Danirixin Dose Ranging Study in Participants With Chronic Obstructive Pulmonary Disease (COPD)

• ClinicalTrials.gov Identifier: NCT03034967
• Recruitment Status: Completed
• First Posted: January 27, 2017
• Results First Posted: November 29, 2019
• Last Update Posted: October 28, 2020
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Pulmonary Disease, Chronic Obstructive
• Interventions: Drug: Danirixin; Drug: Danirixin matching placebo; Drug: Standard of care; Drug: Rescue medication
• Enrollment: 614

Participant Flow

Recruitment Details	This study investigated the dose response and safety of danirixin compared with placebo in Chronic Obstructive Pulmonary Disease (COPD) participants with respiratory symptoms including cough, increased sputum production and dyspnoea.
Pre-assignment Details	A total of 614 participants were randomized in this study across 9 countries.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Period Title: Overall Study
Started	102	102	103	103	102	102
Completed	88	97	90	92	88	87
Not Completed	14	5	13	11	14	15
Reason Not Completed
Withdrawal by Subject	9	2	6	6	9	2
Physician Decision	1	0	1	1	1	0
Lost to Follow-up	0	0	0	1	0	2
Liver function test abnormality	0	0	1	0	0	0
Protocol Violation	1	0	0	0	0	2
Lack of Efficacy	0	1	2	1	1	0
Adverse Event, non-fatal	3	1	2	0	2	8
Adverse Event, Serious Fatal	0	1	1	2	1	1

Baseline Characteristics

Arm/Group Title		Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg	Total
Arm/Group Description		Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		102	102	103	103	102	102	614
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	102 participants	102 participants	103 participants	103 participants	102 participants	102 participants	614 participants
		66.2 (7.31)	66.3 (6.79)	65.7 (7.48)	66.3 (7.28)	65.1 (7.58)	65.7 (6.98)	65.9 (7.23)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	102 participants	102 participants	103 participants	103 participants	102 participants	102 participants	614 participants
	Female	29 28.4%	36 35.3%	32 31.1%	38 36.9%	35 34.3%	32 31.4%	202 32.9%
	Male	73 71.6%	66 64.7%	71 68.9%	65 63.1%	67 65.7%	70 68.6%	412 67.1%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	102 participants	102 participants	103 participants	103 participants	102 participants	102 participants	614 participants
Asian - East Asian Heritage		10 9.8%	6 5.9%	18 17.5%	17 16.5%	10 9.8%	17 16.7%	78 12.7%
Asian - South East Asian Heritage		1 1.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.2%
Black or African American		2 2.0%	2 2.0%	1 1.0%	0 0.0%	0 0.0%	1 1.0%	6 1.0%
Native Hawaiian or other Pacific Islander		1 1.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.2%
White - Arabic/North African Heritage		1 1.0%	1 1.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 0.3%
White - White/Caucasian/European Heritage		87 85.3%	93 91.2%	84 81.6%	86 83.5%	92 90.2%	84 82.4%	526 85.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Respiratory Symptoms Measured by Evaluating Respiratory Symptoms (E-RS) in COPD. E-RS: COPD Total Score
Description	E-RS: COPD is a subset of Exacerbations of Chronic pulmonary Disease Tool (EXACT). E-RS is a tool that consists of 11 items from the 14 item EXACT instrument. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). The total score ranged between 0-40 and higher values indicates severe respiratory symptoms. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Per protocol population included all participants from the mITT population who did not have a protocol deviation considered to impact efficacy. Posterior mean change and standard deviation has been presented.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Only those participants with data available at the specified data points was analyzed.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	86	95	87	91	85	86
Mean (Standard Deviation); Unit of Measure: Scores on a scale
	-2.11 (0.345)	-1.93 (0.289)	-1.47 (0.349)	-0.87 (0.286)	-0.76 (0.259)	-0.71 (0.281)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 5 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 90%; 0.00 to 0.66
	Estimation Comments	Median posterior difference, 90 percent (%) credible interval for Placebo and Danirixin 5 mg has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 10 mg
	Comments	4-parameter Emax model
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 90%; 0.00 to 1.52
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 10 mg has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 25 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 90%; 0.43 to 1.97
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 25 mg has been presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 35 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	1.34
	Confidence Interval	(2-Sided) 90%; 0.72 to 2.03
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 35 mg has been presented.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 50 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 90%; 0.79 to 2.07
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 50 mg has been presented.

2. Primary Outcome

Title	Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Breathlessness Score)
Description	E-RS: COPD is a subset of EXACT. E-RS is a tool that consists of 11 items from the 14 item EXACT instrument. The domains include: RS-BRL comprised of 5 items, score range (0-17), RS-CSP comprised of 3 items, score range (0-11), and RS-CSY comprised of 3 items, score range (0-12). The total score ranged between 0-40 and higher values indicates severe respiratory symptoms. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Posterior mean change and standard deviation has been presented.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Only those participants with available data at the specified time points were analyzed.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	86	95	87	91	85	86
Mean (Standard Deviation); Unit of Measure: Scores on a scale
	-0.82 (0.202)	-0.69 (0.162)	-0.41 (0.183)	-0.15 (0.148)	-0.10 (0.141)	-0.09 (0.158)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 5 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 90%; 0.00 to 0.42
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 5 mg has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 10 mg
	Comments	4-parameter Emax model
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 90%; 0.00 to 0.87
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 10 mg has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 25 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 90%; 0.23 to 1.08
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 25 mg has been presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 35 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 90%; 0.37 to 1.10
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 35 mg has been presented.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 50 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 90%; 0.40 to 1.12
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 50 mg has been presented.

3. Primary Outcome

Title	Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Cough and Sputum Score)
Description	E-RS: COPD is a subset of EXACT. E-RS is a tool that consists of 11 items from the 14 item EXACT instrument. The domains include: RS-BRL comprised of 5 items, score range (0-17), RS-CSP comprised of 3 items, score range (0-11), and RS-CSY comprised of 3 items, score range (0-12). The total score ranged between 0-40 and higher values indicates severe respiratory symptoms. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Posterior mean change and standard deviation has been presented.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Only those participants with available data at the specified time points were analyzed.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	86	95	87	91	85	86
Mean (Standard Deviation); Unit of Measure: Scores on a scale
	-0.83 (0.107)	-0.79 (0.090)	-0.67 (0.109)	-0.46 (0.104)	-0.40 (0.088)	-0.37 (0.098)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 5 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 90%; 0.00 to 0.16
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 5 mg has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 10 mg
	Comments	4-parameter Emax model
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 90%; 0.00 to 0.43
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 10 mg has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 25 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 90%; 0.04 to 0.61
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 25 mg has been presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 35 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.42
	Confidence Interval	(2-Sided) 90%; 0.21 to 0.64
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 35 mg has been presented.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 50 mg
	Comments	4-parameter Emax model selected.
	Type of Statistical Test	Other
	Comments	Emax
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.45
	Confidence Interval	(2-Sided) 90%; 0.26 to 0.66
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 50 mg has been presented.

4. Primary Outcome

Title	Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Chest Symptoms Score)
Description	E-RS: COPD is a subset of EXACT. E-RS is a tool that consists of 11 items from the 14 item EXACT instrument. The domains include: RS-BRL comprised of 5 items, score range (0-17), RS-CSP comprised of 3 items, score range (0-11), and RS-CSY comprised of 3 items, score range (0-12). The total score ranged between 0-40 and higher values indicates severe respiratory symptoms. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Posterior mean change and standard deviation has been presented.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	86	95	87	91	85	86
Mean (Standard Deviation); Unit of Measure: Scores on a scale
	-0.36 (0.148)	-0.35 (0.061)	-0.34 (0.062)	-0.34 (0.069)	-0.34 (0.073)	-0.34 (0.078)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 5 mg
	Comments	Log-linear model.
	Type of Statistical Test	Other
	Comments	Log-linear
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 90%; -0.21 to 0.23
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 5 mg has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 10 mg
	Comments	Log-linear model
	Type of Statistical Test	Other
	Comments	Log-linear
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 90%; -0.23 to 0.25
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 10 mg has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 25 mg
	Comments	Log-linear model
	Type of Statistical Test	Other
	Comments	Log-linear
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 90%; -0.27 to 0.29
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 25 mg has been presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 35 mg
	Comments	Log-linear model
	Type of Statistical Test	Other
	Comments	Log-linear
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 90%; -0.28 to 0.30
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 35 mg has been presented.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 50 mg
	Comments	Log-linear model
	Type of Statistical Test	Other
	Comments	Log-linear
Method of Estimation	Estimation Parameter	Median Posterior Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 90%; -0.29 to 0.31
	Estimation Comments	Median posterior difference, 90% credible interval for Placebo and Danirixin 50 mg has been presented.

5. Primary Outcome

Title	Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Description	AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
Time Frame	Up to Day 196

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) population. mIIT population comprised of all randomized participants who were randomized apart from those randomized in error, received a treatment randomization number, modified and data for this population were based on actual treatment received.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	102	102	103	103	102	102
Measure Type: Count of Participants; Unit of Measure: Participants
Any AE	63 61.8%	63 61.8%	69 67.0%	68 66.0%	63 61.8%	71 69.6%
Any SAE	8 7.8%	7 6.9%	13 12.6%	10 9.7%	7 6.9%	11 10.8%

6. Primary Outcome

Title	Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI)
Description	Blood samples were collected from participants for analysis of following hematology parameters with PCI low and high values: Basophils % (High 5.00x), Eosinophils % (High 2.00x), Mean corpuscular hemoglobin concentration (MCHC) gram per deciliter (g/dL) (Low 0.85x, high 1.10x), Mean corpuscular hemoglobin (MCH) picograms (pg) (Low 0.85x, high 1.20x), Mean corpuscular volume (MCV) femtoliter (fL) (low 0.25x, high 2.00x), Erythrocytes (Ery.)(10^12cells/L) (Low 0.93x, high 1.07x), Hematocrit (Ratio of 1) (Low 0.50x, high 0.50x), Hemoglobin gram per liter (g/L) (Low 0.85x, high 1.20x), Leukocytes (x10^9/L) (Low 0.70x, high 1.60x), Lymphocytes % (Low 0.80x, high 1.20x), Monocytes % (Low 0.80x, high 1.60x), Neutrophils % (Low 0.65x, high 1.50x), Platelets (x10^9cells/L) (Low 0.90x, high 1.10x). Multipliers are identified by "x", otherwise actual comparison values are provided with units. Values above and below this range were considered of PCI.
Time Frame	Up to Day 196

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:		Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed		102	102	103	103	102	102
Measure Type: Count of Participants; Unit of Measure: Participants
Basophils, No change, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		97 100.0%	102 100.0%	101 100.0%	101 100.0%	101 100.0%	99 100.0%
Basophils, High, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Eosinophils,No change,n=97,102,101,101,101,99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		97 100.0%	101 99.0%	101 100.0%	98 97.0%	100 99.0%	98 99.0%
Eosinophils, High, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	1 1.0%	0 0.0%	3 3.0%	1 1.0%	1 1.0%
Ery. MCHC, Low, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Ery. MCHC,No change,n=97,102,101,101,102,99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		97 100.0%	102 100.0%	101 100.0%	101 100.0%	102 100.0%	99 100.0%
Ery. MCHC, High, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Ery. MCH, Low, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.0%
Ery. MCH, No Change, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		97 100.0%	102 100.0%	101 100.0%	101 100.0%	102 100.0%	98 99.0%
Ery. MCH, High, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Ery. MCV, Low, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Ery. MCV, No Change, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		97 100.0%	102 100.0%	101 100.0%	101 100.0%	102 100.0%	99 100.0%
Ery. MCV, High, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Erythrocytes, Low, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		2 2.1%	1 1.0%	3 3.0%	3 3.0%	2 2.0%	2 2.0%
Erythrocytes, No change,n=97,102,101,101,102,99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		93 95.9%	99 97.1%	97 96.0%	97 96.0%	99 97.1%	97 98.0%
Erythrocytes. High, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		2 2.1%	2 2.0%	1 1.0%	1 1.0%	1 1.0%	0 0.0%
Hematocrit, Low, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Hematocrit, No Change, n=97,102,101,101,102,99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		97 100.0%	102 100.0%	101 100.0%	101 100.0%	102 100.0%	99 100.0%
Hematocrit, High, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Hemoglobin, Low, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		1 1.0%	1 1.0%	2 2.0%	0 0.0%	2 2.0%	0 0.0%
Hemoglobin, No change, n=97,102,101,101,102,99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		96 99.0%	101 99.0%	99 98.0%	101 100.0%	100 98.0%	99 100.0%
Hemoglobin, High, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Leukocytes, Low, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.0%
Leukocytes, No change, n=97,102,101,101,102,99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		97 100.0%	102 100.0%	101 100.0%	101 100.0%	102 100.0%	98 99.0%
Leukocytes, High, n=97, 102, 101, 101, 102, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	102 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Lymphocytes, Low, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		3 3.1%	7 6.9%	5 5.0%	8 7.9%	7 6.9%	4 4.0%
Lymphocytes, No change, n=97,102,101,101,101,99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		94 96.9%	95 93.1%	96 95.0%	92 91.1%	93 92.1%	94 94.9%
Lymphocytes, High, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	1 1.0%	1 1.0%	1 1.0%
Monocytes, No change, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		97 100.0%	101 99.0%	99 98.0%	101 100.0%	100 99.0%	98 99.0%
Monocytes, High, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	1 1.0%	2 2.0%	0 0.0%	1 1.0%	1 1.0%
Neutrophils, Low, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	1 1.0%	3 3.0%	1 1.0%
Neutrophils, No change, n=97,102,101,101,101,99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		97 100.0%	102 100.0%	101 100.0%	100 99.0%	98 97.0%	98 99.0%
Neutrophils, High, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Platelets, Low, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	1 1.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Platelets, No change, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		97 100.0%	99 97.1%	100 99.0%	101 100.0%	99 98.0%	99 100.0%
Platelets, High, n=97, 102, 101, 101, 101, 99	Number Analyzed	97 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	2 2.0%	1 1.0%	0 0.0%	2 2.0%	0 0.0%

7. Primary Outcome

Title	Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI
Description	Blood samples were collected from participants for analysis of following chemistry parameters with PCI low and high values: Alanine aminotransferase (ALT) International units per liter (IU/L) (High => 3x ULN), Alkaline phosphatase (ALP) (IU/L) (High ≥ 2x ULN); Aspartate aminotransferase (AST) (IU/L) (High=> 3x ULN); Bilirubin micromole per liter (umol/L) (High ≥ 2x ULN); Calcium millimole per liter (mmol/L) (Low 0.85x, high 1.08x), Chloride (mmol/L) (Low 0.90x, high 1.10x), Creatinine (umol/L) (High 1.30x), Direct bilirubin (umol/L) (High ≥ 2x ULN), Glucose (mmol/L) (Low <0.6x, high >4x), Potassium (mmol/L) (Low 0.75x, high 1.30x); Protein (g/L) (High 1.25x), Sodium (mmol/L) (Low 0.80x, high 1.15x), Multipliers are identified by "x", otherwise actual comparison values are provided with units. Values above and below this range were considered of PCI.
Time Frame	Up to Day 196

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:		Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed		102	102	103	103	102	102
Measure Type: Count of Participants; Unit of Measure: Participants
ALT, No change,n=99,102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		99 100.0%	102 100.0%	101 99.0%	102 100.0%	101 100.0%	100 100.0%
ALT, High, n=99,102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		0 0.0%	0 0.0%	1 1.0%	0 0.0%	0 0.0%	0 0.0%
ALP, No change,n=99,102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		99 100.0%	102 100.0%	102 100.0%	102 100.0%	101 100.0%	100 100.0%
ALP, High, n=99,102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
AST, No change,n=99,102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		99 100.0%	102 100.0%	101 99.0%	102 100.0%	101 100.0%	100 100.0%
AST, High, n=99,102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		0 0.0%	0 0.0%	1 1.0%	0 0.0%	0 0.0%	0 0.0%
Bilirubin, No change, n=99,102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		99 100.0%	101 99.0%	102 100.0%	102 100.0%	101 100.0%	100 100.0%
Bilirubin, High, n=99, 102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		0 0.0%	1 1.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Calcium, Low, n=96,102,101,101,101,99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Calcium, No change, n=96,102,101,101,101,99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		96 100.0%	102 100.0%	101 100.0%	101 100.0%	101 100.0%	99 100.0%
Calcium, High, n=96,102,101,101,101,99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
CO2, Low, n=96,102,101,101,101,99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		1 1.0%	0 0.0%	2 2.0%	1 1.0%	0 0.0%	1 1.0%
CO2, No change, n=96,102,101,101,101,99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		94 97.9%	102 100.0%	99 98.0%	99 98.0%	101 100.0%	98 99.0%
CO2, High, n=96,102,101,101,101,99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		1 1.0%	0 0.0%	0 0.0%	1 1.0%	0 0.0%	0 0.0%
Chloride, Low, n=96,102,101,101,101,99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Chloride, No change, n=96,102,101,101,101,99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		96 100.0%	102 100.0%	101 100.0%	101 100.0%	101 100.0%	99 100.0%
Chloride, High, n=96,102,101,101,101,99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Creatinine, No change, n=96,102,101,101,101,99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		94 97.9%	100 98.0%	99 98.0%	99 98.0%	99 98.0%	99 100.0%
Creatinine, High, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		2 2.1%	2 2.0%	2 2.0%	2 2.0%	2 2.0%	0 0.0%
Direct bilirubin,NoChange,n=99,102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		98 99.0%	102 100.0%	102 100.0%	102 100.0%	101 100.0%	100 100.0%
Direct bilirubin,High,n=99,102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		1 1.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Glucose, Low, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Glucose, No change, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		96 100.0%	102 100.0%	101 100.0%	101 100.0%	101 100.0%	99 100.0%
Glucose, High, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Potassium, Low, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Potassium, No change, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		96 100.0%	102 100.0%	101 100.0%	101 100.0%	101 100.0%	99 100.0%
Potassium, High, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Protein, No change, n=99, 102, 102, 102, 101, 100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		99 100.0%	102 100.0%	102 100.0%	102 100.0%	101 100.0%	100 100.0%
Protein, High, n=99, 102, 102, 102, 101, 100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Sodium, Low, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Sodium, No change, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		96 100.0%	102 100.0%	101 100.0%	101 100.0%	101 100.0%	99 100.0%
Sodium, High, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Urea, Low, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Urea, No change, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		96 100.0%	101 99.0%	101 100.0%	100 99.0%	101 100.0%	98 99.0%
Urea, High, n=96, 102, 101, 101, 101, 99	Number Analyzed	96 participants	102 participants	101 participants	101 participants	101 participants	99 participants
		0 0.0%	1 1.0%	0 0.0%	1 1.0%	0 0.0%	1 1.0%
Bilirubin/ALT,No change,n=99,102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		99 100.0%	102 100.0%	102 100.0%	102 100.0%	101 100.0%	100 100.0%
Bilirubin/ALT, High,n=99,102,102,102,101,100	Number Analyzed	99 participants	102 participants	102 participants	102 participants	101 participants	100 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

8. Primary Outcome

Title	Number of Participants With Worst Case Vital Signs Parameter Results by PCI
Description	Vital signs parameters includes systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse rate and respiration rate were measured in a semi-supine position after 5 minutes rest for the participants at indicated time points. PCI ranges for vital signs parameters were as follows: <90 to >160 millimeters of mercury (mmHg) for SBP and <40 to >110 mmHg for DBP, <35 or >120 beats per minute for heart rate and <8 or >30 breaths per minute for respiration rate. Values above and below this range were considered of PCI.
Time Frame	Up to Day 168

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	96	102	101	101	102	99
Measure Type: Count of Participants; Unit of Measure: Participants
SBP, Low	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.0%
SBP, No change	93 96.9%	92 90.2%	95 94.1%	98 97.0%	98 96.1%	94 94.9%
SBP, High	3 3.1%	10 9.8%	6 5.9%	3 3.0%	4 3.9%	4 4.0%
DBP, Low	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
DBP, No change	96 100.0%	102 100.0%	101 100.0%	101 100.0%	102 100.0%	99 100.0%
DBP, High	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Pulse rate, Low	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Pulse rate, No change	96 100.0%	102 100.0%	99 98.0%	100 99.0%	102 100.0%	98 99.0%
Pulse rate, High	0 0.0%	0 0.0%	2 2.0%	1 1.0%	0 0.0%	1 1.0%
Respiratory rate, Low	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Respiratory rate, No change	96 100.0%	102 100.0%	101 100.0%	101 100.0%	102 100.0%	98 99.0%
Respiratory rate, High	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.0%

9. Primary Outcome

Title	Number of Participants With Worst Case Post-Baseline Abnormal 12-lead Electrocardiogram (ECG) Findings
Description	Triplicate 12-lead ECG obtained to measure PR, QRS, QT, and Corrected QT intervals. Only those participants with worst case post-Baseline data have been represented for abnormal - not clinical significant and abnormal - clinical significant. Day 1 was considered as Baseline.
Time Frame	Baseline and Day 168

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	96	102	101	101	102	99
Measure Type: Count of Participants; Unit of Measure: Participants
Not Clinical significant	52 54.2%	65 63.7%	68 67.3%	67 66.3%	62 60.8%	53 53.5%
Clinical significant	2 2.1%	1 1.0%	1 1.0%	0 0.0%	3 2.9%	1 1.0%

10. Secondary Outcome

Title	Number of Moderate or Severe Healthcare Resource Utilization (HCRU) Exacerbations Per Participant
Description	Participants with moderate or severe COPD exacerbations, i.e. breathlessness, cough, sputum production, chest congestion and chest tightness analyzed. Mild exacerbations are defined as exacerbations that did not require treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization, Emergency Room [ER] visit or resulting in death). Moderate exacerbations are defined as exacerbations that required treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization, ER visit or resulting in death). Severe exacerbations are defined as exacerbations that required hospitalization, ER visit or resulted in death. Number of moderate or severe HCRU exacerbations per participant has been presented, where 0= participants in each treatment group who did not experience an event; 1= participants in each treatment group who experienced 1 event and >=2= participants in each treatment group who experienced 2 or more events.
Time Frame	Up to Day 196

Outcome Measure Data

Analysis Population Description

Per Protocol Population.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	101	102	100	103	100	99
Measure Type: Number; Unit of Measure: Exacerbations per participant
0	66	51	61	63	55	50
1	28	34	23	28	30	36
>=2	7	17	16	12	15	13

11. Secondary Outcome

Title	Number of Responders E-RS in COPD (E-RS): COPD Total Score
Description	E-RS: COPD is a subset of EXACT. E-RS is a tool that consists of 11 items from the 14 item EXACT instrument. E-RS is intended to capture information related to the respiratory symptoms of COPD, i.e. breathlessness, cough, sputum production, chest congestion and chest tightness. The E-RS has a scoring range of 0-40; higher scores indicate more severe symptoms. Response is defined as an E-RS: COPD total score of 2 units below baseline or lower. Non-response is defined as an E-RS: COPD total score higher than 2 units below Baseline.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Number of participants presented represent those with data available at the time point being presented; however, all participants in the per protocol population without missing covariate information and with at least one post baseline measurement are included in the analysis.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	86	95	87	91	85	86
Measure Type: Number; Unit of Measure: Participants
	33	48	33	30	29	32

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 5 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.089
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, relevant Baseline E-RS: COPD score, smoking status at Screening, country, month, Baseline by month and treatment by month interactions.
	Method	linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 90%; 1.02 to 2.86
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 5 mg has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 10 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.881
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, relevant Baseline E-RS: COPD score, smoking status at Screening, country, month, Baseline by month and treatment by month interactions.
	Method	linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 90%; 0.62 to 1.79
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 10 mg has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 25 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.674
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, relevant Baseline E-RS: COPD score, smoking status at Screening, country, month, Baseline by month and treatment by month interactions.
	Method	linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 90%; 0.51 to 1.48
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 25 mg has been presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 35 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.804
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, relevant Baseline E-RS: COPD score, smoking status at Screening, country, month, Baseline by month and treatment by month interactions.
	Method	linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 90%; 0.54 to 1.58
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 35 mg has been presented.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 50 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.987
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, relevant Baseline E-RS: COPD score, smoking status at Screening, country, month, Baseline by month and treatment by month interactions.
	Method	linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 90%; 0.59 to 1.71
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 50 mg has been presented.

12. Secondary Outcome

Title	Number of EXACT Events Per Participant
Description	EXACT is a 14 item patient reported outcome (PRO) instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. The total score for EXACT-PRO ranges from 0-100, higher scores indicate more severe symptoms. Events were categorized as recovered, censored, or persistent worsening. Number of EXACT events per participant has been presented, where 0= participants in each treatment group who did not experience an event; 1= participants in each treatment group who experienced 1 event and >=2= participants in each treatment group who experienced 2 or more events.
Time Frame	Up to Day 196

Outcome Measure Data

Analysis Population Description

Per Protocol Population.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	101	102	100	103	100	99
Measure Type: Number; Unit of Measure: Events
0	92	92	92	92	86	86
1	9	6	7	9	10	10
>=2	0	4	1	2	4	3

13. Secondary Outcome

Title	Time to First EXACT Event
Description	The time to first on-treatment EXACT event was calculated as the onset date of the first on-treatment EXACT event minus date of start of treatment plus 1.
Time Frame	Up to Day 168

Outcome Measure Data

Analysis Population Description

Per Protocol Population.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	101	102	100	103	100	99
Measure Type: Number; Unit of Measure: Days
First quartile (Q1) time to event	NA [1]	NA [1]	NA [1]	NA [1]	NA [1]	NA [1]
Median time to event	NA [2]	NA [2]	NA [2]	NA [2]	NA [2]	NA [2]

[1]

If <25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.

[2]

If <50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 5 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Posterior Hazard Ratio
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 90%; 0.5 to 2.6
	Estimation Comments	Median Posterior Hazard Ratio, 90% credible interval for Placebo and Danirixin 5 mg has been presented.
Other Statistical Analysis		DNX versus (vs.) Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted Forced Expiratory Volume in one second (FEV1)at Screening.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 10 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Posterior Hazard Ratio
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 90%; 0.4 to 2.4
	Estimation Comments	Median Posterior Hazard Ratio, 90% credible interval for Placebo and Danirixin 10 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 25 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Posterior Hazard Ratio
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 90%; 0.6 to 3.2
	Estimation Comments	Median Posterior Hazard Ratio, 90% credible interval for Placebo and Danirixin 25 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 35 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Posterior Hazard Ratio
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 90%; 1.0 to 4.3
	Estimation Comments	Median Posterior Hazard Ratio, 90% credible interval for Placebo and Danirixin 35 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 50 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Posterior Hazard Ratio
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 90%; 0.9 to 4.5
	Estimation Comments	Median Posterior Hazard Ratio, 90% credible interval for Placebo and Danirixin 50 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

14. Secondary Outcome

Title	Severity of EXACT Event
Description	EXACT is a 14 item PRO instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. The total score for EXACT-PRO ranges from 0-100, higher scores indicate more severe symptoms. Severity is the highest EXACT total score during the period from onset to recovery.
Time Frame	Up to Day 168

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Only those participants with data available at the specified data points were analyzed

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	9	15	9	13	19	16
Mean (Standard Deviation); Unit of Measure: Scores on a scale
	22.1 (6.60)	26.7 (3.71)	22.9 (5.28)	28.6 (5.68)	25.0 (5.54)	26.4 (6.36)

15. Secondary Outcome

Title	EXACT Event Duration for All Events
Description	EXACT is a 14 item PRO instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. The total score for EXACT-PRO ranges from 0-100, higher scores indicate more severe symptoms. Severity is the highest EXACT total score during the period from onset to recovery. Duration of EXACT events has been reported.
Time Frame	Up to Day 168

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	9	15	9	13	19	16
Mean (Standard Deviation); Unit of Measure: Days
	45.3 (50.37)	11.6 (10.15)	45.8 (51.97)	25.5 (42.11)	17.6 (16.28)	18.7 (37.75)

16. Secondary Outcome

Title	Time to First HCRU-defined COPD Exacerbation
Description	The time to first on-treatment Moderate/Severe HCRU exacerbation was calculated as exacerbation onset date of first on-treatment moderate or severe on-treatment exacerbation - date of start of treatment +1.
Time Frame	Up to Day 196

Outcome Measure Data

Analysis Population Description

Per Protocol Population.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	101	102	100	103	100	99
Measure Type: Number; Unit of Measure: Days
Q1 time to event	110	47	63	79	70	57
Median time to event	NA [1]	NA [1]	NA [1]	NA [1]	NA [1]	152

[1]

If <50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 5 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Bayesian proportional hazards model
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 90%; 1.0 to 2.2
	Estimation Comments	Hazard Ratio, 90% credible interval for Placebo and Danirixin 5 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator %predicted FEV1 at Screening.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 10 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Bayesian proportional hazards model
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 90%; 0.8 to 1.7
	Estimation Comments	Hazard Ratio, 90% credible interval for Placebo and Danirixin 10 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 25 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Bayesian proportional hazards model
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 90%; 0.7 to 1.6
	Estimation Comments	Hazard Ratio, 90% credible interval for Placebo and Danirixin 25 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 35 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Bayesian proportional hazards model
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 90%; 1.0 to 2.1
	Estimation Comments	Hazard Ratio, 90% credible interval for Placebo and Danirixin 35 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 50 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Bayesian proportional hazards model
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 90%; 1.1 to 2.3
	Estimation Comments	Hazard Ratio, 90% credible interval for Placebo and Danirixin 50 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

17. Secondary Outcome

Title	Time to First Severe HCRU-defined COPD Exacerbation
Description	A COPD exacerbation defined as a severe exacerbation if it requires hospitalization or ER visit or extended observation. The time to first on-treatment Moderate/Severe HCRU exacerbation was calculated as exacerbation onset date of first on-treatment moderate or severe on-treatment exacerbation - date of start of treatment +1.
Time Frame	Up to Day 196

Outcome Measure Data

Analysis Population Description

Per Protocol Population.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	101	102	100	103	100	99
Measure Type: Number; Unit of Measure: Days
Q1 time to event	NA [1]	NA [1]	NA [1]	NA [1]	NA [1]	NA [1]
Median time to event	NA [2]	NA [2]	NA [2]	NA [2]	NA [2]	NA [2]

[1]

If <25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.

[2]

If <50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 5 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Bayesian proportional hazards model
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 90%; 0.7 to 5.5
	Estimation Comments	Hazard Ratio, 90% credible interval for Placebo and Danirixin 5 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 10 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Bayesian proportional hazards model
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 90%; 0.7 to 5.8
	Estimation Comments	Hazard Ratio, 90% credible interval for Placebo and Danirixin 10 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 25 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Bayesian proportional hazards model
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 90%; 0.7 to 5.6
	Estimation Comments	Hazard Ratio, 90% credible interval for Placebo and Danirixin 25 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 35 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Bayesian proportional hazards model
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.3
	Confidence Interval	(2-Sided) 90%; 0.9 to 6.9
	Estimation Comments	Hazard Ratio, 90% credible interval for Placebo and Danirixin 35 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 50 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Bayesian proportional hazards model
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 90%; 0.2 to 2.7
	Estimation Comments	Hazard Ratio, 90% credible interval for Placebo and Danirixin 50 mg has been presented.
Other Statistical Analysis		DNX vs. Placebo statistics calculated using a Bayesian proportional hazards model including treatment, gender, exacerbation history (<=1/>=2 moderate/severe), smoking status at Screening, country and post-bronchodilator % predicted FEV1 at Screening.

18. Secondary Outcome

Title	HCRU-defined Exacerbation Duration
Description	The duration of HCRU exacerbation were determined. The duration of the exacerbation was calculated as (exacerbation resolution date or date of death - exacerbation onset date + 1). For exacerbations which were not resolved but where the participant later died from other causes, the duration was calculated using date of death as the end date of the event.
Time Frame	Up to Day 196

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	44	75	58	56	66	65
Mean (Standard Deviation); Unit of Measure: Days
	10.3 (7.37)	12.3 (8.95)	12.9 (9.58)	14.0 (8.71)	10.7 (7.21)	14.2 (9.29)

19. Secondary Outcome

Title	Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score
Description	The SGRQ-C consists of 40 items aggregated into 3 component scores: Symptoms, Activity, Impacts, and a Total score. Each response to a question is assigned a weight. Component scores are calculated by summing the weights from all positive items in that component, dividing by the sum of weights for all items in that component, and multiplying this number by 100. Component scores could range from 0-100, with a higher component score indicating greater disease burden. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Posterior mean change and standard deviation has been presented.
Time Frame	Baseline, Days 84 and 168

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Number of participants presented represent those with data available at the time point being presented; however, all participants in the per protocol population without missing covariate information and with at least one post baseline measurement are included in the analysis.

Arm/Group Title		Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:		Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed		101	102	100	103	100	99
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Day 84, n=93, 97, 94, 96, 91, 90	Number Analyzed	93 participants	97 participants	94 participants	96 participants	91 participants	90 participants
		-3.79 (1.172)	-3.63 (1.150)	-1.31 (1.146)	-3.19 (1.148)	-2.83 (1.189)	-2.48 (1.175)
Day 168, n=85, 96, 86, 90, 86, 85	Number Analyzed	85 participants	96 participants	86 participants	90 participants	86 participants	85 participants
		-4.11 (1.292)	-3.44 (1.246)	-4.19 (1.292)	-4.94 (1.251)	-4.12 (1.287)	-3.41 (1.302)

20. Secondary Outcome

Title	Number of SGRQ Responder
Description	A participant was consider Responder according to SGRQ total score if their change from Baseline SGRQ total score of 4 units below Baseline or lower.
Time Frame	Day 84 and Day 168

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:		Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed		101	102	100	103	100	99
Measure Type: Number; Unit of Measure: Participants
Day 84, n=93, 97, 94, 96, 91, 90	Number Analyzed	93 participants	97 participants	94 participants	96 participants	91 participants	90 participants
		39	40	35	49	35	38
Day 168, n=85, 96, 86, 90, 86, 85	Number Analyzed	85 participants	96 participants	86 participants	90 participants	86 participants	85 participants
		35	47	40	47	41	34

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 5 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.208
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, Baseline SGRQ total score, smoking status at Screening, country, visit, Baseline by visit and treatment by visit interactions.
	Method	Linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 90%; 0.88 to 2.59
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 5 mg has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 10 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.482
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, Baseline SGRQ total score, smoking status at Screening, country, visit, Baseline by visit and treatment by visit interactions.
	Method	Linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 90%; 0.73 to 2.20
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 10 mg has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 25 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.239
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, Baseline SGRQ total score, smoking status at Screening, country, visit, Baseline by visit and treatment by visit interactions.
	Method	Linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.47
	Confidence Interval	(2-Sided) 90%; 0.86 to 2.53
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 25 mg has been presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 35 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.426
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, Baseline SGRQ total score, smoking status at Screening, country, visit, Baseline by visit and treatment by visit interactions.
	Method	Linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 90%; 0.75 to 2.26
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 35 mg has been presented.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 50 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.763
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, Baseline SGRQ total score, smoking status at Screening, country, visit, Baseline by visit and treatment by visit interactions.
	Method	Linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 90%; 0.52 to 1.58
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 50 mg has been presented.

21. Secondary Outcome

Title	Change From Baseline COPD Assessment Test (CAT) Total Score
Description	The CAT is an 8 item questionnaire (cough, sputum, chest tightness, breathlessness, going up hills/stairs, activity limitation at home, confidence leaving the home, and sleep and energy) that measures health status of participants with COPD. Participants were completed each question by rating their experience on a 6 point scale ranging from 0 (maximum impairment) to 5 (no impairment) with a total scoring range of 0-40; higher scores indicate worse health status. A CAT score was calculated by summing the non-missing scores on the eight items. Individual items are scored from 0 to 5 with a total score range from 0 - 40, higher scores indicate greater disease impact. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Posterior mean change and standard deviation has been presented.
Time Frame	Baseline, Days 84 and 168

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Number of participants presented represent those with data available at the time point being presented; however, all participants in the per protocol population without missing covariate information and with at least one post baseline measurement are included in the analysis.

Arm/Group Title		Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:		Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed		101	102	100	103	100	99
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Day 84, n=89, 97, 92, 89, 88, 85	Number Analyzed	89 participants	97 participants	92 participants	89 participants	88 participants	85 participants
		-2.02 (0.536)	-0.86 (0.525)	-0.63 (0.524)	-0.55 (0.542)	-1.51 (0.543)	-0.36 (0.549)
Day 168, n=84, 94, 86, 87, 85, 83	Number Analyzed	84 participants	94 participants	86 participants	87 participants	85 participants	83 participants
		-1.39 (0.557)	-1.39 (0.537)	-1.23 (0.548)	-0.97 (0.560)	-1.56 (0.560)	-1.32 (0.565)

22. Secondary Outcome

Title	Number of CAT Responder
Description	A participant was considered as a responder according to CAT score if their change from Baseline CAT score 2.0 units below Baseline or lower.
Time Frame	Day 84 and Day 168

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:		Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed		101	102	100	103	100	99
Measure Type: Count of Participants; Unit of Measure: Participants
Day 84, n=89, 97, 92, 89, 88, 85	Number Analyzed	89 participants	97 participants	92 participants	89 participants	88 participants	85 participants
		46 51.7%	44 45.4%	38 41.3%	37 41.6%	43 48.9%	36 42.4%
Day 168, n=84, 94, 86, 87, 85, 83	Number Analyzed	84 participants	94 participants	86 participants	87 participants	85 participants	83 participants
		41 48.8%	44 46.8%	39 45.3%	42 48.3%	46 54.1%	44 53.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 5 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.973
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, Baseline CAT score, smoking status at Screening, country, visit, Baseline by visit and treatment by visit interactions.
	Method	Linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 90%; 0.58 to 1.76
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 5 mg has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 10 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.825
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, Baseline CAT score, smoking status at Screening, country, visit, Baseline by visit and treatment by visit interactions.
	Method	Linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 90%; 0.53 to 1.63
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 10 mg has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 25 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.887
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, Baseline CAT score, smoking status at Screening, country, visit, Baseline by visit and treatment by visit interactions.
	Method	Linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 90%; 0.55 to 1.66
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 25 mg has been presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 35 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.567
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, Baseline CAT score, smoking status at Screening, country, visit, Baseline by visit and treatment by visit interactions.
	Method	Linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 90%; 0.69 to 2.13
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 35 mg has been presented.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Danirixin 50 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.501
	Comments	Analysis performed using a generalized linear mixed model with a logit link function including treatment, Baseline CAT score, smoking status at Screening, country, visit, Baseline by visit and treatment by visit interactions.
	Method	Linear mixed model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 90%; 0.72 to 2.20
	Estimation Comments	Odds Ratio, 90% credible interval for Placebo and Danirixin 50 mg has been presented.

23. Secondary Outcome

Title	Change From Baseline in Post-bronchodilator FEV1 as a Lung Function Assessment
Description	Spirometric analysis was done to determine FEV1. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Least square mean change from Baseline and standard error has been presented.
Time Frame	Baseline, Days 84 and 168

Outcome Measure Data

Analysis Population Description

mITT Population. Number of participants presented represent those with data available at the time point being presented; however, all participants in the mITT population without missing covariate information and with at least one post baseline measurement are included in the analysis.

Arm/Group Title		Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:		Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed		102	102	103	103	102	102
Least Squares Mean (Standard Error); Unit of Measure: Liters
Day 84, n=94, 99, 98, 97, 92, 93	Number Analyzed	94 participants	99 participants	98 participants	97 participants	92 participants	93 participants
		0.016 (0.0208)	-0.031 (0.0203)	-0.029 (0.0204)	-0.018 (0.0206)	-0.027 (0.0211)	0.027 (0.0210)
Day 168, n=88, 97, 90, 90, 88, 86	Number Analyzed	88 participants	97 participants	90 participants	90 participants	88 participants	86 participants
		-0.016 (0.0199)	-0.043 (0.0191)	-0.033 (0.0197)	-0.058 (0.0198)	-0.012 (0.0201)	-0.011 (0.0202)

24. Secondary Outcome

Title	Percent Predicted Normal FEV1
Description	Spirometric analysis was done to determine percent predicted FEVI at screening. FEV1 is forced expiratory volume in one second. Percent predicted FEV1 is defined as the percent FEV1 of the participant is divided by average FEV1 percent in the population of any person similar age, sex and body composition.
Time Frame	At Screening

Outcome Measure Data

Analysis Population Description

Per Protocol Population. Only those participants with available data at the specified time points were analyzed.

Arm/Group Title	Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:	Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed	100	102	100	103	100	99
Mean (Standard Deviation); Unit of Measure: Percent predicted FEV1
	58.98 (12.838)	56.75 (12.038)	56.62 (11.848)	56.84 (12.813)	57.51 (14.076)	57.84 (12.794)

25. Secondary Outcome

Title	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) as a Lung Function Assessment
Description	Spirometric analysis was done to determine FVC. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Least square mean change from Baseline and standard error has been presented.
Time Frame	Baseline, Days 84 and 168

Outcome Measure Data

Analysis Population Description

mITT Population. Number of participants presented represent those with data available at the time point being presented; however, all participants in the mITT population without missing covariate information and with at least one post baseline measurement are included in the analysis.

Arm/Group Title		Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:		Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Number of Participants Analyzed		102	102	103	103	102	102
Least Squares Mean (Standard Error); Unit of Measure: Liters
Day 84, n=94, 99, 98, 97, 92, 93	Number Analyzed	94 participants	99 participants	98 participants	97 participants	92 participants	93 participants
		0.024 (0.0321)	-0.054 (0.0313)	-0.043 (0.0315)	0.027 (0.0317)	-0.049 (0.0326)	0.014 (0.0323)
Day 168, n=88, 97, 90, 90, 88, 86	Number Analyzed	88 participants	97 participants	90 participants	90 participants	88 participants	86 participants
		-0.011 (0.0348)	-0.079 (0.0335)	-0.043 (0.0344)	-0.024 (0.0345)	-0.036 (0.0351)	-0.016 (0.0353)

26. Secondary Outcome

Title	Change From Baseline in Post-bronchodilator FEV1/FVC Ratio as a Lung Function Assessment
Description	Spirometric analysis was done to determine FEV1 and FVC. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline, Days 84 and 168

Outcome Measure Data

Analysis Population Description

mITT Population. Number of participants presented represent those with data available at the time point being presented; however, all participants in the mITT population without missing covariate information and with at least one post baseline measurement are included in the analysis.

Arm/Group Title		Placebo	Danirixin 5 mg	Danirixin 10 mg	Danirixin 25 mg	Danirixin 35 mg	Danirixin 50 mg
Arm/Group Description:		Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.