Trial Outcomes & Findings for Safety And Efficacy Of UK-432,097 In Chronic Obstructive Pulmonary Disease. (NCT NCT00430300)

Last Updated: 2013-07-08

Results Overview

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Trough FEV1 was obtained from spirometry, performed before study treatment administration.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

87 participants

Primary outcome timeframe

Pre-dose at Baseline, Week 6

Results posted on

2013-07-08

Participant Flow

Participant milestones

Participant milestones
Measure	UK-432,097 150 Mcg UK-432,097 150 microgram (mcg) capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide metered dose inhaler (MDI) 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Overall Study STARTED	17	18	35	17
Overall Study COMPLETED	15	16	29	15
Overall Study NOT COMPLETED	2	2	6	2

Reasons for withdrawal

Reasons for withdrawal
Measure	UK-432,097 150 Mcg UK-432,097 150 microgram (mcg) capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide metered dose inhaler (MDI) 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Overall Study Adverse Event	0	2	1	1
Overall Study Withdrawal by Subject	1	0	5	0
Overall Study Laboratory abnormality	1	0	0	0
Overall Study Other	0	0	0	1

Baseline Characteristics

Safety And Efficacy Of UK-432,097 In Chronic Obstructive Pulmonary Disease.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	UK-432,097 150 Mcg n=17 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=18 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=35 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=17 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Total n=87 Participants Total of all reporting groups
Age, Customized 45 to 64 Years	8 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants	9 participants n=4 Participants	36 participants n=21 Participants
Age, Customized Greater Than or Equal to (>=) 65 Years	9 participants n=5 Participants	11 participants n=7 Participants	23 participants n=5 Participants	8 participants n=4 Participants	51 participants n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants	6 Participants n=4 Participants	25 Participants n=21 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants	11 Participants n=4 Participants	62 Participants n=21 Participants

PRIMARY outcome

Timeframe: Pre-dose at Baseline, Week 6

Population: Full analysis set (FAS): all randomized participants, who received at least 2 weeks of dosing and had at least 1 valid FEV1 measurement during treatment. Missing data were imputed using Last Observation Carried Forward (LOCF). Here 'n' signifies participants who were evaluable for this measure at specified time-point for each arm, respectively.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=16 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=17 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=32 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=16 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 6 Baseline (n= 16, 17, 32, 16)	1.40 liter Standard Deviation 0.45	1.48 liter Standard Deviation 0.57	1.41 liter Standard Deviation 0.39	1.33 liter Standard Deviation 0.48
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 6 Change at Week 6 (n= 14, 17, 29, 15)	-0.01 liter Standard Deviation 0.21	-0.05 liter Standard Deviation 0.18	-0.05 liter Standard Deviation 0.18	-0.05 liter Standard Deviation 0.16

SECONDARY outcome

Timeframe: Pre-dose at Baseline, Week 2, 4, 8

Population: FAS: all randomized participants, who received at least 2 weeks of dosing and had at least 1 valid FEV1 measurement during treatment. Here 'n' signifies participants who were evaluable for this measure at specified time-point for each arm, respectively.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=16 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=17 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=32 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=16 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 4 and 8 Change at Week 2 (n= 16, 17, 32, 16)	-0.01 liter Standard Deviation 0.10	-0.10 liter Standard Deviation 0.11	0.01 liter Standard Deviation 0.13	0.01 liter Standard Deviation 0.18
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 4 and 8 Change at Week 4 (n= 15, 17, 30, 16)	-0.08 liter Standard Deviation 0.19	-0.06 liter Standard Deviation 0.15	-0.02 liter Standard Deviation 0.17	-0.01 liter Standard Deviation 0.12
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 4 and 8 Change at Week 8 (n= 14, 16, 27, 16)	0.03 liter Standard Deviation 0.23	-0.07 liter Standard Deviation 0.18	0.04 liter Standard Deviation 0.23	-0.05 liter Standard Deviation 0.17

SECONDARY outcome

Timeframe: Pre-dose at Baseline, Week 2, 4, 6, 8

FEV6 is the maximal volume of air exhaled in the first 6 seconds of a forced expiration from a position of full inspiration. Trough FEV6 was obtained from spirometry, performed before study treatment administration.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=16 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=17 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=32 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=16 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Trough Forced Expiratory Volume in 6 Seconds (FEV6) at Week 2, 4, 6 and 8 Baseline (n= 16, 17, 32, 16)	2.66 liter Standard Deviation 0.73	2.80 liter Standard Deviation 0.81	2.75 liter Standard Deviation 0.69	2.54 liter Standard Deviation 0.73
Change From Baseline in Trough Forced Expiratory Volume in 6 Seconds (FEV6) at Week 2, 4, 6 and 8 Change at Week 2 (n= 16, 17, 32, 16)	-0.02 liter Standard Deviation 0.22	-0.08 liter Standard Deviation 0.18	-0.01 liter Standard Deviation 0.20	0.03 liter Standard Deviation 0.19
Change From Baseline in Trough Forced Expiratory Volume in 6 Seconds (FEV6) at Week 2, 4, 6 and 8 Change at Week 4 (n= 15, 17, 30, 16)	-0.12 liter Standard Deviation 0.24	0.03 liter Standard Deviation 0.19	-0.05 liter Standard Deviation 0.23	-0.01 liter Standard Deviation 0.13
Change From Baseline in Trough Forced Expiratory Volume in 6 Seconds (FEV6) at Week 2, 4, 6 and 8 Change at Week 6 (n= 14, 17, 29, 15)	-0.00 liter Standard Deviation 0.25	0.01 liter Standard Deviation 0.30	-0.06 liter Standard Deviation 0.22	-0.05 liter Standard Deviation 0.18
Change From Baseline in Trough Forced Expiratory Volume in 6 Seconds (FEV6) at Week 2, 4, 6 and 8 Change at Week 8 (n= 14, 16, 27, 16)	0.10 liter Standard Deviation 0.34	-0.05 liter Standard Deviation 0.31	0.04 liter Standard Deviation 0.30	-0.09 liter Standard Deviation 0.26

SECONDARY outcome

Timeframe: Pre-dose at Baseline, Week 2, 4, 6, 8

FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Trough FVC was obtained from spirometry, performed before study treatment administration.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=16 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=17 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=32 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=16 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 2, 4, 6 and 8 Baseline (n= 16, 17, 32, 16)	3.11 liter Standard Deviation 0.85	3.43 liter Standard Deviation 1.16	3.24 liter Standard Deviation 0.91	3.01 liter Standard Deviation 0.94
Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 2, 4, 6 and 8 Change at Week 2 (n= 16, 17, 32, 16)	-0.07 liter Standard Deviation 0.30	-0.09 liter Standard Deviation 0.30	-0.04 liter Standard Deviation 0.25	0.09 liter Standard Deviation 0.31
Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 2, 4, 6 and 8 Change at Week 4 (n= 15, 17, 30, 16)	-0.14 liter Standard Deviation 0.34	0.14 liter Standard Deviation 0.21	-0.02 liter Standard Deviation 0.32	0.05 liter Standard Deviation 0.21
Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 2, 4, 6 and 8 Change at Week 6 (n= 14, 17, 29, 15)	0.01 liter Standard Deviation 0.32	0.01 liter Standard Deviation 0.33	-0.01 liter Standard Deviation 0.31	0.02 liter Standard Deviation 0.17
Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 2, 4, 6 and 8 Change at Week 8 (n= 14, 16, 27, 16)	0.14 liter Standard Deviation 0.46	0.02 liter Standard Deviation 0.40	0.07 liter Standard Deviation 0.33	-0.05 liter Standard Deviation 0.28

SECONDARY outcome

Timeframe: Pre-dose at Baseline, Week 2, 4, 6, 8

IC is the maximum volume of air that can be inhaled into the lungs from the normal resting position after breathing out normally. Trough IC was obtained from spirometry, performed before study treatment administration.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=16 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=17 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=32 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=16 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Trough Inspiratory Capacity (IC) at Week 2, 4, 6 and 8 Baseline (n= 16, 17, 32, 16)	2.44 liter Standard Deviation 0.63	2.81 liter Standard Deviation 0.78	2.53 liter Standard Deviation 0.59	2.41 liter Standard Deviation 0.82
Change From Baseline in Trough Inspiratory Capacity (IC) at Week 2, 4, 6 and 8 Change at Week 2 (n= 16, 17, 32, 16)	0.03 liter Standard Deviation 0.27	-0.06 liter Standard Deviation 0.38	-0.03 liter Standard Deviation 0.30	-0.10 liter Standard Deviation 0.24
Change From Baseline in Trough Inspiratory Capacity (IC) at Week 2, 4, 6 and 8 Change at Week 4 (n= 15, 17, 30, 16)	-0.05 liter Standard Deviation 0.18	-0.03 liter Standard Deviation 0.38	-0.15 liter Standard Deviation 0.28	-0.06 liter Standard Deviation 0.25
Change From Baseline in Trough Inspiratory Capacity (IC) at Week 2, 4, 6 and 8 Change at Week 6 (n= 14, 17, 29, 15)	-0.03 liter Standard Deviation 0.23	-0.08 liter Standard Deviation 0.40	-0.14 liter Standard Deviation 0.28	-0.09 liter Standard Deviation 0.32
Change From Baseline in Trough Inspiratory Capacity (IC) at Week 2, 4, 6 and 8 Change at Week 8 (n= 14, 16, 27, 16)	0.07 liter Standard Deviation 0.22	0.01 liter Standard Deviation 0.44	-0.10 liter Standard Deviation 0.33	-0.05 liter Standard Deviation 0.26

SECONDARY outcome

Timeframe: 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Post-study drug FEV1 was obtained from spirometry, performed 15-30 minutes after study treatment administration.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=16 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=17 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=32 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=16 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Post-Study Drug FEV1 at Week 2, 4, and 6 Baseline (n= 16, 17, 32, 16)	1.40 liter Standard Deviation 0.45	1.48 liter Standard Deviation 0.57	1.41 liter Standard Deviation 0.39	1.33 liter Standard Deviation 0.48
Change From Baseline in Post-Study Drug FEV1 at Week 2, 4, and 6 Change at Week 2 (n= 16, 16, 30, 16)	0.02 liter Standard Deviation 0.11	-0.10 liter Standard Deviation 0.16	-0.02 liter Standard Deviation 0.11	0.03 liter Standard Deviation 0.20
Change From Baseline in Post-Study Drug FEV1 at Week 2, 4, and 6 Change at Week 4 (n= 14, 16, 29, 16)	-0.07 liter Standard Deviation 0.15	-0.04 liter Standard Deviation 0.10	-0.02 liter Standard Deviation 0.15	-0.01 liter Standard Deviation 0.15
Change From Baseline in Post-Study Drug FEV1 at Week 2, 4, and 6 Change at Week 6 (n= 13, 16, 27, 15)	-0.06 liter Standard Deviation 0.23	-0.04 liter Standard Deviation 0.18	-0.04 liter Standard Deviation 0.15	-0.03 liter Standard Deviation 0.20

SECONDARY outcome

Timeframe: 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6

Population: Data for this pre-specified outcome was not analyzed, as the study was terminated due to futility based on results of interim analysis.

FEV6 is the maximal volume of air exhaled in the first 6 seconds of a forced expiration from a position of full inspiration. Post-study drug FEV6 was obtained from spirometry, performed 15-30 minutes after study treatment administration.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6

Population: Data for this pre-specified outcome was not analyzed, as the study was terminated due to futility based on results of interim analysis.

FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Post-study drug FVC was obtained from spirometry, performed 15-30 minutes after study treatment administration.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6

Population: Data for this pre-specified outcome was not analyzed, as the study was terminated due to futility based on results of interim analysis.

IC is the maximum amount of air that can be inhaled into the lungs from the normal resting position after breathing out normally. Post-study drug IC was obtained from spirometry, performed 15-30 minutes after study treatment administration.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6

Population: FAS: all randomized participants, who received at least 2 weeks of dosing and had at least 1 valid FEV1 measurement during treatment. Here 'N'(number of participants analyzed) signifies participants who were evaluable for this measure.

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Post-bronchodilator FEV1 was obtained from spirometry, performed 15-30 minutes after bronchodilator (salbutamol) administration.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=13 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=16 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=27 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=14 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Post-Bronchodilator FEV1 at Week 6 Change at Week 6	0.06 liter Standard Deviation 0.14	0.03 liter Standard Deviation 0.19	-0.02 liter Standard Deviation 0.19	-0.06 liter Standard Deviation 0.14
Change From Baseline in Post-Bronchodilator FEV1 at Week 6 Baseline	0.32 liter Standard Deviation 0.20	0.29 liter Standard Deviation 0.19	0.26 liter Standard Deviation 0.18	0.24 liter Standard Deviation 0.15

SECONDARY outcome

Timeframe: 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6

Population: Data for this pre-specified outcome was not analyzed, as the study was terminated due to futility based on results of interim analysis.

FEV6 is the maximal volume of air exhaled in the first 6 seconds of a forced expiration from a position of full inspiration. Post-bronchodilator FEV6 was obtained from spirometry, performed 15-30 minutes after bronchodilator (salbutamol) administration.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6

Population: Data for this pre-specified outcome was not analyzed, as the study was terminated due to futility based on results of interim analysis.

FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Post-bronchodilator FVC was obtained from spirometry, performed 15-30 minutes after bronchodilator (salbutamol) administration.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6

Population: Data for this pre-specified outcome was not analyzed, as the study was terminated due to futility based on results of interim analysis.

IC is the maximum volume of air that can be inhaled into the lungs from the normal resting position after breathing out normally. Post-bronchodilator IC was obtained from spirometry, performed 15-30 minutes after bronchodilator (salbutamol) administration.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 2, 4, 6

BDI: 24-item questionnaire to assess baseline dyspnea in 3 domains, functional impairment; magnitude of task; magnitude of effort. Each item rated on 5-point scale: 0 (very severe), 4 (no impairment). BDI total score range: 0 to 12, lower score=more severe dyspnea. TDI: 24-item questionnaire to measure changes in dyspnea severity from baseline in same 3 domains, as in BDI. Each item rated on 7-point scale: -3 (major deterioration) to 3 (major improvement). TDI total score range: -9 to 9, lower score=more deterioration. BDI/TDI total scores were obtained by adding scores for each of 3 domains.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=16 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=17 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=32 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=16 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Dyspnea (Baseline Dyspnea Index/Transition Dyspnea Index [BDI/TDI]) at Week 2, 4, and 6 BDI (n= 16, 17, 32, 16)	7.1 units on a scale Standard Deviation 1.9	7.6 units on a scale Standard Deviation 2.1	7.2 units on a scale Standard Deviation 2.1	7.1 units on a scale Standard Deviation 2.0
Change From Baseline in Dyspnea (Baseline Dyspnea Index/Transition Dyspnea Index [BDI/TDI]) at Week 2, 4, and 6 TDI at Week 2 (n= 16, 17, 32, 16)	-0.2 units on a scale Standard Deviation 1.9	0.8 units on a scale Standard Deviation 1.9	0.2 units on a scale Standard Deviation 1.1	1.3 units on a scale Standard Deviation 2.4
Change From Baseline in Dyspnea (Baseline Dyspnea Index/Transition Dyspnea Index [BDI/TDI]) at Week 2, 4, and 6 TDI at Week 4 (n= 15, 17, 31, 16)	0.5 units on a scale Standard Deviation 2.8	0.2 units on a scale Standard Deviation 1.7	-0.3 units on a scale Standard Deviation 1.9	0.3 units on a scale Standard Deviation 2.2
Change From Baseline in Dyspnea (Baseline Dyspnea Index/Transition Dyspnea Index [BDI/TDI]) at Week 2, 4, and 6 TDI at Week 6 (n= 14, 16, 29, 15)	-0.6 units on a scale Standard Deviation 2.3	0.9 units on a scale Standard Deviation 3.1	0.1 units on a scale Standard Deviation 2.4	1.0 units on a scale Standard Deviation 1.9

SECONDARY outcome

Timeframe: Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8

Population: FAS: all randomized participants, who received at least 2 weeks of dosing and had at least 1 valid FEV1 measurement during treatment. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure and 'n' signifies participants who were evaluable for this measure at specified time-point for each arm, respectively.

COPD symptom score: participants rated the severity of their COPD symptoms (cough, breathlessness, and sputum production) in daily symptom dairy according to how they felt during the past 24 hours on a 4-point scale ranging from 0 (none) to 3 (severe). A participant's daily score for each symptom was averaged over each week.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=16 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=17 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=31 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=16 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Cough: Baseline (n= 16, 17, 31, 16)	1.09 units on a scale Standard Deviation 0.50	0.77 units on a scale Standard Deviation 0.75	1.11 units on a scale Standard Deviation 0.67	1.06 units on a scale Standard Deviation 0.61
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Cough: Change at Week 1 (n= 16, 17, 31, 16)	-0.08 units on a scale Standard Deviation 0.46	0.11 units on a scale Standard Deviation 0.48	0.07 units on a scale Standard Deviation 0.41	0.10 units on a scale Standard Deviation 0.50
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Cough: Change at Week 2 (n= 16, 15, 31, 16)	-0.10 units on a scale Standard Deviation 0.43	0.13 units on a scale Standard Deviation 0.31	0.10 units on a scale Standard Deviation 0.53	-0.01 units on a scale Standard Deviation 0.41
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Cough: Change at Week 3 (n= 15, 17, 31, 16)	-0.06 units on a scale Standard Deviation 0.51	0.15 units on a scale Standard Deviation 0.32	0.07 units on a scale Standard Deviation 0.48	0.15 units on a scale Standard Deviation 0.41
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Cough: Change at Week 4 (n= 14, 17, 30, 16)	-0.04 units on a scale Standard Deviation 0.30	0.07 units on a scale Standard Deviation 0.38	-0.03 units on a scale Standard Deviation 0.46	0.18 units on a scale Standard Deviation 0.39
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Cough: Change at Week 5 (n= 15, 17, 30, 16)	-0.13 units on a scale Standard Deviation 0.38	0.04 units on a scale Standard Deviation 0.44	0.10 units on a scale Standard Deviation 0.73	0.00 units on a scale Standard Deviation 0.43
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Cough: Change at Week 6 (n= 15, 17, 30, 15)	-0.10 units on a scale Standard Deviation 0.36	0.04 units on a scale Standard Deviation 0.43	0.07 units on a scale Standard Deviation 0.77	-0.02 units on a scale Standard Deviation 0.40
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Cough: Change at Week 7 (n= 15, 16, 30, 15)	-0.16 units on a scale Standard Deviation 0.38	-0.08 units on a scale Standard Deviation 0.57	0.00 units on a scale Standard Deviation 0.64	0.07 units on a scale Standard Deviation 0.31
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Cough: Change at Week 8 (n= 15, 16, 28, 15)	-0.15 units on a scale Standard Deviation 0.37	0.00 units on a scale Standard Deviation 0.56	-0.15 units on a scale Standard Deviation 0.60	0.07 units on a scale Standard Deviation 0.47
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Breathlessness: Baseline (n= 16, 17, 31, 16)	1.31 units on a scale Standard Deviation 0.59	1.30 units on a scale Standard Deviation 0.60	1.15 units on a scale Standard Deviation 0.75	1.27 units on a scale Standard Deviation 0.54
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Breathlessness: Change at Week 1(n=16, 17, 31, 16)	-0.24 units on a scale Standard Deviation 0.45	-0.10 units on a scale Standard Deviation 0.31	-0.05 units on a scale Standard Deviation 0.23	0.00 units on a scale Standard Deviation 0.32
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Breathlessness: Change at Week 2(n=16, 15, 31, 16)	-0.13 units on a scale Standard Deviation 0.48	-0.11 units on a scale Standard Deviation 0.29	0.00 units on a scale Standard Deviation 0.33	-0.01 units on a scale Standard Deviation 0.38
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Breathlessness: Change at Week 3(n=15, 17, 31, 16)	-0.12 units on a scale Standard Deviation 0.57	-0.15 units on a scale Standard Deviation 0.33	0.02 units on a scale Standard Deviation 0.33	0.13 units on a scale Standard Deviation 0.41
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Breathlessness: Change at Week 4(n=14, 17, 30, 16)	-0.18 units on a scale Standard Deviation 0.50	-0.16 units on a scale Standard Deviation 0.50	-0.07 units on a scale Standard Deviation 0.28	0.18 units on a scale Standard Deviation 0.34
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Breathlessness: Change at Week 5(n=15, 17, 30, 16)	-0.14 units on a scale Standard Deviation 0.47	-0.22 units on a scale Standard Deviation 0.50	-0.06 units on a scale Standard Deviation 0.33	0.13 units on a scale Standard Deviation 0.40
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Breathlessness: Change at Week 6(n=15, 17, 30, 15)	-0.12 units on a scale Standard Deviation 0.56	-0.03 units on a scale Standard Deviation 0.50	-0.05 units on a scale Standard Deviation 0.34	0.12 units on a scale Standard Deviation 0.47
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Breathlessness: Change at Week 7(n=15, 16, 30, 15)	-0.06 units on a scale Standard Deviation 0.43	-0.21 units on a scale Standard Deviation 0.48	0.01 units on a scale Standard Deviation 0.36	0.10 units on a scale Standard Deviation 0.43
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Breathlessness: Change at Week 8(n=15, 16, 28, 15)	-0.04 units on a scale Standard Deviation 0.49	-0.13 units on a scale Standard Deviation 0.51	-0.04 units on a scale Standard Deviation 0.49	0.08 units on a scale Standard Deviation 0.45
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Sputum: Baseline (n= 16, 17, 31, 16)	1.00 units on a scale Standard Deviation 0.62	0.76 units on a scale Standard Deviation 0.79	0.95 units on a scale Standard Deviation 0.59	0.90 units on a scale Standard Deviation 0.61
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Sputum: Change at Week 1 (n= 16, 17, 31, 16)	-0.07 units on a scale Standard Deviation 0.26	0.10 units on a scale Standard Deviation 0.36	0.04 units on a scale Standard Deviation 0.39	0.04 units on a scale Standard Deviation 0.41
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Sputum: Change at Week 2 (n= 16, 15, 31, 16)	-0.05 units on a scale Standard Deviation 0.20	0.17 units on a scale Standard Deviation 0.37	0.14 units on a scale Standard Deviation 0.54	0.05 units on a scale Standard Deviation 0.52
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Sputum: Change at Week 3 (n= 15, 17, 31, 16)	-0.08 units on a scale Standard Deviation 0.32	0.20 units on a scale Standard Deviation 0.37	0.15 units on a scale Standard Deviation 0.52	0.05 units on a scale Standard Deviation 0.41
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Sputum: Change at Week 4 (n= 14, 17, 30, 16)	0.01 units on a scale Standard Deviation 0.21	0.15 units on a scale Standard Deviation 0.36	0.06 units on a scale Standard Deviation 0.51	0.01 units on a scale Standard Deviation 0.47
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Sputum: Change at Week 5 (n= 15, 17, 30, 16)	0.06 units on a scale Standard Deviation 0.23	0.15 units on a scale Standard Deviation 0.33	0.07 units on a scale Standard Deviation 0.48	-0.04 units on a scale Standard Deviation 0.44
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Sputum: Change at Week 6 (n= 15, 17, 30, 15)	0.09 units on a scale Standard Deviation 0.09	0.10 units on a scale Standard Deviation 0.46	0.10 units on a scale Standard Deviation 0.61	-0.02 units on a scale Standard Deviation 0.51
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Sputum: Change at Week 7 (n= 15, 15, 30, 15)	0.08 units on a scale Standard Deviation 0.23	-0.02 units on a scale Standard Deviation 0.39	0.07 units on a scale Standard Deviation 0.56	0.03 units on a scale Standard Deviation 0.51
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 Sputum: Change at Week 8 (n= 15, 15, 28, 15)	0.07 units on a scale Standard Deviation 0.27	-0.06 units on a scale Standard Deviation 0.40	0.02 units on a scale Standard Deviation 0.47	-0.03 units on a scale Standard Deviation 0.55

SECONDARY outcome

Timeframe: Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8

Participants were issued with rescue medication (Salbutamol MDI \[100 mcg/actuation\]) and were instructed to use 1-2 puffs as required, as a rescue therapy. All rescue medication use was recorded in daily paper dairy by participant. A participant's daily use (puffs/day) was averaged over each week.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=14 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=15 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=27 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=15 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Rescue Bronchodilator Use at Week 1, 2, 3, 4, 5, 6, 7, and 8 Baseline (n= 14, 15, 27, 15)	2.87 puffs/day Standard Deviation 2.91	3.32 puffs/day Standard Deviation 2.99	2.97 puffs/day Standard Deviation 2.83	3.46 puffs/day Standard Deviation 3.26
Change From Baseline in Rescue Bronchodilator Use at Week 1, 2, 3, 4, 5, 6, 7, and 8 Change at Week 1 (n= 14, 15, 27, 15)	-0.24 puffs/day Standard Deviation 0.51	-0.17 puffs/day Standard Deviation 0.53	-0.19 puffs/day Standard Deviation 0.61	-0.41 puffs/day Standard Deviation 1.11
Change From Baseline in Rescue Bronchodilator Use at Week 1, 2, 3, 4, 5, 6, 7, and 8 Change at Week 2 (n= 13, 13, 27, 15)	-0.26 puffs/day Standard Deviation 0.58	-0.14 puffs/day Standard Deviation 0.67	-0.08 puffs/day Standard Deviation 0.85	0.01 puffs/day Standard Deviation 1.09
Change From Baseline in Rescue Bronchodilator Use at Week 1, 2, 3, 4, 5, 6, 7, and 8 Change at Week 3 (n= 13, 14, 27, 15)	-0.12 puffs/day Standard Deviation 0.63	-0.10 puffs/day Standard Deviation 0.79	0.03 puffs/day Standard Deviation 0.95	0.17 puffs/day Standard Deviation 1.31
Change From Baseline in Rescue Bronchodilator Use at Week 1, 2, 3, 4, 5, 6, 7, and 8 Change at Week 4 (n= 13, 14, 26, 15)	-0.19 puffs/day Standard Deviation 0.56	-0.01 puffs/day Standard Deviation 0.99	-0.08 puffs/day Standard Deviation 0.99	0.07 puffs/day Standard Deviation 1.00
Change From Baseline in Rescue Bronchodilator Use at Week 1, 2, 3, 4, 5, 6, 7, and 8 Change at Week 5 (n= 13, 14, 26, 15)	-0.44 puffs/day Standard Deviation 0.98	-0.22 puffs/day Standard Deviation 1.39	0.21 puffs/day Standard Deviation 1.32	0.13 puffs/day Standard Deviation 0.93
Change From Baseline in Rescue Bronchodilator Use at Week 1, 2, 3, 4, 5, 6, 7, and 8 Change at Week 6 (n= 13, 14, 24, 14)	-0.39 puffs/day Standard Deviation 1.17	0.15 puffs/day Standard Deviation 1.16	0.26 puffs/day Standard Deviation 1.52	0.30 puffs/day Standard Deviation 1.10
Change From Baseline in Rescue Bronchodilator Use at Week 1, 2, 3, 4, 5, 6, 7, and 8 Change at Week 7 (n= 13, 13, 26, 14)	-0.20 puffs/day Standard Deviation 1.05	-0.01 puffs/day Standard Deviation 1.81	0.38 puffs/day Standard Deviation 1.41	0.24 puffs/day Standard Deviation 0.99
Change From Baseline in Rescue Bronchodilator Use at Week 1, 2, 3, 4, 5, 6, 7, and 8 Change at Week 8 (n= 13, 13, 25, 14)	-0.17 puffs/day Standard Deviation 1.31	0.02 puffs/day Standard Deviation 1.51	0.30 puffs/day Standard Deviation 1.47	0.40 puffs/day Standard Deviation 1.17

SECONDARY outcome

Timeframe: Pre-dose at Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8

The PEFR is a participant's maximum speed of expiration, as measured with a peak flow meter. All participants were issued with a hand-held peak flow device and instructed to perform twice daily (morning and evening) prior to taking any medication. A participant's daily values were averaged over each week.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=16 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=17 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=32 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=16 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Morning PEFR: Baseline (n= 16, 17, 32, 16)	220.0 liter per minute Standard Deviation 113.0	236.4 liter per minute Standard Deviation 121.4	213.6 liter per minute Standard Deviation 72.6	191.0 liter per minute Standard Deviation 77.8
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Morning PEFR: Change at Week 1 (n= 16, 17, 32, 16)	-3.6 liter per minute Standard Deviation 17.5	3.5 liter per minute Standard Deviation 17.8	2.1 liter per minute Standard Deviation 13.9	1.1 liter per minute Standard Deviation 23.0
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Morning PEFR: Change at Week 2 (n= 16, 17, 32, 16)	-5.0 liter per minute Standard Deviation 21.0	-6.0 liter per minute Standard Deviation 18.6	-1.3 liter per minute Standard Deviation 21.3	0.7 liter per minute Standard Deviation 27.2
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Morning PEFR: Change at Week 3 (n= 15, 17, 31, 16)	-8.8 liter per minute Standard Deviation 27.5	-6.2 liter per minute Standard Deviation 17.8	1.9 liter per minute Standard Deviation 26.4	2.6 liter per minute Standard Deviation 22.4
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Morning PEFR: Change at Week 4 (n= 15, 17, 31, 16)	-5.9 liter per minute Standard Deviation 24.2	-2.8 liter per minute Standard Deviation 18.4	3.3 liter per minute Standard Deviation 31.2	2.8 liter per minute Standard Deviation 28.9
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Morning PEFR: Change at Week 5 (n= 15, 17, 30, 16)	-13.4 liter per minute Standard Deviation 27.2	-4.4 liter per minute Standard Deviation 21.5	-9.4 liter per minute Standard Deviation 27.5	5.7 liter per minute Standard Deviation 31.0
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Morning PEFR: Change at Week 6 (n= 15, 17, 30, 15)	-10.5 liter per minute Standard Deviation 27.2	-4.9 liter per minute Standard Deviation 21.0	-3.9 liter per minute Standard Deviation 36.6	-6.1 liter per minute Standard Deviation 26.8
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Morning PEFR: Change at Week 7 (n= 15, 16, 29, 15)	-8.3 liter per minute Standard Deviation 22.1	-0.0 liter per minute Standard Deviation 24.3	1.2 liter per minute Standard Deviation 33.7	-2.8 liter per minute Standard Deviation 26.7
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Morning PEFR: Change at Week 8 (n= 15, 16, 27, 15)	-9.5 liter per minute Standard Deviation 26.8	-6.8 liter per minute Standard Deviation 29.4	0.4 liter per minute Standard Deviation 30.2	0.8 liter per minute Standard Deviation 23.1
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Evening PEFR: Baseline (n= 16, 17, 32, 16)	242.9 liter per minute Standard Deviation 111.8	269.3 liter per minute Standard Deviation 123.1	250.0 liter per minute Standard Deviation 78.7	207.1 liter per minute Standard Deviation 88.2
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Evening PEFR: Change at Week 1 (n= 16, 17, 32, 16)	5.5 liter per minute Standard Deviation 20.5	-0.2 liter per minute Standard Deviation 16.8	3.2 liter per minute Standard Deviation 19.7	5.2 liter per minute Standard Deviation 19.5
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Evening PEFR: Change at Week 2 (n= 16, 17, 32, 16)	4.8 liter per minute Standard Deviation 27.1	-8.7 liter per minute Standard Deviation 19.6	0.4 liter per minute Standard Deviation 25.9	8.5 liter per minute Standard Deviation 37.8
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Evening PEFR: Change at Week 3 (n= 15, 17, 31, 16)	0.1 liter per minute Standard Deviation 16.2	-17.0 liter per minute Standard Deviation 28.6	1.6 liter per minute Standard Deviation 22.9	7.6 liter per minute Standard Deviation 27.7
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Evening PEFR: Change at Week 4 (n= 15, 17, 31, 16)	-1.5 liter per minute Standard Deviation 21.5	-13.7 liter per minute Standard Deviation 19.3	-0.7 liter per minute Standard Deviation 23.6	1.6 liter per minute Standard Deviation 28.5
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Evening PEFR: Change at Week 5 (n= 15, 17, 30, 16)	-5.4 liter per minute Standard Deviation 23.6	-14.2 liter per minute Standard Deviation 24.7	-8.6 liter per minute Standard Deviation 27.0	9.5 liter per minute Standard Deviation 36.7
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Evening PEFR: Change at Week 6 (n= 15, 17, 30, 15)	-5.5 liter per minute Standard Deviation 26.8	-13.6 liter per minute Standard Deviation 23.2	-7.3 liter per minute Standard Deviation 27.7	-4.5 liter per minute Standard Deviation 40.2
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Evening PEFR: Change at Week 7 (n= 15, 16, 30, 15)	0.8 liter per minute Standard Deviation 23.7	-10.7 liter per minute Standard Deviation 21.6	-6.0 liter per minute Standard Deviation 30.7	-1.0 liter per minute Standard Deviation 34.5
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 Evening PEFR: Change at Week 8 (n= 15, 16, 28, 15)	-2.6 liter per minute Standard Deviation 21.9	-16.0 liter per minute Standard Deviation 23.4	-3.4 liter per minute Standard Deviation 30.6	-5.9 liter per minute Standard Deviation 41.9

SECONDARY outcome

Timeframe: Week 6

CGI-C: clinician's global impression of a participant's clinical condition in terms of change relative to the start of treatment. Rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=14 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=16 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=29 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=15 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Number of Participants With Categorical Scores on Clinical Global Impression of Change (CGI-C) Very Much Improved	0 participants	0 participants	0 participants	1 participants
Number of Participants With Categorical Scores on Clinical Global Impression of Change (CGI-C) Much Improved	0 participants	2 participants	2 participants	2 participants
Number of Participants With Categorical Scores on Clinical Global Impression of Change (CGI-C) Minimally Improved	5 participants	4 participants	9 participants	4 participants
Number of Participants With Categorical Scores on Clinical Global Impression of Change (CGI-C) No Change	5 participants	7 participants	14 participants	6 participants
Number of Participants With Categorical Scores on Clinical Global Impression of Change (CGI-C) Minimally Worse	2 participants	3 participants	4 participants	2 participants
Number of Participants With Categorical Scores on Clinical Global Impression of Change (CGI-C) Much Worse	2 participants	0 participants	0 participants	0 participants
Number of Participants With Categorical Scores on Clinical Global Impression of Change (CGI-C) Very Much Worse	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Week 6

PGI-C: participant rated instrument to measure participant's clinical condition in terms of change relative to the start of treatment. Rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=14 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=16 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=29 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=15 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Number of Participants With Categorical Scores on Patient Global Impression of Change (PGI-C) Very Much Worse	0 participants	1 participants	1 participants	0 participants
Number of Participants With Categorical Scores on Patient Global Impression of Change (PGI-C) Very Much Improved	0 participants	0 participants	0 participants	0 participants
Number of Participants With Categorical Scores on Patient Global Impression of Change (PGI-C) Much Improved	2 participants	2 participants	3 participants	2 participants
Number of Participants With Categorical Scores on Patient Global Impression of Change (PGI-C) Minimally Improved	3 participants	4 participants	7 participants	6 participants
Number of Participants With Categorical Scores on Patient Global Impression of Change (PGI-C) No Change	7 participants	8 participants	15 participants	5 participants
Number of Participants With Categorical Scores on Patient Global Impression of Change (PGI-C) Minimally Worse	1 participants	1 participants	2 participants	2 participants
Number of Participants With Categorical Scores on Patient Global Impression of Change (PGI-C) Much Worse	1 participants	0 participants	1 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (pre-dose at Week 0); Pre-dose and 3-hour post-dose on Week 1, 6; 3-hour post-dose on Week 0, 2, 4

Population: Safety analysis set included all participants who received at least 1 dose of study treatment. Here "n" signifies participants who were evaluable for specified time-point for each arm group, respectively.

Pulse rate: the number of pulsations noted in a peripheral artery per unit of time after participant rested supine for 5 minutes, reported as beats per minute (bpm).

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=17 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=18 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=35 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=17 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Pulse Rate at Week 0, 1, 2, 4, and 6 Change at Week 6, Post-Dose (n= 14, 16, 28, 15)	2.2 bpm Standard Deviation 8.23	-0.2 bpm Standard Deviation 7.44	3.5 bpm Standard Deviation 12.85	1.2 bpm Standard Deviation 8.88
Change From Baseline in Pulse Rate at Week 0, 1, 2, 4, and 6 Baseline (n= 17, 18, 35, 17)	68.6 bpm Standard Deviation 11.45	75.2 bpm Standard Deviation 12.37	73.7 bpm Standard Deviation 12.83	74.2 bpm Standard Deviation 13.07
Change From Baseline in Pulse Rate at Week 0, 1, 2, 4, and 6 Change at Week 0, Post-Dose (n= 16, 18, 35, 17)	-0.4 bpm Standard Deviation 6.86	2.5 bpm Standard Deviation 6.72	1.3 bpm Standard Deviation 7.63	0.3 bpm Standard Deviation 7.86
Change From Baseline in Pulse Rate at Week 0, 1, 2, 4, and 6 Change at Week 1, Pre-Dose (n= 15, 18, 33, 16)	3.2 bpm Standard Deviation 7.97	4.7 bpm Standard Deviation 10.97	0.8 bpm Standard Deviation 9.95	-0.3 bpm Standard Deviation 10.10
Change From Baseline in Pulse Rate at Week 0, 1, 2, 4, and 6 Change at Week 1, Post-Dose (n= 17, 15, 32, 16)	2.7 bpm Standard Deviation 10.10	2.2 bpm Standard Deviation 7.47	1.1 bpm Standard Deviation 8.91	0.5 bpm Standard Deviation 10.47
Change From Baseline in Pulse Rate at Week 0, 1, 2, 4, and 6 Change at Week 2, Post-Dose (n= 16, 17, 30, 16)	1.6 bpm Standard Deviation 9.04	-1.7 bpm Standard Deviation 10.80	2.7 bpm Standard Deviation 12.39	0.1 bpm Standard Deviation 6.97
Change From Baseline in Pulse Rate at Week 0, 1, 2, 4, and 6 Change at Week 4, Post-Dose (n= 15, 15, 30, 16)	2.5 bpm Standard Deviation 10.08	1.3 bpm Standard Deviation 10.15	3.8 bpm Standard Deviation 16.52	2.4 bpm Standard Deviation 7.73
Change From Baseline in Pulse Rate at Week 0, 1, 2, 4, and 6 Change at Week 6, Pre-Dose (n= 15, 16, 28, 15)	0.7 bpm Standard Deviation 6.16	-0.1 bpm Standard Deviation 6.70	0.9 bpm Standard Deviation 11.39	-1.2 bpm Standard Deviation 6.57

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (pre-dose at Week 0); Pre-dose and 3-hour post-dose on Week 1, 6; 3-hour post-dose on Week 0, 2, 4

BP is the pressure of the blood within the arteries. It is produced primarily by the contraction of the heart muscle. BP measurement is recorded by 2 numbers: systolic BP (SBP, BP when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle) and diastolic BP (DBP, BP when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles). BP was measured by sphygmomanometer (manual or semi-automated) using appropriate-sized and calibrated cuff after participant rested in supine position for 5 minutes.

Outcome measures

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (pre-dose at Week 0); Pre-dose and 3-hour post-dose on Week 6; 3-hour post-dose on Week 0, 1, 2, 4; Week 8 (follow-up)

Standard 12-lead ECG was performed after participant has rested for at least 10 minutes in supine position. ECG intervals (Int) included PR Int (time between onset of atrial depolarization and onset of ventricular depolarization), QRS Int (represented ventricular depolarization), RR Int (time between 2 QRS complex), QT Int (time corresponding to the beginning of depolarization to repolarization of the ventricles), corrected QT (QTc) Int, QT Int corrected by Fridericia's formula (QTcF=QT divided by cube root of RR Int) and Bazett's formula (QTcB=QT divided by square root of RR Int).

Outcome measures

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (pre-dose at Week 0); Pre-dose and 3-hour post-dose on Week 6; 3-hour post-dose on Week 0, 1, 2, 4; Week 8 (follow-up)

Standard 12-lead ECG was performed after the participant has rested quietly for at least 10 minutes in supine position. The time interval between consecutive heart beats (RR interval) was used to calculate heart rate.

Outcome measures

Outcome measures
Measure	UK-432,097 150 Mcg n=17 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=18 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=35 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=17 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate) at Week 0, 1, 2, 4, 6, and 8 Baseline (n= 17,18,35,17)	66.6 bpm Standard Deviation 11.65	72.1 bpm Standard Deviation 11.00	74.8 bpm Standard Deviation 12.92	72.4 bpm Standard Deviation 13.81
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate) at Week 0, 1, 2, 4, 6, and 8 Change at Week 0, Post-Dose (n= 17,18,35,17)	0.8 bpm Standard Deviation 6.56	4.0 bpm Standard Deviation 5.90	0.3 bpm Standard Deviation 8.69	2.7 bpm Standard Deviation 7.76
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate) at Week 0, 1, 2, 4, 6, and 8 Change at Week 1, Post-Dose (n= 17,17,32,16)	1.1 bpm Standard Deviation 9.76	4.3 bpm Standard Deviation 6.30	-1.5 bpm Standard Deviation 10.13	2.8 bpm Standard Deviation 13.45
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate) at Week 0, 1, 2, 4, 6, and 8 Change at Week 2, Post-Dose (n= 16,17,32,16)	0.7 bpm Standard Deviation 8.98	4.2 bpm Standard Deviation 10.38	-0.2 bpm Standard Deviation 12.76	1.9 bpm Standard Deviation 8.06
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate) at Week 0, 1, 2, 4, 6, and 8 Change at Week 4, Post-Dose (n= 15,17,29,16)	-0.2 bpm Standard Deviation 8.75	2.4 bpm Standard Deviation 8.33	2.5 bpm Standard Deviation 18.51	3.2 bpm Standard Deviation 8.23
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate) at Week 0, 1, 2, 4, 6, and 8 Change at Week 6, Pre-Dose (n= 14,16,29,15)	2.3 bpm Standard Deviation 5.17	1.4 bpm Standard Deviation 7.71	0.6 bpm Standard Deviation 11.82	-1.7 bpm Standard Deviation 7.72
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate) at Week 0, 1, 2, 4, 6, and 8 Change at Week 6, Post-Dose (n= 15,16,28,15)	1.9 bpm Standard Deviation 8.68	2.2 bpm Standard Deviation 6.94	2.6 bpm Standard Deviation 11.84	0.3 bpm Standard Deviation 11.31
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate) at Week 0, 1, 2, 4, 6, and 8 Change at Week 8 (n= 17,18,32,17)	1.9 bpm Standard Deviation 5.94	1.8 bpm Standard Deviation 6.51	-0.8 bpm Standard Deviation 11.16	-2.1 bpm Standard Deviation 9.57

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose and 15 to 30 minutes Post-dose at Week 0, 1, 2, 4, 6

Population: Data for this pre-specified endpoint was not analyzed, as the study was terminated due to futility based on results of interim analysis.

Outcome measures

Outcome data not reported

Adverse Events

UK-432,097 150 Mcg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

UK-432,097 450 Mcg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

UK-432,097 1350 Mcg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	UK-432,097 150 Mcg n=17 Participants UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=18 Participants UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=35 Participants UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=17 Participants Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 SBP: Baseline (n= 17, 18, 35, 17)	128.5 millimeter of mercury (mmHg) Standard Deviation 11.73	137.3 millimeter of mercury (mmHg) Standard Deviation 14.40	129.5 millimeter of mercury (mmHg) Standard Deviation 12.77	132.7 millimeter of mercury (mmHg) Standard Deviation 13.45
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 SBP: Change at Week 0, Post-Dose (n= 16,18,35,17)	2.4 millimeter of mercury (mmHg) Standard Deviation 7.29	-1.3 millimeter of mercury (mmHg) Standard Deviation 11.52	-1.3 millimeter of mercury (mmHg) Standard Deviation 9.70	0.4 millimeter of mercury (mmHg) Standard Deviation 7.36
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 SBP: Change at Week 1, Pre-Dose (n= 15,18,33,16)	1.4 millimeter of mercury (mmHg) Standard Deviation 6.33	-1.4 millimeter of mercury (mmHg) Standard Deviation 15.34	0.7 millimeter of mercury (mmHg) Standard Deviation 12.32	0.3 millimeter of mercury (mmHg) Standard Deviation 11.98
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 SBP: Change at Week 1, Post-Dose (n= 17,15,32,16)	0.5 millimeter of mercury (mmHg) Standard Deviation 9.90	-5.5 millimeter of mercury (mmHg) Standard Deviation 16.17	1.0 millimeter of mercury (mmHg) Standard Deviation 15.41	-4.5 millimeter of mercury (mmHg) Standard Deviation 12.81
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 SBP: Change at Week 2, Post-Dose (n= 16,17,30,16)	1.4 millimeter of mercury (mmHg) Standard Deviation 16.25	2.8 millimeter of mercury (mmHg) Standard Deviation 16.64	0.5 millimeter of mercury (mmHg) Standard Deviation 13.06	-2.2 millimeter of mercury (mmHg) Standard Deviation 14.86
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 SBP: Change at Week 4, Post-Dose (n= 15,15,30,16)	3.1 millimeter of mercury (mmHg) Standard Deviation 6.27	-4.7 millimeter of mercury (mmHg) Standard Deviation 12.96	-1.3 millimeter of mercury (mmHg) Standard Deviation 14.56	-5.8 millimeter of mercury (mmHg) Standard Deviation 15.21
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 SBP: Change at Week 6, Pre-Dose (n= 15,16,28,15)	3.6 millimeter of mercury (mmHg) Standard Deviation 11.57	-7.6 millimeter of mercury (mmHg) Standard Deviation 15.19	-1.5 millimeter of mercury (mmHg) Standard Deviation 9.54	1.2 millimeter of mercury (mmHg) Standard Deviation 10.81
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 SBP: Change at Week 6, Post-Dose (n= 14,16,28,15)	-1.2 millimeter of mercury (mmHg) Standard Deviation 10.14	-7.5 millimeter of mercury (mmHg) Standard Deviation 13.73	-0.9 millimeter of mercury (mmHg) Standard Deviation 8.77	-0.9 millimeter of mercury (mmHg) Standard Deviation 12.68
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 DBP: Baseline (n= 17, 18, 35, 17)	76.9 millimeter of mercury (mmHg) Standard Deviation 7.18	78.5 millimeter of mercury (mmHg) Standard Deviation 10.29	74.3 millimeter of mercury (mmHg) Standard Deviation 8.30	76.5 millimeter of mercury (mmHg) Standard Deviation 7.24
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 DBP: Change at Week 0, Post-Dose (n= 16,18,35,17)	0.1 millimeter of mercury (mmHg) Standard Deviation 5.97	-2.0 millimeter of mercury (mmHg) Standard Deviation 6.21	-0.7 millimeter of mercury (mmHg) Standard Deviation 6.30	0.6 millimeter of mercury (mmHg) Standard Deviation 6.44
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 DBP: Change at Week 1, Pre-Dose (n= 15,18,33,16)	1.1 millimeter of mercury (mmHg) Standard Deviation 10.56	-0.8 millimeter of mercury (mmHg) Standard Deviation 6.18	-0.1 millimeter of mercury (mmHg) Standard Deviation 8.68	1.5 millimeter of mercury (mmHg) Standard Deviation 6.23
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 DBP: Change at Week 1, Post-Dose (n= 17,15,32,16)	-1.9 millimeter of mercury (mmHg) Standard Deviation 9.86	-2.1 millimeter of mercury (mmHg) Standard Deviation 8.72	-0.2 millimeter of mercury (mmHg) Standard Deviation 8.95	-1.0 millimeter of mercury (mmHg) Standard Deviation 7.41
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 DBP: Change at Week 2, Post-Dose (n= 16,17,30,16)	-0.6 millimeter of mercury (mmHg) Standard Deviation 11.28	0.1 millimeter of mercury (mmHg) Standard Deviation 7.96	-0.5 millimeter of mercury (mmHg) Standard Deviation 8.07	0.1 millimeter of mercury (mmHg) Standard Deviation 7.64
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 DBP: Change at Week 4, Post-Dose (n= 15,15,30,16)	-1.8 millimeter of mercury (mmHg) Standard Deviation 7.53	-4.5 millimeter of mercury (mmHg) Standard Deviation 6.49	-1.9 millimeter of mercury (mmHg) Standard Deviation 8.10	-1.2 millimeter of mercury (mmHg) Standard Deviation 7.79
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 DBP: Change at Week 6, Pre-Dose (n= 15,16,28,15)	-2.2 millimeter of mercury (mmHg) Standard Deviation 6.28	-3.9 millimeter of mercury (mmHg) Standard Deviation 8.21	-0.3 millimeter of mercury (mmHg) Standard Deviation 6.74	0.7 millimeter of mercury (mmHg) Standard Deviation 5.09
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 DBP: Change at Week 6, Post-Dose (n= 14,16,28,15)	-5.2 millimeter of mercury (mmHg) Standard Deviation 6.90	-7.3 millimeter of mercury (mmHg) Standard Deviation 7.88	-2.8 millimeter of mercury (mmHg) Standard Deviation 6.87	-3.5 millimeter of mercury (mmHg) Standard Deviation 8.27

Other adverse events
Measure	UK-432,097 150 Mcg n=17 participants at risk UK-432,097 150 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 450 Mcg n=18 participants at risk UK-432,097 450 mcg capsule and 2 matching placebo capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	UK-432,097 1350 Mcg n=35 participants at risk UK-432,097 1350 mcg (3 \* 450 mcg capsules) twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.	Placebo n=17 participants at risk Placebo matching to UK-432,097 capsules twice daily up to Week 6, administered by inhalation using the single pin mono-dose capsule inhaler device. Additionally, participants received ipratropium bromide MDI 2 actuations (20 mcg/actuation) 4 times daily as a maintenance therapy up to Week 8 and salbutamol MDI 1 to 2 actuations (100 mcg/actuation) as rescue therapy whenever required.
Cardiac disorders Atrioventricular block first degree	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye swelling	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.6% 1/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vision blurred	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dry mouth	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	11.8% 2/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Influenza like illness	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.1% 2/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Lower respiratory tract infection	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.6% 1/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	16.7% 3/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.6% 3/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pharyngitis	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Sinusitis	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.6% 1/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Muscle strain	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.6% 1/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood alkaline phosphatase increased	11.8% 2/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Electrocardiogram QT prolonged	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Forced expiratory volume decreased	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.6% 1/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.6% 1/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscle rigidity	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Neck pain	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.6% 1/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.6% 1/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Obstructive uropathy	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	11.8% 2/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.6% 1/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.1% 2/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Productive cough	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.6% 1/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Rhinalgia	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Throat irritation	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Wheezing	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.6% 1/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hot flush	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Varicose vein	0.00% 0/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 1/17 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.