Investigation of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Efficacy of Oral Danirixin in Symptomatic COPD Subjects With Mild to Moderate Airflow Limitation at Risk for Exacerbations

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02130193
• Collaborator: (none)
• Enrollment: 102
• Locations: 16
• Arms: 2
• Actual Duration (Months): 30.5
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The aim of this First Time in Patient study is to obtain initial information on the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical efficacy of repeat daily administration of danirixin in subjects with symptomatic chronic obstructive pulmonary disease (COPD) having mild to moderate airflow limitation and are at high risk for future COPD exacerbations.

The study will be conducted in two parts. Part A will be a two week open label, single arm study in patients with COPD to obtain pharmacokinetic data and safety information of repeat dosing of danirixin in the population of interest. Approximately 10 subjects will be enrolled in Part A of the study. Progression to and dose selection for Part B will occur following review of the data collected in Part A. Part B will be a 52-week, randomized, double-blind (sponsor unblind), placebo-controlled on top of standard of care, parallel group study. Part B will evaluate several clinical efficacy assessments related to exacerbations and respiratory symptoms. Approximately 100 subjects will be enrolled with a target of 80 subjects completing 52 weeks of danirixin administration.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Danirixin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Feb 13, 2014
• Actual Primary Completion Date: Aug 29, 2016
• Actual Study Completion Date: Aug 29, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A Subjects will receive 50 mg danirixin twice daily (BID) orally for 14 days. If the exposure to danirixin is lower than expected, after 14 days of dosing, then the dose may be increased to 75 mg BID for Part B.	Drug: Danirixin; Danirixin is available as 50 or 75 mg white, film coated immediate release tablet.
Experimental: Part B Subjects will be randomized to receive either danirixin BID or placebo BID treatment along with standard care of treatment for 52 weeks. Subjects completing Part A and meeting the eligibility criteria for Part B could also be randomized in Part B.	Drug: Danirixin; Danirixin is available as 50 or 75 mg white, film coated immediate release tablet.; Drug: Placebo; Subjects will receive danirixin matching placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Any Adverse Event (AE) and, Serious Adverse Event (SAE) in Part A [Up to Day 28 in Part A]

   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.

2. Number of Participants With Any AE and SAE in Part B [Up to Day 392 in Part B]

   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.

3. 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 [Up to Day 28 in Part A]

   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.

4. 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 [Up to Day 392 in Part B]

   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).

5. Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) in Part A [Up to Day 28 in Part A]

   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.

6. Number of Participants With Abnormal 12-lead ECG in Part B [Up to Day 392 in Part B]

   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).

7. Number of Participants With Hematology Values of Potential Clinical Importance in Part A [Up to Day 28 in Part A]

   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.

8. Number of Participants With Hematology Values of Potential Clinical Importance in Part B [Up to Day 392 in Part B]

   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).

9. Number of Participants With Clinical Chemistry Values of Potential Clinical Importance in Part A [Up to Day 28 in Part A]

   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.

10. Number of Participants With Clinical Chemistry Values of Potential Clinical Importance in Part B [Up to Day 392 in Part B]

    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. 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).

11. Number of Participants With Urinalysis Dipstick Results in Part A [Up to Day 28 in Part A]

    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. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

12. Number of Participants With Urinalysis Dipstick Results in Part B [Up to Day 392 in Part B]

    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).

13. Change From Baseline in Urine Power of Hydrogen (pH) at Day 14 in Part A [Up to Day 28 in Part A]

    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.

14. Change From Baseline in Urine pH in Part B [Up to Day 392 in Part B]

    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).

15. Change From Baseline in Urine Specific Gravity of Urine in Part A [Up to Day 28 in Part A]

    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.

16. Change From Baseline in Urine Specific Gravity of Urine in Part B [Up to Day 392 in Part B]

    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.

17. Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points in Part A [Up to Day 28 in Part A]

    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.

18. Change From Baseline in FEV1 and FVC at the Indicated Time Points in Part B [Up to Day 392 in Part B]

    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).

19. Maximum Observed Plasma Concentration (Cmax) of Danirixin in Part A [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]

    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.

20. Time of Occurrence of Cmax (Tmax) of Danirixin in Part A [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]

    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.

21. Area Under the Blood Concentration-time Curve (AUC) Over Dosing Interval (AUC[0-12]) of Danirixin in Part A [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]

    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.

22. Number of Health Care Resource Utilization (HCRU) Defined COPD Exacerbations Per Year in Part B [Up to Day 392 in Part B]

    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.

23. Monthly Weighted Means of Exacerbations of Chronic Pulmonary Disease Tool-respiratory Symptoms (EXACT-RS) Total Score in Part B [Up to Day 392 in Part B]

    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).

Secondary Outcome Measures

1. Cmax of Danirixin in Part B [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]

   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).

2. Tmax of Danirixin in Part B [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]

   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).

3. AUC(0-12) of Danirixin in Part B [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]

   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).

4. Number of EXACT-PRO Exacerbations Per Year in Part B [Up to Day 392 in Part B]

   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.

5. Monthly Weighted Means of Exacerbations of EXACT-PRO Total Score in Part B [Up to Day 392 in Part B]

   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).

6. Time to First HCRU COPD Exacerbation in Part B [Up to Day 392 in Part B]

   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.

7. Time to First EXACT-PRO Event in Part B [Up to Day 392 in Part B]

   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.

8. Assessment of Duration of EXACT-PRO Events in Part B [Up to Day 392 in Part B]

   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.

9. Assessment of Severity of EXACT-PRO Events in Part B [Up to Day 392 in Part B]

   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).

10. Monthly Weighted Means of EXACT-RS Domain Scores in Part B [Up to Day 392 in Part B]

    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).

11. Change From Baseline for COPD Assessment Test (CAT) at the Indicated Time Points in Part B [Up to Day 392 in Part B]

    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).

12. Number of Participants With Physician's Global Assessment (PGA) Readings in Part B [Up to Day 392 in Part B]

    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).

13. Number of Participants With Patient Global Rating of Severity (PGRS) Score in Part B [Up to Day 392 in Part B]

    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).

14. Number of Participants With Patient Global Impression of Change (PGIC)Score in Part B [Up to Day 392 in Part B]

    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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female aged between 40 and 70 years of age inclusive, at the time of signing the informed consent

• Subjects with a documented history of COPD exacerbation(s) in the 12 months prior to study participation meeting at least one of the following criteria: >=2 COPD exacerbations resulting in prescription for antibiotics and/or oral corticosteroids or hospitalization or extended observation in a hospital emergency room or outpatient center; 1 COPD exacerbation resulting in prescription for antibiotics and/or oral corticosteroids or hospitalization or extended observation in a hospital emergency room or outpatient center and a plasma fibrinogen concentration at screening >=3.5 milligram/milliliter (mg/mL)

• Diagnosis of symptomatic chronic obstructive pulmonary disease with mild to moderate airflow obstruction (COPD-GOLD I or II) for at least 2 years based on American Thoracic Society (ATS)/ European Respiratory Society (ERS) current guidelines or symptoms consistent with COPD for at least 2 years

• Subjects with a post-bronchodilator FEV1/FVC ratio of < 0.7 and FEV1 >=50% of predicted normal value calculated using National Health and Nutrition Examination Survey (NHANES) III reference equation at Visit 1

• A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)

40 milli international units/mL (MIU/mL) and estradiol < 40 picogram (pg)/mL (<147 picomole/Liter [pmol/L]) is confirmatory]. Females on hormone replacement therapy (HRT) will not be enrolled in the study.

• Body weight >=45 kilogram (kg)

• Current smokers and former smokers with a cigarette smoking history of >=10 pack years (1 pack year =20 cigarettes smoked per day for 1 year or equivalent). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1

• Subjects with a history of respiratory symptoms, including chronic cough and/or mucus hypersecretion on most days for at least the previous 3 months prior to Visit 1

• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <2x upper limit of normal (ULN); alkaline phosphatase and bilirubin <=1.5xULN (isolated bilirubin

1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)

• Able to perform lung function tests reliably

• Based on single or averaged corrected QT (QTc) values of triplicate ECGs obtained over a brief recording period: Fridericia-corrected QTc (QTcF) < 450 milliseconds (msec); or QTc < 480 msec in subjects with Bundle Branch Block

• Subjects must have the ability to use an electronic diary on a daily basis [Part B only]

• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Exclusion Criteria:

• Diagnosis of asthma, or other clinically relevant lung disease (other than COPD), e.g. sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis or lung cancer; Subject with alpha-1-antitrypsin deficiency as the underlying cause of COPD

• Pulse Oximetry levels <88% (at rest on room air) at screening

• Less than 14 days have elapsed from completion of a course of antibiotics or oral corticosteroids for a recent COPD exacerbation.

• Diagnosis of Pneumonia (chest X-Ray or computed tomography [CT] confirmed) within the last 3 months prior to screening

• History or current evidence of clinically significant renal disease, diabetes mellitus/metabolic syndrome, hypertension or any other clinically significant cardiovascular, neurological, endocrine, or hematological abnormalities that are uncontrolled on permitted therapy. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subjects at risk through study participation, or which would affect the safety analysis or other analysis if the disease/condition exacerbated during the study.

• A positive pre-study drug/alcohol screen

• A positive test for human immunodeficiency virus (HIV) antibody

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening

• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• History of regular alcohol consumption within 6 months of the study defined as: For non United States of America (US) sites: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits; For US sites: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

• Current or expected use of proton pump inhibitors or histamine H2-receptor antagonists during the study period

• Chest X-ray (posteroanterior with lateral) or CT scan reveals evidence of pneumonia or a clinically significant abnormality not believed to be due to the presence of COPD (historic data up to 1 yr may be used).

• Subjects with peripheral blood neutrophil count (PBN) <2x10^9/Liter

• Subject with history of previous lung surgery (e.g. lobectomy, pneumonectomy, or lung volume reduction)

• Requiring the use of oral or injectable Cytochrome P450 3A4 (CYP3A4) or breast cancer resistance protein (BCRP) substrates with a narrow therapeutic index

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35294
2	GSK Investigational Site	Denver	Colorado	United States	80206
3	GSK Investigational Site	Iowa City	Iowa	United States	52242
4	GSK Investigational Site	Oaks	Pennsylvania	United States	19456
5	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19140
6	GSK Investigational Site	Spartanburg	South Carolina	United States	29303
7	GSK Investigational Site	Frankfurt	Hessen	Germany	60596
8	GSK Investigational Site	Neu isenburg	Hessen	Germany	63263
9	GSK Investigational Site	Dueren	Nordrhein-Westfalen	Germany	52349
10	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45359
11	GSK Investigational Site	Magdeburg	Sachsen-Anhalt	Germany	39112
12	GSK Investigational Site	Leipzig	Sachsen	Germany	04207
13	GSK Investigational Site	Leipzig	Sachsen	Germany	04275
14	GSK Investigational Site	Grosshansdorf	Schleswig-Holstein	Germany	22927
15	GSK Investigational Site	Berlin		Germany	10787
16	GSK Investigational Site	Berlin		Germany	10789

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02130193
• Other Study ID Numbers: 200163
• First Posted: May 5, 2014
• Last Update Posted: Jul 2, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by GlaxoSmithKline: Efficacy; Danirixin; EXACT-PRO; COPD; Safety; RD; CXCR2 inhibitor; EXACT-RS; PK; HCRU exacerbations; PD
• Additional relevant MeSH terms: Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

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 Detail	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.

Arm/Group Title	Part A: 4-week Open-label Period: DNX 50 mg	Part B: 52-week Double-blind Period: Placebo	Part B: 52-week Double-blind Period: DNX 75 mg
Arm/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).	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).	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).
Period Title: Part A: 4-week Open-label Period
STARTED	9	0	0
COMPLETED	9	0	0
NOT COMPLETED	0	0	0
Period Title: Part A: 4-week Open-label Period
STARTED	0	48	45
COMPLETED	0	38	37
NOT COMPLETED	0	10	8

Baseline Characteristics

Arm/Group Title	Placebo	DNX 75 mg	Total
Arm/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).	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).	Total of all reporting groups
Overall Participants	48	45	93
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.8 (7.32)	62.4 (6.91)	60.5 (7.31)
Sex: Female, Male (Count of Participants)
Female	25 52.1%	23 51.1%	48 51.6%
Male	23 47.9%	22 48.9%	45 48.4%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	1 2.1%	0 0%	1 1.1%
White - White/Caucasian/European Heritage	47 97.9%	45 100%	92 98.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Adverse Event (AE) and, Serious Adverse Event (SAE) in Part A
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.
Time Frame	Up to Day 28 in Part A

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
AE	5 10.4%
SAEs	1 2.1%

2. Primary Outcome

Title	Number of Participants With Any AE and SAE in Part B
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.
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
AE	25 52.1%	25 55.6%
SAEs	10 20.8%	10 22.2%

3. Primary Outcome

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
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.
Time Frame	Up to Day 28 in Part A

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
SBP, Day 14, low	0 0%
SBP, Day 14, high	2 4.2%
DBP, Day 14, low	0 0%
DBP, Day 14, high	1 2.1%

4. Primary Outcome

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
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
SBP, Day 1, low, n=48, 45	0 0%	0 0%
SBP, Day 1, high, n=48, 45	0 0%	2 4.4%
SBP, Day 28, low, n=47, 44	0 0%	0 0%
SBP, Day 28, high, n=47, 44	0 0%	3 6.7%
SBP, Day 56, low, n=46, 41	0 0%	0 0%
SBP, Day 56, high, n=46, 41	2 4.2%	2 4.4%
SBP, Day 112, low, n=46, 40	0 0%	0 0%
SBP, Day 112, high, n=46, 40	3 6.3%	2 4.4%
SBP, Day 168, low, n=44, 39	0 0%	0 0%
SBP, Day 168, high, n=44, 39	2 4.2%	3 6.7%
SBP, Day 280, low, n=39, 37	1 2.1%	0 0%
SBP, Day 280, high, n=39, 37	2 4.2%	2 4.4%
SBP, Day 364, low, n=39, 37	0 0%	0 0%
SBP, Day 364, high, n=39, 37	1 2.1%	4 8.9%
DBP, Day 280, low, n=39, 37	0 0%	0 0%
DBP, Day 280, high, n=39, 37	1 2.1%	0 0%
Respiratory rate, Day 1, low, n=48, 45	1 2.1%	0 0%
Respiratory rate, Day 1, high, n=48, 45	1 2.1%	0 0%
Respiratory rate, Day 56, low, n=46, 41	0 0%	0 0%
Respiratory rate, Day 56, high, n=46, 41	2 4.2%	0 0%
Respiratory rate, Day 112, low, n=46, 40	1 2.1%	0 0%
Respiratory rate, Day 112, high, n=46, 40	0 0%	0 0%
Respiratory rate, Day 168, low, n=44, 39	0 0%	0 0%
Respiratory rate, Day 168, high, n=44, 39	0 0%	1 2.2%

5. Primary Outcome

Title	Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) in Part A
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.
Time Frame	Up to Day 28 in Part A

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
Abnormal-NCS, Day 1, pre-dose	3 6.3%
Abnormal-CS, Day 1, pre-dose	0 0%
Abnormal-NCS, Day 1, pre-dose 2	2 4.2%
Abnormal-CS, Day 1, pre-dose 2	0 0%
Abnormal-NCS, Day 1, pre-dose 3	2 4.2%
Abnormal-CS, Day 1, pre-dose 3	0 0%

6. Primary Outcome

Title	Number of Participants With Abnormal 12-lead ECG in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
Abnormal-NCS, Day 28, n=47, 44	20 41.7%	16 35.6%
Abnormal-CS, Day 28, n=47, 44	0 0%	1 2.2%
Abnormal-NCS, Day 168, n=44, 38	15 31.3%	11 24.4%
Abnormal-CS, Day 168, n=44, 38	0 0%	0 0%

7. Primary Outcome

Title	Number of Participants With Hematology Values of Potential Clinical Importance in Part A
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.
Time Frame	Up to Day 28 in Part A

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
RBC count, Day 14, low	1 2.1%
Category title 2. RBC count, Day 14, high	0 0%

8. Primary Outcome

Title	Number of Participants With Hematology Values of Potential Clinical Importance in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
Platelet count, Day 28, low, n=46, 43	0 0%	1 2.2%
Platelet count, Day 28, high, n=46, 43	0 0%	0 0%
RBC count, Day 28, low, n=46, 43	0 0%	1 2.2%
RBC count, Day 28, high, n=46, 43	0 0%	0 0%
Platelet count, Day 168, low, n=43, 38	0 0%	1 2.2%
Platelet count, Day 168, high, n=43, 38	1 2.1%	0 0%
RBC count, Day 168, low, n=44, 38	2 4.2%	1 2.2%
RBC count, Day 168, high, n=44, 38	0 0%	0 0%
WBC count, Day 168, low, n=44, 38	0 0%	0 0%
WBC count, Day 168, high, n=44, 38	1 2.1%	0 0%
Platelet count, Day 364, low, n=39, 36	0 0%	1 2.2%
Platelet count, Day 364, high, n=39, 36	0 0%	0 0%
RBC count, Day 364, low, n=39, 36	2 4.2%	1 2.2%
RBC count, Day 364, high, n=39, 36	0 0%	0 0%

9. Primary Outcome

Title	Number of Participants With Clinical Chemistry Values of Potential Clinical Importance in Part A
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.
Time Frame	Up to Day 28 in Part A

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
GGT, Day 14, low	0 0%
GGT, Day 14, high	2 4.2%
Uric acid, Day 14, low	0 0%
Uric acid, Day 14, high	8 16.7%

10. Primary Outcome

Title	Number of Participants With Clinical Chemistry Values of Potential Clinical Importance in Part B
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. 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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
Creatinine, Day 28, low, n=47, 44	0 0%	0 0%
Creatinine, Day 28, high, n=47, 44	0 0%	1 2.2%
GGT, Day 28, low, n=47, 44	0 0%	0 0%
GGT, Day 28, high, n=47, 44	7 14.6%	3 6.7%
Uric acid, Day 28, low, n=47, 44	0 0%	0 0%
Uric acid, Day 28, high, n=47, 44	47 97.9%	44 97.8%
ALP, Day 84, low, n=46, 40	0 0%	0 0%
ALP, Day 84, high, n=46, 40	0 0%	1 2.2%
ALT, Day 84, low, n=46, 40	0 0%	0 0%
ALT, Day 84, high, n=46, 40	0 0%	1 2.2%
AST, Day 84, low, n=46, 40	0 0%	0 0%
AST, Day 84, high, n=46, 40	0 0%	1 2.2%
GGT, Day 168, low, n=43, 39	0 0%	0 0%
GGT, Day 168, high, n=43, 39	5 10.4%	1 2.2%
Uric acid, Day 168, low, n=43, 39	0 0%	0 0%
Uric acid, Day 168, high, n=43, 39	43 89.6%	39 86.7%
Direct bilirubin, Day 364, low, n=39, 37	0 0%	0 0%
Direct bilirubin, Day 364, high, n=39, 37	1 2.1%	0 0%
Total bilirubin, Day 364, low, n=39, 37	0 0%	0 0%
Total bilirubin, Day 364, high, n=39, 37	1 2.1%	0 0%
GGT, Day 364, low, n=39, 37	0 0%	0 0%
GGT, Day 364, high, n=39, 37	5 10.4%	1 2.2%
Uric acid, Day 364, low, n=39, 37	0 0%	0 0%
Uric acid, Day 364, high, n=39, 37	39 81.3%	37 82.2%

11. Primary Outcome

Title	Number of Participants With Urinalysis Dipstick Results in Part A
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. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Up to Day 28 in Part A

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
Occult blood, Day 14, negative, n=9	9 18.8%
Glucose, Day 14, negative, n=9	9 18.8%
Ketones, Day 14, negative, n=9	9 18.8%
Protein, Day 14, 1+, n=9	1 2.1%
Protein, Day 14, negative, n=9	8 16.7%
Urine microscopy-RBC, Day 14, not seen, n=1	1 2.1%
Urine microscopy-WBC, Day 14, not seen, n=1	1 2.1%

12. Primary Outcome

Title	Number of Participants With Urinalysis Dipstick Results in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
Occult blood, Day 28, trace, n=47, 44	0 0%	2 4.4%
Occult blood, Day 28, 1+, n=47, 44	3 6.3%	0 0%
Occult blood, Day 28, negative, n=47, 44	44 91.7%	42 93.3%
Glucose, Day 28, trace, n=47, 44	0 0%	1 2.2%
Glucose, Day 28, 1+, n=47, 44	1 2.1%	0 0%
Glucose, Day 28, 3+, n=47, 44	0 0%	2 4.4%
Glucose, Day 28, negative, n=47, 44	46 95.8%	41 91.1%
Ketones, Day 28, trace, n=47, 44	3 6.3%	2 4.4%
Ketones, Day 28, negative, n=47, 44	44 91.7%	42 93.3%
Protein, Day 28, trace, n=47, 44	2 4.2%	1 2.2%
Protein, Day 28, 1+, n=47, 44	2 4.2%	2 4.4%
Protein, Day 28, negative, n=47, 44	43 89.6%	41 91.1%
Occult blood, Day 168, trace, n=42, 36	3 6.3%	2 4.4%
Occult blood, Day 168, 1+, n=42, 36	1 2.1%	1 2.2%
Occult blood, Day 168, 3+, n=42, 36	1 2.1%	0 0%
Occult blood, Day 168, negative, n=42, 36	37 77.1%	33 73.3%
Glucose, Day 168, 2+, n=42, 36	1 2.1%	0 0%
Glucose, Day 168, negative, n=42, 36	41 85.4%	36 80%
Ketones, Day 168, trace, n=42, 36	3 6.3%	0 0%
Ketones, Day 168, negative, n=42, 36	39 81.3%	36 80%
Protein, Day 168, trace, n=42, 36	2 4.2%	1 2.2%
Protein, Day 168, 1+, n=42, 36	1 2.1%	2 4.4%
Protein, Day 168, 2+, n=42, 36	1 2.1%	0 0%
Protein, Day 168, negative, n=42, 36	38 79.2%	33 73.3%
Occult blood, Day 224, negative, n=1, 0	1 2.1%	0 0%
Glucose, Day 224, negative, n=1, 0	1 2.1%	0 0%
Ketones, Day 224, negative, n=1, 0	1 2.1%	0 0%
Protein, Day 224, negative, n=1, 0	1 2.1%	0 0%
Occult blood, Day 364, trace, n=38, 36	3 6.3%	2 4.4%
Occult blood, Day 364, 1+, n=38, 36	2 4.2%	1 2.2%
Occult blood, Day 364, negative, n=38, 36	33 68.8%	33 73.3%
Glucose, Day 364, trace, n=38, 36	1 2.1%	0 0%
Glucose, Day 364, 2+, n=38, 36	1 2.1%	0 0%
Glucose, Day 364, negative, n=38, 36	36 75%	36 80%
Ketones, Day 364, trace, n=38, 36	3 6.3%	0 0%
Ketones, Day 364, negative, n=38, 36	35 72.9%	36 80%
Protein, Day 364, trace, n=38, 36	3 6.3%	0 0%
Protein, Day 364, 1+, n=38, 36	1 2.1%	2 4.4%
Protein, Day 364, 2+, n=38, 36	1 2.1%	1 2.2%
Protein, Day 364, negative, n=38, 36	33 68.8%	33 73.3%

13. Primary Outcome

Title	Change From Baseline in Urine Power of Hydrogen (pH) at Day 14 in Part A
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.
Time Frame	Up to Day 28 in Part A

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
Mean (Standard Deviation) [pH]	-0.06 (1.488)

14. Primary Outcome

Title	Change From Baseline in Urine pH in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
Day 28, n=45, 43	-0.17 (0.648)	-0.10 (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)

15. Primary Outcome

Title	Change From Baseline in Urine Specific Gravity of Urine in Part A
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.
Time Frame	Up to Day 28 in Part A

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
Mean (Standard Deviation) [urine specific gravity]	-0.0008 (0.00817)

16. Primary Outcome

Title	Change From Baseline in Urine Specific Gravity of Urine in Part B
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.
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
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)

17. Primary Outcome

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
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.
Time Frame	Up to Day 28 in Part A

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
FEV1, Day 14	0.0978 (0.10378)
FVC, Day 14	0.2233 (0.25407)

18. Primary Outcome

Title	Change From Baseline in FEV1 and FVC at the Indicated Time Points in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
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 (0.3300)	0.043 (0.2310)
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	-0.020 (0.5966)	0.041 (0.4271)
FVC, Day 364, n=39, 37	-0.021 (0.4290)	0.008 (0.4190)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.18
	Parameter Dispersion	Type: Standard Deviation; Value: 0.06
	Estimation Comments	FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.18
	Parameter Dispersion	Type: Standard Deviation; Value: 0.06
	Estimation Comments	FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.67
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.18
	Parameter Dispersion	Type: Standard Deviation; Value: 0.06
	Estimation Comments	FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.52
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.18
	Parameter Dispersion	Type: Standard Deviation; Value: 0.06
	Estimation Comments	FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.18
	Parameter Dispersion	Type: Standard Deviation; Value: 0.06
	Estimation Comments	FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.18
	Parameter Dispersion	Type: Standard Deviation; Value: 0.06
	Estimation Comments	FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.09
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.09
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.09
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.09
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.09
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.09
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.85
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.23
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.23
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.23
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.23
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.23
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.23
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.47
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.14
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.14
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.14
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.14
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.14
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.14
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments	FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.13
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FVC, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.13
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FVC, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.13
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FVC, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.13
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FVC, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.13
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FVC, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.13
	Parameter Dispersion	Type: Standard Deviation; Value: 0.08
	Estimation Comments	FVC, Day 28. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 43

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.15
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 44

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.15
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 45

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.15
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 46

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.15
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 47

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.15
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 48

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.15
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 56. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 49

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.17
	Parameter Dispersion	Type: Standard Deviation; Value: 0.10
	Estimation Comments	FVC, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 50

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.17
	Parameter Dispersion	Type: Standard Deviation; Value: 0.10
	Estimation Comments	FVC, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 51

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.17
	Parameter Dispersion	Type: Standard Deviation; Value: 0.10
	Estimation Comments	FVC, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 52

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.17
	Parameter Dispersion	Type: Standard Deviation; Value: 0.10
	Estimation Comments	FVC, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 53

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.17
	Parameter Dispersion	Type: Standard Deviation; Value: 0.10
	Estimation Comments	FVC, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 54

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.17
	Parameter Dispersion	Type: Standard Deviation; Value: 0.10
	Estimation Comments	FVC, Day 112. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 55

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.72
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.24
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 56

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.24
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 57

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.24
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 58

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.24
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 59

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.24
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 60

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.24
	Parameter Dispersion	Type: Standard Deviation; Value: 0.09
	Estimation Comments	FVC, Day 168. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 61

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.76
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.32
	Parameter Dispersion	Type: Standard Deviation; Value: 0.12
	Estimation Comments	FVC, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 62

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.32
	Parameter Dispersion	Type: Standard Deviation; Value: 0.12
	Estimation Comments	FVC, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 63

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.32
	Parameter Dispersion	Type: Standard Deviation; Value: 0.12
	Estimation Comments	FVC, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 64

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.32
	Parameter Dispersion	Type: Standard Deviation; Value: 0.12
	Estimation Comments	FVC, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 65

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.32
	Parameter Dispersion	Type: Standard Deviation; Value: 0.12
	Estimation Comments	FVC, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 66

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.46
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.32
	Parameter Dispersion	Type: Standard Deviation; Value: 0.12
	Estimation Comments	FVC, Day 280. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 67

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.28
	Parameter Dispersion	Type: Standard Deviation; Value: 0.11
	Estimation Comments	FVC, Day 364. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 68

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.28
	Parameter Dispersion	Type: Standard Deviation; Value: 0.11
	Estimation Comments	FVC, Day 364. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 69

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.28
	Parameter Dispersion	Type: Standard Deviation; Value: 0.11
	Estimation Comments	FVC, Day 364. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 70

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.46
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.28
	Parameter Dispersion	Type: Standard Deviation; Value: 0.11
	Estimation Comments	FVC, Day 364. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 71

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.28
	Parameter Dispersion	Type: Standard Deviation; Value: 0.11
	Estimation Comments	FVC, Day 364. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 72

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.28
	Parameter Dispersion	Type: Standard Deviation; Value: 0.11
	Estimation Comments	FVC, Day 364. Data presented are for 95% equal-tailed credible intervals

19. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Danirixin in Part A
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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
Day 1 dose	397.785
Day 14 dose	512.576

20. Primary Outcome

Title	Time of Occurrence of Cmax (Tmax) of Danirixin in Part A
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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
Day 1 dose	1.017
Day 14 dose	2.000

21. Primary Outcome

Title	Area Under the Blood Concentration-time Curve (AUC) Over Dosing Interval (AUC[0-12]) of Danirixin in Part A
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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	DNX 50 mg
Arm/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).
Measure Participants	9
Day 1 dose	2203.522
Day 14 dose	2838.526

22. Primary Outcome

Title	Number of Health Care Resource Utilization (HCRU) Defined COPD Exacerbations Per Year in Part B
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.
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	23	20
Mean (Standard Deviation) [Exacerbations per year]	2.9 (3.13)	3.2 (5.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 1.0 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	2.48
	Confidence Interval	(2-Sided) 95%; 0.92 to 4.43
	Parameter Dispersion	Type: Standard Deviation; Value: 0.977
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.9 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	2.48
	Confidence Interval	(2-Sided) 95%; 0.92 to 4.43
	Parameter Dispersion	Type: Standard Deviation; Value: 0.977
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.8 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	2.48
	Confidence Interval	(2-Sided) 95%; 0.92 to 4.43
	Parameter Dispersion	Type: Standard Deviation; Value: 0.977
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.7 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	2.48
	Confidence Interval	(2-Sided) 95%; 0.92 to 4.43
	Parameter Dispersion	Type: Standard Deviation; Value: 0.977
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.6 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	2.48
	Confidence Interval	(2-Sided) 95%; 0.92 to 4.43
	Parameter Dispersion	Type: Standard Deviation; Value: 0.977
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

23. Primary Outcome

Title	Monthly Weighted Means of Exacerbations of Chronic Pulmonary Disease Tool-respiratory Symptoms (EXACT-RS) Total Score in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
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	12.0 (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	13.0 (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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.60
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -2.81 to 2.17
	Parameter Dispersion	Type: Standard Deviation; Value: 1.29
	Estimation Comments	EXACT-RS, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.58
	Confidence Interval	(2-Sided) 95%; -3.11 to 2.37
	Parameter Dispersion	Type: Standard Deviation; Value: 1.42
	Estimation Comments	EXACT-RS, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.46
	Confidence Interval	(2-Sided) 95%; -4.43 to 1.45
	Parameter Dispersion	Type: Standard Deviation; Value: 1.52
	Estimation Comments	EXACT-RS, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.20
	Confidence Interval	(2-Sided) 95%; -4.07 to 1.90
	Parameter Dispersion	Type: Standard Deviation; Value: 1.53
	Estimation Comments	EXACT-RS, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) 95%; -3.82 to 2.28
	Parameter Dispersion	Type: Standard Deviation; Value: 1.56
	Estimation Comments	EXACT-RS, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.72
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.93
	Confidence Interval	(2-Sided) 95%; -4.01 to 2.26
	Parameter Dispersion	Type: Standard Deviation; Value: 1.58
	Estimation Comments	EXACT-RS, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.00
	Confidence Interval	(2-Sided) 95%; -4.15 to 2.09
	Parameter Dispersion	Type: Standard Deviation; Value: 1.58
	Estimation Comments	EXACT-RS, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.81
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.48
	Confidence Interval	(2-Sided) 95%; -4.71 to 1.76
	Parameter Dispersion	Type: Standard Deviation; Value: 1.69
	Estimation Comments	EXACT-RS, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.76
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.23
	Confidence Interval	(2-Sided) 95%; -4.66 to 2.22
	Parameter Dispersion	Type: Standard Deviation; Value: 1.75
	Estimation Comments	EXACT-RS, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.91
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-2.26
	Confidence Interval	(2-Sided) 95%; -5.66 to 0.99
	Parameter Dispersion	Type: Standard Deviation; Value: 1.74
	Estimation Comments	EXACT-RS, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.05
	Confidence Interval	(2-Sided) 95%; -4.73 to 2.13
	Parameter Dispersion	Type: Standard Deviation; Value: 1.73
	Estimation Comments	EXACT-RS, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.35
	Confidence Interval	(2-Sided) 95%; -4.77 to 2.04
	Parameter Dispersion	Type: Standard Deviation; Value: 1.74
	Estimation Comments	EXACT-RS, 12 month. Data presented are for 95% equal-tailed credible intervals

24. Secondary Outcome

Title	Cmax of Danirixin in Part B
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).
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	DNX 75 mg
Arm/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).
Measure Participants	45
Day 1 dose, n=44	517.784
Day 364 dose, n=36	756.391

25. Secondary Outcome

Title	Tmax of Danirixin in Part B
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).
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	DNX 75 mg
Arm/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).
Measure Participants	45
Day 1 dose, n=44	2.000
Day 364 dose, n=36	1.100

26. Secondary Outcome

Title	AUC(0-12) of Danirixin in Part B
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).
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	DNX 75 mg
Arm/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).
Measure Participants	45
Day 1 dose, n=44	2388.303
Day 364 dose, n=36	4366.995

27. Secondary Outcome

Title	Number of EXACT-PRO Exacerbations Per Year in Part B
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.
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	27	28
Mean (Standard Deviation) [Exacerbations per year]	3.6 (2.75)	3.3 (3.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.278
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 1.0 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.63
	Parameter Dispersion	Type: Standard Deviation; Value: 0.242
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.138
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.9 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.63
	Parameter Dispersion	Type: Standard Deviation; Value: 0.242
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.8 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.63
	Parameter Dispersion	Type: Standard Deviation; Value: 0.242
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.7 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.63
	Parameter Dispersion	Type: Standard Deviation; Value: 0.242
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.6 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.63
	Parameter Dispersion	Type: Standard Deviation; Value: 0.242
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

28. Secondary Outcome

Title	Monthly Weighted Means of Exacerbations of EXACT-PRO Total Score in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
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 (12.20)
EXACT-PRO, 11 month, n=39,36	36.0 (11.87)	34.6 (11.49)
EXACT-PRO, 12 month, n=39,35	36.7 (11.57)	35.0 (11.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95%; -4.55 to 3.23
	Parameter Dispersion	Type: Standard Deviation; Value: 2.04
	Estimation Comments	EXACT-PRO, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -5.03 to 3.60
	Parameter Dispersion	Type: Standard Deviation; Value: 2.21
	Estimation Comments	EXACT-PRO, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.81
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.99
	Confidence Interval	(2-Sided) 95%; -6.60 to 2.27
	Parameter Dispersion	Type: Standard Deviation; Value: 2.29
	Estimation Comments	EXACT-PRO, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.64
	Confidence Interval	(2-Sided) 95%; -5.92 to 3.07
	Parameter Dispersion	Type: Standard Deviation; Value: 2.31
	Estimation Comments	EXACT-PRO, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.30
	Confidence Interval	(2-Sided) 95%; -5.70 to 3.55
	Parameter Dispersion	Type: Standard Deviation; Value: 2.40
	Estimation Comments	EXACT-PRO, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.31
	Confidence Interval	(2-Sided) 95%; -6.46 to 3.05
	Parameter Dispersion	Type: Standard Deviation; Value: 2.42
	Estimation Comments	EXACT-PRO, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.60
	Confidence Interval	(2-Sided) 95%; -6.75 to 2.90
	Parameter Dispersion	Type: Standard Deviation; Value: 2.45
	Estimation Comments	EXACT-PRO, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-2.10
	Confidence Interval	(2-Sided) 95%; -6.93 to 3.30
	Parameter Dispersion	Type: Standard Deviation; Value: 2.63
	Estimation Comments	EXACT-PRO, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.92
	Confidence Interval	(2-Sided) 95%; -7.04 to 3.18
	Parameter Dispersion	Type: Standard Deviation; Value: 2.63
	Estimation Comments	EXACT-PRO, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.90
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-3.44
	Confidence Interval	(2-Sided) 95%; -8.74 to 1.87
	Parameter Dispersion	Type: Standard Deviation; Value: 2.72
	Estimation Comments	EXACT-PRO, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.16
	Confidence Interval	(2-Sided) 95%; -6.20 to 4.20
	Parameter Dispersion	Type: Standard Deviation; Value: 2.72
	Estimation Comments	EXACT-PRO, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.73
	Confidence Interval	(2-Sided) 95%; -6.91 to 3.45
	Parameter Dispersion	Type: Standard Deviation; Value: 2.70
	Estimation Comments	EXACT-PRO, 12 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95%; -4.55 to 3.23
	Parameter Dispersion	Type: Standard Deviation; Value: 2.04
	Estimation Comments	EXACT-PRO, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -5.03 to 3.60
	Parameter Dispersion	Type: Standard Deviation; Value: 2.21
	Estimation Comments	EXACT-PRO, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.67
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.99
	Confidence Interval	(2-Sided) 95%; -6.60 to 2.27
	Parameter Dispersion	Type: Standard Deviation; Value: 2.29
	Estimation Comments	EXACT-PRO, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.64
	Confidence Interval	(2-Sided) 95%; -5.92 to 3.07
	Parameter Dispersion	Type: Standard Deviation; Value: 2.31
	Estimation Comments	EXACT-PRO, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.30
	Confidence Interval	(2-Sided) 95%; -5.70 to 3.55
	Parameter Dispersion	Type: Standard Deviation; Value: 2.40
	Estimation Comments	EXACT-PRO, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.31
	Confidence Interval	(2-Sided) 95%; -6.46 to 3.05
	Parameter Dispersion	Type: Standard Deviation; Value: 2.42
	Estimation Comments	EXACT-PRO, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.60
	Confidence Interval	(2-Sided) 95%; -6.75 to 2.90
	Parameter Dispersion	Type: Standard Deviation; Value: 2.45
	Estimation Comments	EXACT-PRO, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-2.10
	Confidence Interval	(2-Sided) 95%; -6.93 to 3.30
	Parameter Dispersion	Type: Standard Deviation; Value: 2.63
	Estimation Comments	EXACT-PRO, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.92
	Confidence Interval	(2-Sided) 95%; -7.04 to 3.18
	Parameter Dispersion	Type: Standard Deviation; Value: 2.63
	Estimation Comments	EXACT-PRO, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.81
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-3.44
	Confidence Interval	(2-Sided) 95%; -8.74 to 1.87
	Parameter Dispersion	Type: Standard Deviation; Value: 2.72
	Estimation Comments	EXACT-PRO, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.52
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.16
	Confidence Interval	(2-Sided) 95%; -6.20 to 4.20
	Parameter Dispersion	Type: Standard Deviation; Value: 2.72
	Estimation Comments	EXACT-PRO, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.60
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.73
	Confidence Interval	(2-Sided) 95%; -6.91 to 3.45
	Parameter Dispersion	Type: Standard Deviation; Value: 2.70
	Estimation Comments	EXACT-PRO, 12 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95%; -4.55 to 3.23
	Parameter Dispersion	Type: Standard Deviation; Value: 2.04
	Estimation Comments	EXACT-PRO, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -5.03 to 3.60
	Parameter Dispersion	Type: Standard Deviation; Value: 2.21
	Estimation Comments	EXACT-PRO, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.99
	Confidence Interval	(2-Sided) 95%; -6.60 to 2.27
	Parameter Dispersion	Type: Standard Deviation; Value: 2.29
	Estimation Comments	EXACT-PRO, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.64
	Confidence Interval	(2-Sided) 95%; -5.92 to 3.07
	Parameter Dispersion	Type: Standard Deviation; Value: 2.31
	Estimation Comments	EXACT-PRO, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.30
	Confidence Interval	(2-Sided) 95%; -5.70 to 3.55
	Parameter Dispersion	Type: Standard Deviation; Value: 2.40
	Estimation Comments	EXACT-PRO, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.31
	Confidence Interval	(2-Sided) 95%; -6.46 to 3.05
	Parameter Dispersion	Type: Standard Deviation; Value: 2.42
	Estimation Comments	EXACT-PRO, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.60
	Confidence Interval	(2-Sided) 95%; -6.75 to 2.90
	Parameter Dispersion	Type: Standard Deviation; Value: 2.45
	Estimation Comments	EXACT-PRO, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-2.10
	Confidence Interval	(2-Sided) 95%; -6.93 to 3.30
	Parameter Dispersion	Type: Standard Deviation; Value: 2.63
	Estimation Comments	EXACT-PRO, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.92
	Confidence Interval	(2-Sided) 95%; -7.04 to 3.18
	Parameter Dispersion	Type: Standard Deviation; Value: 2.63
	Estimation Comments	EXACT-PRO, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-3.44
	Confidence Interval	(2-Sided) 95%; -8.74 to 1.87
	Parameter Dispersion	Type: Standard Deviation; Value: 2.72
	Estimation Comments	EXACT-PRO, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.16
	Confidence Interval	(2-Sided) 95%; -6.20 to 4.20
	Parameter Dispersion	Type: Standard Deviation; Value: 2.72
	Estimation Comments	EXACT-PRO, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -2 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.73
	Confidence Interval	(2-Sided) 95%; -6.91 to 3.45
	Parameter Dispersion	Type: Standard Deviation; Value: 2.70
	Estimation Comments	EXACT-PRO, 12 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95%; -4.55 to 3.23
	Parameter Dispersion	Type: Standard Deviation; Value: 2.04
	Estimation Comments	EXACT-PRO, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -5.03 to 3.60
	Parameter Dispersion	Type: Standard Deviation; Value: 2.21
	Estimation Comments	EXACT-PRO, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.99
	Confidence Interval	(2-Sided) 95%; -6.60 to 2.27
	Parameter Dispersion	Type: Standard Deviation; Value: 2.29
	Estimation Comments	EXACT-PRO, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.64
	Confidence Interval	(2-Sided) 95%; -5.92 to 3.07
	Parameter Dispersion	Type: Standard Deviation; Value: 2.31
	Estimation Comments	EXACT-PRO, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.30
	Confidence Interval	(2-Sided) 95%; -5.70 to 3.55
	Parameter Dispersion	Type: Standard Deviation; Value: 2.40
	Estimation Comments	EXACT-PRO, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.31
	Confidence Interval	(2-Sided) 95%; -6.46 to 3.05
	Parameter Dispersion	Type: Standard Deviation; Value: 2.42
	Estimation Comments	EXACT-PRO, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 43

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.60
	Confidence Interval	(2-Sided) 95%; -6.75 to 2.90
	Parameter Dispersion	Type: Standard Deviation; Value: 2.45
	Estimation Comments	EXACT-PRO, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 44

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-2.10
	Confidence Interval	(2-Sided) 95%; -6.93 to 3.30
	Parameter Dispersion	Type: Standard Deviation; Value: 2.63
	Estimation Comments	EXACT-PRO, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 45

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.35
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.92
	Confidence Interval	(2-Sided) 95%; -7.04 to 3.18
	Parameter Dispersion	Type: Standard Deviation; Value: 2.63
	Estimation Comments	EXACT-PRO, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 46

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-3.44
	Confidence Interval	(2-Sided) 95%; -8.74 to 1.87
	Parameter Dispersion	Type: Standard Deviation; Value: 2.72
	Estimation Comments	EXACT-PRO, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 47

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.16
	Confidence Interval	(2-Sided) 95%; -6.20 to 4.20
	Parameter Dispersion	Type: Standard Deviation; Value: 2.72
	Estimation Comments	EXACT-PRO, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 48

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -3 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-1.73
	Confidence Interval	(2-Sided) 95%; -6.91 to 3.45
	Parameter Dispersion	Type: Standard Deviation; Value: 2.70
	Estimation Comments	EXACT-PRO, 12 month. Data presented are for 95% equal-tailed credible intervals

29. Secondary Outcome

Title	Time to First HCRU COPD Exacerbation in Part B
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.
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	23	20
Mean (Standard Deviation) [Days]	166.3 (97.97)	172.7 (89.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.477
	Comments	Posterior probability that the treatment ratio (DNX 75 mg/ placebo) is less than 1.0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.343
	Comments	Posterior probability that the treatment ratio (DNX 75 mg/ placebo) is less than 0.9 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.221
	Comments	Posterior probability that the treatment ratio (DNX 75 mg/ placebo) is less than 0.8 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.116
	Comments	Posterior probability that the treatment ratio (DNX 75 mg/ placebo) is less than 0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.052
	Comments	Posterior probability that the treatment ratio (DNX 75 mg/ placebo) is less than 0.6 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

30. Secondary Outcome

Title	Time to First EXACT-PRO Event in Part B
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.
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	27	28
Mean (Standard Deviation) [Days]	101.0 (100.18)	114.7 (91.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.212
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 1.0 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.73 to 2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.111
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.9 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.73 to 2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.049
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.8 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.73 to 2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.7 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.73 to 2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.6 is presented.
	Method	Bayesian Cox analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.73 to 2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Data presented are for 95% equal-tailed credible intervals

31. Secondary Outcome

Title	Assessment of Duration of EXACT-PRO Events in Part B
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.
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	45	48
Mean (Standard Deviation) [Days]	33.7 (65.40)	31.5 (59.27)

32. Secondary Outcome

Title	Assessment of Severity of EXACT-PRO Events in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	45	48
Mean (Standard Deviation) [Score on a scale]	48.8 (13.22)	49.7 (12.63)

33. Secondary Outcome

Title	Monthly Weighted Means of EXACT-RS Domain Scores in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
EXACT-RS-breath, 1 month, n=48,45	6.0 (3.40)	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	6.0 (3.79)	5.0 (3.75)
EXACT-RS-breath, 4 month, n=46,41	6.0 (3.91)	5.0 (3.86)
EXACT-RS-breath, 5 month, n=46,40	5.8 (4.05)	5.0 (3.94)
EXACT-RS-breath, 6 month, n=44,39	6.0 (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)	5.0 (4.15)
EXACT-RS-breath, 12 month, n=39,37	5.9 (3.90)	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 (1.90)
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 (2.20)	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	3.0 (2.35)	2.3 (1.78)
EXACT-RS-chest, 12 month, n=39,37	3.0 (2.31)	2.4 (1.83)
EXACT-RS-cough, 1 month, n=48,45	3.8 (1.50)	3.8 (1.32)
EXACT-RS-cough, 2 month, n=47,44	3.5 (1.80)	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 (1.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -1.53 to 1.25
	Parameter Dispersion	Type: Standard Deviation; Value: 0.72
	Estimation Comments	EXACT-RS-breath, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95%; -1.91 to 1.10
	Parameter Dispersion	Type: Standard Deviation; Value: 0.78
	Estimation Comments	EXACT-RS-breath, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -2.09 to 0.98
	Parameter Dispersion	Type: Standard Deviation; Value: 0.80
	Estimation Comments	EXACT-RS-breath, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95%; -2.23 to 0.87
	Parameter Dispersion	Type: Standard Deviation; Value: 0.81
	Estimation Comments	EXACT-RS-breath, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.67
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -1.88 to 1.27
	Parameter Dispersion	Type: Standard Deviation; Value: 0.83
	Estimation Comments	EXACT-RS-breath, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -1.99 to 1.26
	Parameter Dispersion	Type: Standard Deviation; Value: 0.86
	Estimation Comments	EXACT-RS-breath, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.72
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -2.10 to 1.08
	Parameter Dispersion	Type: Standard Deviation; Value: 0.85
	Estimation Comments	EXACT-RS-breath, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -2.11 to 1.14
	Parameter Dispersion	Type: Standard Deviation; Value: 0.87
	Estimation Comments	EXACT-RS-breath, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95%; -2.14 to 1.23
	Parameter Dispersion	Type: Standard Deviation; Value: 0.88
	Estimation Comments	EXACT-RS-breath, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -2.71 to 0.69
	Parameter Dispersion	Type: Standard Deviation; Value: 0.89
	Estimation Comments	EXACT-RS-breath, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -2.15 to 1.41
	Parameter Dispersion	Type: Standard Deviation; Value: 0.91
	Estimation Comments	EXACT-RS-breath, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -2.36 to 1.13
	Parameter Dispersion	Type: Standard Deviation; Value: 0.90
	Estimation Comments	EXACT-RS-breath, 12 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -1.53 to 1.25
	Parameter Dispersion	Type: Standard Deviation; Value: 0.72
	Estimation Comments	EXACT-RS-breath, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95%; -1.91 to 1.10
	Parameter Dispersion	Type: Standard Deviation; Value: 0.78
	Estimation Comments	EXACT-RS-breath, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -2.09 to 0.98
	Parameter Dispersion	Type: Standard Deviation; Value: 0.80
	Estimation Comments	EXACT-RS-breath, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95%; -2.23 to 0.87
	Parameter Dispersion	Type: Standard Deviation; Value: 0.81
	Estimation Comments	EXACT-RS-breath, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -1.88 to 1.27
	Parameter Dispersion	Type: Standard Deviation; Value: 0.83
	Estimation Comments	EXACT-RS-breath, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -1.99 to 1.26
	Parameter Dispersion	Type: Standard Deviation; Value: 0.86
	Estimation Comments	EXACT-RS-breath, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -2.10 to 1.08
	Parameter Dispersion	Type: Standard Deviation; Value: 0.85
	Estimation Comments	EXACT-RS-breath, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -2.11 to 1.14
	Parameter Dispersion	Type: Standard Deviation; Value: 0.87
	Estimation Comments	EXACT-RS-breath, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95%; -2.14 to 1.23
	Parameter Dispersion	Type: Standard Deviation; Value: 0.88
	Estimation Comments	EXACT-RS-breath, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -2.71 to 0.69
	Parameter Dispersion	Type: Standard Deviation; Value: 0.89
	Estimation Comments	EXACT-RS-breath, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -2.15 to 1.41
	Parameter Dispersion	Type: Standard Deviation; Value: 0.91
	Estimation Comments	EXACT-RS-breath, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -2.36 to 1.13
	Parameter Dispersion	Type: Standard Deviation; Value: 0.90
	Estimation Comments	EXACT-RS-breath, 12 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -1.53 to 1.25
	Parameter Dispersion	Type: Standard Deviation; Value: 0.72
	Estimation Comments	EXACT-RS-breath, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95%; -1.91 to 1.10
	Parameter Dispersion	Type: Standard Deviation; Value: 0.78
	Estimation Comments	EXACT-RS-breath, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.46
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -2.09 to 0.98
	Parameter Dispersion	Type: Standard Deviation; Value: 0.80
	Estimation Comments	EXACT-RS-breath, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95%; -2.23 to 0.87
	Parameter Dispersion	Type: Standard Deviation; Value: 0.81
	Estimation Comments	EXACT-RS-breath, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -1.88 to 1.27
	Parameter Dispersion	Type: Standard Deviation; Value: 0.83
	Estimation Comments	EXACT-RS-breath, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -1.99 to 1.26
	Parameter Dispersion	Type: Standard Deviation; Value: 0.86
	Estimation Comments	EXACT-RS-breath, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -2.10 to 1.08
	Parameter Dispersion	Type: Standard Deviation; Value: 0.85
	Estimation Comments	EXACT-RS-breath, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -2.11 to 1.14
	Parameter Dispersion	Type: Standard Deviation; Value: 0.87
	Estimation Comments	EXACT-RS-breath, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.35
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95%; -2.14 to 1.23
	Parameter Dispersion	Type: Standard Deviation; Value: 0.88
	Estimation Comments	EXACT-RS-breath, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.58
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -2.71 to 0.69
	Parameter Dispersion	Type: Standard Deviation; Value: 0.89
	Estimation Comments	EXACT-RS-breath, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -2.15 to 1.41
	Parameter Dispersion	Type: Standard Deviation; Value: 0.91
	Estimation Comments	EXACT-RS-breath, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -2.36 to 1.13
	Parameter Dispersion	Type: Standard Deviation; Value: 0.90
	Estimation Comments	EXACT-RS-breath, 12 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.84 to 0.52
	Parameter Dispersion	Type: Standard Deviation; Value: 0.35
	Estimation Comments	EXACT-RS-chest, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.94 to 0.55
	Parameter Dispersion	Type: Standard Deviation; Value: 0.39
	Estimation Comments	EXACT-RS-chest, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.91
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) 95%; -1.46 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.43
	Estimation Comments	EXACT-RS-chest, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -1.16 to 0.44
	Parameter Dispersion	Type: Standard Deviation; Value: 0.41
	Estimation Comments	EXACT-RS-chest, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -1.24 to 0.41
	Parameter Dispersion	Type: Standard Deviation; Value: 0.42
	Estimation Comments	EXACT-RS-chest, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.81
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -1.23 to 0.47
	Parameter Dispersion	Type: Standard Deviation; Value: 0.44
	Estimation Comments	EXACT-RS-chest, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 43

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.76
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -1.14 to 0.56
	Parameter Dispersion	Type: Standard Deviation; Value: 0.44
	Estimation Comments	EXACT-RS-chest, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 44

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -1.43 to 0.43
	Parameter Dispersion	Type: Standard Deviation; Value: 0.48
	Estimation Comments	EXACT-RS-chest, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 45

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -1.49 to 0.38
	Parameter Dispersion	Type: Standard Deviation; Value: 0.49
	Estimation Comments	EXACT-RS-chest, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 46

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.94
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.73
	Confidence Interval	(2-Sided) 95%; -1.68 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.49
	Estimation Comments	EXACT-RS-chest, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 47

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -1.45 to 0.48
	Parameter Dispersion	Type: Standard Deviation; Value: 0.50
	Estimation Comments	EXACT-RS-chest, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 48

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.81
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -1.36 to 0.55
	Parameter Dispersion	Type: Standard Deviation; Value: 0.50
	Estimation Comments	EXACT-RS-chest, 12 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 49

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.84 to 0.52
	Parameter Dispersion	Type: Standard Deviation; Value: 0.35
	Estimation Comments	EXACT-RS-chest, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 50

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.94 to 0.55
	Parameter Dispersion	Type: Standard Deviation; Value: 0.39
	Estimation Comments	EXACT-RS-chest, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 51

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) 95%; -1.46 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.43
	Estimation Comments	EXACT-RS-chest, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 52

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -1.16 to 0.44
	Parameter Dispersion	Type: Standard Deviation; Value: 0.41
	Estimation Comments	EXACT-RS-chest, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 53

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -1.24 to 0.41
	Parameter Dispersion	Type: Standard Deviation; Value: 0.42
	Estimation Comments	EXACT-RS-chest, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 54

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -1.23 to 0.47
	Parameter Dispersion	Type: Standard Deviation; Value: 0.44
	Estimation Comments	EXACT-RS-chest, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 55

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -1.14 to 0.56
	Parameter Dispersion	Type: Standard Deviation; Value: 0.44
	Estimation Comments	EXACT-RS-chest, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 56

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -1.43 to 0.43
	Parameter Dispersion	Type: Standard Deviation; Value: 0.48
	Estimation Comments	EXACT-RS-chest, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 57

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -1.49 to 0.38
	Parameter Dispersion	Type: Standard Deviation; Value: 0.49
	Estimation Comments	EXACT-RS-chest, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 58

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.73
	Confidence Interval	(2-Sided) 95%; -1.68 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.49
	Estimation Comments	EXACT-RS-chest, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 59

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -1.45 to 0.48
	Parameter Dispersion	Type: Standard Deviation; Value: 0.50
	Estimation Comments	EXACT-RS-chest, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 60

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -1 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -1.36 to 0.55
	Parameter Dispersion	Type: Standard Deviation; Value: 0.50
	Estimation Comments	EXACT-RS-chest, 12 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 61

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.84 to 0.52
	Parameter Dispersion	Type: Standard Deviation; Value: 0.35
	Estimation Comments	EXACT-RS-chest, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 62

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.94 to 0.55
	Parameter Dispersion	Type: Standard Deviation; Value: 0.39
	Estimation Comments	EXACT-RS-chest, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 63

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) 95%; -1.46 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.43
	Estimation Comments	EXACT-RS-chest, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 64

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -1.16 to 0.44
	Parameter Dispersion	Type: Standard Deviation; Value: 0.41
	Estimation Comments	EXACT-RS-chest, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 65

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -1.24 to 0.41
	Parameter Dispersion	Type: Standard Deviation; Value: 0.42
	Estimation Comments	EXACT-RS-chest, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 66

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -1.23 to 0.47
	Parameter Dispersion	Type: Standard Deviation; Value: 0.44
	Estimation Comments	EXACT-RS-chest, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 67

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -1.14 to 0.56
	Parameter Dispersion	Type: Standard Deviation; Value: 0.44
	Estimation Comments	EXACT-RS-chest, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 68

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -1.43 to 0.43
	Parameter Dispersion	Type: Standard Deviation; Value: 0.48
	Estimation Comments	EXACT-RS-chest, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 69

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -1.49 to 0.38
	Parameter Dispersion	Type: Standard Deviation; Value: 0.49
	Estimation Comments	EXACT-RS-chest, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 70

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.52
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.73
	Confidence Interval	(2-Sided) 95%; -1.68 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.49
	Estimation Comments	EXACT-RS-chest, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 71

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -1.45 to 0.48
	Parameter Dispersion	Type: Standard Deviation; Value: 0.50
	Estimation Comments	EXACT-RS-chest, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 72

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -1.36 to 0.55
	Parameter Dispersion	Type: Standard Deviation; Value: 0.50
	Estimation Comments	EXACT-RS-chest, 12 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 73

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.59 to 0.62
	Parameter Dispersion	Type: Standard Deviation; Value: 0.31
	Estimation Comments	EXACT-RS-cough, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 74

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; -0.53 to 0.85
	Parameter Dispersion	Type: Standard Deviation; Value: 0.35
	Estimation Comments	EXACT-RS-cough, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 75

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.94 to 0.52
	Parameter Dispersion	Type: Standard Deviation; Value: 0.38
	Estimation Comments	EXACT-RS-cough, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 76

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.92 to 0.50
	Parameter Dispersion	Type: Standard Deviation; Value: 0.37
	Estimation Comments	EXACT-RS-cough, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 77

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.82 to 0.61
	Parameter Dispersion	Type: Standard Deviation; Value: 0.37
	Estimation Comments	EXACT-RS-cough, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 78

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.69 to 0.69
	Parameter Dispersion	Type: Standard Deviation; Value: 0.36
	Estimation Comments	EXACT-RS-cough, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 79

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.58
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.79 to 0.62
	Parameter Dispersion	Type: Standard Deviation; Value: 0.36
	Estimation Comments	EXACT-RS-cough, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 80

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -1.12 to 0.43
	Parameter Dispersion	Type: Standard Deviation; Value: 0.40
	Estimation Comments	EXACT-RS-cough, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 81

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 95%; -1.07 to 0.52
	Parameter Dispersion	Type: Standard Deviation; Value: 0.41
	Estimation Comments	EXACT-RS-cough, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 82

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.89
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95%; -1.40 to 0.29
	Parameter Dispersion	Type: Standard Deviation; Value: 0.43
	Estimation Comments	EXACT-RS-cough, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 83

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -0.89 to 0.69
	Parameter Dispersion	Type: Standard Deviation; Value: 0.41
	Estimation Comments	EXACT-RS-cough, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 84

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -1.12 to 0.54
	Parameter Dispersion	Type: Standard Deviation; Value: 0.42
	Estimation Comments	EXACT-RS-cough, 12 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 85

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.59 to 0.62
	Parameter Dispersion	Type: Standard Deviation; Value: 0.31
	Estimation Comments	EXACT-RS-cough, 1 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 86

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; -0.53 to 0.85
	Parameter Dispersion	Type: Standard Deviation; Value: 0.35
	Estimation Comments	EXACT-RS-cough, 2 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 87

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.94 to 0.52
	Parameter Dispersion	Type: Standard Deviation; Value: 0.38
	Estimation Comments	EXACT-RS-cough, 3 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 88

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.92 to 0.50
	Parameter Dispersion	Type: Standard Deviation; Value: 0.37
	Estimation Comments	EXACT-RS-cough, 4 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 89

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.82 to 0.61
	Parameter Dispersion	Type: Standard Deviation; Value: 0.37
	Estimation Comments	EXACT-RS-cough, 5 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 90

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.69 to 0.69
	Parameter Dispersion	Type: Standard Deviation; Value: 0.36
	Estimation Comments	EXACT-RS-cough, 6 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 91

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.79 to 0.62
	Parameter Dispersion	Type: Standard Deviation; Value: 0.36
	Estimation Comments	EXACT-RS-cough, 7 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 92

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -1.12 to 0.43
	Parameter Dispersion	Type: Standard Deviation; Value: 0.40
	Estimation Comments	EXACT-RS-cough, 8 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 93

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 95%; -1.07 to 0.52
	Parameter Dispersion	Type: Standard Deviation; Value: 0.41
	Estimation Comments	EXACT-RS-cough, 9 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 94

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95%; -1.40 to 0.29
	Parameter Dispersion	Type: Standard Deviation; Value: 0.43
	Estimation Comments	EXACT-RS-cough, 10 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 95

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -0.89 to 0.69
	Parameter Dispersion	Type: Standard Deviation; Value: 0.41
	Estimation Comments	EXACT-RS-cough, 11 month. Data presented are for 95% equal-tailed credible intervals

Statistical Analysis 96

Statistical Analysis Overview	Comparison Group Selection	DNX 50 mg, DNX 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments	Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than -0.7 is presented.
	Method	Bayesian analysis
	Comments	P-value is actually a posterior probability.
Method of Estimation	Estimation Parameter	Posterior mean difference
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -1.12 to 0.54
	Parameter Dispersion	Type: Standard Deviation; Value: 0.42
	Estimation Comments	EXACT-RS-cough, 12 month. Data presented are for 95% equal-tailed credible intervals

34. Secondary Outcome

Title	Change From Baseline for COPD Assessment Test (CAT) at the Indicated Time Points in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
Day 28; n= 43, 37	-0.6 (5.19)	-0.7 (7.00)
Day 112; n= 44, 39	-0.5 (5.53)	-1.0 (9.50)
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)

35. Secondary Outcome

Title	Number of Participants With Physician's Global Assessment (PGA) Readings in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
Baseline; mild; n= 47, 43	5 10.4%	2 4.4%
Baseline; moderate; n= 47, 43	35 72.9%	37 82.2%
Baseline; severe; n= 47, 43	7 14.6%	4 8.9%
Baseline; very severe; n= 47, 43	0 0%	0 0%
Week 4; mild; n= 44, 39	10 20.8%	8 17.8%
Week 4; moderate; n= 44, 39	28 58.3%	27 60%
Week 4; severe; n= 44, 39	6 12.5%	3 6.7%
Week 4; very severe; n= 44, 39	0 0%	1 2.2%
Week 8; mild; n= 44, 40	10 20.8%	8 17.8%
Week 8; moderate; n= 44, 40	31 64.6%	30 66.7%
Week 8; severe; n= 44, 40	3 6.3%	2 4.4%
Week 8; very severe; n= 44, 40	0 0%	0 0%
Week 16; mild; n= 46, 40	12 25%	6 13.3%
Week 16; moderate; n= 46, 40	29 60.4%	32 71.1%
Week 16; severe; n= 46, 40	5 10.4%	2 4.4%
Week 16; very severe; n= 46, 40	0 0%	0 0%
Week 24; mild; n= 44, 38	8 16.7%	9 20%
Week 24; moderate; n= 44, 38	32 66.7%	25 55.6%
Week 24; severe; n= 44, 38	4 8.3%	4 8.9%
Week 24; very severe; n= 44, 38	0 0%	0 0%
Week 40; mild; n= 37, 36	4 8.3%	6 13.3%
Week 40; moderate; n= 37, 36	30 62.5%	28 62.2%
Week 40; severe; n= 37, 36	3 6.3%	2 4.4%
Week 40; very severe; n= 37, 36	0 0%	0 0%
Week 52; mild; n= 39, 36	7 14.6%	11 24.4%
Week 52; n= moderate; n= 39, 36	28 58.3%	24 53.3%
Week 52; severe; n= 39, 36	4 8.3%	1 2.2%
Week 52; very severe; n= 39, 36	0 0%	0 0%

36. Secondary Outcome

Title	Number of Participants With Patient Global Rating of Severity (PGRS) Score in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
Baseline; mild; n= 47, 43	10 20.8%	6 13.3%
Baseline; moderate; n= 47, 43	21 43.8%	29 64.4%
Baseline; severe; n= 47, 43	15 31.3%	8 17.8%
Baseline; very severe; n= 47, 43	1 2.1%	0 0%
Week 4; mild; n= 44, 39	7 14.6%	7 15.6%
Week 4; moderate; n= 44, 39	27 56.3%	27 60%
Week 4; severe; n= 44, 39	10 20.8%	4 8.9%
Week 4; very severe; n= 44, 39	0 0%	1 2.2%
Week 8; mild; n= 44, 40	4 8.3%	7 15.6%
Week 8; moderate; n= 44, 40	32 66.7%	29 64.4%
Week 8; severe; n= 44, 40	7 14.6%	4 8.9%
Week 8; very severe; n= 44, 40	1 2.1%	0 0%
Week 16; mild; n= 45, 40	6 12.5%	8 17.8%
Week 16; moderate; n= 45, 40	28 58.3%	26 57.8%
Week 16; severe; n= 45, 40	11 22.9%	6 13.3%
Week 16; very severe; n= 45, 40	0 0%	0 0%
Week 24; mild; n= 44, 38	6 12.5%	9 20%
Week 24; moderate; n= 44, 38	31 64.6%	23 51.1%
Week 24; severe; n= 44, 38	7 14.6%	6 13.3%
Week 24; very severe; n= 44, 38	0 0%	0 0%
Week 40; mild; n= 37, 36	7 14.6%	9 20%
Week 40; moderate; n= 37, 36	21 43.8%	21 46.7%
Week 40; severe; n= 37, 36	9 18.8%	6 13.3%
Week 40; very severe; n= 37, 36	0 0%	0 0%
Week 52; mild; n= 39, 36	6 12.5%	7 15.6%
Week 52; n= moderate; n= 39, 36	24 50%	23 51.1%
Week 52; severe; n= 39, 36	9 18.8%	6 13.3%
Week 52; very severe; n= 39, 36	0 0%	0 0%

37. Secondary Outcome

Title	Number of Participants With Patient Global Impression of Change (PGIC)Score in Part B
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).
Time Frame	Up to Day 392 in Part B

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	DNX 75 mg
Arm/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).	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).
Measure Participants	48	45
Week 4; much worse; n= 44, 39	0 0%	1 2.2%
Week 4; worse; n= 44, 39	1 2.1%	4 8.9%
Week 4; slightly worse; n= 44, 39	1 2.1%	0 0%
Week 4; no change; n= 44, 39	18 37.5%	17 37.8%
Week 4; slightly better; n= 44, 39	15 31.3%	12 26.7%
Week 4; better; n= 44, 39	9 18.8%	4 8.9%
Week 4; much better; n= 44, 39	0 0%	1 2.2%
Week 8; much worse; n= 44, 39	1 2.1%	0 0%
Week 8; worse; n= 44, 39	1 2.1%	1 2.2%
Week 8; slightly worse; n= 44, 39	6 12.5%	5 11.1%
Week 8; no change; n= 44, 39	16 33.3%	18 40%
Week 8; slightly better; n= 44, 39	15 31.3%	10 22.2%
Week 8; better; n= 44, 39	4 8.3%	4 8.9%
Week 8; much better; n= 44, 39	1 2.1%	1 2.2%
Week 16; much worse; n= 45, 40	0 0%	1 2.2%
Week 16; worse; n= 45, 40	0 0%	1 2.2%
Week 16; slightly worse; n= 45, 40	0 0%	3 6.7%
Week 16; no change; n= 45, 40	21 43.8%	17 37.8%
Week 16; slightly better; n= 45, 40	20 41.7%	13 28.9%
Week 16; better; n= 45, 40	3 6.3%	2 4.4%
Week 16; much better; n= 45, 40	1 2.1%	3 6.7%
Week 24; much worse; n= 44, 38	0 0%	1 2.2%
Week 4; worse; n= 44, 38	1 2.1%	2 4.4%
Week 24; slightly worse; n= 44, 38	3 6.3%	3 6.7%
Week 24; no change; n= 44, 38	15 31.3%	13 28.9%
Week 24; slightly better; n= 44, 38	16 33.3%	9 20%
Week 24; better; n= 44, 38	8 16.7%	8 17.8%
Week 24; much better; n= 44, 38	1 2.1%	2 4.4%
Week 40; much worse; n= 37, 36	0 0%	0 0%
Week 40; worse; n= 37, 36	2 4.2%	1 2.2%
Week 40; slightly worse; n= 37, 36	3 6.3%	7 15.6%
Week 40; no change; n=37, 36	9 18.8%	12 26.7%
Week 40; slightly better; n=37, 36	14 29.2%	7 15.6%
Week 40; better; n= 37, 36	7 14.6%	7 15.6%
Week 40; much better; n= 37, 36	2 4.2%	2 4.4%
Week 52; much worse; n= 39, 35	0 0%	1 2.2%
Week 52; worse; n= 39, 35	1 2.1%	0 0%
Week 52; slightly worse; n= 39, 35	3 6.3%	7 15.6%
Week 52; no change; n= 39, 35	14 29.2%	15 33.3%
Week 52; slightly better; n= 39, 35	9 18.8%	4 8.9%
Week 52; better; n= 39, 35	11 22.9%	5 11.1%
Week 52; much better; n= 39, 35	1 2.1%	3 6.7%

Adverse Events

Time Frame	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 Description	On treatment SAEs and non-serious AEs were reported for the All Subjects Population.
Arm/Group Title	DNX 50 mg		Placebo		DNX 75 mg
Arm/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).		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).		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).
All Cause Mortality
	DNX 50 mg		Placebo		DNX 75 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	DNX 50 mg		Placebo		DNX 75 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		10/48 (20.8%)		10/45 (22.2%)
Blood and lymphatic system disorders
Anaemia	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Cardiac disorders
Atrial fibrillation	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Atrioventricular block complete	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Cardiac arrest	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Coronary artery stenosis	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Myocardial infarction	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Ventricular fibrillation	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Subileus	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
General disorders
Pain	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Hepatobiliary disorders
Cholangitis sclerosing	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Cholecystitis acute	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Cholelithiasis	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Cholestasis	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Drug-induced liver injury	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Hepatic failure	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Infections and infestations
Pneumonia	0/9 (0%)		3/48 (6.3%)		0/45 (0%)
Cholangitis infective	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Staphylococcal infection	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Injury, poisoning and procedural complications
Craniocerebral injury	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Foreign body	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Fall	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Investigations
Blood sodium decreased	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Metabolism and nutrition disorders
Hypokalaemia	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Obesity	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/9 (11.1%)		0/48 (0%)		1/45 (2.2%)
Arthritis	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gallbladder adenoma	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Non-small cell lung cancer	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Nervous system disorders
Brain injury	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Product Issues
Device loosening	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/9 (0%)		4/48 (8.3%)		2/45 (4.4%)
Hypoxia	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Pneumothorax	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Sleep apnoea syndrome	0/9 (0%)		1/48 (2.1%)		0/45 (0%)
Vocal cord leukoplakia	0/9 (0%)		0/48 (0%)		1/45 (2.2%)
Other (Not Including Serious) Adverse Events
	DNX 50 mg		Placebo		DNX 75 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)		25/48 (52.1%)		25/45 (55.6%)
Gastrointestinal disorders
Nausea	1/9 (11.1%)		2/48 (4.2%)		0/45 (0%)
Abdominal pain upper	0/9 (0%)		3/48 (6.3%)		0/45 (0%)
General disorders
Fatigue	1/9 (11.1%)		0/48 (0%)		3/45 (6.7%)
Malaise	1/9 (11.1%)		0/48 (0%)		0/45 (0%)
Diarrhoea	0/9 (0%)		8/48 (16.7%)		4/45 (8.9%)
Infections and infestations
Nasopharyngitis	1/9 (11.1%)		16/48 (33.3%)		13/45 (28.9%)
Cystitis	0/9 (0%)		3/48 (6.3%)		5/45 (11.1%)
Musculoskeletal and connective tissue disorders
Back pain	0/9 (0%)		0/48 (0%)		5/45 (11.1%)
Nervous system disorders
Headache	1/9 (11.1%)		4/48 (8.3%)		4/45 (8.9%)
Respiratory, thoracic and mediastinal disorders
Cough	1/9 (11.1%)		3/48 (6.3%)		5/45 (11.1%)
Dyspnoea	1/9 (11.1%)		0/48 (0%)		1/45 (2.2%)
Hyperhidrosis	1/9 (11.1%)		0/48 (0%)		0/45 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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