Trial Outcomes & Findings for A Study to Investigate the Efficacy, Safety, and Tolerability of Repeat Doses of Inhaled GSK2269557 in Adults With Persistent, Uncontrolled Asthma (NCT NCT02567708)
NCT ID: NCT02567708
Last Updated: 2018-08-01
Results Overview
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is the maximum volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug. FEV1 was measured using a spirometer. Change from Baseline is calculated as post-Baseline value minus Baseline value where Baseline is defined as Day 1 (pre-dose).
COMPLETED
PHASE2
50 participants
Baseline and Day 28 for each treatment period
2018-08-01
Participant Flow
Eligible participants entered the 2 week Run-in phase and participants who met the randomization eligibility criteria entered into the 4 week Double-blind treatment period (DBTP) 1 followed by a 4-week wash-out period, 4 weeks DBTP 2 and a 2 week follow-up phase. The total duration of participation in the study was 16 weeks.
A total of 108 participants with persistent uncontrolled asthma, currently not treated with an inhaled corticosteroid (ICS) or long acting beta2 agonist (LABA) were screened, of these, 58 were screen failures and 50 entered the Run-in phase. All 50 par. were randomized into the study and received study treatments.
Participant milestones
| Measure |
Placebo, Then GSK2269557
Participants received placebo drug once daily via dry powder inhaler for 28 days during Treatment Period 1. After a washout period of 4 weeks, participants received GSK2269557 1000 micrograms (µg) drug once daily via dry powder inhaler for 28 days during Treatment Period 2. In addition, salbutamol was provided to participants to use on an as-needed basis for relief of asthma symptoms.
|
GSK2269557, Then Placebo
Participants received GSK2269557 1000 µg drug once daily via dry powder inhaler for the 28 days during Treatment Period 1. After a washout period of 4 weeks, participants received placebo drug once daily via dry powder inhaler for 28 days during Treatment Period 2. In addition, salbutamol was provided to participants to use on an as-needed basis for relief of asthma symptoms.
|
|---|---|---|
|
Treatment Period 1 (Up to 4 Weeks)
STARTED
|
24
|
26
|
|
Treatment Period 1 (Up to 4 Weeks)
COMPLETED
|
22
|
23
|
|
Treatment Period 1 (Up to 4 Weeks)
NOT COMPLETED
|
2
|
3
|
|
Washout Period (Up to 4 Weeks)
STARTED
|
22
|
23
|
|
Washout Period (Up to 4 Weeks)
COMPLETED
|
22
|
23
|
|
Washout Period (Up to 4 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2 (Up to 4 Weeks)
STARTED
|
22
|
23
|
|
Treatment Period 2 (Up to 4 Weeks)
COMPLETED
|
22
|
20
|
|
Treatment Period 2 (Up to 4 Weeks)
NOT COMPLETED
|
0
|
3
|
Reasons for withdrawal
| Measure |
Placebo, Then GSK2269557
Participants received placebo drug once daily via dry powder inhaler for 28 days during Treatment Period 1. After a washout period of 4 weeks, participants received GSK2269557 1000 micrograms (µg) drug once daily via dry powder inhaler for 28 days during Treatment Period 2. In addition, salbutamol was provided to participants to use on an as-needed basis for relief of asthma symptoms.
|
GSK2269557, Then Placebo
Participants received GSK2269557 1000 µg drug once daily via dry powder inhaler for the 28 days during Treatment Period 1. After a washout period of 4 weeks, participants received placebo drug once daily via dry powder inhaler for 28 days during Treatment Period 2. In addition, salbutamol was provided to participants to use on an as-needed basis for relief of asthma symptoms.
|
|---|---|---|
|
Treatment Period 1 (Up to 4 Weeks)
Adverse Event
|
0
|
2
|
|
Treatment Period 1 (Up to 4 Weeks)
Protocol Violation
|
0
|
1
|
|
Treatment Period 1 (Up to 4 Weeks)
Other: Reached stopping criteria
|
2
|
0
|
|
Treatment Period 2 (Up to 4 Weeks)
Other: Reached stopping criteria
|
0
|
3
|
Baseline Characteristics
A Study to Investigate the Efficacy, Safety, and Tolerability of Repeat Doses of Inhaled GSK2269557 in Adults With Persistent, Uncontrolled Asthma
Baseline characteristics by cohort
| Measure |
All Participants
n=50 Participants
In Sequence 1 participants received placebo drug once daily via dry powder inhaler for 28 days during Treatment Period 1. After a washout period of 4 weeks, participants received GSK2269557 1000 micrograms (µg) drug once daily via dry powder inhaler for 28 days during Treatment Period 2. In addition, salbutamol was provided to participants to use on an as-needed basis for relief of asthma symptoms. In Sequence 2 participants received GSK2269557 1000 micrograms (µg) drug once daily via dry powder inhaler for 28 days during Treatment Period 1. After a washout period of 4 weeks, participants received placebo drug once daily via dry powder inhaler for 28 days during Treatment Period 2. In addition, salbutamol was provided to participants to use on an as-needed basis for relief of asthma symptoms.
|
|---|---|
|
Age, Continuous
|
44.5 Years
STANDARD_DEVIATION 13.86 • n=5 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
50 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 28 for each treatment periodPopulation: The analysis was performed on the ITT Population which comprised of all participants who received at least one dose of trial medication and have at least one post-dose efficacy assessment. Six participants had entered the study without spirometric evidence of disease, and were excluded from the ITT population prior to unblinding.
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is the maximum volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug. FEV1 was measured using a spirometer. Change from Baseline is calculated as post-Baseline value minus Baseline value where Baseline is defined as Day 1 (pre-dose).
Outcome measures
| Measure |
Placebo
n=37 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=39 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 28 in Intent-To-Treat (ITT) Population
|
0.027 Liters
Interval -0.066 to 0.117
|
0.035 Liters
Interval -0.061 to 0.124
|
PRIMARY outcome
Timeframe: Baseline and Day 28 for each treatment periodPopulation: PP Population
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is the maximum volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug. FEV1 was measured using a spirometer. Change from Baseline is calculated as post-Baseline value minus Baseline value where Baseline is defined as Day 1 (pre-dose). The analysis was performed on the PP Population which comprised of all participants in the ITT Population not identified as major protocol violators.
Outcome measures
| Measure |
Placebo
n=35 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=37 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 28 in Per Protocol (PP) Population
|
0.029 Liters
Interval -0.073 to 0.119
|
0.042 Liters
Interval -0.058 to 0.132
|
SECONDARY outcome
Timeframe: Day 28 for each treatment periodPopulation: ITT Population. Only those participants with data available at specific time point were analyzed.
The weighted mean FEV1 on Day 28 was calculated using data collected pre-dose and at 1 hour, 2 hours, 3 hours, and 4 hours post-dose. The weighted mean FEV1 was derived by calculating the average area under the curve using the trapezoidal rule, and then dividing by the relevant time interval.
Outcome measures
| Measure |
Placebo
n=38 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=40 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Weighted Mean (0-4 Hours) FEV1 at Day 28
|
2.672 Liters
Interval 2.556 to 2.783
|
2.722 Liters
Interval 2.607 to 2.836
|
SECONDARY outcome
Timeframe: Baseline, Day 7 and Day 14 for each treatment periodPopulation: ITT Population.
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The trough FEV1 is the maximum volume of air that can be forced out in one second after taking a deep breath approximately 24 hrs after the last administration of study drug. Change from Baseline values were calculated as post-Baseline values minus Baseline value where Baseline was defined as Day 1 (pre-dose). The number of participants with data available at the specified time points are represented by n=X in the category titles.
Outcome measures
| Measure |
Placebo
n=42 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=42 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Change From Baseline in Trough FEV1 at Day 7 and Day 14
Day 7; n= 39, 40
|
0.012 Liters
Interval -0.102 to 0.131
|
0.003 Liters
Interval -0.113 to 0.119
|
|
Change From Baseline in Trough FEV1 at Day 7 and Day 14
Day 14; n= 38,41
|
0.016 Liters
Interval -0.086 to 0.116
|
0.040 Liters
Interval -0.061 to 0.137
|
SECONDARY outcome
Timeframe: Baseline, Day 7, Day 14 and Day 28 for each treatment periodPopulation: ITT Population.
FVC is defined as the total amount of air exhaled during the FEV test. Data was collected pre-dose at Baseline (Day 1), Day 7, Day 14 and Day 28. Change from Baseline was calculated as the post-Baseline value minus the Baseline value where Baseline was defined as Day 1 (pre-dose). The number of participants with data available at the specified time points are represented by n=X in the category titles.
Outcome measures
| Measure |
Placebo
n=42 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=42 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Change From Baseline in Forced Vital Capacity (FVC) at Day 7, Day 14 and Day 28
Day 7; n= 39,40
|
0.036 Liter
Interval -0.075 to 0.146
|
0.015 Liter
Interval -0.097 to 0.126
|
|
Change From Baseline in Forced Vital Capacity (FVC) at Day 7, Day 14 and Day 28
Day 14; n= 38,41
|
-0.002 Liter
Interval -0.11 to 0.107
|
0.038 Liter
Interval -0.069 to 0.146
|
|
Change From Baseline in Forced Vital Capacity (FVC) at Day 7, Day 14 and Day 28
Day 28; n= 37,39
|
0.017 Liter
Interval -0.092 to 0.124
|
0.054 Liter
Interval -0.052 to 0.159
|
SECONDARY outcome
Timeframe: Baseline, Day 7, Day 14 and Day 28 for each treatment periodPopulation: ITT Population.
FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the total amount of air exhaled during the FEV test. Change from Baseline in FEV1/FVC at Day 7, Day 14 and Day 28 was calculated as post-Baseline value minus Baseline value where Baseline was defined as Day 1 (pre-dose). The number of participants with data available at the specified time points are represented by n=X in the category titles.
Outcome measures
| Measure |
Placebo
n=42 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=42 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Change From Baseline in FEV1/FVC at Day 7, Day 14 and Day 28
Day 7; n= 39,40
|
-0.956 Percentage of exhaled air
Interval -2.337 to 0.495
|
-0.855 Percentage of exhaled air
Interval -2.285 to 0.517
|
|
Change From Baseline in FEV1/FVC at Day 7, Day 14 and Day 28
Day 14; n= 38,41
|
-0.456 Percentage of exhaled air
Interval -1.944 to 0.986
|
-0.444 Percentage of exhaled air
Interval -1.899 to 0.992
|
|
Change From Baseline in FEV1/FVC at Day 7, Day 14 and Day 28
Day 28; n= 37,39
|
-0.691 Percentage of exhaled air
Interval -2.05 to 0.638
|
-0.791 Percentage of exhaled air
Interval -2.163 to 0.516
|
SECONDARY outcome
Timeframe: Baseline and Day 28 for each treatment periodPopulation: ITT Population. Only those participants with data available at specified time point were analyzed.
The total ACT score is the sum of five-item questionnaires developed as a measurement of asthma control. Total score can range from five (worse control) to 25 (full control), with higher scores reflecting greater asthma control. Total ACT score at Day 1 (Baseline) and Day 28 in both Treatment Periods was used for this analysis. Change from Baseline in ACT was calculated as post-Baseline value minus Baseline value where Baseline was defined as Day 1 (pre-dose).
Outcome measures
| Measure |
Placebo
n=38 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=40 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Change From Baseline in Asthma Control Test (ACT) Score at Day 28
|
1.4 Score on a scale
Interval 0.5 to 2.2
|
1.9 Score on a scale
Interval 1.0 to 2.7
|
SECONDARY outcome
Timeframe: Baseline and up to Day 28 for each treatment periodPopulation: ITT Population.
Triplicate measurements of FEV1 were collected in an eDiary pre-dose before breakfast \[ante meridiem (AM)\], and approximately 12 hours later at evening \[post-meridiem (PM)\]. The average change from Baseline was calculated by summing the total value of the endpoint (i.e. change from Baseline) within the time period of interest and dividing by the number of days with non-missing data for that endpoint to obtain an average for each subject. The AM Baseline is the Day 1 AM value, the PM Baseline is the last PM reading prior to taking the first dose of blinded study medication within that Treatment Period. The number of participants with data available at the specified time points are represented by n=X in the category titles.
Outcome measures
| Measure |
Placebo
n=42 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=42 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Change From Baseline in Daily FEV1 Averaged Over the Treatment Period
AM; n= 38, 40
|
0.000 Liter
Standard Deviation 0.2019
|
0.065 Liter
Standard Deviation 0.2974
|
|
Change From Baseline in Daily FEV1 Averaged Over the Treatment Period
PM; n= 34, 39
|
0.013 Liter
Standard Deviation 0.2634
|
0.115 Liter
Standard Deviation 0.3802
|
SECONDARY outcome
Timeframe: Baseline and up to Day 28 for each treatment periodPopulation: ITT Population
Triplicate measurements of PEF were collected in an eDiary pre-dose before breakfast (AM), and approximately 12 hours later at evening (PM). The average change from Baseline was calculated by summing the total value of the endpoint (i.e. change from Baseline) within the time period of interest and dividing by the number of days with non-missing data for that endpoint to obtain an average for each subject. The AM Baseline is the Day 1 AM value, the PM Baseline is the last PM reading prior to taking the first dose of blinded study medication within that Treatment Period. The number of participants with data available at the specified time points are represented by n=X in the category titles.
Outcome measures
| Measure |
Placebo
n=42 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=42 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Change From Baseline in Daily Peak Expiratory Flow (PEF) Averaged Over the Treatment Period
PM; n= 34, 39
|
9.8 Liter/minute
Standard Deviation 36.05
|
29.8 Liter/minute
Standard Deviation 64.28
|
|
Change From Baseline in Daily Peak Expiratory Flow (PEF) Averaged Over the Treatment Period
AM; n= 38,40
|
-4.8 Liter/minute
Standard Deviation 32.44
|
14.2 Liter/minute
Standard Deviation 46.11
|
SECONDARY outcome
Timeframe: Baseline, Day 7, Day 14 and Day 28 for each treatment periodPopulation: ITT Population.
Participants with asthma have high levels of NO in their exhaled breath. Evaluation of FeNO is a quantitative, noninvasive method of measuring airway inflammation to assess airway diseases including asthma. FeNO was measured in the clinic using a handheld electronic device. Change from Baseline for Day 7, Day 14 and Day 28 was calculated as the post-Baseline value minus the Baseline value where Baseline was defined as Day 1 (pre-dose). The number of participants with data available at the specified time points are represented by n=X in the category titles.
Outcome measures
| Measure |
Placebo
n=42 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=42 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Change From Baseline in Trough Fractional Exhaled Nitric Oxide (FeNO) at Day 7, Day 14 and Day 28
Day 7; n= 38,34
|
1.03 Part per billion (PPB)
Interval 0.93 to 1.13
|
0.91 Part per billion (PPB)
Interval 0.82 to 1.01
|
|
Change From Baseline in Trough Fractional Exhaled Nitric Oxide (FeNO) at Day 7, Day 14 and Day 28
Day 14; n= 34,35
|
0.99 Part per billion (PPB)
Interval 0.89 to 1.11
|
0.95 Part per billion (PPB)
Interval 0.85 to 1.05
|
|
Change From Baseline in Trough Fractional Exhaled Nitric Oxide (FeNO) at Day 7, Day 14 and Day 28
Day 28; n= 34,34
|
1.03 Part per billion (PPB)
Interval 0.91 to 1.17
|
1.03 Part per billion (PPB)
Interval 0.91 to 1.17
|
SECONDARY outcome
Timeframe: Up to Day 28 for each treatment periodPopulation: ITT Population. Only those participants with data available at specified time point were analyzed.
Daily recordings of rescue medication use were collected in an eDiary by participants. The mean number of inhalations per day of rescue medication was calculated for each participant as number of inhalations over the time period of interest divided by number of days when rescue medication was taken over the time period of interest.
Outcome measures
| Measure |
Placebo
n=38 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=39 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Mean Number of Inhalations Per Day of Rescue Medication (Salbutamol) Over the Treatment Period
|
3.0 Inhalations/day
Standard Deviation 1.86
|
2.7 Inhalations/day
Standard Deviation 1.53
|
SECONDARY outcome
Timeframe: Up to Day 28 for each treatment periodPopulation: ITT Population.
Daily recordings of rescue medication use were collected in an eDiary by participants. Percentage of rescue free days was calculated as the number of rescue free days divided by length of treatment period.
Outcome measures
| Measure |
Placebo
n=42 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=42 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Percentage of Rescue Free Days Over the Treatment Period
|
49.5 Percentage of days
Standard Deviation 35.04
|
47.3 Percentage of days
Standard Deviation 34.79
|
SECONDARY outcome
Timeframe: From the Start of IP up to Week 14Population: Safety Population
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The analysis was performed on Safety Population which comprised of all participants who were randomized into the study.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=48 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Number of Participants With On-treatment Serious Adverse Events (SAEs) and Non-serious Adverse Events (AEs)
non-SAE
|
13 Participants
|
19 Participants
|
|
Number of Participants With On-treatment Serious Adverse Events (SAEs) and Non-serious Adverse Events (AEs)
SAE
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From start of IP up to Week 14Population: Safety Population
Blood samples were collected from participants for evaluation of clinical chemistry parameters by Potential Clinical Importance Criteria. The clinical chemistry parameters included albumin, calcium, creatinine, glucose, potassium and sodium. Participants were counted in the category that their value changes to (low, normal or high), unless there is no change in their category. The number of participants with data available at the specified data points are represented by n=X in the category titles.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=48 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Albumin; Day 1; Change to low; n= 47, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Albumin; Day 14; Change to low; n= 42, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Albumin; Day 28; Change to low; n= 41, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Calcium; Day 1; Change to low; n= 47, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Calcium; Day 1; Change to high; n= 47, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Calcium; Day 14; Change to low; n= 42, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Calcium; Day 14; Change to high; n= 42, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Calcium; Day 28; Change to high; n= 40, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Calcium; Day 28; Change to low; n= 40, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Glucose; Day 1; Change to low; n= 47, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Glucose; Day 1; change to high; n= 47, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Glucose; Day 14; Change to low; n= 42, 48
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Glucose; Day 14; change to high; n= 42, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Glucose; Day 28; Change to low; n= 41, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Glucose; Day 28; Change to high; n= 41, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Potassium; Day 1; Change to low; n= 47, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Potassium; Day 1; Change to high; n= 47, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Potassium; Day 14; Change to low; n= 42, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Potassium; Day 14; Change to high; n= 42, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Potassium; Day 28; Change to low; n= 40, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Potassium; Day 28; Change to high; n= 40, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Sodium; Day 1; Change to low; n= 47, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Sodium; Day 1; Change to high; n= 47, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Sodium; Day 14; Change to low; n= 42, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Sodium; Day 14; Change to high; n= 42, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Sodium; Day 28; Change to low; n= 41, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Sodium; Day 28; Change to high; n= 41, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Hematocrit; Day 1; Change to high; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Hematocrit; Day 14; Change to high; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Hematocrit; Day 28; Change to high; n= 42, 44
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Hemoglobin; Day 1; Change to high; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Hemoglobin; Day 14; Change to high; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Hemoglobin; Day 28; Change to high; n= 42, 44
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Lymphocytes; Day 1; Change to low; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Lymphocytes; Day 14; Change to low; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Lymphocytes; Day 28; Change to low; n= 42, 44
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Platelet count; Day 1; Change to low; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Platelet count; Day 1; Change to high; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Platelet count; Day 14; Change to low; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Platelet count; Day 14; Change to high; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Platelet count; Day 28; Change to low; n= 42, 43
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Platelet count; Day 28; Change to high; n= 42, 43
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Total neutrophils; Day 1; Change to low; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Total neutrophils;Day 14; Change to low; n= 43, 47
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Total neutrophils; Day 28; Change to low; n= 42,44
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
WBC; Day 1; Change to low; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
WBC; Day 1; Change to high; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
WBC; Day 14; Change to low; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
WBC; Day 14; Change to high; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
WBC; Day 28; Change to low; n= 42, 44
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
WBC; Day 28; Change to high; n= 42, 44
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From start of IP up to Week 14Population: Safety Population
Blood samples were collected from participants for evaluation of hematology parameters by Potential Clinical Importance Criteria. The hematology parameters included hematocrit, hemoglobin, lymphocytes, total neutrophils, platelets and white blood cells (WBC). Participants were counted in the category that their value changes to (low, normal or high), unless there is no change in their category. The number of participants with data available at the specified data points are represented by n=X in the category titles.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=48 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Number of Participants With Abnormal Values of Hematology Parameters
Hematocrit; Day 1; Change to high; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Hematocrit; Day 14; Change to high; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Hematocrit; Day 28; Change to high; n= 42, 44
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Hemoglobin; Day 1; Change to high; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Hemoglobin; Day 14; Change to high; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Hemoglobin; Day 28; Change to high; n= 42, 44
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Lymphocytes; Day 1; Change to low; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Lymphocytes; Day 14; Change to low; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Lymphocytes; Day 28; Change to low; n= 42, 44
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Platelet count; Day 1; Change to low; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Platelet count; Day 1; Change to high; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Platelet count; Day 14; Change to low; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Platelet count; Day 14; Change to high; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Platelet count; Day 28; Change to low; n= 42, 43
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Platelet count; Day 28; Change to high; n= 42, 43
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Total neutrophils; Day 1; Change to low; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Total neutrophils;Day 14; Change to low; n= 43, 47
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
Total neutrophils; Day 28; Change to low; n= 42,44
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
WBC; Day 1; Change to low; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
WBC; Day 1; Change to high; n= 46, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
WBC; Day 14; Change to low; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
WBC; Day 14; Change to high; n= 43, 47
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
WBC; Day 28; Change to low; n= 42, 44
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Values of Hematology Parameters
WBC; Day 28; Change to high; n= 42, 44
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From start of IP up to Week 14Population: Safety Population
Number of participants with abnormal values of vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were evaluated. Vital signs outside the range of potential clinical importance are presented at the indicated timepoints: Day 7, Day 14, Day 28 and follow-up/Early withdrawal. The number of participants with data available at the specified data points are represented by n=X in the category titles.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=48 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Number of Participants With Abnormal Vital Sign Values
DBP; Day 7; Change to low; n= 46, 46
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
DBP; Day 7; Change to high; n= 46, 46
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
DBP; Day 14; Change to low; n= 43, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
DBP; Day 14; Change to high; n= 43, 48
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
DBP; Day 28; Change to low; n= 42, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
DBP; Day 28; Change to high; n= 42, 45
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
SBP; Day 7; Change to low; n= 46, 46
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
SBP; Day 7; Change to high; n= 46, 46
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
SBP; Day 14; Change to low; n= 43, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
SBP; Day 14; Change to high; n= 43, 48
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
SBP; Day 28; Change to low; n= 42, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
SBP; Day 28; Change to high; n= 42, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
Heart rate; Day 7; Change to low; n= 46, 46
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
Heart rate; Day 7; Change to high; n= 46, 46
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
Heart rate; Day 14; Change to low; n= 43, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
Heart rate; Day 14; Change to high; n= 43, 48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
Heart rate; Day 28; Change to low; n= 42, 45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Sign Values
Heart rate; Day 28; Change to high; n= 42, 45
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 28 for each treatment periodPopulation: Safety Population
Single measurements of 12-lead ECGs were obtained after 5 minutes rest in a semi-supine position at Baseline (Day 1 pre dose) , Day 7, Day 28 pre-dose in each treatment period using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc). ECG values were recorded as abnormal not clinically significant (NCS) and abnormal clinically significant (CS). The number of participants with data available at the specified data points are represented by n= X in the category titles.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=48 Participants
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Day 1; abnormal NCS; n= 47,48
|
2 Participants
|
5 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Day 1; abnormal CS; n= 47,48
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Day 7; abnormal NCS; n= 46,46
|
1 Participants
|
4 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Day 7; abnormal CS; n= 46,46
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Day 28; abnormal NCS; n= 42, 45
|
0 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Day 28; abnormal CS; n= 42,45
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Any time Post-Baseline; abnormal NCS; n= 47,48
|
1 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Any time Post Baseline; abnormal CS; n= 47,48
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre dose at Day 7 and Day 14. At Day 28 pre dose, 5-10 minutes and 2.5-3.5 hours post dosePopulation: PK Population
Blood samples were collected from participants for pharmacokinetic (PK) analysis at Day 7, Day 14 and Day 28 pre dose. On Day 28 samples were also collected between 5-10 minutes post dose and between 2.5-3.5 hours post dose. The analysis was performed on PK Population which comprised of participants in the ITT Population for whom a PK sample was obtained and analyzed. The number of participants with data available at the specified data points are represented by n= X in the category titles.
Outcome measures
| Measure |
Placebo
n=42 Participants
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Plasma Concentration of GSK2269557
Day 7; pre dose; n= 40
|
555.7 Picograms per Milliliter (Pg/mL)
Interval 446.2 to 692.0
|
—
|
|
Plasma Concentration of GSK2269557
Day 14; pre dose; n= 40
|
520.7 Picograms per Milliliter (Pg/mL)
Interval 380.3 to 712.9
|
—
|
|
Plasma Concentration of GSK2269557
Day 28; pre dose; n= 38
|
649.2 Picograms per Milliliter (Pg/mL)
Interval 519.9 to 810.8
|
—
|
|
Plasma Concentration of GSK2269557
Day 28; 5-10 minutes post dose; n= 40
|
1188.8 Picograms per Milliliter (Pg/mL)
Interval 990.5 to 1426.8
|
—
|
|
Plasma Concentration of GSK2269557
Day 28; 2.5-3.5 hours post dose; n= 40
|
1170.8 Picograms per Milliliter (Pg/mL)
Interval 976.1 to 1404.4
|
—
|
Adverse Events
Placebo
GSK2269557 1000 µg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=47 participants at risk
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
GSK2269557 1000 µg
n=48 participants at risk
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
14.9%
7/47 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment up to Week 14.
Non-SAEs and SAEs were collected in Safety Population which comprised of all participants who were randomized.
|
4.2%
2/48 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment up to Week 14.
Non-SAEs and SAEs were collected in Safety Population which comprised of all participants who were randomized.
|
|
Nervous system disorders
Headache
|
8.5%
4/47 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment up to Week 14.
Non-SAEs and SAEs were collected in Safety Population which comprised of all participants who were randomized.
|
4.2%
2/48 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment up to Week 14.
Non-SAEs and SAEs were collected in Safety Population which comprised of all participants who were randomized.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.5%
4/47 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment up to Week 14.
Non-SAEs and SAEs were collected in Safety Population which comprised of all participants who were randomized.
|
35.4%
17/48 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment up to Week 14.
Non-SAEs and SAEs were collected in Safety Population which comprised of all participants who were randomized.
|
Additional Information
GSK Response Center
GlaxoSmithKline
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