An Open-label Study to Evaluate Correct Use and Ease of Use of the ELLIPTA Dry Powder Inhaler (DPI) in Pediatric Patients Currently Receiving Inhaled Therapy for Treatment of Their Asthma
Phase: PHASE4
Conditions: Asthma
Sponsor: GlaxoSmithKline

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TITLE PAGE
Protocol Title: An open-label study to evaluate correct use and ease of use of the 
ELLIPTA Dry Powder Inhaler (DPI) in pediatric patients currently receiving inhaled 
therapy for treatment of their asthma
Protocol Number: 206924 
Short Title: An open-label study to evaluate correct use and ease of use of the ELLIPTA 
DPI in pediatric patients with asthma
Compound Number:
GSK2285997 
Sponsor Name and Legal Registered Address: 
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual
Regulatory Agency Identifying Number(s): N/A
Approval Date: 23-JAN-2018
Copyright 2018 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorized copying or use of this information is prohibited.

PPD
PPD

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TABLE OF CONTENTS
PAGE
1.
SYNOPSIS...............................................................................................................6
2.
SCHEDULE OF ACTIVITIES (SOA).........................................................................9
3.
INTRODUCTION....................................................................................................12
3.1.
Study Rationale ..........................................................................................12
3.2.
Background ................................................................................................12
3.3.
Benefit/Risk Assessment ............................................................................13
3.3.1.
Risk Assessment .........................................................................14
3.3.2.
Benefit Assessment.....................................................................15
3.3.3.
Overall Benefit:Risk Conclusion...................................................15
4.
OBJECTIVES AND ENDPOINTS...........................................................................15
5.
STUDY DESIGN ....................................................................................................17
5.1.
Overall Design ............................................................................................17
5.1.1.
Visit 0...........................................................................................18
5.1.2.
Visit 1...........................................................................................18
5.1.3.
Visit 2...........................................................................................19
5.2.
Number of Participants ...............................................................................19
5.3.
Participant and Study Completion...............................................................19
5.4.
Scientific Rationale for Study Design ..........................................................20
5.5.
Dose Justification........................................................................................20
6.
STUDY POPULATION...........................................................................................20
6.1.
Inclusion Criteria.........................................................................................20
6.2.
Exclusion Criteria........................................................................................21
6.3.
Lifestyle Restrictions...................................................................................22
6.3.1.
Meals and Dietary Restrictions ....................................................23
6.3.2.
Activity .........................................................................................23
6.4.
Screen Failures...........................................................................................23
7.
TREATMENTS.......................................................................................................24
7.1.
Treatments Administered............................................................................24
7.2.
Dose Modification .......................................................................................24
7.3.
Method of Treatment Assignment ...............................................................24
7.4.
Blinding.......................................................................................................25
7.5.
Preparation/Handling/Storage/Accountability..............................................25
7.6.
Treatment Compliance................................................................................26
7.7.
Concomitant Therapy..................................................................................26
7.8.
Treatment after the End of the Study ..........................................................26
8.
DISCONTINUATION CRITERIA.............................................................................27
8.1.
Discontinuation of Study Treatment ............................................................27
8.1.1.
Liver Chemistry Stopping Criteria ................................................27
8.1.2.
QTc Stopping Criteria ..................................................................27
8.1.3.
Temporary Discontinuation ..........................................................27
8.2.
Withdrawal from the Study..........................................................................28

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8.3.
Lost to Follow Up........................................................................................28
9.
STUDY ASSESSMENTS AND PROCEDURES .....................................................29
9.1.
Assessments ..............................................................................................29
9.1.1.
Screening and Critical Baseline Assessments .............................29
9.1.1.1.
Visit 1 .........................................................................29
9.1.1.1.1.
Training and correct use 
Assessments ..........................................29
9.1.2.
V2 Assessments..........................................................................30
9.1.2.1.
Ease of use Questionnaire .........................................30
9.1.2.2.
Correct Use ................................................................30
9.2.
Adverse Events...........................................................................................31
9.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information...................................................................................31
9.2.2.
Method of Detecting AEs and SAEs.............................................32
9.2.3.
Follow-up of AEs and SAEs.........................................................32
9.2.4.
Regulatory Reporting Requirements for SAEs .............................32
9.2.5.
Death Events...............................................................................32
9.2.6.
Asthma Exacerbation...................................................................33
9.3.
Treatment of Overdose...............................................................................33
9.4.
Safety Assessments ...................................................................................33
9.4.1.
Physical Examinations.................................................................34
9.4.2.
Vital Signs....................................................................................34
9.4.3.
Electrocardiograms......................................................................34
9.4.4.
Clinical Safety Laboratory Assessments ......................................34
9.4.5.
Suicidal Risk Monitoring...............................................................34
9.5.
Pharmacokinetics .......................................................................................34
9.6.
Pharmacodynamics ....................................................................................34
9.7.
Genetics .....................................................................................................34
9.8.
Biomarkers .................................................................................................34
9.9.
Health Economics OR Medical Resource Utilization and Health 
Economics..................................................................................................34
10. STATISTICAL CONSIDERATIONS........................................................................35
10.1.
Hypothesis..................................................................................................35
10.2.
Sample Size Determination ........................................................................35
10.2.1.
Sample Size Assumptions ...........................................................35
10.2.2.
Sample Size Sensitivity................................................................35
10.3.
Populations for Analyses ............................................................................36
10.4.
Statistical Analyses.....................................................................................36
10.4.1.
Efficacy Analyses.........................................................................37
10.4.2.
Safety Analyses...........................................................................37
10.4.3.
Other Analyses ............................................................................38
10.4.4.
Interim Analyses ..........................................................................38
11. REFERENCES.......................................................................................................39
12. APPENDICES........................................................................................................41
12.1.
Appendix 1: Abbreviations and Trademarks................................................41
12.2.
Appendix 2: Study Governance Considerations..........................................42
12.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......................................46

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12.4.
Appendix 4: Country-specific requirements.................................................51
12.5.
Appendix 5: ELLIPTA DPI correct use and critical error checklist ...............52
12.5.1.
Checklist......................................................................................52
12.6.
Appendix 6: Ease of use Questionnaire(s)..................................................54
12.6.1.
Ease of use Questionnaire (Participant Stratum 1, ages 5-
7 years) .......................................................................................54
12.6.1.1.
Version A....................................................................54
12.6.1.2.
Version B....................................................................54
12.6.2.
Ease of use Questionnaire (Participant Stratum 2, ages 8-
11 years)......................................................................................54
12.6.2.1.
Version A....................................................................55
12.6.2.2.
Version B....................................................................55
12.6.3.
Ease of use Questionnaire (Parent/Guardian) .............................55
12.6.3.1.
Version A....................................................................55
12.6.3.2.
Version B....................................................................56
12.7.
Appendix 7: Protocol Amendment History...................................................57

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1.
SYNOPSIS
Protocol Title: An open-label study to evaluate correct use and ease of use of the 
ELLIPTA Dry Powder Inhaler in pediatric patients currently receiving inhaled therapy 
for treatment of their asthma
Short Title: An open-label study to evaluate correct use and ease of use of the ELLIPTA 
Inhaler in pediatric patients with asthma
Rationale:
The ELLIPTA Dry Powder Inhaler (DPI) requires few steps, achieves consistent dosing 
and eliminates the hand-breath coordination required by metered dose inhalers (MDIs).  
While much research has assessed various features, including ease of use, correct use, 
critical errors and participant preference of the ELLIPTA DPI in an adult asthmatic 
population, there is very little information regarding these features in the pediatric 
population.
This study has been designed to assess the correct use of the ELLIPTA DPI in pediatric 
participants with asthma.  It will also assess the ease of use of the ELLIPTA DPI, as 
evaluated by participants who have been deemed able to use the ELLIPTA DPI correctly.
Objectives and Endpoints:
-
Stratum 1: 5 to 7 years old at V0 (inclusive)
-
Stratum 2: 8 to 11 years old at V0 (inclusive)
Objectives
Endpoints
Primary

To determine the proportion of participants 
from each stratum who demonstrate 
correct use of the ELLIPTA DPI after the 
study period at V2.

The percentage of participants from each 
stratum who demonstrate correct use of the 
ELLIPTA DPI after the study period at V2.

To determine the proportion of participants 
from each stratum who rate the use of the 
ELLIPTA DPI as easy to use, from those 
who could demonstrate correct use of the 
ELLIPTA DPI after the study period at V2.

The percentage of participants from each 
stratum who rate the ELLIPTA DPI as easy 
to use, from those who could demonstrate 
correct use of the ELLIPTA DPI after the 
study period at V2.
Secondary

To determine the proportion of participants 
from each stratum who demonstrate 
correct use of the ELLIPTA DPI after initial 
training from healthcare professional (HCP) 
at V1.

The percentage of participants from each 
stratum who demonstrate correct use of the 
ELLIPTA DPI after initial training from HCP 
at V1.

To determine the proportion of participants 
who demonstrate correct use of the 
ELLIPTA DPI after the study period at V2.

The percentage of participants who 
demonstrate correct use of the ELLIPTA DPI 
after the study period at V2.

To determine the proportion of participants 

The percentage of participants who rate the 

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Objectives
Endpoints
who rate the use of the ELLIPTA DPI as 
easy to use, from those who could 
demonstrate correct use of the ELLIPTA 
DPI after the study period at V2.
ELLIPTA DPI as easy to use, from those 
who could demonstrate correct use of the 
ELLIPTA DPI after the study period at V2.

To determine the proportion of participants 
who made at least one critical error during 
use of the ELLIPTA DPI after initial training 
from HCP at V1.

The percentage of participants who made at 
least one critical error during use of the 
ELLIPTA DPI after initial training from HCP 
at V1.
Overall Design:
This is a multi-center, single arm, stratified, open-label, randomized (version of the 
ELLIPTA DPI ease of use questionnaire) placebo study.  The study will involve up to 
3 study visits.  Participants will continue to use their prescribed asthma medications after 
meeting the eligibility criteria for the duration of the study.  The study will consist of 
pediatric asthmatic patients and it will be stratified by age (Stratum 1; 5-7 years old 
inclusive and Stratum 2; 8-11 years old inclusive).  Only participants who are naïve to the 
ELLIPTA DPI, have a documented history of symptoms consistent with a diagnosis of 
asthma and have been receiving inhaled therapy for treatment of their asthmatic 
symptoms for at least 3 months prior to V0 will be considered eligible.
V0 and V1 may take place on the same day.  At V1, participants will be trained and 
demonstrate correct use of the ELLIPTA DPI.  If successful, they will take the placebo 
ELLIPTA DPI home for the duration of the study period (28 ± 2 days) and take one dose 
daily.  Upon return to the study clinic at V2, participants will complete the ease of use 
questionnaire to which they have been randomized and then demonstrate correct use of 
the ELLIPTA DPI prior to any re-training.  Compliance with once daily usage of the 
ELLIPTA DPI during the study period will be recorded.
The protocol specific study requirements will be reviewed with each participant and their 
parent/guardian.  Informed consent and the appropriate assent will be obtained from all 
who volunteer to take part in the study, prior to the initiation of the first study procedure.

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Number of Participants:
Approximately 88 participants from Stratum 1 and 131 participants from Stratum 2 will 
need to be screened. Assuming a withdrawal rate during the study period of 3%, 
approximately 80 participants from strata 1 and 120 participants from strata 2 will 
complete the treatment period, return for V2 and be randomized to a version of ease of 
use questionnaire.
Treatment Groups and Duration:
The study population will be stratified by age (Stratum 1, 5 to 7 years old and Stratum 2, 
8 to 11 years old). The study consists of up to 3 visits and a study period of 28 ± 2 days.  
Participants will be randomized to a version of the ease of use questionnaire in a 1:1 
allocation by strata, as is defined below:
Randomization Group
Ease of Use 
Questionnaire Version
Stratum 1
A
B
Stratum 2
A
B
There is no active treatment provided during this study and participants will continue to 
take their own prescribed asthma medication for the duration of the study.

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2.
SCHEDULE OF ACTIVITIES (SOA)
The schedule of activities (SoA) in Table 1 details the timing of procedures / assessments 
to be performed in this study.
Any changes in the timing or addition of time points for any planned study assessments 
must be documented and approved by the relevant study team member and then archived 
in the sponsor and site study files, but will not constitute a protocol amendment. The 
institutional review boards (IRB)/ independent ethics committees (IEC) will be informed 
of any safety issues that require alteration of the safety monitoring scheme or amendment 
of the informed consent form (ICF).

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Table 1
Schedule of Activities
Procedure
Visit 0-
Screening 
(up to 30 
days before 
Day 1)
Treatment Period
Notes
Visit 1 (can 
occur on 
same day as 
screening)
Early 
Withdrawal
Visit 2
Day
-30
0
28 ± 2
All assessments concern study participants only, unless otherwise 
stated (parent/guardians).
Screening
Informed consent and assent
X
Visit 1 must occur within 30 days of signing of providing informed 
consent.  Must be signed before any study procedures.  Assent 
must be provided.
Inclusion and exclusion criteria
X
All of the inclusion and none of the exclusion criteria must be met 
prior to inclusion at V0. This includes ability to demonstrate correct 
use of the ELLIPTA DPI after training.
Demography
X
Age, sex, race, ethnicity.
Physical Examination
X
Including height and weight, 
Concomitant medications
X
Concomitant medications pertaining to the participant’s diagnosis 
of asthma collected (minimum previous 3 months).
Past and current medical conditions  
X
Asthma History
X
Participant will have a medical history of symptoms consistent with 
a diagnosis of asthma. 
Exacerbation History
X
Asthma exacerbation history for the previous year will be collected.
Randomization
X
Randomization refers to the version of the questionnaire only.
Safety
AE review
===============================
Collected from Visit 1 until the completion of the final assessment 
at Visit 2.
SAE review
=====================================
Collected from time of informed consent/assent until the completion 
of the final assessment at Visit 2.
Concomitant medications review
=====================================
Review any changes in concomitant medications.
Asthma exacerbations
=====================================
Asthma exacerbation information will be collected for the duration 
of the study (see Section 9.2.6)
Questionnaires and Assessments

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Procedure
Visit 0-
Screening 
(up to 30 
days before 
Day 1)
Treatment Period
Notes
Visit 1 (can 
occur on 
same day as 
screening)
Early 
Withdrawal
Visit 2
First training in correct use of ELLIPTA DPI 
by HCP 
X
Initial training by HCP
Correct use of ELLIPTA DPI after first 
instruction by HCP
X
First demonstration of correct use of ELLIPTA DPI.
Second and third training in correct use of 
ELLIPTA DPI by HCP
X
Training only if necessary (participant made errors)
Correct use of ELLIPTA DPI after second 
and third instruction by HCP
X
Second and third demonstrations of correct use of ELLIPTA DPI
Fourth and fifth training in correct use of 
ELLIPTA DPI by HCP and parent/guardian
X
Training only if necessary (participant made errors)
Correct use of ELLIPTA DPI after fourth 
and fifth instruction by HCP and 
parent/guardian
X
Fourth and fifth demonstrations of correct use of ELLIPTA DPI. 
After which time they will be registered as a screen failure if correct 
use has not been demonstrated.
Ease of use Questionnaire completion
X
This is completed upon return to the site after the study period. 
This must occur before any other assessments at V2.
Compliance with ELLIPTA DPI
X
X
This will be taken from the dose counter.
Correct use of ELLIPTA DPI after treatment 
period
X
Demonstration of correct use of ELLIPTA DPI without any 
instruction at V2.
Correct use of ELLIPTA DPI with 
instruction from parent/guardian 
X
Demonstration of correct use of ELLIPTA DPI with instruction from 
parent/guardian at V2. Only necessary if correct use is not 
demonstrated during first attempt.
Placebo ELLIPTA DPI
Dispense Placebo ELLIPTA DPI(s)
X
Procedures for dispensation and return of clinical supplies will be 
described in detail in the Study Reference Manual (SRM).  If a 
participant completes all study requirements, they will need 2 
ELLIPTA DPIs.  One will remain at site and the other will be used 
during the study period.
Return Placebo ELLIPTA DPI
X
X
X
AE – Adverse Event, DPI - Dry Powder Inhaler, HCP - Healthcare Professional, SAE - Serious Adverse Events, 

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3.
INTRODUCTION
3.1.
Study Rationale
The ELLIPTA Dry Powder Inhaler (DPI) requires few steps, achieves consistent dosing 
and eliminates the hand-breath coordination required by metered dose inhalers (MDIs).  
While much research has assessed various features, including ease of use, correct use, 
critical errors (defined as an error that is likely to significantly inhibit delivery of the 
prescribed dose of medication to the patient) and patient preference of the ELLIPTA DPI 
in an adult asthmatic population, there is very little information regarding these features 
in the pediatric population [GlaxoSmithKline Document Number 2015N230821_00; 
GlaxoSmithKline Document Number 2017N314003_00; GlaxoSmithKline Document 
Number 2016N269989_01; Van der Palen, 2016a; Van der Palen, 2016b; Van der Palen, 
2016c].  Previous studies in the pediatric population have shown that rates of correct use 
of inhalers is low, and even after instruction, patients still demonstrate poor inhalation 
technique when using a variety of Dry powder and Metered Dose Inhalers (MDI) 
[Kamps, 2000a; Kamps, 2002b].  Therefore, an inhaler that overcomes such barriers may 
be of high clinical relevance.
Accordingly, this study has been designed to assess the correct use of the ELLIPTA DPI
in pediatric participants with asthma.  It will also assess the ease of use of the ELLIPTA 
DPI, as evaluated by participants who have been deemed able to use the ELLIPTA DPI 
correctly. Recent work carried out by the GSK has helped guide the development of 
meaningful questionnaires for use within this study. The primary outcomes of this work 
illustrated that binary response options (easy and hard) were more meaningful in this 
population. Furthermore, it helped guide the method of delivery, in that, the 5-7 year old 
strata would need assistance when completing the questionnaire, unlike the 8-11 year old 
strata, who would be able to self-complete the questionnaire [NCT03315572, 2018].
3.2.
Background
Asthma is a chronic inflammatory disease of the airways and lungs that results in 
hyperreactivity and clinically relevant episodes of wheezing.  The global prevalence of 
asthma is on the rise.  As of 2015, 358 million people globally suffer from asthma and it 
is one of the leading causes of disability in children between 5 and 11 years of age [GBD
2015, 2016]. It is most commonly treated with Inhaled Corticosteroids (ICS) alone or in 
combination with a long acting β2 adrenergic agonist (LABA) [GINA, 2017].
Instances of problematic asthma cases in the pediatric population have been attributed to
either; misdiagnosis, environmental factors and/or adherence to medication prescription
[Bush, 2015].  The failure of a patient to adhere to their medication includes the inability 
to use their inhalation device correctly and subsequently receive their prescribed dose, the 
impact of which depends primarily upon the severity of the condition [Burgess, 2011].
Interventions to address issues related to adherence in pediatric populations have had 
limited success, with the most effective containing both educational and behavioral 
aspects [Morton, 2014].

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Consequently, the ability of pediatric asthmatic patients to achieve and maintain correct 
use over time, which is defined as use of the inhaler in the manner described in the 
Instructions for Use (IFU) is becoming increasingly recognized.
The choice of inhalation device is an important decision when considering treatment for 
asthma in this age group.  This has been illustrated in a recent study of 8-16 year-old 
asthmatic patients, where only 8% could use their MDI correctly, while 16% 
(Turbuhaler) and 22% (Diskus) were able to use their DPI correctly [Sleath, 2011].
Furthermore, inadequate technique reduces the effects of inhalation, thus a device that is 
easy to use and delivers drug to the lungs effectively is important. 
In order to combat such educational and behavioral barriers, the ELLIPTA DPI has been 
designed to be simple for patients to use based on the number of steps required to use it 
correctly and the amount of time required to be trained in correct use.  Previous studies in 
other populations have shown that the number of errors made while using the ELLIPTA 
DPI and the amount of time required to train users are reduced [Van der Palen, 2016a;
Van der Palen, 2016b; Van der Palen, 2016c].  Therefore, the ELLIPTA DPI has the 
potential to address some of the limitations regarding the correct use of other inhalers in 
the pediatric asthmatic population [Kamps, 2002b].
Ultimately, the prescription and subsequent use of easy to use DPIs is paramount and 
could be of high clinical value for the treatment and management of asthma in this 
population.  This study is designed to assess the correct use and ease of use of the 
ELLIPTA DPI by pediatric participants with asthma, a population yet to be studied for 
their use of the ELLIPTA DPI.
3.3.
Benefit/Risk Assessment
This study involves use of placebo ELLIPTA DPI, which does not contain any active 
treatment.  Participants will continue to take their own prescribed asthma medication and 
other concomitant medication for the duration of the study.
The placebo ELLIPTA DPI contains the excipients lactose blended with magnesium 
stearate. Excipients of the study inhaler are noted in Section 7.1. Participants with a 
known hypersensitivity to any of these or severe milk protein allergy that could 
contraindicate study participation are excluded from the study (Section 6). Participants
who meet the inclusion/exclusion criteria will continue their asthma treatment as 
prescribed by their healthcare provider during their participation in the study. 
Participants should continue to follow up with their regular physician for their asthma
healthcare during the study.

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3.3.1.
Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (IP)
Paradoxical bronchospasm, which may occur
with an immediate increase in wheezing after 
inhalation.
As with other inhalation therapy, paradoxical 
bronchospasm may occur with an immediate 
increase in wheezing after dosing.  From post-
marketing data, paradoxical bronchospasm has 
been reported at a frequency of <1/10,000, 
including isolated reports [Nicklas, 1990].
This should be treated immediately with a fast 
and short acting inhaled bronchodilator.
Investigators will be instructed to assess the 
subject’s condition to determine their eligibility to 
continue in the study and the need for alternative 
therapy.
Allergic reaction due to hypersensitivity to 
placebo excipients.
The placebo inhalers contain the excipients 
lactose and lactose blended with magnesium 
stearate. There are known allergies to these 
ingredients.
Participants with a known hypersensitivity to any 
of these, or severe milk protein allergy that could 
contraindicate study participation are excluded 
from the study (Section 6). If an allergic reaction 
occurs, it should be treated immediately with a 
fast and short acting inhaled bronchodilator. 
Investigators will be instructed to assess the 
subject’s condition to determine their eligibility to 
continue in the study and the need for alternative 
therapy.

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3.3.2.
Benefit Assessment
As this is a placebo only study, no direct benefit to the participant is expected as a result 
of taking part in the study.  No active treatment will be provided during the study. All 
participants will continue to receive their own asthma therapy as prescribed for the 
duration of the study. 
3.3.3.
Overall Benefit:Risk Conclusion
The overall potential risk identified is minimal, due to the nature of the study.
4.
OBJECTIVES AND ENDPOINTS
The study will evaluate different aspects of correct use and ease of use of the ELLIPTA 
DPI in pediatric patients with asthma. The population will be stratified into two different 
age groups and will be referred to as Stratum 1 and Stratum 2 throughout this protocol.
-
Stratum 1: 5 to 7 years old at V0 (inclusive)
-
Stratum 2: 8 to 11 years old at V0 (inclusive)
Objectives
Endpoints
Primary

To determine the proportion of participants 
from each stratum who demonstrate 
correct use of the ELLIPTA DPI after the 
study period at V2.

The percentage of participants from each 
stratum who demonstrate correct use of the 
ELLIPTA DPI after the study period at V2.

To determine the proportion of participants 
from each stratum who rate the use of the 
ELLIPTA DPI as easy to use, from those 
who could demonstrate correct use of the 
ELLIPTA DPI after the study period at V2.

The percentage of participants from each 
stratum who rate the ELLIPTA DPI as easy 
to use, from those who could demonstrate 
correct use of the ELLIPTA DPI after the 
study period at V2.
Secondary

To determine the proportion of participants 
from each stratum who demonstrate 
correct use of the ELLIPTA DPI after initial 
training from HCP at V1.

The percentage of participants from each 
stratum who demonstrate correct use of the 
ELLIPTA DPI after initial training from HCP 
at V1.

To determine the proportion of participants 
who demonstrate correct use of the 
ELLIPTA DPI after the study period at V2.

The percentage of participants who 
demonstrate correct use of the ELLIPTA DPI 
after the study period at V2.

To determine the proportion of participants 
who rate the use of the ELLIPTA DPI as 
easy to use, from those who could 
demonstrate correct use of the ELLIPTA 
DPI after the study period at V2.

The percentage of participants who rate the 
ELLIPTA DPI as easy to use, from those 
who could demonstrate correct use of the 
ELLIPTA DPI after the study period at V2.

To determine the proportion of participants 
from each stratum who made at least one 
critical error during use of the ELLIPTA DPI 
after initial training from HCP at V1.

The percentage of participants from each 
stratum who made at least one critical error 
during use of the ELLIPTA DPI after initial 
training from HCP at V1.

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Objectives
Endpoints
Exploratory

To determine the proportion of participants
from each stratum who rate the ability to 
tell how many puffs are left in the ELLIPTA 
DPI as easy after the study period at V2.

The percentage of participants from each 
stratum who rate the ability to tell how many 
puffs are left in the ELLIPTA DPI as easy 
after the study period at V2.

To determine the proportion of participant’s 
parents/guardians who rate the ability to 
tell how many doses are remaining in the 
ELLIPTA DPI as easy or very easy after 
the study period at V2.

The percentage of participant’s 
parents/guardians who rate the ability to tell 
how many doses are remaining in the 
ELLIPTA DPI as easy or very easy after the 
study period at V2.

To determine the proportion of participant’s 
parents/guardians who would be ‘likely’ or 
‘very likely’ to ask their doctor for the 
ELLIPTA DPI if the participants current 
daily inhaled medication(s) were available 
in the ELLIPTA DPI after the study period 
at V2.

The percentage of participant’s 
parents/guardians who would be likely or 
very likely to ask their doctor for the 
ELLIPTA DPI if the participants current daily 
inhaled medication(s) were available in the 
ELLIPTA DPI after the study period at V2.

To determine the proportion of participants 
from each stratum who can demonstrate 
correct use after the study period at V2
with assistance from parents/guardians.

The percentage of participants from each 
stratum who demonstrated correct use after 
the study period at V2 with assistance from 
parents/guardians.

To determine the proportion of participants 
from each stratum who made at least one 
critical error during use of the ELLIPTA DPI 
after the study period at V2.

The percentage of participants from each 
stratum who made at least one critical error 
during use of the ELLIPTA DPI after the 
study period at V2.

To determine the proportion of participants 
who made at least one critical error during 
use of the ELLIPTA DPI after initial training 
from HCP at V1.

The percentage of participants who made at 
least one critical error during use of the 
ELLIPTA DPI after initial training from HCP 
at V1.

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5.
STUDY DESIGN
5.1.
Overall Design
Figure 1
Study Schematic

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This is a multi-center, single arm, stratified, open-label, randomized (version of the 
ELLIPTA DPI ease of use questionnaire) placebo-only study.  The study will involve up 
to 3 study visits.  Participants will continue to use their prescribed asthma medications 
after meeting the eligibility criteria for the duration of the study.  Further information 
regarding the assessments that will occur at each visit will be locate in the Study 
Reference Manual (SRM).
5.1.1.
Visit 0
Visit 0 (V0) and Visit 1 (V1) can occur on the same day.  Participants between 5 and 11 
years old (inclusive) at V0, who are naive to the ELLIPTA DPI (with no previous 
treatment experience with any medication administered by the ELLIPTA DPI), have a 
documented history of symptoms consistent with a diagnosis of asthma and are currently 
receiving maintenance and/or rescue therapy for asthma treatment, will be considered 
eligible to participate in the study.
At V0, written informed consent will be obtained from eligible participant’s 
parent/guardian and the respective assent, along with medical history, demography and 
current asthma therapy.  Participants will also be stratified by age into one of two strata:
-
Stratum 1: 5 to 7 years old at V0 (inclusive)
-
Stratum 2: 8 to 11 years old at V0 (inclusive)
5.1.2.
Visit 1
At V1, all participants will be trained in correct use of the ELLIPTA DPI by a Healthcare 
Professional (HCP) as would occur in general practice.  Participants will then be asked to 
attempt to use the ELLIPTA DPI, without guidance from either the HCP or their 
parent/guardian.  Should the study participant be unable to use the ELLIPTA DPI 
correctly, the HCP will be allowed to instruct the participant two more times.  After each 
round of instruction, the participant will attempt to correctly use the ELLIPTA DPI.  If 
the study participant is still unable to demonstrate correct use of the ELLIPTA DPI after 
all three instructions by the HCP, the parent/guardian of the participant will be able to 
assist in the instruction of correct use of the ELLIPTA DPI for another two attempts.  It is 
therefore important that the parent/guardian is engaged with the HCP during delivery of 
the instructions on correct use.  If the participant still cannot demonstrate correct use after 
all five attempts, they will be registered as a screen failure.  All participants who can 
demonstrate correct use at any stage in this process will be informed of their correct use 
and will perform no further demonstrations at this visit.  
Participants will then take a placebo ELLIPTA DPI home for the duration of the study 
period (28 (±2) days).  Participants will be instructed to take one inhalation from the 
ELLIPTA DPI as would be prescribed (once daily) at approximately the same time every 
day.  Participant’s parent/guardian will need to make note of the date and time of each 
dose administered of the ELLIPTA DPI on the worksheet provided.  This worksheet can 
also be used to make note of any adverse or serious adverse events (AEs/SAEs) that 
occur during the study period.  Participant’s parents/guardians must contact the 
investigative site if the participant experiences any clinical worsening of their asthma. 
Further information on this procedure is located in Section 9.1.1.

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5.1.3.
Visit 2
Participants will return to the site for V2 after the study period, and will be randomized 
(1:1 allocation) to determine the version of the ease of use questionnaire they will receive 
(Version A or Version B) located in Appendix 6.  Prior to the correct use assessment, the 
participant will complete the version of the ease of use questionnaire according to their 
randomization allocation.  The participant’s parent/guardian will then complete a 
questionnaire to assess various features of the ELLIPTA DPI (Appendix 6) according to 
the same randomization allocation as their dependent.
After completion of the ELLIPTA questionnaire(s), the participant’s ability to correctly 
use the ELLIPTA DPI will be assessed.  At this visit during attempt 1, there will be no 
instruction, coaching, comment or direction given by the HCP or parent/guardian.  Only 
one attempt to correctly use the inhaler will be conducted during this assessment.  If the 
participant is unable to demonstrate correct use in their first attempt at this visit, they will 
have another attempt, in which, they will receive assistance from their parent/guardian.
At this visit, the number of doses administered by the participant during the study period 
will be noted and participants will be discharged from the study.
5.2.
Number of Participants
Approximately 219 participants between 5 and 11 years old (inclusive) with a 
documented history of symptoms consistent with a diagnosis of asthma (88 participants 
from Stratum 1 and 131 participants from Stratum 2) will need to be screened to achieve 
83 participants from stratum 1 and 124 participants from stratum 2 who meet the 
eligibility criteria at V1, assuming a 5% failure rate of being able to correctly use the 
ELLIPTA DPI at V1.  Further participants may be screened to ensure that at least 83 
participants from strata 1 and 124 participants from strata 2 enter the study period.
Assuming a withdrawal rate during the treatment period of 3%, approximately 80
participants from strata 1 and 120 participants from strata 2 will complete the treatment 
period, return for V2 and be randomized to a version of ease of use questionnaire. Based 
on the assumption that 80% of participants from both strata will be able to demonstrate 
correct use of the ELLIPTA DPI at V2. it is expected that 64 participants from stratum 1 
and 96 participants from stratum 2 will be included in the analysis of the second primary 
endpoint regarding ‘ease of use’. 
5.3.
Participant and Study Completion
A participant is considered to have completed the study if he/she has completed all 
phases of the study including the last scheduled procedure shown in the SoA (Section 2).
The end of the study is defined as the date of the last visit of the last participant in the 
study.

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5.4.
Scientific Rationale for Study Design
Participants are required to be naïve to (have no previous experience with) the ELLIPTA 
DPI in order to appropriately assess their ability to be trained in, demonstrate correct use 
and assess its ease of use.  
Stratification by age of the participants involved in the study was chosen in order to 
appropriately account for the potential differences in cognitive ability with respect to the 
ease of use questionnaires.  This enables analysis of these two strata separately for this 
study and allows for the variation in delivery of the questionnaires distributed.  Previous 
questionnaires have been modified for suitability in this pediatric population. The 
development of these questionnaires and suggestions for their delivery has been informed 
by earlier work conducted by the Value Evidence Outcomes team with GSK
[NCT03315572, 2018].  
Inactive treatment was chosen as it avoids the potential bias related to the possible 
clinical improvement of the participant’s attitudes and perceptions on the ease of use of 
the DPI an inactive treatment was chosen.  Furthermore, adding a placebo ELLIPTA DPI 
to the participants existing asthma therapy avoids the need for wash-in/out periods and 
the need to discontinue current asthma medications for study visits.
The requirement for two study visits excluding screening is to assess the ability of the 
participant to be taught, retain that teaching/training and carry out a correct use 
demonstration.  It will also determine if the ability of a pediatric participant to correctly 
use their inhaler diminishes or is lost over time after input from the participant’s 
parent/guardian only.  The time between visits of 4 weeks was chosen as this is deemed 
long enough to lose the ability to correctly use an inhaler and to accurately assess the ease 
of use of the ELLIPTA DPI. It also has been the time frame used in previous correct use 
studies in other populations [GlaxoSmithKline Document Number 2017N314003_00; 
GlaxoSmithKline Document Number 2016N269989_01].  Furthermore, this treatment 
period (approximately one month) resembles the timing of inhaler refill and potential 
education at a pharmacy or by a HCP.
5.5.
Dose Justification
This is not applicable as this is a placebo-only study.
6.
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted.
6.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria 
apply:

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Age
1.
Participants between 5 and 11 years old (inclusive), at the time of the V0.
Type of Participant and Disease Characteristics
2.
Participants with a documented history of symptoms consistent with a diagnosis of 
asthma for at least 6 months prior to V0 (includes asthma diagnosis).
Sex
3.
Males and premenarchial females.
Informed Consent
4.
Written informed consent from at least one parent/guardian and the accompanying 
informed assent from the participant (where the participant is able to provide assent) 
prior to admission to the study.
a.
If applicable, the participant must be able and willing to give assent to take 
part in the study according to the local requirement. The study 
investigator is accountable for determining a child's capacity to assent to 
participation in a research study, taking into consideration any standards 
set by the responsible IEC/IRB.
5.
Participant and their legal guardian understand and are willing, able, and likely to 
comply with study procedures and assessments.
Current Asthma Therapy
6.
Participant must have been receiving asthma treatment (rescue or maintenance) for 3 
months prior to entry onto the study.
7.
Participant must have never been trained in correct use of, or used the ELLIPTA 
DPI previously.
Study Procedures
8.
Participants must be able to demonstrate correct use of the ELLIPTA DPI after 
coaching/training at V1.
9.
Participants must be able to converse and understand verbal instruction in English. 
6.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1.
Concurrent diagnosis of other respiratory disorders including active tuberculosis, 
lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, 
interstitial lung diseases, cystic fibrosis or other active pulmonary diseases.
2.
Concurrent diagnosis of psychiatric or psychological or any other disorders that in 
the opinion of the investigator may affect the ability of the participant to comply 
with study procedures or requirements.

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Asthma exacerbation history:
3.
Has experienced an exacerbation which required oral/systemic corticosteroids in the 
three months prior to V0.
4.
Has been hospitalized for an episode of asthma within three months of V0.
5.
Has had an asthmatic episode requiring intubation, associated with hypercapnea, 
respiratory arrest or hypoxic seizures.
Contraindications: 
6.
Has exhibited symptoms of a recent acute respiratory tract infection within one week 
of V0.
7.
History of hypersensitivity to any components of the study inhalers (e.g., lactose, 
magnesium stearate). In addition, participants with a history of severe milk protein 
allergy that, in the opinion of the study physician, contraindicates participation will 
also be excluded.
8.
Historical or current evidence of clinically significant or rapidly progressing or 
unstable cardiovascular, neurological, renal, hepatic, immunological, endocrine
(including diabetes or thyroid disease) or hematological abnormalities that are 
uncontrolled. Significant is defined as any disease that, in the opinion of the 
investigator, would put the safety of the participant at risk through participation, or 
which would affect the analysis if the disease/condition exacerbated during the 
study.
Diagnostic assessments and other criteria
9.
Parent or Guardian with a history of psychiatric disease, intellectual deficiency, 
substance abuse or other condition (e.g. inability to read, comprehend or write) 
which may affect:

Validity of consent to participate in the study.

Adequate supervision of the participant during the study.

Compliance of participant with study medication and study procedures

Participant safety and well-being.
10. Participants who have received an investigational drug and/or medical device within 
30 days of entry into this study (Screening), or within five drug half-lives of the 
investigational drug, whichever is longer.
11. A participant will not be eligible for this study if he/she is an immediate family 
member of the participating investigator, sub-investigator, study coordinator, or 
employee of the participating investigator.
6.3.
Lifestyle Restrictions
There are no lifestyle restrictions.

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6.3.1.
Meals and Dietary Restrictions
There are no meals or dietary restrictions.
6.3.2.
Activity
There are no restrictions on activity.
6.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study 
but do not subsequently enter the 28-day treatment period.  This includes any participant 
who is not able to demonstrate correct use of the ELLIPTA DPI at V1.  A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any 
SAEs.
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened once. Rescreened participants should be assigned a new participant 
number. Participants are not eligible for rescreening if they attended V1 and were 
instructed and/or assessed for their correct use of the ELLIPTA DPI in any way.

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7.
TREATMENTS
Study treatment is defined as any investigational treatment(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol.
Participants will need 2 placebo ELLIPTA DPIs during the study. One of which will be 
used at the site for assessments and will remain at site during the study period.  The other 
placebo ELLIPTA DPI will be taken home by the participant and will be used as directed 
for the duration of the study period. 
7.1.
Treatments Administered
Study Treatment Name:
Placebo ELLIPTA DPI
Dosage formulation:
Placebo DPI with two strips and 30 blisters per strip.
First strip: lactose monohydrate
Second strip: lactose monohydrate blended with magnesium 
stearate
Route of Administration 
Oral Inhalation
Dosing instructions:
Once Daily
Packaging and Labelling
Placebo DPI will be provided in the appropriate container. Each 
container will be labelled as required per country requirement. 
Manufacturer
GSK
Device
NA
7.2.
Dose Modification
This is not applicable as this is a placebo only study and there will be no dose 
modification during this study.
7.3.
Method of Treatment Assignment
Participants will be assigned to the ease of use questionnaire version (Appendix 6) they 
receive in accordance with the randomization schedule devised by clinical statistics. 
Participants will be randomized using an Interactive Web Response System (IWRS). The 
system will be used by the investigator or designee to register and randomize the 
participant. It will assign the participant to one of two questionnaire versions (Version A 
or Version B), see Appendix 6.

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Eligible subjects will be randomized to receive 1 of the following 2 possible 
questionnaire versions (1:1 allocation) at V2.  The variation between versions concerns 
the order of the response options provided to participants.  This reduces the response bias 
caused by the ordering of the questionnaire responses (Appendix 6).  Parents/guardians 
will receive the same ordering of responses as their dependent.
Randomization Group
Ease of Use 
Questionnaire Version
Stratum 1
A
B
Stratum 2
A
B
7.4.
Blinding
This is an open-label study.  The participants and the investigator will be able to 
recognize the study inhaler that the participant is receiving.  The participant will be 
informed that the study inhalers contain no active treatment.  However, the version of the 
ease of use questionnaire that will be answered by a participant and their legal guardian 
will be assigned using an IWRS.  The site will use the IWRS prior to any assessments by 
the participant at V2.  The site will record the randomization assignment on the 
applicable case report form, if required.  Potential response bias will be reduced by 
randomizing the ease of use questionnaire answered by participants, which differ on the 
ordering of responses provided in each question. 
7.5.
Preparation/Handling/Storage/Accountability
-
The investigator or designee must confirm appropriate temperature conditions 
have been maintained during transit for all study treatment received and any 
discrepancies are reported and resolved before use of the study treatment.  Details 
regarding transit and storage conditions for study treatments will be included in 
the SRM.
-
Only participants enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment. All study 
treatments must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions 
with access limited to the investigator and authorized site staff.
-
The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study treatment accountability, reconciliation, and 
record maintenance (i.e. receipt, reconciliation, and final disposition records).
-
Further guidance and information for the final disposition of unused study 
treatment are provided in the SRM. 

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-
Under normal conditions of handling and administration, study treatment is not 
expected to pose significant safety risks to site staff.  
-
Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request 
from GSK.
7.6.
Treatment Compliance
When participants are dosed at the site, they will receive study treatment directly from 
the investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the source documents.  The dose of study 
treatment and study participant identification will be confirmed at the time of dosing by a 
member of the study site staff other than the person administering the study treatment.
When participants self-administer study treatment at home, compliance with the 
ELLIPTA DPI dosing regimen will be assessed by recording the number of ELLIPTA 
DPI doses dispensed by each participant obtained by reading the dose counter upon 
return of the participant at V2. The participant’s parent/guardian will also receive a 
worksheet to note the date and time of each dose administered during the study period.
This information must be maintained and reconciled with study treatment and compliance 
records.  Compliance from the dose counter only will be entered will be recorded in the 
electronic case report form (eCRF).
7.7.
Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrolment or receives during the study must be recorded along with:

reason for use

dates of administration including start and end dates

dosage information including dose and frequency
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy.
7.8.
Treatment after the End of the Study
There is no active treatment administered during this study.  This is a placebo only study 
and participants will not receive any specific post-study treatments.

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8.
DISCONTINUATION CRITERIA
8.1.
Discontinuation of Study Treatment
Participants will be considered to have completed the study upon completion of all study 
procedures at V2 (final clinic visit).
The definition of an early withdrawal from the study will be any participant who 
demonstrates correct use of the ELLIPTA DPI at V1, but is withdrawn or withdraws prior 
to completion of the V2 procedures.
A participant may voluntarily discontinue participation in the study at any time.  The 
investigator may also, at his/her discretion; discontinue the participant from the study at 
any time.  In addition, the investigator must make every effort to have the participant 
return to the clinic as soon as possible after discontinuation of study inhaler for an early 
withdrawal visit.  
The participant will be withdrawn from the study if any of the following criteria apply:

The participant experiences an asthma exacerbation (see Section 9.2.6) that in the 
opinion of the investigator may affect their ability to complete the requirements of 
the protocol.

The participant begins using a medication that is delivered by the ELLIPTA DPI 
(excluding the study placebo ELLIPTA DPI).
After premature discontinuation from the study, the following evaluations and procedures 
should be completed at the early withdrawal visit and must be recorded in the eCRF as 
required.

Concomitant medication assessment

Adverse event assessment

Asthma exacerbation assessment

Collect used study inhaler

Assess compliance with study inhaler
8.1.1.
Liver Chemistry Stopping Criteria
Not applicable as this is a placebo only study and there is not active treatment.
8.1.2.
QTc Stopping Criteria
Not applicable as this is a placebo only study and there is not active treatment.
8.1.3.
Temporary Discontinuation
Participants who withdraw from the study treatment will not be able to continue in the 
study.

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8.2.
Withdrawal from the Study

A participant may withdraw from the study at any time at his/her own request, 
or may be withdrawn at any time at the discretion of the investigator for safety, 
behavioural, compliance or administrative reasons.

If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent.

Refer to the SoA (Section 2) for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be 
completed.
8.3.
Lost to Follow Up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit:

The site must attempt to contact the participant and reschedule the missed visit 
as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow up, the investigator or designee 
must make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record.

Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study with a primary reason of lost to follow-up.

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9.
STUDY ASSESSMENTS AND PROCEDURES
Study procedures and their timing are summarized in the SoA (Section 2).  Protocol 
waivers or exemptions are not allowed.  Immediate safety concerns should be discussed 
with the sponsor immediately upon occurrence or awareness to determine if the 
participant should continue or discontinue study treatment.  Adherence to the study 
design requirements, including those specified in the SoA (Section 2), is essential and 
required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
Procedures conducted as part of the participant’s routine clinical management and 
obtained before signing of ICF may be utilized for screening or baseline purposes 
provided the procedure met the protocol-specified criteria and was performed within the 
time frame defined in the SoA (Section 2).
9.1.
Assessments
9.1.1.
Screening and Critical Baseline Assessments
The following will be recorded in the eCRF at V1:
9.1.1.1.
Visit 1
9.1.1.1.1.
Training and correct use Assessments
During V1, participants will be trained in the correct use of the ELLIPTA DPI by the 
HCP.  The course of events during the training and assessments that occur at V1 is shown 
in Figure 2 below.  During training, parental/guardian involvement is important, as they 
will have to assist in the training of the participant if the participant is unable to 
demonstrate correct use after the first 3 attempts.
Figure 2
Training and assessments of correct use of ELLIPTA DPI at V1

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9.1.2.
V2 Assessments
After the 28-day treatment period, participants will return for V2. During this visit, the 
primary assessments occur. Detail regarding the order of assessments at V2 is provided in 
Figure 3.
The following will be recorded in the eCRF at V2:
9.1.2.1.
Ease of use Questionnaire
Prior to any other assessments at V2, participants will answer the ease of use 
questionnaire. The exact wording that will be used in this questionnaire and further 
instructions for administration of these questionnaires is located in Appendix 6.  

For Stratum 1, the questionnaire will be administered by the interviewer. 
Responses will be provided according to the version to which the participant has 
been randomized.

For Stratum 2, the questionnaire will be self-administered. Responses will be 
provided according to the version to which the participant has been randomized.  
If the participant is unable to self-administer the questionnaire, then they will be 
able to complete the questionnaire in the same manner as for stratum 1 
(interviewer administered).

Parents/Guardians will be assigned to the same version letter (A or B) of 
questionnaire to which their child/dependent was randomized.
9.1.2.2.
Correct Use
At V2, participants will be assessed for their ability to demonstrate correct use of the 
ELLIPTA DPI.  There will be no training in correct use prior to the assessment.  There 
will also be no input from the participant’s parent/guardian during the first attempt at V2.  
If the participant is unable to demonstrate correct use at V2 after the initial attempt, the 
participant’s parent/guardian will be asked to instruct the participant in how to use the 
device correctly before they have their second attempt.

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Figure 3
Assessments regarding correct use and ease of use of the ELLIPTA 
DPI at V2
9.2.
Adverse Events
The definitions of an AE or SAE can be found in Appendix 3.
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study treatment or the study,
or that caused the participant to discontinue the study (see Section 8). 
9.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information

All SAEs will be collected from the signing of the ICF until the time point 
specified in the SoA (Section 2).

All AEs will be collected from the beginning of V1 until the timepoint specified 
in the SoA (Section 2).

Medical occurrences that begin before the start of study treatment but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the eCRF not the AE section.

All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor 
within 24 hours of it being available.

Investigators are not obligated to actively seek AEs or SAEs in former study 
participants. However, if the investigator learns of any SAE, including a death, 
at any time after a participant has been discharged from the study, and he/she 
considers the event to be reasonably related to the study treatment or study 
participation, the investigator must promptly notify the sponsor.

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
The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Appendix 3.
9.2.2.
Method of Detecting AEs and SAEs
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence. On the same worksheet that will be provided to note compliance (date 
and time) to their ELLIPTA DPI regimen, the participant’s parent/guardian will be able 
to note any AEs and SAEs that occur during the study period.
9.2.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost to follow-up (as 
defined in Section 8.3). Further information on follow-up procedures is given in 
Appendix 3.
9.2.4.
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to the sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study treatment under clinical investigation are 
met. 

The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study treatment 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), and 
investigators.

Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions (SUSAR) according to local regulatory requirements and 
sponsor policy and forwarded to investigators as necessary.

An investigator who receives an investigator safety report describing a SAE or 
other specific safety information, e.g. summary or listing of SAE) from the 
sponsor will review and then file it along with the Investigator’s Brochure and 
will notify the IRB/IEC, if appropriate according to local requirements.
9.2.5.
Death Events
For all deaths, whether or not they are considered SAEs, specific Death sections of the 
eCRF will be required to be completed. These sections include questions regarding 
cardiovascular (including sudden cardiac death) and non-cardiovascular death. 

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The Death eCRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported.
9.2.6.
Asthma Exacerbation
An exacerbation is defined as deterioration of asthma requiring the use of systemic or 
oral corticosteroids (tablets, suspension, or injection) for at least 3 days or a 
hospitalization or emergency department visit due to asthma that required systemic 
corticosteroids.
Subjects who experience an asthma exacerbation during the treatment period may remain 
in the study and should continue to use their placebo ELLIPTA DPI if possible. 
Treatment of asthma exacerbations with short term antibiotics (less than or equal to 14 
days) and systemic corticosteroids (less than or equal to 10 days) is permitted.
For worsening asthma symptoms/exacerbations requiring: 

Emergency treatment: the decision whether such a subject would continue in the 
study or be withdrawn would be determined per investigator discretion. The Study 
Medical Monitor would be available to discuss any related questions with the 
investigator.

Hospitalization: such a subject should be withdrawn from the study 
Asthma exacerbations should not be recorded as an AE, unless they meet the definition of 
a SAE and these SAEs will be recorded on the appropriate eCRF section and should be 
reported to GSK for all subjects. For the purposes of this study, asthma exacerbations 
will be collected and recorded on the asthma exacerbation log in the eCRF for all 
subjects. The time period for collection of asthma exacerbations on the asthma 
exacerbation log in the eCRF will begin from Visit 1 and will end when Visit 2/EW visit 
has been completed. 
Signs and symptoms of asthma included on the diary cards will not be considered AEs 
and will not be recorded in the eCRF.
9.3.
Treatment of Overdose
This study only contains placebo inhalers, with no active treatment. Therefore, 
management of an overdose does not apply.
9.4.
Safety Assessments
There are no mandated safety assessments, other than monitoring for AEs and SAEs. 
This is described in detail in Section 9.2.

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9.4.1.
Physical Examinations

A physical examination will include, at a minimum, assessments of the 
Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Height 
and weight will also be measured and recorded.

Investigators should pay special attention to clinical signs related to previous 
serious illnesses.
9.4.2.
Vital Signs
This is not applicable as it is a placebo only study.
9.4.3.
Electrocardiograms
This is not applicable as it is a placebo only study.
9.4.4.
Clinical Safety Laboratory Assessments
This is not applicable as it is a placebo only study.
9.4.5.
Suicidal Risk Monitoring
This is not applicable as it is a placebo only study.
9.5.
Pharmacokinetics
Pharmacokinetic parameters are not evaluated in this study.
9.6.
Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study
9.7.
Genetics
Genetics are not evaluated in this study.
9.8.
Biomarkers
Biomarkers are not evaluated in this study.
9.9.
Health Economics OR Medical Resource Utilization and 
Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are 
not evaluated in this study.

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10.
STATISTICAL CONSIDERATIONS
10.1.
Hypothesis
This is a descriptive, placebo only study and no formal inference is planned.  The two 
primary objectives of the study are:
To determine the proportion of participants from each stratum who demonstrate 
correct use of the ELLIPTA DPI after the study period at V2
To determine the proportion of participants from each stratum who rate the use of 
the ELLIPTA DPI as easy to use, from those who could demonstrate correct use 
of the ELLIPTA DPI after the study period at V2.
10.2.
Sample Size Determination
10.2.1.
Sample Size Assumptions
The sample size calculation is based on the co-primary endpoints, the percentage of 
subjects who demonstrate correct use of the ELLIPTA DPI at V2, and the percentage of 
subjects who rate the use of the ELLIPTA DPI as easy, among those who demonstrate 
correct use of the inhaler at V2. 
Approximately 219 subjects (i.e. 88 in stratum 1 and 131 in stratum 2) will be needed for 
screening in order to obtain 200 subjects (i.e. 80 in stratum 1 and 120 in stratum 2) with 
available data to be randomized to an “ease of use” questionnaire, in anticipation of a 5% 
V0/V1 screen failure rate and then a 3% drop-out in the 4-week interim period.
If the proportion of participants demonstrating correct use of the ELLIPTA DPI at V2 is 
80% for both strata 1 and 2, a total sample size of 80 participants in stratum 1 and 120 
participants in stratum 2 will produce a confidence interval (CI) equal to the sample 
proportion ± 9.28 and ± 7.51 percentage points.  In addition, given the assumption that 
the proportion of participants demonstrating correct use and evaluating the ELLIPTA 
DPI at V2 as easy to use is 80% for both strata 1 and 2, a total sample size of 64 
participants in stratum 1 and 96 participants in stratum 2 will produce a CI equal to the 
sample proportion ± 10.42 and ± 8.44 percentage points. The sample size software used 
to estimate the precision and following sensitivity analysis estimates is PASS version 12 
[Hintze, 2013].
10.2.2.
Sample Size Sensitivity
With an assumed sample size, the difference between the hypothesized and observed 
proportions of participants able to demonstrate correct use of the ELLIPTA DPI at V2 
can affect the precision of the estimate.  If it is hypothesized that the proportion of 
participants considered to be using the DPI correctly (observed proportion) is 80%, a 
sample size of 80 participants in stratum 1 could narrow the precision of the estimated 
proportion by as little as ± 5.47% if the observed proportion is 95%, or widen the 
precision to as large as ± 11.18% if the observed proportion is 60%.  A sample size of 
120 participants in stratum 2 could narrow the precision of the estimated proportion by as 

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little as ± 4.35% if the observed proportion is 95%, or widen the precision to as large as ± 
9.09% if the observed proportion is 60%.
Also, the difference between the hypothesized and observed proportions of participants 
rating the ease of use of the ELLIPTA DPI at V2 as easy can also affect the precision of 
the estimate.  If it is hypothesized that the proportion of participants who can correctly 
use the ELLIPTA DPI correctly is 80% and thus can rate the ELLIPTA DPI as easy to 
use (observed proportion), a sample size of 64 participants in stratum 1 could narrow the 
precision of the estimated proportion by as little as ± 6.21% if the observed proportion is 
95%, or widen the precision to as large as ± 12.53% if the observed proportion is 60%.  A 
sample size of 96 participants in stratum 2 could narrow the precision of the estimated 
proportion by as little as ± 4.93% if the observed proportion is 95%, or widen the 
precision to as large as ± 10.19% if the observed proportion is 60%.
10.3.
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign the ICF
Intent-to-Treat (ITT)
The Intent-to-Treat (ITT) population is defined as all subjects who 
have been screened and received at least one dose of the study 
medication (placebo). This will constitute the primary population for 
all study population and safety displays, and for some secondary 
and exploratory efficacy endpoint displays.
Modified Intent-to-Treat 
(MITT)
The Modified Intent-to-Treat (MITT) population is defined as all 
subjects who have been screened, received at least one dose of the 
study medication (placebo) and were randomized to a questionnaire 
at V2. This will constitute the primary population for the primary and 
most secondary efficacy endpoint displays.
10.4.
Statistical Analyses
Where possible, data from subjects who withdraw prematurely from the study treatment
or the study will be included in any relevant analyses. Specific details for inclusion will 
be detailed in the Reporting and Analysis Plan (RAP).

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10.4.1.
Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary
The first primary analysis will calculate the proportion of subjects from each 
age stratum (5 to 7 years old (inclusive) and 8 to 11 years old (inclusive) who 
demonstrate correct use of the ELLIPTA DPI at V2. The proportion will be 
reported for both strata and calculated as those who demonstrate correct 
use at V2 / the number of participants whose use of the ELLIPTA DPI was 
evaluated at V2. This will be reported along with a 95% CI for the proportion 
calculated using the exact binomial distribution.
The second primary analysis will calculate the proportion of subjects from 
each age stratum who rate the ELLIPTA DPI as ‘easy to use’, from those 
who demonstrated correct use of the ELLIPTA DPI at the end of the study 
period V2. The proportion will be reported for both strata and calculated as 
those who rate the ELLIPTA DPI as easy to use / those who demonstrate 
correct use of the ELLIPTA DPI at V2. This proportion will be presented 
along with a 95% CI calculated using the exact binomial distribution. 
Secondary
The secondary endpoints will be reported in a similar fashion as the primary 
endpoints, with the proportion reported for each age stratum or collectively 
where necessary along with a 95% CI for the proportion calculated using the 
exact binomial distribution.
Exploratory
Will be described in the reporting and analysis plan
10.4.2.
Safety Analyses
All safety analyses will be performed on the Safety Population. 
Endpoint
Statistical Analysis Methods
Safety
Non-serious AEs, SAEs and AEs leading to study withdrawal will be collected.
Safety endpoints will include:

Incidence and type of serious adverse events

Incidence and type of non-serious adverse events

Incidence and type of non-serious AEs leading to study withdrawal

Incidence of Asthma Exacerbations

Incidence of Pneumonia
The incidence of any given adverse event is defined as the proportion of subjects 
who have experienced at least one such adverse event during the study period.
The number and percentage of subjects with SAEs, non-serious AEs and AEs 
leading to study withdrawal will be summarized by preferred term. 

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10.4.3.
Other Analyses
All other exploratory endpoints will be detailed in the RAP.
10.4.4.
Interim Analyses
No interim analyses are planned for this study.

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11.
REFERENCES
Burgess S, Sly P, Devadason S. Adherence with Preventive Medication in Childhood 
Asthma. Pulmonary Medicine. 2011.
Bush A, Fleming L. Diagnosis and management of asthma in children. BMJ. 
2015;350:h996.
GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, 
and national incidence, prevalence, and years lived with disability for 310 disease and 
injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. 
The Lancet. 2016;388:1545-602. 
GINA , Global Initiative for Asthma. Global Strategy for Asthma Management and 
Prevention. http://www.ginasthma.org/guidelines-gina-report-global-strategy-for-
asthma.html. 2017. 
GlaxoSmithKline Document Number 2015N230821_00 Study ID 200330. An open-label 
study of inhaler device attributes investigating critical and overall errors, and ease of use 
and preference between a number of inhaler devices (ELLIPTA, 
DISKUS/ACCUHALER, TURBUHALER, and MDI) in adult subjects with asthma 
(Study 200330). Report Date 15-OCT-2015. 
GlaxoSmithKline Document Number 2016N269989_01 Study ID 201594. An open-label 
study of the ease of use and correct use of placebo ELLIPTA dry powder inhaler in 
subjects with asthma. Report Date 21-JUL-2016. 
GlaxoSmithKline Document Number 2017N314003_00 Study ID 204980. An open-label 
study to evaluate the correct use of placebo ELLIPTA™ dry powder inhaler (DPI) 
compared to placebo metered dose inhalers (MDI) in subjects with moderate persistent 
asthma. Report Date 31-JUL-2017. 
Hintze J. PASS Version 12. NCSS, LLC, Kaysville, Utah, USA. 2013. 
Kamps A, Brand P, Roorda R. Determinants of correct inhalation technique in children 
attending a hospital-based asthma clinic. Acta Paediatrica. 2002b;91:159-63. 
Kamps A, Van Ewijk B, Roorda R, Brand P. Poor inhalation technique, even after 
inhalation instruction, in children with asthma. Pediatric Pulmonology. 2000a;29:39-42. 
Morton R, Everald M, Elphick H. Adherence in childhood asthma: the elephant in the 
room. Archives of Disease in Childhood. 2014;99:949-53.
NCT03315572. Pediatric Ease of Use ELLIPTA Items. RTI Health Solutions and GSK, 
2018. clinicaltrials.gov. 
Nicklas R. Paradoxical bronchospasm associated with the use of inhaled beta agonists. 
Journal of Allergy and Clinical Immunology. 1990;85:959-64. 

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Sleath B, Ayala G, Gillette C, Williams D, Davis S, Tudor G, Yeatts K, Washington D. 
Provider Demonstration and Assessment of Child Device Technique During Pediatric 
Asthma Visits. Pediatrics. 2011;1206:642-48.
Van der Palen J, Thomas M, Chrystyn H, Sharma R, Imber V, Zhu C-Q, Svedsater H. 
Training and Time to Achieve Correct Inhaler Use: A Comparison Between Inhalers in 
Patients with COPD. Am J Respir Crit Care Med. 2016b;193:A6811. 
Van der Palen J, Thomas M, Chrystyn H, Sharma R, Van Der Walk P, Goosens M, 
Wilkinson M, Wilkinson T, Stonham C, Chauhan A, Imber V, Zhu C-Q, Svedsater H, 
Barnes N. A randomised open-label cross-over study of inhaler errors, preference and 
time to achieve correct inhaler use in patients with COPD or asthma: Comparison of 
ELLIPTA with other inhaler devices. NPJ Primary Care Respiratory Medicine. 
2016a;26:16079. 
Van der Palen J, Thomas M. Chrystyn H, Sharma R, Imber V, Zhu C-Q, Barnes N. 
Inhaler Preference in Patients with COPD: A Comparison of Ellipta with Five Inhaler 
Devices. Am J Respir Crit Care Med. 2016c;193:A6813. 

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12.
APPENDICES
12.1.
Appendix 1: Abbreviations and Trademarks
AE
Adverse Event
CFR
Code of Federal Regulation
CI
Confidence Interval
CIOMS
Council for International Organizations of Medical Sciences
CONSORT
Consolidated Standards of Reporting trials
CSR
Clinical Study Report
DPI
Dry Powder Inhaler
EC
Ethics Committee
ECG
Electrocardiogram 
eCRF 
Electronic Case Report Form
EW
Early Withdrawal
GCP
Good Clinical Practice
HCP
Healthcare Professional
HIPAA
Health Insurance Portability and Accountability Act
IB
Investigator Brochure
ICF
Informed Consent Form
ICH
International Council for Harmonisation of Technical Requirements 
ICS
Inhaled Corticosteroids
IEC
Independent Ethics Committees
IFU
Instructions for Use
IP
Investigational Product
IRB
Institutional Review Boards
ITT
Intent-to-Treat
IWRS
Interactive Web Response System
MDI
Metered Dose Inhaler
MITT
Modified Intent-to-Treat
LABA
Long Acting 2-Agonist
MSDS
Material Safety Data Sheet
PIF
Peak inspiratory Flow
RAP
Reporting and Analysis Plan
SAE
Serious Adverse Events 
SoA
Schedule of Activities
SRM 
Study Reference Manual
SUSAR
Suspected Unexpected Serious Adverse Reactions
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
ELLIPTA
None

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12.2.
Appendix 2: Study Governance Considerations
Regulatory and Ethical Considerations

This study will be conducted in accordance with the protocol and with:

Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines

Applicable International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical 
Practice (GCP) Guidelines

Applicable laws and regulations

The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (e.g. advertisements) must be submitted to an IRB/IEC by 
the investigator and reviewed and approved by the IRB/IEC before the study is 
initiated. 

Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants. 

The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/ethics committee (EC)

Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulation (CFR), ICH guidelines, the 
IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), 
and all other applicable local regulations
Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study.
Informed Consent Process

The investigator or his/her representative will explain the nature of the study to 
the participant or his/her legally authorized representative and answer all 
questions regarding the study. 

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
Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study centre. 

The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF.

Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study. 

A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized representative. 

Participants who are rescreened are required to sign a new ICF.

Signed assent will be obtained where considered appropriate according to the 
subject’s age and comprehension, as determined by the Investigator.
Data Protection

Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred. 

The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant. 

The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities.
Committees Structure
Not Applicable
Publication Policy

The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.

The sponsor will comply with the requirements for publication of study results. 
In accordance with standard editorial and ethical practice, the sponsor will 
generally support publication of multi center studies only in their entirety and 

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not as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement.

Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements.
Dissemination of Clinical Study Data

Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report.  The investigator 
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
GSK site or other mutually-agreeable location.

GSK will also provide the investigator with the full summary of the study 
results.  The investigator is encouraged to share the summary results with the 
study subjects, as appropriate.

GSK will provide the investigator with the randomization codes for their site 
only after completion of the full statistical analysis.

The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK 
Policy.

A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge.
Data Quality Assurance

All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g. laboratory 
data). The investigator is responsible for verifying that data entries are accurate 
and correct by physically or electronically signing the eCRF. 

The investigator must maintain accurate documentation (source data) that 
supports the information entered in the eCRF. 

The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents. 

The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 

Study monitors will perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements. 

Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 

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Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without 
written notification to the sponsor. 
Source Documents

Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site.

Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. 
The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be 
available.

Definition of what constitutes source data can be found in the source data 
agreement or source data verification form.
Study and Site Closure
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to:
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines
Inadequate recruitment of participants by the investigator
Discontinuation of further study treatment development

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12.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
Definition of AE
AE Definition
An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of a study treatment, whether or not considered related to the 
study treatment.
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study treatment.
Events Meeting the AE Definition 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g. ECG [electrocardiogram], radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e. not related to 
progression of underlying disease).
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
New conditions detected or diagnosed after study treatment administration even though it 
may have been present before the start of the study.
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae.
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfill the definition of an AE or SAE. Also, "lack of 
efficacy" or "failure of expected pharmacological action" constitutes an AE or SAE.
Events NOT Meeting the AE Definition 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

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Medical or surgical procedure (e.g. endoscopy, appendectomy): the condition that leads 
to the procedure is the AE.
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g. hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease).
A SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AE. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred, or was necessary, the 
AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE.
d.
Results in persistent disability/incapacity
The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions.
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (e.g. sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 

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appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered 
serious.
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse.
Recording AE and SAE
AE and SAE Recording
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) related 
to the event.
The investigator will then record all relevant AE/SAE information in the eCRF.
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to GSK in lieu of completion of the GSK /AE/SAE eCRF page.
There may be instances when copies of medical records for certain cases are requested by 
GSK. In this case, all participant identifiers, with the exception of the participant number, 
will be redacted on the copies of the medical records before submission to GSK.
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
Mild: An event that is easily tolerated by the participant, causing minimal discomfort and 
not interfering with everyday activities.
Moderate: An event that causes sufficiently discomfort and interferes with normal 
everyday activities.
Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE. Severe is a category utilized for rating the 
intensity of an event; and both AE and SAE can be assessed as severe.
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe.

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Assessment of Causality
The investigator is obligated to assess the relationship between study treatment and each 
occurrence of each AE/SAE.
A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.
The investigator will use clinical judgment to determine the relationship.
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study treatment administration 
will be considered and investigated.
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK. However, it is very important that 
the investigator always make an assessment of causality for every event before the 
initial transmission of the SAE data to GSK.
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE and SAE
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals.
If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide GSK with a copy of any post-mortem findings 
including histopathology.
New or updated information will be recorded in the originally completed eCRF.
The investigator will submit any updated SAE data to GSK within 24 hours of receipt of 
the information.
Reporting of SAE to GSK
SAE Reporting to GSK via Electronic Data Collection Tool
The primary mechanism for reporting SAE to GSK will be the electronic data collection 

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tool.
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.
The site will enter the SAE data into the electronic system as soon as it becomes 
available.
The investigator or medically-qualified sub-investigator must show evidence within the 
eCRF (e.g., check review box, signature, etc.) of review and verification of the 
relationship of each SAE to IP/study participation (causality) within 72 hours of SAE 
entry into the eCRF.
After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.
If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken off-
line, then the site can report this information on a paper SAE form (see next section) or to 
the medical monitor by telephone.
Contacts for SAE reporting can be found in the SRM.

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12.4.
Appendix 4: Country-specific requirements
N/A

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12.5.
Appendix 5: ELLIPTA DPI correct use and critical error 
checklist
12.5.1.
Checklist
The Checklist for correct use of the ELLIPTA DPI, based on the steps identified in the 
IFU are included in the table below. This will be filled out by the HCP during the 
demonstration by the participant. Following removal of the inhaler from the packaging, 
an eligible study participant will be guided per the instructions in the (Schedule of 
Activities (SoA) (Section 2)) to demonstrate correct use of the ELLIPTA DPI. The steps 
outlined in these instructions require that actions be checked by an ELLIPTA trained 
HCP at both Visit 1 (up to 3 attempts with HCP and 2 further attempts with HCP and 
parent/guardian) and at Visit 2 (1 attempt with no training or instruction and then 1 
attempt after instruction from parent/guardian).
The formatting or layout may change prior to use by the site. Furthermore, the IFU 
wording may alter depending the country involved in the study. However, the specific 
definition of correct use outlined in these checklists will not change.
Critical errors are indicated by the steps that are underlined in the checklists.  
Protocol Identifier
206924
Subject Identifier
ELLIPTA DPI correct 
use/critical error checklist
Visit #
Date of Assessment:
DAY
MONTH
YEAR
IFU  
Step
IFU Wording (2017)
Correct use (Critical errors 
denoted by underlined steps)
YES
NO
1
Open the cover of the inhaler
• Slide the cover down to expose the 
mouthpiece. You should hear a “click”.
You do not need to shake this kind of 
inhaler.
Your inhaler is now ready to use
• If the counter does not count down as 
you hear the click, the inhaler will not 
deliver the medicine. Call your 
healthcare provider or pharmacist if this 
happens.
Participant slides the cover 
completely down to expose the 
mouthpiece until a “click” is heard.
Participant does not shake the 
inhaler 
(Note: a “Yes” response indicates 
that the participant did not shake 
the inhaler after the click is heard)

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IFU  
Step
IFU Wording (2017)
Correct use (Critical errors 
denoted by underlined steps)
YES
NO
2
Breathe out
• While holding the inhaler away from 
your mouth, breathe out (exhale) fully. • 
• Do not breathe out into the 
mouthpiece.
Participant breathes out (exhales) 
while holding the inhaler away from 
their mouth.
Participant does not breathe into 
the mouthpiece. 
(Note: a “Yes” response indicates 
that the participant did not breathe 
into the mouthpiece)
3
Inhale your medicine
• Put the mouthpiece between your 
lips, and close your lips firmly around it.
Your lips should fit over the curved 
shape of the mouthpiece
• Take one long, steady, deep breath in
through your mouth. Do not breathe in 
through your nose
• Do not block the air vent with your 
fingers.
• Remove the inhaler from your 
mouth and hold your breath for 
about 3 to 4 seconds (or as long as is 
comfortable for you).
Participant places mouthpiece 
between lips, and closes lips firmly 
around it.
Participant takes one long steady 
deep breath in through their mouth.
Participant does not block air vent 
with fingers.
(Note: a “Yes” response indicates 
that the participant did not block 
the air vent with their fingers)
Participant removes inhaler from 
his/her mouth and holds his/her 
breath.
4
Breathe out slowly and gently.
• You may not taste or feel the 
medicine, even when you are using the 
inhaler correctly
• Do not take another dose from the 
inhaler even if you do not feel or taste 
the medicine
Participant breathes out slowly and 
gently.
5
Close the inhaler 
• You can clean the mouthpiece if 
needed, using a dry tissue, before you 
close the cover. Routine cleaning is not 
required.
• Slide the cover upwards as far as it 
will go to cover the mouthpiece.
Participant closes the inhaler 
completely.
6
Rinse your mouth
• Rinse your mouth with water after you 
have used the inhaler and spit the 
water out. Do not swallow the water.

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12.6.
Appendix 6: Ease of use Questionnaire(s)
Paper copies of the ease of use questions will be used by the administrator (Investigator 
or designee) to record participants’ answers to the questions. The site will enter the 
answers into the electronic case report form (eCRF). 
INSTRUCTIONS: The administrator (Investigator or designee) will complete the 
following questions related to the ELLIPTA inhalers used during this study. 
Check only one response for the question asked. 
Survey questions VERSION “A” OR “B” to be completed at Visit 2 as per 
randomization at Visit 2.
12.6.1.
Ease of use Questionnaire (Participant Stratum 1, ages 5-7 years)
Instructions: “I am going to ask you some questions about using this inhaler [interviewer 
has placebo ELLIPTA DPI]. The name of the inhaler is ELLIPTA. I will read the 
question and answers to you. Then I will ask you to choose the answer that matches what 
you thought about using the ELLIPTA at home. Do you have any questions for me?” 
12.6.1.1.
Version A
1) Is it easy or hard to use the ELLIPTA inhaler?
□ Easy 
□ Hard   
2) Is it easy or hard is it to tell how many puffs are left in the ELLIPTA inhaler?
□ Easy 
□ Hard   
12.6.1.2.
Version B
1) Is it hard or easy to use the ELLIPTA inhaler?
□ Hard
□ Easy   
2) Is it hard or easy is it to tell how many puffs are left in the ELLIPTA inhaler?
□ Hard 
□ Easy   
12.6.2.
Ease of use Questionnaire (Participant Stratum 2, ages 8-11 
years)
Instructions: “I am going to give you a paper with three questions about the inhaler you 
used during the study [interviewer has placebo ELLIPTA DPI]. The name of the inhaler 
is ELLIPTA. Read the questions and choose the answer that best matches what you 

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thought about using the ELLIPTA at home. Do you have any questions?” [Pause and 
answer any questions from participant. If participant needs help in understanding the 
questions or responses, you can explain or define individual words but please take care 
not to influence his or her answer].
For participants that have difficulty completing the self-administered version, they may 
receive the questionnaire in the same manner as is provided for stratum 1.
12.6.2.1.
Version A
1) Is it easy or hard to use the ELLIPTA inhaler?
□ Easy 
□ Hard   
2) Is it easy or hard is it to tell how many puffs are left in the ELLIPTA inhaler?
□ Easy 
□ Hard   
12.6.2.2.
Version B
1) Is it hard or easy to use the ELLIPTA inhaler?
□ Hard
□ Easy   
2) Is it hard or easy to tell how many puffs are left in the ELLIPTA inhaler?
□ Hard 
□ Easy   
12.6.3.
Ease of use Questionnaire (Parent/Guardian)
Parents/Guardians will be assigned to the same version letter (A or B) to which their 
child/dependent was randomized.
12.6.3.1.
Version A
1) How easy or difficult was it for you to tell how many doses were left in the ELLIPTA 
inhaler?
□ Very Easy
□ Easy
□ Difficult
□ Very Difficult
2) If your child’s current inhaled asthma medication was available in the ELLIPTA 
inhaler, how likely would you be to request the ELLIPTA inhaler from your child’s 
doctor?

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□ Very Likely
□ Likely
□ Unlikely
□ Very Unlikely
12.6.3.2.
Version B
1) How difficult or easy was it for you to tell how many doses were left in the ELLIPTA 
inhaler?
□ Very Difficult
□ Difficult
□ Easy 
□ Very Easy
2) If your child’s current inhaled asthma medication was available in the ELLIPTA 
inhaler, how likely would you be to request the ELLIPTA inhaler from your child’s 
doctor?
□ Very Unlikely
□ Unlikely
□ Likely
□ Very Likely

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12.7.
Appendix 7: Protocol Amendment History
N/A