Trial Outcomes & Findings for Dose Finding Study of Nemiralisib (GSK2269557) in Subjects With an Acute Moderate or Severe Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT03345407)

Last Updated: 2021-07-14

Results Overview

FEV1 is maximal amount of air exhaled forcefully from lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after participant was administered 4 inhalations of albuterol (salbutamol) via MDI using spacer/valved-holding chamber or via one nebulized treatment. Post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and post-bronchodilator. Change from Baseline in clinic visit trough FEV1 at Day 84 measured post-bronchodilator is FEV1 measured prior to dosing and post-bronchodilator on Day 84 minus post-bronchodilator Baseline FEV1. Bayesian repeated measure model adjusted for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender was used. Posterior adjusted median change from Baseline and 95% highest posterior density (HPD) credible interval (CrI) was presented.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

943 participants

Primary outcome timeframe

Baseline and Day 84

Results posted on

2021-07-14

Participant Flow

This was a Phase IIb, multicenter, randomized, stratified, double-blind (sponsor open), placebo controlled parallel-group study in participants who presented with an acute moderate or severe exacerbation of chronic obstructive pulmonary disease (COPD) requiring Standard of Care (SoC).

A total of 943 participants were randomized, and 938 participants who received at least one dose of study treatment were included in the modified intent to treat (MITT) Population. The study included participants enrolled from 16 countries.

Participant milestones

Participant milestones
Measure	Placebo Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 100 mcg Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Overall Study STARTED	276	22	91	92	90	89	278
Overall Study COMPLETED	244	19	79	81	75	73	233
Overall Study NOT COMPLETED	32	3	12	11	15	16	45

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 100 mcg Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Overall Study Withdrawal by Subject	11	1	5	6	3	6	16
Overall Study Physician Decision	3	1	0	0	1	2	3
Overall Study Lost to Follow-up	2	0	1	0	1	2	3
Overall Study Protocol-defined stopping criteria	9	0	0	0	2	1	1
Overall Study Protocol Violation	2	0	0	0	1	0	3
Overall Study Lack of Efficacy	1	1	1	1	1	0	3
Overall Study Adverse Event	4	0	5	4	6	5	16

Baseline Characteristics

Dose Finding Study of Nemiralisib (GSK2269557) in Subjects With an Acute Moderate or Severe Exacerbation of Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Total n=938 Participants Total of all reporting groups
Age, Continuous	65.4 Years STANDARD_DEVIATION 7.94 • n=5 Participants	67.8 Years STANDARD_DEVIATION 7.20 • n=7 Participants	63.1 Years STANDARD_DEVIATION 7.61 • n=5 Participants	65.1 Years STANDARD_DEVIATION 7.43 • n=4 Participants	66.0 Years STANDARD_DEVIATION 6.94 • n=21 Participants	64.9 Years STANDARD_DEVIATION 8.04 • n=8 Participants	64.8 Years STANDARD_DEVIATION 7.61 • n=8 Participants	65.0 Years STANDARD_DEVIATION 7.68 • n=24 Participants
Sex: Female, Male Female	86 Participants n=5 Participants	6 Participants n=7 Participants	35 Participants n=5 Participants	29 Participants n=4 Participants	31 Participants n=21 Participants	22 Participants n=8 Participants	100 Participants n=8 Participants	309 Participants n=24 Participants
Sex: Female, Male Male	190 Participants n=5 Participants	16 Participants n=7 Participants	56 Participants n=5 Participants	63 Participants n=4 Participants	59 Participants n=21 Participants	67 Participants n=8 Participants	178 Participants n=8 Participants	629 Participants n=24 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=8 Participants	6 Participants n=8 Participants	15 Participants n=24 Participants
Race/Ethnicity, Customized Asian-East Asian Heritage	18 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	2 Participants n=4 Participants	9 Participants n=21 Participants	7 Participants n=8 Participants	19 Participants n=8 Participants	66 Participants n=24 Participants
Race/Ethnicity, Customized Asian-South East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants	4 Participants n=24 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants	6 Participants n=8 Participants	14 Participants n=24 Participants
Race/Ethnicity, Customized White-Arabic/North African Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	4 Participants n=24 Participants
Race/Ethnicity, Customized White-White Caucasian/European Heritage	252 Participants n=5 Participants	17 Participants n=7 Participants	79 Participants n=5 Participants	86 Participants n=4 Participants	79 Participants n=21 Participants	76 Participants n=8 Participants	246 Participants n=8 Participants	835 Participants n=24 Participants

PRIMARY outcome

Timeframe: Baseline and Day 84

Population: MITT Population consisted of all randomized participants who received at least 1 dose of study treatment.. Only those participants with data available at the specified data points were analyzed.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=75 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=69 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=58 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=216 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=215 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=16 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=72 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator	0.014 Liters Interval -0.044 to 0.073	0.058 Liters Interval -0.002 to 0.118	0.049 Liters Interval -0.017 to 0.113	0.049 Liters Interval 0.012 to 0.086	0.052 Liters Interval 0.018 to 0.091	0.031 Liters Interval -0.09 to 0.149	0.026 Liters Interval -0.036 to 0.084

SECONDARY outcome

Timeframe: Up to Week 12

Population: MITT Population.

Moderate COPD exacerbations are defined as worsening symptoms of COPD treated with short-acting bronchodilators (SABDs) plus antibiotics and/or oral/systemic corticosteroids. Severe COPD exacerbations are defined as worsening symptoms of COPD that require hospitalization or visit to the emergency room. Severe exacerbation may also be associated with acute respiratory failure. Rate of exacerbations was analyzed using Bayesian Poisson model adjusting for length of on-treatment follow-up, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior median exacerbation rate and 95% HPD CrI has been presented.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period	0.28 No.of exacerbation per 84 Days Interval 0.2 to 0.38	0.32 No.of exacerbation per 84 Days Interval 0.23 to 0.43	0.20 No.of exacerbation per 84 Days Interval 0.13 to 0.29	0.36 No.of exacerbation per 84 Days Interval 0.29 to 0.43	0.31 No.of exacerbation per 84 Days Interval 0.25 to 0.39	NA No.of exacerbation per 84 Days The participants randomized to Nemiralisib 12.5 mcg were excluded from this analysis due to insufficient participants with data.	0.29 No.of exacerbation per 84 Days Interval 0.2 to 0.39

SECONDARY outcome

Timeframe: Up to Week 12

Population: MITT Population.

Number of participants with time to next (on-treatment) moderate/severe exacerbation following index exacerbation during the 12-Week Treatment Period was defined as time from the date of randomization until the date of onset of the first moderate/severe exacerbation whilst on study treatment. Participants who did not have an exacerbation whilst on study treatment were censored at the date of their last dose of study treatment. Time to next exacerbation was analyzed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation	25 Participants	26 Participants	15 Participants	80 Participants	72 Participants	3 Participants	24 Participants

SECONDARY outcome

Timeframe: Baseline and Days 14, 28, 56 (pre and post bronchodilaor), 84 (pre-bronchodilator) and at hospital discharge (maximum 24 Weeks)

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

Pulmonary function was measured by FEV1, defined as maximal amount of air exhaled forcefully from the lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after participant was administered with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre-bronchodilator and post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and pre-bronchodilator and post-bronchodilator, respectively. Change from Baseline in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre-bronchodilator is defined as FEV1 measured prior to dosing and pre-bronchodilator on Days 14, 28, 56 and 84 minus pre-bronchodilator Baseline FEV1.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 14, Post, n=248, 20, 86, 83, 77, 78, 241	-0.050 Liters Standard Deviation 0.2477	0.054 Liters Standard Deviation 0.2983	0.073 Liters Standard Deviation 0.2655	0.044 Liters Standard Deviation 0.2216	0.034 Liters Standard Deviation 0.2707	0.075 Liters Standard Deviation 0.2425	0.010 Liters Standard Deviation 0.2168
Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 56, Post, n=237, 19, 78, 77, 74, 69, 224	0.004 Liters Standard Deviation 0.2373	0.026 Liters Standard Deviation 0.2556	-0.011 Liters Standard Deviation 0.2260	0.011 Liters Standard Deviation 0.2470	0.020 Liters Standard Deviation 0.2614	-0.002 Liters Standard Deviation 0.2252	-0.012 Liters Standard Deviation 0.2524
Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 14, Pre, n=240, 20, 85, 83, 76, 76, 238	-0.013 Liters Standard Deviation 0.2509	0.053 Liters Standard Deviation 0.2958	0.041 Liters Standard Deviation 0.2738	0.023 Liters Standard Deviation 0.2561	0.008 Liters Standard Deviation 0.2729	0.100 Liters Standard Deviation 0.2511	-0.021 Liters Standard Deviation 0.2657
Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 28, Pre, n=239, 20, 82, 79, 75, 71, 232	-0.010 Liters Standard Deviation 0.2333	0.064 Liters Standard Deviation 0.2592	0.016 Liters Standard Deviation 0.2713	0.020 Liters Standard Deviation 0.2512	0.017 Liters Standard Deviation 0.2585	0.081 Liters Standard Deviation 0.2661	-0.034 Liters Standard Deviation 0.2875
Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 28, Post, n=245, 19, 83, 81, 76, 72, 232	-0.034 Liters Standard Deviation 0.2401	0.049 Liters Standard Deviation 0.2639	0.027 Liters Standard Deviation 0.2369	0.029 Liters Standard Deviation 0.2307	0.036 Liters Standard Deviation 0.2647	0.059 Liters Standard Deviation 0.2575	0.004 Liters Standard Deviation 0.2183
Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 56, Pre, n=230, 20, 78, 76, 73, 67, 224	0.011 Liters Standard Deviation 0.2415	0.022 Liters Standard Deviation 0.2522	-0.004 Liters Standard Deviation 0.2233	-0.001 Liters Standard Deviation 0.2858	0.005 Liters Standard Deviation 0.2295	-0.006 Liters Standard Deviation 0.2636	-0.024 Liters Standard Deviation 0.3210
Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 84, Pre, n=210, 17, 71, 73, 66, 58, 212	0.005 Liters Standard Deviation 0.2668	0.015 Liters Standard Deviation 0.2739	0.007 Liters Standard Deviation 0.2461	0.010 Liters Standard Deviation 0.2829	0.000 Liters Standard Deviation 0.2566	0.003 Liters Standard Deviation 0.2232	-0.049 Liters Standard Deviation 0.2549
Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Hospital discharge, Pre, n=23, 2, 8, 8, 7, 3, 22	0.056 Liters Standard Deviation 0.1782	0.052 Liters Standard Deviation 0.3481	0.162 Liters Standard Deviation 0.1426	0.075 Liters Standard Deviation 0.1974	0.071 Liters Standard Deviation 0.1586	0.168 Liters Standard Deviation 0.2652	0.108 Liters Standard Deviation 0.3888
Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Hospital discharge, Post, n=8, 2, 1, 1, 1, 0, 6	-0.076 Liters Standard Deviation NA NA indicates standard deviation could not be calculated as single participant was analyzed.	0.094 Liters Standard Deviation NA NA indicates standard deviation could not be calculated as single participant was analyzed.	—	-0.006 Liters Standard Deviation 0.1079	0.134 Liters Standard Deviation 0.1514	0.153 Liters Standard Deviation 0.0933	0.083 Liters Standard Deviation NA Not applicable (NA) indicates standard deviation could not be calculated as single participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and pre- and post-bronchodilator on Days 14, 28, 56 and 84

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

Pulmonary function was measured by FEV1, defined as maximal amount of air exhaled forcefully from the lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10 to 30 minutes after participant was administered with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre-bronchodilator and post-bronchodilator Baseline FEV1 is defined as latest FEV1 measured prior to first dose of study treatment and pre-bronchodilator and post-bronchodilator, respectively. Change from hospital discharge in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre- and post-bronchodilator is defined as FEV1 measured prior to dosing and pre- and post-bronchodilator on Days 14, 28, 56 and 84 minus pre and post-bronchodilator Baseline FEV1.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 14, Post, n=5, 2, 1, 1, 1, 0, 5	0.310 Liters Standard Deviation NA NA indicates standard deviation could not be calculated as single participant was analyzed.	-0.305 Liters Standard Deviation NA NA indicates standard deviation could not be calculated as single participant was analyzed.	—	-0.021 Liters Standard Deviation 0.1326	0.056 Liters Standard Deviation 0.3372	0.431 Liters Standard Deviation 0.5190	0.119 Liters Standard Deviation NA NA indicates standard deviation could not be calculated as single participant was analyzed.
Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 56, Pre, n=37, 2, 14, 8, 9, 10, 36	0.014 Liters Standard Deviation 0.1938	-0.074 Liters Standard Deviation 0.3847	-0.042 Liters Standard Deviation 0.1840	-0.054 Liters Standard Deviation 0.2942	0.019 Liters Standard Deviation 0.2282	0.106 Liters Standard Deviation 0.6138	0.019 Liters Standard Deviation 0.3509
Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 14, Pre, n=20, 2, 8, 8, 6, 4, 20	-0.049 Liters Standard Deviation 0.1882	-0.069 Liters Standard Deviation 0.4905	0.173 Liters Standard Deviation 0.5137	0.002 Liters Standard Deviation 0.2343	0.082 Liters Standard Deviation 0.2783	0.355 Liters Standard Deviation 0.4207	0.069 Liters Standard Deviation 0.3012
Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 28, Pre, n=37, 2, 14, 8, 10, 9, 37	-0.085 Liters Standard Deviation 0.2072	0.012 Liters Standard Deviation 0.4020	0.030 Liters Standard Deviation 0.4029	-0.046 Liters Standard Deviation 0.2639	0.026 Liters Standard Deviation 0.2691	0.261 Liters Standard Deviation 0.5204	0.012 Liters Standard Deviation 0.2910
Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 28, Post, n=22, 2, 8, 1, 4, 4, 22	0.130 Liters Standard Deviation NA NA indicates standard deviation could not be calculated as single participant was analyzed.	0.009 Liters Standard Deviation 0.2006	0.007 Liters Standard Deviation 0.3237	-0.094 Liters Standard Deviation 0.2293	0.034 Liters Standard Deviation 0.2779	0.334 Liters Standard Deviation 0.5614	0.130 Liters Standard Deviation 0.2327
Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 56, Post, n=22, 2, 7, 1, 4, 5, 21	0.098 Liters Standard Deviation NA NA indicates standard deviation could not be calculated as single participant was analyzed.	-0.056 Liters Standard Deviation 0.3572	-0.072 Liters Standard Deviation 0.1490	-0.135 Liters Standard Deviation 0.2410	-0.014 Liters Standard Deviation 0.2896	0.139 Liters Standard Deviation 0.6838	0.042 Liters Standard Deviation 0.3068
Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 84, Pre, n=37, 2, 12, 8, 7, 10, 35	-0.081 Liters Standard Deviation 0.1738	-0.072 Liters Standard Deviation 0.4391	0.043 Liters Standard Deviation 0.2511	-0.062 Liters Standard Deviation 0.2816	0.007 Liters Standard Deviation 0.2741	-0.027 Liters Standard Deviation 0.4554	0.121 Liters Standard Deviation 0.2770
Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator Day 84, Post, n=22, 2, 6, 1, 4, 5, 22	0.108 Liters Standard Deviation NA NA indicates standard deviation could not be calculated as single participant was analyzed.	0.021 Liters Standard Deviation 0.3151	0.006 Liters Standard Deviation 0.2180	-0.106 Liters Standard Deviation 0.2956	-0.039 Liters Standard Deviation 0.2610	0.133 Liters Standard Deviation 0.5162	0.037 Liters Standard Deviation 0.3341

SECONDARY outcome

Timeframe: Days 14, 28, 56 and 84

Population: MITT Population.

EXACT patient-reported outcome (EXACT-PRO), 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an electronic diary (eDiary). Total score ranges from 0-100, higher score indicates more severe condition. Participants were required to complete EXACT-PRO every evening; however, on the day of randomization it was to be completed in the morning. Response was decrease in rolling average EXACT Total Score \>=9 points from maximum observed value, sustained for \>=7 days, with first of 7 days defined as recovery day. Analysis was performed using Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation Day 14	29 Percentage of participants	28 Percentage of participants	24 Percentage of participants	32 Percentage of participants	29 Percentage of participants	27 Percentage of participants	37 Percentage of participants
Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation Day 28	43 Percentage of participants	42 Percentage of participants	27 Percentage of participants	42 Percentage of participants	40 Percentage of participants	41 Percentage of participants	52 Percentage of participants
Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation Day 56	52 Percentage of participants	50 Percentage of participants	31 Percentage of participants	50 Percentage of participants	49 Percentage of participants	45 Percentage of participants	59 Percentage of participants
Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation Day 84	54 Percentage of participants	50 Percentage of participants	37 Percentage of participants	54 Percentage of participants	51 Percentage of participants	50 Percentage of participants	59 Percentage of participants

SECONDARY outcome

Timeframe: From randomization to Week 12

Population: MITT Population.

Time to EXACT-defined recovery from index exacerbation is defined as time from the date of randomization until date of the first EXACT-defined recovery day during the 12-Week Treatment Period. EXACT-defined recovery from the index exacerbation is defined as a decrease in the Rolling Average EXACT total Score \>=9 points from the Maximum Observed Value, sustained for \>=7 days, with the first of the 7 days defined as the recovery day. Analysis was performed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Number of participants reporting events is presented.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool	50 Participants	45 Participants	34 Participants	149 Participants	141 Participants	11 Participants	54 Participants

SECONDARY outcome

Timeframe: Up to Week 12

Population: Severity was derived for participants from MITT Population who had reported subsequent exacerbation. Only those participants with data available at specified data points were analyzed (represented by n=X in the category title).

Severity of subsequent HCRU-defined exacerbations defined by EXACT was defined as the highest EXACT Total Score (not using the 3-day Rolling Average) during the period from date of onset of the subsequent HCRU-exacerbation until date of EXACT-defined recovery of subsequent exacerbation. EXACT-PRO, 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an eDiary. Total score ranges from 0-100, higher score indicates more severe condition. For participants with more than one subsequent exacerbation, severity was calculated for each subsequent exacerbation.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=25 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=26 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=15 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=78 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=66 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=3 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=23 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT Moderate/Severe, n=66, 3, 23, 25, 26, 15, 78	50.5 Scores on a scale Standard Deviation 10.76	47.5 Scores on a scale Standard Deviation 13.95	57.6 Scores on a scale Standard Deviation 10.30	51.9 Scores on a scale Standard Deviation 10.78	53.3 Scores on a scale Standard Deviation 12.16	64.6 Scores on a scale Standard Deviation 25.20	59.8 Scores on a scale Standard Deviation 12.82
Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT Moderate, n=55, 3, 15, 23, 17, 10, 63	50.0 Scores on a scale Standard Deviation 11.15	46.3 Scores on a scale Standard Deviation 14.20	53.8 Scores on a scale Standard Deviation 9.28	50.0 Scores on a scale Standard Deviation 10.17	53.1 Scores on a scale Standard Deviation 11.54	60.0 Scores on a scale Standard Deviation 26.56	57.4 Scores on a scale Standard Deviation 11.08
Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT Severe, n=13, 1, 9, 3, 10, 6, 20	55.3 Scores on a scale Standard Deviation 5.69	49.5 Scores on a scale Standard Deviation 13.95	64.1 Scores on a scale Standard Deviation 8.99	58.8 Scores on a scale Standard Deviation 10.34	54.0 Scores on a scale Standard Deviation 15.53	83.0 Scores on a scale Standard Deviation NA NA indicates standard deviation could not be calculated as only one participant was analyzed.	64.0 Scores on a scale Standard Deviation 15.01

SECONDARY outcome

Timeframe: Days 28, 56 and 84

Population: MITT Population.

The CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score is calculated by summing the scores of all items and ranges from 0 to 40, higher scores indicating severe condition. The percentage of responders using the CAT is defined as number of participants with a decrease from Baseline in CAT Total Score \>=2 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Percentage of responders using CAT was derived only for participants with a Baseline CAT Total Score \>=2. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation Day 28	39 Percentage of responders	38 Percentage of responders	34 Percentage of responders	25 Percentage of responders	32 Percentage of responders	36 Percentage of responders	34 Percentage of responders
Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation Day 56	61 Percentage of responders	69 Percentage of responders	55 Percentage of responders	61 Percentage of responders	63 Percentage of responders	50 Percentage of responders	73 Percentage of responders
Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation Day 84	65 Percentage of responders	72 Percentage of responders	60 Percentage of responders	66 Percentage of responders	70 Percentage of responders	55 Percentage of responders	78 Percentage of responders

SECONDARY outcome

Timeframe: Baseline and at Days 28, 56 and 84

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

The CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score was calculated by summing the scores of all items and ranges from 0 to 40, higher scores indicating more severe condition. Baseline (Day 1) is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in CAT Total Score is defined as CAT Total Score on Days 28, 56 and 84 minus Baseline CAT Total Score. Analysis was performed using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI has been presented.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Change From Baseline in CAT Total Score Day 28, n=234, 19, 86, 80, 77, 74, 229	-3.9 Scores on a scale Interval -5.4 to -2.4	-5.1 Scores on a scale Interval -6.5 to -3.7	-3.1 Scores on a scale Interval -4.5 to -1.6	-4.7 Scores on a scale Interval -5.6 to -3.8	-4.7 Scores on a scale Interval -5.6 to -3.8	-2.3 Scores on a scale Interval -5.1 to 0.5	-4.0 Scores on a scale Interval -5.4 to -2.7
Change From Baseline in CAT Total Score Day 56, n=231, 20, 78, 77, 76, 69, 222	-4.5 Scores on a scale Interval -6.0 to -2.9	-4.8 Scores on a scale Interval -6.4 to -3.4	-3.8 Scores on a scale Interval -5.5 to -2.3	-4.4 Scores on a scale Interval -5.4 to -3.5	-4.2 Scores on a scale Interval -5.2 to -3.3	-1.9 Scores on a scale Interval -4.7 to 1.0	-3.4 Scores on a scale Interval -5.0 to -1.9
Change From Baseline in CAT Total Score Day 84, n=218, 17, 75, 75, 69, 62, 213	-5.1 Scores on a scale Interval -6.7 to -3.5	-4.7 Scores on a scale Interval -6.3 to -3.1	-3.8 Scores on a scale Interval -5.4 to -2.1	-4.2 Scores on a scale Interval -5.2 to -3.2	-4.6 Scores on a scale Interval -5.6 to -3.6	-2.7 Scores on a scale Interval -6.0 to 0.3	-3.5 Scores on a scale Interval -5.0 to -1.9

SECONDARY outcome

Timeframe: Days 28, 56 and 84

Population: MITT Population.

SGRQ-C is a 40-item questionnaire designed specifically to focus on COPD participants and was scored equivalent to the SGRQ Total Score, ranging from 0 to 100, where higher scores reflect worse health-related quality of life. The percentage of responders on the SGRQ Total Score was derived for participants with a Baseline SGRQ Total Score \>=4. Percentage of responders on the SGRQ Total Score is defined as number of participants with a decrease from Baseline in SGRQ Total Score \>=4 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 Day 56	55 Percentage of responders	60 Percentage of responders	49 Percentage of responders	53 Percentage of responders	50 Percentage of responders	36 Percentage of responders	56 Percentage of responders
Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 Day 84	63 Percentage of responders	68 Percentage of responders	57 Percentage of responders	62 Percentage of responders	61 Percentage of responders	50 Percentage of responders	66 Percentage of responders
Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 Day 28	26 Percentage of responders	32 Percentage of responders	24 Percentage of responders	21 Percentage of responders	21 Percentage of responders	14 Percentage of responders	19 Percentage of responders

SECONDARY outcome

Timeframe: Baseline and Days 28, 56 and 84

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

SGRQ-C is a 40-item questionnaire designed specifically to focus on COPD participants and was scored equivalent to SGRQ Total Score, ranging from 0 to 100, where higher scores reflect worse health-related quality of life. Scores on a scale were calculated as 100 multiplied by summed weights from positive items in questionnaire divided by sum of weights of all items in questionnaire. Baseline (Day 1) is defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in SGRQ Total Score is defined as SGRQ Total Score on Days 28, 56 and 84 minus Baseline SGRQ Total Score. Analysis was performed using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI was presented

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 Day 28, n=232, 19, 86, 78, 77, 72, 225	-10.6 Scores on a scale Interval -13.8 to -7.1	-10.9 Scores on a scale Interval -14.2 to -7.6	-7.8 Scores on a scale Interval -11.2 to -4.3	-7.9 Scores on a scale Interval -9.9 to -5.9	-7.7 Scores on a scale Interval -9.8 to -5.7	-5.7 Scores on a scale Interval -12.2 to 0.5	-8.2 Scores on a scale Interval -11.4 to -5.1
Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 Day 56, n=227, 20, 78, 77, 74, 68, 219	-10.7 Scores on a scale Interval -14.1 to -7.3	-11.3 Scores on a scale Interval -14.6 to -7.6	-8.9 Scores on a scale Interval -12.6 to -5.5	-8.4 Scores on a scale Interval -10.6 to -6.3	-8.0 Scores on a scale Interval -10.2 to -6.0	-3.9 Scores on a scale Interval -10.4 to 2.8	-9.3 Scores on a scale Interval -12.5 to -5.9
Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 Day 84, n=218, 17, 74, 74, 69, 60, 209	-11.3 Scores on a scale Interval -14.8 to -7.7	-10.9 Scores on a scale Interval -14.4 to -7.2	-9.4 Scores on a scale Interval -13.1 to -5.5	-7.9 Scores on a scale Interval -10.1 to -5.7	-9.1 Scores on a scale Interval -11.3 to -6.8	-6.6 Scores on a scale Interval -13.6 to 0.3	-9.3 Scores on a scale Interval -12.8 to -6.0

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 of treatment and over the Week 12 treatment period

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

Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Rescue medication use was recorded as the number of occasions of rescue medication use each day. The mean number of occasions of rescue medication use per day is defined as sum of the number of occasions of rescue medication use each day within the time-period divided by the total number of days with non-missing values within the time-period. Over the 12-Week treatment period is defined as Day 1 to Day of last dose.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Mean Number of Occasions of Rescue Medication Use Per Day Week 3, n=256, 21, 90, 88, 80, 81, 245	1.693 No. of occasions of rescue use per day Standard Deviation 1.9679	1.488 No. of occasions of rescue use per day Standard Deviation 1.6611	1.742 No. of occasions of rescue use per day Standard Deviation 1.8380	1.655 No. of occasions of rescue use per day Standard Deviation 1.7430	1.729 No. of occasions of rescue use per day Standard Deviation 1.8157	2.021 No. of occasions of rescue use per day Standard Deviation 2.2926	1.495 No. of occasions of rescue use per day Standard Deviation 1.3943
Mean Number of Occasions of Rescue Medication Use Per Day Week 6, n=250, 20, 86, 84, 78, 72, 234	1.792 No. of occasions of rescue use per day Standard Deviation 2.0822	1.636 No. of occasions of rescue use per day Standard Deviation 1.8042	1.936 No. of occasions of rescue use per day Standard Deviation 2.0729	1.780 No. of occasions of rescue use per day Standard Deviation 1.8083	1.741 No. of occasions of rescue use per day Standard Deviation 1.9543	2.378 No. of occasions of rescue use per day Standard Deviation 2.6904	1.382 No. of occasions of rescue use per day Standard Deviation 1.4000
Mean Number of Occasions of Rescue Medication Use Per Day Week 1, n=254, 21, 87, 88, 80, 79, 254	1.926 No. of occasions of rescue use per day Standard Deviation 2.1569	1.670 No. of occasions of rescue use per day Standard Deviation 1.5728	1.917 No. of occasions of rescue use per day Standard Deviation 1.9298	1.747 No. of occasions of rescue use per day Standard Deviation 1.7332	1.699 No. of occasions of rescue use per day Standard Deviation 1.7674	2.112 No. of occasions of rescue use per day Standard Deviation 2.2977	1.633 No. of occasions of rescue use per day Standard Deviation 1.4320
Mean Number of Occasions of Rescue Medication Use Per Day Week 2, n=259, 21, 88, 89, 80, 82, 252	1.712 No. of occasions of rescue use per day Standard Deviation 2.0310	1.497 No. of occasions of rescue use per day Standard Deviation 1.5700	1.611 No. of occasions of rescue use per day Standard Deviation 1.7717	1.587 No. of occasions of rescue use per day Standard Deviation 1.6531	1.650 No. of occasions of rescue use per day Standard Deviation 1.8711	2.231 No. of occasions of rescue use per day Standard Deviation 2.7169	1.469 No. of occasions of rescue use per day Standard Deviation 1.4036
Mean Number of Occasions of Rescue Medication Use Per Day Week 4, n=250, 21, 89, 87, 81, 77, 243	1.720 No. of occasions of rescue use per day Standard Deviation 2.0083	1.489 No. of occasions of rescue use per day Standard Deviation 1.6734	2.009 No. of occasions of rescue use per day Standard Deviation 2.0506	1.707 No. of occasions of rescue use per day Standard Deviation 1.7512	1.684 No. of occasions of rescue use per day Standard Deviation 1.7706	2.190 No. of occasions of rescue use per day Standard Deviation 2.3657	1.514 No. of occasions of rescue use per day Standard Deviation 1.5022
Mean Number of Occasions of Rescue Medication Use Per Day Week 5, n=251, 20, 88, 85, 78, 76, 240	1.750 No. of occasions of rescue use per day Standard Deviation 2.0380	1.535 No. of occasions of rescue use per day Standard Deviation 1.8384	1.949 No. of occasions of rescue use per day Standard Deviation 1.9685	1.737 No. of occasions of rescue use per day Standard Deviation 1.8030	1.735 No. of occasions of rescue use per day Standard Deviation 1.8662	2.329 No. of occasions of rescue use per day Standard Deviation 2.6394	1.533 No. of occasions of rescue use per day Standard Deviation 1.5706
Mean Number of Occasions of Rescue Medication Use Per Day Week 7, n=250, 20, 85, 83, 77, 71, 231	1.697 No. of occasions of rescue use per day Standard Deviation 2.0769	1.628 No. of occasions of rescue use per day Standard Deviation 1.8741	1.899 No. of occasions of rescue use per day Standard Deviation 2.1694	1.826 No. of occasions of rescue use per day Standard Deviation 1.8778	1.703 No. of occasions of rescue use per day Standard Deviation 1.9914	2.479 No. of occasions of rescue use per day Standard Deviation 2.6976	1.531 No. of occasions of rescue use per day Standard Deviation 1.6374
Mean Number of Occasions of Rescue Medication Use Per Day Week 8, n=250, 20, 84, 83, 77, 71, 231	1.616 No. of occasions of rescue use per day Standard Deviation 1.9444	1.572 No. of occasions of rescue use per day Standard Deviation 1.8294	2.006 No. of occasions of rescue use per day Standard Deviation 2.2242	1.824 No. of occasions of rescue use per day Standard Deviation 1.8397	1.656 No. of occasions of rescue use per day Standard Deviation 1.8606	2.736 No. of occasions of rescue use per day Standard Deviation 3.1579	1.553 No. of occasions of rescue use per day Standard Deviation 1.5884
Mean Number of Occasions of Rescue Medication Use Per Day Week 9, n=244, 20, 82, 81, 76, 71, 229	1.658 No. of occasions of rescue use per day Standard Deviation 2.0646	1.720 No. of occasions of rescue use per day Standard Deviation 1.8918	1.953 No. of occasions of rescue use per day Standard Deviation 2.1838	1.775 No. of occasions of rescue use per day Standard Deviation 1.8753	1.708 No. of occasions of rescue use per day Standard Deviation 1.8709	2.765 No. of occasions of rescue use per day Standard Deviation 3.1104	1.608 No. of occasions of rescue use per day Standard Deviation 1.7699
Mean Number of Occasions of Rescue Medication Use Per Day Week 10, n=241, 20, 81, 80, 73, 71, 227	1.596 No. of occasions of rescue use per day Standard Deviation 1.9809	1.546 No. of occasions of rescue use per day Standard Deviation 1.8824	1.927 No. of occasions of rescue use per day Standard Deviation 2.1613	1.705 No. of occasions of rescue use per day Standard Deviation 1.7646	1.698 No. of occasions of rescue use per day Standard Deviation 1.9023	2.543 No. of occasions of rescue use per day Standard Deviation 2.8753	1.589 No. of occasions of rescue use per day Standard Deviation 1.6571
Mean Number of Occasions of Rescue Medication Use Per Day Week 11, n=241, 20, 79, 80, 73, 71, 226	1.602 No. of occasions of rescue use per day Standard Deviation 1.9435	1.672 No. of occasions of rescue use per day Standard Deviation 1.9447	1.926 No. of occasions of rescue use per day Standard Deviation 2.3243	1.716 No. of occasions of rescue use per day Standard Deviation 1.7421	1.729 No. of occasions of rescue use per day Standard Deviation 1.9406	2.164 No. of occasions of rescue use per day Standard Deviation 2.2504	1.404 No. of occasions of rescue use per day Standard Deviation 1.4897
Mean Number of Occasions of Rescue Medication Use Per Day Week 12, n=240, 20, 78, 80, 73, 70, 225	1.671 No. of occasions of rescue use per day Standard Deviation 1.9612	1.712 No. of occasions of rescue use per day Standard Deviation 1.9532	1.790 No. of occasions of rescue use per day Standard Deviation 2.1140	1.731 No. of occasions of rescue use per day Standard Deviation 1.7245	1.666 No. of occasions of rescue use per day Standard Deviation 1.7913	2.386 No. of occasions of rescue use per day Standard Deviation 2.8157	1.414 No. of occasions of rescue use per day Standard Deviation 1.3920
Mean Number of Occasions of Rescue Medication Use Per Day Over 12 Week, n=273, 21, 91, 91, 86, 83, 268	1.750 No. of occasions of rescue use per day Standard Deviation 1.9048	1.620 No. of occasions of rescue use per day Standard Deviation 1.5994	1.921 No. of occasions of rescue use per day Standard Deviation 1.9201	1.733 No. of occasions of rescue use per day Standard Deviation 1.6618	1.684 No. of occasions of rescue use per day Standard Deviation 1.6903	2.330 No. of occasions of rescue use per day Standard Deviation 2.4715	1.553 No. of occasions of rescue use per day Standard Deviation 1.4044

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 of treatment and over the Week 12 treatment period

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

Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Percentage of Rescue-Free Days is defined as sum of the number of days where the number of occasions of rescue medication use is zero within the time-period divided by total number of days with non-missing values within the time-period multiplied by 100 where the time-period is defined as follows: Week 1: Day 1-7; Week 2: Day 8 - 14; Week 3: Day 15-21; Week 4: Day 22-28; Week 5: Day 29-35; Week 6: Day 36-42; Week 7: Day 43-49; Week 8: Day 50-56; Week 9: Day 57-63; Week 10: Day 64-70; Week 11: Day 71-77; Week 12: Day 78 to Day of last dose; Over the 12-Week: Day 1 to Day of last dose.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Percentage of Rescue-free Days Week 1, n=254, 21, 87, 88, 80, 79, 254	33.392 Percentage of rescue free days Standard Deviation 39.7372	32.583 Percentage of rescue free days Standard Deviation 38.3577	34.453 Percentage of rescue free days Standard Deviation 35.9802	29.779 Percentage of rescue free days Standard Deviation 36.1498	34.898 Percentage of rescue free days Standard Deviation 37.7118	36.076 Percentage of rescue free days Standard Deviation 44.3182	29.849 Percentage of rescue free days Standard Deviation 38.3385
Percentage of Rescue-free Days Week 3, n=256, 21, 90, 88, 80, 81, 245	39.964 Percentage of rescue free days Standard Deviation 40.3936	41.191 Percentage of rescue free days Standard Deviation 42.1751	34.923 Percentage of rescue free days Standard Deviation 40.4026	33.006 Percentage of rescue free days Standard Deviation 38.4986	38.204 Percentage of rescue free days Standard Deviation 39.0621	38.776 Percentage of rescue free days Standard Deviation 44.0612	31.643 Percentage of rescue free days Standard Deviation 38.0943
Percentage of Rescue-free Days Week 4, n=250, 21, 89, 87, 81, 77, 243	42.202 Percentage of rescue free days Standard Deviation 43.0692	43.194 Percentage of rescue free days Standard Deviation 41.0201	30.986 Percentage of rescue free days Standard Deviation 38.5941	32.394 Percentage of rescue free days Standard Deviation 39.0174	39.678 Percentage of rescue free days Standard Deviation 40.8359	35.376 Percentage of rescue free days Standard Deviation 43.9405	32.531 Percentage of rescue free days Standard Deviation 39.0078
Percentage of Rescue-free Days Week 9, n=244, 20, 82, 81, 76, 71, 229	42.505 Percentage of rescue free days Standard Deviation 41.2121	39.476 Percentage of rescue free days Standard Deviation 42.2376	36.823 Percentage of rescue free days Standard Deviation 42.3513	33.606 Percentage of rescue free days Standard Deviation 39.4690	39.268 Percentage of rescue free days Standard Deviation 40.5300	32.145 Percentage of rescue free days Standard Deviation 44.6657	32.759 Percentage of rescue free days Standard Deviation 39.2972
Percentage of Rescue-free Days Week 10, n=241, 20, 81, 80, 73, 71, 227	43.396 Percentage of rescue free days Standard Deviation 42.3040	41.492 Percentage of rescue free days Standard Deviation 42.1984	37.024 Percentage of rescue free days Standard Deviation 41.2291	33.483 Percentage of rescue free days Standard Deviation 40.1924	40.608 Percentage of rescue free days Standard Deviation 41.0492	35.000 Percentage of rescue free days Standard Deviation 42.3430	32.456 Percentage of rescue free days Standard Deviation 40.7192
Percentage of Rescue-free Days Week 12, n=240, 20, 78, 80, 73, 70, 225	41.300 Percentage of rescue free days Standard Deviation 39.8199	39.981 Percentage of rescue free days Standard Deviation 40.8296	42.236 Percentage of rescue free days Standard Deviation 42.1567	33.906 Percentage of rescue free days Standard Deviation 38.4851	41.390 Percentage of rescue free days Standard Deviation 40.8871	39.415 Percentage of rescue free days Standard Deviation 45.0442	37.369 Percentage of rescue free days Standard Deviation 40.2613
Percentage of Rescue-free Days Week 2, n=259, 21, 88, 89, 80, 82, 252	43.017 Percentage of rescue free days Standard Deviation 43.9884	38.573 Percentage of rescue free days Standard Deviation 40.3629	40.595 Percentage of rescue free days Standard Deviation 41.1717	33.639 Percentage of rescue free days Standard Deviation 38.9767	41.002 Percentage of rescue free days Standard Deviation 40.9566	40.819 Percentage of rescue free days Standard Deviation 46.7899	32.145 Percentage of rescue free days Standard Deviation 41.2227
Percentage of Rescue-free Days Week 5, n=251, 20, 88, 85, 78, 76, 240	41.682 Percentage of rescue free days Standard Deviation 41.3648	41.026 Percentage of rescue free days Standard Deviation 42.1584	33.912 Percentage of rescue free days Standard Deviation 37.9973	33.168 Percentage of rescue free days Standard Deviation 39.0654	38.262 Percentage of rescue free days Standard Deviation 40.7807	35.005 Percentage of rescue free days Standard Deviation 41.8344	35.552 Percentage of rescue free days Standard Deviation 40.5745
Percentage of Rescue-free Days Week 6, n=250, 20, 86, 84, 78, 72, 234	41.720 Percentage of rescue free days Standard Deviation 44.0117	39.196 Percentage of rescue free days Standard Deviation 41.6575	35.519 Percentage of rescue free days Standard Deviation 42.2122	32.351 Percentage of rescue free days Standard Deviation 39.2542	40.287 Percentage of rescue free days Standard Deviation 42.2167	37.870 Percentage of rescue free days Standard Deviation 40.2125	35.384 Percentage of rescue free days Standard Deviation 40.9175
Percentage of Rescue-free Days Week 7, n=250, 20, 85, 83, 77, 71, 231	45.266 Percentage of rescue free days Standard Deviation 43.5910	40.409 Percentage of rescue free days Standard Deviation 42.0560	38.232 Percentage of rescue free days Standard Deviation 41.0296	31.975 Percentage of rescue free days Standard Deviation 39.4910	41.373 Percentage of rescue free days Standard Deviation 43.4266	32.145 Percentage of rescue free days Standard Deviation 43.1992	35.634 Percentage of rescue free days Standard Deviation 41.3319
Percentage of Rescue-free Days Week 8, n=250, 20, 84, 83, 77, 71, 231	44.118 Percentage of rescue free days Standard Deviation 41.6682	42.918 Percentage of rescue free days Standard Deviation 42.8354	34.811 Percentage of rescue free days Standard Deviation 39.3585	32.357 Percentage of rescue free days Standard Deviation 39.9221	42.058 Percentage of rescue free days Standard Deviation 41.2168	34.290 Percentage of rescue free days Standard Deviation 42.8300	33.029 Percentage of rescue free days Standard Deviation 41.0867
Percentage of Rescue-free Days Week 11, n=241, 20, 79, 80, 73, 71, 226	42.859 Percentage of rescue free days Standard Deviation 41.7845	39.337 Percentage of rescue free days Standard Deviation 42.3061	39.841 Percentage of rescue free days Standard Deviation 43.7237	33.127 Percentage of rescue free days Standard Deviation 39.1842	39.701 Percentage of rescue free days Standard Deviation 41.9689	38.575 Percentage of rescue free days Standard Deviation 44.2366	35.624 Percentage of rescue free days Standard Deviation 42.6625
Percentage of Rescue-free Days Over 12 Week, n=273, 21, 91, 91, 86, 83, 268	40.441 Percentage of rescue free days Standard Deviation 37.6285	39.631 Percentage of rescue free days Standard Deviation 36.5157	35.820 Percentage of rescue free days Standard Deviation 34.6377	32.743 Percentage of rescue free days Standard Deviation 33.9362	39.743 Percentage of rescue free days Standard Deviation 36.8957	35.533 Percentage of rescue free days Standard Deviation 39.0694	33.590 Percentage of rescue free days Standard Deviation 36.6456

SECONDARY outcome

Timeframe: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

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

Plasma samples were collected at indicated time points and analyzed for concentrations of Nemiralisb. Pharmacokinetic (PK) Population consists of all participants in the Safety population who had at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values will be considered as non-missing values). Participants were summarized according to the treatment that they actually received.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=19 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=20 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=73 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=5 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=24 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Plasma Concentration of Nemiralisib Day 14, Pre-dose, n=2, 19, 24, 16, 18, 69	416.0 Picograms per milliliter Geometric Coefficient of Variation 59	687.3 Picograms per milliliter Geometric Coefficient of Variation 53	1069.6 Picograms per milliliter Geometric Coefficient of Variation 70	—	113.6 Picograms per milliliter Geometric Coefficient of Variation 6	62.0 Picograms per milliliter Geometric Coefficient of Variation 46	142.8 Picograms per milliliter Geometric Coefficient of Variation 44
Plasma Concentration of Nemiralisib Day 14, 0-1 hour, n=4, 19, 24, 15, 18, 67	767.6 Picograms per milliliter Geometric Coefficient of Variation 71	1492.0 Picograms per milliliter Geometric Coefficient of Variation 59	1972.0 Picograms per milliliter Geometric Coefficient of Variation 110	—	54.9 Picograms per milliliter Geometric Coefficient of Variation 43	109.9 Picograms per milliliter Geometric Coefficient of Variation 51	253.7 Picograms per milliliter Geometric Coefficient of Variation 73
Plasma Concentration of Nemiralisib Day 14, >1-6 hours, n=4, 20, 23, 15, 18, 65	657.0 Picograms per milliliter Geometric Coefficient of Variation 61	1146.7 Picograms per milliliter Geometric Coefficient of Variation 56	1622.7 Picograms per milliliter Geometric Coefficient of Variation 90	—	35.0 Picograms per milliliter Geometric Coefficient of Variation 57	93.1 Picograms per milliliter Geometric Coefficient of Variation 58	231.8 Picograms per milliliter Geometric Coefficient of Variation 53
Plasma Concentration of Nemiralisib Day 28, Pre-dose, n=2, 18, 23, 16, 16, 67	315.6 Picograms per milliliter Geometric Coefficient of Variation 85	528.3 Picograms per milliliter Geometric Coefficient of Variation 110	937.6 Picograms per milliliter Geometric Coefficient of Variation 101	—	23.6 Picograms per milliliter Geometric Coefficient of Variation 24	60.5 Picograms per milliliter Geometric Coefficient of Variation 45	129.4 Picograms per milliliter Geometric Coefficient of Variation 46
Plasma Concentration of Nemiralisib Day 28, 0-1 hour, n=3, 19, 23, 16, 15, 63	807.0 Picograms per milliliter Geometric Coefficient of Variation 66	1552.2 Picograms per milliliter Geometric Coefficient of Variation 83	1717.6 Picograms per milliliter Geometric Coefficient of Variation 114	—	36.2 Picograms per milliliter Geometric Coefficient of Variation 26	104.9 Picograms per milliliter Geometric Coefficient of Variation 70	253.3 Picograms per milliliter Geometric Coefficient of Variation 52
Plasma Concentration of Nemiralisib Day 28, >1-6 hours, n=3, 18, 23, 16, 14, 64	598.8 Picograms per milliliter Geometric Coefficient of Variation 39	1079.5 Picograms per milliliter Geometric Coefficient of Variation 80	1388.1 Picograms per milliliter Geometric Coefficient of Variation 101	—	28.1 Picograms per milliliter Geometric Coefficient of Variation 15	85.4 Picograms per milliliter Geometric Coefficient of Variation 40	211.4 Picograms per milliliter Geometric Coefficient of Variation 41

SECONDARY outcome

Timeframe: Up to Week 24

Population: Safety Population.

An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect and other important medical events. Safety Population consists of all randomized participants who received at least one dose of study treatment. Participants were summarized according to treatment that they actually received.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) Any SAE	13 Participants	16 Participants	6 Participants	26 Participants	23 Participants	2 Participants	9 Participants
Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) Any non-SAE	19 Participants	25 Participants	36 Participants	101 Participants	31 Participants	1 Participants	14 Participants
Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) Any AESI	10 Participants	21 Participants	29 Participants	93 Participants	9 Participants	0 Participants	10 Participants

SECONDARY outcome

Timeframe: Up to Week 16

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

The DBP, SBP and pulse rate were measured with participants seated at least 5 minutes before the assessments. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=88 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=88 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=266 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=271 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=21 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate DBP, To low	0 Participants	4 Participants	4 Participants	7 Participants	8 Participants	3 Participants	3 Participants
Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate DBP, To within range/no change	91 Participants	79 Participants	82 Participants	256 Participants	260 Participants	17 Participants	85 Participants
Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate DBP, To high	1 Participants	5 Participants	2 Participants	3 Participants	3 Participants	1 Participants	3 Participants
Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate Pulse rate,To within range/no change	90 Participants	82 Participants	83 Participants	258 Participants	265 Participants	21 Participants	84 Participants
Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate Pulse rate, To high	2 Participants	6 Participants	5 Participants	8 Participants	5 Participants	0 Participants	7 Participants
Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate SBP, To withinn range/no change	82 Participants	79 Participants	80 Participants	239 Participants	250 Participants	18 Participants	83 Participants
Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate SBP, To high	7 Participants	8 Participants	6 Participants	19 Participants	10 Participants	2 Participants	3 Participants
Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate Pulse rate, To low	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate SBP, To low	3 Participants	2 Participants	3 Participants	8 Participants	11 Participants	1 Participants	5 Participants

SECONDARY outcome

Timeframe: Screening, Days 14, 84, 112 and at early withdrawal

Population: Safety Population.

A single 12-lead ECG with a 15-second rhythm strip was obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. Abnormal ECG findings are presented.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Screening	37 Participants	28 Participants	21 Participants	86 Participants	93 Participants	10 Participants	25 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Day 14	33 Participants	29 Participants	18 Participants	74 Participants	88 Participants	8 Participants	24 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Day 84	27 Participants	24 Participants	18 Participants	64 Participants	79 Participants	8 Participants	22 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Day 112	28 Participants	25 Participants	20 Participants	75 Participants	77 Participants	11 Participants	28 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Early withdrawal	1 Participants	3 Participants	1 Participants	4 Participants	3 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Upto Week 16

Population: Safety 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 for the analysis of clinical chemistry parameters including: blood urea nitrogen (BUN), creatinine (Crt), glucose (Glu), potassium (Pot), sodium (Sod), calcium (Cal), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubin, total protein and albumin (Alb). Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Alb,w/in range/no change,n=266,21,91,90,87,85,263	90 Participants	85 Participants	84 Participants	261 Participants	264 Participants	21 Participants	90 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Cal,To high, n=266,21,90,90,87,85,263	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Crt,To low, n=266, 21, 91, 90, 87, 85, 263	7 Participants	4 Participants	9 Participants	32 Participants	27 Participants	3 Participants	10 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Crt,w/in range/no change,n=266,21,91,90,87,85,263	82 Participants	80 Participants	76 Participants	231 Participants	237 Participants	18 Participants	81 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Crt,To high, n=266,21,91,90,87,85,263	1 Participants	3 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Glu,To high, n=266,21,91,90,87,85,263	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Pot,To low, n=266, 21, 90, 90, 87, 85, 263	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Sod,To low, n=266, 21, 91, 90, 87, 85, 263	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Cal,To low, n=266, 21, 90, 90, 87, 85, 263	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Alb,To low, n=266, 21, 91, 90, 87, 85, 263	0 Participants	1 Participants	1 Participants	2 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Alb,To high,n=266,21,91,90,87,85,263	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Cal,w/in range/no change,n=266,21,90,90,87,85,263	90 Participants	87 Participants	84 Participants	262 Participants	265 Participants	21 Participants	90 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Glu,To low, n=266, 21, 91, 90, 87, 85, 263	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Glu,w/in range/no change,n=266,21,91,90,87,85,263	89 Participants	87 Participants	85 Participants	263 Participants	266 Participants	21 Participants	91 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Pot,w/in range/no change,n=266,21,90,90,87,85,263	90 Participants	86 Participants	84 Participants	262 Participants	264 Participants	21 Participants	90 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Pot,To high, n=266,21,90,90,87,85,263	0 Participants	1 Participants	1 Participants	1 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Sod,w/in range/no change,n=266,21,91,90,87,85,263	90 Participants	87 Participants	85 Participants	263 Participants	266 Participants	21 Participants	91 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values Sod,To high, n=266,21,91,90,87,85,263	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values BUN,To low, n=266, 21, 91, 90, 87, 85, 263	2 Participants	2 Participants	3 Participants	6 Participants	7 Participants	0 Participants	3 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values BUN,w/in range/no change,n=266,21,91,90,87,85,263	86 Participants	85 Participants	82 Participants	253 Participants	256 Participants	21 Participants	88 Participants
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values BUN,To high, n=266,21,91,90,87,85,263	2 Participants	0 Participants	0 Participants	4 Participants	3 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Upto Week 16

Population: Safety 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 for the analysis of hematology parameters including: platelets (Pla), red blood cells count, Hemoglobin (Hb), Hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), percentage reticulocytes, neutrophils (Neu), lymphocytes (Lym), monocytes, eosinophils, leukocytes (Leu) and basophils. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Number of Participants With Worst Case Post Baseline Hematology Values Leu,To low,n=259, 20, 90, 90, 83, 78, 251	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Neu, To low, n=256,20,85,88,82,77,249	1 Participants	0 Participants	0 Participants	2 Participants	3 Participants	0 Participants	1 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Pla,w/in range/no change,n=253,19,88,90,84,78,245	90 Participants	84 Participants	78 Participants	245 Participants	253 Participants	19 Participants	88 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Pla,To high, n=253,19,88,90,84,78,245	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Hb,To low, n=260, 20, 90, 90, 84, 81, 254	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Hb,w/in range/no change,n=260,20,90,90,84,81,254	90 Participants	84 Participants	81 Participants	253 Participants	260 Participants	20 Participants	90 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Hb,To high,n=260, 20, 90, 90, 84, 81, 254	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Leu,w/in range/no change,n=259,20,90,90,83,78,251	74 Participants	63 Participants	62 Participants	201 Participants	211 Participants	16 Participants	81 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Leu,To high, n=259,20,90,90,83,78,251	16 Participants	20 Participants	16 Participants	50 Participants	48 Participants	4 Participants	9 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Lym,To low, n=256, 20, 85, 88, 82, 77, 249	7 Participants	7 Participants	2 Participants	11 Participants	8 Participants	1 Participants	6 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Lym,w/in range/no change,n=256,20,85,88,82,77,249	76 Participants	70 Participants	73 Participants	226 Participants	239 Participants	19 Participants	79 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Lym,To high,n=256,20,85,88,82,77,249	5 Participants	5 Participants	2 Participants	12 Participants	9 Participants	0 Participants	0 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Neu,w/in range/no change,n=256,20,85,88,82,77,249	76 Participants	68 Participants	60 Participants	213 Participants	215 Participants	17 Participants	73 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Neu,To high, n=256,20,85,88,82,77,249	11 Participants	14 Participants	17 Participants	34 Participants	38 Participants	3 Participants	11 Participants
Number of Participants With Worst Case Post Baseline Hematology Values Pla,To low, n=253, 19, 88, 90, 84, 78, 245	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 16

Population: Safety Population.

Participants reporting acute COPD exacerbations during the study period has been presented.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=92 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 Participants Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=276 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Number of Participants Reporting COPD Exacerbations	4 Participants	4 Participants	3 Participants	17 Participants	8 Participants	1 Participants	6 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

Population: PK Population.

Plasma samples were collected at indicated time points and analyzed.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=19 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=20 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=73 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=5 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=24 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Area Under the Concentration Time Curve (AUC) From Time Zero to 24 Hours [AUC(0-24)] of Nemiralisib	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	—	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary population pharmacokinetic (Pop PK) analyses were not conducted	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

Population: PK Population.

Plasma samples were collected at indicated time points and analyzed.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=19 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=20 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=73 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=5 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=24 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
AUC From Time Zero to Time 't' [AUC(0-t)] of Nemiralisib	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	—	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Hours*picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

Population: PK Population.

Plasma samples were collected at indicated time points and analyzed.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=19 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=20 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=73 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=5 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=24 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Maximum Observed Plasma Drug Concentration (Cmax) of Nemiralisib	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	—	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

Population: PK Population.

Plasma samples were collected at indicated time points and analyzed.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=19 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=20 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=73 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=5 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=24 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Time to Reach Cmax (Tmax) of Nemiralisib	NA Hours This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Hours This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Hours This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	—	NA Hours This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Hours This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Hours This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

Population: PK Population.

Plasma samples were collected at indicated time points and analyzed.

Outcome measures

Outcome measures
Measure	Nemiralisib 100 mcg n=19 Participants Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=20 Participants Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=73 Participants Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Placebo n=5 Participants Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 Participants Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=24 Participants Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Plasma Drug Concentration at Pre-dose (Ctrough) of Nemiralisib	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	—	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted	NA Picograms per milliliter Geometric Coefficient of Variation NA This was a conditional secondary endpoint for which results are not available because development of the associated asset was terminated and therefore secondary Pop PK analyses were not conducted

Adverse Events

Placebo

Serious events: 23 serious events

Other events: 31 other events

Deaths: 1 deaths

Nemiralisib 12.5 mcg

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Nemiralisib 50 mcg

Serious events: 9 serious events

Other events: 14 other events

Deaths: 3 deaths

Nemiralisib 100 mcg

Serious events: 13 serious events

Other events: 19 other events

Deaths: 1 deaths

Nemiralisib 250 mcg

Serious events: 16 serious events

Other events: 25 other events

Deaths: 0 deaths

Nemiralisib 500 mcg

Serious events: 6 serious events

Other events: 36 other events

Deaths: 0 deaths

Nemiralisib 750 mcg

Serious events: 26 serious events

Other events: 101 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=276 participants at risk Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 participants at risk Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 participants at risk Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 100 mcg n=92 participants at risk Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 participants at risk Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 participants at risk Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 participants at risk Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Respiratory, thoracic and mediastinal disorders Chroni obstructive pulmonary disease	2.9% 8/276 • Number of events 8 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	4.5% 1/22 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	6.6% 6/91 • Number of events 7 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	4.3% 4/92 • Number of events 4 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	4.4% 4/90 • Number of events 5 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	3.4% 3/89 • Number of events 3 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	6.1% 17/278 • Number of events 17 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/92 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/92 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/90 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/90 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/92 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Infections and infestations Pneumonia	1.4% 4/276 • Number of events 4 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/91 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	2.2% 2/92 • Number of events 2 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	3.3% 3/90 • Number of events 3 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Infections and infestations Influenza	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/91 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/92 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/90 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Infections and infestations Diverticulitis	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/92 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Infections and infestations Cystitis klebsiella	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/91 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Infections and infestations Sepsis	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Cardiac disorders Angina unstable	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/92 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	2.2% 2/90 • Number of events 2 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Cardiac disorders Acute myocardial infarction	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/90 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Cardiac disorders Myocardial ischaemia	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/90 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/89 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Cardiac disorders Atrial fibrillation	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Cardiac disorders Atrioventricular block	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/92 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Cardiac disorders Bradycardia	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Cardiac disorders Cardiac arrest	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Cardiac disorders Cardiac failure congestive	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Cardiac disorders Myocardial infarction	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Cardiac disorders Sinus arrhythmia	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Cardiac disorders Ventricular tachycardia	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/89 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchial carcinoma	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/91 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/90 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/90 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Gastrointestinal disorders Enterocele	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/90 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Gastrointestinal disorders Haematochezia	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/89 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/91 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Injury, poisoning and procedural complications Contusion	0.36% 1/276 • Number of events 2 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Injury, poisoning and procedural complications Fall	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/92 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Investigations Alanine aminotransferase increased	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/89 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Investigations Blood bilirubin increased	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/89 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Investigations C-reactive protein increased	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Investigations Hepatic enzyme increased	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Metabolism and nutrition disorders Dehydration	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	4.5% 1/22 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Vascular disorders Arterial thrombosis	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/92 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Vascular disorders Hypertension	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Vascular disorders Hypotension	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
General disorders Non-cardiac chest pain	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/90 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
General disorders Swelling	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/92 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Hepatobiliary disorders Cholelithiasis	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Hepatobiliary disorders Bile duct stone	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Renal and urinary disorders Acute kidney injury	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Renal and urinary disorders Renal impairment	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	4.5% 1/22 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Blood and lymphatic system disorders Anaemia	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	1.1% 1/91 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Nervous system disorders Intracranial hematoma	0.00% 0/276 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.36% 1/278 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Psychiatric disorders Conversion disorder	0.36% 1/276 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/92 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/90 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/89 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/278 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.

Other adverse events

Other adverse events
Measure	Placebo n=276 participants at risk Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.	Nemiralisib 12.5 mcg n=22 participants at risk Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 50 mcg n=91 participants at risk Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 100 mcg n=92 participants at risk Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 250 mcg n=90 participants at risk Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 500 mcg n=89 participants at risk Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.	Nemiralisib 750 mcg n=278 participants at risk Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.
Respiratory, thoracic and mediastinal disorders Cough	4.7% 13/276 • Number of events 13 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	11.0% 10/91 • Number of events 12 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	12.0% 11/92 • Number of events 17 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	25.6% 23/90 • Number of events 27 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	34.8% 31/89 • Number of events 58 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	34.5% 96/278 • Number of events 141 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.72% 2/276 • Number of events 2 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/22 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.00% 0/91 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	2.2% 2/92 • Number of events 2 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	3.3% 3/90 • Number of events 3 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	5.6% 5/89 • Number of events 5 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	0.72% 2/278 • Number of events 2 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.
Nervous system disorders Headache	8.3% 23/276 • Number of events 41 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	4.5% 1/22 • Number of events 1 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	6.6% 6/91 • Number of events 8 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	8.7% 8/92 • Number of events 10 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	4.4% 4/90 • Number of events 5 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	2.2% 2/89 • Number of events 2 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.	5.4% 15/278 • Number of events 18 • Non-serious AEs and SAEs were collected up to Week 24 Non-serious AEs and SAEs were summarized for the Safety Population.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER