Clinical Trial Results:
A multi-centre, randomised, double-blind, placebo-controlled, crossover study to investigate the efficacy, safety, and tolerability of repeat doses of inhaled GSK2269557 in adults with persistent, uncontrolled asthma
Summary
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EudraCT number |
2014-003808-77 |
Trial protocol |
DE |
Global end of trial date |
28 Sep 2016
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Results information
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Results version number |
v3(current) |
This version publication date |
04 Aug 2018
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First version publication date |
04 Jun 2017
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Other versions |
v1 , v2 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
201543
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Dec 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Sep 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Sep 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To investigate the efficacy of inhaledGSK2269557 administered once daily for 28 days in subjects with persistent uncontrolled asthma, compared with placebo.
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Protection of trial subjects |
The study protocol has included the following stopping criteria:
- Liver Chemistry Stopping Criteria
- QTc Stopping Criteria
- Other Safety stopping criteria like
Unacceptable adverse events related to study drug or study procedures.
Clinically significant and relevant changes in laboratory parameters or ECG recordings.
Paradoxical bronchospasm
Pregnancy (female subjects)
- Efficacy stopping criteria
- A subjects may withdraw from study treatment at any time at his/her own request, or may be withdrawn at any time at the discretion of the investigator for safety, behavioural or administrative reasons.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Oct 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 50
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Worldwide total number of subjects |
50
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EEA total number of subjects |
50
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
47
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
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. | |||||||||||||||||||||
Pre-assignment
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Screening details |
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. | |||||||||||||||||||||
Period 1
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Period 1 title |
Treatment Period 1 (Up to 4 weeks)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo, then GSK2269557 | |||||||||||||||||||||
Arm description |
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. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
2 inhalations of lactose were administered every day before breakfast by using DISKUS DPI. Inhalations were taken approximately 30 seconds apart.
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Investigational medicinal product name |
GSK2269557
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
2 inhalations of GSK269557 were administered every day before breakfast by using DISKUS dry powder inhaler (DPI). Inhalations were taken approximately 30 seconds apart.
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Arm title
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GSK2269557, then Placebo | |||||||||||||||||||||
Arm description |
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. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
GSK2269557
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
2 inhalations of GSK269557 were administered every day before breakfast by using DISKUS dry powder inhaler (DPI). Inhalations were taken approximately 30 seconds apart.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
2 inhalations of lactose were administered every day before breakfast by using DISKUS DPI. Inhalations were taken approximately 30 seconds apart.
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Period 2
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Period 2 title |
Washout period (Up to 4 weeks)
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Is this the baseline period? |
No | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo, then GSK2269557 | |||||||||||||||||||||
Arm description |
The two treatment periods were separated by a four-week wash-out period in which all participants did not receive study medication, but were provided a salbutamol inhaler for symptomatic relief of asthma symptoms. | |||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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GSK2269557, then Placebo | |||||||||||||||||||||
Arm description |
The two treatment periods were separated by a four-week wash-out period in which all participants did not receive study medication, but were provided a salbutamol inhaler for symptomatic relief of asthma symptoms. | |||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Period 3
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Period 3 title |
Treatment period 2 (Up to 4 weeks)
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Is this the baseline period? |
No | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo, then GSK2269557 | |||||||||||||||||||||
Arm description |
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. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
2 inhalations of lactose were administered every day before breakfast by using DISKUS DPI. Inhalations were taken approximately 30 seconds apart.
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Investigational medicinal product name |
GSK2269557
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
2 inhalations of GSK269557 were administered every day before breakfast by using DISKUS dry powder inhaler (DPI). Inhalations were taken approximately 30 seconds apart.
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Arm title
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GSK2269557, then Placebo | |||||||||||||||||||||
Arm description |
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. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
GSK2269557
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
2 inhalations of GSK269557 were administered every day before breakfast by using DISKUS dry powder inhaler (DPI). Inhalations were taken approximately 30 seconds apart.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
2 inhalations of lactose were administered every day before breakfast by using DISKUS DPI. Inhalations were taken approximately 30 seconds apart.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment Period 1 (Up to 4 weeks)
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Reporting group description |
Treatment Period 1 (Up to 4 weeks) | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo, then GSK2269557
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Reporting group description |
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. | ||
Reporting group title |
GSK2269557, then Placebo
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Reporting group description |
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. | ||
Reporting group title |
Placebo, then GSK2269557
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Reporting group description |
The two treatment periods were separated by a four-week wash-out period in which all participants did not receive study medication, but were provided a salbutamol inhaler for symptomatic relief of asthma symptoms. | ||
Reporting group title |
GSK2269557, then Placebo
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Reporting group description |
The two treatment periods were separated by a four-week wash-out period in which all participants did not receive study medication, but were provided a salbutamol inhaler for symptomatic relief of asthma symptoms. | ||
Reporting group title |
Placebo, then GSK2269557
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Reporting group description |
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. | ||
Reporting group title |
GSK2269557, then Placebo
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Reporting group description |
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. | ||
Subject analysis set title |
Placebo
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
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Subject analysis set title |
GSK2269557 1000 µg
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2.
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End point title |
Change from Baseline in trough forced expiratory volume in one second (FEV1) at Day 28 in Intent-To-Treat (ITT) Population | |||||||||||||||
End point description |
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 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.
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End point type |
Primary
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End point timeframe |
Baseline and Day 28 for each treatment period
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Notes [1] - ITT Population [2] - ITT Population |
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Statistical analysis title |
Statistical analysis 1 | |||||||||||||||
Statistical analysis description |
The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo. The total number of participants included in the analysis is 84; however, the value calculated by the system (76) is incorrect.
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Comparison groups |
GSK2269557 1000 µg v Placebo
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Number of subjects included in analysis |
76
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | |||||||||||||||
P-value |
= 0.57 [4] | |||||||||||||||
Method |
Bayesian repeated measures model | |||||||||||||||
Parameter type |
Posterior median difference. | |||||||||||||||
Point estimate |
0.007
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.083 | |||||||||||||||
upper limit |
0.102 | |||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0.0468
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Notes [3] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [4] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
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End point title |
Change from Baseline in trough forced expiratory volume in one second (FEV1) at Day 28 in Per Protocol (PP) Population | |||||||||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
Baseline and Day 28 for each treatment period
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Notes [5] - PP Population [6] - PP Population |
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Statistical analysis title |
Statistical analysis 1 | |||||||||||||||
Statistical analysis description |
The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo. The total number of participants included in the analysis is 78; however, the value calculated by the system (72) is incorrect.
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Comparison groups |
Placebo v GSK2269557 1000 µg
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Number of subjects included in analysis |
72
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Analysis specification |
Pre-specified
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Analysis type |
other [7] | |||||||||||||||
P-value |
= 0.61 [8] | |||||||||||||||
Method |
Bayesian repeated measures model | |||||||||||||||
Parameter type |
Posterior median difference. | |||||||||||||||
Point estimate |
0.013
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.084 | |||||||||||||||
upper limit |
0.113 | |||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0.0501
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Notes [7] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [8] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
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End point title |
Weighted mean (0-4 hours) FEV1 at Day 28 | |||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Day 28 for each treatment period
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Notes [9] - Only those participants with data available at specific time point were analyzed. [10] - Only those participants with data available at specific time point were analyzed. |
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Statistical analysis title |
Statistical analysis 1 | |||||||||||||||
Statistical analysis description |
The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo. The total number of participants included in the analysis is 84; however, the value calculated by the system (78) is incorrect.
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Comparison groups |
GSK2269557 1000 µg v Placebo
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
other [11] | |||||||||||||||
P-value |
= 0.731 [12] | |||||||||||||||
Method |
Bayesian model | |||||||||||||||
Parameter type |
Posterior median difference | |||||||||||||||
Point estimate |
0.05
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.111 | |||||||||||||||
upper limit |
0.21 | |||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0.0818
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Notes [11] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [12] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
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End point title |
Change from Baseline in trough FEV1 at Day 7 and Day 14 | ||||||||||||||||||
End point description |
The pH scale measures how acidic or basic a substance is. The pH scale ranges from 0 to 14. A pH of 7 is neutral. A pH less than 7 is acidic. A pH greater than 7 is basic. 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.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 7 and Day 14 for each treatment period
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Notes [13] - ITT Population |
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||
Statistical analysis description |
Day 7. The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo.
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Comparison groups |
Placebo v GSK2269557 1000 µg
|
||||||||||||||||||
Number of subjects included in analysis |
84
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
other [14] | ||||||||||||||||||
P-value |
= 0.44 [15] | ||||||||||||||||||
Method |
Bayesian repeated measures model | ||||||||||||||||||
Parameter type |
Posterior median difference | ||||||||||||||||||
Point estimate |
-0.009
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-0.151 | ||||||||||||||||||
upper limit |
0.131 | ||||||||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||||||||
Dispersion value |
0.0712
|
||||||||||||||||||
Notes [14] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [15] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
|||||||||||||||||||
Statistical analysis title |
Statistical analysis 2 | ||||||||||||||||||
Statistical analysis description |
Day 14. The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo.
|
||||||||||||||||||
Comparison groups |
Placebo v GSK2269557 1000 µg
|
||||||||||||||||||
Number of subjects included in analysis |
84
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
other [16] | ||||||||||||||||||
P-value |
= 0.66 [17] | ||||||||||||||||||
Method |
Bayesian repeated measures model | ||||||||||||||||||
Parameter type |
Posterior median difference | ||||||||||||||||||
Point estimate |
0.024
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-0.087 | ||||||||||||||||||
upper limit |
0.137 | ||||||||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||||||||
Dispersion value |
0.057
|
||||||||||||||||||
Notes [16] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [17] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
|
||||||||||||||||||||||
End point title |
Change from Baseline in Forced Vital Capacity (FVC) at Day 7, Day 14 and Day 28 | |||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Day 7, Day 14 and Day 28 for each treatment period
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [18] - ITT Population |
||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||||||||||||||
Statistical analysis description |
Day 7. The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo.
|
|||||||||||||||||||||
Comparison groups |
GSK2269557 1000 µg v Placebo
|
|||||||||||||||||||||
Number of subjects included in analysis |
84
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [19] | |||||||||||||||||||||
P-value |
= 0.35 [20] | |||||||||||||||||||||
Method |
Bayesian repeated measures model | |||||||||||||||||||||
Parameter type |
Posterior median difference | |||||||||||||||||||||
Point estimate |
-0.021
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-0.14 | |||||||||||||||||||||
upper limit |
0.099 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.0609
|
|||||||||||||||||||||
Notes [19] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [20] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 2 | |||||||||||||||||||||
Statistical analysis description |
Day 14. The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo.
|
|||||||||||||||||||||
Comparison groups |
GSK2269557 1000 µg v Placebo
|
|||||||||||||||||||||
Number of subjects included in analysis |
84
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [21] | |||||||||||||||||||||
P-value |
= 0.76 [22] | |||||||||||||||||||||
Method |
Bayesian repeated measures model | |||||||||||||||||||||
Parameter type |
Posterior median difference | |||||||||||||||||||||
Point estimate |
0.04
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-0.071 | |||||||||||||||||||||
upper limit |
0.156 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.0578
|
|||||||||||||||||||||
Notes [21] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [22] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 3 | |||||||||||||||||||||
Statistical analysis description |
Day 28. The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo.
|
|||||||||||||||||||||
Comparison groups |
GSK2269557 1000 µg v Placebo
|
|||||||||||||||||||||
Number of subjects included in analysis |
84
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [23] | |||||||||||||||||||||
P-value |
= 0.76 [24] | |||||||||||||||||||||
Method |
Bayesian repeated measures model | |||||||||||||||||||||
Parameter type |
Posterior median difference | |||||||||||||||||||||
Point estimate |
0.038
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-0.073 | |||||||||||||||||||||
upper limit |
0.148 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.0559
|
|||||||||||||||||||||
Notes [23] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [24] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
|
||||||||||||||||||||||
End point title |
Change from Baseline in FEV1/FVC at Day 7, Day 14 and Day 28 | |||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Day 7, Day 14 and Day 28 for each treatment period
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [25] - ITT Population |
||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||||||||||||||
Statistical analysis description |
Day 7. The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo.
|
|||||||||||||||||||||
Comparison groups |
Placebo v GSK2269557 1000 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
84
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [26] | |||||||||||||||||||||
P-value |
= 0.56 [27] | |||||||||||||||||||||
Method |
Bayesian repeated measures model | |||||||||||||||||||||
Parameter type |
Posterior median difference | |||||||||||||||||||||
Point estimate |
0.083
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-1.102 | |||||||||||||||||||||
upper limit |
1.346 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.6175
|
|||||||||||||||||||||
Notes [26] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [27] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 2 | |||||||||||||||||||||
Statistical analysis description |
Day 14. The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo.
|
|||||||||||||||||||||
Comparison groups |
Placebo v GSK2269557 1000 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
84
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [28] | |||||||||||||||||||||
P-value |
= 0.51 [29] | |||||||||||||||||||||
Method |
Bayesian repeated measures model | |||||||||||||||||||||
Parameter type |
Posterior median difference | |||||||||||||||||||||
Point estimate |
0.014
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-1.271 | |||||||||||||||||||||
upper limit |
1.341 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.6672
|
|||||||||||||||||||||
Notes [28] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [29] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 3 | |||||||||||||||||||||
Statistical analysis description |
Day 28. The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo.
|
|||||||||||||||||||||
Comparison groups |
Placebo v GSK2269557 1000 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
84
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [30] | |||||||||||||||||||||
P-value |
= 0.41 [31] | |||||||||||||||||||||
Method |
Bayesian repeated measures model | |||||||||||||||||||||
Parameter type |
Posterior median difference | |||||||||||||||||||||
Point estimate |
-0.113
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-1.125 | |||||||||||||||||||||
upper limit |
0.908 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.5148
|
|||||||||||||||||||||
Notes [30] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [31] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
|
||||||||||||||||
End point title |
Change from Baseline in Asthma Control Test (ACT) score at Day 28 | |||||||||||||||
End point description |
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).
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Baseline and Day 28 for each treatment period
|
|||||||||||||||
|
||||||||||||||||
Notes [32] - Only those participants with data available at specified time point were analyzed. [33] - Only those participants with data available at specified time point were analyzed. |
||||||||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||||||||
Statistical analysis description |
The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median difference is calculated as GSK2269557 1000 μg minus Placebo. The total number of participants included in the analysis is 84; however, the value calculated by the system (78) is incorrect.
|
|||||||||||||||
Comparison groups |
GSK2269557 1000 µg v Placebo
|
|||||||||||||||
Number of subjects included in analysis |
78
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
other [34] | |||||||||||||||
P-value |
= 0.81 [35] | |||||||||||||||
Method |
Bayesian model | |||||||||||||||
Parameter type |
Posterior median difference | |||||||||||||||
Point estimate |
0.5
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
-0.6 | |||||||||||||||
upper limit |
1.7 | |||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||
Dispersion value |
0.59
|
|||||||||||||||
Notes [34] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [35] - The data entered for the p-value represents the posterior probability that the true treatment difference is greater than zero. |
|
|||||||||||||||||||
End point title |
Change from Baseline in daily FEV1 averaged over the treatment period | ||||||||||||||||||
End point description |
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.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline and Up to Day 28 for each treatment period
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [36] - ITT Population [37] - ITT Population |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from Baseline in daily Peak Expiratory Flow (PEF) averaged over the treatment period | ||||||||||||||||||
End point description |
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.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline and up to Day 28 for each treatment period
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [38] - ITT Population |
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Change from Baseline in trough Fractional exhaled Nitric Oxide (FeNO) at Day 7, Day 14 and Day 28 | |||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Day 7, Day 14 and Day 28 for each treatment period
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [39] - ITT Population |
||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||||||||||||||
Statistical analysis description |
Day 7. The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median ratio is calculated as GSK2269557 1000 μg/ Placebo.
|
|||||||||||||||||||||
Comparison groups |
GSK2269557 1000 µg v Placebo
|
|||||||||||||||||||||
Number of subjects included in analysis |
84
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [40] | |||||||||||||||||||||
P-value |
= 0.97 [41] | |||||||||||||||||||||
Method |
Bayesian repeated measures model | |||||||||||||||||||||
Parameter type |
Posterior median ratio | |||||||||||||||||||||
Point estimate |
0.89
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
0.78 | |||||||||||||||||||||
upper limit |
1 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.063
|
|||||||||||||||||||||
Notes [40] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [41] - The data entered for the p-value represents the posterior probability that the true treatment ratio is less than 1. |
||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 3 | |||||||||||||||||||||
Statistical analysis description |
Day 28. The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median ratio is calculated as GSK2269557 1000 μg/ Placebo.
|
|||||||||||||||||||||
Comparison groups |
Placebo v GSK2269557 1000 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
84
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [42] | |||||||||||||||||||||
P-value |
= 0.51 [43] | |||||||||||||||||||||
Method |
Bayesian repeated measures model | |||||||||||||||||||||
Parameter type |
Posterior median ratio | |||||||||||||||||||||
Point estimate |
1
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
0.84 | |||||||||||||||||||||
upper limit |
1.18 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.085
|
|||||||||||||||||||||
Notes [42] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [43] - The data entered for the p-value represents the posterior probability that the true treatment ratio is less than one. |
||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 2 | |||||||||||||||||||||
Statistical analysis description |
Day 14. The data entered as the 95% confidence interval represents the 95% equi-tailed credible interval. The posterior median ratio is calculated as GSK2269557 1000 μg/ Placebo.
|
|||||||||||||||||||||
Comparison groups |
GSK2269557 1000 µg v Placebo
|
|||||||||||||||||||||
Number of subjects included in analysis |
84
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [44] | |||||||||||||||||||||
P-value |
= 0.76 [45] | |||||||||||||||||||||
Method |
Bayesian repeated measures model | |||||||||||||||||||||
Parameter type |
Posterior median ratio | |||||||||||||||||||||
Point estimate |
0.95
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
0.83 | |||||||||||||||||||||
upper limit |
1.09 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.071
|
|||||||||||||||||||||
Notes [44] - Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted. [45] - The data entered for the p-value represents the posterior probability that the true treatment ratio is less than 1. |
|
||||||||||||||||
End point title |
Mean number of inhalations per day of rescue medication (salbutamol) over the treatment period | |||||||||||||||
End point description |
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.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Up to Day 28 for each treatment period
|
|||||||||||||||
|
||||||||||||||||
Notes [46] - Only those participants with data available at specified time point were analyzed. [47] - Only those participants with data available at specified time point were analyzed. |
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Percentage of rescue free days over the treatment period | |||||||||||||||
End point description |
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.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Up to Day 28 for each treatment period
|
|||||||||||||||
|
||||||||||||||||
Notes [48] - ITT Population |
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of participants with on-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) | |||||||||||||||
End point description |
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.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From the Start of IP up to Week 14
|
|||||||||||||||
|
||||||||||||||||
Notes [49] - Safety Population [50] - Safety Population |
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with abnormal values of clinical chemistry parameters | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From start of IP up to Week 14
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Notes [51] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with abnormal values of hematology parameters | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From start of IP up to Week 14
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [52] - Safety Population |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with abnormal vital sign values | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From start of IP up to Week 14
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [53] - Safety Population |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Number of participants with abnormal electrocardiogram (ECG) findings | |||||||||||||||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Up to Day 28 for each treatment period
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
Notes [54] - Safety Population |
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Plasma concentration of GSK2269557 | ||||||||||||||||||
End point description |
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.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Pre dose at Day 7 and Day 14. At Day 28 pre dose, 5-10 minutes and 2.5-3.5 hours post dose
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [55] - PK Population |
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
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.
|
|||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Non-SAEs and SAEs were collected in Safety Population which comprised of all participants who were randomized.
|
|||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants who received matching placebo once daily via dry powder inhaler for 28 days in either treatment period 1 or 2. | |||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
GSK2269557 1000 µg
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants who received GSK2269557 1000 µg once daily via dry powder inhaler for 28 days in either treatment period 1 or 2. | |||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
12 Feb 2016 |
Removal of instruction on the need for precautionary measures to protect against potential photosensitive effects of GSK2269557; Addition of 2 secondary efficacy endpoints; Clarification to the requirements surrounding pregnancy testing at screening compared to other time points; Addition of nicotine replacement or containing products to the prohibited medicines list; Alignment of background information to reflect the current status of ongoing clinical investigations pertaining to this investigational medicinal product. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |