Trial Outcomes & Findings for A Study To Assess Efficacy And Safety Of Different Doses Of GW642444 In Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00606684)

Last Updated: 2016-12-16

Results Overview

Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcibly exhaled from the lungs in one second. Baseline FEV1 is defined as the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1. If one of these two assessments was missing then Baseline is defined as the single pre-dose FEV1 value at Day 1. The trough FEV1 is defined as the mean of the FEV1 values obtained at 23 and 24-hours after dosing on Day 28 and the Baseline FEV1 is defined as the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1. Change from Baseline in trough FEV1 was calculated as the value on Day 29 minus the value at Baseline. Analysis was performed using Analysis of Covariance (ANCOVA) using Last Observation Carried Forward (LOCF) with covariates of baseline, sex, age, smoking status (at screening), reversibility stratum, and treatment (trt).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

602 participants

Primary outcome timeframe

Baseline (BL) and Day 29

Results posted on

2016-12-16

Participant Flow

At Visit (V) 1, eligible participants (par.) entered a 2-week, single-blind placebo Run-in Period (RIP) to establish a stable Baseline. At V 2, eligible par. were randomized to a 28 day, double-blind Treatment Period. 1206 par. were screened, 851 par. entered the RIP and 605 par. were randomized, out of which 602 par. received \>=1 treatment dose.

Participant milestones

Participant milestones
Measure	Placebo Run-in Participants received placebo once daily (OD) in the morning from the novel dual strip dry powder inhaler. In addition, all participants were provided supplemental albuterol (salbutamol) (metered dose inhaler \[MDI\] and/or nebules) to be used asneeded throughout the study.	Placebo Participants received placebo (1 actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 3 µg Participants received GW642444M 3 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 6.25 µg Participants received GW642444M 6.25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 12.5 µg Participants received GW642444M 12.5 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 25 µg Participants received GW642444M 25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 50 µg Participants received GW642444M 50 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.
2-week Single-Blind Run-in Period STARTED	851	0	0	0	0	0	0
2-week Single-Blind Run-in Period COMPLETED	605	0	0	0	0	0	0
2-week Single-Blind Run-in Period NOT COMPLETED	246	0	0	0	0	0	0
Double-Blind Treatment Period STARTED	0	101	99	101	101	101	99
Double-Blind Treatment Period COMPLETED	0	85	88	91	92	92	91
Double-Blind Treatment Period NOT COMPLETED	0	16	11	10	9	9	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Run-in Participants received placebo once daily (OD) in the morning from the novel dual strip dry powder inhaler. In addition, all participants were provided supplemental albuterol (salbutamol) (metered dose inhaler \[MDI\] and/or nebules) to be used asneeded throughout the study.	Placebo Participants received placebo (1 actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 3 µg Participants received GW642444M 3 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 6.25 µg Participants received GW642444M 6.25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 12.5 µg Participants received GW642444M 12.5 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 25 µg Participants received GW642444M 25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 50 µg Participants received GW642444M 50 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.
2-week Single-Blind Run-in Period Did Not Meet Continuation Criteria	173	0	0	0	0	0	0
2-week Single-Blind Run-in Period Study Closed/Terminated	32	0	0	0	0	0	0
2-week Single-Blind Run-in Period Physician Decision	18	0	0	0	0	0	0
2-week Single-Blind Run-in Period Withdrawal by Subject	15	0	0	0	0	0	0
2-week Single-Blind Run-in Period Lost to Follow-up	5	0	0	0	0	0	0
2-week Single-Blind Run-in Period Adverse Event	2	0	0	0	0	0	0
2-week Single-Blind Run-in Period Received Study Medication in Error	1	0	0	0	0	0	0
Double-Blind Treatment Period Adverse Event	0	3	2	4	2	0	1
Double-Blind Treatment Period Lack of Efficacy	0	1	0	0	1	0	0
Double-Blind Treatment Period Protocol Violation	0	5	5	3	0	3	4
Double-Blind Treatment Period Met Protocol Defined Stopping Criteria	0	1	2	1	2	3	1
Double-Blind Treatment Period Physician Decision	0	5	1	0	3	1	2
Double-Blind Treatment Period Withdrawal by Subject	0	1	1	2	1	2	0

Baseline Characteristics

A Study To Assess Efficacy And Safety Of Different Doses Of GW642444 In Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=101 Participants Participants received placebo (1 actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 3 µg OD n=99 Participants Participants received GW642444M 3 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 6.25 µg OD n=101 Participants Participants received GW642444M 6.25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 12.5 µg OD n=101 Participants Participants received GW642444M 12.5 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 25 µg OD n=101 Participants Participants received GW642444M 25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 50 µg OD n=99 Participants Participants received GW642444M 50 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	Total n=602 Participants Total of all reporting groups
Age, Continuous	61.6 Years STANDARD_DEVIATION 8.53 • n=5 Participants	61.1 Years STANDARD_DEVIATION 8.57 • n=7 Participants	62.0 Years STANDARD_DEVIATION 7.94 • n=5 Participants	62.6 Years STANDARD_DEVIATION 8.03 • n=4 Participants	62.6 Years STANDARD_DEVIATION 8.88 • n=21 Participants	61.4 Years STANDARD_DEVIATION 8.12 • n=10 Participants	61.9 Years STANDARD_DEVIATION 8.34 • n=115 Participants
Gender Female	44 Participants n=5 Participants	31 Participants n=7 Participants	37 Participants n=5 Participants	44 Participants n=4 Participants	42 Participants n=21 Participants	34 Participants n=10 Participants	232 Participants n=115 Participants
Gender Male	57 Participants n=5 Participants	68 Participants n=7 Participants	64 Participants n=5 Participants	57 Participants n=4 Participants	59 Participants n=21 Participants	65 Participants n=10 Participants	370 Participants n=115 Participants
Race/Ethnicity, Customized African American/African Heritage (HER)	3 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants	3 Participants n=10 Participants	16 Participants n=115 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	2 Participants n=21 Participants	3 Participants n=10 Participants	11 Participants n=115 Participants
Race/Ethnicity, Customized Central/South Asian HER	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Race/Ethnicity, Customized Japanese/East Asian HER/South East Asian HER	7 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants	8 Participants n=4 Participants	10 Participants n=21 Participants	6 Participants n=10 Participants	55 Participants n=115 Participants
Race/Ethnicity, Customized White	90 Participants n=5 Participants	84 Participants n=7 Participants	84 Participants n=5 Participants	86 Participants n=4 Participants	84 Participants n=21 Participants	87 Participants n=10 Participants	515 Participants n=115 Participants
Race/Ethnicity, Customized American Indian or Alaska Native & White	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	4 Participants n=115 Participants

PRIMARY outcome

Timeframe: Baseline (BL) and Day 29

Population: Intent-to-Treat (ITT) Population: all participants who were randomized to trt and received \>= 1 dose of study medication. When the endpoint was missing, the last valid non-missing on-trt, post-BL trough assessment was used instead. Only those participants available at the specified time points without missing covariate information were analyzed.

Outcome measures

Outcome measures
Measure	GW642444M 3 µg OD n=99 Participants Participants received GW642444M 3 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 6.25 µg OD n=100 Participants Participants received GW642444M 6.25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 12.5 µg OD n=99 Participants Participants received GW642444M 12.5 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 25 µg OD n=99 Participants Participants received GW642444M 25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 50 µg OD n=99 Participants Participants received GW642444M 50 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	Placebo n=101 Participants Participants received placebo (1 actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.
Mean Change From Baseline in Trough (Pre Bronchodilator and Pre Dose) FEV1 on Day 29	0.120 Liters Standard Error 0.0190	0.127 Liters Standard Error 0.0188	0.138 Liters Standard Error 0.0190	0.166 Liters Standard Error 0.0190	0.194 Liters Standard Error 0.0190	0.029 Liters Standard Error 0.0188

SECONDARY outcome

Timeframe: Baseline to Day 28

Population: ITT Population. The number of participants presented represents those with data available at either of time points being presented. The numbers given in the category titles represent the number of participants with data available at the time point given.

Weighted mean was derived by calculating the AUC, and then dividing by the relevant time interval. The weighted mean change from Baseline was calculated as the weighted mean of the 24 hour serial FEV1 measures on Day 1 and Day 28 minus the Baseline value. Serial FEV1 measurements were taken on Day 1 and Day 28 (post-dose FEV1 after 5, 15, 30 minutes and 1, 2, 4, 8, 12, 23 and 24 hours). AUC was calculated only when there was at least 3 non-missing values between 0 and 24 hours and must have a value at 23 or 24 hours. Analysis performed used a repeated measures model with covariates of treatment, baseline, sex, age, smoking status (at Screening), reversibility stratum, Day (nominal), day by Baseline, and day by treatment interactions.

Outcome measures

Outcome measures
Measure	GW642444M 3 µg OD n=99 Participants Participants received GW642444M 3 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 6.25 µg OD n=100 Participants Participants received GW642444M 6.25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 12.5 µg OD n=99 Participants Participants received GW642444M 12.5 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 25 µg OD n=99 Participants Participants received GW642444M 25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 50 µg OD n=99 Participants Participants received GW642444M 50 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	Placebo n=101 Participants Participants received placebo (1 actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.
Time-adjusted Area Under the Curve (AUC) (i.e. Weighted Mean Change From Baseline) for 24 Hour Serial FEV1 on Days 1 and 28 Day 28, n=84, 88, 91, 92	0.114 Liters Standard Error 0.0187	0.135 Liters Standard Error 0.0185	0.152 Liters Standard Error 0.0185	0.168 Liters Standard Error 0.0185	0.186 Liters Standard Error 0.0186	0.010 Liters Standard Error 0.0189
Time-adjusted Area Under the Curve (AUC) (i.e. Weighted Mean Change From Baseline) for 24 Hour Serial FEV1 on Days 1 and 28 Day 1, n=100, 97, 100, 99	0.085 Liters Standard Error 0.0137	0.132 Liters Standard Error 0.0135	0.149 Liters Standard Error 0.0136	0.178 Liters Standard Error 0.0136	0.202 Liters Standard Error 0.0137	0.028 Liters Standard Error 0.0135

SECONDARY outcome

Timeframe: Baseline and Day 1

Population: ITT Population. Only participants available at the indicated time points were assessed.

Forced expiratory volume in one second (FEV1) is a measure of lung function defined as the maximal amount of air that can be forcibly exhaled from the lungs in one second. Time until participants achieved a \>=12% increase from Baseline FEV1 (0-4 hours post-dose) are presented. Baseline FEV1 is defined as the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1. If one of these two assessments was missing then Baseline is defined as the single pre-dose FEV1 on Day 1.Time to \>= 12% increase from Baseline (on Day 1) is defined as the time when the first post-dose FEV1 (on Day 1) is \>=12% above Baseline FEV1. Time to \>= 12% increase from Baseline was assessed over the 0-4 hour time period and only used lung function data recorded up to 6 hours post the Day 1 dose.

Outcome measures

Outcome measures
Measure	GW642444M 3 µg OD n=99 Participants Participants received GW642444M 3 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 6.25 µg OD n=101 Participants Participants received GW642444M 6.25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 12.5 µg OD n=100 Participants Participants received GW642444M 12.5 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 25 µg OD n=100 Participants Participants received GW642444M 25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 50 µg OD n=99 Participants Participants received GW642444M 50 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	Placebo n=101 Participants Participants received placebo (1 actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.
Time to >= 12% Increase From Baseline in FEV1 (0-4 Hours Post-dose)	120 Minutes Interval 5.0 to 240.0	30 Minutes Interval 5.0 to 240.0	30 Minutes Interval 5.0 to 240.0	18 Minutes Interval 5.0 to 240.0	16 Minutes Interval 5.0 to 240.0	NA Minutes Interval 5.0 to 240.0 \> 50% of subjects were censored; therefore, the median could not be calculated.

SECONDARY outcome

Timeframe: Baseline and Day 1

Population: ITT Population. Only participants available at the indicated time points were assessed.

Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcibly exhaled from the lungs in one second. Time until participants achieve \>=100 mL increase from Baseline FEV1 (0-4 hours post-dose) are presented. Baseline FEV1 is defined as the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1. Time to \>= 100mL increase from Baseline (on Day 1) is defined as the time until the first post-dose FEV1 (on Day 1) is \>= 100mL above Baseline FEV1. Time to \>= 100mL increase from Baseline (on Day 1) was calculated only if there was at least one non-missing FEV1 value recorded within the first hour of dosing. Time to \>= 100mL increase from Baseline was assessed over the 0-4 time period and only used lung function data recorded up to 6 hours post the Day 1 dose. Participants who did not achieve \>= 100mL increase from Baseline over this time period were censored.

Outcome measures

Outcome measures
Measure	GW642444M 3 µg OD n=99 Participants Participants received GW642444M 3 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 6.25 µg OD n=101 Participants Participants received GW642444M 6.25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 12.5 µg OD n=100 Participants Participants received GW642444M 12.5 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 25 µg OD n=100 Participants Participants received GW642444M 25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 50 µg OD n=99 Participants Participants received GW642444M 50 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	Placebo n=101 Participants Participants received placebo (1 actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.
Time to >= 100 Milliliter (mL) Increase From Baseline in FEV1 (0-4 Hours Post-dose)	32 Minutes Interval 5.0 to 240.0	16 Minutes Interval 5.0 to 240.0	16 Minutes Interval 5.0 to 240.0	6 Minutes Interval 5.0 to 240.0	6 Minutes Interval 5.0 to 240.0	NA Minutes Interval 5.0 to 240.0 \> 50% of subjects were censored; therefore, the median could not be calculated.

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

GW642444M 3 µg OD

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

GW642444M 6.25 µg OD

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

GW642444M 12.5 µg OD

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

GW642444M 25 µg OD

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

GW642444M 50 µg OD

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=101 participants at risk Participants received placebo (1 actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 3 µg OD n=99 participants at risk Participants received GW642444M 3 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 6.25 µg OD n=101 participants at risk Participants received GW642444M 6.25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 12.5 µg OD n=101 participants at risk Participants received GW642444M 12.5 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 25 µg OD n=101 participants at risk Participants received GW642444M 25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 50 µg OD n=99 participants at risk Participants received GW642444M 50 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.
Cardiac disorders Atrial fibrillation	0.00% 0/101 • 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 Day 28). 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% 0/99 • 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 Day 28). 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% 0/101 • 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 Day 28). 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.	0.99% 1/101 • 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 Day 28). 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% 0/101 • 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 Day 28). 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% 0/99 • 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 Day 28). 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 Pneumonia	0.00% 0/101 • 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 Day 28). 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% 0/99 • 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 Day 28). 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% 0/101 • 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 Day 28). 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.	0.99% 1/101 • 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 Day 28). 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% 0/101 • 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 Day 28). 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% 0/99 • 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 Day 28). 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.
Nervous system disorders Syncope vasovagal	0.00% 0/101 • 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 Day 28). 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% 1/99 • 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 Day 28). 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% 0/101 • 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 Day 28). 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% 0/101 • 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 Day 28). 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% 0/101 • 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 Day 28). 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% 0/99 • 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 Day 28). 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 Chronic obstructive pulmonary disease	0.00% 0/101 • 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 Day 28). 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% 0/99 • 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 Day 28). 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% 0/101 • 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 Day 28). 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.	0.99% 1/101 • 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 Day 28). 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% 0/101 • 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 Day 28). 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% 0/99 • 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 Day 28). 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 Aortic aneurysm	0.00% 0/101 • 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 Day 28). 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% 0/99 • 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 Day 28). 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.	0.99% 1/101 • 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 Day 28). 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% 0/101 • 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 Day 28). 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% 0/101 • 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 Day 28). 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% 0/99 • 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 Day 28). 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=101 participants at risk Participants received placebo (1 actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 3 µg OD n=99 participants at risk Participants received GW642444M 3 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 6.25 µg OD n=101 participants at risk Participants received GW642444M 6.25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 12.5 µg OD n=101 participants at risk Participants received GW642444M 12.5 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 25 µg OD n=101 participants at risk Participants received GW642444M 25 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.	GW642444M 50 µg OD n=99 participants at risk Participants received GW642444M 50 µg (one actuation) OD in the morning from the novel dual strip dry powder inhaler for 28 days. In addition, participants were provided supplemental salbutamol (MDI and/or nebules) inhalation to be used as needed throughout the study.
Nervous system disorders Headache	9.9% 10/101 • 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 Day 28). 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.	6.1% 6/99 • 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 Day 28). 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.	5.0% 5/101 • 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 Day 28). 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% 3/101 • 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 Day 28). 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% 3/101 • 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 Day 28). 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.	7.1% 7/99 • 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 Day 28). 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 Nausea	4.0% 4/101 • 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 Day 28). 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% 1/99 • 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 Day 28). 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% 3/101 • 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 Day 28). 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% 2/101 • 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 Day 28). 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% 2/101 • 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 Day 28). 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% 1/99 • 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 Day 28). 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	3.0% 3/101 • 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 Day 28). 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% 2/99 • 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 Day 28). 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.	5.0% 5/101 • 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 Day 28). 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% 0/101 • 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 Day 28). 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.	0.99% 1/101 • 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 Day 28). 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% 0/99 • 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 Day 28). 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.
Cardiac disorders Ventricular extrasystoles	2.0% 2/101 • 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 Day 28). 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% 0/99 • 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 Day 28). 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.	0.99% 1/101 • 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 Day 28). 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% 0/101 • 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 Day 28). 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% 0/101 • 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 Day 28). 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% 3/99 • 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 Day 28). 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.

Additional Information

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