Trial Outcomes & Findings for A Study To Assess The Safety And Tolerability Of GW642444 In Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00372112)
NCT ID: NCT00372112
Last Updated: 2018-04-02
Results Overview
An 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. An 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, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
68 participants
Primary outcome timeframe
Up to Follow-up (17 days)
Results posted on
2018-04-02
Participant Flow
The study was planned on 80 male or female participants with moderate chronic obstructive pulmonary disease (COPD), aged 40 years or older from 03 November 2006 to 10 May 2007, across 14 centers of 6 countries (10 centers in Europe, 2 centers in Australia and 2 centers in New Zealand).
Out of 145 participants screened, 77 were screen failures and remaining 68 participants were randomized in the study to receive placebo, GW642444H (100 microgram \[mcg\] or 400 mcg once daily or Salmeterol 50 mcg twice daily (BD) via the DISKUS® dry powder inhaler (DPI).
Participant milestones
| Measure |
Placebo
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
17
|
16
|
17
|
18
|
|
Overall Study
COMPLETED
|
16
|
15
|
13
|
14
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
4
|
4
|
Reasons for withdrawal
| Measure |
Placebo
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
2
|
1
|
|
Overall Study
Exacerbation
|
0
|
0
|
0
|
1
|
|
Overall Study
PR >240 at Visit 3
|
0
|
0
|
0
|
1
|
|
Overall Study
Hepatitis B
|
1
|
0
|
0
|
0
|
|
Overall Study
Other-protocol violation
|
0
|
0
|
1
|
0
|
Baseline Characteristics
A Study To Assess The Safety And Tolerability Of GW642444 In Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Total
n=68 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
61.4 Years
STANDARD_DEVIATION 8.79 • n=5 Participants
|
65.8 Years
STANDARD_DEVIATION 9.06 • n=7 Participants
|
66.6 Years
STANDARD_DEVIATION 9.16 • n=5 Participants
|
60.2 Years
STANDARD_DEVIATION 7.37 • n=4 Participants
|
63.4 Years
STANDARD_DEVIATION 8.86 • n=21 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
44 Participants
n=21 Participants
|
|
Race (NIH/OMB)
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
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
66 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Up to Follow-up (17 days)Population: Safety Population comprised of all participants who were randomized and received at least one dose of study medication.
An 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. An 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, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Any AE
|
4 Participants
|
5 Participants
|
7 Participants
|
6 Participants
|
|
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Any SAE
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose) up to Day 14Population: Safety Population. Only those participants available at the specified time points were analyzed.
HR was measured using 28.5h ABPM on Day 1, Day 7 and Day 14. Baseline was defined as the pre-dose weighted mean of Day 1. Weighted mean was calculated by calculating the area under curve (AUC) of measurements made pre-dose on each day, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean change from Baseline was the average AUC minus Baseline (AAUCMB).
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Change From Baseline in Pre-dose Weighted Mean Heart Rate (HR) Derived From 28.5 Hour (h) Ambulatory Blood Pressure Monitoring (ABPM) at Day 7 and 14
Day 14
|
1.13 Beats per minute (bpm)
Standard Deviation 7.151
|
-1.31 Beats per minute (bpm)
Standard Deviation 9.724
|
4.29 Beats per minute (bpm)
Standard Deviation 9.646
|
-0.22 Beats per minute (bpm)
Standard Deviation 7.345
|
|
Change From Baseline in Pre-dose Weighted Mean Heart Rate (HR) Derived From 28.5 Hour (h) Ambulatory Blood Pressure Monitoring (ABPM) at Day 7 and 14
Day 7
|
4.60 Beats per minute (bpm)
Standard Deviation 5.689
|
0.18 Beats per minute (bpm)
Standard Deviation 7.253
|
0.17 Beats per minute (bpm)
Standard Deviation 6.443
|
0.95 Beats per minute (bpm)
Standard Deviation 8.793
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose) up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
HR was measured using 28.5 h ABPM on Day 1 (continued till Day 2), Day 7 (continued till Day 8) and Day 14 (continued till Day 15). Baseline was defined as the pre-dose weighted mean of Day 1. Weighted mean was calculated by calculating the AUC of measurements made 0-4 h post-dose on Day 1, 2, 7, 8, 14 and 15 and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean change from Baseline was the AAUCMB.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Change From Baseline in 0-4 h Weighted Mean HR Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 1
|
2.14 bpm
Standard Error 2.134
|
4.25 bpm
Standard Error 1.848
|
7.47 bpm
Standard Error 1.993
|
4.63 bpm
Standard Error 2.020
|
|
Change From Baseline in 0-4 h Weighted Mean HR Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 2
|
1.01 bpm
Standard Error 2.208
|
0.63 bpm
Standard Error 1.838
|
5.37 bpm
Standard Error 1.987
|
5.61 bpm
Standard Error 2.138
|
|
Change From Baseline in 0-4 h Weighted Mean HR Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 7
|
8.21 bpm
Standard Error 2.357
|
3.95 bpm
Standard Error 2.051
|
7.76 bpm
Standard Error 2.403
|
6.75 bpm
Standard Error 2.324
|
|
Change From Baseline in 0-4 h Weighted Mean HR Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 8
|
1.11 bpm
Standard Error 2.341
|
1.27 bpm
Standard Error 2.046
|
9.41 bpm
Standard Error 2.377
|
4.94 bpm
Standard Error 2.317
|
|
Change From Baseline in 0-4 h Weighted Mean HR Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 14
|
3.64 bpm
Standard Error 2.307
|
2.54 bpm
Standard Error 2.037
|
10.42 bpm
Standard Error 2.528
|
6.92 bpm
Standard Error 2.476
|
|
Change From Baseline in 0-4 h Weighted Mean HR Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 15
|
2.17 bpm
Standard Error 2.460
|
1.04 bpm
Standard Error 2.138
|
5.76 bpm
Standard Error 2.666
|
4.28 bpm
Standard Error 2.440
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose) up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
HR was measured using 28.5 h ABPM on Day 1, Day 7 and Day 14. Baseline was defined as the pre-dose weighted mean of Day 1. Weighted mean was calculated by calculating the AUC of measurements made 0-24 h post-dose on Day 7 and 14, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean change from Baseline was the AAUCMB.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Change From Baseline in 0-24 h Weighted Mean HR Derived From 28.5 ABPM at Day 7 and 14
Day 14
|
2.77 bpm
Standard Deviation 7.495
|
1.84 bpm
Standard Deviation 7.389
|
9.23 bpm
Standard Deviation 8.173
|
5.87 bpm
Standard Deviation 6.420
|
|
Change From Baseline in 0-24 h Weighted Mean HR Derived From 28.5 ABPM at Day 7 and 14
Day 7
|
6.50 bpm
Standard Deviation 6.696
|
3.07 bpm
Standard Deviation 7.261
|
7.16 bpm
Standard Deviation 6.567
|
6.47 bpm
Standard Deviation 6.885
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose) up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
HR was measured using 28.5 h ABPM on Day 1 (continued till Day 2), Day 7 (continued till Day 8) and Day 14 (continued till Day 15). For the calculation of 0-4 h maximum change from Baseline, measurements post-dose up to 6 h (actual time) was included. Baseline was defined as the pre-dose weighted mean of Day 1. Maximum change from Baseline was calculated by subtracting the Baseline value (weighted mean pre-dose Day 1) from the maximum assessment value (during 0-4 h) of the individual post-Baseline time points.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Change From Baseline in Maximum HR During 0-4 h Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 1
|
20.6 bpm
Standard Error 3.71
|
22.7 bpm
Standard Error 3.35
|
23.5 bpm
Standard Error 3.61
|
20.5 bpm
Standard Error 3.51
|
|
Change From Baseline in Maximum HR During 0-4 h Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 2
|
9.7 bpm
Standard Error 3.17
|
11.9 bpm
Standard Error 2.66
|
15.5 bpm
Standard Error 2.88
|
11.3 bpm
Standard Error 2.90
|
|
Change From Baseline in Maximum HR During 0-4 h Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 7
|
26.8 bpm
Standard Error 4.21
|
21.9 bpm
Standard Error 3.68
|
25.0 bpm
Standard Error 4.37
|
22.0 bpm
Standard Error 4.36
|
|
Change From Baseline in Maximum HR During 0-4 h Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 8
|
9.0 bpm
Standard Error 2.85
|
12.4 bpm
Standard Error 2.49
|
19.8 bpm
Standard Error 2.96
|
12.1 bpm
Standard Error 2.95
|
|
Change From Baseline in Maximum HR During 0-4 h Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 14
|
26.1 bpm
Standard Error 3.73
|
19.0 bpm
Standard Error 3.25
|
31.5 bpm
Standard Error 4.29
|
23.2 bpm
Standard Error 3.86
|
|
Change From Baseline in Maximum HR During 0-4 h Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15
Day 15
|
10.2 bpm
Standard Error 3.04
|
10.5 bpm
Standard Error 2.65
|
17.0 bpm
Standard Error 3.27
|
14.6 bpm
Standard Error 3.13
|
SECONDARY outcome
Timeframe: Day 1 up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
HR was measured using 28.5 h ABPM. Weighted mean HR at 0-4 h was obtained from measurements made over 0-4 h post-dose on Day 1, 2, 7, 8, 14 and 15. Weighted mean HR at 0-24 h was obtained from measurements made 0-24 h post-dose on Day 1, 7 and 14. Maximum HR at 0-4 h was obtained from measurements made over 0-4 h post-dose on Day 1, 2, 7, 8, 14 and 15. Baseline was defined as the pre-dose weighted mean of Day 1.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Weighted mean HR 0-4, Day 14
|
76.49 bpm
Standard Deviation 12.635
|
71.14 bpm
Standard Deviation 11.771
|
73.74 bpm
Standard Deviation 11.469
|
80.39 bpm
Standard Deviation 10.801
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Weighted mean HR 0-4, Day 15
|
75.64 bpm
Standard Deviation 18.666
|
68.82 bpm
Standard Deviation 12.980
|
73.00 bpm
Standard Deviation 11.033
|
77.60 bpm
Standard Deviation 10.298
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Maximum HR 0-4 h, Day 7
|
97.9 bpm
Standard Deviation 13.76
|
90.5 bpm
Standard Deviation 18.85
|
88.7 bpm
Standard Deviation 17.07
|
94.6 bpm
Standard Deviation 14.86
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Maximum HR 0-4 h, Day 8
|
82.2 bpm
Standard Deviation 19.23
|
80.6 bpm
Standard Deviation 18.06
|
82.0 bpm
Standard Deviation 16.14
|
86.9 bpm
Standard Deviation 14.31
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Weighted mean HR 0-4, Day 1
|
70.08 bpm
Standard Deviation 10.722
|
72.23 bpm
Standard Deviation 12.766
|
73.03 bpm
Standard Deviation 13.251
|
77.50 bpm
Standard Deviation 10.092
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Weighted mean HR 0-4, Day 2
|
71.07 bpm
Standard Deviation 14.743
|
68.24 bpm
Standard Deviation 10.081
|
70.47 bpm
Standard Deviation 11.771
|
77.12 bpm
Standard Deviation 11.461
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Weighted mean HR 0-4, Day 7
|
78.69 bpm
Standard Deviation 12.493
|
73.01 bpm
Standard Deviation 12.943
|
73.63 bpm
Standard Deviation 10.354
|
78.44 bpm
Standard Deviation 13.191
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Weighted mean HR 0-4, Day 8
|
73.82 bpm
Standard Deviation 15.927
|
70.17 bpm
Standard Deviation 11.353
|
73.20 bpm
Standard Deviation 13.379
|
77.76 bpm
Standard Deviation 13.003
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Weighted mean HR 0-24, Day 14
|
75.72 bpm
Standard Deviation 11.473
|
70.45 bpm
Standard Deviation 10.977
|
72.42 bpm
Standard Deviation 10.097
|
78.93 bpm
Standard Deviation 8.054
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Maximum HR 0-4 h, Day 1
|
94.9 bpm
Standard Deviation 18.38
|
90.3 bpm
Standard Deviation 17.72
|
88.6 bpm
Standard Deviation 13.91
|
92.7 bpm
Standard Deviation 13.90
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Maximum HR 0-4 h, Day 2
|
82.4 bpm
Standard Deviation 17.80
|
79.4 bpm
Standard Deviation 15.90
|
79.5 bpm
Standard Deviation 16.07
|
86.3 bpm
Standard Deviation 14.03
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Maximum HR 0-4 h, Day 14
|
95.2 bpm
Standard Deviation 12.16
|
87.0 bpm
Standard Deviation 14.68
|
92.9 bpm
Standard Deviation 20.08
|
96.2 bpm
Standard Deviation 12.21
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Maximum HR 0-4 h, Day 15
|
84.8 bpm
Standard Deviation 19.24
|
78.7 bpm
Standard Deviation 16.37
|
82.6 bpm
Standard Deviation 10.95
|
88.7 bpm
Standard Deviation 13.90
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Weighted mean HR 0-24, Day 1
|
70.07 bpm
Standard Deviation 10.079
|
72.33 bpm
Standard Deviation 11.592
|
71.83 bpm
Standard Deviation 11.772
|
78.53 bpm
Standard Deviation 8.525
|
|
Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM
Weighted mean HR 0-24, Day 7
|
75.83 bpm
Standard Deviation 11.085
|
72.35 bpm
Standard Deviation 11.046
|
74.05 bpm
Standard Deviation 11.298
|
78.18 bpm
Standard Deviation 9.649
|
SECONDARY outcome
Timeframe: Day 1 up to Day 14Population: Safety Population. Only those participants available at the specified time points were analyzed.
HR was measured using 28.5 h ABPM. The assessments were analyzed hourly as 0-1 h, 1-2 h, 2-3 h, 3-4 h, 4-5 h, 5-6 h, 6-7 h, 7-8 h, 8-9 h, 9-10 h, 10-11 h, 11-12 h, 12-13 h, 13-14 h, 14-15 h, 15-16 h, 16-17 h, 17-18 h, 18-19 h, 19-20 h, 20-21 h, 21-22 h, 22-23 h and 23-24 h at Day 1, Day 7 and Day 14.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 7-8 h
|
90.93 bpm
Standard Deviation 16.769
|
74.63 bpm
Standard Deviation 12.662
|
74.56 bpm
Standard Deviation 13.507
|
81.15 bpm
Standard Deviation 13.423
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 21-22 h
|
81.25 bpm
Standard Deviation 17.242
|
70.39 bpm
Standard Deviation 14.987
|
75.08 bpm
Standard Deviation 18.779
|
81.10 bpm
Standard Deviation 18.165
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 0-1 h
|
72.58 bpm
Standard Deviation 13.911
|
69.26 bpm
Standard Deviation 12.264
|
71.43 bpm
Standard Deviation 12.365
|
71.31 bpm
Standard Deviation 11.094
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 1-2 h
|
70.73 bpm
Standard Deviation 12.767
|
67.31 bpm
Standard Deviation 10.363
|
73.09 bpm
Standard Deviation 14.935
|
79.42 bpm
Standard Deviation 14.377
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 2-3 h
|
69.30 bpm
Standard Deviation 15.013
|
69.00 bpm
Standard Deviation 13.952
|
73.79 bpm
Standard Deviation 15.563
|
80.38 bpm
Standard Deviation 11.531
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 3-4 h
|
74.81 bpm
Standard Deviation 16.120
|
69.70 bpm
Standard Deviation 11.730
|
72.72 bpm
Standard Deviation 11.496
|
77.95 bpm
Standard Deviation 10.489
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 4-5 h
|
83.09 bpm
Standard Deviation 18.120
|
76.30 bpm
Standard Deviation 15.787
|
77.08 bpm
Standard Deviation 12.802
|
81.46 bpm
Standard Deviation 13.089
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 9-10 h
|
77.38 bpm
Standard Deviation 14.157
|
80.21 bpm
Standard Deviation 18.824
|
77.65 bpm
Standard Deviation 16.831
|
82.89 bpm
Standard Deviation 7.669
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 11-12 h
|
78.78 bpm
Standard Deviation 12.658
|
74.60 bpm
Standard Deviation 11.558
|
76.65 bpm
Standard Deviation 14.867
|
79.75 bpm
Standard Deviation 8.512
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 12-13 h
|
76.53 bpm
Standard Deviation 12.925
|
71.40 bpm
Standard Deviation 14.023
|
73.85 bpm
Standard Deviation 12.556
|
80.54 bpm
Standard Deviation 8.434
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 17-18 h
|
69.53 bpm
Standard Deviation 12.929
|
63.87 bpm
Standard Deviation 12.354
|
72.96 bpm
Standard Deviation 11.684
|
72.46 bpm
Standard Deviation 8.439
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 18-19 h
|
66.72 bpm
Standard Deviation 10.807
|
64.60 bpm
Standard Deviation 12.689
|
69.83 bpm
Standard Deviation 12.394
|
71.43 bpm
Standard Deviation 8.408
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 21-22 h
|
79.67 bpm
Standard Deviation 17.424
|
70.73 bpm
Standard Deviation 13.157
|
79.31 bpm
Standard Deviation 17.590
|
77.92 bpm
Standard Deviation 12.715
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 22-23 h
|
77.15 bpm
Standard Deviation 14.389
|
71.67 bpm
Standard Deviation 14.608
|
75.58 bpm
Standard Deviation 10.004
|
78.46 bpm
Standard Deviation 9.268
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 23-24 h
|
79.06 bpm
Standard Deviation 16.986
|
67.82 bpm
Standard Deviation 11.478
|
70.23 bpm
Standard Deviation 10.633
|
78.39 bpm
Standard Deviation 16.352
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 0-1 h
|
68.20 bpm
Standard Deviation 12.487
|
68.38 bpm
Standard Deviation 11.616
|
72.51 bpm
Standard Deviation 14.025
|
73.48 bpm
Standard Deviation 10.304
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 1-2 h
|
68.84 bpm
Standard Deviation 14.022
|
69.89 bpm
Standard Deviation 13.158
|
73.50 bpm
Standard Deviation 14.366
|
72.88 bpm
Standard Deviation 10.279
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 2-3 h
|
72.87 bpm
Standard Deviation 18.200
|
66.83 bpm
Standard Deviation 14.839
|
70.09 bpm
Standard Deviation 16.775
|
76.29 bpm
Standard Deviation 11.530
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 3-4 h
|
68.69 bpm
Standard Deviation 14.133
|
72.29 bpm
Standard Deviation 15.321
|
70.43 bpm
Standard Deviation 12.784
|
75.09 bpm
Standard Deviation 10.270
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 4-5 h
|
80.07 bpm
Standard Deviation 22.088
|
74.82 bpm
Standard Deviation 17.671
|
77.72 bpm
Standard Deviation 13.937
|
83.50 bpm
Standard Deviation 12.022
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 5-6 h
|
90.46 bpm
Standard Deviation 17.075
|
79.68 bpm
Standard Deviation 16.218
|
83.83 bpm
Standard Deviation 11.544
|
84.77 bpm
Standard Deviation 16.272
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 6-7 h
|
85.64 bpm
Standard Deviation 16.974
|
78.23 bpm
Standard Deviation 17.370
|
76.54 bpm
Standard Deviation 12.801
|
81.46 bpm
Standard Deviation 11.896
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 7-8 h
|
81.67 bpm
Standard Deviation 16.306
|
78.28 bpm
Standard Deviation 15.727
|
78.14 bpm
Standard Deviation 15.623
|
81.40 bpm
Standard Deviation 11.960
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 8-9 h
|
81.07 bpm
Standard Deviation 15.185
|
81.41 bpm
Standard Deviation 17.908
|
77.97 bpm
Standard Deviation 12.859
|
82.38 bpm
Standard Deviation 11.944
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 9-10 h
|
79.38 bpm
Standard Deviation 16.201
|
79.31 bpm
Standard Deviation 16.239
|
75.53 bpm
Standard Deviation 14.272
|
82.94 bpm
Standard Deviation 11.000
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 10-11 h
|
76.54 bpm
Standard Deviation 19.338
|
76.03 bpm
Standard Deviation 15.206
|
72.33 bpm
Standard Deviation 11.083
|
81.88 bpm
Standard Deviation 10.888
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 11-12 h
|
74.33 bpm
Standard Deviation 17.192
|
74.16 bpm
Standard Deviation 14.162
|
69.25 bpm
Standard Deviation 10.907
|
79.76 bpm
Standard Deviation 9.416
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 12-13 h
|
74.70 bpm
Standard Deviation 16.493
|
71.53 bpm
Standard Deviation 16.620
|
71.16 bpm
Standard Deviation 13.766
|
80.17 bpm
Standard Deviation 11.182
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 13-14 h
|
70.17 bpm
Standard Deviation 16.547
|
71.00 bpm
Standard Deviation 13.837
|
70.50 bpm
Standard Deviation 11.540
|
79.26 bpm
Standard Deviation 9.203
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 14-15 h
|
68.47 bpm
Standard Deviation 15.015
|
69.41 bpm
Standard Deviation 14.053
|
70.19 bpm
Standard Deviation 11.542
|
77.41 bpm
Standard Deviation 7.912
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 15-16 h
|
67.30 bpm
Standard Deviation 13.618
|
66.69 bpm
Standard Deviation 14.791
|
68.27 bpm
Standard Deviation 13.843
|
75.00 bpm
Standard Deviation 8.828
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 16-17 h
|
65.75 bpm
Standard Deviation 12.667
|
65.75 bpm
Standard Deviation 12.031
|
67.87 bpm
Standard Deviation 11.999
|
73.84 bpm
Standard Deviation 8.408
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 17-18 h
|
64.20 bpm
Standard Deviation 12.078
|
66.50 bpm
Standard Deviation 12.102
|
65.37 bpm
Standard Deviation 11.592
|
72.00 bpm
Standard Deviation 8.823
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 18-19 h
|
63.34 bpm
Standard Deviation 11.705
|
66.53 bpm
Standard Deviation 10.848
|
67.82 bpm
Standard Deviation 17.133
|
72.35 bpm
Standard Deviation 6.451
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 19-20 h
|
63.58 bpm
Standard Deviation 11.302
|
63.31 bpm
Standard Deviation 9.889
|
70.86 bpm
Standard Deviation 19.586
|
74.17 bpm
Standard Deviation 11.231
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 20-21 h
|
68.81 bpm
Standard Deviation 13.465
|
66.88 bpm
Standard Deviation 14.906
|
70.82 bpm
Standard Deviation 17.638
|
76.72 bpm
Standard Deviation 11.240
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 21-22 h
|
75.23 bpm
Standard Deviation 14.859
|
78.79 bpm
Standard Deviation 17.327
|
71.47 bpm
Standard Deviation 18.402
|
82.03 bpm
Standard Deviation 13.237
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 22-23 h
|
75.08 bpm
Standard Deviation 15.643
|
74.10 bpm
Standard Deviation 11.235
|
70.37 bpm
Standard Deviation 10.167
|
80.55 bpm
Standard Deviation 13.168
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 23-24 h
|
70.21 bpm
Standard Deviation 13.674
|
70.51 bpm
Standard Deviation 12.439
|
69.63 bpm
Standard Deviation 12.911
|
76.94 bpm
Standard Deviation 12.137
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 0-1 h
|
73.97 bpm
Standard Deviation 12.115
|
68.25 bpm
Standard Deviation 12.667
|
69.79 bpm
Standard Deviation 10.700
|
75.07 bpm
Standard Deviation 13.723
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 1-2 h
|
76.66 bpm
Standard Deviation 16.264
|
70.17 bpm
Standard Deviation 13.754
|
72.63 bpm
Standard Deviation 12.989
|
74.05 bpm
Standard Deviation 12.343
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 2-3 h
|
74.21 bpm
Standard Deviation 16.735
|
65.96 bpm
Standard Deviation 13.524
|
69.89 bpm
Standard Deviation 14.077
|
76.96 bpm
Standard Deviation 14.353
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 3-4 h
|
75.30 bpm
Standard Deviation 15.794
|
71.35 bpm
Standard Deviation 16.210
|
69.30 bpm
Standard Deviation 11.496
|
77.71 bpm
Standard Deviation 14.097
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 4-5 h
|
83.21 bpm
Standard Deviation 12.349
|
80.61 bpm
Standard Deviation 14.581
|
78.96 bpm
Standard Deviation 12.857
|
85.25 bpm
Standard Deviation 16.055
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 5-6 h
|
90.63 bpm
Standard Deviation 11.828
|
79.65 bpm
Standard Deviation 17.860
|
79.12 bpm
Standard Deviation 15.687
|
86.54 bpm
Standard Deviation 15.224
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 6-7 h
|
90.50 bpm
Standard Deviation 17.096
|
78.07 bpm
Standard Deviation 13.867
|
74.69 bpm
Standard Deviation 14.010
|
81.28 bpm
Standard Deviation 11.328
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 8-9 h
|
85.50 bpm
Standard Deviation 12.923
|
76.53 bpm
Standard Deviation 14.341
|
76.40 bpm
Standard Deviation 14.970
|
81.57 bpm
Standard Deviation 15.587
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 9-10 h
|
78.60 bpm
Standard Deviation 12.900
|
75.73 bpm
Standard Deviation 14.007
|
76.88 bpm
Standard Deviation 12.395
|
88.00 bpm
Standard Deviation 14.735
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 10-11 h
|
78.80 bpm
Standard Deviation 12.846
|
75.83 bpm
Standard Deviation 15.496
|
79.63 bpm
Standard Deviation 15.493
|
82.17 bpm
Standard Deviation 12.757
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 11-12 h
|
77.17 bpm
Standard Deviation 12.349
|
73.61 bpm
Standard Deviation 12.435
|
75.55 bpm
Standard Deviation 13.549
|
82.03 bpm
Standard Deviation 9.553
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 12-13 h
|
74.47 bpm
Standard Deviation 16.722
|
72.23 bpm
Standard Deviation 13.522
|
75.23 bpm
Standard Deviation 12.760
|
81.47 bpm
Standard Deviation 9.021
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 13-14 h
|
73.90 bpm
Standard Deviation 16.245
|
70.10 bpm
Standard Deviation 13.925
|
73.26 bpm
Standard Deviation 13.101
|
80.37 bpm
Standard Deviation 8.423
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 14-15 h
|
67.97 bpm
Standard Deviation 14.851
|
70.10 bpm
Standard Deviation 13.288
|
72.50 bpm
Standard Deviation 11.970
|
80.37 bpm
Standard Deviation 8.943
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 15-16 h
|
69.00 bpm
Standard Deviation 14.210
|
66.70 bpm
Standard Deviation 11.188
|
71.98 bpm
Standard Deviation 10.818
|
75.80 bpm
Standard Deviation 8.988
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 16-17 h
|
66.47 bpm
Standard Deviation 13.970
|
65.60 bpm
Standard Deviation 10.524
|
70.83 bpm
Standard Deviation 10.822
|
74.73 bpm
Standard Deviation 9.243
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 17-18 h
|
66.60 bpm
Standard Deviation 13.494
|
65.57 bpm
Standard Deviation 10.962
|
70.75 bpm
Standard Deviation 12.194
|
74.23 bpm
Standard Deviation 8.542
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 18-19 h
|
65.27 bpm
Standard Deviation 14.732
|
66.64 bpm
Standard Deviation 9.976
|
69.07 bpm
Standard Deviation 10.887
|
74.10 bpm
Standard Deviation 10.369
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 19-20 h
|
67.89 bpm
Standard Deviation 15.134
|
67.17 bpm
Standard Deviation 11.047
|
68.86 bpm
Standard Deviation 13.388
|
73.47 bpm
Standard Deviation 9.066
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 20-21 h
|
69.75 bpm
Standard Deviation 15.978
|
67.35 bpm
Standard Deviation 15.498
|
68.39 bpm
Standard Deviation 14.531
|
75.12 bpm
Standard Deviation 13.670
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 22-23 h
|
78.27 bpm
Standard Deviation 17.026
|
71.85 bpm
Standard Deviation 22.724
|
72.96 bpm
Standard Deviation 13.181
|
83.00 bpm
Standard Deviation 16.501
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 23-24 h
|
73.90 bpm
Standard Deviation 16.937
|
69.51 bpm
Standard Deviation 10.521
|
71.79 bpm
Standard Deviation 12.076
|
76.50 bpm
Standard Deviation 12.890
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 5-6 h
|
87.17 bpm
Standard Deviation 13.308
|
76.63 bpm
Standard Deviation 13.348
|
81.53 bpm
Standard Deviation 11.850
|
89.15 bpm
Standard Deviation 14.899
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 6-7 h
|
81.62 bpm
Standard Deviation 11.162
|
75.29 bpm
Standard Deviation 12.525
|
77.92 bpm
Standard Deviation 15.697
|
87.79 bpm
Standard Deviation 16.734
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 7-8 h
|
79.77 bpm
Standard Deviation 14.674
|
77.10 bpm
Standard Deviation 15.826
|
76.32 bpm
Standard Deviation 15.363
|
77.67 bpm
Standard Deviation 13.774
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 8-9 h
|
79.97 bpm
Standard Deviation 13.840
|
77.03 bpm
Standard Deviation 13.345
|
76.77 bpm
Standard Deviation 12.882
|
81.17 bpm
Standard Deviation 10.069
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 10-11 h
|
81.14 bpm
Standard Deviation 11.396
|
74.27 bpm
Standard Deviation 15.734
|
78.85 bpm
Standard Deviation 18.580
|
80.71 bpm
Standard Deviation 7.844
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 13-14 h
|
74.09 bpm
Standard Deviation 13.790
|
71.33 bpm
Standard Deviation 13.282
|
74.96 bpm
Standard Deviation 14.060
|
77.43 bpm
Standard Deviation 8.216
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 14-15 h
|
71.41 bpm
Standard Deviation 14.672
|
69.73 bpm
Standard Deviation 11.654
|
74.78 bpm
Standard Deviation 13.677
|
78.18 bpm
Standard Deviation 10.622
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 15-16 h
|
70.72 bpm
Standard Deviation 12.920
|
68.87 bpm
Standard Deviation 12.238
|
71.62 bpm
Standard Deviation 12.805
|
76.21 bpm
Standard Deviation 7.300
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 16-17 h
|
69.16 bpm
Standard Deviation 11.226
|
65.10 bpm
Standard Deviation 11.382
|
73.65 bpm
Standard Deviation 11.067
|
74.79 bpm
Standard Deviation 8.937
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 19-20 h
|
66.25 bpm
Standard Deviation 11.703
|
65.33 bpm
Standard Deviation 13.591
|
67.59 bpm
Standard Deviation 11.334
|
72.04 bpm
Standard Deviation 8.734
|
|
Mean Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 20-21 h
|
72.56 bpm
Standard Deviation 16.361
|
68.31 bpm
Standard Deviation 16.095
|
71.17 bpm
Standard Deviation 15.336
|
70.63 bpm
Standard Deviation 9.163
|
SECONDARY outcome
Timeframe: Day 1 up to Day 14Population: Safety Population. Only those participants available at the specified time points were analyzed.
HR was measured using 28.5 h ABPM. The assessments for maximum HR were analyzed hourly as 0-1 h, 1-2 h, 2-3 h, 3-4 h, 4-5 h, 5-6 h, 6-7 h, 7-8 h, 8-9 h, 9-10 h, 10-11 h, 11-12 h, 12-13 h, 13-14 h, 14-15 h, 15-16 h, 16-17 h, 17-18 h, 18-19 h, 19-20 h, 20-21 h, 21-22 h, 22-23 h and 23-24 h at Day 1, Day 7 and Day 14.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 18-19 h
|
66.3 bpm
Standard Deviation 14.80
|
68.9 bpm
Standard Deviation 9.86
|
72.5 bpm
Standard Deviation 12.40
|
76.3 bpm
Standard Deviation 11.03
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 19-20 h
|
71.7 bpm
Standard Deviation 18.46
|
69.9 bpm
Standard Deviation 12.47
|
71.2 bpm
Standard Deviation 13.45
|
75.3 bpm
Standard Deviation 9.36
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 23-24 h
|
81.2 bpm
Standard Deviation 17.96
|
70.1 bpm
Standard Deviation 11.82
|
71.5 bpm
Standard Deviation 10.64
|
83.2 bpm
Standard Deviation 22.59
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 11-12 h
|
75.9 bpm
Standard Deviation 17.39
|
75.9 bpm
Standard Deviation 14.90
|
71.3 bpm
Standard Deviation 12.00
|
82.0 bpm
Standard Deviation 9.87
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 12-13 h
|
77.3 bpm
Standard Deviation 17.59
|
73.4 bpm
Standard Deviation 17.79
|
74.3 bpm
Standard Deviation 17.66
|
83.0 bpm
Standard Deviation 12.34
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 0-1 h
|
70.6 bpm
Standard Deviation 13.01
|
71.1 bpm
Standard Deviation 12.33
|
74.4 bpm
Standard Deviation 15.08
|
76.6 bpm
Standard Deviation 10.98
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 2-3 h
|
75.8 bpm
Standard Deviation 19.33
|
70.1 bpm
Standard Deviation 17.21
|
71.8 bpm
Standard Deviation 17.31
|
78.6 bpm
Standard Deviation 12.08
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 3-4 h
|
71.2 bpm
Standard Deviation 14.27
|
74.4 bpm
Standard Deviation 15.90
|
72.8 bpm
Standard Deviation 12.69
|
78.2 bpm
Standard Deviation 11.11
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 6-7 h
|
89.6 bpm
Standard Deviation 18.90
|
80.5 bpm
Standard Deviation 17.73
|
78.9 bpm
Standard Deviation 13.44
|
83.1 bpm
Standard Deviation 12.07
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 7-8 h
|
84.9 bpm
Standard Deviation 17.74
|
84.5 bpm
Standard Deviation 19.89
|
80.2 bpm
Standard Deviation 16.38
|
84.4 bpm
Standard Deviation 13.92
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 8-9 h
|
85.0 bpm
Standard Deviation 17.26
|
84.2 bpm
Standard Deviation 19.19
|
81.1 bpm
Standard Deviation 13.49
|
85.1 bpm
Standard Deviation 13.11
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 9-10 h
|
82.4 bpm
Standard Deviation 15.48
|
82.2 bpm
Standard Deviation 15.71
|
77.3 bpm
Standard Deviation 14.85
|
84.6 bpm
Standard Deviation 11.70
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 13-14 h
|
71.5 bpm
Standard Deviation 16.84
|
72.4 bpm
Standard Deviation 14.33
|
72.7 bpm
Standard Deviation 12.04
|
81.4 bpm
Standard Deviation 10.35
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 14-15 h
|
69.7 bpm
Standard Deviation 14.69
|
70.8 bpm
Standard Deviation 14.61
|
71.8 bpm
Standard Deviation 12.41
|
79.8 bpm
Standard Deviation 7.82
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 20-21 h
|
71.7 bpm
Standard Deviation 14.17
|
71.3 bpm
Standard Deviation 17.68
|
72.6 bpm
Standard Deviation 18.91
|
79.9 bpm
Standard Deviation 12.54
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 1-2 h
|
78.9 bpm
Standard Deviation 16.88
|
73.0 bpm
Standard Deviation 15.46
|
75.5 bpm
Standard Deviation 13.53
|
74.8 bpm
Standard Deviation 12.30
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 5-6 h
|
94.0 bpm
Standard Deviation 13.05
|
82.1 bpm
Standard Deviation 17.81
|
80.7 bpm
Standard Deviation 16.52
|
88.8 bpm
Standard Deviation 16.11
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 6-7 h
|
92.5 bpm
Standard Deviation 16.78
|
85.4 bpm
Standard Deviation 15.58
|
76.6 bpm
Standard Deviation 13.91
|
83.8 bpm
Standard Deviation 12.81
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 7-8 h
|
96.7 bpm
Standard Deviation 20.74
|
77.9 bpm
Standard Deviation 13.02
|
77.6 bpm
Standard Deviation 16.31
|
83.9 bpm
Standard Deviation 14.41
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 8-9 h
|
89.2 bpm
Standard Deviation 12.96
|
78.5 bpm
Standard Deviation 15.27
|
77.8 bpm
Standard Deviation 15.41
|
84.1 bpm
Standard Deviation 17.28
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 9-10 h
|
81.9 bpm
Standard Deviation 14.09
|
77.5 bpm
Standard Deviation 13.84
|
80.0 bpm
Standard Deviation 13.27
|
91.2 bpm
Standard Deviation 16.05
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 10-11 h
|
83.2 bpm
Standard Deviation 13.12
|
78.5 bpm
Standard Deviation 17.13
|
83.1 bpm
Standard Deviation 16.04
|
84.6 bpm
Standard Deviation 13.56
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 11-12 h
|
81.2 bpm
Standard Deviation 12.64
|
75.3 bpm
Standard Deviation 12.58
|
77.2 bpm
Standard Deviation 14.04
|
83.6 bpm
Standard Deviation 9.63
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 12-13 h
|
77.2 bpm
Standard Deviation 17.63
|
74.5 bpm
Standard Deviation 13.51
|
77.3 bpm
Standard Deviation 13.33
|
83.4 bpm
Standard Deviation 8.86
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 13-14 h
|
76.5 bpm
Standard Deviation 16.76
|
71.7 bpm
Standard Deviation 14.67
|
75.6 bpm
Standard Deviation 14.16
|
82.1 bpm
Standard Deviation 9.38
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 14-15 h
|
69.4 bpm
Standard Deviation 15.55
|
72.6 bpm
Standard Deviation 13.56
|
74.4 bpm
Standard Deviation 12.64
|
83.2 bpm
Standard Deviation 10.35
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 15-16 h
|
71.3 bpm
Standard Deviation 15.41
|
68.5 bpm
Standard Deviation 11.80
|
74.0 bpm
Standard Deviation 11.31
|
77.1 bpm
Standard Deviation 8.83
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 16-17 h
|
68.3 bpm
Standard Deviation 15.42
|
67.3 bpm
Standard Deviation 11.30
|
73.4 bpm
Standard Deviation 11.95
|
76.7 bpm
Standard Deviation 8.67
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 17-18 h
|
68.9 bpm
Standard Deviation 14.09
|
67.1 bpm
Standard Deviation 11.08
|
72.7 bpm
Standard Deviation 13.78
|
75.7 bpm
Standard Deviation 9.43
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 20-21 h
|
77.1 bpm
Standard Deviation 16.13
|
69.6 bpm
Standard Deviation 17.11
|
70.9 bpm
Standard Deviation 15.08
|
76.5 bpm
Standard Deviation 13.96
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 21-22 h
|
88.0 bpm
Standard Deviation 20.26
|
72.0 bpm
Standard Deviation 15.09
|
79.1 bpm
Standard Deviation 22.11
|
83.5 bpm
Standard Deviation 17.91
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 22-23 h
|
79.9 bpm
Standard Deviation 18.30
|
77.2 bpm
Standard Deviation 30.30
|
74.9 bpm
Standard Deviation 13.45
|
86.2 bpm
Standard Deviation 16.30
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 23-24 h
|
77.0 bpm
Standard Deviation 17.25
|
72.1 bpm
Standard Deviation 11.53
|
73.8 bpm
Standard Deviation 11.45
|
78.0 bpm
Standard Deviation 13.19
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 0-1 h
|
75.9 bpm
Standard Deviation 15.22
|
73.1 bpm
Standard Deviation 14.62
|
72.8 bpm
Standard Deviation 13.24
|
74.2 bpm
Standard Deviation 9.69
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 1-2 h
|
73.3 bpm
Standard Deviation 12.25
|
69.8 bpm
Standard Deviation 10.50
|
77.6 bpm
Standard Deviation 16.51
|
81.7 bpm
Standard Deviation 15.38
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 2-3 h
|
71.5 bpm
Standard Deviation 15.13
|
70.8 bpm
Standard Deviation 15.09
|
75.8 bpm
Standard Deviation 17.29
|
81.6 bpm
Standard Deviation 11.05
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 3-4 h
|
78.0 bpm
Standard Deviation 17.88
|
72.9 bpm
Standard Deviation 13.43
|
75.4 bpm
Standard Deviation 11.35
|
79.1 bpm
Standard Deviation 11.09
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 4-5 h
|
87.1 bpm
Standard Deviation 16.80
|
78.6 bpm
Standard Deviation 17.84
|
81.5 bpm
Standard Deviation 22.85
|
83.9 bpm
Standard Deviation 13.79
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 5-6 h
|
90.1 bpm
Standard Deviation 13.99
|
81.1 bpm
Standard Deviation 12.15
|
84.3 bpm
Standard Deviation 11.71
|
91.7 bpm
Standard Deviation 14.65
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 6-7 h
|
84.8 bpm
Standard Deviation 9.97
|
77.8 bpm
Standard Deviation 12.97
|
79.6 bpm
Standard Deviation 16.19
|
88.8 bpm
Standard Deviation 16.61
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 7-8 h
|
82.9 bpm
Standard Deviation 14.36
|
81.5 bpm
Standard Deviation 17.22
|
79.1 bpm
Standard Deviation 16.53
|
80.2 bpm
Standard Deviation 14.88
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 8-9 h
|
82.5 bpm
Standard Deviation 14.33
|
78.6 bpm
Standard Deviation 14.21
|
78.8 bpm
Standard Deviation 13.74
|
82.4 bpm
Standard Deviation 9.98
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 9-10 h
|
80.0 bpm
Standard Deviation 15.11
|
83.6 bpm
Standard Deviation 19.68
|
80.2 bpm
Standard Deviation 16.58
|
85.5 bpm
Standard Deviation 8.06
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 10-11 h
|
84.4 bpm
Standard Deviation 11.60
|
76.3 bpm
Standard Deviation 15.94
|
81.2 bpm
Standard Deviation 19.62
|
82.8 bpm
Standard Deviation 7.90
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 11-112 h
|
81.6 bpm
Standard Deviation 12.96
|
75.9 bpm
Standard Deviation 12.31
|
78.6 bpm
Standard Deviation 15.41
|
81.5 bpm
Standard Deviation 8.69
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 12-13 h
|
79.8 bpm
Standard Deviation 15.21
|
74.7 bpm
Standard Deviation 14.00
|
76.5 bpm
Standard Deviation 13.40
|
82.6 bpm
Standard Deviation 9.41
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 13-14 h
|
76.3 bpm
Standard Deviation 14.07
|
73.3 bpm
Standard Deviation 14.41
|
77.1 bpm
Standard Deviation 16.06
|
80.0 bpm
Standard Deviation 7.62
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 14-15 h
|
73.3 bpm
Standard Deviation 14.92
|
71.9 bpm
Standard Deviation 11.68
|
77.1 bpm
Standard Deviation 14.58
|
79.9 bpm
Standard Deviation 11.16
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 15-16 h
|
72.9 bpm
Standard Deviation 13.94
|
70.7 bpm
Standard Deviation 13.11
|
74.1 bpm
Standard Deviation 14.21
|
78.0 bpm
Standard Deviation 7.81
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 16-17 h
|
70.8 bpm
Standard Deviation 11.48
|
66.3 bpm
Standard Deviation 11.78
|
76.1 bpm
Standard Deviation 11.97
|
77.4 bpm
Standard Deviation 10.28
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 17-18 h
|
72.8 bpm
Standard Deviation 15.25
|
65.4 bpm
Standard Deviation 12.55
|
75.4 bpm
Standard Deviation 12.27
|
73.8 bpm
Standard Deviation 8.49
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 18-19 h
|
69.1 bpm
Standard Deviation 11.03
|
67.1 bpm
Standard Deviation 14.08
|
71.6 bpm
Standard Deviation 12.67
|
73.5 bpm
Standard Deviation 8.92
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 19-20 h
|
68.5 bpm
Standard Deviation 12.76
|
66.9 bpm
Standard Deviation 14.52
|
68.8 bpm
Standard Deviation 11.45
|
73.9 bpm
Standard Deviation 8.53
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 20-21 h
|
75.1 bpm
Standard Deviation 17.38
|
72.5 bpm
Standard Deviation 20.28
|
73.3 bpm
Standard Deviation 14.81
|
72.8 bpm
Standard Deviation 10.21
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 21-22 h
|
82.0 bpm
Standard Deviation 19.41
|
72.9 bpm
Standard Deviation 13.44
|
81.8 bpm
Standard Deviation 17.49
|
81.4 bpm
Standard Deviation 15.05
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 14, 22-23 h
|
79.8 bpm
Standard Deviation 14.88
|
74.0 bpm
Standard Deviation 14.39
|
79.8 bpm
Standard Deviation 8.92
|
81.4 bpm
Standard Deviation 10.13
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 1-2 h
|
72.2 bpm
Standard Deviation 15.32
|
72.8 bpm
Standard Deviation 16.72
|
76.4 bpm
Standard Deviation 16.21
|
74.1 bpm
Standard Deviation 10.19
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 4-5 h
|
84.6 bpm
Standard Deviation 22.67
|
78.0 bpm
Standard Deviation 18.81
|
81.6 bpm
Standard Deviation 14.40
|
86.4 bpm
Standard Deviation 12.91
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 5-6 h
|
94.2 bpm
Standard Deviation 18.14
|
82.3 bpm
Standard Deviation 16.45
|
86.4 bpm
Standard Deviation 11.38
|
88.5 bpm
Standard Deviation 18.88
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 21-22 h
|
77.6 bpm
Standard Deviation 15.88
|
85.0 bpm
Standard Deviation 25.45
|
72.7 bpm
Standard Deviation 19.60
|
84.3 bpm
Standard Deviation 14.31
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 10-11 h
|
78.7 bpm
Standard Deviation 19.80
|
78.9 bpm
Standard Deviation 17.02
|
74.1 bpm
Standard Deviation 11.79
|
84.4 bpm
Standard Deviation 12.47
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 15-16 h
|
68.9 bpm
Standard Deviation 13.69
|
68.9 bpm
Standard Deviation 17.61
|
69.2 bpm
Standard Deviation 13.96
|
76.1 bpm
Standard Deviation 8.84
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 16-17 h
|
68.1 bpm
Standard Deviation 13.32
|
67.6 bpm
Standard Deviation 12.10
|
70.9 bpm
Standard Deviation 13.24
|
76.2 bpm
Standard Deviation 9.06
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 17-18 h
|
65.6 bpm
Standard Deviation 11.67
|
68.9 bpm
Standard Deviation 13.30
|
67.0 bpm
Standard Deviation 11.47
|
74.2 bpm
Standard Deviation 9.28
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 18-19 h
|
64.9 bpm
Standard Deviation 11.94
|
70.9 bpm
Standard Deviation 13.15
|
70.4 bpm
Standard Deviation 17.35
|
75.7 bpm
Standard Deviation 7.54
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 19-20 h
|
65.5 bpm
Standard Deviation 12.14
|
64.7 bpm
Standard Deviation 10.82
|
73.8 bpm
Standard Deviation 19.57
|
77.2 bpm
Standard Deviation 13.61
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 22-23 h
|
77.1 bpm
Standard Deviation 15.50
|
79.5 bpm
Standard Deviation 15.12
|
71.9 bpm
Standard Deviation 10.79
|
82.9 bpm
Standard Deviation 14.73
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 1, 23-24 h
|
72.6 bpm
Standard Deviation 12.87
|
72.1 bpm
Standard Deviation 12.83
|
71.7 bpm
Standard Deviation 12.59
|
79.1 bpm
Standard Deviation 12.78
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 0-1 h
|
78.4 bpm
Standard Deviation 12.21
|
71.4 bpm
Standard Deviation 13.82
|
73.2 bpm
Standard Deviation 12.13
|
77.2 bpm
Standard Deviation 14.04
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 2-3 h
|
75.5 bpm
Standard Deviation 16.70
|
67.2 bpm
Standard Deviation 13.83
|
71.4 bpm
Standard Deviation 14.32
|
77.9 bpm
Standard Deviation 14.93
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 3-4 h
|
77.5 bpm
Standard Deviation 15.32
|
73.3 bpm
Standard Deviation 17.38
|
71.0 bpm
Standard Deviation 11.78
|
80.0 bpm
Standard Deviation 14.22
|
|
Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14
Day 7, 4-5 h
|
88.8 bpm
Standard Deviation 13.85
|
87.8 bpm
Standard Deviation 18.56
|
83.1 bpm
Standard Deviation 18.52
|
88.8 bpm
Standard Deviation 15.42
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose) up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
BP was measured using 28.5 h ABPM. Weighted mean SBP and DBP at 0-4 h post-dose was obtained on Day 1, 2, 7, 8, 14 and 15. Weighted mean SBP and DBP at 0-24 h post-dose was obtained on Day 1, 7 and 14. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. Baseline was defined as the weighted mean SBP and DBP on pre-dose Day 1. The weighted mean change from Baseline was the AAUCMB. Data is reported for change from Baseline in weighted mean pre-dose values at Day 7 and Day 14; change from Baseline in weighted mean over 0-4 h at Day 1, 2, 7, 8, 14 and 15; and change from Baseline in weighted mean over 0-24 h at Day 1, 7 and 14.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
SBP, Day 14, pre-dose
|
-6.17 Millimeter of mercury (mmHg)
Standard Deviation 9.602
|
-4.15 Millimeter of mercury (mmHg)
Standard Deviation 17.991
|
-1.39 Millimeter of mercury (mmHg)
Standard Deviation 10.228
|
-12.06 Millimeter of mercury (mmHg)
Standard Deviation 14.143
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
SBP, Day 7, 0-4 h
|
-8.98 Millimeter of mercury (mmHg)
Standard Deviation 9.838
|
-7.86 Millimeter of mercury (mmHg)
Standard Deviation 10.724
|
-2.43 Millimeter of mercury (mmHg)
Standard Deviation 8.855
|
-8.34 Millimeter of mercury (mmHg)
Standard Deviation 11.266
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
SBP, Day 15, 0-4 h
|
-7.96 Millimeter of mercury (mmHg)
Standard Deviation 9.639
|
-11.86 Millimeter of mercury (mmHg)
Standard Deviation 13.264
|
-11.27 Millimeter of mercury (mmHg)
Standard Deviation 11.249
|
-14.97 Millimeter of mercury (mmHg)
Standard Deviation 11.794
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
SBP, Day 7, 0-24 h
|
-13.76 Millimeter of mercury (mmHg)
Standard Deviation 10.592
|
-15.34 Millimeter of mercury (mmHg)
Standard Deviation 11.591
|
-7.75 Millimeter of mercury (mmHg)
Standard Deviation 7.552
|
-14.82 Millimeter of mercury (mmHg)
Standard Deviation 10.810
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
DBP, Day 7, pre-dose
|
-0.60 Millimeter of mercury (mmHg)
Standard Deviation 8.011
|
0.21 Millimeter of mercury (mmHg)
Standard Deviation 9.021
|
-0.33 Millimeter of mercury (mmHg)
Standard Deviation 5.888
|
-5.59 Millimeter of mercury (mmHg)
Standard Deviation 7.151
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
DBP, Day 14, pre-dose
|
-0.71 Millimeter of mercury (mmHg)
Standard Deviation 7.733
|
-0.88 Millimeter of mercury (mmHg)
Standard Deviation 8.530
|
-0.17 Millimeter of mercury (mmHg)
Standard Deviation 8.108
|
-6.89 Millimeter of mercury (mmHg)
Standard Deviation 9.168
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
DBP, Day 7, 0-4 h
|
0.90 Millimeter of mercury (mmHg)
Standard Deviation 6.246
|
-1.39 Millimeter of mercury (mmHg)
Standard Deviation 5.360
|
-1.39 Millimeter of mercury (mmHg)
Standard Deviation 4.325
|
-7.13 Millimeter of mercury (mmHg)
Standard Deviation 8.469
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
DBP, Day 8, 0-4 h
|
-1.13 Millimeter of mercury (mmHg)
Standard Deviation 7.097
|
-3.64 Millimeter of mercury (mmHg)
Standard Deviation 5.083
|
-0.97 Millimeter of mercury (mmHg)
Standard Deviation 6.468
|
-10.18 Millimeter of mercury (mmHg)
Standard Deviation 10.093
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
DBP, Day 1, 0-4 h
|
2.72 Millimeter of mercury (mmHg)
Standard Deviation 5.654
|
-1.49 Millimeter of mercury (mmHg)
Standard Deviation 5.611
|
0.95 Millimeter of mercury (mmHg)
Standard Deviation 7.894
|
-5.04 Millimeter of mercury (mmHg)
Standard Deviation 4.220
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
DBP, Day 2, 0-4 h
|
-0.11 Millimeter of mercury (mmHg)
Standard Deviation 5.750
|
-5.02 Millimeter of mercury (mmHg)
Standard Deviation 6.872
|
-2.24 Millimeter of mercury (mmHg)
Standard Deviation 4.980
|
-5.29 Millimeter of mercury (mmHg)
Standard Deviation 3.166
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
DBP, Day 14, 0-4 h
|
-2.62 Millimeter of mercury (mmHg)
Standard Deviation 7.857
|
-2.89 Millimeter of mercury (mmHg)
Standard Deviation 5.849
|
-3.20 Millimeter of mercury (mmHg)
Standard Deviation 7.134
|
-7.43 Millimeter of mercury (mmHg)
Standard Deviation 10.323
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
DBP, Day 15, 0-4 h
|
-1.26 Millimeter of mercury (mmHg)
Standard Deviation 4.685
|
-2.78 Millimeter of mercury (mmHg)
Standard Deviation 4.980
|
-4.76 Millimeter of mercury (mmHg)
Standard Deviation 5.665
|
-9.34 Millimeter of mercury (mmHg)
Standard Deviation 10.566
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
DBP, Day 7, 0-24 h
|
-5.46 Millimeter of mercury (mmHg)
Standard Deviation 7.290
|
-7.28 Millimeter of mercury (mmHg)
Standard Deviation 5.863
|
-4.50 Millimeter of mercury (mmHg)
Standard Deviation 4.737
|
-13.97 Millimeter of mercury (mmHg)
Standard Deviation 7.610
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
DBP, Day 14, 0-24 h
|
-7.75 Millimeter of mercury (mmHg)
Standard Deviation 7.996
|
-7.95 Millimeter of mercury (mmHg)
Standard Deviation 6.409
|
-5.91 Millimeter of mercury (mmHg)
Standard Deviation 6.979
|
-12.53 Millimeter of mercury (mmHg)
Standard Deviation 8.622
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
SBP, Day 7, pre-dose
|
-7.21 Millimeter of mercury (mmHg)
Standard Deviation 10.073
|
-4.54 Millimeter of mercury (mmHg)
Standard Deviation 16.602
|
-1.67 Millimeter of mercury (mmHg)
Standard Deviation 9.823
|
-6.55 Millimeter of mercury (mmHg)
Standard Deviation 8.572
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
SBP, Day 1, 0-4 h
|
-3.99 Millimeter of mercury (mmHg)
Standard Deviation 7.343
|
-6.18 Millimeter of mercury (mmHg)
Standard Deviation 7.152
|
-3.23 Millimeter of mercury (mmHg)
Standard Deviation 10.613
|
-4.27 Millimeter of mercury (mmHg)
Standard Deviation 8.566
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
SBP, Day 2, 0-4 h
|
-8.96 Millimeter of mercury (mmHg)
Standard Deviation 12.423
|
-11.76 Millimeter of mercury (mmHg)
Standard Deviation 11.715
|
-5.73 Millimeter of mercury (mmHg)
Standard Deviation 7.883
|
-7.12 Millimeter of mercury (mmHg)
Standard Deviation 8.388
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
SBP, Day 8, 0-4 h
|
-11.11 Millimeter of mercury (mmHg)
Standard Deviation 11.261
|
-10.67 Millimeter of mercury (mmHg)
Standard Deviation 10.713
|
-6.14 Millimeter of mercury (mmHg)
Standard Deviation 14.561
|
-13.42 Millimeter of mercury (mmHg)
Standard Deviation 13.907
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
SBP, Day 14, 0-4 h
|
-8.82 Millimeter of mercury (mmHg)
Standard Deviation 12.338
|
-8.14 Millimeter of mercury (mmHg)
Standard Deviation 9.324
|
-9.36 Millimeter of mercury (mmHg)
Standard Deviation 10.142
|
-11.06 Millimeter of mercury (mmHg)
Standard Deviation 13.844
|
|
Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time
SBP, Day 14, 0-24 h
|
-14.29 Millimeter of mercury (mmHg)
Standard Deviation 12.265
|
-14.13 Millimeter of mercury (mmHg)
Standard Deviation 11.422
|
-12.79 Millimeter of mercury (mmHg)
Standard Deviation 10.319
|
-14.34 Millimeter of mercury (mmHg)
Standard Deviation 10.636
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose) up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
BP was measured using 28.5 h ABPM. Maximum SBP and minimum DBP at 0-4 h post-dose was obtained on Day 1, 2, 7, 8, 14 and 15. For the calculation of 0-4 h maximum/minimum change from Baseline, measurements post-dose up to 6 h (actual time) was included. Baseline was defined as the pre-dose weighted mean of Day 1 for SBP and DBP. Maximum/minimum change from Baseline was calculated by subtracting the Baseline value (weighted mean pre-dose Day 1 for SBP and DBP) from the maximum/minimum assessment value (during 0-4 h) of the individual post-Baseline time points.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Maximum SBP, Day 1
|
11.2 mmHg
Standard Deviation 9.46
|
11.8 mmHg
Standard Deviation 6.77
|
14.5 mmHg
Standard Deviation 11.26
|
9.3 mmHg
Standard Deviation 9.56
|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Maximum SBP, Day 2
|
2.8 mmHg
Standard Deviation 14.31
|
2.8 mmHg
Standard Deviation 12.34
|
10.2 mmHg
Standard Deviation 11.49
|
4.4 mmHg
Standard Deviation 9.38
|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Maximum SBP, Day 7
|
6.9 mmHg
Standard Deviation 10.06
|
8.8 mmHg
Standard Deviation 13.91
|
14.5 mmHg
Standard Deviation 8.55
|
2.8 mmHg
Standard Deviation 13.80
|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Maximum SBP, Day 8
|
2.1 mmHg
Standard Deviation 11.92
|
4.2 mmHg
Standard Deviation 15.20
|
7.2 mmHg
Standard Deviation 17.17
|
-1.2 mmHg
Standard Deviation 16.82
|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Maximum SBP, Day 14
|
9.1 mmHg
Standard Deviation 10.25
|
9.4 mmHg
Standard Deviation 12.89
|
8.1 mmHg
Standard Deviation 9.44
|
2.9 mmHg
Standard Deviation 14.52
|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Maximum SBP, Day 15
|
5.7 mmHg
Standard Deviation 15.38
|
-2.5 mmHg
Standard Deviation 13.39
|
3.3 mmHg
Standard Deviation 12.11
|
-3.3 mmHg
Standard Deviation 12.07
|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Minimum, DBP, Day 1
|
-8.3 mmHg
Standard Deviation 5.79
|
-12.7 mmHg
Standard Deviation 7.93
|
-11.5 mmHg
Standard Deviation 9.07
|
-14.5 mmHg
Standard Deviation 4.88
|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Minimum, DBP, Day 2
|
-8.8 mmHg
Standard Deviation 7.83
|
-14.0 mmHg
Standard Deviation 9.59
|
-12.5 mmHg
Standard Deviation 7.21
|
-15.0 mmHg
Standard Deviation 5.19
|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Minimum, DBP, Day 7
|
-9.3 mmHg
Standard Deviation 7.84
|
-15.4 mmHg
Standard Deviation 9.69
|
-12.2 mmHg
Standard Deviation 8.60
|
-14.7 mmHg
Standard Deviation 9.33
|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Minimum, DBP, Day 8
|
-8.0 mmHg
Standard Deviation 9.67
|
-13.4 mmHg
Standard Deviation 9.22
|
-10.4 mmHg
Standard Deviation 8.31
|
-19.2 mmHg
Standard Deviation 11.90
|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Minimum, DBP, Day 14
|
-17.0 mmHg
Standard Deviation 12.93
|
-15.8 mmHg
Standard Deviation 9.62
|
-16.5 mmHg
Standard Deviation 12.85
|
-14.3 mmHg
Standard Deviation 10.72
|
|
Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time
Minimum, DBP, Day 15
|
-10.2 mmHg
Standard Deviation 6.95
|
-12.2 mmHg
Standard Deviation 7.13
|
-14.3 mmHg
Standard Deviation 12.37
|
-17.3 mmHg
Standard Deviation 12.12
|
SECONDARY outcome
Timeframe: Day 1 up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
BP was measured using 28.5 h ABPM. Weighted mean SBP and DBP at 0-4 h post-dose was obtained on Day 1, 2, 7, 8, 14 and 15. Weighted mean SBP and DBP at 0-24 h post-dose was obtained on Day 1, 7 and 14. Maximum SBP and minimum DBP at 0-4 h post-dose was obtained on Day 1, 2, 7, 8, 14 and 15. Baseline was defined as the pre-dose weighted mean of Day 1.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean SBP 0-4, Day 1
|
130.55 mmHg
Standard Deviation 15.052
|
128.47 mmHg
Standard Deviation 11.670
|
130.66 mmHg
Standard Deviation 16.508
|
126.05 mmHg
Standard Deviation 14.111
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean SBP 0-4, Day 2
|
128.15 mmHg
Standard Deviation 18.616
|
122.90 mmHg
Standard Deviation 13.129
|
129.23 mmHg
Standard Deviation 16.139
|
124.03 mmHg
Standard Deviation 16.147
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean SBP 0-4, Day 7
|
129.32 mmHg
Standard Deviation 16.655
|
126.46 mmHg
Standard Deviation 15.897
|
130.52 mmHg
Standard Deviation 13.432
|
123.10 mmHg
Standard Deviation 12.523
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean SBP 0-4, Day 8
|
128.54 mmHg
Standard Deviation 16.817
|
123.65 mmHg
Standard Deviation 15.120
|
127.55 mmHg
Standard Deviation 13.141
|
117.26 mmHg
Standard Deviation 11.281
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean SBP 0-4, Day 14
|
130.71 mmHg
Standard Deviation 17.527
|
124.59 mmHg
Standard Deviation 9.640
|
124.86 mmHg
Standard Deviation 13.833
|
122.94 mmHg
Standard Deviation 11.670
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean SBP 0-4, Day 15
|
128.84 mmHg
Standard Deviation 17.647
|
120.74 mmHg
Standard Deviation 14.472
|
124.68 mmHg
Standard Deviation 14.886
|
118.52 mmHg
Standard Deviation 14.773
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean SBP 0-24, Day 1
|
122.64 mmHg
Standard Deviation 16.675
|
117.48 mmHg
Standard Deviation 11.246
|
124.41 mmHg
Standard Deviation 13.961
|
117.94 mmHg
Standard Deviation 11.565
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean SBP 0-24, Day 7
|
124.22 mmHg
Standard Deviation 16.893
|
118.98 mmHg
Standard Deviation 11.587
|
124.60 mmHg
Standard Deviation 12.774
|
116.34 mmHg
Standard Deviation 11.150
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean SBP 0-24, Day 14
|
125.45 mmHg
Standard Deviation 16.546
|
118.60 mmHg
Standard Deviation 8.748
|
122.71 mmHg
Standard Deviation 16.117
|
119.11 mmHg
Standard Deviation 9.109
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Maximum SBP 0-4 h, Day 1
|
150.0 mmHg
Standard Deviation 18.72
|
146.4 mmHg
Standard Deviation 15.61
|
147.6 mmHg
Standard Deviation 18.78
|
141.3 mmHg
Standard Deviation 15.03
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Maximum SBP 0-4 h, Day 2
|
140.0 mmHg
Standard Deviation 19.98
|
137.4 mmHg
Standard Deviation 15.78
|
145.9 mmHg
Standard Deviation 21.48
|
136.0 mmHg
Standard Deviation 16.71
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Maximum SBP 0-4 h, Day 7
|
143.9 mmHg
Standard Deviation 20.10
|
142.7 mmHg
Standard Deviation 20.02
|
148.4 mmHg
Standard Deviation 18.60
|
135.5 mmHg
Standard Deviation 15.97
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Maximum SBP 0-4 h, Day 8
|
141.1 mmHg
Standard Deviation 17.13
|
138.1 mmHg
Standard Deviation 19.26
|
141.8 mmHg
Standard Deviation 17.64
|
129.4 mmHg
Standard Deviation 14.06
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Maximum SBP 0-4 h, Day 14
|
148.4 mmHg
Standard Deviation 20.04
|
143.3 mmHg
Standard Deviation 14.06
|
141.3 mmHg
Standard Deviation 14.43
|
135.1 mmHg
Standard Deviation 12.94
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Maximum SBP 0-4 h, Day 15
|
142.8 mmHg
Standard Deviation 21.83
|
131.4 mmHg
Standard Deviation 16.91
|
138.4 mmHg
Standard Deviation 13.08
|
129.8 mmHg
Standard Deviation 15.02
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean DBP 0-4, Day 1
|
82.48 mmHg
Standard Deviation 9.817
|
77.54 mmHg
Standard Deviation 8.200
|
77.46 mmHg
Standard Deviation 11.603
|
78.14 mmHg
Standard Deviation 10.879
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean DBP 0-4, Day 2
|
80.81 mmHg
Standard Deviation 9.182
|
74.01 mmHg
Standard Deviation 7.959
|
74.67 mmHg
Standard Deviation 12.607
|
77.07 mmHg
Standard Deviation 12.058
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean DBP 0-4, Day 7
|
82.83 mmHg
Standard Deviation 10.367
|
78.07 mmHg
Standard Deviation 8.744
|
74.87 mmHg
Standard Deviation 11.216
|
74.63 mmHg
Standard Deviation 8.888
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean DBP 0-4, Day 8
|
81.88 mmHg
Standard Deviation 11.151
|
75.82 mmHg
Standard Deviation 9.090
|
74.77 mmHg
Standard Deviation 10.137
|
71.24 mmHg
Standard Deviation 10.305
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean DBP 0-4, Day 14
|
81.49 mmHg
Standard Deviation 10.037
|
76.31 mmHg
Standard Deviation 4.101
|
72.14 mmHg
Standard Deviation 10.218
|
76.10 mmHg
Standard Deviation 8.595
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean DBP 0-4, Day 15
|
79.25 mmHg
Standard Deviation 9.154
|
75.25 mmHg
Standard Deviation 7.330
|
71.94 mmHg
Standard Deviation 11.908
|
73.61 mmHg
Standard Deviation 12.810
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean DBP 0-24, Day 1
|
74.44 mmHg
Standard Deviation 8.758
|
70.53 mmHg
Standard Deviation 7.941
|
71.58 mmHg
Standard Deviation 10.670
|
70.49 mmHg
Standard Deviation 10.530
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean DBP 0-24, Day 7
|
76.20 mmHg
Standard Deviation 9.831
|
72.18 mmHg
Standard Deviation 6.598
|
71.10 mmHg
Standard Deviation 10.471
|
67.46 mmHg
Standard Deviation 7.075
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Weighted mean DBP 0-24, Day 14
|
76.07 mmHg
Standard Deviation 9.443
|
71.24 mmHg
Standard Deviation 5.775
|
69.95 mmHg
Standard Deviation 11.156
|
71.00 mmHg
Standard Deviation 7.793
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Minimum DBP 0-4 h, Day 1
|
73.1 mmHg
Standard Deviation 9.14
|
66.4 mmHg
Standard Deviation 9.73
|
65.4 mmHg
Standard Deviation 12.03
|
69.3 mmHg
Standard Deviation 9.99
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Minimum DBP 0-4 h, Day 2
|
73.6 mmHg
Standard Deviation 11.43
|
65.1 mmHg
Standard Deviation 9.74
|
63.4 mmHg
Standard Deviation 12.27
|
68.1 mmHg
Standard Deviation 12.84
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Minimum DBP 0-4 h, Day 7
|
72.6 mmHg
Standard Deviation 10.55
|
63.3 mmHg
Standard Deviation 12.12
|
63.9 mmHg
Standard Deviation 11.53
|
67.1 mmHg
Standard Deviation 8.07
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Minimum DBP 0-4 h, Day 8
|
74.1 mmHg
Standard Deviation 10.49
|
65.2 mmHg
Standard Deviation 11.95
|
65.1 mmHg
Standard Deviation 11.10
|
62.6 mmHg
Standard Deviation 12.38
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Minimum DBP 0-4 h, Day 14
|
65.8 mmHg
Standard Deviation 14.53
|
62.8 mmHg
Standard Deviation 7.75
|
59.3 mmHg
Standard Deviation 13.32
|
67.4 mmHg
Standard Deviation 10.67
|
|
Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM
Minimum DBP 0-4 h, Day 15
|
70.6 mmHg
Standard Deviation 9.17
|
66.4 mmHg
Standard Deviation 8.60
|
64.0 mmHg
Standard Deviation 15.06
|
65.6 mmHg
Standard Deviation 13.92
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose) up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
A 12-lead ECG was recorded on Day 1, 2, 7, 8, 14 and 15 with the participant in a supine position having rested in that position for at least 5 min before each reading. A total of 3 measurements separated by at least 1 min was taken at each visit and the mean recorded. The Baseline for pre-dose QTcF and QTcB measurements was the pre-dose assessment on Day 1. Weighted mean at 0-4 h for QTcF and QTcB was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean change from Baseline was the AAUCMB. The change from Baseline in maximum QTcF and QTcB at 0-4 h was calculated by subtracting the Baseline (pre-dose Day 1) value from the individual post-Baseline values.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Maximum 0-4 h, Day 14
|
7.713 Millisecond (msec)
Standard Deviation 14.0810
|
6.651 Millisecond (msec)
Standard Deviation 8.6838
|
16.715 Millisecond (msec)
Standard Deviation 9.8480
|
-0.394 Millisecond (msec)
Standard Deviation 13.4669
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Weighted mean 0-4 h, Day 2
|
-0.8322 Millisecond (msec)
Standard Deviation 11.91468
|
4.5011 Millisecond (msec)
Standard Deviation 12.15813
|
12.1052 Millisecond (msec)
Standard Deviation 24.42441
|
0.4464 Millisecond (msec)
Standard Deviation 10.89990
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Weighted mean 0-4 h, Day 8
|
-2.1592 Millisecond (msec)
Standard Deviation 13.74186
|
-2.5879 Millisecond (msec)
Standard Deviation 12.83153
|
12.5741 Millisecond (msec)
Standard Deviation 22.22059
|
-3.9026 Millisecond (msec)
Standard Deviation 16.69124
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Day 7, pre-dose
|
2.548 Millisecond (msec)
Standard Deviation 14.3648
|
4.166 Millisecond (msec)
Standard Deviation 10.8863
|
4.557 Millisecond (msec)
Standard Deviation 12.5535
|
-1.622 Millisecond (msec)
Standard Deviation 14.8225
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Day 14, pre-dose
|
2.445 Millisecond (msec)
Standard Deviation 14.8051
|
-2.215 Millisecond (msec)
Standard Deviation 8.8487
|
1.450 Millisecond (msec)
Standard Deviation 11.8828
|
-5.803 Millisecond (msec)
Standard Deviation 12.6960
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Weighted mean 0-4 h, Day 1
|
1.5102 Millisecond (msec)
Standard Deviation 9.80314
|
1.2546 Millisecond (msec)
Standard Deviation 7.47433
|
5.1325 Millisecond (msec)
Standard Deviation 9.99564
|
-0.2457 Millisecond (msec)
Standard Deviation 6.77374
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Weighted mean 0-4 h, Day 2
|
1.4515 Millisecond (msec)
Standard Deviation 9.95165
|
4.3733 Millisecond (msec)
Standard Deviation 7.91878
|
10.5957 Millisecond (msec)
Standard Deviation 16.92211
|
-1.0685 Millisecond (msec)
Standard Deviation 8.45786
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Weighted mean 0-4 h, Day 7
|
0.5278 Millisecond (msec)
Standard Deviation 11.61138
|
3.4646 Millisecond (msec)
Standard Deviation 10.28713
|
8.8287 Millisecond (msec)
Standard Deviation 10.77947
|
-2.6011 Millisecond (msec)
Standard Deviation 14.22194
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Weighted mean 0-4 h, Day 8
|
-0.2753 Millisecond (msec)
Standard Deviation 13.37615
|
-1.5941 Millisecond (msec)
Standard Deviation 9.79215
|
8.7690 Millisecond (msec)
Standard Deviation 14.91393
|
-5.8609 Millisecond (msec)
Standard Deviation 15.48314
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Weighted mean 0-4 h, Day 14
|
3.8254 Millisecond (msec)
Standard Deviation 14.80602
|
0.8731 Millisecond (msec)
Standard Deviation 8.87134
|
9.0192 Millisecond (msec)
Standard Deviation 10.65315
|
-3.7270 Millisecond (msec)
Standard Deviation 14.27827
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Weighted mean 0-4 h, Day 15
|
0.2258 Millisecond (msec)
Standard Deviation 15.48959
|
-2.3710 Millisecond (msec)
Standard Deviation 9.06406
|
9.3434 Millisecond (msec)
Standard Deviation 10.40650
|
-7.9229 Millisecond (msec)
Standard Deviation 9.51166
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Maximum 0-4 h, Day 1
|
6.138 Millisecond (msec)
Standard Deviation 8.3179
|
8.099 Millisecond (msec)
Standard Deviation 9.3911
|
11.169 Millisecond (msec)
Standard Deviation 9.4879
|
6.334 Millisecond (msec)
Standard Deviation 7.0411
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Maximum 0-4 h, Day 2
|
7.238 Millisecond (msec)
Standard Deviation 9.8912
|
8.860 Millisecond (msec)
Standard Deviation 7.1928
|
16.650 Millisecond (msec)
Standard Deviation 18.1579
|
3.940 Millisecond (msec)
Standard Deviation 8.4250
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Maximum 0-4 h, Day 7
|
7.422 Millisecond (msec)
Standard Deviation 10.5173
|
8.586 Millisecond (msec)
Standard Deviation 11.5664
|
14.866 Millisecond (msec)
Standard Deviation 11.4977
|
2.146 Millisecond (msec)
Standard Deviation 13.5782
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Maximum 0-4 h, Day 8
|
4.765 Millisecond (msec)
Standard Deviation 14.1015
|
3.434 Millisecond (msec)
Standard Deviation 8.9030
|
15.425 Millisecond (msec)
Standard Deviation 14.2054
|
-0.707 Millisecond (msec)
Standard Deviation 16.9799
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcF, Maximum 0-4 h, Day 15
|
5.690 Millisecond (msec)
Standard Deviation 15.6489
|
1.254 Millisecond (msec)
Standard Deviation 7.5156
|
15.698 Millisecond (msec)
Standard Deviation 11.7395
|
0.585 Millisecond (msec)
Standard Deviation 13.3811
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Weighted mean 0-4 h, Day 14
|
1.5770 Millisecond (msec)
Standard Deviation 16.69052
|
1.1100 Millisecond (msec)
Standard Deviation 12.02700
|
11.8220 Millisecond (msec)
Standard Deviation 16.58898
|
-1.9538 Millisecond (msec)
Standard Deviation 15.99966
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Weighted mean 0-4 h, Day 15
|
0.2536 Millisecond (msec)
Standard Deviation 13.32367
|
-2.1912 Millisecond (msec)
Standard Deviation 13.19232
|
11.8730 Millisecond (msec)
Standard Deviation 19.06660
|
-5.4291 Millisecond (msec)
Standard Deviation 11.64105
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Maximum 0-4 h, Day 1
|
4.600 Millisecond (msec)
Standard Deviation 9.0150
|
9.902 Millisecond (msec)
Standard Deviation 12.1193
|
15.314 Millisecond (msec)
Standard Deviation 12.8527
|
8.448 Millisecond (msec)
Standard Deviation 9.0077
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Maximum 0-4 h, Day 2
|
5.130 Millisecond (msec)
Standard Deviation 12.9391
|
10.797 Millisecond (msec)
Standard Deviation 11.0215
|
19.846 Millisecond (msec)
Standard Deviation 26.4494
|
6.038 Millisecond (msec)
Standard Deviation 10.0240
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Maximum 0-4 h, Day 7
|
9.599 Millisecond (msec)
Standard Deviation 15.2443
|
9.884 Millisecond (msec)
Standard Deviation 10.8668
|
19.748 Millisecond (msec)
Standard Deviation 18.6338
|
5.125 Millisecond (msec)
Standard Deviation 15.1542
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Maximum 0-4 h, Day 8
|
4.930 Millisecond (msec)
Standard Deviation 15.4632
|
3.308 Millisecond (msec)
Standard Deviation 10.8675
|
22.344 Millisecond (msec)
Standard Deviation 21.0882
|
2.949 Millisecond (msec)
Standard Deviation 17.3141
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Maximum 0-4 h, Day 14
|
6.941 Millisecond (msec)
Standard Deviation 16.7794
|
7.250 Millisecond (msec)
Standard Deviation 12.2421
|
20.698 Millisecond (msec)
Standard Deviation 14.3145
|
1.685 Millisecond (msec)
Standard Deviation 15.2440
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Maximum 0-4 h, Day 15
|
6.646 Millisecond (msec)
Standard Deviation 14.1139
|
3.569 Millisecond (msec)
Standard Deviation 10.9642
|
19.933 Millisecond (msec)
Standard Deviation 19.5949
|
3.343 Millisecond (msec)
Standard Deviation 14.0019
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Day 7, pre-dose
|
3.490 Millisecond (msec)
Standard Deviation 14.8170
|
4.033 Millisecond (msec)
Standard Deviation 11.4412
|
3.491 Millisecond (msec)
Standard Deviation 17.2891
|
-0.982 Millisecond (msec)
Standard Deviation 18.2505
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Day 14, pre-dose
|
2.236 Millisecond (msec)
Standard Deviation 18.0863
|
-2.150 Millisecond (msec)
Standard Deviation 12.5311
|
0.364 Millisecond (msec)
Standard Deviation 13.4871
|
-6.254 Millisecond (msec)
Standard Deviation 14.4987
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Weighted mean 0-4 h, Day 1
|
-1.4368 Millisecond (msec)
Standard Deviation 10.48286
|
1.9240 Millisecond (msec)
Standard Deviation 9.38964
|
7.2528 Millisecond (msec)
Standard Deviation 14.91350
|
0.4135 Millisecond (msec)
Standard Deviation 7.78546
|
|
Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time
QTcB, Weighted mean 0-4 h, Day 7
|
0.6551 Millisecond (msec)
Standard Deviation 14.84890
|
3.1554 Millisecond (msec)
Standard Deviation 11.81255
|
10.6108 Millisecond (msec)
Standard Deviation 16.58029
|
-1.1323 Millisecond (msec)
Standard Deviation 16.11649
|
SECONDARY outcome
Timeframe: Day 1 up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
A 12-lead ECG was recorded on Day 1, 2, 7, 8, 14 and 15 with the participant in a supine position having rested in that position for at least 5 min before each reading. A total of 3 measurements separated by at least 1 min was taken at each visit and the mean recorded. The pre-dose QTcF and QTcB assessment was done at Day 1, 7 and 14. Weighted mean at 0-4 h for QTcF and QTcB at Day 1, 2, 7, 8, 14 and 15 was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The maximum QTcF and QTcB at 0-4 h was obtained at Day 1, 2, 7, 8, 14 and 15.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Day 14, pre-dose
|
409.909 msec
Standard Deviation 19.5835
|
402.505 msec
Standard Deviation 25.5206
|
398.524 msec
Standard Deviation 21.6747
|
403.905 msec
Standard Deviation 15.6393
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Maximum 0-4 h, Day 14
|
405.360 msec
Standard Deviation 13.6156
|
406.050 msec
Standard Deviation 20.5479
|
407.790 msec
Standard Deviation 20.6278
|
398.931 msec
Standard Deviation 18.9056
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Maximum 0-4 h, Day 15
|
403.337 msec
Standard Deviation 16.9640
|
400.653 msec
Standard Deviation 18.6693
|
406.773 msec
Standard Deviation 19.4447
|
399.910 msec
Standard Deviation 17.1580
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Day 1, pre-dose
|
396.518 msec
Standard Deviation 18.9384
|
397.667 msec
Standard Deviation 17.9057
|
391.300 msec
Standard Deviation 23.3733
|
396.361 msec
Standard Deviation 16.7847
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Day 7, pre-dose
|
398.828 msec
Standard Deviation 14.5763
|
403.565 msec
Standard Deviation 23.5668
|
396.804 msec
Standard Deviation 19.9587
|
396.897 msec
Standard Deviation 16.8340
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Day 14, pre-dose
|
399.599 msec
Standard Deviation 14.8681
|
397.184 msec
Standard Deviation 20.8546
|
392.524 msec
Standard Deviation 24.7455
|
393.522 msec
Standard Deviation 15.5437
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Weighted mean 0-4 h, Day 1
|
399.1571 msec
Standard Deviation 20.93784
|
398.9213 msec
Standard Deviation 18.95805
|
396.4321 msec
Standard Deviation 23.12234
|
396.6588 msec
Standard Deviation 18.71828
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Weighted mean 0-4 h, Day 2
|
399.0984 msec
Standard Deviation 20.76430
|
402.0399 msec
Standard Deviation 18.98919
|
401.8953 msec
Standard Deviation 23.15689
|
397.3482 msec
Standard Deviation 17.29841
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Weighted mean 0-4 h, Day 7
|
397.6228 msec
Standard Deviation 13.80395
|
402.8639 msec
Standard Deviation 23.36556
|
401.0754 msec
Standard Deviation 24.39809
|
395.9180 msec
Standard Deviation 19.47963
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Weighted mean 0-4 h, Day 8
|
397.3716 msec
Standard Deviation 18.94814
|
396.6669 msec
Standard Deviation 19.88573
|
401.0157 msec
Standard Deviation 22.80350
|
393.4643 msec
Standard Deviation 19.93914
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Weighted mean 0-4 h, Day 14
|
399.8488 msec
Standard Deviation 13.18337
|
400.2724 msec
Standard Deviation 19.00353
|
400.0939 msec
Standard Deviation 20.11137
|
395.5983 msec
Standard Deviation 19.45327
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Weighted mean 0-4 h, Day 15
|
397.8727 msec
Standard Deviation 16.14803
|
397.0283 msec
Standard Deviation 20.64521
|
400.4180 msec
Standard Deviation 19.18469
|
392.3686 msec
Standard Deviation 16.99407
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Maximum 0-4 h, Day 1
|
402.656 msec
Standard Deviation 20.3503
|
405.766 msec
Standard Deviation 20.3313
|
402.468 msec
Standard Deviation 22.2225
|
402.696 msec
Standard Deviation 16.6072
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Maximum 0-4 h, Day 2
|
404.885 msec
Standard Deviation 21.1074
|
406.526 msec
Standard Deviation 19.2241
|
407.950 msec
Standard Deviation 23.4527
|
400.844 msec
Standard Deviation 18.8346
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Maximum 0-4 h, Day 7
|
405.069 msec
Standard Deviation 16.2300
|
407.985 msec
Standard Deviation 24.5587
|
407.113 msec
Standard Deviation 24.2679
|
400.665 msec
Standard Deviation 18.8396
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcF, Maximum 0-4 h, Day 8
|
402.412 msec
Standard Deviation 17.9804
|
402.833 msec
Standard Deviation 19.0273
|
407.671 msec
Standard Deviation 21.7779
|
398.618 msec
Standard Deviation 20.0406
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Day 1, pre-dose
|
405.222 msec
Standard Deviation 20.8892
|
402.023 msec
Standard Deviation 22.2404
|
396.975 msec
Standard Deviation 24.1244
|
406.463 msec
Standard Deviation 21.3658
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Day 7, pre-dose
|
407.380 msec
Standard Deviation 17.7924
|
408.688 msec
Standard Deviation 24.8189
|
401.221 msec
Standard Deviation 16.6437
|
409.064 msec
Standard Deviation 19.5591
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Weighted mean 0-4 h, Day 1
|
405.1192 msec
Standard Deviation 22.72290
|
403.9471 msec
Standard Deviation 22.10540
|
404.2282 msec
Standard Deviation 23.22646
|
408.8990 msec
Standard Deviation 21.51019
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Weighted mean 0-4 h, Day 2
|
405.7239 msec
Standard Deviation 21.67872
|
406.5243 msec
Standard Deviation 19.43633
|
409.0807 msec
Standard Deviation 23.78119
|
411.1034 msec
Standard Deviation 18.99910
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Weighted mean 0-4 h, Day 7
|
405.1001 msec
Standard Deviation 14.32210
|
407.8107 msec
Standard Deviation 24.03156
|
408.3410 msec
Standard Deviation 20.23969
|
408.9141 msec
Standard Deviation 21.56424
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Weighted mean 0-4 h, Day 8
|
404.3968 msec
Standard Deviation 22.29983
|
401.5862 msec
Standard Deviation 24.75626
|
410.3044 msec
Standard Deviation 20.92796
|
406.2555 msec
Standard Deviation 20.30000
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Weighted mean 0-4 h, Day 14
|
409.5049 msec
Standard Deviation 18.03324
|
405.7653 msec
Standard Deviation 22.29165
|
409.9818 msec
Standard Deviation 19.36717
|
408.2043 msec
Standard Deviation 20.49320
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Weighted mean 0-4 h, Day 15
|
406.8096 msec
Standard Deviation 20.18685
|
402.4642 msec
Standard Deviation 25.07009
|
410.0328 msec
Standard Deviation 18.49302
|
406.7532 msec
Standard Deviation 16.53736
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Maximum 0-4 h, Day 1
|
409.821 msec
Standard Deviation 20.9888
|
411.925 msec
Standard Deviation 22.5302
|
412.289 msec
Standard Deviation 22.9219
|
414.910 msec
Standard Deviation 20.9889
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Maximum 0-4 h, Day 2
|
411.686 msec
Standard Deviation 21.7606
|
412.820 msec
Standard Deviation 20.3513
|
416.821 msec
Standard Deviation 24.7489
|
414.524 msec
Standard Deviation 21.3863
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Maximum 0-4 h, Day 7
|
416.155 msec
Standard Deviation 18.5802
|
414.540 msec
Standard Deviation 22.8711
|
417.478 msec
Standard Deviation 21.5061
|
415.172 msec
Standard Deviation 20.2556
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Maximum 0-4 h, Day 8
|
411.486 msec
Standard Deviation 23.2760
|
407.963 msec
Standard Deviation 22.5265
|
420.074 msec
Standard Deviation 17.7199
|
413.107 msec
Standard Deviation 18.3979
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Maximum 0-4 h, Day 14
|
413.498 msec
Standard Deviation 16.8864
|
411.906 msec
Standard Deviation 22.0750
|
418.858 msec
Standard Deviation 20.5848
|
411.843 msec
Standard Deviation 18.6525
|
|
Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time
QTcB, Maximum 0-4 h, Day 15
|
413.202 msec
Standard Deviation 22.3810
|
408.224 msec
Standard Deviation 23.3075
|
418.093 msec
Standard Deviation 18.7721
|
413.501 msec
Standard Deviation 14.6549
|
SECONDARY outcome
Timeframe: Day 1 up to Day 14Population: Safety Population. Only those participants available at the specified time points were analyzed.
A holter monitor is a machine that continuously records the heart's electrical activity. A 3-lead holter ECG monitoring device was used. The monitor was worn for 24 h during normal activity to record the ECG intervals. The assesmment for hourly maximums QTcF and QTcB was done on Day 1, Day 7 and Day 14. For each h of holter monitoring the maximum QTcF for that h was calculated using the maximum QT and mean HR of that given h as Maximum QT divided by (60/Mean HR)\^1/3. For each h of holter monitoring the maximum QTcB for that h was calculated using the maximum QT and mean HR of that given h as Maximum QT divided by (60/Mean HR)\^1/2.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Mean of Hourly Maximums QTcF and QTcB Derived From 24 h 3-lead Holter ECG Monitoring Over Time
Day 1, QTcF
|
474.2567 msec
Standard Deviation 26.91319
|
470.3755 msec
Standard Deviation 21.52200
|
468.4990 msec
Standard Deviation 28.95477
|
470.6075 msec
Standard Deviation 20.80669
|
|
Mean of Hourly Maximums QTcF and QTcB Derived From 24 h 3-lead Holter ECG Monitoring Over Time
Day 7, QTcF
|
471.3443 msec
Standard Deviation 17.96397
|
470.9166 msec
Standard Deviation 18.10351
|
471.2125 msec
Standard Deviation 30.75404
|
469.7194 msec
Standard Deviation 17.22701
|
|
Mean of Hourly Maximums QTcF and QTcB Derived From 24 h 3-lead Holter ECG Monitoring Over Time
Day 14, QTcF
|
471.3571 msec
Standard Deviation 14.87705
|
478.8226 msec
Standard Deviation 20.29032
|
461.4473 msec
Standard Deviation 32.41893
|
462.4090 msec
Standard Deviation 18.50928
|
|
Mean of Hourly Maximums QTcF and QTcB Derived From 24 h 3-lead Holter ECG Monitoring Over Time
Day 1, QTcB
|
491.2731 msec
Standard Deviation 32.55948
|
486.3962 msec
Standard Deviation 21.76741
|
484.1421 msec
Standard Deviation 31.72641
|
493.5255 msec
Standard Deviation 21.80365
|
|
Mean of Hourly Maximums QTcF and QTcB Derived From 24 h 3-lead Holter ECG Monitoring Over Time
Day 7, QTcB
|
491.1749 msec
Standard Deviation 21.97287
|
486.1238 msec
Standard Deviation 22.36925
|
488.0985 msec
Standard Deviation 33.52830
|
493.4279 msec
Standard Deviation 19.59523
|
|
Mean of Hourly Maximums QTcF and QTcB Derived From 24 h 3-lead Holter ECG Monitoring Over Time
Day 14, QTcB
|
489.5294 msec
Standard Deviation 18.51699
|
494.0542 msec
Standard Deviation 23.18669
|
479.8827 msec
Standard Deviation 36.11264
|
484.5300 msec
Standard Deviation 16.67519
|
SECONDARY outcome
Timeframe: Day 1 up to Day 14Population: Safety Population. Only those participants available at the specified time points were analyzed.
A holter monitor is a machine that continuously records the heart's electrical activity. A 3-lead holter ECG monitoring device was used. The monitor was worn for 24 h during normal activity to record the heart's rhythm. The assessment for the events of supra ventricular ectopics, ventricular ectopics and ventricular runs per 24 h was done on Day 1, Day 7 and Day 14.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Number of Events of Supra Ventricular Ectopics, Ventricular Ectopics and Ventricular Runs Per 24 h Derived From 3-lead Holter ECG Monitoring Over Time
Day 1, Ventricular ectopics
|
0.0 Number of events
Standard Deviation 0.00
|
0.8 Number of events
Standard Deviation 1.65
|
3.6 Number of events
Standard Deviation 10.80
|
0.3 Number of events
Standard Deviation 1.00
|
|
Number of Events of Supra Ventricular Ectopics, Ventricular Ectopics and Ventricular Runs Per 24 h Derived From 3-lead Holter ECG Monitoring Over Time
Day 1, Ventricular runs
|
0.0 Number of events
Standard Deviation 0.00
|
0.2 Number of events
Standard Deviation 0.40
|
1.0 Number of events
Standard Deviation 3.16
|
0.1 Number of events
Standard Deviation 0.25
|
|
Number of Events of Supra Ventricular Ectopics, Ventricular Ectopics and Ventricular Runs Per 24 h Derived From 3-lead Holter ECG Monitoring Over Time
Day 1, Supra ventricular ectopics
|
107.2 Number of events
Standard Deviation 259.78
|
397.3 Number of events
Standard Deviation 982.72
|
134.9 Number of events
Standard Deviation 249.35
|
61.9 Number of events
Standard Deviation 128.69
|
|
Number of Events of Supra Ventricular Ectopics, Ventricular Ectopics and Ventricular Runs Per 24 h Derived From 3-lead Holter ECG Monitoring Over Time
Day 7, Supra ventricular ectopics
|
97.8 Number of events
Standard Deviation 220.23
|
321.4 Number of events
Standard Deviation 985.25
|
442.5 Number of events
Standard Deviation 900.98
|
73.0 Number of events
Standard Deviation 120.87
|
|
Number of Events of Supra Ventricular Ectopics, Ventricular Ectopics and Ventricular Runs Per 24 h Derived From 3-lead Holter ECG Monitoring Over Time
Day 7, Ventricular ectopics
|
1.0 Number of events
Standard Deviation 4.00
|
0.2 Number of events
Standard Deviation 0.77
|
0.2 Number of events
Standard Deviation 0.80
|
0.0 Number of events
Standard Deviation 0.00
|
|
Number of Events of Supra Ventricular Ectopics, Ventricular Ectopics and Ventricular Runs Per 24 h Derived From 3-lead Holter ECG Monitoring Over Time
Day 7, Ventricular runs
|
0.1 Number of events
Standard Deviation 0.25
|
0.1 Number of events
Standard Deviation 0.26
|
0.1 Number of events
Standard Deviation 0.27
|
0.0 Number of events
Standard Deviation 0.00
|
|
Number of Events of Supra Ventricular Ectopics, Ventricular Ectopics and Ventricular Runs Per 24 h Derived From 3-lead Holter ECG Monitoring Over Time
Day 14, Supra ventricular ectopics
|
27.5 Number of events
Standard Deviation 42.17
|
398.1 Number of events
Standard Deviation 1005.29
|
333.5 Number of events
Standard Deviation 821.98
|
93.3 Number of events
Standard Deviation 121.83
|
|
Number of Events of Supra Ventricular Ectopics, Ventricular Ectopics and Ventricular Runs Per 24 h Derived From 3-lead Holter ECG Monitoring Over Time
Day 14, Ventricular ectopics
|
0.5 Number of events
Standard Deviation 1.87
|
0.4 Number of events
Standard Deviation 1.55
|
0.0 Number of events
Standard Deviation 0.00
|
0.0 Number of events
Standard Deviation 0.00
|
|
Number of Events of Supra Ventricular Ectopics, Ventricular Ectopics and Ventricular Runs Per 24 h Derived From 3-lead Holter ECG Monitoring Over Time
Day 14, Ventricular runs
|
0.1 Number of events
Standard Deviation 0.27
|
0.1 Number of events
Standard Deviation 0.52
|
0.0 Number of events
Standard Deviation 0.00
|
0.0 Number of events
Standard Deviation 0.00
|
SECONDARY outcome
Timeframe: Baseline (Day 1) up to Day 14Population: Safety Population. Only those participants available at the specified time points were analyzed.
The parameters of biochemistry with their normal range included: alanine amino transferase (\[ALT\] 0-48 international units per liter \[IU/L\]), albumin (32-50 gram \[g\]/L), alkaline phosphatase (\[ALP\] 20-125 IU/L), aspartate amino transferase (\[AST\] 0-42 IU/L), calcium (2.12-2.56 millimole \[mmol\]/L, chloride (95-108 mmol/L), creatine kinase (\[CK\] 0-235 IU/L), creatinine (44-124 micromole \[µmol\]/L), direct bilirubin (0-6 µmol/L), gamma glutamyl transferase (\[GGT\] 0-65 IU/L), glucose (3.9-6.9 mmol/L), lactate dehydrogenase (\[LDH\] 0-250 IU/L), potassium (3.5-5.3 mmol/L), sodium (135-146 mmol/L), total bilirubin (0-22 µmol/L), total protein (60-85 g/L), urea (2.5-9 mmol/L) and uric acid (250-510 µmol/L). The assessments were performed on Day 1, Day 7 and Day 14. Baseline was defined as the assessment done on Day 1. Only those parameters for which at least one value of abnormality (to low or to high) change from Baseline, relative to normal ranges were reported are summarized.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Total Protein, change to low, Day 7
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
ALT, change to high, Day 7
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
AST, change to high, Day 7
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
AST, change to high, Day 14
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Calcium, change to low, Day 14
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Chloride, change to low, Day 7
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Chloride, change to high, Day 7
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Chloride, change to high, Day 14
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
CK, change to high, Day 14
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Direct Bilirubin, change to high, Day 7
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
GGT, change to high, Day 7
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
GGT, change to high, Day 14
|
0 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Glucose, change to high, Day 7
|
0 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Glucose, change to low, Day 14
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Glucose, change to high, Day 14
|
1 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
LDH, change to high, Day 7
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
LDH, change to high, Day 14
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Potassium, change to high, Day 14
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Sodium, change to low, Day 7
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Sodium, change to high, Day 7
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Sodium, change to high, Day 14
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Total Bilirubin, change to high, Day 7
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Total Protein, change to low, Day 14
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Urea, change to high, Day 7
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Urea, change to low, Day 14
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Uric acid, change to low, Day 14
|
0 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Uric acid, change to high, Day 14
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1) up to Day 14Population: Safety Population. Only those participants available at the specified time points were analyzed.
The parameters of biochemistry with their normal range included: basophils (0-0.2 giga cells \[GI\]/L), eosinophils (0.05-0.55 GI/L), haematocrit (0.41-0.5 ratio), hemoglobin (138-172 g/L), lymphocytes (0.85-4.1 GI/L), mean corpuscle hemoglobin (\[MCH\] 27-33 picogram \[pg\]), mean corpuscle hemoglobin concentration (\[MCHC\] 320-360 g/L), mean corpuscle volume (\[MCV\] 80-100 femtoliter \[fl\]), monocytes (0.2-1.1 GI/L), segmented neutrophils (1.8-8 GI/L), total neutrophils (1.8-8 GI/L), platelet count (130-400 GI/L), red blood cell (\[RBC\] 4.4-5.8 trillion cells \[TI\]/L) count and white blood cell (\[WBC\] 3.8-10.8 GI/L) count. The assessments were performed on Day 1, Day 7 and Day 14. Baseline was defined as the assessment done on Day 1. Only those parameters for which at least one value of abnormality (to low or to high) change from Baseline, relative to normal ranges were reported are summarized.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Eosinophils, change to low, Day 7
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Eosinophils, change to high, Day 7
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Eosinophils, change to high, Day 14
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Hematocrit, change to low, Day 7
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Hematocrit, change to high, Day 7
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Hematocrit, change to low, Day 14
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Hemoglobin, change to low, Day 7
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Hemoglobin, change to low, Day 14
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Lymphocytes, change to low, Day 7
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Lymphocytes, change to high, Day 7
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Lymphocytes, change to low, Day 14
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
MCH, change to high, Day 7
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
MCH, change to high, Day 14
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
MCV, change to high, Day 7
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
MCV, change to high, Day 14
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Monocytes, change to low, Day 7
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Monocytes, change to high, Day 7
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Monocytes, change to low, Day 14
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Monocytes, change to high, Day 14
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Platelet count, change to high, Day 14
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
RBC count, change to low, Day 7
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
RBC count, change to low, Day 14
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Segmented Neutrophils, change to low, Day 7
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Segmented Neutrophils, change to high, Day 7
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Segmented Neutrophils, change to low, Day 14
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Segmented Neutrophils, change to high, Day 14
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Total Neutrophils, change to low, Day 7
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Total Neutrophils, change to high, Day 7
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Total Neutrophils, change to low, Day 14
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
Total Neutrophils, change to high, Day 14
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
WBC count, change to low, Day 7
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
WBC count, change to high, Day 7
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
WBC count, change to low, Day 14
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14
WBC count, change to high, Day 14
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose) up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
FEV1 is defined as the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was assessed pre-dose at Day 1, 2, 7, 8, 14 and 15. FEV1 was assessed post-dose at Day 1, 2, 7, 8 and 14. Lung function test of FEV1 was performed at the approximately same time at each visit in the morning and highest of the 3 measurements were recorded. Baseline was defined as the assessment done on pre-dose Day 1. The change from Baseline pre-dose was calculated by subtracting the Baseline value (pre-dose Day 1) from the individual post Baseline (Day 2, 7, 8, 14 and 15) values. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean FEV1 0-4 h change from Baseline was the AAUCMB obtained at Day 1, 2, 7, 8, 14 and 15. The maximum FEV1 0-4 h change from Baseline was obtained at Day 1, Day 2, Day 7, Day 8, Day 14 and Day 15.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Weighted mean 0-4 h, Day 15
|
0.0339 Litres (L)
Standard Deviation 0.25474
|
0.2096 Litres (L)
Standard Deviation 0.10678
|
0.1973 Litres (L)
Standard Deviation 0.16988
|
0.1938 Litres (L)
Standard Deviation 0.28321
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Maximum 0-4 h, Day 7
|
0.137 Litres (L)
Standard Deviation 0.2752
|
0.251 Litres (L)
Standard Deviation 0.1196
|
0.317 Litres (L)
Standard Deviation 0.2080
|
0.283 Litres (L)
Standard Deviation 0.2459
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Day 7, Pre-dose
|
-0.019 Litres (L)
Standard Deviation 0.3068
|
0.139 Litres (L)
Standard Deviation 0.1159
|
0.149 Litres (L)
Standard Deviation 0.1934
|
0.181 Litres (L)
Standard Deviation 0.2584
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Day 14, Pre-dose
|
-0.006 Litres (L)
Standard Deviation 0.2975
|
0.155 Litres (L)
Standard Deviation 0.1449
|
0.183 Litres (L)
Standard Deviation 0.2502
|
0.055 Litres (L)
Standard Deviation 0.2349
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Weighted mean 0-4 h, Day 1
|
0.0513 Litres (L)
Standard Deviation 0.11220
|
0.1794 Litres (L)
Standard Deviation 0.10171
|
0.2099 Litres (L)
Standard Deviation 0.14168
|
0.2012 Litres (L)
Standard Deviation 0.12209
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Weighted mean 0-4 h, Day 2
|
0.0609 Litres (L)
Standard Deviation 0.17522
|
0.2427 Litres (L)
Standard Deviation 0.11735
|
0.2890 Litres (L)
Standard Deviation 0.17558
|
0.1829 Litres (L)
Standard Deviation 0.26427
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Weighted mean 0-4 h, Day 7
|
0.0480 Litres (L)
Standard Deviation 0.24623
|
0.2001 Litres (L)
Standard Deviation 0.12189
|
0.2463 Litres (L)
Standard Deviation 0.19308
|
0.2195 Litres (L)
Standard Deviation 0.23573
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Weighted mean 0-4 h, Day 8
|
0.0563 Litres (L)
Standard Deviation 0.25677
|
0.2313 Litres (L)
Standard Deviation 0.12148
|
0.2419 Litres (L)
Standard Deviation 0.17906
|
0.1542 Litres (L)
Standard Deviation 0.26356
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Weighted mean 0-4 h, Day 14
|
0.0557 Litres (L)
Standard Deviation 0.27371
|
0.1899 Litres (L)
Standard Deviation 0.13425
|
0.2798 Litres (L)
Standard Deviation 0.25865
|
0.1290 Litres (L)
Standard Deviation 0.29444
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Maximum 0-4 h, Day 1
|
0.125 Litres (L)
Standard Deviation 0.1348
|
0.241 Litres (L)
Standard Deviation 0.1191
|
0.276 Litres (L)
Standard Deviation 0.1587
|
0.272 Litres (L)
Standard Deviation 0.1500
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Maximum 0-4 h, Day 2
|
0.152 Litres (L)
Standard Deviation 0.1888
|
0.285 Litres (L)
Standard Deviation 0.1254
|
0.356 Litres (L)
Standard Deviation 0.1853
|
0.264 Litres (L)
Standard Deviation 0.2887
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Maximum 0-4 h, Day 8
|
0.133 Litres (L)
Standard Deviation 0.2888
|
0.277 Litres (L)
Standard Deviation 0.1150
|
0.295 Litres (L)
Standard Deviation 0.1852
|
0.224 Litres (L)
Standard Deviation 0.2524
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Maximum 0-4 h, Day 14
|
0.093 Litres (L)
Standard Deviation 0.2785
|
0.227 Litres (L)
Standard Deviation 0.1391
|
0.332 Litres (L)
Standard Deviation 0.2697
|
0.191 Litres (L)
Standard Deviation 0.2881
|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time
Maximum 0-4 h, Day 15
|
0.121 Litres (L)
Standard Deviation 0.2500
|
0.245 Litres (L)
Standard Deviation 0.1445
|
0.289 Litres (L)
Standard Deviation 0.1721
|
0.283 Litres (L)
Standard Deviation 0.2909
|
SECONDARY outcome
Timeframe: Day 1 up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
FEV1 is defined as the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was assessed pre-dose and post-dose at Day 1, 2, 7, 8, 14 and 15. Lung function test of FEV1 was performed at the approximately same time at each visit in the morning and highest of the 3 measurements were recorded. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean FEV1 0-4 h and maximum FEV1 0-4 h was obtained at Day 1, 2, 7, 8, 14 and 15.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Maximum 0-4 h, Day 15
|
1.704 L
Standard Deviation 0.5020
|
1.587 L
Standard Deviation 0.5060
|
2.156 L
Standard Deviation 0.5717
|
1.745 L
Standard Deviation 0.5673
|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Weighted mean 0-4, Day 1
|
1.6180 L
Standard Deviation 0.49986
|
1.5294 L
Standard Deviation 0.49878
|
2.0224 L
Standard Deviation 0.62567
|
1.6674 L
Standard Deviation 0.47398
|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Weighted mean 0-4, Day 2
|
1.6498 L
Standard Deviation 0.44952
|
1.5796 L
Standard Deviation 0.52525
|
2.1015 L
Standard Deviation 0.62389
|
1.6480 L
Standard Deviation 0.53142
|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Weighted mean 0-4, Day 7
|
1.6261 L
Standard Deviation 0.43336
|
1.5427 L
Standard Deviation 0.51959
|
2.0355 L
Standard Deviation 0.61827
|
1.7053 L
Standard Deviation 0.52221
|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Weighted mean 0-4, Day 8
|
1.6375 L
Standard Deviation 0.53044
|
1.6027 L
Standard Deviation 0.51660
|
2.0637 L
Standard Deviation 0.61246
|
1.6599 L
Standard Deviation 0.51218
|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Weighted mean 0-4, Day 14
|
1.6861 L
Standard Deviation 0.50464
|
1.5326 L
Standard Deviation 0.51142
|
2.1411 L
Standard Deviation 0.61845
|
1.6457 L
Standard Deviation 0.61933
|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Weighted mean 0-4, Day 15
|
1.6155 L
Standard Deviation 0.49847
|
1.4719 L
Standard Deviation 0.47004
|
2.0638 L
Standard Deviation 0.53939
|
1.6611 L
Standard Deviation 0.51360
|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Maximum 0-4 h, Day 1
|
1.698 L
Standard Deviation 0.4811
|
1.578 L
Standard Deviation 0.5034
|
2.089 L
Standard Deviation 0.6341
|
1.708 L
Standard Deviation 0.4848
|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Maximum 0-4 h, Day 2
|
1.741 L
Standard Deviation 0.4597
|
1.622 L
Standard Deviation 0.5329
|
2.168 L
Standard Deviation 0.6217
|
1.726 L
Standard Deviation 0.5514
|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Maximum 0-4 h, Day 7
|
1.712 L
Standard Deviation 0.4639
|
1.593 L
Standard Deviation 0.5196
|
2.104 L
Standard Deviation 0.6429
|
1.766 L
Standard Deviation 0.5245
|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Maximum 0-4 h, Day 8
|
1.717 L
Standard Deviation 0.5510
|
1.620 L
Standard Deviation 0.5182
|
2.120 L
Standard Deviation 0.6170
|
1.729 L
Standard Deviation 0.5083
|
|
Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time
Maximum 0-4 h, Day 14
|
1.684 L
Standard Deviation 0.5236
|
1.569 L
Standard Deviation 0.5193
|
2.203 L
Standard Deviation 0.6287
|
1.664 L
Standard Deviation 0.5901
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose) up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
FEV1 is defined as the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Lung function test of FEV1 was performed at the approximately same time at each visit in the morning and highest of the 3 measurements were recorded. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean FEV1 over 22-24 h was obtained at Day 1, Day 7 and Day 14 which was recorded up to Day 2, Day 8 and Day 15. Baseline was defined as the assessment on Day 1 pre-dose. Change from Baseline was calculated by subtracting the Baseline (Day 1, pre-dose) value from the individual post Baseline (Day 1, Day 7 and Day 14) values.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Change From Baseline in Weighted Mean FEV1 Over 22- 24 h on Days 1, 7 and 14
Day 1
|
0.0191 L
Standard Error 0.04224
|
0.1322 L
Standard Error 0.04171
|
0.1781 L
Standard Error 0.04194
|
0.0955 L
Standard Error 0.04043
|
|
Change From Baseline in Weighted Mean FEV1 Over 22- 24 h on Days 1, 7 and 14
Day 7
|
-0.0174 L
Standard Error 0.05640
|
0.1568 L
Standard Error 0.05818
|
0.1539 L
Standard Error 0.06073
|
0.1204 L
Standard Error 0.05723
|
|
Change From Baseline in Weighted Mean FEV1 Over 22- 24 h on Days 1, 7 and 14
Day 14
|
-0.0225 L
Standard Error 0.05719
|
0.1166 L
Standard Error 0.06178
|
0.1681 L
Standard Error 0.06615
|
0.0732 L
Standard Error 0.05827
|
SECONDARY outcome
Timeframe: Up to Follow-up (Day 17)Population: Safety Population. Only those participants available at the specified time points were analyzed.
PEF is a measure of lung function and measures how fast a person can breathe out. It was measured using a peak flow meter by the participants and recorded on daily record cards each day in the morning and evening from Screening up to Follow-up. The morning measurements were performed prior to the participant taking the morning dose of study medication or rescue medication. The evening measurements were performed prior to the participant taking the evening dose of study medication or rescue medication. The highest of the 3 values of morning and evening PEF were recorded on the diary card. The mean of 7 days of each morning and evening measurements were reported for the Run-in Week, Week 1, Week 2 and Follow-up.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over Time
Morning PEFR, Week 2
|
264.52 Liters per minute (L/min)
Standard Deviation 89.793
|
265.23 Liters per minute (L/min)
Standard Deviation 66.178
|
295.75 Liters per minute (L/min)
Standard Deviation 106.748
|
257.84 Liters per minute (L/min)
Standard Deviation 74.086
|
|
Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over Time
Morning PEFR, Follow-up
|
270.16 Liters per minute (L/min)
Standard Deviation 95.536
|
262.83 Liters per minute (L/min)
Standard Deviation 55.709
|
297.69 Liters per minute (L/min)
Standard Deviation 111.329
|
264.64 Liters per minute (L/min)
Standard Deviation 83.106
|
|
Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over Time
Morning PEFR, Run-in
|
268.20 Liters per minute (L/min)
Standard Deviation 85.986
|
249.99 Liters per minute (L/min)
Standard Deviation 78.848
|
276.45 Liters per minute (L/min)
Standard Deviation 95.245
|
244.44 Liters per minute (L/min)
Standard Deviation 52.722
|
|
Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over Time
Morning PEFR, Week 1
|
271.37 Liters per minute (L/min)
Standard Deviation 85.186
|
266.22 Liters per minute (L/min)
Standard Deviation 61.112
|
299.22 Liters per minute (L/min)
Standard Deviation 99.017
|
254.39 Liters per minute (L/min)
Standard Deviation 63.273
|
|
Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over Time
Evening PEFR, Run-in
|
266.76 Liters per minute (L/min)
Standard Deviation 79.352
|
251.85 Liters per minute (L/min)
Standard Deviation 63.927
|
270.10 Liters per minute (L/min)
Standard Deviation 93.699
|
252.64 Liters per minute (L/min)
Standard Deviation 66.592
|
|
Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over Time
Evening PEFR, Week 1
|
273.45 Liters per minute (L/min)
Standard Deviation 82.356
|
278.80 Liters per minute (L/min)
Standard Deviation 65.325
|
311.46 Liters per minute (L/min)
Standard Deviation 99.984
|
264.45 Liters per minute (L/min)
Standard Deviation 78.755
|
|
Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over Time
Evening PEFR, Week 2
|
274.13 Liters per minute (L/min)
Standard Deviation 84.622
|
275.12 Liters per minute (L/min)
Standard Deviation 59.122
|
302.04 Liters per minute (L/min)
Standard Deviation 110.097
|
263.01 Liters per minute (L/min)
Standard Deviation 88.672
|
|
Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over Time
Evening PEFR, Follow-up
|
284.75 Liters per minute (L/min)
Standard Deviation 84.680
|
262.14 Liters per minute (L/min)
Standard Deviation 55.737
|
319.09 Liters per minute (L/min)
Standard Deviation 110.336
|
314.44 Liters per minute (L/min)
Standard Deviation 99.858
|
SECONDARY outcome
Timeframe: Up to Follow-up (Day 17)Population: Safety Population. Only those participants available at the specified time points were analyzed.
Ipratropium bromide was provided as the rescue medication. The use of rescue medication was recorded by the participants on daily record cards each day in the morning and evening from Screening up to Follow-up. The mean of 7 days (puffs per 24 h) were reported for the Run-in Week, Week 1, Week 2 and Follow-up.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Mean Use of Rescue Medication Over Period
Run-in
|
3.12 Puffs per 24 h
Standard Deviation 2.525
|
2.46 Puffs per 24 h
Standard Deviation 2.464
|
1.38 Puffs per 24 h
Standard Deviation 1.554
|
1.66 Puffs per 24 h
Standard Deviation 1.363
|
|
Mean Use of Rescue Medication Over Period
Week 1
|
1.99 Puffs per 24 h
Standard Deviation 2.453
|
1.63 Puffs per 24 h
Standard Deviation 1.755
|
0.73 Puffs per 24 h
Standard Deviation 1.133
|
1.25 Puffs per 24 h
Standard Deviation 2.003
|
|
Mean Use of Rescue Medication Over Period
Week 2
|
2.24 Puffs per 24 h
Standard Deviation 3.053
|
1.61 Puffs per 24 h
Standard Deviation 2.021
|
0.79 Puffs per 24 h
Standard Deviation 1.159
|
0.93 Puffs per 24 h
Standard Deviation 0.962
|
|
Mean Use of Rescue Medication Over Period
Follow-up
|
2.17 Puffs per 24 h
Standard Deviation 2.552
|
1.38 Puffs per 24 h
Standard Deviation 1.502
|
1.11 Puffs per 24 h
Standard Deviation 1.364
|
0.86 Puffs per 24 h
Standard Deviation 1.574
|
SECONDARY outcome
Timeframe: Up to Follow-up (Day 17)Population: Safety Population. Only those participants available at the specified time points were analyzed.
Ipratropium bromide was provided as the rescue medication. The use of rescue medication was recorded by the participants on daily record cards each day in the morning and evening from Screening up to Follow-up. The percentage of rescue free days during the Run-in week, Week 1, Week 2 and Follow-up Week were assessed. Data is reported for number of participants with \< 20%, \>=20 to \<40%, \>=40 to \<60%, \>=60 to \<80% and \>=80% rescue free days.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Number of Participants With Rescue Free Days
Run-in · < 20%
|
10 Participants
|
9 Participants
|
5 Participants
|
10 Participants
|
|
Number of Participants With Rescue Free Days
Run-in · >=20 to <40%
|
0 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Rescue Free Days
Run-in · >=80%
|
1 Participants
|
3 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With Rescue Free Days
Run-in · >=40 to <60%
|
3 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Rescue Free Days
Run-in · >=60 to <80%
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Rescue Free Days
Week 1 · < 20%
|
7 Participants
|
5 Participants
|
3 Participants
|
4 Participants
|
|
Number of Participants With Rescue Free Days
Week 1 · >=20 to <40%
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Rescue Free Days
Week 1 · >=40 to <60%
|
2 Participants
|
1 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Rescue Free Days
Week 1 · >=60 to <80%
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Rescue Free Days
Week 1 · >=80%
|
6 Participants
|
5 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Rescue Free Days
Week 2 · < 20%
|
7 Participants
|
4 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Rescue Free Days
Week 2 · >=20 to <40%
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Rescue Free Days
Week 2 · >=40 to <60%
|
1 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Rescue Free Days
Week 2 · >=60 to <80%
|
1 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Rescue Free Days
Week 2 · >=80%
|
6 Participants
|
5 Participants
|
5 Participants
|
3 Participants
|
|
Number of Participants With Rescue Free Days
Follow-up · < 20%
|
9 Participants
|
8 Participants
|
5 Participants
|
2 Participants
|
|
Number of Participants With Rescue Free Days
Follow-up · >=20 to <40%
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Rescue Free Days
Follow-up · >=40 to <60%
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Rescue Free Days
Follow-up · >=60 to <80%
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Rescue Free Days
Follow-up · >=80%
|
3 Participants
|
5 Participants
|
4 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose) up to Day 14Population: Safety Population. Only those participants available at the specified time points were analyzed.
Blood samples were collected at pre-dose on Day 1, Day 7 and Day 14. Baseline was defined as the assessment done on pre-dose, Day 1. Change from Baseline was calculated by subtracting the Baseline (Day 1, pre-dose) value from the individual post Baseline (Day 7 and Day 14) values.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Change From Baseline in Pre-dose Fasting Glucose and Potassium at Day 7 and 14
Fasting Potassium, Day 14
|
0.00 Millimole (mmol)/L)
Standard Deviation 0.285
|
-0.16 Millimole (mmol)/L)
Standard Deviation 0.500
|
0.02 Millimole (mmol)/L)
Standard Deviation 0.354
|
0.33 Millimole (mmol)/L)
Standard Deviation 0.504
|
|
Change From Baseline in Pre-dose Fasting Glucose and Potassium at Day 7 and 14
Fasting Glucose, Day 7
|
-0.22 Millimole (mmol)/L)
Standard Deviation 0.742
|
0.61 Millimole (mmol)/L)
Standard Deviation 1.175
|
0.11 Millimole (mmol)/L)
Standard Deviation 0.673
|
0.22 Millimole (mmol)/L)
Standard Deviation 1.103
|
|
Change From Baseline in Pre-dose Fasting Glucose and Potassium at Day 7 and 14
Fasting Glucose, Day 14
|
0.08 Millimole (mmol)/L)
Standard Deviation 1.229
|
0.57 Millimole (mmol)/L)
Standard Deviation 0.856
|
0.19 Millimole (mmol)/L)
Standard Deviation 0.639
|
0.13 Millimole (mmol)/L)
Standard Deviation 1.040
|
|
Change From Baseline in Pre-dose Fasting Glucose and Potassium at Day 7 and 14
Fasting Potassium, Day 7
|
0.22 Millimole (mmol)/L)
Standard Deviation 0.328
|
-0.11 Millimole (mmol)/L)
Standard Deviation 0.436
|
0.03 Millimole (mmol)/L)
Standard Deviation 0.675
|
0.17 Millimole (mmol)/L)
Standard Deviation 0.737
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose) up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
Blood samples were collected at pre-dose and 4 h post-dose on Day 1, Day 2, Day 7, Day 8, Day 14 and Day 15. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. Baseline was defined as the assessment on Day 1 pre-dose. The weighted mean change from Baseline was the AAUCMB. Change from Baseline in maximum glucose 0-4 h and minimum potassium 0-4 h was calculated by subtracting the Baseline (Day 1, pre-dose) value from the individual post Baseline (Day 1 to Day 15) values.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 8
|
-0.183 mmol/L
Standard Error 0.3111
|
0.061 mmol/L
Standard Error 0.3200
|
0.613 mmol/L
Standard Error 0.3614
|
-0.039 mmol/L
Standard Error 0.3097
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 14
|
0.218 mmol/L
Standard Error 0.1140
|
-0.081 mmol/L
Standard Error 0.1233
|
-0.053 mmol/L
Standard Error 0.1325
|
0.123 mmol/L
Standard Error 0.1224
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 2
|
0.21 mmol/L
Standard Error 0.363
|
0.61 mmol/L
Standard Error 0.357
|
0.89 mmol/L
Standard Error 0.350
|
0.44 mmol/L
Standard Error 0.337
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 1
|
-0.12 mmol/L
Standard Error 0.094
|
-0.31 mmol/L
Standard Error 0.104
|
-0.35 mmol/L
Standard Error 0.095
|
-0.32 mmol/L
Standard Error 0.096
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 1
|
0.048 mmol/L
Standard Error 0.2097
|
0.057 mmol/L
Standard Error 0.2061
|
0.285 mmol/L
Standard Error 0.2068
|
0.140 mmol/L
Standard Error 0.1946
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 2
|
-0.137 mmol/L
Standard Error 0.2749
|
0.062 mmol/L
Standard Error 0.2689
|
0.497 mmol/L
Standard Error 0.2711
|
-0.072 mmol/L
Standard Error 0.2550
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 7
|
-0.002 mmol/L
Standard Error 0.1978
|
0.095 mmol/L
Standard Error 0.1994
|
0.406 mmol/L
Standard Error 0.2349
|
0.078 mmol/L
Standard Error 0.1929
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 14
|
0.193 mmol/L
Standard Error 0.2104
|
0.250 mmol/L
Standard Error 0.2046
|
0.055 mmol/L
Standard Error 0.2309
|
0.006 mmol/L
Standard Error 0.1956
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 15
|
-0.100 mmol/L
Standard Error 0.2505
|
-0.006 mmol/L
Standard Error 0.2404
|
0.258 mmol/L
Standard Error 0.2737
|
0.078 mmol/L
Standard Error 0.2413
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 1
|
0.183 mmol/L
Standard Error 0.0999
|
-0.110 mmol/L
Standard Error 0.1062
|
-0.188 mmol/L
Standard Error 0.1016
|
0.030 mmol/L
Standard Error 0.1063
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 2
|
0.376 mmol/L
Standard Error 0.1575
|
0.160 mmol/L
Standard Error 0.1634
|
-0.160 mmol/L
Standard Error 0.1609
|
0.358 mmol/L
Standard Error 0.1576
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 7
|
0.267 mmol/L
Standard Error 0.1318
|
-0.219 mmol/L
Standard Error 0.1421
|
-0.295 mmol/L
Standard Error 0.1664
|
0.077 mmol/L
Standard Error 0.1415
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 8
|
0.247 mmol/L
Standard Error 0.1051
|
0.322 mmol/L
Standard Error 0.1115
|
-0.027 mmol/L
Standard Error 0.1311
|
0.350 mmol/L
Standard Error 0.1154
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 15
|
0.155 mmol/L
Standard Error 0.1120
|
0.328 mmol/L
Standard Error 0.1197
|
-0.041 mmol/L
Standard Error 0.1276
|
0.293 mmol/L
Standard Error 0.1234
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 1
|
0.65 mmol/L
Standard Error 0.361
|
0.51 mmol/L
Standard Error 0.365
|
0.94 mmol/L
Standard Error 0.357
|
0.48 mmol/L
Standard Error 0.336
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 7
|
0.52 mmol/L
Standard Error 0.367
|
0.47 mmol/L
Standard Error 0.368
|
1.05 mmol/L
Standard Error 0.402
|
0.65 mmol/L
Standard Error 0.359
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 8
|
0.28 mmol/L
Standard Error 0.431
|
0.53 mmol/L
Standard Error 0.425
|
1.13 mmol/L
Standard Error 0.464
|
0.60 mmol/L
Standard Error 0.429
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 14
|
0.37 mmol/L
Standard Error 0.434
|
0.42 mmol/L
Standard Error 0.431
|
1.12 mmol/L
Standard Error 0.473
|
0.37 mmol/L
Standard Error 0.433
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 15
|
0.21 mmol/L
Standard Error 0.348
|
0.43 mmol/L
Standard Error 0.345
|
1.05 mmol/L
Standard Error 0.392
|
0.70 mmol/L
Standard Error 0.346
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 2
|
0.07 mmol/L
Standard Error 0.127
|
-0.03 mmol/L
Standard Error 0.135
|
-0.31 mmol/L
Standard Error 0.125
|
0.05 mmol/L
Standard Error 0.130
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 7
|
0.07 mmol/L
Standard Error 0.143
|
-0.47 mmol/L
Standard Error 0.158
|
-0.47 mmol/L
Standard Error 0.161
|
-0.27 mmol/L
Standard Error 0.156
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 8
|
0.09 mmol/L
Standard Error 0.099
|
0.13 mmol/L
Standard Error 0.109
|
-0.30 mmol/L
Standard Error 0.111
|
0.13 mmol/L
Standard Error 0.113
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 14
|
-0.06 mmol/L
Standard Error 0.091
|
-0.21 mmol/L
Standard Error 0.100
|
-0.29 mmol/L
Standard Error 0.103
|
-0.12 mmol/L
Standard Error 0.103
|
|
Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 15
|
-0.02 mmol/L
Standard Error 0.099
|
0.03 mmol/L
Standard Error 0.109
|
-0.37 mmol/L
Standard Error 0.117
|
0.02 mmol/L
Standard Error 0.113
|
SECONDARY outcome
Timeframe: Day 1 up to Day 15Population: Safety Population. Only those participants available at the specified time points were analyzed.
Blood samples were collected at pre-dose and 4 h post-dose on Day 1, Day 2, Day 7, Day 8, Day 14 and Day 15. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 Participants
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 1
|
5.917 mmol/L
Standard Deviation 1.4350
|
5.202 mmol/L
Standard Deviation 0.6244
|
5.537 mmol/L
Standard Deviation 0.8241
|
5.744 mmol/L
Standard Deviation 1.0359
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 2
|
5.913 mmol/L
Standard Deviation 1.4064
|
5.237 mmol/L
Standard Deviation 1.0555
|
5.763 mmol/L
Standard Deviation 1.1516
|
5.626 mmol/L
Standard Deviation 1.3748
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 7
|
5.860 mmol/L
Standard Deviation 1.0459
|
5.271 mmol/L
Standard Deviation 0.6604
|
5.636 mmol/L
Standard Deviation 1.0571
|
5.649 mmol/L
Standard Deviation 1.2134
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 8
|
5.679 mmol/L
Standard Deviation 1.4463
|
5.266 mmol/L
Standard Deviation 0.9408
|
5.839 mmol/L
Standard Deviation 1.5742
|
5.461 mmol/L
Standard Deviation 1.2427
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 14
|
6.035 mmol/L
Standard Deviation 1.1987
|
5.406 mmol/L
Standard Deviation 0.4841
|
5.384 mmol/L
Standard Deviation 0.6367
|
5.460 mmol/L
Standard Deviation 0.8837
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Glucose 0-4 h, Day 15
|
5.927 mmol/L
Standard Deviation 1.3819
|
5.196 mmol/L
Standard Deviation 0.8684
|
5.599 mmol/L
Standard Deviation 1.1422
|
5.557 mmol/L
Standard Deviation 1.2105
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 1
|
4.491 mmol/L
Standard Deviation 0.5698
|
4.271 mmol/L
Standard Deviation 0.6109
|
4.174 mmol/L
Standard Deviation 0.3005
|
4.352 mmol/L
Standard Deviation 0.3550
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 2
|
4.645 mmol/L
Standard Deviation 0.5498
|
4.541 mmol/L
Standard Deviation 0.3952
|
4.220 mmol/L
Standard Deviation 0.2719
|
4.628 mmol/L
Standard Deviation 0.8501
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 7
|
4.494 mmol/L
Standard Deviation 0.8933
|
4.212 mmol/L
Standard Deviation 0.4412
|
4.154 mmol/L
Standard Deviation 0.3908
|
4.258 mmol/L
Standard Deviation 0.4597
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 8
|
4.525 mmol/L
Standard Deviation 0.4862
|
4.549 mmol/L
Standard Deviation 0.4950
|
4.240 mmol/L
Standard Deviation 0.3727
|
4.503 mmol/L
Standard Deviation 0.3247
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 14
|
4.458 mmol/L
Standard Deviation 0.5101
|
4.298 mmol/L
Standard Deviation 0.5123
|
4.250 mmol/L
Standard Deviation 0.3694
|
4.321 mmol/L
Standard Deviation 0.2958
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Weighted Mean Potassium 0-4 h, Day 15
|
4.400 mmol/L
Standard Deviation 0.4552
|
4.582 mmol/L
Standard Deviation 0.3869
|
4.241 mmol/L
Standard Deviation 0.4811
|
4.466 mmol/L
Standard Deviation 0.2841
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 1
|
6.62 mmol/L
Standard Deviation 2.434
|
5.54 mmol/L
Standard Deviation 0.801
|
6.11 mmol/L
Standard Deviation 1.582
|
6.12 mmol/L
Standard Deviation 1.235
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 2
|
6.29 mmol/L
Standard Deviation 1.735
|
5.77 mmol/L
Standard Deviation 1.411
|
6.21 mmol/L
Standard Deviation 1.439
|
6.13 mmol/L
Standard Deviation 1.728
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 7
|
6.49 mmol/L
Standard Deviation 1.539
|
5.60 mmol/L
Standard Deviation 0.967
|
6.24 mmol/L
Standard Deviation 2.103
|
6.28 mmol/L
Standard Deviation 1.560
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 8
|
6.16 mmol/L
Standard Deviation 1.990
|
5.64 mmol/L
Standard Deviation 0.993
|
6.25 mmol/L
Standard Deviation 1.850
|
6.14 mmol/L
Standard Deviation 1.914
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 14
|
6.30 mmol/L
Standard Deviation 1.477
|
5.67 mmol/L
Standard Deviation 0.976
|
6.50 mmol/L
Standard Deviation 2.724
|
5.86 mmol/L
Standard Deviation 1.241
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Maximum Glucose 0-4 h, Day 15
|
6.28 mmol/L
Standard Deviation 1.636
|
5.61 mmol/L
Standard Deviation 1.113
|
6.37 mmol/L
Standard Deviation 1.592
|
6.19 mmol/L
Standard Deviation 1.664
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 1
|
4.18 mmol/L
Standard Deviation 0.427
|
4.05 mmol/L
Standard Deviation 0.584
|
4.02 mmol/L
Standard Deviation 0.307
|
3.94 mmol/L
Standard Deviation 0.341
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 2
|
4.35 mmol/L
Standard Deviation 0.346
|
4.24 mmol/L
Standard Deviation 0.412
|
4.03 mmol/L
Standard Deviation 0.291
|
4.28 mmol/L
Standard Deviation 0.810
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 7
|
4.28 mmol/L
Standard Deviation 0.835
|
3.91 mmol/L
Standard Deviation 0.501
|
3.89 mmol/L
Standard Deviation 0.355
|
3.91 mmol/L
Standard Deviation 0.535
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 8
|
4.34 mmol/L
Standard Deviation 0.468
|
4.34 mmol/L
Standard Deviation 0.473
|
4.00 mmol/L
Standard Deviation 0.338
|
4.28 mmol/L
Standard Deviation 0.328
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 14
|
4.20 mmol/L
Standard Deviation 0.388
|
4.15 mmol/L
Standard Deviation 0.467
|
4.00 mmol/L
Standard Deviation 0.163
|
4.08 mmol/L
Standard Deviation 0.376
|
|
Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time
Minimum Potassium 0-4 h, Day 15
|
4.24 mmol/L
Standard Deviation 0.430
|
4.29 mmol/L
Standard Deviation 0.366
|
3.93 mmol/L
Standard Deviation 0.379
|
4.22 mmol/L
Standard Deviation 0.279
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)Population: Pharmacokinetic (PK) Concentration Population comprised of those participants in the Safety Population for whom a PK sample was obtained and analyzed. Only those participants available at the specified time points were analyzed.
Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The AUC over 4 h as AUC from zero (pre-dose) to 2 h post-dose (AUC \[0-2\]), AUC from zero (pre-dose) to 4 h post-dose (AUC \[0-4\]) and AUC from zero (pre-dose) to time of last quantifiable concentration (AUC \[0-t\]) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
AUC of GW642444H Over 0 to 4 h (AUC [0-4]) on Day 1, 7 and 14
AUC (0-2), Day 1
|
151.067 Picogram (pg)*h/mL
Geometric Coefficient of Variation 39.92
|
NA Picogram (pg)*h/mL
Geometric Coefficient of Variation NA
AUC0-2 was not calculated for GW642444 400 mcg once daily.
|
—
|
—
|
|
AUC of GW642444H Over 0 to 4 h (AUC [0-4]) on Day 1, 7 and 14
AUC (0-2), Day 7
|
164.374 Picogram (pg)*h/mL
Geometric Coefficient of Variation 57.30
|
NA Picogram (pg)*h/mL
Geometric Coefficient of Variation NA
AUC0-2 was not calculated for GW642444 400 mcg once daily.
|
—
|
—
|
|
AUC of GW642444H Over 0 to 4 h (AUC [0-4]) on Day 1, 7 and 14
AUC (0-2), Day 14
|
166.055 Picogram (pg)*h/mL
Geometric Coefficient of Variation 40.98
|
NA Picogram (pg)*h/mL
Geometric Coefficient of Variation NA
AUC0-2 was not calculated for GW642444 400 mcg once daily.
|
—
|
—
|
|
AUC of GW642444H Over 0 to 4 h (AUC [0-4]) on Day 1, 7 and 14
AUC (0-4), Day 1
|
277.582 Picogram (pg)*h/mL
Geometric Coefficient of Variation 14.92
|
699.719 Picogram (pg)*h/mL
Geometric Coefficient of Variation 60.50
|
—
|
—
|
|
AUC of GW642444H Over 0 to 4 h (AUC [0-4]) on Day 1, 7 and 14
AUC (0-4), Day 7
|
412.496 Picogram (pg)*h/mL
Geometric Coefficient of Variation 31.95
|
945.893 Picogram (pg)*h/mL
Geometric Coefficient of Variation 58.35
|
—
|
—
|
|
AUC of GW642444H Over 0 to 4 h (AUC [0-4]) on Day 1, 7 and 14
AUC (0-4), Day 14
|
300.921 Picogram (pg)*h/mL
Geometric Coefficient of Variation 40.05
|
772.694 Picogram (pg)*h/mL
Geometric Coefficient of Variation 35.59
|
—
|
—
|
|
AUC of GW642444H Over 0 to 4 h (AUC [0-4]) on Day 1, 7 and 14
AUC (0-t), Day 1
|
192.799 Picogram (pg)*h/mL
Geometric Coefficient of Variation 51.42
|
702.937 Picogram (pg)*h/mL
Geometric Coefficient of Variation 60.22
|
—
|
—
|
|
AUC of GW642444H Over 0 to 4 h (AUC [0-4]) on Day 1, 7 and 14
AUC (0-t), Day 7
|
212.547 Picogram (pg)*h/mL
Geometric Coefficient of Variation 86.45
|
840.634 Picogram (pg)*h/mL
Geometric Coefficient of Variation 63.50
|
—
|
—
|
|
AUC of GW642444H Over 0 to 4 h (AUC [0-4]) on Day 1, 7 and 14
AUC (0-t), Day 14
|
275.621 Picogram (pg)*h/mL
Geometric Coefficient of Variation 49.02
|
736.842 Picogram (pg)*h/mL
Geometric Coefficient of Variation 40.06
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)Population: PK Concentration Population. Only those participants available at the specified time points were analyzed.
Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The first occurrence of the Cmax was determined directly from the raw concentration-time data.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Maximum Concentration (Cmax) of GW642444H at Day 1, 7 and 14
Day 1
|
78.851 pg/mL
Geometric Coefficient of Variation 45.85
|
226.407 pg/mL
Geometric Coefficient of Variation 108.53
|
—
|
—
|
|
Maximum Concentration (Cmax) of GW642444H at Day 1, 7 and 14
Day 7
|
82.642 pg/mL
Geometric Coefficient of Variation 64.09
|
427.282 pg/mL
Geometric Coefficient of Variation 49.41
|
—
|
—
|
|
Maximum Concentration (Cmax) of GW642444H at Day 1, 7 and 14
Day 14
|
92.089 pg/mL
Geometric Coefficient of Variation 50.15
|
308.546 pg/mL
Geometric Coefficient of Variation 24.25
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)Population: PK Concentration Population. Only those participants available at the specified time points were analyzed.
Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The time at which Cmax was observed and tlast was determined directly from the raw concentration-time data.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Time to Maximum Concentration (Tmax) and Time of Last Quantifiable Concentration (Tlast) of GW642444H at Day 1, 7 and 14
Tmax, Day 1
|
1.000 h
Interval 0.08 to 4.0
|
1.000 h
Interval 0.08 to 1.08
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) and Time of Last Quantifiable Concentration (Tlast) of GW642444H at Day 1, 7 and 14
Tmax, Day 7
|
1.000 h
Interval 0.08 to 4.0
|
0.130 h
Interval 0.08 to 1.02
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) and Time of Last Quantifiable Concentration (Tlast) of GW642444H at Day 1, 7 and 14
Tmax, Day 14
|
0.555 h
Interval 0.08 to 2.0
|
0.525 h
Interval 0.07 to 2.02
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) and Time of Last Quantifiable Concentration (Tlast) of GW642444H at Day 1, 7 and 14
Tlast, Day 1
|
2.000 h
Interval 0.98 to 4.0
|
4.000 h
Interval 0.08 to 4.23
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) and Time of Last Quantifiable Concentration (Tlast) of GW642444H at Day 1, 7 and 14
Tlast, Day 7
|
2.000 h
Interval 1.0 to 4.0
|
4.000 h
Interval 1.97 to 4.17
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) and Time of Last Quantifiable Concentration (Tlast) of GW642444H at Day 1, 7 and 14
Tlast, Day 14
|
4.000 h
Interval 0.08 to 4.12
|
4.000 h
Interval 2.0 to 4.88
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)Population: PK Concentration Population. Only those participants available at the specified time points were analyzed.
CCI2189 is a counterion of GW642444H. Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The AUC (0-4) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
AUC (0-4) of CCI2189 at Day 1, 7 and 14
Day 1
|
11.779 Nanogram (ng)*h/mL
Geometric Coefficient of Variation 34.10
|
45.664 Nanogram (ng)*h/mL
Geometric Coefficient of Variation 25.35
|
—
|
—
|
|
AUC (0-4) of CCI2189 at Day 1, 7 and 14
Day 7
|
12.155 Nanogram (ng)*h/mL
Geometric Coefficient of Variation 33.83
|
52.866 Nanogram (ng)*h/mL
Geometric Coefficient of Variation 41.09
|
—
|
—
|
|
AUC (0-4) of CCI2189 at Day 1, 7 and 14
Day 14
|
13.683 Nanogram (ng)*h/mL
Geometric Coefficient of Variation 34.35
|
48.348 Nanogram (ng)*h/mL
Geometric Coefficient of Variation 36.69
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)Population: PK Concentration Population. Only those participants available at the specified time points were analyzed.
CCI2189 is a counterion of GW642444H. Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The first occurrence of the Cmax was determined directly from the raw concentration-time data.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Cmax of CCI2189 at Day 1, 7 and 14
Day 1
|
4.692 ng/mL
Geometric Coefficient of Variation 34.06
|
15.650 ng/mL
Geometric Coefficient of Variation 55.22
|
—
|
—
|
|
Cmax of CCI2189 at Day 1, 7 and 14
Day 7
|
4.578 ng/mL
Geometric Coefficient of Variation 27.23
|
21.293 ng/mL
Geometric Coefficient of Variation 37.74
|
—
|
—
|
|
Cmax of CCI2189 at Day 1, 7 and 14
Day 14
|
5.115 ng/mL
Geometric Coefficient of Variation 34.66
|
18.315 ng/mL
Geometric Coefficient of Variation 28.69
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)Population: PK Concentration Population. Only those participants available at the specified time points were analyzed.
GW630200 and GSK932009 are metabolites of GW642444H. Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The AUC (0-4) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
AUC (0-4) of GW630200 and GSK932009 at Day 1, 7 and 14
GW630200, Day 7
|
NA pg*h/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
NA pg*h/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
—
|
—
|
|
AUC (0-4) of GW630200 and GSK932009 at Day 1, 7 and 14
GW630200, Day 1
|
NA pg*h/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
NA pg*h/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
—
|
—
|
|
AUC (0-4) of GW630200 and GSK932009 at Day 1, 7 and 14
GW630200, Day 14
|
NA pg*h/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
NA pg*h/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
—
|
—
|
|
AUC (0-4) of GW630200 and GSK932009 at Day 1, 7 and 14
GSK932009, Day 1
|
—
|
1222.771 pg*h/mL
Geometric Coefficient of Variation 19.18
|
—
|
—
|
|
AUC (0-4) of GW630200 and GSK932009 at Day 1, 7 and 14
GSK932009, Day 7
|
897.695 pg*h/mL
Geometric Coefficient of Variation NA
Only one participant was analyzed.
|
1866.738 pg*h/mL
Geometric Coefficient of Variation 58.04
|
—
|
—
|
|
AUC (0-4) of GW630200 and GSK932009 at Day 1, 7 and 14
GSK932009, Day 14
|
797.075 pg*h/mL
Geometric Coefficient of Variation NA
Only one participant was analyzed.
|
1527.671 pg*h/mL
Geometric Coefficient of Variation 20.22
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)Population: PK Concentration Population. Only those participants available at the specified time points were analyzed.
GW630200 and GSK932009 are metabolites of GW642444H. Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The first occurrence of the Cmax was determined directly from the raw concentration-time data.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Cmax of GW630200 and GSK932009 at Day 1, 7 and 14
GW630200, Day 14
|
NA pg/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
NA pg/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
—
|
—
|
|
Cmax of GW630200 and GSK932009 at Day 1, 7 and 14
GW630200, Day 1
|
NA pg/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
NA pg/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
—
|
—
|
|
Cmax of GW630200 and GSK932009 at Day 1, 7 and 14
GW630200, Day 7
|
NA pg/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
NA pg/mL
Geometric Coefficient of Variation NA
Data was not quantifiable.
|
—
|
—
|
|
Cmax of GW630200 and GSK932009 at Day 1, 7 and 14
GSK932009, Day 1
|
—
|
311.740 pg/mL
Geometric Coefficient of Variation 36.96
|
—
|
—
|
|
Cmax of GW630200 and GSK932009 at Day 1, 7 and 14
GSK932009, Day 7
|
235.459 pg/mL
Geometric Coefficient of Variation 17.81
|
460.352 pg/mL
Geometric Coefficient of Variation 69.16
|
—
|
—
|
|
Cmax of GW630200 and GSK932009 at Day 1, 7 and 14
GSK932009, Day 14
|
228.419 pg/mL
Geometric Coefficient of Variation 19.25
|
391.680 pg/mL
Geometric Coefficient of Variation 37.49
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)Population: PK Concentration Population. Only those participants available at the specified time points were analyzed.
GW630200 and GSK932009 are metabolites of GW642444H. CCI2189 is a counterion of GW642444H. Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The time at which Cmax was observed was determined directly from the raw concentration-time data.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 Participants
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of CCI2189, GW630200 and GSK932009 at Day 1, 7 and 14
CC12189, Day 7
|
1.010 h
Interval 0.95 to 4.0
|
1.000 h
Interval 0.1 to 2.0
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of CCI2189, GW630200 and GSK932009 at Day 1, 7 and 14
CC12189, Day 14
|
1.000 h
Interval 0.08 to 4.0
|
1.000 h
Interval 0.07 to 4.0
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of CCI2189, GW630200 and GSK932009 at Day 1, 7 and 14
GW630200, Day 1
|
NA h
Data was not quantifiable.
|
NA h
Data was not quantifiable.
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of CCI2189, GW630200 and GSK932009 at Day 1, 7 and 14
CC12189, Day 1
|
1.285 h
Interval 0.93 to 4.0
|
1.000 h
Interval 0.08 to 4.0
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of CCI2189, GW630200 and GSK932009 at Day 1, 7 and 14
GW630200, Day 7
|
NA h
Data was not quantifiable.
|
NA h
Data was not quantifiable.
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of CCI2189, GW630200 and GSK932009 at Day 1, 7 and 14
GW630200, Day 14
|
NA h
Data was not quantifiable.
|
NA h
Data was not quantifiable.
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of CCI2189, GW630200 and GSK932009 at Day 1, 7 and 14
GSK932009, Day 1
|
—
|
2.050 h
Interval 1.0 to 4.23
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of CCI2189, GW630200 and GSK932009 at Day 1, 7 and 14
GSK932009, Day 7
|
2.500 h
Interval 1.0 to 4.0
|
2.000 h
Interval 1.0 to 4.0
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of CCI2189, GW630200 and GSK932009 at Day 1, 7 and 14
GSK932009, Day 14
|
1.500 h
Interval 1.0 to 2.0
|
2.000 h
Interval 1.0 to 4.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)Population: PK Concentration Population. Only those participants available at the specified time points were analyzed.
Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The AUC (0-4) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
AUC (0-4) of Salmeterol at Day 1, 7 and 14
Day 1
|
225.334 pg*h/mL
Geometric Coefficient of Variation 14.83
|
—
|
—
|
—
|
|
AUC (0-4) of Salmeterol at Day 1, 7 and 14
Day 7
|
226.708 pg*h/mL
Geometric Coefficient of Variation 34.42
|
—
|
—
|
—
|
|
AUC (0-4) of Salmeterol at Day 1, 7 and 14
Day 14
|
178.656 pg*h/mL
Geometric Coefficient of Variation 33.47
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)Population: PK Concentration Population. Only those participants available at the specified time points were analyzed.
Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The first occurrence of the Cmax was determined directly from the raw concentration-time data.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Cmax of Salmeterol at Day 1, 7 and 14
Day 1
|
50.218 pg*h/mL
Geometric Coefficient of Variation 45.71
|
—
|
—
|
—
|
|
Cmax of Salmeterol at Day 1, 7 and 14
Day 7
|
59.943 pg*h/mL
Geometric Coefficient of Variation 49.73
|
—
|
—
|
—
|
|
Cmax of Salmeterol at Day 1, 7 and 14
Day 14
|
51.983 pg*h/mL
Geometric Coefficient of Variation 29.13
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose)Population: PK Concentration Population. Only those participants available at the specified time points were analyzed.
Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The time at which Cmax was observed was determined directly from the raw concentration-time data.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Tmax of Salmeterol at Day 1, 7 and 14
Day 1
|
1.000 h
Interval 0.08 to 2.0
|
—
|
—
|
—
|
|
Tmax of Salmeterol at Day 1, 7 and 14
Day 7
|
1.000 h
Interval 0.08 to 2.0
|
—
|
—
|
—
|
|
Tmax of Salmeterol at Day 1, 7 and 14
Day 14
|
1.000 h
Interval 0.08 to 4.05
|
—
|
—
|
—
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
GW642444 100 mcg Once Daily
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
GW642444 400 mcg Once Daily
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Salmeterol 50 mcg BD
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=17 participants at risk
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 participants at risk
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 participants at risk
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 participants at risk
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Cardiac disorders
Ventricular extrasystoles
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.6%
1/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
Other adverse events
| Measure |
Placebo
n=17 participants at risk
Participants received oral inhalations of matching placebo via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of placebo from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 100 mcg Once Daily
n=16 participants at risk
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
GW642444 400 mcg Once Daily
n=17 participants at risk
Participants received oral inhalations of GW642444 100 mcg via DISKUS DPI, once daily for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of GW642444 100 mcg from Inhaler A and 3 inhalations of GW642444 100 mcg (3 inhalations x GW642444 100 mcg) from Inhaler B and evening dose of 1 inhalation of placebo from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
Salmeterol 50 mcg BD
n=18 participants at risk
Participants received oral inhalations of salmeterol 50 mcg via DISKUS DPI, BD for 2 weeks of treatment period. Participants were provided with 3 inhalers (Inhaler A, B and C) to maintain the blinding. Participants received morning dose of 1 inhalation of salmeterol 50 mcg from Inhaler A and 3 inhalations of placebo from Inhaler B and evening dose of 1 inhalation of salmeterol 50 mcg from Inhaler C. Inhaled short acting beta-agonists, ipratropium bromide was provided as rescue medication throughout the study.
|
|---|---|---|---|---|
|
Nervous system disorders
Dizziness
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
6.2%
1/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
11.1%
2/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
11.8%
2/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Nervous system disorders
Headache
|
11.8%
2/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
12.5%
2/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
23.5%
4/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
16.7%
3/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Nervous system disorders
Tension headache
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
6.2%
1/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.6%
1/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
12.5%
2/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.6%
1/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
6.2%
1/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
6.2%
1/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.6%
1/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Gastrointestinal disorders
Crohn's disease
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Gastrointestinal disorders
Tongue coated
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
6.2%
1/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
General disorders
Chest discomfort
|
11.8%
2/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
General disorders
Chest pain
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.6%
1/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
General disorders
Application site rash
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
General disorders
Application site reaction
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
6.2%
1/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Infections and infestations
Oral herpes
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Cardiac disorders
Extrasystoles
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
6.2%
1/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Cardiac disorders
Sinus arrest
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
6.2%
1/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Cardiac disorders
Supraventricular extrasystoles
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
6.2%
1/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Skin and subcutaneous tissue disorders
Skin reaction
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Eye disorders
Eye irritation
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
6.2%
1/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Investigations
Blood pressure decreased
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
6.2%
1/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/16 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
5.9%
1/17 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
0.00%
0/18 • AEs were collected up to Follow-up (17 days)
Safety Population was used.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER