Population
    [237] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [238]
    P-value
    		 = 0.278 [239]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.63
    Variability estimate
    Standard deviation
    Dispersion value
    0.242
    Notes
    [238] - P-value is actually a posterior probability.
    [239] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 1.0 is presented.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [240]
    P-value
    		 = 0.138 [241]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.63
    Variability estimate
    Standard deviation
    Dispersion value
    0.242
    Notes
    [240] - P-value is actually a posterior probability.
    [241] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.9 is presented.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [242]
    P-value
    		 = 0.05 [243]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.63
    Variability estimate
    Standard deviation
    Dispersion value
    0.242
    Notes
    [242] - P-value is actually a posterior probability.
    [243] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.8 is presented.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [244]
    P-value
    		 = 0.011 [245]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.63
    Variability estimate
    Standard deviation
    Dispersion value
    0.242
    Notes
    [244] - P-value is actually a posterior probability.
    [245] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [246]
    P-value
    		 = 0.002 [247]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.63
    Variability estimate
    Standard deviation
    Dispersion value
    0.242
    Notes
    [246] - P-value is actually a posterior probability.
    [247] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.6 is presented.

    Secondary: Monthly weighted means of exacerbations of EXACT-PRO total score in Part B

    		 Close Top of page
    End point title
    		 Monthly weighted means of exacerbations of EXACT-PRO total score in Part B
    End point description
    EXACT-PRO is a 14 item patient reported outcome instrument designed to capture information on the occurrence, frequency, severity, and duration of COPD exacerbations. The total score for EXACT-PRO ranges from 0-100, higher scores indicate more severe symptoms. A par. had at least 10 days of diary data in any month to contribute a non-missing weighted mean AUC of daily values; otherwise the weighted mean for that month were considered missing. A mixed effects model in a Bayesian framework with repeated measures were performed on the EXACT-PRO monthly weighted mean AUC data. The posterior mean and corresponding 95 percent credible interval were calculated. Only those participants with data 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 Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [248]
    45 [249]
    Units: Score on a scale
    arithmetic mean (standard deviation)
        EXACT-PRO, 1 month, n=48,45
    36.5 ± 9.53
    35.5 ± 9.81
        EXACT-PRO, 2 month, n=47,44
    36.5 ± 10.77
    35.3 ± 10.69
        EXACT-PRO, 3 month, n=46,41
    36.4 ± 11.23
    33.6 ± 10.84
        EXACT-PRO, 4 month, n=46,41
    36.4 ± 11.35
    33.9 ± 10.91
        EXACT-PRO, 5 month, n=46,40
    35.9 ± 11.84
    33.8 ± 11.28
        EXACT-PRO, 6 month, n=44,39
    36.8 ± 11.58
    33.8 ± 10.75
        EXACT-PRO, 7 month, n=44,39
    36.5 ± 11.61
    33.3 ± 11.15
        EXACT-PRO, 8 month, n=43,38
    36.5 ± 11.82
    33.7 ± 11.73
        EXACT-PRO, 9 month, n=40,36
    36.3 ± 11.25
    35.2 ± 11.22
        EXACT-PRO, 10 month, n=39,37
    37.4 ± 11.71
    33.7 ± 12.2
        EXACT-PRO, 11 month, n=39,36
    36 ± 11.87
    34.6 ± 11.49
        EXACT-PRO, 12 month, n=39,35
    36.7 ± 11.57
    35 ± 11.28
    Notes
    [248] - ITT Population
    [249] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    EXACT-PRO, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [250]
    P-value
    		 = 0.62 [251]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.55
         upper limit
    		 3.23
    Variability estimate
    Standard deviation
    Dispersion value
    2.04
    Notes
    [250] - P-value is actually a posterior probability.
    [251] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    EXACT-PRO, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [252]
    P-value
    		 = 0.64 [253]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.03
         upper limit
    		 3.6
    Variability estimate
    Standard deviation
    Dispersion value
    2.21
    Notes
    [252] - P-value is actually a posterior probability.
    [253] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    EXACT-PRO, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [254]
    P-value
    		 = 0.81 [255]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.6
         upper limit
    		 2.27
    Variability estimate
    Standard deviation
    Dispersion value
    2.29
    Notes
    [254] - P-value is actually a posterior probability.
    [255] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    EXACT-PRO, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [256]
    P-value
    		 = 0.77 [257]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.92
         upper limit
    		 3.07
    Variability estimate
    Standard deviation
    Dispersion value
    2.31
    Notes
    [256] - P-value is actually a posterior probability.
    [257] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    EXACT-PRO, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [258]
    P-value
    		 = 0.71 [259]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.7
         upper limit
    		 3.55
    Variability estimate
    Standard deviation
    Dispersion value
    2.4
    Notes
    [258] - P-value is actually a posterior probability.
    [259] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    EXACT-PRO, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [260]
    P-value
    		 = 0.7 [261]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.46
         upper limit
    		 3.05
    Variability estimate
    Standard deviation
    Dispersion value
    2.42
    Notes
    [260] - P-value is actually a posterior probability.
    [261] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    EXACT-PRO, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [262]
    P-value
    		 = 0.74 [263]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.75
         upper limit
    		 2.9
    Variability estimate
    Standard deviation
    Dispersion value
    2.45
    Notes
    [262] - P-value is actually a posterior probability.
    [263] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    EXACT-PRO, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [264]
    P-value
    		 = 0.79 [265]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.93
         upper limit
    		 3.3
    Variability estimate
    Standard deviation
    Dispersion value
    2.63
    Notes
    [264] - P-value is actually a posterior probability.
    [265] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    EXACT-PRO, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [266]
    P-value
    		 = 0.77 [267]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.04
         upper limit
    		 3.18
    Variability estimate
    Standard deviation
    Dispersion value
    2.63
    Notes
    [266] - P-value is actually a posterior probability.
    [267] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    EXACT-PRO, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [268]
    P-value
    		 = 0.9 [269]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -3.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.74
         upper limit
    		 1.87
    Variability estimate
    Standard deviation
    Dispersion value
    2.72
    Notes
    [268] - P-value is actually a posterior probability.
    [269] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    EXACT-PRO, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [270]
    P-value
    		 = 0.66 [271]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.2
         upper limit
    		 4.2
    Variability estimate
    Standard deviation
    Dispersion value
    2.72
    Notes
    [270] - P-value is actually a posterior probability.
    [271] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 13
    Statistical analysis description
    EXACT-PRO, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [272]
    P-value
    		 = 0.43 [273]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.55
         upper limit
    		 3.23
    Variability estimate
    Standard deviation
    Dispersion value
    2.04
    Notes
    [272] - P-value is actually a posterior probability.
    [273] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    EXACT-PRO, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [274]
    P-value
    		 = 0.74 [275]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.91
         upper limit
    		 3.45
    Variability estimate
    Standard deviation
    Dispersion value
    2.7
    Notes
    [274] - P-value is actually a posterior probability.
    [275] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 14
    Statistical analysis description
    EXACT-PRO, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [276]
    P-value
    		 = 0.45 [277]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.03
         upper limit
    		 3.6
    Variability estimate
    Standard deviation
    Dispersion value
    2.21
    Notes
    [276] - P-value is actually a posterior probability.
    [277] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 16
    Statistical analysis description
    EXACT-PRO, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [278]
    P-value
    		 = 0.62 [279]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.92
         upper limit
    		 3.07
    Variability estimate
    Standard deviation
    Dispersion value
    2.31
    Notes
    [278] - P-value is actually a posterior probability.
    [279] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 15
    Statistical analysis description
    EXACT-PRO, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [280]
    P-value
    		 = 0.67 [281]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.6
         upper limit
    		 2.27
    Variability estimate
    Standard deviation
    Dispersion value
    2.29
    Notes
    [280] - P-value is actually a posterior probability.
    [281] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 17
    Statistical analysis description
    EXACT-PRO, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [282]
    P-value
    		 = 0.55 [283]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.7
         upper limit
    		 3.55
    Variability estimate
    Standard deviation
    Dispersion value
    2.4
    Notes
    [282] - P-value is actually a posterior probability.
    [283] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 18
    Statistical analysis description
    EXACT-PRO, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [284]
    P-value
    		 = 0.55 [285]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.46
         upper limit
    		 3.05
    Variability estimate
    Standard deviation
    Dispersion value
    2.42
    Notes
    [284] - P-value is actually a posterior probability.
    [285] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 19
    Statistical analysis description
    EXACT-PRO, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [286]
    P-value
    		 = 0.59 [287]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.75
         upper limit
    		 2.9
    Variability estimate
    Standard deviation
    Dispersion value
    2.45
    Notes
    [286] - P-value is actually a posterior probability.
    [287] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 20
    Statistical analysis description
    EXACT-PRO, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [288]
    P-value
    		 = 0.65 [289]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.93
         upper limit
    		 3.3
    Variability estimate
    Standard deviation
    Dispersion value
    2.63
    Notes
    [288] - P-value is actually a posterior probability.
    [289] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 22
    Statistical analysis description
    EXACT-PRO, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [290]
    P-value
    		 = 0.81 [291]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -3.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.74
         upper limit
    		 1.87
    Variability estimate
    Standard deviation
    Dispersion value
    2.72
    Notes
    [290] - P-value is actually a posterior probability.
    [291] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 21
    Statistical analysis description
    EXACT-PRO, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [292]
    P-value
    		 = 0.63 [293]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.04
         upper limit
    		 3.18
    Variability estimate
    Standard deviation
    Dispersion value
    2.63
    Notes
    [292] - P-value is actually a posterior probability.
    [293] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 23
    Statistical analysis description
    EXACT-PRO, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [294]
    P-value
    		 = 0.52 [295]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.2
         upper limit
    		 4.2
    Variability estimate
    Standard deviation
    Dispersion value
    2.72
    Notes
    [294] - P-value is actually a posterior probability.
    [295] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 24
    Statistical analysis description
    EXACT-PRO, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [296]
    P-value
    		 = 0.6 [297]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.91
         upper limit
    		 3.45
    Variability estimate
    Standard deviation
    Dispersion value
    2.7
    Notes
    [296] - P-value is actually a posterior probability.
    [297] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 25
    Statistical analysis description
    EXACT-PRO, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [298]
    P-value
    		 = 0.24 [299]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.55
         upper limit
    		 3.23
    Variability estimate
    Standard deviation
    Dispersion value
    2.04
    Notes
    [298] - P-value is actually a posterior probability.
    [299] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 26
    Statistical analysis description
    EXACT-PRO, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [300]
    P-value
    		 = 0.28 [301]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.03
         upper limit
    		 3.6
    Variability estimate
    Standard deviation
    Dispersion value
    2.21
    Notes
    [300] - P-value is actually a posterior probability.
    [301] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 28
    Statistical analysis description
    EXACT-PRO, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [302]
    P-value
    		 = 0.43 [303]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.92
         upper limit
    		 3.07
    Variability estimate
    Standard deviation
    Dispersion value
    2.31
    Notes
    [302] - P-value is actually a posterior probability.
    [303] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 27
    Statistical analysis description
    EXACT-PRO, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [304]
    P-value
    		 = 0.5 [305]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.6
         upper limit
    		 2.27
    Variability estimate
    Standard deviation
    Dispersion value
    2.29
    Notes
    [304] - P-value is actually a posterior probability.
    [305] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 29
    Statistical analysis description
    EXACT-PRO, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [306]
    P-value
    		 = 0.37 [307]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.7
         upper limit
    		 3.55
    Variability estimate
    Standard deviation
    Dispersion value
    2.4
    Notes
    [306] - P-value is actually a posterior probability.
    [307] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 30
    Statistical analysis description
    EXACT-PRO, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [308]
    P-value
    		 = 0.38 [309]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.46
         upper limit
    		 3.05
    Variability estimate
    Standard deviation
    Dispersion value
    2.42
    Notes
    [308] - P-value is actually a posterior probability.
    [309] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 32
    Statistical analysis description
    EXACT-PRO, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [310]
    P-value
    		 = 0.51 [311]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.93
         upper limit
    		 3.3
    Variability estimate
    Standard deviation
    Dispersion value
    2.63
    Notes
    [310] - P-value is actually a posterior probability.
    [311] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 31
    Statistical analysis description
    EXACT-PRO, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [312]
    P-value
    		 = 0.43 [313]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.75
         upper limit
    		 2.9
    Variability estimate
    Standard deviation
    Dispersion value
    2.45
    Notes
    [312] - P-value is actually a posterior probability.
    [313] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 33
    Statistical analysis description
    EXACT-PRO, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [314]
    P-value
    		 = 0.5 [315]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.04
         upper limit
    		 3.18
    Variability estimate
    Standard deviation
    Dispersion value
    2.63
    Notes
    [314] - P-value is actually a posterior probability.
    [315] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 35
    Statistical analysis description
    EXACT-PRO, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [316]
    P-value
    		 = 0.38 [317]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.2
         upper limit
    		 4.2
    Variability estimate
    Standard deviation
    Dispersion value
    2.72
    Notes
    [316] - P-value is actually a posterior probability.
    [317] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 34
    Statistical analysis description
    EXACT-PRO, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [318]
    P-value
    		 = 0.7 [319]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -3.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.74
         upper limit
    		 1.87
    Variability estimate
    Standard deviation
    Dispersion value
    2.72
    Notes
    [318] - P-value is actually a posterior probability.
    [319] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 36
    Statistical analysis description
    EXACT-PRO, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [320]
    P-value
    		 = 0.45 [321]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.91
         upper limit
    		 3.45
    Variability estimate
    Standard deviation
    Dispersion value
    2.7
    Notes
    [320] - P-value is actually a posterior probability.
    [321] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
    Statistical analysis title
    		 Statistical analysis 37
    Statistical analysis description
    EXACT-PRO, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [322]
    P-value
    		 = 0.11 [323]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.55
         upper limit
    		 3.23
    Variability estimate
    Standard deviation
    Dispersion value
    2.04
    Notes
    [322] - P-value is actually a posterior probability.
    [323] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
    Statistical analysis title
    		 Statistical analysis 38
    Statistical analysis description
    EXACT-PRO, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [324]
    P-value
    		 = 0.15 [325]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.03
         upper limit
    		 3.6
    Variability estimate
    Standard deviation
    Dispersion value
    2.21
    Notes
    [324] - P-value is actually a posterior probability.
    [325] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
    Statistical analysis title
    		 Statistical analysis 39
    Statistical analysis description
    EXACT-PRO, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [326]
    P-value
    		 = 0.32 [327]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.6
         upper limit
    		 2.27
    Variability estimate
    Standard deviation
    Dispersion value
    2.29
    Notes
    [326] - P-value is actually a posterior probability.
    [327] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
    Statistical analysis title
    		 Statistical analysis 41
    Statistical analysis description
    EXACT-PRO, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [328]
    P-value
    		 = 0.23 [329]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.7
         upper limit
    		 3.55
    Variability estimate
    Standard deviation
    Dispersion value
    2.4
    Notes
    [328] - P-value is actually a posterior probability.
    [329] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
    Statistical analysis title
    		 Statistical analysis 40
    Statistical analysis description
    EXACT-PRO, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [330]
    P-value
    		 = 0.28 [331]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.92
         upper limit
    		 3.07
    Variability estimate
    Standard deviation
    Dispersion value
    2.31
    Notes
    [330] - P-value is actually a posterior probability.
    [331] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
    Statistical analysis title
    		 Statistical analysis 42
    Statistical analysis description
    EXACT-PRO, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [332]
    P-value
    		 = 0.24 [333]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.46
         upper limit
    		 3.05
    Variability estimate
    Standard deviation
    Dispersion value
    2.42
    Notes
    [332] - P-value is actually a posterior probability.
    [333] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
    Statistical analysis title
    		 Statistical analysis 43
    Statistical analysis description
    EXACT-PRO, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [334]
    P-value
    		 = 0.29 [335]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.75
         upper limit
    		 2.9
    Variability estimate
    Standard deviation
    Dispersion value
    2.45
    Notes
    [334] - P-value is actually a posterior probability.
    [335] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
    Statistical analysis title
    		 Statistical analysis 44
    Statistical analysis description
    EXACT-PRO, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [336]
    P-value
    		 = 0.36 [337]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.93
         upper limit
    		 3.3
    Variability estimate
    Standard deviation
    Dispersion value
    2.63
    Notes
    [336] - P-value is actually a posterior probability.
    [337] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
    Statistical analysis title
    		 Statistical analysis 45
    Statistical analysis description
    EXACT-PRO, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [338]
    P-value
    		 = 0.35 [339]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.04
         upper limit
    		 3.18
    Variability estimate
    Standard deviation
    Dispersion value
    2.63
    Notes
    [338] - P-value is actually a posterior probability.
    [339] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
    Statistical analysis title
    		 Statistical analysis 46
    Statistical analysis description
    EXACT-PRO, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [340]
    P-value
    		 = 0.57 [341]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -3.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.74
         upper limit
    		 1.87
    Variability estimate
    Standard deviation
    Dispersion value
    2.72
    Notes
    [340] - P-value is actually a posterior probability.
    [341] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
    Statistical analysis title
    		 Statistical analysis 48
    Statistical analysis description
    EXACT-PRO, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [342]
    P-value
    		 = 0.32 [343]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.91
         upper limit
    		 3.45
    Variability estimate
    Standard deviation
    Dispersion value
    2.7
    Notes
    [342] - P-value is actually a posterior probability.
    [343] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
    Statistical analysis title
    		 Statistical analysis 47
    Statistical analysis description
    EXACT-PRO, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [344]
    P-value
    		 = 0.25 [345]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.2
         upper limit
    		 4.2
    Variability estimate
    Standard deviation
    Dispersion value
    2.72
    Notes
    [344] - P-value is actually a posterior probability.
    [345] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.

    Secondary: Time to first HCRU COPD exacerbation in Part B

    		 Close Top of page
    End point title
    		 Time to first HCRU COPD exacerbation in Part B
    End point description
    HCRU COPD exacerbations are defined as moderate or severe exacerbations based on requirement of new prescription antibiotics or oral corticosteroids, hospitalization or emergency room visits for management of COPD exacerbation. The time to the first on-treatment HRCU exacerbation were summarized by treatment group. It was analyzed using a Bayesian Cox proportional hazards model. The hazard ratio for the danirixin vs. placebo comparison, along with 95 percent credible interval, was derived, with terms for treatment group, smoking status and country. Posterior probabilities of the ratio of the percentage of par. with an HCRU exacerbation, adjusted for time to first exacerbation, in the danirixin group relative to the placebo group were calculated. 1 par. was excluded from analysis.
    End point type
    Secondary
    End point timeframe
    Up to Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    23 [346]
    20 [347]
    Units: Days
        arithmetic mean (standard deviation)
    166.3 ± 97.97
    172.7 ± 89.66
    Notes
    [346] - ITT Population
    [347] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 [348]
    P-value
    		 = 0.477 [349]
    Method
    		 Bayesian analysis
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 1.82
    Notes
    [348] - P-value is actually a posterior probability.
    [349] - Posterior probability that the treatment ratio (DNX 75 mg/ placebo) is less than 1.0 is presented.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 [350]
    P-value
    		 = 0.343 [351]
    Method
    		 Bayesian analysis
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 1.82
    Notes
    [350] - P-value is actually a posterior probability.
    [351] - Posterior probability that the treatment ratio (DNX 75 mg/ placebo) is less than 0.9 is presented.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 [352]
    P-value
    		 = 0.221 [353]
    Method
    		 Bayesian analysis
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 1.82
    Notes
    [352] - P-value is actually a posterior probability.
    [353] - Posterior probability that the treatment ratio (DNX 75 mg/ placebo) is less than 0.8 is presented.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 [354]
    P-value
    		 = 0.116 [355]
    Method
    		 Bayesian analysis
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 1.82
    Notes
    [354] - P-value is actually a posterior probability.
    [355] - Posterior probability that the treatment ratio (DNX 75 mg/ placebo) is less than 0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 [356]
    P-value
    		 = 0.052 [357]
    Method
    		 Bayesian analysis
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 1.82
    Notes
    [356] - P-value is actually a posterior probability.
    [357] - Posterior probability that the treatment ratio (DNX 75 mg/ placebo) is less than 0.6 is presented.

    Secondary: Time to first EXACT-PRO event in Part B

    		 Close Top of page
    End point title
    		 Time to first EXACT-PRO event in Part B
    End point description
    The hazard ratio for the DNX versus placebo comparison, along with 95% credible interval and posterior probability was derived and a Bayesian Cox proportional hazards model was used for statistical analysis. The analysis was performed on ITT Population. One participant was excluded from analysis.
    End point type
    Secondary
    End point timeframe
    Up to Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    27 [358]
    28 [359]
    Units: Days
        arithmetic mean (standard deviation)
    101 ± 100.18
    114.7 ± 91.16
    Notes
    [358] - ITT Population
    [359] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 [360]
    P-value
    		 = 0.212 [361]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 2.11
    Notes
    [360] - P-value is actually a posterior probability.
    [361] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 1.0 is presented.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 [362]
    P-value
    		 = 0.111 [363]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 2.11
    Notes
    [362] - P-value is actually a posterior probability.
    [363] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.9 is presented.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 [364]
    P-value
    		 = 0.049 [365]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 2.11
    Notes
    [364] - P-value is actually a posterior probability.
    [365] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.8 is presented.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 [366]
    P-value
    		 = 0.012 [367]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 2.11
    Notes
    [366] - P-value is actually a posterior probability.
    [367] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 [368]
    P-value
    		 = 0.001 [369]
    Method
    		 Bayesian Cox analysis
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 2.11
    Notes
    [368] - P-value is actually a posterior probability.
    [369] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.6 is presented.

    Secondary: Assessment of duration of EXACT-PRO events in Part B

    		 Close Top of page
    End point title
    		 Assessment of duration of EXACT-PRO events in Part B
    End point description
    Duration is the length of time in days from onset to recovery. It was calculated as the difference in days between day of onset and day of recovery. Onset of event was identified as either an increase in EXACT-PRO score of >=12 points above the par. current mean Baseline for 2 consecutive days, with Day 1 of the 2 days serving as Day 1 onset of the event, or an increase of >=9 points above the par. current mean Baseline for 3 consecutive days, with Day 1 of the 3 days serving as Day 1 onset of the event. Duration was 3-day rolling average was used, which was initiated on Day 1 of onset and ended on Day 1 of Recovery. Recovery was defined as the first day in which par. experienced a persistent, sustained improvement in their condition i.e. decrease in the rolling average EXACT-PRO total score >=9 point from the maximum observed value (highest rolling average EXACT-PRO total score observed the first 14 days of the event) during the first 14 days of an event that is sustained for 7 days.
    End point type
    Secondary
    End point timeframe
    Up to Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    45 [370]
    48 [371]
    Units: Days
        arithmetic mean (standard deviation)
    33.7 ± 65.4
    31.5 ± 59.27
    Notes
    [370] - ITT Population
    [371] - ITT Population
    No statistical analyses for this end point

    Secondary: Assessment of severity of EXACT-PRO events in Part B

    		 Close Top of page
    End point title
    		 Assessment of severity of EXACT-PRO events in Part B
    End point description
    EXACT-PRO tool was used to measure severity of COPD exacerbations in participants. Severity was indicated by the maximum EXACT-PRO total score during the course of event (from day of onset to day of recovery).
    End point type
    Secondary
    End point timeframe
    Up to Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    45 [372]
    48 [373]
    Units: Score on a scale
        arithmetic mean (standard deviation)
    48.8 ± 13.22
    49.7 ± 12.63
    Notes
    [372] - ITT Population
    [373] - ITT Population
    No statistical analyses for this end point

    Secondary: Monthly weighted means of EXACT-RS domain scores in Part B

    		 Close Top of page
    End point title
    		 Monthly weighted means of EXACT-RS domain scores in Part B
    End point description
    EXACT-RS is a tool which consists of 11 items from the 14 item EXACT-PRO instrument, intended to capture information related to the respiratory symptoms of COPD. EXACT-RS domains included breathlessness, cough and chest symptoms. The EXACT-RS has a scoring range of 0-40, higher scores indicate more severe symptoms. A par. had at least 10 days of diary data in any month to contribute a non-missing weighted mean AUC of daily values; otherwise the weighted mean for that month were considered missing. A mixed effects model in a Bayesian framework with repeated measures were performed. The posterior mean and corresponding 95 percent credible interval were calculated. Only those participants with data 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 Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [374]
    45 [375]
    Units: Score on a scale
    arithmetic mean (standard deviation)
        EXACT-RS-breath, 1 month, n=48,45
    6 ± 3.4
    5.5 ± 3.59
        EXACT-RS-breath, 2 month, n=47,44
    6.3 ± 3.77
    5.5 ± 3.83
        EXACT-RS-breath, 3 month, n=46,41
    6 ± 3.79
    5 ± 3.75
        EXACT-RS-breath, 4 month, n=46,41
    6 ± 3.91
    5 ± 3.86
        EXACT-RS-breath, 5 month, n=46,40
    5.8 ± 4.05
    5 ± 3.94
        EXACT-RS-breath, 6 month, n=44,39
    6 ± 4.11
    4.8 ± 3.73
        EXACT-RS-breath, 7 month, n=44,39
    5.9 ± 4.17
    4.6 ± 3.83
        EXACT-RS-breath, 8 month, n=43,39
    5.9 ± 3.93
    4.9 ± 3.91
        EXACT-RS-breath, 9 month, n=40,38
    5.8 ± 3.87
    5.1 ± 4.05
        EXACT-RS-breath, 10 month, n=39,38
    6.1 ± 3.95
    4.8 ± 4.12
        EXACT-RS-breath, 11 month, n=39,37
    5.8 ± 3.96
    5 ± 4.15
        EXACT-RS-breath, 12 month, n=39,37
    5.9 ± 3.9
    4.9 ± 4.19
        EXACT-RS-chest, 1 month, n=48,45
    2.6 ± 1.69
    2.5 ± 1.59
        EXACT-RS-chest, 2 month, n=47,44
    2.7 ± 1.94
    2.4 ± 1.76
        EXACT-RS-chest, 3 month, n=46,41
    2.9 ± 2.13
    2.2 ± 1.85
        EXACT-RS-chest, 4 month, n=46,41
    2.8 ± 2.04
    2.3 ± 1.9
        EXACT-RS-chest, 5 month, n=46,40
    2.8 ± 2.08
    2.3 ± 1.87
        EXACT-RS-chest, 6 month, n=44,39
    2.9 ± 2.2
    2.3 ± 1.67
        EXACT-RS-chest, 7 month, n=44,39
    2.8 ± 2.16
    2.2 ± 1.74
        EXACT-RS-chest, 8 month, n=43,39
    2.9 ± 2.27
    2.3 ± 1.91
        EXACT-RS-chest, 9 month, n=40,38
    2.9 ± 2.23
    2.4 ± 1.87
        EXACT-RS-chest, 10 month, n=39,38
    3.1 ± 2.21
    2.2 ± 1.86
        EXACT-RS-chest, 11 month, n=39,37
    3 ± 2.35
    2.3 ± 1.78
        EXACT-RS-chest, 12 month, n=39,37
    3 ± 2.31
    2.4 ± 1.83
        EXACT-RS-cough, 1 month, n=48,45
    3.8 ± 1.5
    3.8 ± 1.32
        EXACT-RS-cough, 2 month, n=47,44
    3.5 ± 1.8
    3.7 ± 1.42
        EXACT-RS-cough, 3 month, n=46,41
    3.6 ± 1.87
    3.3 ± 1.55
        EXACT-RS-cough, 4 month, n=46,41
    3.6 ± 1.79
    3.3 ± 1.57
        EXACT-RS-cough, 5 month, n=46,40
    3.4 ± 1.76
    3.3 ± 1.58
        EXACT-RS-cough, 6 month, n=44,39
    3.5 ± 1.76
    3.4 ± 1.54
        EXACT-RS-cough, 7 month, n=44,39
    3.6 ± 1.58
    3.4 ± 1.72
        EXACT-RS-cough, 8 month, n=43,39
    3.6 ± 1.74
    3.2 ± 1.82
        EXACT-RS-cough, 9 month, n=40,38
    3.5 ± 1.72
    3.3 ± 1.83
        EXACT-RS-cough, 10 month, n=39,38
    3.8 ± 1.91
    3.2 ± 1.82
        EXACT-RS-cough, 11 month, n=39,37
    3.5 ± 1.88
    3.3 ± 1.75
        EXACT-RS-cough, 12 month, n=39,37
    3.6 ± 1.91
    3.2 ± 1.7
    Notes
    [374] - ITT Population
    [375] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    EXACT-RS-breath, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [376]
    P-value
    		 = 0.64 [377]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.53
         upper limit
    		 1.25
    Variability estimate
    Standard deviation
    Dispersion value
    0.72
    Notes
    [376] - P-value is actually a posterior probability.
    [377] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    EXACT-RS-breath, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [378]
    P-value
    		 = 0.75 [379]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.91
         upper limit
    		 1.1
    Variability estimate
    Standard deviation
    Dispersion value
    0.78
    Notes
    [378] - P-value is actually a posterior probability.
    [379] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    EXACT-RS-breath, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [380]
    P-value
    		 = 0.77 [381]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.09
         upper limit
    		 0.98
    Variability estimate
    Standard deviation
    Dispersion value
    0.8
    Notes
    [380] - P-value is actually a posterior probability.
    [381] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    EXACT-RS-breath, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [382]
    P-value
    		 = 0.74 [383]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.23
         upper limit
    		 0.87
    Variability estimate
    Standard deviation
    Dispersion value
    0.81
    Notes
    [382] - P-value is actually a posterior probability.
    [383] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    EXACT-RS-breath, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [384]
    P-value
    		 = 0.67 [385]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.88
         upper limit
    		 1.27
    Variability estimate
    Standard deviation
    Dispersion value
    0.83
    Notes
    [384] - Posterior mean difference
    [385] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    EXACT-RS-breath, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [386]
    P-value
    		 = 0.69 [387]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.99
         upper limit
    		 1.26
    Variability estimate
    Standard deviation
    Dispersion value
    0.86
    Notes
    [386] - P-value is actually a posterior probability.
    [387] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    EXACT-RS-breath, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [388]
    P-value
    		 = 0.72 [389]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 1.08
    Variability estimate
    Standard deviation
    Dispersion value
    0.85
    Notes
    [388] - Posterior mean difference
    [389] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    EXACT-RS-breath, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [390]
    P-value
    		 = 0.71 [391]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.11
         upper limit
    		 1.14
    Variability estimate
    Standard deviation
    Dispersion value
    0.87
    Notes
    [390] - P-value is actually a posterior probability.
    [391] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    EXACT-RS-breath, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [392]
    P-value
    		 = 0.66 [393]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.14
         upper limit
    		 1.23
    Variability estimate
    Standard deviation
    Dispersion value
    0.88
    Notes
    [392] - P-value is actually a posterior probability.
    [393] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    EXACT-RS-breath, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [394]
    P-value
    		 = 0.84 [395]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.71
         upper limit
    		 0.69
    Variability estimate
    Standard deviation
    Dispersion value
    0.89
    Notes
    [394] - P-value is actually a posterior probability.
    [395] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    EXACT-RS-breath, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [396]
    P-value
    		 = 0.65 [397]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.15
         upper limit
    		 1.41
    Variability estimate
    Standard deviation
    Dispersion value
    0.91
    Notes
    [396] - P-value is actually a posterior probability.
    [397] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    EXACT-RS-breath, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [398]
    P-value
    		 = 0.71 [399]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.36
         upper limit
    		 1.13
    Variability estimate
    Standard deviation
    Dispersion value
    0.9
    Notes
    [398] - P-value is actually a posterior probability.
    [399] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 13
    Statistical analysis description
    EXACT-RS-breath, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [400]
    P-value
    		 = 0.13 [401]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.53
         upper limit
    		 1.25
    Variability estimate
    Standard deviation
    Dispersion value
    0.72
    Notes
    [400] - P-value is actually a posterior probability.
    [401] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 14
    Statistical analysis description
    EXACT-RS-breath, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [402]
    P-value
    		 = 0.27 [403]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.91
         upper limit
    		 1.1
    Variability estimate
    Standard deviation
    Dispersion value
    0.78
    Notes
    [402] - P-value is actually a posterior probability.
    [403] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 15
    Statistical analysis description
    EXACT-RS-breath, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [404]
    P-value
    		 = 0.31 [405]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.09
         upper limit
    		 0.98
    Variability estimate
    Standard deviation
    Dispersion value
    0.8
    Notes
    [404] - P-value is actually a posterior probability.
    [405] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 16
    Statistical analysis description
    EXACT-RS-breath, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [406]
    P-value
    		 = 0.29 [407]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.23
         upper limit
    		 0.87
    Variability estimate
    Standard deviation
    Dispersion value
    0.81
    Notes
    [406] - P-value is actually a posterior probability.
    [407] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 17
    Statistical analysis description
    EXACT-RS-breath, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [408]
    P-value
    		 = 0.23 [409]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.88
         upper limit
    		 1.27
    Variability estimate
    Standard deviation
    Dispersion value
    0.83
    Notes
    [408] - P-value is actually a posterior probability.
    [409] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 18
    Statistical analysis description
    EXACT-RS-breath, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [410]
    P-value
    		 = 0.26 [411]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.99
         upper limit
    		 1.26
    Variability estimate
    Standard deviation
    Dispersion value
    0.86
    Notes
    [410] - P-value is actually a posterior probability.
    [411] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 19
    Statistical analysis description
    EXACT-RS-breath, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [412]
    P-value
    		 = 0.28 [413]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 1.08
    Variability estimate
    Standard deviation
    Dispersion value
    0.85
    Notes
    [412] - P-value is actually a posterior probability.
    [413] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 20
    Statistical analysis description
    EXACT-RS-breath, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [414]
    P-value
    		 = 0.29 [415]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.11
         upper limit
    		 1.14
    Variability estimate
    Standard deviation
    Dispersion value
    0.87
    Notes
    [414] - P-value is actually a posterior probability.
    [415] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 21
    Statistical analysis description
    EXACT-RS-breath, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [416]
    P-value
    		 = 0.23 [417]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.14
         upper limit
    		 1.23
    Variability estimate
    Standard deviation
    Dispersion value
    0.88
    Notes
    [416] - P-value is actually a posterior probability.
    [417] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 22
    Statistical analysis description
    EXACT-RS-breath, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [418]
    P-value
    		 = 0.45 [419]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.71
         upper limit
    		 0.69
    Variability estimate
    Standard deviation
    Dispersion value
    0.89
    Notes
    [418] - P-value is actually a posterior probability.
    [419] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 23
    Statistical analysis description
    EXACT-RS-breath, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [420]
    P-value
    		 = 0.24 [421]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.15
         upper limit
    		 1.41
    Variability estimate
    Standard deviation
    Dispersion value
    0.91
    Notes
    [420] - P-value is actually a posterior probability.
    [421] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 24
    Statistical analysis description
    EXACT-RS-breath, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [422]
    P-value
    		 = 0.28 [423]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.36
         upper limit
    		 1.13
    Variability estimate
    Standard deviation
    Dispersion value
    0.9
    Notes
    [422] - P-value is actually a posterior probability.
    [423] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 25
    Statistical analysis description
    EXACT-RS-breath, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [424]
    P-value
    		 = 0.26 [425]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.53
         upper limit
    		 1.25
    Variability estimate
    Standard deviation
    Dispersion value
    0.72
    Notes
    [424] - P-value is actually a posterior probability.
    [425] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 26
    Statistical analysis description
    EXACT-RS-breath, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [426]
    P-value
    		 = 0.41 [427]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.91
         upper limit
    		 1.1
    Variability estimate
    Standard deviation
    Dispersion value
    0.78
    Notes
    [426] - P-value is actually a posterior probability.
    [427] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 27
    Statistical analysis description
    EXACT-RS-breath, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [428]
    P-value
    		 = 0.46 [429]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.09
         upper limit
    		 0.98
    Variability estimate
    Standard deviation
    Dispersion value
    0.8
    Notes
    [428] - P-value is actually a posterior probability.
    [429] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 28
    Statistical analysis description
    EXACT-RS-breath, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [430]
    P-value
    		 = 0.43 [431]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.23
         upper limit
    		 0.87
    Variability estimate
    Standard deviation
    Dispersion value
    0.81
    Notes
    [430] - P-value is actually a posterior probability.
    [431] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 29
    Statistical analysis description
    EXACT-RS-breath, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [432]
    P-value
    		 = 0.36 [433]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.88
         upper limit
    		 1.27
    Variability estimate
    Standard deviation
    Dispersion value
    0.83
    Notes
    [432] - P-value is actually a posterior probability.
    [433] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 30
    Statistical analysis description
    EXACT-RS-breath, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [434]
    P-value
    		 = 0.39 [435]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.99
         upper limit
    		 1.26
    Variability estimate
    Standard deviation
    Dispersion value
    0.86
    Notes
    [434] - P-value is actually a posterior probability.
    [435] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 31
    Statistical analysis description
    EXACT-RS-breath, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [436]
    P-value
    		 = 0.42 [437]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 1.08
    Variability estimate
    Standard deviation
    Dispersion value
    0.85
    Notes
    [436] - P-value is actually a posterior probability.
    [437] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 32
    Statistical analysis description
    EXACT-RS-breath, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [438]
    P-value
    		 = 0.42 [439]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.11
         upper limit
    		 1.14
    Variability estimate
    Standard deviation
    Dispersion value
    0.87
    Notes
    [438] - P-value is actually a posterior probability.
    [439] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 33
    Statistical analysis description
    EXACT-RS-breath, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [440]
    P-value
    		 = 0.35 [441]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.14
         upper limit
    		 1.23
    Variability estimate
    Standard deviation
    Dispersion value
    0.88
    Notes
    [440] - P-value is actually a posterior probability.
    [441] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 34
    Statistical analysis description
    EXACT-RS-breath, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [442]
    P-value
    		 = 0.58 [443]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.71
         upper limit
    		 0.69
    Variability estimate
    Standard deviation
    Dispersion value
    0.89
    Notes
    [442] - P-value is actually a posterior probability.
    [443] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 35
    Statistical analysis description
    EXACT-RS-breath, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [444]
    P-value
    		 = 0.36 [445]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.15
         upper limit
    		 1.41
    Variability estimate
    Standard deviation
    Dispersion value
    0.91
    Notes
    [444] - P-value is actually a posterior probability.
    [445] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 36
    Statistical analysis description
    EXACT-RS-breath, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [446]
    P-value
    		 = 0.41 [447]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.36
         upper limit
    		 1.13
    Variability estimate
    Standard deviation
    Dispersion value
    0.9
    Notes
    [446] - P-value is actually a posterior probability.
    [447] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 37
    Statistical analysis description
    EXACT-RS-chest, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [448]
    P-value
    		 = 0.66 [449]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.84
         upper limit
    		 0.52
    Variability estimate
    Standard deviation
    Dispersion value
    0.35
    Notes
    [448] - P-value is actually a posterior probability.
    [449] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 38
    Statistical analysis description
    EXACT-RS-chest, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [450]
    P-value
    		 = 0.66 [451]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.94
         upper limit
    		 0.55
    Variability estimate
    Standard deviation
    Dispersion value
    0.39
    Notes
    [450] - P-value is actually a posterior probability.
    [451] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 39
    Statistical analysis description
    EXACT-RS-chest, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [452]
    P-value
    		 = 0.91 [453]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.46
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.43
    Notes
    [452] - P-value is actually a posterior probability.
    [453] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 40
    Statistical analysis description
    EXACT-RS-chest, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [454]
    P-value
    		 = 0.79 [455]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.16
         upper limit
    		 0.44
    Variability estimate
    Standard deviation
    Dispersion value
    0.41
    Notes
    [454] - P-value is actually a posterior probability.
    [455] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 41
    Statistical analysis description
    EXACT-RS-chest, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [456]
    P-value
    		 = 0.84 [457]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.24
         upper limit
    		 0.41
    Variability estimate
    Standard deviation
    Dispersion value
    0.42
    Notes
    [456] - P-value is actually a posterior probability.
    [457] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 42
    Statistical analysis description
    EXACT-RS-chest, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [458]
    P-value
    		 = 0.81 [459]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.23
         upper limit
    		 0.47
    Variability estimate
    Standard deviation
    Dispersion value
    0.44
    Notes
    [458] - P-value is actually a posterior probability.
    [459] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 43
    Statistical analysis description
    EXACT-RS-chest, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [460]
    P-value
    		 = 0.76 [461]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.14
         upper limit
    		 0.56
    Variability estimate
    Standard deviation
    Dispersion value
    0.44
    Notes
    [460] - P-value is actually a posterior probability.
    [461] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 44
    Statistical analysis description
    EXACT-RS-chest, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [462]
    P-value
    		 = 0.84 [463]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.43
         upper limit
    		 0.43
    Variability estimate
    Standard deviation
    Dispersion value
    0.48
    Notes
    [462] - P-value is actually a posterior probability.
    [463] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 45
    Statistical analysis description
    EXACT-RS-chest, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [464]
    P-value
    		 = 0.83 [465]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.49
         upper limit
    		 0.38
    Variability estimate
    Standard deviation
    Dispersion value
    0.49
    Notes
    [464] - P-value is actually a posterior probability.
    [465] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 46
    Statistical analysis description
    EXACT-RS-chest, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [466]
    P-value
    		 = 0.94 [467]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.68
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.49
    Notes
    [466] - P-value is actually a posterior probability.
    [467] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 47
    Statistical analysis description
    EXACT-RS-chest, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [468]
    P-value
    		 = 0.84 [469]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.45
         upper limit
    		 0.48
    Variability estimate
    Standard deviation
    Dispersion value
    0.5
    Notes
    [468] - P-value is actually a posterior probability.
    [469] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 48
    Statistical analysis description
    EXACT-RS-chest, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [470]
    P-value
    		 = 0.81 [471]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.36
         upper limit
    		 0.55
    Variability estimate
    Standard deviation
    Dispersion value
    0.5
    Notes
    [470] - P-value is actually a posterior probability.
    [471] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 49
    Statistical analysis description
    EXACT-RS-chest, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [472]
    P-value
    		 = 0.01 [473]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.84
         upper limit
    		 0.52
    Variability estimate
    Standard deviation
    Dispersion value
    0.35
    Notes
    [472] - P-value is actually a posterior probability.
    [473] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 50
    Statistical analysis description
    EXACT-RS-chest, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [474]
    P-value
    		 = 0.02 [475]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.94
         upper limit
    		 0.55
    Variability estimate
    Standard deviation
    Dispersion value
    0.39
    Notes
    [474] - P-value is actually a posterior probability.
    [475] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 51
    Statistical analysis description
    EXACT-RS-chest, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [476]
    P-value
    		 = 0.15 [477]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.46
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.43
    Notes
    [476] - P-value is actually a posterior probability.
    [477] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 52
    Statistical analysis description
    EXACT-RS-chest, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [478]
    P-value
    		 = 0.05 [479]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.16
         upper limit
    		 0.44
    Variability estimate
    Standard deviation
    Dispersion value
    0.41
    Notes
    [478] - P-value is actually a posterior probability.
    [479] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 53
    Statistical analysis description
    EXACT-RS-chest, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [480]
    P-value
    		 = 0.08 [481]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.24
         upper limit
    		 0.41
    Variability estimate
    Standard deviation
    Dispersion value
    0.42
    Notes
    [480] - P-value is actually a posterior probability.
    [481] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 54
    Statistical analysis description
    EXACT-RS-chest, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [482]
    P-value
    		 = 0.08 [483]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.23
         upper limit
    		 0.47
    Variability estimate
    Standard deviation
    Dispersion value
    0.44
    Notes
    [482] - P-value is actually a posterior probability.
    [483] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 55
    Statistical analysis description
    EXACT-RS-chest, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [484]
    P-value
    		 = 0.06 [485]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.14
         upper limit
    		 0.56
    Variability estimate
    Standard deviation
    Dispersion value
    0.44
    Notes
    [484] - P-value is actually a posterior probability.
    [485] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 56
    Statistical analysis description
    EXACT-RS-chest, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [486]
    P-value
    		 = 0.14 [487]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.43
         upper limit
    		 0.43
    Variability estimate
    Standard deviation
    Dispersion value
    0.48
    Notes
    [486] - P-value is actually a posterior probability.
    [487] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 57
    Statistical analysis description
    EXACT-RS-chest, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [488]
    P-value
    		 = 0.14 [489]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.49
         upper limit
    		 0.38
    Variability estimate
    Standard deviation
    Dispersion value
    0.49
    Notes
    [488] - P-value is actually a posterior probability.
    [489] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 58
    Statistical analysis description
    EXACT-RS-chest, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [490]
    P-value
    		 = 0.29 [491]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.68
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.49
    Notes
    [490] - P-value is actually a posterior probability.
    [491] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 59
    Statistical analysis description
    EXACT-RS-chest, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [492]
    P-value
    		 = 0.15 [493]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.45
         upper limit
    		 0.48
    Variability estimate
    Standard deviation
    Dispersion value
    0.5
    Notes
    [492] - P-value is actually a posterior probability.
    [493] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 60
    Statistical analysis description
    EXACT-RS-chest, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [494]
    P-value
    		 = 0.13 [495]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.36
         upper limit
    		 0.55
    Variability estimate
    Standard deviation
    Dispersion value
    0.5
    Notes
    [494] - P-value is actually a posterior probability.
    [495] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
    Statistical analysis title
    		 Statistical analysis 61
    Statistical analysis description
    EXACT-RS-chest, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [496]
    P-value
    		 = 0.06 [497]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.84
         upper limit
    		 0.52
    Variability estimate
    Standard deviation
    Dispersion value
    0.35
    Notes
    [496] - P-value is actually a posterior probability.
    [497] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 62
    Statistical analysis description
    EXACT-RS-chest, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [498]
    P-value
    		 = 0.09 [499]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.94
         upper limit
    		 0.55
    Variability estimate
    Standard deviation
    Dispersion value
    0.39
    Notes
    [498] - P-value is actually a posterior probability.
    [499] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 63
    Statistical analysis description
    EXACT-RS-chest, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [500]
    P-value
    		 = 0.37 [501]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.46
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.43
    Notes
    [500] - P-value is actually a posterior probability.
    [501] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 64
    Statistical analysis description
    EXACT-RS-chest, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [502]
    P-value
    		 = 0.18 [503]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.16
         upper limit
    		 0.44
    Variability estimate
    Standard deviation
    Dispersion value
    0.41
    Notes
    [502] - P-value is actually a posterior probability.
    [503] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 65
    Statistical analysis description
    EXACT-RS-chest, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [504]
    P-value
    		 = 0.24 [505]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.24
         upper limit
    		 0.41
    Variability estimate
    Standard deviation
    Dispersion value
    0.42
    Notes
    [504] - P-value is actually a posterior probability.
    [505] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 66
    Statistical analysis description
    EXACT-RS-chest, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [506]
    P-value
    		 = 0.24 [507]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.23
         upper limit
    		 0.47
    Variability estimate
    Standard deviation
    Dispersion value
    0.44
    Notes
    [506] - P-value is actually a posterior probability.
    [507] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 67
    Statistical analysis description
    EXACT-RS-chest, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [508]
    P-value
    		 = 0.19 [509]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.14
         upper limit
    		 0.56
    Variability estimate
    Standard deviation
    Dispersion value
    0.44
    Notes
    [508] - P-value is actually a posterior probability.
    [509] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 68
    Statistical analysis description
    EXACT-RS-chest, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [510]
    P-value
    		 = 0.32 [511]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.43
         upper limit
    		 0.43
    Variability estimate
    Standard deviation
    Dispersion value
    0.48
    Notes
    [510] - P-value is actually a posterior probability.
    [511] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 69
    Statistical analysis description
    EXACT-RS-chest, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [512]
    P-value
    		 = 0.32 [513]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.49
         upper limit
    		 0.38
    Variability estimate
    Standard deviation
    Dispersion value
    0.49
    Notes
    [512] - P-value is actually a posterior probability.
    [513] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 70
    Statistical analysis description
    EXACT-RS-chest, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [514]
    P-value
    		 = 0.52 [515]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.68
         upper limit
    		 0.2
    Variability estimate
    Standard deviation
    Dispersion value
    0.49
    Notes
    [514] - P-value is actually a posterior probability.
    [515] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 71
    Statistical analysis description
    EXACT-RS-chest, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [516]
    P-value
    		 = 0.33 [517]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.45
         upper limit
    		 0.48
    Variability estimate
    Standard deviation
    Dispersion value
    0.5
    Notes
    [516] - P-value is actually a posterior probability.
    [517] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 72
    Statistical analysis description
    EXACT-RS-chest, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [518]
    P-value
    		 = 0.29 [519]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.36
         upper limit
    		 0.55
    Variability estimate
    Standard deviation
    Dispersion value
    0.5
    Notes
    [518] - P-value is actually a posterior probability.
    [519] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 73
    Statistical analysis description
    EXACT-RS-cough, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [520]
    P-value
    		 = 0.43 [521]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.59
         upper limit
    		 0.62
    Variability estimate
    Standard deviation
    Dispersion value
    0.31
    Notes
    [520] - P-value is actually a posterior probability.
    [521] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 74
    Statistical analysis description
    EXACT-RS-cough, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [522]
    P-value
    		 = 0.29 [523]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.53
         upper limit
    		 0.85
    Variability estimate
    Standard deviation
    Dispersion value
    0.35
    Notes
    [522] - P-value is actually a posterior probability.
    [523] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 75
    Statistical analysis description
    EXACT-RS-cough, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [524]
    P-value
    		 = 0.7 [525]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.94
         upper limit
    		 0.52
    Variability estimate
    Standard deviation
    Dispersion value
    0.38
    Notes
    [524] - P-value is actually a posterior probability.
    [525] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 76
    Statistical analysis description
    EXACT-RS-cough, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [526]
    P-value
    		 = 0.71 [527]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.92
         upper limit
    		 0.5
    Variability estimate
    Standard deviation
    Dispersion value
    0.37
    Notes
    [526] - P-value is actually a posterior probability.
    [527] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 77
    Statistical analysis description
    EXACT-RS-cough, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [528]
    P-value
    		 = 0.61 [529]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.82
         upper limit
    		 0.61
    Variability estimate
    Standard deviation
    Dispersion value
    0.37
    Notes
    [528] - P-value is actually a posterior probability.
    [529] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 78
    Statistical analysis description
    EXACT-RS-cough, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [530]
    P-value
    		 = 0.48 [531]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.69
         upper limit
    		 0.69
    Variability estimate
    Standard deviation
    Dispersion value
    0.36
    Notes
    [530] - P-value is actually a posterior probability.
    [531] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 79
    Statistical analysis description
    EXACT-RS-cough, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [532]
    P-value
    		 = 0.58 [533]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.79
         upper limit
    		 0.62
    Variability estimate
    Standard deviation
    Dispersion value
    0.36
    Notes
    [532] - P-value is actually a posterior probability.
    [533] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 80
    Statistical analysis description
    EXACT-RS-cough, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [534]
    P-value
    		 = 0.83 [535]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.12
         upper limit
    		 0.43
    Variability estimate
    Standard deviation
    Dispersion value
    0.4
    Notes
    [534] - P-value is actually a posterior probability.
    [535] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 81
    Statistical analysis description
    EXACT-RS-cough, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [536]
    P-value
    		 = 0.74 [537]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.07
         upper limit
    		 0.52
    Variability estimate
    Standard deviation
    Dispersion value
    0.41
    Notes
    [536] - P-value is actually a posterior probability.
    [537] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 82
    Statistical analysis description
    EXACT-RS-cough, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [538]
    P-value
    		 = 0.89 [539]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0.29
    Variability estimate
    Standard deviation
    Dispersion value
    0.43
    Notes
    [538] - P-value is actually a posterior probability.
    [539] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 83
    Statistical analysis description
    EXACT-RS-cough, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [540]
    P-value
    		 = 0.59 [541]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.89
         upper limit
    		 0.69
    Variability estimate
    Standard deviation
    Dispersion value
    0.41
    Notes
    [540] - P-value is actually a posterior probability.
    [541] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 84
    Statistical analysis description
    EXACT-RS-cough, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [542]
    P-value
    		 = 0.77 [543]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.12
         upper limit
    		 0.54
    Variability estimate
    Standard deviation
    Dispersion value
    0.42
    Notes
    [542] - P-value is actually a posterior probability.
    [543] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
    Statistical analysis title
    		 Statistical analysis 85
    Statistical analysis description
    EXACT-RS-cough, 1 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [544]
    P-value
    		 = 0.01 [545]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.59
         upper limit
    		 0.62
    Variability estimate
    Standard deviation
    Dispersion value
    0.31
    Notes
    [544] - P-value is actually a posterior probability.
    [545] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 86
    Statistical analysis description
    EXACT-RS-cough, 2 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [546]
    P-value
    		 = 0.01 [547]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.53
         upper limit
    		 0.85
    Variability estimate
    Standard deviation
    Dispersion value
    0.35
    Notes
    [546] - P-value is actually a posterior probability.
    [547] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 87
    Statistical analysis description
    EXACT-RS-cough, 3 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [548]
    P-value
    		 = 0.09 [549]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.94
         upper limit
    		 0.52
    Variability estimate
    Standard deviation
    Dispersion value
    0.38
    Notes
    [548] - P-value is actually a posterior probability.
    [549] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 88
    Statistical analysis description
    EXACT-RS-cough, 4 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [550]
    P-value
    		 = 0.09 [551]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.92
         upper limit
    		 0.5
    Variability estimate
    Standard deviation
    Dispersion value
    0.37
    Notes
    [550] - P-value is actually a posterior probability.
    [551] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 89
    Statistical analysis description
    EXACT-RS-cough, 5 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [552]
    P-value
    		 = 0.05 [553]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.82
         upper limit
    		 0.61
    Variability estimate
    Standard deviation
    Dispersion value
    0.37
    Notes
    [552] - P-value is actually a posterior probability.
    [553] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 90
    Statistical analysis description
    EXACT-RS-cough, 6 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [554]
    P-value
    		 = 0.02 [555]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.69
         upper limit
    		 0.69
    Variability estimate
    Standard deviation
    Dispersion value
    0.36
    Notes
    [554] - P-value is actually a posterior probability.
    [555] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 91
    Statistical analysis description
    EXACT-RS-cough, 7 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [556]
    P-value
    		 = 0.04 [557]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.79
         upper limit
    		 0.62
    Variability estimate
    Standard deviation
    Dispersion value
    0.36
    Notes
    [556] - P-value is actually a posterior probability.
    [557] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 92
    Statistical analysis description
    EXACT-RS-cough, 8 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [558]
    P-value
    		 = 0.22 [559]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.12
         upper limit
    		 0.43
    Variability estimate
    Standard deviation
    Dispersion value
    0.4
    Notes
    [558] - P-value is actually a posterior probability.
    [559] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 93
    Statistical analysis description
    EXACT-RS-cough, 9 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [560]
    P-value
    		 = 0.14 [561]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.07
         upper limit
    		 0.52
    Variability estimate
    Standard deviation
    Dispersion value
    0.41
    Notes
    [560] - P-value is actually a posterior probability.
    [561] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 94
    Statistical analysis description
    EXACT-RS-cough, 10 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [562]
    P-value
    		 = 0.36 [563]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0.29
    Variability estimate
    Standard deviation
    Dispersion value
    0.43
    Notes
    [562] - P-value is actually a posterior probability.
    [563] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 95
    Statistical analysis description
    EXACT-RS-cough, 11 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [564]
    P-value
    		 = 0.07 [565]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.89
         upper limit
    		 0.69
    Variability estimate
    Standard deviation
    Dispersion value
    0.41
    Notes
    [564] - P-value is actually a posterior probability.
    [565] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
    Statistical analysis title
    		 Statistical analysis 96
    Statistical analysis description
    EXACT-RS-cough, 12 month. Data presented are for 95% equal-tailed credible intervals
    Comparison groups
    Placebo v DNX 75 mg
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [566]
    P-value
    		 = 0.17 [567]
    Method
    		 Bayesian analysis
    Parameter type
    		 Posterior mean difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.12
         upper limit
    		 0.54
    Variability estimate
    Standard deviation
    Dispersion value
    0.42
    Notes
    [566] - P-value is actually a posterior probability.
    [567] - Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.

    Secondary: Change from Baseline for COPD assessment test (CAT) at the indicated time points in Part B

    		 Close Top of page
    End point title
    		 Change from Baseline for COPD assessment test (CAT) at the indicated time points in Part B
    End point description
    The CAT is a validated, 8 item questionnaire which has been developed designed to measure overall COPD-related health status for the initial assessment and longitudinal follow up of par. with COPD. Participants completed each question by rating their experience on a 6 point scale ranging from 0 (no impairment) to 5 (maximum impairment) with a total scoring range of 0 - 40. CAT was assessed at Baseline (Day 1), Day 28, Day 112, Day 168, Day 280 and Day 364 where Baseline was considered as score on Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Only those participants with data 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 Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [568]
    45 [569]
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Day 28; n= 43, 37
    -0.6 ± 5.19
    -0.7 ± 7
        Day 112; n= 44, 39
    -0.5 ± 5.53
    -1 ± 9.5
        Day 168; n= 43, 37
    -0.8 ± 5.72
    -1.5 ± 9.11
        Day 280; n= 36, 35
    -0.6 ± 6.02
    -1.2 ± 9.59
        Day 364; n= 38, 34
    0.7 ± 5.78
    -2.1 ± 8.77
    Notes
    [568] - ITT Population
    [569] - ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with physician’s global assessment (PGA) readings in Part B

    		 Close Top of page
    End point title
    		 Number of participants with physician’s global assessment (PGA) readings in Part B
    End point description
    The PGA is a single item clinician reported outcome measure assessing the overall severity of COPD. Physicians rated disease severity on a four point scale ranging from 1-4 (1=mild, 2=moderate, 3=severe, 4=very severe) at Week 0, 4, 8, 16, 24, 40 and 52. Baseline was considered as score on Day 1. A categorical summary of PGA is presented by treatment and visit.Only those participants with data 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 Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [570]
    45 [571]
    Units: Participants
        Baseline; mild; n= 47, 43
    5
    2
        Baseline; moderate; n= 47, 43
    35
    37
        Baseline; severe; n= 47, 43
    7
    4
        Baseline; very severe; n= 47, 43
    0
    0
        Week 4; mild; n= 44, 39
    10
    8
        Week 4; moderate; n= 44, 39
    28
    27
        Week 4; severe; n= 44, 39
    6
    3
        Week 4; very severe; n= 44, 39
    0
    1
        Week 8; mild; n= 44, 40
    10
    8
        Week 8; moderate; n= 44, 40
    31
    30
        Week 8; severe; n= 44, 40
    3
    2
        Week 8; very severe; n= 44, 40
    0
    0
        Week 16; mild; n= 46, 40
    12
    6
        Week 16; moderate; n= 46, 40
    29
    32
        Week 16; severe; n= 46, 40
    5
    2
        Week 16; very severe; n= 46, 40
    0
    0
        Week 24; mild; n= 44, 38
    8
    9
        Week 24; moderate; n= 44, 38
    32
    25
        Week 24; severe; n= 44, 38
    4
    4
        Week 24; very severe; n= 44, 38
    0
    0
        Week 40; mild; n= 37, 36
    4
    6
        Week 40; moderate; n= 37, 36
    30
    28
        Week 40; severe; n= 37, 36
    3
    2
        Week 40; very severe; n= 37, 36
    0
    0
        Week 52; mild; n= 39, 36
    7
    11
        Week 52; n= moderate; n= 39, 36
    28
    24
        Week 52; severe; n= 39, 36
    4
    1
        Week 52; very severe; n= 39, 36
    0
    0
    Notes
    [570] - ITT Population
    [571] - ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with patient global rating of severity (PGRS) score in Part B

    		 Close Top of page
    End point title
    		 Number of participants with patient global rating of severity (PGRS) score in Part B
    End point description
    PGRS is a single global question and was asked to participants to rate their COPD severity on a four point scale ranging from 1-4 (1=mild, 2=moderate, 3=severe, 4=very severe). Participants completed PGRS at Week 0, 4, 8, 16, 24, 40 and 52. Baseline was considered as score on Day 1. A categorical summary of PGRS is presented by treatment and visit.Only those participants with data 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 Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [572]
    45 [573]
    Units: Participants
        Baseline; mild; n= 47, 43
    10
    6
        Baseline; moderate; n= 47, 43
    21
    29
        Baseline; severe; n= 47, 43
    15
    8
        Baseline; very severe; n= 47, 43
    1
    0
        Week 4; mild; n= 44, 39
    7
    7
        Week 4; moderate; n= 44, 39
    27
    27
        Week 4; severe; n= 44, 39
    10
    4
        Week 4; very severe; n= 44, 39
    0
    1
        Week 8; mild; n= 44, 40
    4
    7
        Week 8; moderate; n= 44, 40
    32
    29
        Week 8; severe; n= 44, 40
    7
    4
        Week 8; very severe; n= 44, 40
    1
    0
        Week 16; mild; n= 45, 40
    6
    8
        Week 16; moderate; n= 45, 40
    28
    26
        Week 16; severe; n= 45, 40
    11
    6
        Week 16; very severe; n= 45, 40
    0
    0
        Week 24; mild; n= 44, 38
    6
    9
        Week 24; moderate; n= 44, 38
    31
    23
        Week 24; severe; n= 44, 38
    7
    6
        Week 24; very severe; n= 44, 38
    0
    0
        Week 40; mild; n= 37, 36
    7
    9
        Week 40; moderate; n= 37, 36
    21
    21
        Week 40; severe; n= 37, 36
    9
    6
        Week 40; very severe; n= 37, 36
    0
    0
        Week 52; mild; n= 39, 36
    6
    7
        Week 52; n= moderate; n= 39, 36
    24
    23
        Week 52; severe; n= 39, 36
    9
    6
        Week 52; very severe; n= 39, 36
    0
    0
    Notes
    [572] - ITT Population
    [573] - ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with patient global impression of change (PGIC)score in Part B

    		 Close Top of page
    End point title
    		 Number of participants with patient global impression of change (PGIC)score in Part B
    End point description
    Participants completed a PGIC questions at Week 4, 8, 16, 24, 40 and 52. Response options were on a 7 point Likert scale ranging from much better to much worse. PGIC was re-coded from a categorical to numerical value prior to analysis as: much worse = -3, worse = -2, slightly worse = -1, no change = 0, slightly better = 1, better = 2, much better = 3.A categorical summary of PGIC is presented by treatment and visit.Only those participants with data 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 Day 392 in Part B
    End point values
    		 Placebo DNX 75 mg
    Number of subjects analysed
    48 [574]
    45 [575]
    Units: Participants
        Week 4; much worse; n= 44, 39
    0
    1
        Week 4; worse; n= 44, 39
    1
    4
        Week 4; slightly worse; n= 44, 39
    1
    0
        Week 4; no change; n= 44, 39
    18
    17
        Week 4; slightly better; n= 44, 39
    15
    12
        Week 4; better; n= 44, 39
    9
    4
        Week 4; much better; n= 44, 39
    0
    1
        Week 8; much worse; n= 44, 39
    1
    0
        Week 8; worse; n= 44, 39
    1
    1
        Week 8; slightly worse; n= 44, 39
    6
    5
        Week 8; no change; n= 44, 39
    16
    18
        Week 8; slightly better; n= 44, 39
    15
    10
        Week 8; better; n= 44, 39
    4
    4
        Week 8; much better; n= 44, 39
    1
    1
        Week 16; much worse; n= 45, 40
    0
    1
        Week 16; worse; n= 45, 40
    0
    1
        Week 16; slightly worse; n= 45, 40
    0
    3
        Week 16; no change; n= 45, 40
    21
    17
        Week 16; slightly better; n= 45, 40
    20
    13
        Week 16; better; n= 45, 40
    3
    2
        Week 16; much better; n= 45, 40
    1
    3
        Week 24; much worse; n= 44, 38
    0
    1
        Week 4; worse; n= 44, 38
    1
    2
        Week 24; slightly worse; n= 44, 38
    3
    3
        Week 24; no change; n= 44, 38
    15
    13
        Week 24; slightly better; n= 44, 38
    16
    9
        Week 24; better; n= 44, 38
    8
    8
        Week 24; much better; n= 44, 38
    1
    2
        Week 40; much worse; n= 37, 36
    0
    0
        Week 40; worse; n= 37, 36
    2
    1
        Week 40; slightly worse; n= 37, 36
    3
    7
        Week 40; no change; n=37, 36
    9
    12
        Week 40; slightly better; n=37, 36
    14
    7
        Week 40; better; n= 37, 36
    7
    7
        Week 40; much better; n= 37, 36
    2
    2
        Week 52; much worse; n= 39, 35
    0
    1
        Week 52; worse; n= 39, 35
    1
    0
        Week 52; slightly worse; n= 39, 35
    3
    7
        Week 52; no change; n= 39, 35
    14
    15
        Week 52; slightly better; n= 39, 35
    9
    4
        Week 52; better; n= 39, 35
    11
    5
        Week 52; much better; n= 39, 35
    1
    3
    Notes
    [574] - ITT Population
    [575] - ITT Population
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment up to Day 28 in Part A and up to Day 392 in Part B.
    Adverse event reporting additional description
    On treatment SAEs and non-serious AEs were reported for the All Subjects Population.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    DNX 50 mg
    Reporting group description
    		 Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).

    Reporting group title
    DNX 75 mg
    Reporting group description
    		 Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant’s current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant’s current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).

    Serious adverse events
    		 DNX 50 mg DNX 75 mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 9 (11.11%)
    10 / 45 (22.22%)
    10 / 48 (20.83%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Gallbladder adenoma
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pain
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 45 (4.44%)
    4 / 48 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vocal cord leukoplakia
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood sodium decreased
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Craniocerebral injury
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foreign body
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device loosening
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain injury
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis sclerosing
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    3 / 48 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholangitis infective
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 DNX 50 mg DNX 75 mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 9 (55.56%)
    25 / 45 (55.56%)
    25 / 48 (52.08%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 9 (11.11%)
    4 / 45 (8.89%)
    4 / 48 (8.33%)
         occurrences all number
    1
    5
    5
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 9 (11.11%)
    3 / 45 (6.67%)
    0 / 48 (0.00%)
         occurrences all number
    1
    3
    0
    Malaise
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 45 (2.22%)
    2 / 48 (4.17%)
         occurrences all number
    1
    1
    3
    Abdominal pain upper
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 45 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    0
    0
    5
    Diarrhoea
         subjects affected / exposed
    0 / 9 (0.00%)
    4 / 45 (8.89%)
    8 / 48 (16.67%)
         occurrences all number
    0
    4
    8
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 9 (11.11%)
    5 / 45 (11.11%)
    3 / 48 (6.25%)
         occurrences all number
    1
    6
    4
    Hyperhidrosis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 45 (0.00%)
    0 / 48 (0.00%)
         occurrences all number
    1
    0
    0
    Dyspnoea
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 45 (2.22%)
    0 / 48 (0.00%)
         occurrences all number
    1
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 9 (0.00%)
    5 / 45 (11.11%)
    0 / 48 (0.00%)
         occurrences all number
    0
    5
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 9 (11.11%)
    13 / 45 (28.89%)
    16 / 48 (33.33%)
         occurrences all number
    1
    14
    28
    Cystitis
         subjects affected / exposed
    0 / 9 (0.00%)
    5 / 45 (11.11%)
    3 / 48 (6.25%)
         occurrences all number
    0
    8
    5

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Jul 2014
    Amendment included changes to fibrinogen inclusion criteria; addition of macrolide exclusion criteria; addition of screen failure data collection; addition of COPD exacerbation or pneumonia confirmation criteria. Also included are several minor clarifications. In appendix 4 the study questionnaires and diary were added for reference purposes
    08 Oct 2014
    Amendment included changes to the age inclusion criteria and supplemental information on requirements for participants receiving oxygen therapy.
    05 Aug 2015
    Amendment included a change which allow data from the interim analysis for EXACT-RS to be externally disclosed prior to study end or release of the clinical pharmacology study report (CPSR). The scope of the exit interview expanded to include study sites in Germany in addition to the United States. Stopping of recruitment prior to reaching the estimated approximate number of participants to be enrolled in Part B was also addressed.

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

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

    European Medicines Agency © 1995-Fri Apr 26 23:10:40 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA