Trial Outcomes & Findings for A Randomized Study To Evaluate The Efficacy And Safety Of An Investigational Drug In Adolescent And Adult Subjects With Asthma Uncontrolled on Non-steroidal Therapy. (NCT NCT00603382)

Last Updated: 2018-04-18

Results Overview

Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Pre-dose and pre-rescue bronchodilator (albuterol/salbutamol) trough FEV1(the measurement of FEV1 performed at the end of the dosing interval) was measured electronically by spirometry in the evening at the Baseline through Week 8 clinic visits. Trough FEV1 is the FEV1 measured approximately 24 hours after the last administration of study drug. The highest of 3 technically acceptable measurements was recorded. The Visit 3 FEV1 assessment was used as the Baseline value. Change from Baseline in trough FEV1 was calculated as the value at Week 8 minus the value at Baseline. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline trough FEV1, country, sex, age, and treatment group.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

599 participants

Primary outcome timeframe

Baseline and Week 8

Results posted on

2018-04-18

Participant Flow

Participants (par.) meeting eligibility criteria at the Screening visit completed a 28-day Run-in Period for Baseline, safety evaluations and measures of asthma status. Par. were then randomized to an 8-week Treatment Period. Total 1459 par. were screened, 601 were randomized of which 598 par. received at least one dose of study treatment.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) and placebo twice daily (BID) from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD Participants received GW685698X 25 micrograms (µg) OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID Participants received fluticasone propionate (FP) 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Overall Study STARTED	94	97	100	110	95	102
Overall Study COMPLETED	76	83	91	98	86	84
Overall Study NOT COMPLETED	18	14	9	12	9	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) and placebo twice daily (BID) from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD Participants received GW685698X 25 micrograms (µg) OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID Participants received fluticasone propionate (FP) 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Overall Study Adverse Event	0	1	1	2	1	2
Overall Study Lack of Efficacy	14	9	3	6	6	11
Overall Study Protocol Violation	1	0	1	2	1	0
Overall Study Lost to Follow-up	0	1	1	1	0	1
Overall Study Physician Decision	0	0	2	0	1	3
Overall Study Withdrawal by Subject	3	3	1	1	0	1

Baseline Characteristics

A Randomized Study To Evaluate The Efficacy And Safety Of An Investigational Drug In Adolescent And Adult Subjects With Asthma Uncontrolled on Non-steroidal Therapy.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	Total n=598 Participants Total of all reporting groups
Age, Continuous	39.2 Years STANDARD_DEVIATION 15.82 • n=5 Participants	37.7 Years STANDARD_DEVIATION 15.40 • n=7 Participants	38.3 Years STANDARD_DEVIATION 14.49 • n=5 Participants	36.8 Years STANDARD_DEVIATION 15.56 • n=4 Participants	40.7 Years STANDARD_DEVIATION 15.96 • n=21 Participants	39.9 Years STANDARD_DEVIATION 15.03 • n=10 Participants	38.7 Years STANDARD_DEVIATION 15.37 • n=115 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	57 Participants n=7 Participants	59 Participants n=5 Participants	60 Participants n=4 Participants	60 Participants n=21 Participants	56 Participants n=10 Participants	339 Participants n=115 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	40 Participants n=7 Participants	41 Participants n=5 Participants	50 Participants n=4 Participants	35 Participants n=21 Participants	46 Participants n=10 Participants	259 Participants n=115 Participants
Race/Ethnicity, Customized African American/African Heritage (AA/AHER)	5 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants	8 participants n=4 Participants	6 participants n=21 Participants	5 participants n=10 Participants	32 participants n=115 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	5 participants n=5 Participants	7 participants n=7 Participants	5 participants n=5 Participants	6 participants n=4 Participants	6 participants n=21 Participants	5 participants n=10 Participants	34 participants n=115 Participants
Race/Ethnicity, Customized Asian	7 participants n=5 Participants	13 participants n=7 Participants	9 participants n=5 Participants	10 participants n=4 Participants	10 participants n=21 Participants	10 participants n=10 Participants	59 participants n=115 Participants
Race/Ethnicity, Customized White	69 participants n=5 Participants	64 participants n=7 Participants	72 participants n=5 Participants	76 participants n=4 Participants	64 participants n=21 Participants	74 participants n=10 Participants	419 participants n=115 Participants
Race/Ethnicity, Customized AA/AHER & American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants	0 participants n=10 Participants	1 participants n=115 Participants
Race/Ethnicity, Customized American Indian or Alaska Native & White	8 participants n=5 Participants	8 participants n=7 Participants	9 participants n=5 Participants	10 participants n=4 Participants	8 participants n=21 Participants	8 participants n=10 Participants	51 participants n=115 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander & White	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=10 Participants	2 participants n=115 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of study medication. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-BL on-treatment measurement (scheduled and unscheduled visits) was used to impute missing measurements.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=94 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=97 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=109 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=94 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=101 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Mean Change From Baseline in Trough (Evening Pre-dose and Pre- Rescue Bronchodilator) FEV1 at Week 8	0.137 Liters Standard Error 0.0428	0.239 Liters Standard Error 0.0428	0.266 Liters Standard Error 0.0420	0.341 Liters Standard Error 0.0396	0.367 Liters Standard Error 0.0428	0.243 Liters Standard Error 0.0411

SECONDARY outcome

Timeframe: From Baseline up to Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Trough PEF is defined as the PEF measurement performed at the end of the dosing interval. PEF was measured by the participants using a hand-held electronic peak flow meter each evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. The best of three attempts was recorded by the participants in a daily diary. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the value of the averaged daily evening PEF over the 8-week treatment period minus the value at Baseline. The analysis was performed using an ANCOVA model with covariates of Baseline trough evening PEF, country, sex, age, and treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=96 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=98 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Mean Change From Baseline in Daily Trough (Pre-dose and Pre-rescue Bronchodilator) Evening Peak Expiratory Flow (PEF) Averaged Over the 8-week Treatment Period	9.6 Liters per minute Standard Error 4.21	23.6 Liters per minute Standard Error 4.17	30.3 Liters per minute Standard Error 4.12	25.7 Liters per minute Standard Error 3.90	31.3 Liters per minute Standard Error 4.20	24.4 Liters per minute Standard Error 4.04

SECONDARY outcome

Timeframe: From Baseline up to Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Trough PEF is defined as the PEF measurement performed at th end of the dosing interval. PEF was measured by the participants using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. The best of three attempts was recorded by the participants in a daily diary. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the value of the averaged daily morning PEF over the 8-week treatment period minus the value at Baseline. The analysis was performed using an ANCOVA model with covariates of Baseline trough morning PEF, country, sex, age, and treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=96 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=98 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Mean Change From Baseline in Daily Morning PEF Averaged Over the 8-week Treatment Period	13.6 Liters per minute Standard Error 4.27	27.2 Liters per minute Standard Error 4.23	33.5 Liters per minute Standard Error 4.17	29.5 Liters per minute Standard Error 3.95	35.6 Liters per minute Standard Error 4.26	25.6 Liters per minute Standard Error 4.09

SECONDARY outcome

Timeframe: From Baseline up to Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Asthma symptoms were recorded in a daily dairy by the participants every day in the morning and evening before taking any rescue or study medication and before PEF measurement. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered as symptom-free. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 8-week Treatment Period minus the value at Baseline. The analysis was performed using an ANCOVA model with covariates of Baseline, country, sex, age, and treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=96 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=98 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Mean Change From Baseline in the Percentage of Symptom-free 24 Hour (hr) Periods During the 8-week Treatment Period	18.4 Percentage of symptom-free 24-hr periods Standard Error 3.21	25.3 Percentage of symptom-free 24-hr periods Standard Error 3.17	31.1 Percentage of symptom-free 24-hr periods Standard Error 3.14	38.7 Percentage of symptom-free 24-hr periods Standard Error 2.97	31.7 Percentage of symptom-free 24-hr periods Standard Error 3.20	33.3 Percentage of symptom-free 24-hr periods Standard Error 3.08

SECONDARY outcome

Timeframe: From Baseline up to Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The number of inhalations of rescue albuterol/salbutamol inhalation aerosol used during the day and night was recorded by the participants in a daily diary. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered as rescue-free. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 8-week Treatment Period minus the value at Baseline. The analysis was performed using an ANCOVA model with covariates of Baseline, country, sex, age, and treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=96 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=98 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Mean Change From Baseline in the Percentage of Rescue Free 24-hour (hr) Periods During the 8-week Treatment Period	21.9 Percentage of rescue-free 24-hr periods Standard Error 3.32	29.3 Percentage of rescue-free 24-hr periods Standard Error 3.28	34.5 Percentage of rescue-free 24-hr periods Standard Error 3.24	40.8 Percentage of rescue-free 24-hr periods Standard Error 3.08	32.0 Percentage of rescue-free 24-hr periods Standard Error 3.31	35.5 Percentage of rescue-free 24-hr periods Standard Error 3.18

SECONDARY outcome

Timeframe: From the first dose of study medication up to Week 8/Early Withdrawal

Population: ITT Population

The number of participants whose primary reason for withdrawal was lack of efficacy was analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Number of Participants Who Withdrew Due to Lack of Efficacy During the 8-Week Treatment Period	14 participants	9 participants	3 participants	6 participants	6 participants	11 participants

SECONDARY outcome

Timeframe: From the first dose of study medication up to Week 8/Early Withdrawal

Population: ITT Population

An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; or is a congenital anomaly/birth defect. Medical or scientific judgment should have been exercised in other situations. Refer to the general AE/SAE module for a list of AEs (occurring at a frequency threshold \>=3%) and SAEs.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Number of Participants With Any On-treatment Adverse Events or Serious Adverse Events Throughout the 8-week Treatment Period Any AE	24 participants	19 participants	28 participants	35 participants	27 participants	35 participants
Number of Participants With Any On-treatment Adverse Events or Serious Adverse Events Throughout the 8-week Treatment Period Any SAE	0 participants	1 participants	0 participants	1 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: From Baseline up to Week 8/Early Withdrawal

Population: ITT Population

A detailed oropharyngeal examination for visual evidence of oral candidiasis was performed.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Number of Participants With Clinical/Visual Evidence of Oropharyngeal Candidiasis Clinical evidence	0 participants	0 participants	4 participants	4 participants	2 participants	2 participants
Number of Participants With Clinical/Visual Evidence of Oropharyngeal Candidiasis No clinical evidence	94 participants	97 participants	96 participants	106 participants	93 participants	100 participants

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8 Basophils, BL, n=92, 94, 95, 106, 92, 97	0.31 Percentage Standard Deviation 0.199	0.32 Percentage Standard Deviation 0.200	0.31 Percentage Standard Deviation 0.194	0.32 Percentage Standard Deviation 0.190	0.33 Percentage Standard Deviation 0.205	0.33 Percentage Standard Deviation 0.234
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8 Basophils,W8, n=72, 80, 83, 94, 82, 79	0.30 Percentage Standard Deviation 0.186	0.26 Percentage Standard Deviation 0.153	0.31 Percentage Standard Deviation 0.169	0.35 Percentage Standard Deviation 0.236	0.35 Percentage Standard Deviation 0.220	0.34 Percentage Standard Deviation 0.264
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8 Total Neutrophils, BL, n=92, 94, 95, 106, 92, 97	56.74 Percentage Standard Deviation 9.220	60.24 Percentage Standard Deviation 9.620	57.68 Percentage Standard Deviation 8.309	56.34 Percentage Standard Deviation 9.832	55.80 Percentage Standard Deviation 10.281	56.60 Percentage Standard Deviation 9.226
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8 Total Neutrophils, W8, n=72, 80, 83, 94, 82, 79	57.08 Percentage Standard Deviation 9.543	62.19 Percentage Standard Deviation 11.580	60.95 Percentage Standard Deviation 9.008	60.86 Percentage Standard Deviation 8.054	59.20 Percentage Standard Deviation 8.881	59.19 Percentage Standard Deviation 8.672
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8 Eosinophils, BL, n=92, 94, 95, 106, 92, 97	3.87 Percentage Standard Deviation 3.022	3.38 Percentage Standard Deviation 2.693	3.95 Percentage Standard Deviation 2.503	4.40 Percentage Standard Deviation 3.286	4.75 Percentage Standard Deviation 3.358	3.88 Percentage Standard Deviation 3.073
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8 Eosinophils, W8, n=72, 80, 83, 94, 82, 79	4.31 Percentage Standard Deviation 3.544	3.38 Percentage Standard Deviation 3.300	3.76 Percentage Standard Deviation 2.608	3.77 Percentage Standard Deviation 3.066	3.96 Percentage Standard Deviation 2.867	3.34 Percentage Standard Deviation 2.364
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8 Lymphocytes, BL, n=92, 94, 95, 106, 92, 97	33.96 Percentage Standard Deviation 8.378	31.57 Percentage Standard Deviation 8.821	33.33 Percentage Standard Deviation 7.768	33.69 Percentage Standard Deviation 8.682	34.32 Percentage Standard Deviation 8.806	34.25 Percentage Standard Deviation 8.514
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8 Lymphocytes, W8, n=72, 80, 83, 94, 82, 79	32.88 Percentage Standard Deviation 8.063	29.82 Percentage Standard Deviation 10.120	30.36 Percentage Standard Deviation 8.322	30.39 Percentage Standard Deviation 7.326	31.97 Percentage Standard Deviation 7.440	32.22 Percentage Standard Deviation 7.877
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8 Monocytes, BL, n=92, 94, 95, 106, 92, 97	5.09 Percentage Standard Deviation 2.379	4.41 Percentage Standard Deviation 1.851	4.70 Percentage Standard Deviation 2.056	5.20 Percentage Standard Deviation 2.113	4.78 Percentage Standard Deviation 2.301	4.92 Percentage Standard Deviation 2.093
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8 Monocytes, W8, n=72, 80, 83, 94, 82, 79	5.41 Percentage Standard Deviation 3.042	4.32 Percentage Standard Deviation 2.098	4.60 Percentage Standard Deviation 2.486	4.60 Percentage Standard Deviation 2.178	4.50 Percentage Standard Deviation 2.174	4.87 Percentage Standard Deviation 2.380

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of Hematocrit at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Hematocrit at Baseline and Week 8 Hematocrit, BL, n=92, 94, 95, 106, 92, 97	0.43 Proportion of 1 Standard Deviation 0.041	0.42 Proportion of 1 Standard Deviation 0.039	0.42 Proportion of 1 Standard Deviation 0.040	0.43 Proportion of 1 Standard Deviation 0.043	0.42 Proportion of 1 Standard Deviation 0.039	0.43 Proportion of 1 Standard Deviation 0.034
Hematocrit at Baseline and Week 8 Hematocrit, W8, n=72, 79, 83, 94, 82, 79	0.43 Proportion of 1 Standard Deviation 0.038	0.42 Proportion of 1 Standard Deviation 0.038	0.42 Proportion of 1 Standard Deviation 0.037	0.43 Proportion of 1 Standard Deviation 0.040	0.42 Proportion of 1 Standard Deviation 0.033	0.43 Proportion of 1 Standard Deviation 0.039

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of hemoglobin at Baseline (BL)and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Hemoglobin at Baseline and Week 8 Hemoglobin, BL, n=92, 94, 95, 106, 92, 96	141.54 Grams per liter (G/L) Standard Deviation 14.116	138.05 Grams per liter (G/L) Standard Deviation 13.178	140.70 Grams per liter (G/L) Standard Deviation 13.769	141.14 Grams per liter (G/L) Standard Deviation 14.625	139.50 Grams per liter (G/L) Standard Deviation 12.978	141.90 Grams per liter (G/L) Standard Deviation 11.632
Hemoglobin at Baseline and Week 8 Hemoglobin, W8, n=72, 79, 83, 94, 82, 79	140.81 Grams per liter (G/L) Standard Deviation 12.973	137.86 Grams per liter (G/L) Standard Deviation 12.862	138.95 Grams per liter (G/L) Standard Deviation 12.785	140.16 Grams per liter (G/L) Standard Deviation 13.647	136.32 Grams per liter (G/L) Standard Deviation 11.594	139.81 Grams per liter (G/L) Standard Deviation 13.009

SECONDARY outcome

Timeframe: Baseline and Week 8

Blood samples were collected for the measurement of platelet count and WBC count at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Platelet Count and White Blood Cell (WBC) Count at Baseline and Week 8 Platelet count, BL, n=91, 91, 95, 106, 92, 95	271.68 10^9 cells per liter (GI/L) Standard Deviation 62.861	265.75 10^9 cells per liter (GI/L) Standard Deviation 51.446	279.38 10^9 cells per liter (GI/L) Standard Deviation 57.658	272.20 10^9 cells per liter (GI/L) Standard Deviation 61.111	268.37 10^9 cells per liter (GI/L) Standard Deviation 60.442	281.26 10^9 cells per liter (GI/L) Standard Deviation 66.492
Platelet Count and White Blood Cell (WBC) Count at Baseline and Week 8 Platelet count, W8, n=72, 76, 83, 93, 81, 78	265.47 10^9 cells per liter (GI/L) Standard Deviation 49.978	262.07 10^9 cells per liter (GI/L) Standard Deviation 45.837	271.03 10^9 cells per liter (GI/L) Standard Deviation 47.156	278.57 10^9 cells per liter (GI/L) Standard Deviation 58.302	272.53 10^9 cells per liter (GI/L) Standard Deviation 68.404	274.46 10^9 cells per liter (GI/L) Standard Deviation 61.819
Platelet Count and White Blood Cell (WBC) Count at Baseline and Week 8 WBC, BL, n=92, 94, 95, 106, 92, 97	7.82 10^9 cells per liter (GI/L) Standard Deviation 2.018	7.96 10^9 cells per liter (GI/L) Standard Deviation 1.892	8.01 10^9 cells per liter (GI/L) Standard Deviation 2.095	7.62 10^9 cells per liter (GI/L) Standard Deviation 1.878	7.79 10^9 cells per liter (GI/L) Standard Deviation 2.055	7.94 10^9 cells per liter (GI/L) Standard Deviation 1.982
Platelet Count and White Blood Cell (WBC) Count at Baseline and Week 8 WBC, W8, n=72, 79, 83, 94, 82, 79	7.56 10^9 cells per liter (GI/L) Standard Deviation 1.679	8.26 10^9 cells per liter (GI/L) Standard Deviation 2.169	8.34 10^9 cells per liter (GI/L) Standard Deviation 2.211	7.94 10^9 cells per liter (GI/L) Standard Deviation 2.046	7.94 10^9 cells per liter (GI/L) Standard Deviation 1.769	8.00 10^9 cells per liter (GI/L) Standard Deviation 2.292

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of RBC count at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Red Blood Cells (RBC) Count at Baseline and Week 8 RBC, BL, n=92, 94, 95, 106, 92, 97	4.71 10^12 cells per liter (TI/L) Standard Deviation 0.429	4.65 10^12 cells per liter (TI/L) Standard Deviation 0.438	4.68 10^12 cells per liter (TI/L) Standard Deviation 0.425	4.71 10^12 cells per liter (TI/L) Standard Deviation 0.460	4.68 10^12 cells per liter (TI/L) Standard Deviation 0.422	4.71 10^12 cells per liter (TI/L) Standard Deviation 0.416
Red Blood Cells (RBC) Count at Baseline and Week 8 RBC, W8, n=72, 79, 83, 94, 82, 79	4.65 10^12 cells per liter (TI/L) Standard Deviation 0.410	4.61 10^12 cells per liter (TI/L) Standard Deviation 0.445	4.63 10^12 cells per liter (TI/L) Standard Deviation 0.435	4.67 10^12 cells per liter (TI/L) Standard Deviation 0.450	4.60 10^12 cells per liter (TI/L) Standard Deviation 0.369	4.65 10^12 cells per liter (TI/L) Standard Deviation 0.462

SECONDARY outcome

Timeframe: Baseline and Week 8

Blood samples were collected for the measurement of ALP, ALT, AST, LD and GGT at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at Screening (Visit 1).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LD), and Gamma Glutamyltransferase (GGT) at Baseline and Week 8 ALT, BL, n=94, 97, 99, 106, 94, 101	21.8 International units per liter (IU/L) Standard Deviation 15.91	21.5 International units per liter (IU/L) Standard Deviation 14.57	23.6 International units per liter (IU/L) Standard Deviation 19.40	22.3 International units per liter (IU/L) Standard Deviation 16.61	20.7 International units per liter (IU/L) Standard Deviation 11.38	20.1 International units per liter (IU/L) Standard Deviation 9.84
Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LD), and Gamma Glutamyltransferase (GGT) at Baseline and Week 8 ALP, BL, n=94, 97, 99, 106, 94, 101	82.7 International units per liter (IU/L) Standard Deviation 36.11	79.7 International units per liter (IU/L) Standard Deviation 32.21	83.5 International units per liter (IU/L) Standard Deviation 40.07	90.3 International units per liter (IU/L) Standard Deviation 56.43	94.4 International units per liter (IU/L) Standard Deviation 71.94	84.7 International units per liter (IU/L) Standard Deviation 62.31
Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LD), and Gamma Glutamyltransferase (GGT) at Baseline and Week 8 ALP, W8, n=78, 84, 90, 97, 85, 83	83.0 International units per liter (IU/L) Standard Deviation 40.83	74.8 International units per liter (IU/L) Standard Deviation 27.91	82.9 International units per liter (IU/L) Standard Deviation 41.61	87.0 International units per liter (IU/L) Standard Deviation 49.65	90.8 International units per liter (IU/L) Standard Deviation 76.22	84.0 International units per liter (IU/L) Standard Deviation 59.81
Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LD), and Gamma Glutamyltransferase (GGT) at Baseline and Week 8 ALT, W8, n=78, 84, 90, 97, 86, 83	22.3 International units per liter (IU/L) Standard Deviation 22.79	20.3 International units per liter (IU/L) Standard Deviation 11.92	20.7 International units per liter (IU/L) Standard Deviation 10.39	20.8 International units per liter (IU/L) Standard Deviation 14.01	19.5 International units per liter (IU/L) Standard Deviation 12.03	19.9 International units per liter (IU/L) Standard Deviation 10.04
Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LD), and Gamma Glutamyltransferase (GGT) at Baseline and Week 8 AST, BL, n=94, 96, 99, 105, 93, 101	21.0 International units per liter (IU/L) Standard Deviation 7.64	22.8 International units per liter (IU/L) Standard Deviation 11.39	22.8 International units per liter (IU/L) Standard Deviation 13.35	21.9 International units per liter (IU/L) Standard Deviation 9.68	21.3 International units per liter (IU/L) Standard Deviation 7.20	20.3 International units per liter (IU/L) Standard Deviation 5.10
Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LD), and Gamma Glutamyltransferase (GGT) at Baseline and Week 8 AST, W8, n=78, 83, 90, 97, 86, 82	22.2 International units per liter (IU/L) Standard Deviation 10.76	20.8 International units per liter (IU/L) Standard Deviation 6.48	21.1 International units per liter (IU/L) Standard Deviation 7.52	20.5 International units per liter (IU/L) Standard Deviation 8.07	20.2 International units per liter (IU/L) Standard Deviation 5.91	20.5 International units per liter (IU/L) Standard Deviation 5.38
Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LD), and Gamma Glutamyltransferase (GGT) at Baseline and Week 8 LD, BL, n=94, 96, 99, 105, 93, 101	157.9 International units per liter (IU/L) Standard Deviation 47.78	170.7 International units per liter (IU/L) Standard Deviation 59.82	169.3 International units per liter (IU/L) Standard Deviation 64.08	165.6 International units per liter (IU/L) Standard Deviation 70.56	172.9 International units per liter (IU/L) Standard Deviation 62.38	164.2 International units per liter (IU/L) Standard Deviation 57.04
Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LD), and Gamma Glutamyltransferase (GGT) at Baseline and Week 8 LD, W8, n=78, 83, 90, 97, 86, 82	151.8 International units per liter (IU/L) Standard Deviation 32.37	159.1 International units per liter (IU/L) Standard Deviation 31.46	159.9 International units per liter (IU/L) Standard Deviation 32.14	153.8 International units per liter (IU/L) Standard Deviation 26.90	161.9 International units per liter (IU/L) Standard Deviation 36.79	157.3 International units per liter (IU/L) Standard Deviation 27.36
Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LD), and Gamma Glutamyltransferase (GGT) at Baseline and Week 8 GGT, BL, n=94, 97, 99, 106, 94, 101	27.6 International units per liter (IU/L) Standard Deviation 20.00	33.0 International units per liter (IU/L) Standard Deviation 30.67	33.1 International units per liter (IU/L) Standard Deviation 31.42	30.1 International units per liter (IU/L) Standard Deviation 22.29	29.9 International units per liter (IU/L) Standard Deviation 26.30	28.2 International units per liter (IU/L) Standard Deviation 21.40
Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LD), and Gamma Glutamyltransferase (GGT) at Baseline and Week 8 GGT, W8, n=78, 84, 90, 97, 86, 83	29.7 International units per liter (IU/L) Standard Deviation 27.53	31.1 International units per liter (IU/L) Standard Deviation 24.61	32.4 International units per liter (IU/L) Standard Deviation 30.84	31.9 International units per liter (IU/L) Standard Deviation 24.96	29.3 International units per liter (IU/L) Standard Deviation 32.75	27.9 International units per liter (IU/L) Standard Deviation 21.24

SECONDARY outcome

Timeframe: Baseline and Week 8

Blood samples were collected for the measurement of albumin and total protein at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at Screening (Visit 1).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Clinical Chemistry Parameters of Albumin and Total Protein at Baseline and Week 8 Albumin,BL, n=94, 97, 99, 106, 94, 101	45.2 Grams per liter (g/L) Standard Deviation 3.18	45.6 Grams per liter (g/L) Standard Deviation 3.08	45.1 Grams per liter (g/L) Standard Deviation 2.86	45.9 Grams per liter (g/L) Standard Deviation 3.00	45.3 Grams per liter (g/L) Standard Deviation 2.96	45.2 Grams per liter (g/L) Standard Deviation 3.01
Clinical Chemistry Parameters of Albumin and Total Protein at Baseline and Week 8 Albumin, W8, n= 78, 84, 90, 97, 86, 83	44.9 Grams per liter (g/L) Standard Deviation 3.12	44.8 Grams per liter (g/L) Standard Deviation 3.30	44.9 Grams per liter (g/L) Standard Deviation 2.97	45.6 Grams per liter (g/L) Standard Deviation 2.91	44.5 Grams per liter (g/L) Standard Deviation 3.22	44.9 Grams per liter (g/L) Standard Deviation 2.62
Clinical Chemistry Parameters of Albumin and Total Protein at Baseline and Week 8 Total protein, BL, n=94, 97, 99, 106, 94, 101	73.2 Grams per liter (g/L) Standard Deviation 4.04	74.0 Grams per liter (g/L) Standard Deviation 4.46	73.1 Grams per liter (g/L) Standard Deviation 4.60	74.1 Grams per liter (g/L) Standard Deviation 4.63	73.4 Grams per liter (g/L) Standard Deviation 4.50	73.2 Grams per liter (g/L) Standard Deviation 4.23
Clinical Chemistry Parameters of Albumin and Total Protein at Baseline and Week 8 Total protein, W8, n= 78, 84, 90, 97, 86, 83	71.9 Grams per liter (g/L) Standard Deviation 3.65	72.6 Grams per liter (g/L) Standard Deviation 4.21	72.6 Grams per liter (g/L) Standard Deviation 4.62	73.4 Grams per liter (g/L) Standard Deviation 4.58	72.0 Grams per liter (g/L) Standard Deviation 4.66	72.5 Grams per liter (g/L) Standard Deviation 4.05

SECONDARY outcome

Timeframe: Baseline and Week 8

Blood samples were collected for the measurement of chloride, calcium, CO2/BI, cholesterol, glucose, PI, potassium, sodium, and urea/blood urea nitrogen at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Chloride, BL, n=94, 97, 99, 106, 94, 101	104.4 Millimoles per liter (mmol/L) Standard Deviation 2.25	104.7 Millimoles per liter (mmol/L) Standard Deviation 2.38	104.5 Millimoles per liter (mmol/L) Standard Deviation 2.50	104.4 Millimoles per liter (mmol/L) Standard Deviation 2.41	104.8 Millimoles per liter (mmol/L) Standard Deviation 2.17	104.4 Millimoles per liter (mmol/L) Standard Deviation 2.49
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Chloride, W8, n=78, 84, 90, 97, 86, 83	104.8 Millimoles per liter (mmol/L) Standard Deviation 2.24	104.8 Millimoles per liter (mmol/L) Standard Deviation 2.36	104.7 Millimoles per liter (mmol/L) Standard Deviation 2.55	104.2 Millimoles per liter (mmol/L) Standard Deviation 2.15	104.7 Millimoles per liter (mmol/L) Standard Deviation 2.11	104.6 Millimoles per liter (mmol/L) Standard Deviation 2.67
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Calcium, BL, n=94, 96, 99, 105, 93, 101	2.4 Millimoles per liter (mmol/L) Standard Deviation 0.10	2.4 Millimoles per liter (mmol/L) Standard Deviation 0.10	2.3 Millimoles per liter (mmol/L) Standard Deviation 0.09	2.4 Millimoles per liter (mmol/L) Standard Deviation 0.11	2.4 Millimoles per liter (mmol/L) Standard Deviation 0.13	2.3 Millimoles per liter (mmol/L) Standard Deviation 0.09
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Calcium, W8, n=78, 83, 90, 97, 85, 82	2.4 Millimoles per liter (mmol/L) Standard Deviation 0.10	2.3 Millimoles per liter (mmol/L) Standard Deviation 0.10	2.3 Millimoles per liter (mmol/L) Standard Deviation 0.10	2.4 Millimoles per liter (mmol/L) Standard Deviation 0.10	2.4 Millimoles per liter (mmol/L) Standard Deviation 0.11	2.4 Millimoles per liter (mmol/L) Standard Deviation 0.09
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 CO2/BI, BL, n=94, 96, 99, 105, 93, 101	23.2 Millimoles per liter (mmol/L) Standard Deviation 2.58	22.8 Millimoles per liter (mmol/L) Standard Deviation 2.71	23.0 Millimoles per liter (mmol/L) Standard Deviation 2.31	23.4 Millimoles per liter (mmol/L) Standard Deviation 2.49	23.5 Millimoles per liter (mmol/L) Standard Deviation 2.45	23.5 Millimoles per liter (mmol/L) Standard Deviation 2.74
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 CO2/BI, W8, n=78, 83, 90, 97, 86, 82	23.1 Millimoles per liter (mmol/L) Standard Deviation 2.57	22.8 Millimoles per liter (mmol/L) Standard Deviation 2.62	22.7 Millimoles per liter (mmol/L) Standard Deviation 2.61	23.3 Millimoles per liter (mmol/L) Standard Deviation 2.55	22.7 Millimoles per liter (mmol/L) Standard Deviation 2.42	22.8 Millimoles per liter (mmol/L) Standard Deviation 2.60
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Cholesterol, BL, n=94, 97, 99, 106, 94, 101	4.9 Millimoles per liter (mmol/L) Standard Deviation 1.02	5.0 Millimoles per liter (mmol/L) Standard Deviation 1.04	5.2 Millimoles per liter (mmol/L) Standard Deviation 1.14	5.0 Millimoles per liter (mmol/L) Standard Deviation 0.97	5.0 Millimoles per liter (mmol/L) Standard Deviation 1.08	5.0 Millimoles per liter (mmol/L) Standard Deviation 1.10
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Cholesterol, W8, n=78, 84, 90, 97, 86, 83	5.0 Millimoles per liter (mmol/L) Standard Deviation 1.24	4.9 Millimoles per liter (mmol/L) Standard Deviation 1.05	5.1 Millimoles per liter (mmol/L) Standard Deviation 1.05	5.2 Millimoles per liter (mmol/L) Standard Deviation 1.16	5.0 Millimoles per liter (mmol/L) Standard Deviation 1.03	5.0 Millimoles per liter (mmol/L) Standard Deviation 1.07
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Glucose, BL, n=94, 97, 99, 106, 94, 101	5.2 Millimoles per liter (mmol/L) Standard Deviation 0.99	5.5 Millimoles per liter (mmol/L) Standard Deviation 2.05	5.2 Millimoles per liter (mmol/L) Standard Deviation 1.18	5.1 Millimoles per liter (mmol/L) Standard Deviation 0.89	5.1 Millimoles per liter (mmol/L) Standard Deviation 0.83	5.3 Millimoles per liter (mmol/L) Standard Deviation 1.54
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Glucose, W8, n=78, 84, 90, 97, 86, 83	5.2 Millimoles per liter (mmol/L) Standard Deviation 1.07	5.4 Millimoles per liter (mmol/L) Standard Deviation 1.96	5.2 Millimoles per liter (mmol/L) Standard Deviation 1.20	5.0 Millimoles per liter (mmol/L) Standard Deviation 0.88	5.2 Millimoles per liter (mmol/L) Standard Deviation 1.21	5.1 Millimoles per liter (mmol/L) Standard Deviation 1.18
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 PI, BL, n=94, 97, 99, 106, 94, 101	1.2 Millimoles per liter (mmol/L) Standard Deviation 0.22	1.1 Millimoles per liter (mmol/L) Standard Deviation 0.20	1.2 Millimoles per liter (mmol/L) Standard Deviation 0.17	1.2 Millimoles per liter (mmol/L) Standard Deviation 0.22	1.2 Millimoles per liter (mmol/L) Standard Deviation 0.21	1.2 Millimoles per liter (mmol/L) Standard Deviation 0.18
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 PI, W8, n=78, 84, 90, 97, 86, 83	1.3 Millimoles per liter (mmol/L) Standard Deviation 0.21	1.2 Millimoles per liter (mmol/L) Standard Deviation 0.17	1.2 Millimoles per liter (mmol/L) Standard Deviation 0.18	1.3 Millimoles per liter (mmol/L) Standard Deviation 0.20	1.2 Millimoles per liter (mmol/L) Standard Deviation 0.21	1.2 Millimoles per liter (mmol/L) Standard Deviation 0.20
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Potassium, BL, n=94, 96, 99, 105, 93, 101	4.1 Millimoles per liter (mmol/L) Standard Deviation 0.39	4.2 Millimoles per liter (mmol/L) Standard Deviation 0.44	4.1 Millimoles per liter (mmol/L) Standard Deviation 0.38	4.2 Millimoles per liter (mmol/L) Standard Deviation 0.40	4.2 Millimoles per liter (mmol/L) Standard Deviation 0.45	4.2 Millimoles per liter (mmol/L) Standard Deviation 0.40
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Potassium, W8, n=78, 83, 90, 97, 85, 82	4.2 Millimoles per liter (mmol/L) Standard Deviation 0.34	4.2 Millimoles per liter (mmol/L) Standard Deviation 0.41	4.2 Millimoles per liter (mmol/L) Standard Deviation 0.32	4.2 Millimoles per liter (mmol/L) Standard Deviation 0.38	4.2 Millimoles per liter (mmol/L) Standard Deviation 0.38	4.2 Millimoles per liter (mmol/L) Standard Deviation 0.36
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Sodium, BL, n=94, 97, 99, 106, 94, 101	140.8 Millimoles per liter (mmol/L) Standard Deviation 1.82	140.5 Millimoles per liter (mmol/L) Standard Deviation 2.05	140.6 Millimoles per liter (mmol/L) Standard Deviation 1.92	140.8 Millimoles per liter (mmol/L) Standard Deviation 2.16	141.1 Millimoles per liter (mmol/L) Standard Deviation 1.91	140.8 Millimoles per liter (mmol/L) Standard Deviation 2.04
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 Sodium, W8, n=78, 84, 90, 97, 86, 83	140.7 Millimoles per liter (mmol/L) Standard Deviation 2.09	140.5 Millimoles per liter (mmol/L) Standard Deviation 2.01	140.7 Millimoles per liter (mmol/L) Standard Deviation 2.02	140.6 Millimoles per liter (mmol/L) Standard Deviation 1.63	140.9 Millimoles per liter (mmol/L) Standard Deviation 2.36	140.8 Millimoles per liter (mmol/L) Standard Deviation 1.97
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 BUN, BL, n=94, 97, 99, 106, 94, 101	5.4 Millimoles per liter (mmol/L) Standard Deviation 1.75	5.3 Millimoles per liter (mmol/L) Standard Deviation 1.66	5.3 Millimoles per liter (mmol/L) Standard Deviation 1.92	5.7 Millimoles per liter (mmol/L) Standard Deviation 1.94	5.7 Millimoles per liter (mmol/L) Standard Deviation 2.09	5.4 Millimoles per liter (mmol/L) Standard Deviation 1.72
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8 BUN, W8, n=78, 84, 90, 97, 86, 83	5.5 Millimoles per liter (mmol/L) Standard Deviation 1.68	5.2 Millimoles per liter (mmol/L) Standard Deviation 1.97	5.0 Millimoles per liter (mmol/L) Standard Deviation 1.30	5.5 Millimoles per liter (mmol/L) Standard Deviation 1.44	5.2 Millimoles per liter (mmol/L) Standard Deviation 1.54	5.0 Millimoles per liter (mmol/L) Standard Deviation 1.43

SECONDARY outcome

Timeframe: Baseline and Week 8

Blood samples were collected for the measurement of creatinine, direct bilirubin (DBIL), total bilirubin (TBIL), and uric acid at Baseline and Week 8. The Baseline value was the measurement taken at screening (Visit 1).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Clinical Chemistry Parameters of Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid at Baseline and Week 8 DBIL, BL, n=94, 97, 99, 106, 94, 101	2.1 Micromoles per liter (µmol/L) Standard Deviation 1.26	2.1 Micromoles per liter (µmol/L) Standard Deviation 1.29	2.0 Micromoles per liter (µmol/L) Standard Deviation 1.04	2.0 Micromoles per liter (µmol/L) Standard Deviation 1.13	1.8 Micromoles per liter (µmol/L) Standard Deviation 1.17	2.0 Micromoles per liter (µmol/L) Standard Deviation 1.04
Clinical Chemistry Parameters of Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid at Baseline and Week 8 DBIL, W8, n=77, 84, 89, 97, 86, 83	2.0 Micromoles per liter (µmol/L) Standard Deviation 1.03	2.0 Micromoles per liter (µmol/L) Standard Deviation 0.94	1.9 Micromoles per liter (µmol/L) Standard Deviation 0.98	1.9 Micromoles per liter (µmol/L) Standard Deviation 1.02	1.7 Micromoles per liter (µmol/L) Standard Deviation 0.93	1.9 Micromoles per liter (µmol/L) Standard Deviation 1.05
Clinical Chemistry Parameters of Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid at Baseline and Week 8 TBIL, BL, n=94, 97, 99, 106, 94, 101	9.6 Micromoles per liter (µmol/L) Standard Deviation 6.10	9.7 Micromoles per liter (µmol/L) Standard Deviation 6.08	9.0 Micromoles per liter (µmol/L) Standard Deviation 4.39	9.3 Micromoles per liter (µmol/L) Standard Deviation 4.35	8.7 Micromoles per liter (µmol/L) Standard Deviation 4.11	9.0 Micromoles per liter (µmol/L) Standard Deviation 3.93
Clinical Chemistry Parameters of Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid at Baseline and Week 8 TBIL, W8, n=78, 84, 90, 97, 86, 83	10.3 Micromoles per liter (µmol/L) Standard Deviation 5.57	9.1 Micromoles per liter (µmol/L) Standard Deviation 4.14	8.7 Micromoles per liter (µmol/L) Standard Deviation 3.99	9.1 Micromoles per liter (µmol/L) Standard Deviation 3.88	8.5 Micromoles per liter (µmol/L) Standard Deviation 3.46	9.4 Micromoles per liter (µmol/L) Standard Deviation 4.39
Clinical Chemistry Parameters of Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid at Baseline and Week 8 Uric acid, BL, n=94, 97, 99, 105, 94, 101	337.8 Micromoles per liter (µmol/L) Standard Deviation 88.15	327.2 Micromoles per liter (µmol/L) Standard Deviation 85.64	325.6 Micromoles per liter (µmol/L) Standard Deviation 85.82	334.1 Micromoles per liter (µmol/L) Standard Deviation 90.63	326.6 Micromoles per liter (µmol/L) Standard Deviation 85.37	324.5 Micromoles per liter (µmol/L) Standard Deviation 78.64
Clinical Chemistry Parameters of Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid at Baseline and Week 8 Uric acid, W8, n=78, 84, 90, 96, 86, 83	353.6 Micromoles per liter (µmol/L) Standard Deviation 86.64	327.5 Micromoles per liter (µmol/L) Standard Deviation 84.69	321.9 Micromoles per liter (µmol/L) Standard Deviation 91.90	340.9 Micromoles per liter (µmol/L) Standard Deviation 89.48	316.5 Micromoles per liter (µmol/L) Standard Deviation 81.29	325.4 Micromoles per liter (µmol/L) Standard Deviation 80.48
Clinical Chemistry Parameters of Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid at Baseline and Week 8 Creatinine, BL, n=94, 97, 99, 106, 94, 101	83.2 Micromoles per liter (µmol/L) Standard Deviation 19.89	79.8 Micromoles per liter (µmol/L) Standard Deviation 14.72	77.7 Micromoles per liter (µmol/L) Standard Deviation 14.52	81.9 Micromoles per liter (µmol/L) Standard Deviation 16.68	78.3 Micromoles per liter (µmol/L) Standard Deviation 15.21	79.3 Micromoles per liter (µmol/L) Standard Deviation 15.08
Clinical Chemistry Parameters of Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid at Baseline and Week 8 Creatinine, W8, n=78, 84, 90, 97, 86, 83	84.5 Micromoles per liter (µmol/L) Standard Deviation 19.21	79.7 Micromoles per liter (µmol/L) Standard Deviation 15.67	79.0 Micromoles per liter (µmol/L) Standard Deviation 13.45	81.7 Micromoles per liter (µmol/L) Standard Deviation 14.90	77.7 Micromoles per liter (µmol/L) Standard Deviation 14.32	80.4 Micromoles per liter (µmol/L) Standard Deviation 15.97

SECONDARY outcome

Timeframe: Baseline and Week 8/Early Withdrawal

Urinalysis parameters included: Urine Occult Blood (UOB), Urine Glucose (UG), Urine Ketones (UK), Urine Protein (UP), and Urine Leukocyte Esterase test for detecting White Blood Cell (UWBC). The dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as large, moderate (Mod), negative (Neg), small, Trace, 1+, 2+, 3+ and 4+, and for UG the result can be read as Neg, Trace, Trace or 1/10 G/dL, 1+ or 1/4 G/dL, 3+ or 1 G/dL, indicating proportional concentrations in the urine sample. Data are reported as the number of participants who had neg, Trace, 1+, 2+, 3+ and 4+ levels at Baseline (BL) and Week 8 (W8)/Early Withdrawal (EW). The Baseline value was the measurement taken at screening (Visit 1).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, 1+, W8, n=71, 81, 82, 93, 82, 77	1 participants	3 participants	2 participants	3 participants	7 participants	4 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, Neg, W8, n=71, 81, 82, 93, 82, 77	62 participants	71 participants	73 participants	83 participants	69 participants	66 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, 1+, BL, n=92, 94, 95, 106, 93, 96	2 participants	1 participants	3 participants	4 participants	3 participants	2 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, 2+, BL, n=92, 94, 95, 106, 93, 96	3 participants	1 participants	2 participants	0 participants	1 participants	1 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, 3+, BL, n=92, 94, 95, 106, 93, 96	2 participants	0 participants	0 participants	2 participants	2 participants	2 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, 4+, BL, n=92, 94, 95, 106, 93, 96	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, Mod, BL, n=92, 94, 95, 106, 93, 96	1 participants	0 participants	0 participants	0 participants	0 participants	1 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, Neg, BL, n=92, 94, 95, 106, 93, 96	79 participants	91 participants	83 participants	97 participants	81 participants	82 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, Small, BL, n=92, 94, 95, 106, 93, 96	0 participants	0 participants	3 participants	0 participants	1 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, Trace, BL, n=92, 94, 95, 106, 93, 96	5 participants	1 participants	4 participants	2 participants	5 participants	8 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, 1+, W8, n=71, 81, 82, 93, 82, 77	1 participants	1 participants	1 participants	0 participants	4 participants	3 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, 2+, W8, n=71, 81, 82, 93, 82, 77	4 participants	2 participants	2 participants	2 participants	2 participants	3 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, 3+, W8, n=71, 81, 82, 93, 82, 77	0 participants	3 participants	0 participants	0 participants	0 participants	1 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, Large, W8, n=71, 81, 82, 93, 82, 77	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, Mod, W8, n=71, 81, 82, 93, 82, 77	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, Trace, W8, n=71, 81, 82, 93, 82, 77	4 participants	4 participants	6 participants	8 participants	5 participants	4 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UOB, Neg, EW, n=2, 1, 2, 3, 1, 7	2 participants	1 participants	2 participants	3 participants	1 participants	7 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, 1+ or 1/4 G/DL, BL, n=92, 94, 95, 106, 93, 96	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, 3+ or 1 G/DL, BL, n=92, 94, 95, 106, 93, 96	0 participants	2 participants	1 participants	0 participants	0 participants	1 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, 4+ or 2 or more G/DL, n=92, 94, 95, 106, 93,96	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, Neg, BL, n=92, 94, 95, 106, 93, 96	90 participants	91 participants	94 participants	105 participants	91 participants	94 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, Trace, BL, n=92, 94, 95, 106, 93, 96	1 participants	0 participants	0 participants	1 participants	1 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, Trace or 1/10 G/DL, BL, n=92, 94, 95,106,93,96	1 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, 1+ or 1/4 G/DL, W8, n=71, 81, 82, 93, 82, 77	0 participants	1 participants	1 participants	0 participants	0 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, 3+ or 1 G/DL, W8, n=71, 81, 82, 93, 82, 77	0 participants	3 participants	1 participants	0 participants	0 participants	1 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, Neg, W8, n=71, 81, 82, 93, 82, 77	71 participants	77 participants	80 participants	92 participants	78 participants	76 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, Trace, W8, n=71, 81, 82, 93, 82, 77	0 participants	0 participants	0 participants	0 participants	2 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, Trace or 1/10 G/DL, W8, n=71, 81, 82, 93,82,77	0 participants	0 participants	0 participants	1 participants	2 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UG, Neg, EW, n=2, 1, 2, 3, 1, 7	2 participants	1 participants	2 participants	3 participants	1 participants	7 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UK, 1+, BL, n=92, 94, 95, 106, 93, 96	0 participants	0 participants	1 participants	1 participants	1 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UK, 2+, BL, n=92, 94, 95, 106, 93, 96	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UK, Neg, BL, n=92, 94, 95, 106, 93, 96	91 participants	89 participants	92 participants	104 participants	90 participants	95 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UK, Trace, BL, n=92, 94, 95, 106, 93, 96	1 participants	5 participants	2 participants	1 participants	1 participants	1 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UK, 2+, W8, n=71, 81, 82, 93, 82, 77	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UK, Neg, W8, n=71, 81, 82, 93, 82, 77	67 participants	77 participants	78 participants	91 participants	79 participants	69 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UK, Trace, W8, n=71, 81, 82, 93, 82, 77	4 participants	4 participants	4 participants	1 participants	3 participants	8 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UK, Neg, EW, n=2, 1, 2, 3, 1, 7	2 participants	1 participants	2 participants	3 participants	1 participants	7 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, 1+, BL, n=92, 94, 95, 106, 93, 96	7 participants	7 participants	6 participants	8 participants	5 participants	4 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, 2+, BL, n=92, 94, 95, 106, 93, 96	0 participants	0 participants	2 participants	1 participants	1 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, 3+, BL, n=92, 94, 95, 106, 93, 96	1 participants	1 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, Neg, BL, n=92, 94, 95, 106, 93, 96	70 participants	76 participants	80 participants	89 participants	80 participants	78 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, Trace, BL, n=92, 94, 95, 106, 93, 96	14 participants	10 participants	7 participants	8 participants	7 participants	14 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, 1+, W8, n=71, 81, 82, 93, 82, 77	3 participants	2 participants	5 participants	1 participants	4 participants	2 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, 2+, W8, n=71, 81, 82, 93, 82, 77	2 participants	1 participants	0 participants	1 participants	1 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, 3+, W8, n=71, 81, 82, 93, 82, 77	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, Neg, W8,n=71, 81, 82, 93, 82, 77	60 participants	70 participants	68 participants	78 participants	64 participants	71 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, Trace, W8, n=71, 81, 82, 93, 82, 77	6 participants	8 participants	9 participants	13 participants	12 participants	4 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, Neg, EW, n=2, 1, 2, 3, 1, 7, 1, 7	2 participants	1 participants	2 participants	3 participants	1 participants	5 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UP, Trace, EW, n=2, 1, 2, 3, 1, 7	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, 1+, BL, n=92, 94, 95, 106, 93, 96	1 participants	1 participants	6 participants	1 participants	6 participants	3 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, 2+, BL, n=92, 94, 95, 106, 93, 96	1 participants	3 participants	1 participants	7 participants	2 participants	3 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, 3+, BL, n=92, 94, 95, 106, 93, 96	0 participants	3 participants	2 participants	2 participants	1 participants	2 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, Mod, BL, n=92, 94, 95, 106, 93, 96	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, Neg, W8, n=71, 81, 82, 93, 82, 77	66 participants	71 participants	69 participants	81 participants	67 participants	67 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, Neg, BL, n=92, 94, 95, 106, 93, 96	88 participants	84 participants	82 participants	92 participants	81 participants	85 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, Trace, BL, n=92, 94, 95, , 93, 96	2 participants	3 participants	4 participants	4 participants	2 participants	3 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, 2+, W8, n=71, 81, 82, 93, 82, 77	1 participants	1 participants	4 participants	3 participants	2 participants	3 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, 3+, W8, n=71, 81, 82, 93, 82, 77	0 participants	0 participants	2 participants	1 participants	0 participants	1 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, Small, W8, n=71, 81, 82, 93, 82, 77	1 participants	0 participants	1 participants	0 participants	0 participants	0 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, Trace, W8, n=71, 81, 82, 93, 82, 77	2 participants	6 participants	4 participants	5 participants	6 participants	2 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, 2+, EW, n=2, 1, 2, 3, 1, 7	0 participants	1 participants	0 participants	0 participants	0 participants	1 participants
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal UWBC, Neg, EW, n=2, 1, 2, 3, 1, 7	2 participants	0 participants	2 participants	3 participants	1 participants	6 participants

SECONDARY outcome

Timeframe: Baseline and Week 8/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Urine samples were collected for the measurement of urine specific gravity by dipstick method at Baseline and at Week 8/Early Withdrawal. The Baseline value was the measurement taken at screening (Visit 1). Specific gravity is a measure of the amount of material dissolved in the urine. Specific gravity is the ratio of the density (mass of a unit volume) of a substance to the density (mass of the same unit volume) of a reference substance. Normal urine has a specific gravity between 1.010 and 1.020.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Urine Specific Gravity at Baseline and Week 8/Early Withdrawal Baseline, n=92, 94, 95, 106, 93, 96	1.0230 ratio Standard Deviation 0.00707	1.0240 ratio Standard Deviation 0.00690	1.0236 ratio Standard Deviation 0.00682	1.0230 ratio Standard Deviation 0.00687	1.0242 ratio Standard Deviation 0.00620	1.0227 ratio Standard Deviation 0.00760
Urine Specific Gravity at Baseline and Week 8/Early Withdrawal Week 8, n=71, 81, 82, 93, 82, 77	1.0238 ratio Standard Deviation 0.00731	1.0227 ratio Standard Deviation 0.00735	1.0230 ratio Standard Deviation 0.00714	1.0223 ratio Standard Deviation 0.00738	1.0235 ratio Standard Deviation 0.00727	1.0217 ratio Standard Deviation 0.00751
Urine Specific Gravity at Baseline and Week 8/Early Withdrawal EW, n=2, 1, 2, 3, 1, 7	1.0265 ratio Standard Deviation 0.00071	1.0121 ratio Standard Deviation 0	1.0200 ratio Standard Deviation 0.00141	1.0233 ratio Standard Deviation 0.00987	1.0190 ratio Standard Deviation 0	1.0240 ratio Standard Deviation 0.00653

SECONDARY outcome

Timeframe: Baseline and Week 8/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Urine samples were collected for the measurement of urine pH by dipstick method at Baseline and at Week 8/Early Withdrawal. The Baseline value was the measurement taken at screening (Visit 1). Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Urine pH at Baseline and Week 8/Early Withdrawal Baseline, n=92, 94, 95, 106, 93, 96	6.04 scores on a scale Standard Deviation 0.487	6.05 scores on a scale Standard Deviation 0.418	6.06 scores on a scale Standard Deviation 0.455	6.13 scores on a scale Standard Deviation 0.488	6.05 scores on a scale Standard Deviation 0.489	6.08 scores on a scale Standard Deviation 0.415
Urine pH at Baseline and Week 8/Early Withdrawal Week 8, n=71, 81, 82, 93, 82, 77	6.03 scores on a scale Standard Deviation 0.422	6.01 scores on a scale Standard Deviation 0.418	6.12 scores on a scale Standard Deviation 0.462	6.06 scores on a scale Standard Deviation 0.435	6.06 scores on a scale Standard Deviation 0.523	5.96 scores on a scale Standard Deviation 0.342
Urine pH at Baseline and Week 8/Early Withdrawal EW, n=2, 1, 2, 3, 1, 7	6.00 scores on a scale Standard Deviation 0.707	6.00 scores on a scale Standard Deviation 0	5.75 scores on a scale Standard Deviation 0.354	6.83 scores on a scale Standard Deviation 0.289	7.50 scores on a scale Standard Deviation 0	5.86 scores on a scale Standard Deviation 0.556

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Urine Cortisol (UC) Population: all participants whose urine samples did not have confounding factors that could affect the interpretation of results.

A 24-hour urine sample was collected for the measurement of 24 hr urinary cortisol excretion at the following scheduled time points: within 7 days prior to Study Visits 3 (Week 0) and Visit 8 (Week 8). The Baseline value for 24 hr urinary cortisol was taken from Visit 3.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=72 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=72 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=76 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=69 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=70 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
24-hour Urinary Cortisol Excretion at Baseline and Week 8 Week 8	79.25 Nanomoles per 24 hours (nmol/24 hours) Interval 7.5 to 275.0	76.74 Nanomoles per 24 hours (nmol/24 hours) Interval 5.2 to 306.6	79.15 Nanomoles per 24 hours (nmol/24 hours) Interval 13.9 to 680.9	81.0 Nanomoles per 24 hours (nmol/24 hours) Interval 10.6 to 506.6	62.10 Nanomoles per 24 hours (nmol/24 hours) Interval 8.0 to 366.7	82.14 Nanomoles per 24 hours (nmol/24 hours) Interval 4.7 to 231.0
24-hour Urinary Cortisol Excretion at Baseline and Week 8 Baseline	70.20 Nanomoles per 24 hours (nmol/24 hours) Interval 10.1 to 382.7	74.45 Nanomoles per 24 hours (nmol/24 hours) Interval 6.1 to 645.2	65.80 Nanomoles per 24 hours (nmol/24 hours) Interval 5.9 to 341.1	65.56 Nanomoles per 24 hours (nmol/24 hours) Interval 8.8 to 457.3	66.80 Nanomoles per 24 hours (nmol/24 hours) Interval 4.6 to 396.2	66.20 Nanomoles per 24 hours (nmol/24 hours) Interval 6.4 to 338.6

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Change from Baseline was calculated as the Week 8 value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=78 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=85 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=91 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=98 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=86 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=84 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 8 DBP	-1.1 Millimeters of mercury (mmHg) Standard Deviation 8.16	0.3 Millimeters of mercury (mmHg) Standard Deviation 7.65	0.2 Millimeters of mercury (mmHg) Standard Deviation 7.50	-0.3 Millimeters of mercury (mmHg) Standard Deviation 8.41	0.1 Millimeters of mercury (mmHg) Standard Deviation 8.50	-0.2 Millimeters of mercury (mmHg) Standard Deviation 8.55
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 8 SBP	-2.5 Millimeters of mercury (mmHg) Standard Deviation 9.29	1.5 Millimeters of mercury (mmHg) Standard Deviation 10.54	0.9 Millimeters of mercury (mmHg) Standard Deviation 10.35	-0.4 Millimeters of mercury (mmHg) Standard Deviation 10.46	1.4 Millimeters of mercury (mmHg) Standard Deviation 9.53	0.2 Millimeters of mercury (mmHg) Standard Deviation 10.64

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Change from Baseline was calculated as the Week 8 value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=78 Participants Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=85 Participants Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=91 Participants Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=98 Participants Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=86 Participants Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=84 Participants Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Change From Baseline in Heart Rate at Week 8	2.9 Beats per minute Standard Deviation 9.23	0.4 Beats per minute Standard Deviation 8.26	1.5 Beats per minute Standard Deviation 8.35	0.8 Beats per minute Standard Deviation 8.12	-2.3 Beats per minute Standard Deviation 8.32	0.8 Beats per minute Standard Deviation 9.14

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

GW685698X 25 µg OD

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

GW685698X 50 µg OD

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

GW685698X 100 µg OD

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

GW685698X 200 µg OD

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

FP 100 µg BID

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=94 participants at risk Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 participants at risk Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 participants at risk Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 participants at risk Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 participants at risk Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 participants at risk Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
General disorders Chest pain	0.00% 0/94 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/97 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/110 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/95 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.98% 1/102 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Injury, poisoning and procedural complications Snake bite	0.00% 0/94 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	1.0% 1/97 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/110 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/95 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/102 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Psychiatric disorders Depression	0.00% 0/94 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/97 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.91% 1/110 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/95 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/102 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Gastrointestinal disorders Gastritis	0.00% 0/94 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/97 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/110 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/95 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.98% 1/102 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/94 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/97 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/110 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/95 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.98% 1/102 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Vascular disorders Hypertension	0.00% 0/94 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/97 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/110 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/95 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.98% 1/102 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.

Other adverse events

Other adverse events
Measure	Placebo n=94 participants at risk Participants received placebo OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.	GW685698X 25 µg OD n=97 participants at risk Participants received GW685698X 25 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 50 µg OD n=100 participants at risk Participants received GW685698X 50 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 100 µg OD n=110 participants at risk Participants received GW685698X 100 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	GW685698X 200 µg OD n=95 participants at risk Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	FP 100 µg BID n=102 participants at risk Participants received FP 100 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Nervous system disorders Headache	10.6% 10/94 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	6.2% 6/97 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	6.0% 6/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	10.9% 12/110 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	5.3% 5/95 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	11.8% 12/102 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Respiratory, thoracic and mediastinal disorders Oropharyngitis	1.1% 1/94 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/97 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	1.0% 1/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	3.6% 4/110 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	3.2% 3/95 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	2.0% 2/102 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Infections and infestations Nasopharyngitis	1.1% 1/94 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/97 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	3.6% 4/110 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	3.2% 3/95 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	2.0% 2/102 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/94 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/97 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	3.0% 3/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/110 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	1.1% 1/95 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.98% 1/102 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.

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