Trial Outcomes & Findings for Danirixin Dose Ranging Study in Participants With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT03034967)

NCT ID: NCT03034967

Last Updated: 2020-10-28

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 614 participants
• Primary outcome timeframe: Baseline and Month 6
• Results posted on: 2020-10-28

Participant Flow

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.

A total of 614 participants were randomized in this study across 9 countries.

Participant milestones

Measure	Placebo Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Study STARTED	102	102	103	103	102	102
Overall Study COMPLETED	88	97	90	92	88	87
Overall Study NOT COMPLETED	14	5	13	11	14	15

Reasons for withdrawal

Measure	Placebo Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Overall Study Withdrawal by Subject	9	2	6	6	9	2
Overall Study Physician Decision	1	0	1	1	1	0
Overall Study Lost to Follow-up	0	0	0	1	0	2
Overall Study Liver function test abnormality	0	0	1	0	0	0
Overall Study Protocol Violation	1	0	0	0	0	2
Overall Study Lack of Efficacy	0	1	2	1	1	0
Overall Study Adverse Event, non-fatal	3	1	2	0	2	8
Overall Study Adverse Event, Serious Fatal	0	1	1	2	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=102 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=103 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=102 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=102 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Total n=614 Participants Total of all reporting groups
Age, Continuous	66.2 Years STANDARD_DEVIATION 7.31 • n=5 Participants	66.3 Years STANDARD_DEVIATION 6.79 • n=7 Participants	65.7 Years STANDARD_DEVIATION 7.48 • n=5 Participants	66.3 Years STANDARD_DEVIATION 7.28 • n=4 Participants	65.1 Years STANDARD_DEVIATION 7.58 • n=21 Participants	65.7 Years STANDARD_DEVIATION 6.98 • n=10 Participants	65.9 Years STANDARD_DEVIATION 7.23 • n=115 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	36 Participants n=7 Participants	32 Participants n=5 Participants	38 Participants n=4 Participants	35 Participants n=21 Participants	32 Participants n=10 Participants	202 Participants n=115 Participants
Sex: Female, Male Male	73 Participants n=5 Participants	66 Participants n=7 Participants	71 Participants n=5 Participants	65 Participants n=4 Participants	67 Participants n=21 Participants	70 Participants n=10 Participants	412 Participants n=115 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	10 Participants n=5 Participants	6 Participants n=7 Participants	18 Participants n=5 Participants	17 Participants n=4 Participants	10 Participants n=21 Participants	17 Participants n=10 Participants	78 Participants n=115 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	6 Participants n=115 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	87 Participants n=5 Participants	93 Participants n=7 Participants	84 Participants n=5 Participants	86 Participants n=4 Participants	92 Participants n=21 Participants	84 Participants n=10 Participants	526 Participants n=115 Participants

PRIMARY outcome

Timeframe: Baseline and Month 6

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

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.

Outcome measures

Measure	Placebo n=86 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=95 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=87 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=91 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=85 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=86 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Change From Baseline in Respiratory Symptoms Measured by Evaluating Respiratory Symptoms (E-RS) in COPD. E-RS: COPD Total Score	-2.11 Scores on a scale Standard Deviation 0.345	-1.93 Scores on a scale Standard Deviation 0.289	-1.47 Scores on a scale Standard Deviation 0.349	-0.87 Scores on a scale Standard Deviation 0.286	-0.76 Scores on a scale Standard Deviation 0.259	-0.71 Scores on a scale Standard Deviation 0.281

PRIMARY outcome

Timeframe: Baseline and Month 6

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

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.

Outcome measures

Measure	Placebo n=86 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=95 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=87 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=91 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=85 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=86 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Breathlessness Score)	-0.82 Scores on a scale Standard Deviation 0.202	-0.69 Scores on a scale Standard Deviation 0.162	-0.41 Scores on a scale Standard Deviation 0.183	-0.15 Scores on a scale Standard Deviation 0.148	-0.10 Scores on a scale Standard Deviation 0.141	-0.09 Scores on a scale Standard Deviation 0.158

PRIMARY outcome

Timeframe: Baseline and Month 6

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

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.

Outcome measures

Measure	Placebo n=86 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=95 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=87 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=91 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=85 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=86 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Cough and Sputum Score)	-0.83 Scores on a scale Standard Deviation 0.107	-0.79 Scores on a scale Standard Deviation 0.090	-0.67 Scores on a scale Standard Deviation 0.109	-0.46 Scores on a scale Standard Deviation 0.104	-0.40 Scores on a scale Standard Deviation 0.088	-0.37 Scores on a scale Standard Deviation 0.098

PRIMARY outcome

Timeframe: Baseline and Month 6

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

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.

Outcome measures

Measure	Placebo n=86 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=95 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=87 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=91 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=85 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=86 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Chest Symptoms Score)	-0.36 Scores on a scale Standard Deviation 0.148	-0.35 Scores on a scale Standard Deviation 0.061	-0.34 Scores on a scale Standard Deviation 0.062	-0.34 Scores on a scale Standard Deviation 0.069	-0.34 Scores on a scale Standard Deviation 0.073	-0.34 Scores on a scale Standard Deviation 0.078

PRIMARY outcome

Timeframe: Up to Day 196

Population: 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.

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.

Outcome measures

Measure	Placebo n=102 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=103 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=102 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=102 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Any AE	63 Participants	63 Participants	69 Participants	68 Participants	63 Participants	71 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Any SAE	8 Participants	7 Participants	13 Participants	10 Participants	7 Participants	11 Participants

PRIMARY outcome

Timeframe: Up to Day 196

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

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.

Outcome measures

Measure	Placebo n=102 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=103 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=102 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=102 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Platelets, High, n=97, 102, 101, 101, 101, 99	0 Participants	2 Participants	1 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Basophils, High, n=97, 102, 101, 101, 101, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Basophils, No change, n=97, 102, 101, 101, 101, 99	97 Participants	102 Participants	101 Participants	101 Participants	101 Participants	99 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Eosinophils,No change,n=97,102,101,101,101,99	97 Participants	101 Participants	101 Participants	98 Participants	100 Participants	98 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Eosinophils, High, n=97, 102, 101, 101, 101, 99	0 Participants	1 Participants	0 Participants	3 Participants	1 Participants	1 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Ery. MCHC, Low, n=97, 102, 101, 101, 102, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Ery. MCHC,No change,n=97,102,101,101,102,99	97 Participants	102 Participants	101 Participants	101 Participants	102 Participants	99 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Ery. MCHC, High, n=97, 102, 101, 101, 102, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Ery. MCH, Low, n=97, 102, 101, 101, 102, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Ery. MCH, No Change, n=97, 102, 101, 101, 102, 99	97 Participants	102 Participants	101 Participants	101 Participants	102 Participants	98 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Ery. MCH, High, n=97, 102, 101, 101, 102, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Ery. MCV, Low, n=97, 102, 101, 101, 102, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Ery. MCV, No Change, n=97, 102, 101, 101, 102, 99	97 Participants	102 Participants	101 Participants	101 Participants	102 Participants	99 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Ery. MCV, High, n=97, 102, 101, 101, 102, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Erythrocytes, Low, n=97, 102, 101, 101, 102, 99	2 Participants	1 Participants	3 Participants	3 Participants	2 Participants	2 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Erythrocytes, No change,n=97,102,101,101,102,99	93 Participants	99 Participants	97 Participants	97 Participants	99 Participants	97 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Erythrocytes. High, n=97, 102, 101, 101, 102, 99	2 Participants	2 Participants	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Hematocrit, Low, n=97, 102, 101, 101, 102, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Hematocrit, No Change, n=97,102,101,101,102,99	97 Participants	102 Participants	101 Participants	101 Participants	102 Participants	99 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Hematocrit, High, n=97, 102, 101, 101, 102, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Hemoglobin, Low, n=97, 102, 101, 101, 102, 99	1 Participants	1 Participants	2 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Hemoglobin, No change, n=97,102,101,101,102,99	96 Participants	101 Participants	99 Participants	101 Participants	100 Participants	99 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Hemoglobin, High, n=97, 102, 101, 101, 102, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Leukocytes, Low, n=97, 102, 101, 101, 102, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Leukocytes, No change, n=97,102,101,101,102,99	97 Participants	102 Participants	101 Participants	101 Participants	102 Participants	98 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Leukocytes, High, n=97, 102, 101, 101, 102, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Lymphocytes, Low, n=97, 102, 101, 101, 101, 99	3 Participants	7 Participants	5 Participants	8 Participants	7 Participants	4 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Lymphocytes, No change, n=97,102,101,101,101,99	94 Participants	95 Participants	96 Participants	92 Participants	93 Participants	94 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Lymphocytes, High, n=97, 102, 101, 101, 101, 99	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Monocytes, No change, n=97, 102, 101, 101, 101, 99	97 Participants	101 Participants	99 Participants	101 Participants	100 Participants	98 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Monocytes, High, n=97, 102, 101, 101, 101, 99	0 Participants	1 Participants	2 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Neutrophils, Low, n=97, 102, 101, 101, 101, 99	0 Participants	0 Participants	0 Participants	1 Participants	3 Participants	1 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Neutrophils, No change, n=97,102,101,101,101,99	97 Participants	102 Participants	101 Participants	100 Participants	98 Participants	98 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Neutrophils, High, n=97, 102, 101, 101, 101, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Platelets, Low, n=97, 102, 101, 101, 101, 99	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI) Platelets, No change, n=97, 102, 101, 101, 101, 99	97 Participants	99 Participants	100 Participants	101 Participants	99 Participants	99 Participants

PRIMARY outcome

Timeframe: Up to Day 196

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

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.

Outcome measures

Measure	Placebo n=102 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=103 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=102 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=102 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI ALT, No change,n=99,102,102,102,101,100	99 Participants	102 Participants	101 Participants	102 Participants	101 Participants	100 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI ALT, High, n=99,102,102,102,101,100	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI ALP, No change,n=99,102,102,102,101,100	99 Participants	102 Participants	102 Participants	102 Participants	101 Participants	100 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI ALP, High, n=99,102,102,102,101,100	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI AST, No change,n=99,102,102,102,101,100	99 Participants	102 Participants	101 Participants	102 Participants	101 Participants	100 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI AST, High, n=99,102,102,102,101,100	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Bilirubin, No change, n=99,102,102,102,101,100	99 Participants	101 Participants	102 Participants	102 Participants	101 Participants	100 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Bilirubin, High, n=99, 102,102,102,101,100	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Calcium, Low, n=96,102,101,101,101,99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Calcium, No change, n=96,102,101,101,101,99	96 Participants	102 Participants	101 Participants	101 Participants	101 Participants	99 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Calcium, High, n=96,102,101,101,101,99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI CO2, Low, n=96,102,101,101,101,99	1 Participants	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI CO2, No change, n=96,102,101,101,101,99	94 Participants	102 Participants	99 Participants	99 Participants	101 Participants	98 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI CO2, High, n=96,102,101,101,101,99	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Chloride, Low, n=96,102,101,101,101,99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Chloride, No change, n=96,102,101,101,101,99	96 Participants	102 Participants	101 Participants	101 Participants	101 Participants	99 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Chloride, High, n=96,102,101,101,101,99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Creatinine, No change, n=96,102,101,101,101,99	94 Participants	100 Participants	99 Participants	99 Participants	99 Participants	99 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Creatinine, High, n=96, 102, 101, 101, 101, 99	2 Participants	2 Participants	2 Participants	2 Participants	2 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Direct bilirubin,NoChange,n=99,102,102,102,101,100	98 Participants	102 Participants	102 Participants	102 Participants	101 Participants	100 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Direct bilirubin,High,n=99,102,102,102,101,100	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Glucose, Low, n=96, 102, 101, 101, 101, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Glucose, No change, n=96, 102, 101, 101, 101, 99	96 Participants	102 Participants	101 Participants	101 Participants	101 Participants	99 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Glucose, High, n=96, 102, 101, 101, 101, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Potassium, Low, n=96, 102, 101, 101, 101, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Potassium, No change, n=96, 102, 101, 101, 101, 99	96 Participants	102 Participants	101 Participants	101 Participants	101 Participants	99 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Potassium, High, n=96, 102, 101, 101, 101, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Protein, No change, n=99, 102, 102, 102, 101, 100	99 Participants	102 Participants	102 Participants	102 Participants	101 Participants	100 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Protein, High, n=99, 102, 102, 102, 101, 100	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Sodium, Low, n=96, 102, 101, 101, 101, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Sodium, No change, n=96, 102, 101, 101, 101, 99	96 Participants	102 Participants	101 Participants	101 Participants	101 Participants	99 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Sodium, High, n=96, 102, 101, 101, 101, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Urea, Low, n=96, 102, 101, 101, 101, 99	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Urea, No change, n=96, 102, 101, 101, 101, 99	96 Participants	101 Participants	101 Participants	100 Participants	101 Participants	98 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Urea, High, n=96, 102, 101, 101, 101, 99	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Bilirubin/ALT,No change,n=99,102,102,102,101,100	99 Participants	102 Participants	102 Participants	102 Participants	101 Participants	100 Participants
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI Bilirubin/ALT, High,n=99,102,102,102,101,100	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 168

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

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.

Outcome measures

Measure	Placebo n=96 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=101 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=101 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=102 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Number of Participants With Worst Case Vital Signs Parameter Results by PCI DBP, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Vital Signs Parameter Results by PCI DBP, No change	96 Participants	102 Participants	101 Participants	101 Participants	102 Participants	99 Participants
Number of Participants With Worst Case Vital Signs Parameter Results by PCI SBP, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Worst Case Vital Signs Parameter Results by PCI SBP, No change	93 Participants	92 Participants	95 Participants	98 Participants	98 Participants	94 Participants
Number of Participants With Worst Case Vital Signs Parameter Results by PCI SBP, High	3 Participants	10 Participants	6 Participants	3 Participants	4 Participants	4 Participants
Number of Participants With Worst Case Vital Signs Parameter Results by PCI DBP, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Vital Signs Parameter Results by PCI Pulse rate, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Vital Signs Parameter Results by PCI Pulse rate, No change	96 Participants	102 Participants	99 Participants	100 Participants	102 Participants	98 Participants
Number of Participants With Worst Case Vital Signs Parameter Results by PCI Pulse rate, High	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Worst Case Vital Signs Parameter Results by PCI Respiratory rate, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Vital Signs Parameter Results by PCI Respiratory rate, No change	96 Participants	102 Participants	101 Participants	101 Participants	102 Participants	98 Participants
Number of Participants With Worst Case Vital Signs Parameter Results by PCI Respiratory rate, High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline and Day 168

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

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.

Outcome measures

Measure	Placebo n=96 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=101 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=101 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=102 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Number of Participants With Worst Case Post-Baseline Abnormal 12-lead Electrocardiogram (ECG) Findings Not Clinical significant	52 Participants	65 Participants	68 Participants	67 Participants	62 Participants	53 Participants
Number of Participants With Worst Case Post-Baseline Abnormal 12-lead Electrocardiogram (ECG) Findings Clinical significant	2 Participants	1 Participants	1 Participants	0 Participants	3 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Day 196

Population: Per Protocol Population.

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.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=100 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=100 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Number of Moderate or Severe Healthcare Resource Utilization (HCRU) Exacerbations Per Participant 0	66 Exacerbations per participant	51 Exacerbations per participant	61 Exacerbations per participant	63 Exacerbations per participant	55 Exacerbations per participant	50 Exacerbations per participant
Number of Moderate or Severe Healthcare Resource Utilization (HCRU) Exacerbations Per Participant 1	28 Exacerbations per participant	34 Exacerbations per participant	23 Exacerbations per participant	28 Exacerbations per participant	30 Exacerbations per participant	36 Exacerbations per participant
Number of Moderate or Severe Healthcare Resource Utilization (HCRU) Exacerbations Per Participant >=2	7 Exacerbations per participant	17 Exacerbations per participant	16 Exacerbations per participant	12 Exacerbations per participant	15 Exacerbations per participant	13 Exacerbations per participant

SECONDARY outcome

Timeframe: Month 6

Population: 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.

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.

Outcome measures

Measure	Placebo n=86 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=95 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=87 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=91 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=85 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=86 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Number of Responders E-RS in COPD (E-RS): COPD Total Score	33 Participants	48 Participants	33 Participants	30 Participants	29 Participants	32 Participants

SECONDARY outcome

Timeframe: Up to Day 196

Population: Per Protocol Population.

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.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=100 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=100 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Number of EXACT Events Per Participant 0	92 Events	92 Events	92 Events	92 Events	86 Events	86 Events
Number of EXACT Events Per Participant 1	9 Events	6 Events	7 Events	9 Events	10 Events	10 Events
Number of EXACT Events Per Participant >=2	0 Events	4 Events	1 Events	2 Events	4 Events	3 Events

SECONDARY outcome

Timeframe: Up to Day 168

Population: Per Protocol Population.

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.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=100 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=100 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Time to First EXACT Event First quartile (Q1) time to event	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.
Time to First EXACT Event Median time to event	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.

SECONDARY outcome

Timeframe: Up to Day 168

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

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.

Outcome measures

Measure	Placebo n=9 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=15 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=9 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=13 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=19 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=16 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Severity of EXACT Event	22.1 Scores on a scale Standard Deviation 6.60	26.7 Scores on a scale Standard Deviation 3.71	22.9 Scores on a scale Standard Deviation 5.28	28.6 Scores on a scale Standard Deviation 5.68	25.0 Scores on a scale Standard Deviation 5.54	26.4 Scores on a scale Standard Deviation 6.36

SECONDARY outcome

Timeframe: Up to Day 168

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

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.

Outcome measures

Measure	Placebo n=9 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=15 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=9 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=13 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=19 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=16 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
EXACT Event Duration for All Events	45.3 Days Standard Deviation 50.37	11.6 Days Standard Deviation 10.15	45.8 Days Standard Deviation 51.97	25.5 Days Standard Deviation 42.11	17.6 Days Standard Deviation 16.28	18.7 Days Standard Deviation 37.75

SECONDARY outcome

Timeframe: Up to Day 196

Population: Per Protocol Population.

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.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=100 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=100 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Time to First HCRU-defined COPD Exacerbation Median time to event	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	152 Days
Time to First HCRU-defined COPD Exacerbation Q1 time to event	110 Days	47 Days	63 Days	79 Days	70 Days	57 Days

SECONDARY outcome

Timeframe: Up to Day 196

Population: Per Protocol Population.

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.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=100 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=100 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Time to First Severe HCRU-defined COPD Exacerbation Q1 time to event	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<25% of participants experienced the event within a treatment then Q1 time to event are displayed as NA (not applicable) for that treatment.
Time to First Severe HCRU-defined COPD Exacerbation Median time to event	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.	NA Days If \<50% of participants experienced the event within a treatment then median time to event are displayed as NA (not applicable) for that treatment.

SECONDARY outcome

Timeframe: Up to Day 196

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

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.

Outcome measures

Measure	Placebo n=44 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=75 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=58 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=56 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=66 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=65 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
HCRU-defined Exacerbation Duration	10.3 Days Standard Deviation 7.37	12.3 Days Standard Deviation 8.95	12.9 Days Standard Deviation 9.58	14.0 Days Standard Deviation 8.71	10.7 Days Standard Deviation 7.21	14.2 Days Standard Deviation 9.29

SECONDARY outcome

Timeframe: Baseline, Days 84 and 168

Population: 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.

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.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=100 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=100 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score Day 84, n=93, 97, 94, 96, 91, 90	-3.79 Scores on a scale Standard Deviation 1.172	-3.63 Scores on a scale Standard Deviation 1.150	-1.31 Scores on a scale Standard Deviation 1.146	-3.19 Scores on a scale Standard Deviation 1.148	-2.83 Scores on a scale Standard Deviation 1.189	-2.48 Scores on a scale Standard Deviation 1.175
Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score Day 168, n=85, 96, 86, 90, 86, 85	-4.11 Scores on a scale Standard Deviation 1.292	-3.44 Scores on a scale Standard Deviation 1.246	-4.19 Scores on a scale Standard Deviation 1.292	-4.94 Scores on a scale Standard Deviation 1.251	-4.12 Scores on a scale Standard Deviation 1.287	-3.41 Scores on a scale Standard Deviation 1.302

SECONDARY outcome

Timeframe: Day 84 and Day 168

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

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Baseline, Days 84 and 168

Population: 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.

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.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=100 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=100 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Change From Baseline COPD Assessment Test (CAT) Total Score Day 84, n=89, 97, 92, 89, 88, 85	-2.02 Scores on a scale Standard Deviation 0.536	-0.86 Scores on a scale Standard Deviation 0.525	-0.63 Scores on a scale Standard Deviation 0.524	-0.55 Scores on a scale Standard Deviation 0.542	-1.51 Scores on a scale Standard Deviation 0.543	-0.36 Scores on a scale Standard Deviation 0.549
Change From Baseline COPD Assessment Test (CAT) Total Score Day 168, n=84, 94, 86, 87, 85, 83	-1.39 Scores on a scale Standard Deviation 0.557	-1.39 Scores on a scale Standard Deviation 0.537	-1.23 Scores on a scale Standard Deviation 0.548	-0.97 Scores on a scale Standard Deviation 0.560	-1.56 Scores on a scale Standard Deviation 0.560	-1.32 Scores on a scale Standard Deviation 0.565

SECONDARY outcome

Timeframe: Day 84 and Day 168

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

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.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=100 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=100 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Number of CAT Responder Day 84, n=89, 97, 92, 89, 88, 85	46 Participants	44 Participants	38 Participants	37 Participants	43 Participants	36 Participants
Number of CAT Responder Day 168, n=84, 94, 86, 87, 85, 83	41 Participants	44 Participants	39 Participants	42 Participants	46 Participants	44 Participants

SECONDARY outcome

Timeframe: Baseline, Days 84 and 168

Population: 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.

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.

Outcome measures

Measure	Placebo n=102 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=103 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=102 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=102 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Change From Baseline in Post-bronchodilator FEV1 as a Lung Function Assessment Day 84, n=94, 99, 98, 97, 92, 93	0.016 Liters Standard Error 0.0208	-0.031 Liters Standard Error 0.0203	-0.029 Liters Standard Error 0.0204	-0.018 Liters Standard Error 0.0206	-0.027 Liters Standard Error 0.0211	0.027 Liters Standard Error 0.0210
Change From Baseline in Post-bronchodilator FEV1 as a Lung Function Assessment Day 168, n=88, 97, 90, 90, 88, 86	-0.016 Liters Standard Error 0.0199	-0.043 Liters Standard Error 0.0191	-0.033 Liters Standard Error 0.0197	-0.058 Liters Standard Error 0.0198	-0.012 Liters Standard Error 0.0201	-0.011 Liters Standard Error 0.0202

SECONDARY outcome

Timeframe: At Screening

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

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.

Outcome measures

Measure	Placebo n=100 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=100 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=100 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Percent Predicted Normal FEV1	58.98 Percent predicted FEV1 Standard Deviation 12.838	56.75 Percent predicted FEV1 Standard Deviation 12.038	56.62 Percent predicted FEV1 Standard Deviation 11.848	56.84 Percent predicted FEV1 Standard Deviation 12.813	57.51 Percent predicted FEV1 Standard Deviation 14.076	57.84 Percent predicted FEV1 Standard Deviation 12.794

SECONDARY outcome

Timeframe: Baseline, Days 84 and 168

Population: 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.

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.

Outcome measures

Measure	Placebo n=102 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=103 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=102 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=102 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) as a Lung Function Assessment Day 84, n=94, 99, 98, 97, 92, 93	0.024 Liters Standard Error 0.0321	-0.054 Liters Standard Error 0.0313	-0.043 Liters Standard Error 0.0315	0.027 Liters Standard Error 0.0317	-0.049 Liters Standard Error 0.0326	0.014 Liters Standard Error 0.0323
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) as a Lung Function Assessment Day 168, n=88, 97, 90, 90, 88, 86	-0.011 Liters Standard Error 0.0348	-0.079 Liters Standard Error 0.0335	-0.043 Liters Standard Error 0.0344	-0.024 Liters Standard Error 0.0345	-0.036 Liters Standard Error 0.0351	-0.016 Liters Standard Error 0.0353

SECONDARY outcome

Timeframe: Baseline, Days 84 and 168

Population: 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.

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.

Outcome measures

Measure	Placebo n=102 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=103 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=102 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=102 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Change From Baseline in Post-bronchodilator FEV1/FVC Ratio as a Lung Function Assessment Day 84, n=94, 99, 98, 97, 92, 93	-0.003 Ratio of FEV1/FVC Standard Deviation 0.0543	-0.001 Ratio of FEV1/FVC Standard Deviation 0.0554	-0.000 Ratio of FEV1/FVC Standard Deviation 0.0453	-0.013 Ratio of FEV1/FVC Standard Deviation 0.0630	-0.000 Ratio of FEV1/FVC Standard Deviation 0.0402	0.014 Ratio of FEV1/FVC Standard Deviation 0.1636
Change From Baseline in Post-bronchodilator FEV1/FVC Ratio as a Lung Function Assessment Day 168, n=88, 97, 90, 90, 88, 86	-0.007 Ratio of FEV1/FVC Standard Deviation 0.0622	-0.003 Ratio of FEV1/FVC Standard Deviation 0.0555	0.003 Ratio of FEV1/FVC Standard Deviation 0.0420	-0.015 Ratio of FEV1/FVC Standard Deviation 0.0610	0.002 Ratio of FEV1/FVC Standard Deviation 0.0495	-0.002 Ratio of FEV1/FVC Standard Deviation 0.0385

SECONDARY outcome

Timeframe: Baseline, Months 1, 2, 3, 4, 5 and 6

Population: 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.

The mean number of puffs of rescue per day was calculated over the same time periods and using the same assumptions as rescue use via diary. 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.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=100 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=100 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Change From Baseline Number of Puffs of Rescue Medication Per Day Month 6, n=86, 95, 88, 91, 85, 86	-0.17 Puffs per day Standard Error 0.196	0.21 Puffs per day Standard Error 0.191	0.10 Puffs per day Standard Error 0.195	0.15 Puffs per day Standard Error 0.193	0.04 Puffs per day Standard Error 0.197	0.28 Puffs per day Standard Error 0.198
Change From Baseline Number of Puffs of Rescue Medication Per Day Month 1, n=100, 102, 100, 102, 98, 99	0.00 Puffs per day Standard Error 0.132	0.36 Puffs per day Standard Error 0.130	0.28 Puffs per day Standard Error 0.132	0.15 Puffs per day Standard Error 0.130	-0.03 Puffs per day Standard Error 0.133	0.28 Puffs per day Standard Error 0.133
Change From Baseline Number of Puffs of Rescue Medication Per Day Month 2, n=96, 100, 98, 97, 98, 96	-0.22 Puffs per day Standard Error 0.187	0.42 Puffs per day Standard Error 0.184	0.18 Puffs per day Standard Error 0.186	0.35 Puffs per day Standard Error 0.185	0.07 Puffs per day Standard Error 0.187	0.33 Puffs per day Standard Error 0.188
Change From Baseline Number of Puffs of Rescue Medication Per Day Month 3, n=95, 100, 95, 97, 94, 92	-0.18 Puffs per day Standard Error 0.184	0.29 Puffs per day Standard Error 0.181	0.21 Puffs per day Standard Error 0.184	0.25 Puffs per day Standard Error 0.182	0.07 Puffs per day Standard Error 0.185	0.27 Puffs per day Standard Error 0.186
Change From Baseline Number of Puffs of Rescue Medication Per Day Month 4, n=92, 98, 92, 97, 90, 90	-0.18 Puffs per day Standard Error 0.193	0.27 Puffs per day Standard Error 0.189	0.27 Puffs per day Standard Error 0.192	0.21 Puffs per day Standard Error 0.190	-0.04 Puffs per day Standard Error 0.194	0.44 Puffs per day Standard Error 0.195
Change From Baseline Number of Puffs of Rescue Medication Per Day Month 5, n=88, 97, 88, 94, 87, 87	-0.16 Puffs per day Standard Error 0.190	0.17 Puffs per day Standard Error 0.186	0.19 Puffs per day Standard Error 0.190	0.25 Puffs per day Standard Error 0.187	-0.06 Puffs per day Standard Error 0.191	0.29 Puffs per day Standard Error 0.192

SECONDARY outcome

Timeframe: Days 84 and 168

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

The Clinical Visit PROactive Physical Activity in COPD (C-PPAC) tool is a designed for intermittent use within a clinical study. PROactive Total Score and two domain scores (amount and difficulty) are derived using data from the C-PPAC questionnaire and a physical activity monitor worn for 7 days prior to the questionnaire.C-PPAC is a 12 item questionnaire. The PROactive tools are scored from 0 to 100 with higher scores indicating greater disease impact. It was implemented in a subset of approximately 50% of participants. The amount domain is calculated using 2 items from the C-PPAC questionnaire (amount of walking outside and chores outside) and 2 activity monitor outputs (vector magnitude units per minute (VMU/min) and steps/day). Each domain score is based on the addition of items (0-15 for amount and 0-40 for difficulty) and then scaled from 0-100. The total score is calculated as (amount+difficulty)/2.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=100 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=100 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=99 Participants Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Participant Experience of Physical Activity Measured Using PROactive Physical Activity in COPD (C-PPAC) Questionnaire Total score, Day 84, n=8, 4, 6, 6, 10, 6	3.00 Scores on a scale Standard Deviation 5.964	-5.75 Scores on a scale Standard Deviation 6.035	-3.83 Scores on a scale Standard Deviation 12.754	0.42 Scores on a scale Standard Deviation 2.635	-1.20 Scores on a scale Standard Deviation 8.453	2.33 Scores on a scale Standard Deviation 2.677
Participant Experience of Physical Activity Measured Using PROactive Physical Activity in COPD (C-PPAC) Questionnaire Total score, Day 168, n=13, 7, 9, 8, 6, 7	-0.96 Scores on a scale Standard Deviation 13.266	1.86 Scores on a scale Standard Deviation 9.344	2.11 Scores on a scale Standard Deviation 5.878	1.25 Scores on a scale Standard Deviation 3.423	4.08 Scores on a scale Standard Deviation 6.492	0.43 Scores on a scale Standard Deviation 7.607
Participant Experience of Physical Activity Measured Using PROactive Physical Activity in COPD (C-PPAC) Questionnaire Amount score, Day 84, n=8, 4, 6, 6, 10, 6	2.25 Scores on a scale Standard Deviation 5.825	-8.50 Scores on a scale Standard Deviation 7.937	-4.00 Scores on a scale Standard Deviation 19.204	0.00 Scores on a scale Standard Deviation 6.957	-4.20 Scores on a scale Standard Deviation 10.706	-0.83 Scores on a scale Standard Deviation 5.345
Participant Experience of Physical Activity Measured Using PROactive Physical Activity in COPD (C-PPAC) Questionnaire Amount score, Day 168, n=13, 7, 9, 8, 6, 7	-3.69 Scores on a scale Standard Deviation 14.733	-0.43 Scores on a scale Standard Deviation 8.810	2.11 Scores on a scale Standard Deviation 9.558	1.25 Scores on a scale Standard Deviation 9.161	3.67 Scores on a scale Standard Deviation 11.708	-4.14 Scores on a scale Standard Deviation 12.522
Participant Experience of Physical Activity Measured Using PROactive Physical Activity in COPD (C-PPAC) Questionnaire Difficult score, Day 84, n=29, 22, 18, 19, 24, 14	6.38 Scores on a scale Standard Deviation 9.511	1.64 Scores on a scale Standard Deviation 8.301	-0.17 Scores on a scale Standard Deviation 7.679	1.89 Scores on a scale Standard Deviation 11.704	2.79 Scores on a scale Standard Deviation 9.278	4.50 Scores on a scale Standard Deviation 9.598
Participant Experience of Physical Activity Measured Using PROactive Physical Activity in COPD (C-PPAC) Questionnaire Difficult score, Day 168, n=29, 20, 18, 19, 25, 15	3.03 Scores on a scale Standard Deviation 14.409	2.20 Scores on a scale Standard Deviation 11.039	2.11 Scores on a scale Standard Deviation 7.553	0.63 Scores on a scale Standard Deviation 11.413	1.52 Scores on a scale Standard Deviation 9.687	4.87 Scores on a scale Standard Deviation 8.887

SECONDARY outcome

Timeframe: Pre-dose on Days 1, 56, 84 and 168; 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Days 1 and 168

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

Blood samples were collected from the participants for the analysis of blood pharmacokinetic concentration-time data. All participants in the mITT population who had at least 1 non-missing Pharmacokinetic assessment obtained and analyzed whilst on treatment with danirixin were included Pharmacokinetic population.

Outcome measures

Measure	Placebo n=102 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=103 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=102 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=102 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=101 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 168, 4 hours, n=13, 11, 16, 18, 16	90.5 Nanogram per milliliter Standard Deviation 53.67	190.9 Nanogram per milliliter Standard Deviation 103.35	452.8 Nanogram per milliliter Standard Deviation 289.44	805.0 Nanogram per milliliter Standard Deviation 346.87	1459.9 Nanogram per milliliter Standard Deviation 909.32	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 168, 6 hours, n=13, 13, 16, 18, 15	55.6 Nanogram per milliliter Standard Deviation 26.36	135.5 Nanogram per milliliter Standard Deviation 87.39	289.6 Nanogram per milliliter Standard Deviation 188.04	554.8 Nanogram per milliliter Standard Deviation 313.52	960.4 Nanogram per milliliter Standard Deviation 633.37	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 168, 8 hours, n=13, 13, 17, 18, 15	41.5 Nanogram per milliliter Standard Deviation 19.75	102.6 Nanogram per milliliter Standard Deviation 60.14	245.1 Nanogram per milliliter Standard Deviation 165.40	444.9 Nanogram per milliliter Standard Deviation 298.69	760.8 Nanogram per milliliter Standard Deviation 679.30	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 168, 10 hours, n=13, 12, 17, 18, 15	42.4 Nanogram per milliliter Standard Deviation 35.98	76.6 Nanogram per milliliter Standard Deviation 56.95	193.9 Nanogram per milliliter Standard Deviation 128.42	380.2 Nanogram per milliliter Standard Deviation 285.81	715.0 Nanogram per milliliter Standard Deviation 840.54	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 168, 12 hours, n=13, 12, 17, 18, 15	42.2 Nanogram per milliliter Standard Deviation 41.29	73.1 Nanogram per milliliter Standard Deviation 41.21	169.7 Nanogram per milliliter Standard Deviation 114.20	481.2 Nanogram per milliliter Standard Deviation 640.17	662.4 Nanogram per milliliter Standard Deviation 877.91	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 1, Pre-dose, n=97, 99, 102, 102, 100	2.1 Nanogram per milliliter Standard Deviation 19.41	0.4 Nanogram per milliliter Standard Deviation 3.92	0.3 Nanogram per milliliter Standard Deviation 3.06	17.2 Nanogram per milliliter Standard Deviation 169.33	3.9 Nanogram per milliliter Standard Deviation 39.10	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 1, 0.5 hour, n=16, 19, 24, 26, 19	86.7 Nanogram per milliliter Standard Deviation 85.73	210.4 Nanogram per milliliter Standard Deviation 207.54	730.5 Nanogram per milliliter Standard Deviation 1046.42	976.1 Nanogram per milliliter Standard Deviation 839.37	1331.0 Nanogram per milliliter Standard Deviation 1220.06	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 1, 1 hour, n=16, 18, 24, 26, 19	148.3 Nanogram per milliliter Standard Deviation 104.75	343.3 Nanogram per milliliter Standard Deviation 228.66	822.0 Nanogram per milliliter Standard Deviation 527.47	1183.5 Nanogram per milliliter Standard Deviation 760.02	1846.2 Nanogram per milliliter Standard Deviation 979.95	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 1, 2 hours, n=16, 19, 24, 26, 19	115.3 Nanogram per milliliter Standard Deviation 46.00	277.7 Nanogram per milliliter Standard Deviation 245.32	707.7 Nanogram per milliliter Standard Deviation 256.63	1011.2 Nanogram per milliliter Standard Deviation 398.82	1472.8 Nanogram per milliliter Standard Deviation 858.49	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 1, 4 hours, n=16, 19, 24, 26, 19	59.2 Nanogram per milliliter Standard Deviation 17.79	165.3 Nanogram per milliliter Standard Deviation 136.50	401.5 Nanogram per milliliter Standard Deviation 188.75	591.5 Nanogram per milliliter Standard Deviation 302.96	904.6 Nanogram per milliliter Standard Deviation 599.85	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 1, 6 hours, n=16, 19, 24, 26, 19	34.4 Nanogram per milliliter Standard Deviation 12.32	100.6 Nanogram per milliliter Standard Deviation 84.26	270.0 Nanogram per milliliter Standard Deviation 169.37	371.5 Nanogram per milliliter Standard Deviation 335.23	594.9 Nanogram per milliliter Standard Deviation 525.00	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 1, 8 hours, n=15, 19, 24, 26, 19	26.1 Nanogram per milliliter Standard Deviation 13.54	67.8 Nanogram per milliliter Standard Deviation 61.02	213.8 Nanogram per milliliter Standard Deviation 162.24	325.8 Nanogram per milliliter Standard Deviation 359.79	428.2 Nanogram per milliliter Standard Deviation 398.16	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 1, 10 hours, n=16, 18, 22, 26, 19	42.5 Nanogram per milliliter Standard Deviation 67.85	61.5 Nanogram per milliliter Standard Deviation 56.67	265.0 Nanogram per milliliter Standard Deviation 396.25	274.5 Nanogram per milliliter Standard Deviation 328.04	302.3 Nanogram per milliliter Standard Deviation 255.81	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 1, 12 hours, n=16, 16, 21, 26, 18	87.2 Nanogram per milliliter Standard Deviation 174.14	74.7 Nanogram per milliliter Standard Deviation 82.51	188.2 Nanogram per milliliter Standard Deviation 188.27	232.8 Nanogram per milliliter Standard Deviation 316.67	459.3 Nanogram per milliliter Standard Deviation 561.53	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 56, Pre-dose, n=94, 91, 94, 95, 92	53.2 Nanogram per milliliter Standard Deviation 73.19	91.8 Nanogram per milliliter Standard Deviation 102.43	252.3 Nanogram per milliliter Standard Deviation 295.15	372.1 Nanogram per milliliter Standard Deviation 427.41	572.0 Nanogram per milliliter Standard Deviation 738.28	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 84, Pre-dose, n=97, 94, 96, 91, 90	50.2 Nanogram per milliliter Standard Deviation 77.78	76.2 Nanogram per milliliter Standard Deviation 106.86	212.3 Nanogram per milliliter Standard Deviation 211.35	342.8 Nanogram per milliliter Standard Deviation 411.28	484.3 Nanogram per milliliter Standard Deviation 527.47	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 168, Pre-dose, n=92, 85, 89, 85, 84	41.2 Nanogram per milliliter Standard Deviation 38.02	99.5 Nanogram per milliliter Standard Deviation 138.00	217.9 Nanogram per milliliter Standard Deviation 221.92	350.7 Nanogram per milliliter Standard Deviation 336.07	459.5 Nanogram per milliliter Standard Deviation 421.30	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 168, 0.5 hours, n=14, 12, 17, 18, 16	147.7 Nanogram per milliliter Standard Deviation 91.51	248.3 Nanogram per milliliter Standard Deviation 189.30	530.5 Nanogram per milliliter Standard Deviation 536.75	1449.5 Nanogram per milliliter Standard Deviation 949.00	1635.6 Nanogram per milliliter Standard Deviation 1077.48	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 168, 1 hours, n=14, 13, 17, 18, 16	162.1 Nanogram per milliliter Standard Deviation 108.88	314.0 Nanogram per milliliter Standard Deviation 157.04	681.2 Nanogram per milliliter Standard Deviation 630.86	1590.3 Nanogram per milliliter Standard Deviation 1019.32	1725.4 Nanogram per milliliter Standard Deviation 870.79	—
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data Day 168, 2 hours, n=14, 13, 17, 18, 16	127.4 Nanogram per milliliter Standard Deviation 88.80	331.9 Nanogram per milliliter Standard Deviation 164.10	574.7 Nanogram per milliliter Standard Deviation 445.85	1045.2 Nanogram per milliliter Standard Deviation 414.21	1736.6 Nanogram per milliliter Standard Deviation 592.51	—

SECONDARY outcome

Timeframe: Days 1 and 168

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

Blood samples were collected at indicated timepoints for the analysis of phamacokinetic parameter. All participants in the PK population who had at least 1 non-missing PK assessment obtained and analyzed whilst on treatment with danirixin from a dry blood spot sample and corresponding wet whole blood sample were included in Pharmacokinetic population.

Outcome measures

Measure	Placebo n=102 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=103 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=102 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=102 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=101 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Area Under the Plasma Concentration-time Curve From Time Zero to Last Time of Quantifiable Concentration [AUC(0-t)] of Danirixin in Whole Blood Using Dried Blood Spot Day 1, n=17, 19, 24, 26, 19	543.0 Hour*nanogram per milliliter Interval 354.9 to 830.8	1373.1 Hour*nanogram per milliliter Interval 1081.7 to 1743.0	3851.5 Hour*nanogram per milliliter Interval 3136.7 to 4729.2	5485.1 Hour*nanogram per milliliter Interval 4604.8 to 6533.8	8073.4 Hour*nanogram per milliliter Interval 6591.3 to 9888.7	—
Area Under the Plasma Concentration-time Curve From Time Zero to Last Time of Quantifiable Concentration [AUC(0-t)] of Danirixin in Whole Blood Using Dried Blood Spot Day 168, n=14, 13, 17, 18, 16	752.1 Hour*nanogram per milliliter Interval 546.8 to 1034.4	1701.8 Hour*nanogram per milliliter Interval 1257.2 to 2303.7	4170.1 Hour*nanogram per milliliter Interval 3198.1 to 5437.6	7682.6 Hour*nanogram per milliliter Interval 6384.8 to 9244.0	11538.0 Hour*nanogram per milliliter Interval 9313.4 to 14294.0	—

SECONDARY outcome

Timeframe: Days 1 and 168

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

Blood samples were collected from the participants for the analysis of pharmacokinetic parameter.

Outcome measures

Measure	Placebo n=102 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=103 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=102 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=102 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=101 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Concentration Maximum (Cmax) of Danirixin in Whole Blood Using Dried Blood Spots Day 1, n=17, 19, 24, 26, 19	164.9 Nanogram per milliliter Interval 119.5 to 227.5	343.1 Nanogram per milliliter Interval 264.1 to 445.6	1028.8 Nanogram per milliliter Interval 818.2 to 1293.7	1386.2 Nanogram per milliliter Interval 1172.1 to 1639.3	2119.1 Nanogram per milliliter Interval 1728.9 to 2597.4	—
Concentration Maximum (Cmax) of Danirixin in Whole Blood Using Dried Blood Spots Day 168, n=14, 13, 17, 18, 16	171.9 Nanogram per milliliter Interval 123.5 to 239.4	357.3 Nanogram per milliliter Interval 274.4 to 465.4	821.2 Nanogram per milliliter Interval 570.9 to 1181.2	1695.0 Nanogram per milliliter Interval 1285.8 to 2234.5	2390.5 Nanogram per milliliter Interval 2014.6 to 2836.5	—

SECONDARY outcome

Timeframe: Days 1 and 168

Population: Pharmacokinetic Population.

Blood samples were collected from the participants for the analysis of pharmacokinetic parameter.

Outcome measures

Measure	Placebo n=102 Participants Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=103 Participants Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=102 Participants Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=102 Participants Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=101 Participants Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Time to Reach Maximum Plasma Concentration (Tmax) of Danirixin in Whole Blood Using Dried Blood Spots Day 1, n=17, 19, 24, 26, 19	1.000 Hours Interval 0.58 to 11.8	1.000 Hours Interval 0.5 to 12.0	1.000 Hours Interval 0.5 to 10.08	1.000 Hours Interval 0.48 to 5.85	1.000 Hours Interval 0.5 to 12.0	—
Time to Reach Maximum Plasma Concentration (Tmax) of Danirixin in Whole Blood Using Dried Blood Spots Day 168, n=14, 13, 17, 18, 16	1.000 Hours Interval 0.5 to 11.78	1.000 Hours Interval 0.5 to 2.0	1.000 Hours Interval 0.33 to 10.0	1.000 Hours Interval 0.48 to 11.87	1.542 Hours Interval 0.5 to 11.77	—

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 20 other events

Deaths: 0 deaths

Danirixin 5 mg

Serious events: 7 serious events

Other events: 24 other events

Deaths: 0 deaths

Danirixin 10 mg

Serious events: 13 serious events

Other events: 22 other events

Deaths: 1 deaths

Danirixin 25 mg

Serious events: 10 serious events

Other events: 31 other events

Deaths: 2 deaths

Danirixin 35 mg

Serious events: 7 serious events

Other events: 27 other events

Deaths: 1 deaths

Danirixin 50 mg

Serious events: 11 serious events

Other events: 27 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo n=102 participants at risk Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 participants at risk Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=103 participants at risk Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 participants at risk Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=102 participants at risk Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=102 participants at risk Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Infections and infestations Pneumonia	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	1.9% 2/103 • Number of events 2 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	3.9% 4/102 • Number of events 4 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Infections and infestations Arthritis bacterial	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Infections and infestations Metapneumovirus infection	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Infections and infestations Perichondritis	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Infections and infestations Pilonidal cyst	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Infections and infestations Psoas abscess	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Infections and infestations Pyelonephritis acute	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Infections and infestations Septic shock	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Anal prolapse	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Chronic gastritis	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Faecaloma	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Gastrointestinal perforation	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Haemorrhoids	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Large intestine perforation	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Large intestine polyp	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Pancreatitis	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Pancreatitis chronic	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	1.9% 2/103 • Number of events 2 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	2.0% 2/102 • Number of events 2 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Cardiac disorders Atrial fibrillation	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 2 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	1.9% 2/103 • Number of events 2 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Cardiac disorders Angina pectoris	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Cardiac disorders Coronary artery disease	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Cardiac disorders Ischaemic cardiomyopathy	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Cardiac disorders Mitral valve incompetence	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Cardiac disorders Myocardial infarction	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 2 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder papilloma	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cardiac neoplasm unspecified	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal adenocarcinoma	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Musculoskeletal and connective tissue disorders Ankylosing spondylitis	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
General disorders Death	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	1.9% 2/103 • Number of events 2 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
General disorders Sudden death	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Nervous system disorders Diabetic neuropathy	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Nervous system disorders Hemiparesis	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Nervous system disorders Sciatica	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Blood and lymphatic system disorders Anaemia	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Hepatobiliary disorders Hepatic cyst	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Hepatobiliary disorders Hepatic steatosis	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Metabolism and nutrition disorders Decreased appetite	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Ear and labyrinth disorders Vertigo	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Renal and urinary disorders Haematuria	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.98% 1/102 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Vascular disorders Deep vein thrombosis	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/103 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.97% 1/103 • Number of events 1 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	0.00% 0/102 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.

Other adverse events

Measure	Placebo n=102 participants at risk Participants received placebo film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 5 mg n=102 participants at risk Participants received danirixin 5 milligram (mg) film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 10 mg n=103 participants at risk Participants received danirixin 10 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 25 mg n=103 participants at risk Participants received danirixin 25 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 35 mg n=102 participants at risk Participants received danirixin 35 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.	Danirixin 50 mg n=102 participants at risk Participants received danirixin 50 mg film coated tablets orally twice daily with food and standard care of treatment for 24 weeks.
Infections and infestations Nasopharyngitis	11.8% 12/102 • Number of events 13 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	7.8% 8/102 • Number of events 8 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	8.7% 9/103 • Number of events 11 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	11.7% 12/103 • Number of events 14 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	13.7% 14/102 • Number of events 16 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	9.8% 10/102 • Number of events 14 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Infections and infestations Upper respiratory tract infection	4.9% 5/102 • Number of events 6 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	6.9% 7/102 • Number of events 7 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	6.8% 7/103 • Number of events 8 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	8.7% 9/103 • Number of events 12 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	4.9% 5/102 • Number of events 8 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	5.9% 6/102 • Number of events 8 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Nervous system disorders Headache	2.0% 2/102 • Number of events 2 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	3.9% 4/102 • Number of events 4 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	5.8% 6/103 • Number of events 6 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	4.9% 5/103 • Number of events 8 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	7.8% 8/102 • Number of events 9 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	7.8% 8/102 • Number of events 8 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.
Musculoskeletal and connective tissue disorders Back pain	3.9% 4/102 • Number of events 4 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	6.9% 7/102 • Number of events 7 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	3.9% 4/103 • Number of events 4 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	5.8% 6/103 • Number of events 7 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	4.9% 5/102 • Number of events 6 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.	4.9% 5/102 • Number of events 5 • On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 196 days mITT 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. SAEs and AEs were reported for mITT Population.

Additional Information

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GlaxoSmithKline

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