Clinical trial NCT03478657
Conditions: Asthma
Keywords: Asthma Dry Powder Inhaler Metered Dose Inhaler Long Acting beta 2 Agonist ELLIPTA
Sponsor: GlaxoSmithKline
Start date: 2018-06-18; Completion date: 2018-12-07
Enrollment: 222 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Asthma is a chronic inflammatory disease of airways and lungs that results in hyper-reactivity and clinically relevant episodes of wheezing. This study has been designed to assess the correct use and ease of use of the ELLIPTA® DPI in pediatric subjects with asthma. ELLIPTA DPI is easy to use, requires few steps, is consistent in dosing and eliminates the hand-breath co-ordination required for metered dose inhalers (MDIs). Subjects will be stratified by age into two strata: Stratum 1: subjects in the age group of 5 to 7 years and Stratum 2: Subjects in the age group of 8 to 11 years. All subjects will be trained by Health care professionals (HCP) for the correct use of ELLIPTA DPI. Subjects will be given three chances to attempt correct use of ELLIPTA DPI; subsequently, if the subject is not successful, the parent/guardian will be able to help instruct the subject on the correct use of the ELLIPTA DPI, for two more attempts. The subjects who will be enrolled in the study will take placebo ELLIPTA DPI once daily. After 28 days subjects will be randomized in 1:1 to receive a questionnaire (Version A and B). After completion of the questionnaire on ELLIPTA DPI ease of use, subject's ability to use ELLIPTA DPI correctly will be re-assessed. Approximately 219 subjects will be screened to participate in the study. The study will be conducted for 28 days. ELLIPTA is a registered trademark of GlaxoSmithKline (GSK) group of companies.

Detailed description:

Arms: arm 1: Subjects in stratum 1 and stratum 2 will be of age group from 5 to 7 years and 8 to 11 years respectively. Subjects will take placebo ELLIPTA DPI once daily. During Visit 2 (Day 28) subjects will be randomized to receive questionnaire on ELLIPTA DPI usage either version A or B.
Interventions: intervention 1: Placebo DPI intervention 2: ELLIPTA DPI intervention 3: Ease of use questionnaires
Intervention descriptions: intervention 1: Subjects will receive placebo via oral inhalation route using ELLIPTA once daily. Placebo DPI will be available in two strips of 30 blisters per strip. First strip will contain lactose monohydrate and second strip will have lactose monohydrate blended with magnesium stearate. intervention 2: Subjects will receive placebo DPI via ELLIPTA. ELLIPTA is trademark of GSK intervention 3: Subjects from both stratum after use of ELLIPTA DPI will be randomized to receive either version A or B of the questionnaires. Subjects will be asked questions on ease of use of ELLIPTA. Parent/guardian will also complete a questionnaire about the ELLIPTA DPI.

Protocol documents:
Prot_000.pdf: 
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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

SAP_001.pdf: 
CONFIDENTIAL
The GlaxoSmithKline group of companies
206924
1
Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
Reporting and Analysis Plan for 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
Compound Number 
:
GSK2285997 (GW685698 + GW642444)
Effective Date 
:
12-MAR-2019
Description:

The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol 206924.

This RAP is intended to describe the planned analyses required for the study and 
output to be included in the Clinical Study Report for Protocol 206924. 

This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable.
RAP Author(s):
Author
Date
Lead
06-MAR-2019
Statistician (Respiratory Clinical Statistics)
Copyright 2019 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD


CONFIDENTIAL
The GlaxoSmithKline group of companies
206924
2
RAP Team Review Confirmations (Method: E-mail):
Clinical Statistics and Clinical Programming Line Approvals (Method: Pharma 
TMF eSignature):
Approver(s)
Date
08-MAR-2019
Senior Statistics Director (Respiratory Clinical Statistics)
12-MAR-2019
Programming Manager (Respiratory Clinical Programming)
Reviewer(s)
Date
(review confirmation on behalf of 
07-MAR-2019
Clinical Development Director (Respiratory, HUP Clinical 
Development)
07-MAR-2019
Programming Manager (Respiratory Clinical Programming)
Associate Manager (Biostatistics)
08-MAR-2019
PPD
PPD
PPD
PPD
PPD
PPD


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TABLE OF CONTENTS
PAGE
1.
INTRODUCTION......................................................................................................8
2.
SUMMARY OF KEY PROTOCOL INFORMATION ..................................................8
2.1.
Changes to the Protocol Defined Statistical Analysis Plan............................8
2.2.
Study Objective(s) and Endpoint(s)...............................................................8
2.3.
Study Design ..............................................................................................10
2.4.
Statistical Hypotheses / Statistical Analyses ...............................................11
3.
PLANNED ANALYSES ..........................................................................................12
3.1.
Interim Analyses .........................................................................................12
3.2.
Final Analyses ............................................................................................12
4.
ANALYSIS POPULATIONS ...................................................................................12
4.1.
Protocol Deviations.....................................................................................12
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS.....................................................................................................14
5.1.
Study Treatment & Sub-group Display Descriptors.....................................14
5.2.
Baseline Definitions ....................................................................................14
5.3.
Multicentre Studies .....................................................................................14
5.4.
Examination of Covariates, Other Strata and Subgroups............................15
5.4.1.
Covariates and Other Strata ........................................................15
5.4.2.
Examination of Subgroups...........................................................15
5.5.
Multiple Comparisons and Multiplicity .........................................................15
5.6.
Other Considerations for Data Analyses and Data Handling 
Conventions................................................................................................15
6.
STUDY POPULATION ANALYSES .......................................................................16
6.1.
Overview of Planned Study Population Analyses........................................16
6.2.
Participant Disposition ................................................................................16
6.3.
Medical Conditions .....................................................................................16
6.4.
Concomitant Medications............................................................................16
6.5.
Incorrect Use at Visit 1................................................................................17
7.
EFFICACY ANALYSES..........................................................................................18
7.1.
Primary Efficacy Analyses ..........................................................................18
7.1.1.
Endpoints.....................................................................................18
7.1.2.
Summary Measure ......................................................................18
7.1.3.
Population of Interest...................................................................18
7.1.4.
Strategy for Intercurrent (Post-Randomization) Events ................18
7.1.4.1.
Percentage of participants from each stratum 
who demonstrate correct use of the ELLIPTA 
DPI after the study period at V2..................................19
7.1.4.2.
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...............................................................................19


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7.1.5.
Statistical Analyses / Methods .....................................................20
7.1.5.1.
Statistical Methodology Specification..........................20
7.1.5.1.1.
Percentage of participants from 
each stratum who demonstrate 
correct use of the ELLIPTA DPI 
after the study period at V2.....................20
7.1.5.1.2.
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.....................21
7.2.
Secondary Efficacy Analyses......................................................................21
7.2.1.
Endpoints.....................................................................................22
7.2.2.
Summary Measure ......................................................................22
7.2.3.
Population of Interest...................................................................22
7.2.4.
Strategy for Intercurrent (Post-Randomization) Events ................22
7.2.4.1.
Percentage of participants from each stratum 
who demonstrate correct use of the ELLIPTA 
DPI after initial training from HCP at V1......................22
7.2.4.2.
Percentage of participants who demonstrate 
correct use of the ELLIPTA DPI after the study 
period at V2................................................................23
7.2.4.3.
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..................................23
7.2.4.4.
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 ..................................................................24
7.2.5.
Statistical Analyses / Methods .....................................................25
7.2.5.1.
Statistical Methodology Specification..........................25
7.2.5.1.1.
Percentage of participants from 
each stratum who demonstrate 
correct use of the ELLIPTA DPI 
after initial training from HCP at 
V1...........................................................25
7.2.5.1.2.
Percentage of participants who 
demonstrate correct use of the 
ELLIPTA DPI after the study 
period at V2............................................25
7.2.5.1.3.
Percentage 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............................................26
7.2.5.1.4.
Percentage of participants from 
each stratum who made at least 
one critical error during use of the 


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ELLIPTA DPI after initial training 
from HCP at V1. .....................................26
7.3.
Exploratory Efficacy Analyses.....................................................................27
7.3.1.
Endpoints.....................................................................................27
7.3.2.
Summary Measures.....................................................................28
7.3.3.
Population of Interest...................................................................28
7.3.4.
Strategy for Intercurrent (Post-Randomization) Events ................28
7.3.4.1.
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................................................................28
7.3.4.2.
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. ...............................29
7.3.4.3.
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................................................................30
7.3.4.4.
Percentage of participants from each stratum 
who demonstrate correct use after the study 
period at V2 with assistance from 
parents/guardians.......................................................30
7.3.4.5.
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...............................................................................31
7.3.4.6.
Percentage of participants who made at least 
one critical error during use of the ELLIPTA 
DPI after initial training from HCP at V1......................31
7.3.5.
Statistical Analyses / Methods .....................................................32
7.3.5.1.
Statistical Methodology Specification..........................32
7.3.5.1.1.
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...................................32
7.3.5.1.2.
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............................................33
7.3.5.1.3.
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 


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the ELLIPTA DPI after the study 
period at V2............................................33
7.3.5.1.4.
Percentage of participants from 
each stratum who demonstrate 
correct use after the study period 
at V2 with assistance from 
parents/guardians...................................34
7.3.5.1.5.
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............................................35
7.3.5.1.6.
Percentage of participants who 
made at least one critical error 
during use of the ELLIPTA DPI 
after initial training from HCP at 
V1...........................................................35
8.
SAFETY ANALYSES .............................................................................................36
8.1.
Adverse Events...........................................................................................36
8.2.
Adverse Events of Special Interest Analyses..............................................36
9.
REFERENCES.......................................................................................................37
10. APPENDICES........................................................................................................38
10.1.
Appendix 1: Protocol Deviation Management .............................................38
10.1.1.
Exclusions from Per Protocol Population .....................................38
10.2.
Appendix 2: Schedule of Activities ..............................................................39
10.2.1.
Protocol Defined Schedule of Events...........................................39
10.3.
Appendix 3: Assessment Windows .............................................................41
10.3.1.
Definitions of Assessment Windows for Analyses........................41
10.4.
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................42
10.4.1.
Study Phases ..............................................................................42
10.4.1.1.
Study Phases for Concomitant Medication .................42
10.4.2.
Treatment Emergent Flag for Adverse Events .............................43
10.5.
Appendix 5: Data Display Standards & Handling Conventions....................44
10.5.1.
Reporting Process .......................................................................44
10.5.2.
Reporting Standards....................................................................44
10.6.
Appendix 6: Derived and Transformed Data ...............................................46
10.6.1.
General........................................................................................46
10.6.2.
Study Population..........................................................................46
10.6.3.
Efficacy........................................................................................46
10.6.4.
Safety ..........................................................................................47
10.7.
Appendix 7: Reporting Standards for Missing Data.....................................48
10.7.1.
Premature Withdrawals................................................................48
10.7.2.
Handling of Missing Data.............................................................48
10.7.2.1.
Handling of Missing and Partial Dates ........................48
10.8.
Appendix 8: Values of Potential Clinical Importance ...................................50
10.8.1.
Vital Signs....................................................................................50
10.9.
Appendix 9: Abbreviations & Trade Marks ..................................................51
10.9.1.
Abbreviations...............................................................................51


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10.9.2.
Trademarks .................................................................................51
10.10. Appendix 10: List of Data Displays..............................................................52
10.10.1. Data Display Numbering..............................................................52
10.10.2. Mock Example Shell Referencing ................................................52
10.10.3. Deliverables.................................................................................52
10.10.4. Study Population Tables..............................................................53
10.10.5. Efficacy Tables ............................................................................57
10.10.6. Efficacy Figures ...........................................................................60
10.10.7. Safety Tables...............................................................................62
10.10.8. ICH Listings .................................................................................64
10.10.9. Non-ICH Listings..........................................................................68
10.11. Appendix 11: Example Mock Shells for Data Displays ................................70


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1.
INTRODUCTION
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for Protocol: 206924.
Revision Chronology:
2017N346371_00
23-JAN-2018
Original
2.
SUMMARY OF KEY PROTOCOL INFORMATION
2.1.
Changes to the Protocol Defined Statistical Analysis Plan
Changes from the originally planned statistical analysis specified in the protocol (dated: 
23/JAN/2018) are outlined in Table 1.
Table 1
Changes to Protocol Defined Analysis Plan
Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes
Protocol Section 10.3 Populations for 
Analyses
RAP Section 4 Analysis 
Populations
The analysis populations have 
been updated to follow the study 
populations standard definitions 
and statistical displays
RAP Section 7.1.5.1.2, Section 
7.2.5.1.3., Section 7.3.4.1.
Removed sensitivity analysis 
proposed in the critical 
components RAP “participants 
who completed demonstration 
of correct use before answering 
the ease of use questionnaire” 
due to the information not being 
recorded.
2.2.
Study Objective(s) and Endpoint(s)
Objectives
Endpoints
Primary Objectives
Primary Endpoints

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.


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Objectives
Endpoints
Secondary Objectives
Secondary Endpoints

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 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.
Exploratory Objectives
Exploratory Endpoints

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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2.3.
Study Design
Overview of Study Design and Key Features
Design
Features

This is an open-label study to evaluate correct use and ease of use of the ELLIPTA 
Dry Powder Inhaler (DPI) in pediatric patients who are currently receiving inhaled 
therapy for treatment of their asthma. 

Only participants who are naïve to the ELLIPTA DPI and have an established 
diagnosis of asthma will be considered eligible to participate in the study.

Participants will continue to use their current asthma therapy (rescue or maintenance)
throughout the study.

The participants will be stratified in to two strata based on their age (5-7 year olds, 8-
11 year olds) at the screening visit (Visit 0).
Dosing

Participants will be instructed to take one inhalation from the placebo ELLIPTA DPI no 
more than once daily at the same time each day during the 4-week study treatment 
period.
Time & 
Events

[Refer to Appendix 2: Schedule of Activities]
Treatment 
Assignment

All participants who pass screening (Visit 0) are given a placebo ELLIPTA DPI at Visit 
1. 

All participants at V1 are then trained and assessed in correct use of the ELLIPTA DPI
up to a maximum of five times. For the first three attempts, the participant is trained by 
the HCP. For the fourth and fifth attempts, the participants’ parent/guardian assists in 
the training of the ELLIPTA DPI placebo.

Participants who demonstrate correct use at V1 are then given a placebo ELLIPTA 
DPI to take away from the site to continue use for 4 weeks. Participants should take 
one dose a day at roughly the same time every day.

Approximately 219 participants will be enrolled in the study and stratified by age 
(approximately 88 5-7 year olds, and 131 8-11 year olds) such that 200 evaluable 
participants reach Visit 2 and complete the study.

Participants will be randomised at Visit 2 to one of two ELLIPTA DPI ease of use 
questionnaires.
Interim 
Analysis

No interim analysis will be conducted during this study


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2.4.
Statistical Hypotheses / Statistical Analyses
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.


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3.
PLANNED ANALYSES
3.1.
Interim Analyses
No interim analysis is planned for this study.
3.2.
Final Analyses
The final planned primary analyses will be performed after the completion of the 
following sequential steps:
1.
All participants have completed the study as defined in the protocol.
2.
All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data 
Management.
3.
All criteria for unblinding the randomization codes have been met. 
4.
Randomization codes have been distributed according to RandAll NG
procedures.
4.
ANALYSIS POPULATIONS
Population
Definition / Criteria
Analyses Evaluated
All Subjects
Enrolled (ASE)

All participants whose parent/guardian has signed the 
Informed Consent Form (ICF) and the accompanying 
informed assent from the participant (where applicable) 
has been acquired, and for whom a record exists in the 
study database, including screen failures and any
participant who was not screened but experienced an 
SAE between the date of informed consent and the 
planned date of the Screening visit.

Study Population

Safety
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).

Study Population

Safety

Efficacy
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 version of the ease 
of use questionnaire at V2.

Study Population

Efficacy
Refer to Appendix 10: List of Data Displays which details the population used for each display. – Appendix 10 to be 
defined in full RAP
4.1.
Protocol Deviations
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be 
summarised and listed.


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Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan 8-JUN-2018, Version 1.0.
o Data will be reviewed prior to freezing the database to ensure all important 
deviations are captured and categorised on the protocol deviations dataset. 
o This dataset will be the basis for the summaries and listings of protocol 
deviations.
A separate summary and listing of all inclusion/exclusion criteria deviations will also be 
provided. This summary will be based on data as recorded on the inclusion/exclusion 
page of the eCRF.


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5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA
HANDLING CONVENTIONS
5.1.
Study Treatment & Sub-group Display Descriptors
All participants during screening will be provided an ELLIPTA DPI placebo to
demonstrate correct use at Visit 1 at site and provided another ELLIPTA DPI to take 
away from site for the study period. The ELLIPTA DPI placebo is the only ‘treatment’
being provided in this study, hence no formal treatment comparisons will be performed.
All participants will be stratified in to two strata based on their age at visit 0 (5-7 and 8-
11 years old).
The participants who make it through visit 1 and return at visit 2 will be randomised to 
one of two ELLIPTA DPI ease of use questionnaires (version A or version B). The 
version of the ease of use questionnaires will be considered the “treatment groups” in this 
study. The parents/guardians are also assigned to one of two ease of use questionnaires. 
The participant’s questions are different to the parents/guardian’s versions, however, the 
parents/guardians are assigned the same version (A or B) as their child’s randomised 
version.
Treatment Group Descriptions
RandAll NG
Data Displays for Reporting 
Code
Description
Description
Order in TLF 
A
Placebo Ease of Use Questionnaire 
Version A
Questionnaire: Version A
1
B
Placebo Ease of Use Questionnaire 
Version B
Questionnaire: Version B
2
5.2.
Baseline Definitions
For all endpoints, the baseline value will be the latest pre-dose assessment with a non-
missing value, including those from unscheduled visits. If time is not collected, Day 1 
assessments are assumed to be taken prior to first dose and used as baseline.
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing.
5.3.
Multicentre Studies
In this multicentre global study, enrolment will be presented by country.
Region
Countries
Northern America
United States, Canada


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5.4.
Examination of Covariates, Other Strata and Subgroups
5.4.1.
Covariates and Other Strata
The list of covariates and other strata may be used in descriptive summaries and 
statistical analyses, some of which may also be used for subgroup analyses. Additional 
covariates and other strata of clinical interest may also be considered.
Category
Details
Strata
Age Group at Screening (5-7 years old, 8-11 years old), Ease of Use Questionnaire
(Version A, Version B)
Covariates
Country
5.4.2.
Examination of Subgroups
The list of subgroups may be used in descriptive summaries and statistical analyses.
Additional subgroups of clinical interest may also be considered.

If the percentage of subjects is small within a particular subgroup, then the subgroup 
categories may be refined prior to unblinding the trial.

If the category cannot be refined further, then descriptive rather than statistical 
comparisons may be performed for the particular subgroup.
Subgroup
Categories 
Country
United States, Canada
Gender
Female, Male
Duration of Asthma
< 1 year, >=1 year to < 3 years, >=3 years to < 5 years, >=5 years
Main Current Asthma Therapy
Rescue Only, Maintenance with or without Rescue
Main Current Asthma Therapy
Device Type
DPI, MDI, Other
5.5.
Multiple Comparisons and Multiplicity
There are no planned adjustments for multiple comparisons or multiplicity.
5.6.
Other Considerations for Data Analyses and Data Handling 
Conventions
Other considerations for data analyses and data handling conventions are outlined in the 
appendices:
Section
Component
10.3
Appendix 3: Assessment Windows
10.4
Appendix 4: Study Phases and Treatment Emergent Adverse Events
10.5
Appendix 5: Data Display Standards & Handling Conventions
10.6
Appendix 6: Derived and Transformed Data


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Section
Component
10.7
Appendix 7: Reporting Standards for Missing Data
10.8
Appendix 8: Values of Potential Clinical Importance
6.
STUDY POPULATION ANALYSES
6.1.
Overview of Planned Study Population Analyses
The study population analyses will be based on the Intent-to-Treat (ITT) population, 
unless otherwise specified.
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
and exposure and treatment compliance will be based on GSK Core Data Standards.  
Details of the planned displays are presented in Appendix 10: List of Data Displays
6.2.
Participant Disposition
The study population summary will use the ASE population and show the number of 
participants overall who were screened, the number of screen failures and the number 
with each reason for the screen failure. The display will also showcase the number of 
participants who are in the ITT population (complete screening and demonstrate correct 
use at visit 1) and MITT population (attend visit 2 and are randomised to a version of the 
ease of use questionnaire). 
For the ITT population, reasons for withdrawal summary will present the number and 
percentage of participants who completed the study, those who withdrew prematurely 
from the study and those who reported a primary and sub-reason for the withdrawal. 
6.3.
Medical Conditions 
The number and percentage of participants reporting each current medical condition will 
be presented. All medical conditions will be summarised in the displays regardless of the 
frequencies. This applies to both the current and past medical condition displays. 
6.4.
Concomitant Medications
Concomitant medications will be coded using the GSK Drug coding dictionary. A
summary of the number and percentage of subjects with concomitant medications will be
displayed by GSK-Drug Anatomical Therapeutic Chemical (ATC) classification level 1
(Body System) and ingredient. This summary will present drugs that are composed of a
combination of ingredients and will be displayed according to the ATC classifications of
the ingredients (combination) and will also include single-ingredient medications.
Summaries will be split into those taken pre-treatment, during treatment, and post-
treatment.


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6.5.
Incorrect Use at Visit 1
Participants will be asked to demonstrate correct use of the ELLIPTA at visit 1. The 
participants will have up to 5 attempts to demonstrate correct use. The number of 
participants who attempt correct use will be presented along with the number and 
percentages of those who did not demonstrate correct use after attempts number 1 to 5. 
The number and percentages of each item not performed correctly at each attempt will be 
summarised in the display for all participants.  The summary will be based on the ITT 
population.


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7.
EFFICACY ANALYSES
7.1.
Primary Efficacy Analyses
The primary analyses will include:

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.
7.1.1.
Endpoints
The primary endpoints are:

The percentage 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 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.
7.1.2.
Summary Measure
The percentage for both endpoints will be reported for each stratum for the single 
treatment group along with a 95% confidence interval (CI) for the percentage, calculated 
using the exact binomial distribution. 
7.1.3.
Population of Interest 
The primary efficacy analyses will be based on the Modified Intent-to-Treat (MITT) 
population, unless otherwise specified.
7.1.4.
Strategy for Intercurrent (Post-Randomization) Events
The MITT population composes of participants who have been screened, received at least 
one dose of the study medication (placebo) and were randomized to a version of the ease 
of use questionnaire at V2. Therefore, we can only identify intercurrent events that occur 
at V2 only.
Intercurrent events are defined as:

Early discontinuation of study drug

Early withdrawal from study (not completing correct use checklist or ease of use 
questionnaire)

Use of prohibited medications
The “Treatment policy” strategy will be applied to handle the “Use of prohibited 
medications” and “Early discontinuation of drug” in the analysis for all endpoints. The 
strategy implies direct use of data irrespective of the occurrence of the intercurrent 


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events. This means the participant’s data will be included in the analysis regardless 
whether they discontinued the ELLIPTA DPI placebo or used a prohibited medication at 
Visit 2. The “Treatment policy” strategy is the same as de facto type estimand. The 
strategy for the Early withdrawal from study intercurrent events is mentioned below for 
the endpoints.
7.1.4.1.
Percentage of participants from each stratum who demonstrate correct 
use of the ELLIPTA DPI after the study period at V2.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. Participants who make it to V2 will be randomised to a version of the ease of use 
questionnaire and complete this questionnaire. The participants will then be asked to 
demonstrate correct use of the ELLIPTA DPI. A participant is expected to complete the 
full demonstration, however there is a possibility the participant might choose to no 
longer participate and not complete the full demonstration (i.e. decide to stop half way 
through the demonstration of the required steps for correct use of the ELLIPTA DPI). In 
the occurrence of this intercurrent event, the endpoint will be the percentage of 
participants from each stratum who demonstrate correct use of the ELLIPTA DPI after 
the study period at V2, where those who are deemed “not correct use” will comprise of 
the participants who did not demonstrate correct use of the ELLIPTA DPI and those who 
did not complete the demonstration of correct use. The strategy modifies the definition of 
the summary measure, such that the intercurrent event becomes a component of the 
outcome. A footnote will be included on displays to indicate this composite endpoint, if 
this intercurrent event should occur.
If a participant withdraws from the study, or a parent no longer consents their child 
before the correct use demonstration can be started, then they will be deemed an early 
withdrawal and no data will be collected for this endpoint.
7.1.4.2.
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.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. Participants who make it to V2 will be randomised to a version of the ease of use 
questionnaire, asked to complete the questionnaire and then will perform a demonstration 
of correct use of the ELLIPTA DPI. The first question relates to the ease of use of the 
ELLIPTA DPI, while the second question relates to the ease of telling the number of 
doses remaining in the ELLIPTA DPI. A participant is expected to complete the 
questionnaire before the correct use demonstration, however there is a possibility the 
participant might only answer one or zero of the questions, and still able to perform the
correct use demonstration, or choose to no longer participate in the study. In the 
occurrence of this intercurrent event, the endpoint will be 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, where those 
who rate the ease of use of ELLIPTA DPI as “hard” comprise of the participants who 
rated the ELLIPTA DPI as “hard” and those who did not answer the ease of use question. 
A footnote will be included on displays to indicate this composite endpoint, if this 
intercurrent event should occur.


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If a participant withdraws from the study, or a parent no longer consents their child 
before the questionnaire can be started, then they will be deemed an early withdrawal and 
no data will be collected for this endpoint.
7.1.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 7.1.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and
listed.
7.1.5.1.
Statistical Methodology Specification
7.1.5.1.1.
Percentage of participants from each stratum who demonstrate correct 
use of the ELLIPTA DPI after the study period at V2
Endpoint / Variables

The percentage of participants from each stratum who demonstrate correct use of the 
ELLIPTA DPI after the study period at V2.
Model Specification

The primary endpoint of the percentage of participants from each stratum who demonstrate 
correct use of the ELLIPTA DPI after the study period at V2 will be analysed using the Modified 
Intent-to-Treat population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI
Model Checking & Diagnostics

Computation of the confidence intervals for the proportions is based on the exact (Clopper-
Pearson) binomial distribution.
Model Results Presentation

The percentage will be reported for each stratum for the single treatment group along with a 
95% confidence interval (CI) for the percentage, calculated using the exact binomial 
distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the primary composite estimand display, an observed data 
display with no imputation may be presented if a substantial amount (10% of the total 
population) of participants do not complete the correct use demonstration. This display will 
include the correct use demonstration completers only.


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7.1.5.1.2.
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
Endpoint / Variables

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.
Model Specification

The primary endpoint of 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 will be analysed using the Modified Intent-to-Treat population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI
Model Checking & Diagnostics

Computation of the confidence intervals for the proportions is based on the exact (Clopper-
Pearson) binomial distribution.
Model Results Presentation

The percentage will be reported for each stratum for the single treatment group along with a 
95% confidence interval (CI) for the percentage, calculated using the exact binomial 
distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the primary composite estimand display, an observed data 
display with no imputation may be presented if a substantial amount (10% of the total 
population) of participants do not answer ease of use questionnaire. This display will include 
the ease of use question completers only.
7.2.
Secondary Efficacy Analyses
The secondary efficacy analyses will include:

To determine the proportion of participants from each stratum who demonstrate 
correct use of the ELLIPTA DPI after initial training from HCP only at V1.

To determine the proportion 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.

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 only at 
V1.


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7.2.1.
Endpoints
The secondary endpoints are:

The percentage of participants from each stratum who demonstrate correct use of the 
ELLIPTA DPI after initial training from HCP at V1.

The percentage of participants who 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.

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.
7.2.2.
Summary Measure
The percentage for all secondary endpoints will be reported for the single treatment group 
along with a 95% confidence interval (CI) for the percentage, calculated using the exact 
binomial distribution. 
7.2.3.
Population of Interest 
The secondary efficacy analyses will be based on the Intent-To-Treat or Modified Intent-
to-Treat populations, unless otherwise specified.
7.2.4.
Strategy for Intercurrent (Post-Randomization) Events
Intercurrent events are defined as:

Early discontinuation of study drug

Early withdrawal from study

Use of prohibited medications
The “Treatment policy” strategy will be applied to handle the “Use of prohibited 
medications” and “Early discontinuation of study drug” in the analysis for all endpoints. 
The strategy implies direct use of data irrespective of the occurrence of the intercurrent 
events. The “Treatment policy” strategy is the same as de facto type estimand. The 
strategy for the Early withdrawal from study intercurrent events is mentioned below for 
the endpoints.
7.2.4.1.
Percentage of participants from each stratum who demonstrate correct 
use of the ELLIPTA DPI after initial training from HCP at V1.
The population of interest will be based on the Intent-to-Treat population.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. Participants who pass the screening visit (Visit 0) will then be taught by the HCP 
how to correctly use the ELLIPTA DPI. The participant is then provided with their own 
ELLIPTA DPI and will be asked to demonstrate correct use. If the participant
demonstrates correct use of the ELLIPTA DPI, they will progress through the study and 


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deemed correct use at V1, attempt one. If the participant cannot perform correct use on 
their first attempt, then they will have four more attempts, and will be deemed a “not 
correct use” on the first attempt. A participant is expected to complete the full correct use 
demonstration, however there is a possibility the participant might choose to no longer 
participate and not complete the full demonstration. In the occurrence of this intercurrent 
event, the endpoint will be the percentage of participants from each stratum who 
demonstrate correct use of the ELLIPTA DPI after initial training from the HCP at V1, 
where those who are deemed “not correct use” will comprise of participants who did not 
perform correct use of the ELLIPTA DPI on attempt one and those who did not complete 
the demonstration of correct use on attempt one. A footnote will be included on displays 
to indicate this composite endpoint, if this intercurrent event should occur.
If a participant withdraws from the study, or a parent no longer consents their child 
before the correct use demonstration can be started, then they will be deemed a screen 
failure and no data will be collected for this endpoint.
7.2.4.2.
Percentage of participants who demonstrate correct use of the 
ELLIPTA DPI after the study period at V2.
The population of interest will be based on the Modified Intent-to-Treat population.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. Participants who make it to V2 will be randomised to a version of the ease of use 
questionnaire and asked to complete the questionnaire. The participants will then be 
asked to demonstrate correct use of the ELLIPTA DPI. A participant is expected to 
complete the full demonstration, however there is a possibility the participant might 
choose to no longer participate and not complete the full demonstration (i.e. decide to 
stop half way through the demonstration of the required steps for correct use of the 
ELLIPTA DPI). In the occurrence of this intercurrent event, the endpoint will be the 
percentage of participants who demonstrate correct use of the ELLIPTA DPI after the 
study period at V2, where those who are deemed “not correct use” will comprise of the 
participants who did not demonstrate correct use of the ELLIPTA DPI and those who did 
not complete the demonstration of correct use. A footnote will be included on displays to 
indicate this composite endpoint, if this intercurrent event should occur.
If a participant withdraws from the study, or a parent no longer consents their child 
before the correct use demonstration can be started, then they will be deemed an early 
withdrawal and no data will be collected for this endpoint.
7.2.4.3.
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.
The population of interest will be based on the Modified Intent-to-Treat population.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. Participants who make it to V2 will be randomised to a version of the ease of use 
questionnaire, asked to complete the questionnaire and then will perform a demonstration 
of correct use of the ELLIPTA DPI. The first question relates to the ease of use of the 


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ELLIPTA DPI, while the second question relates to the ease of telling the number of 
doses remaining in the ELLIPTA DPI. A participant is expected to complete the 
questionnaire before the correct use demonstration, however there is a possibility the 
participant might only answer one or zero of the questions, and still able to perform the 
correct use demonstration, or choose to no longer participate in the study. In the 
occurrence of this intercurrent event, the endpoint will be 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, where those who rate the ease of use of 
ELLIPTA DPI as “hard” comprise of the participants who rated the ELLIPTA DPI as 
“hard” and those who did not answer the ease of use question. A footnote will be 
included on displays to indicate this composite endpoint, if this intercurrent event should 
occur.
If a participant withdraws from the study, or a parent no longer consents their child 
before the questionnaire can be started, then they will be deemed an early withdrawal and 
no data will be collected for this endpoint.
7.2.4.4.
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
The population of interest will be based on the Intent-to-Treat population.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. Participants who pass the screening visit (Visit 0) will then be taught by the HCP 
how to correctly use the ELLIPTA DPI. The participant is then provided with their own 
ELLIPTA DPI and will be asked to demonstrate correct use. Four of the ten correct use 
checklist items are deemed as “critical errors” (see Section 10.6.3 for the details on 
critical errors). A participant is expected to perform throughout the whole correct use 
demonstration, however there is a possibility the participant might choose to no longer 
participate and not complete the full demonstration (i.e. only perform 2 of the 4 critical 
error items during the correct use demonstration). In the occurrence of this intercurrent 
event, the endpoint will be 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. If a participant withdraws at any point throughout the correct use demonstration and 
performed a critical error, then the participant will be deemed as one who performed at 
least one critical error. If the participant withdraws at any point throughout the correct 
use demonstration and did not perform all the critical error items, then taking the 
conservative approach, the participant will also be deemed as one who performed at least 
one critical error. If the participant withdraws at any point during the correct use 
demonstration and performs all critical error items correctly, then the participant will be 
deemed as one who did not perform at least one critical error. A footnote will be included 
on displays to indicate this composite endpoint, if this intercurrent event should occur.
If a participant withdraws from the study, or a parent no longer consents their child 
before the correct use demonstration can be started, then they will be deemed a screen 
failure and no data will be collected for this endpoint.


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7.2.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.
7.2.5.1.
Statistical Methodology Specification
7.2.5.1.1.
Percentage of participants from each stratum who demonstrate correct 
use of the ELLIPTA DPI after initial training from HCP at V1
Endpoint / Variables

The percentage of participants from each stratum who demonstrate correct use of the ELLIPTA 
DPI after initial training from HCP at V1.
Model Specification

The endpoint of the percentage of participants from each stratum who demonstrate correct use 
of the ELLIPTA DPI after initial training from HCP at V1 will be analysed using the Intent-to-
Treat population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI
Model Results Presentation

The percentage will be reported for each stratum for the single treatment group along with a 
95% confidence interval (CI) for the percentage, calculated using the exact binomial 
distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the composite estimand display, an observed data display with 
no imputation may be presented if a substantial amount (10% of the total population) of 
participants do not complete the correct use demonstration. This display will include the correct 
use demonstration completers only.
7.2.5.1.2.
Percentage of participants who demonstrate correct use of the 
ELLIPTA DPI after the study period at V2.
Endpoint / Variables

The percentage of participants who demonstrate correct use of the ELLIPTA DPI after the 
study period at V2.
Model Specification

The endpoint of the percentage of participants who demonstrate correct use of the ELLIPTA 
DPI after the study period at V2 will be analysed using the Modified Intent-to-Treat population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI


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Model Results Presentation

The percentage will be reported for the single treatment group along with a 95% confidence 
interval (CI) for the percentage, calculated using the exact binomial distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the composite estimand display, an observed data display with 
no imputation may be presented if a substantial amount (10% of the total population) of 
participants do not complete the correct use demonstration. This display will include the correct 
use demonstration completers only.
7.2.5.1.3.
Percentage 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.
Endpoint / Variables

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.
Model Specification

The endpoint of 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 will 
be analysed using the Modified Intent-to-Treat population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI
Model Results Presentation

The percentage will be reported for the single treatment group along with a 95% confidence 
interval (CI) for the percentage, calculated using the exact binomial distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the primary composite estimand display, an observed data 
display with no imputation may be presented if a substantial amount (10% of the total 
population) of participants do not answer ease of use questionnaire. This display will include 
the ease of use question completers only.
7.2.5.1.4.
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.
Endpoint / Variables

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.
Model Specification

The endpoint of 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 will be 


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analysed using the Intent-to-Treat population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI
Model Results Presentation

The percentage will be reported for each stratum for the single treatment group along with a 
95% confidence interval (CI) for the percentage, calculated using the exact binomial 
distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the composite estimand display, an observed data display with 
no imputation may be presented if a substantial amount (10% of the total population) of 
participants do not complete the correct use demonstration. This display will include the correct 
use demonstration completers only.
7.3.
Exploratory Efficacy Analyses
The exploratory efficacy analyses will include:

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.

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.

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.

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.

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.

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.
7.3.1.
Endpoints
The exploratory efficacy endpoints are:

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.

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.


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
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.

The percentage of participants from each stratum who demonstrated correct use after 
the study period at V2 with assistance from parents/guardians.

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.

The percentage of participants who made at least one critical error during use of the 
ELLIPTA DPI after initial training from HCP at V1.
7.3.2.
Summary Measures
The percentage for all exploratory efficacy endpoints will be reported for the single 
treatment group along with a 95% confidence interval (CI) for the percentage, calculated 
using the exact binomial distribution.
7.3.3.
Population of Interest 
The exploratory efficacy analyses will be based on the Intent-To-Treat or Modified 
Intent-to-Treat populations, unless otherwise specified.
7.3.4.
Strategy for Intercurrent (Post-Randomization) Events
Intercurrent events are defined as:

Early discontinuation of study drug

Early withdrawal from study

Use of prohibited medications
The “Treatment policy” strategy will be applied to handle the “Use of prohibited 
medications” and “Early discontinuation of study drug” in the analysis for all endpoints. 
The strategy implies direct use of data irrespective of the occurrence of the intercurrent 
events. The “Treatment policy” strategy is the same as de facto type estimand. The 
strategy for the Early withdrawal from study intercurrent events is mentioned below for 
the endpoints.
7.3.4.1.
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
The population of interest will be based on the Modified Intent-to-Treat population.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. Participants who make it to V2 will be randomised to a version of the ease of use 
questionnaire, asked to complete the questionnaire and then will perform a demonstration 
of correct use of the ELLIPTA DPI. The first question relates to the ease of use of the 
ELLIPTA DPI, while the second question relates to the ease of telling the number of 
doses remaining in the ELLIPTA DPI. A participant is expected to complete the 
questionnaire before the correct use demonstration, however there is a possibility the 


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participant might only answer one or zero of the questions, and still able to perform the 
correct use demonstration, or choose to no longer participate in the study. In the 
occurrence of this intercurrent event, the endpoint will be the percentage of participants 
who rate the ability to tell how many puffs are left in the ELLIPTA DPI as easy after the 
study period at V2, where those who rate the ease of telling the number of puffs 
remaining in the ELLIPTA DPI as “hard” comprise of the participants who answered the 
question as “hard” and those who did not answer the ease of number of puffs question. A 
footnote will be included on displays to indicate this composite endpoint, if this 
intercurrent event should occur.
If a participant withdraws from the study, or a parent no longer consents their child 
before the questionnaire can be started, then they will be deemed an early withdrawal and 
no data will be collected for this endpoint.
7.3.4.2.
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.
The population of interest will be based on the Modified Intent-to-Treat population.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. Participants who make it to V2 will be randomised to a version of the ease of use 
questionnaire and asked to complete the questionnaire. The parent/guardian will also be
given the same version (A or B) of their own questionnaire. The parent’s questionnaire 
contains two questions, and these relate to: the ease or difficulty of telling how many 
doses were left in the ELLIPTA DPI, and whether you would be likely to request your 
child’s asthma medication in the ELLIPTA DPI if it were available. Similarly, as the 
participant, the parent is expected to fully complete the questionnaire, however there is a 
possibility the parent might only answer one or zero of the questions or choose to no 
longer allow their child to participate in the study. In the occurrence of this intercurrent 
event, the endpoint will be 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, where those who rate the ease of telling the number of doses 
remaining in the ELLIPTA DPI other than “easy” or “very easy” comprise of the 
participants parents who answered the question as “hard” or “very hard” and those who 
did not answer the ease of number of doses question. These parents will be grouped as 
“Hard/Very Hard” i.e. those parents who do not answer the question will contribute to the 
overall denominator of the population. A footnote will be included on displays to indicate 
this composite endpoint, if this intercurrent event should occur.
If a participant withdraws from the study, or a parent no longer consents their child
before the questionnaire can be started, then they will be deemed an early withdrawal and 
no data will be collected for this endpoint.


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7.3.4.3.
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.
The population of interest will be based on the Modified Intent-to-Treat population.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. This endpoint will use the same strategy as detailed in 7.3.4.2. In the occurrence of 
this intercurrent event, the endpoint will be 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, where those who answer the second question of the ease 
of use questionnaire other than “likely” or “very likely” comprise of the participants 
parents who answered the question as “unlikely” or “very unlikely” and those who did 
not answer the second ease of use question. These parents will be grouped as 
“Unlikely/Very Unlikely”. i.e. those parents who do not answer the question will 
contribute to the overall denominator of the population. A footnote will be included on 
displays to indicate this composite endpoint, if this intercurrent event should occur.
If a participant withdraws from the study, or a parent no longer consents their child 
before the questionnaire can be started, then they will be deemed an early withdrawal and 
no data will be collected for this endpoint.
7.3.4.4.
Percentage of participants from each stratum who demonstrate correct 
use after the study period at V2 with assistance from parents/guardians
The population of interest will be based on the Modified Intent-to-Treat population.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. Participants who make it to V2 will be randomised to a version of the ease of use 
questionnaire, asked to complete the questionnaire and then will perform a demonstration 
of correct use of the ELLIPTA DPI. After a participant has performed the demonstration 
of correct use, they will either have performed it correctly and finish the study or have 
not demonstrated correct use and will be asked to try again with the assistance of their 
parent/guardian. A similar strategy will be applied for this intercurrent event as detailed 
in 7.1.4.1. In the occurrence of this intercurrent event, the endpoint will be the percentage 
of participants from each stratum who demonstrate correct use of the ELLIPTA DPI after 
the study period at V2 with assistance from parents/guardians, where those who are 
deemed “not correct use” will comprise of the participants who did not demonstrate 
correct use of the ELLIPTA DPI and those who did not complete the demonstration of 
correct use. A footnote will be included on displays to indicate this composite endpoint, if 
this intercurrent event should occur.
If a participant withdraws from the study, or a parent no longer consents their child 
before the correct use demonstration can be started, then they will be deemed an early 
withdrawal and no data will be collected for this endpoint.


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7.3.4.5.
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.
The population of interest will be based on the Modified Intent-to-Treat population.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. This endpoint only considers the first correct use attempt at visit 2, and not both 
correct use attempts (i.e. the second attempt with the assistance from the parent/guardian 
is not included). A similar strategy for this incurrent event will be applied as detailed in 
7.2.4.4. In the occurrence of this intercurrent event, the endpoint will be 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. If a participant withdraws at any point 
throughout the correct use demonstration and performed a critical error, then the 
participant will be deemed as one who performed at least one critical error. If the 
participant withdraws at any point throughout the correct use demonstration and did not 
perform all the critical error items, then taking the conservative approach, the participant 
will also be deemed as one who performed at least one critical error. If the participant 
withdraws at any point during the correct use demonstration and performs all critical 
error items correctly, then the participant will be deemed as one who did not perform at 
least one critical error. A footnote will be included on displays to indicate this composite 
endpoint, if this intercurrent event should occur.
If a participant withdraws from the study, or a parent no longer consents their child 
before the correct use demonstration can be started, then they will be deemed an early 
withdrawal and no data will be collected for this endpoint.
7.3.4.6.
Percentage of participants who made at least one critical error during 
use of the ELLIPTA DPI after initial training from HCP at V1.
The population of interest will be based on the Intent-to-Treat population.
The “Composite” strategy will be used for the “Early withdrawal from study” intercurrent 
event. A similar strategy for this incurrent event will be applied as detailed in 7.2.4.4. In 
the occurrence of this intercurrent event, the endpoint will be the percentage of 
participants who made at least one critical error during use of the ELLIPTA DPI after 
initial training from HCP at V1. If a participant withdraws at any point throughout the 
correct use demonstration and performed a critical error, then the participant will be 
deemed as one who performed at least one critical error. If the participant withdraws at 
any point throughout the correct use demonstration and did not perform all the critical 
error items, then taking the conservative approach, the participant will also be deemed as 
one who performed at least one critical error. If the participant withdraws at any point 
during the correct use demonstration and performs all critical error items correctly, then 
the participant will be deemed as one who did not perform at least one critical error. A 
footnote will be included on displays to indicate this composite endpoint, if this 
intercurrent event should occur.


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If a participant withdraws from the study, or a parent no longer consents their child 
before the correct use demonstration can be started, then they will be deemed a screen 
failure and no data will be collected for this endpoint.
7.3.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 7.3.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.
7.3.5.1.
Statistical Methodology Specification
7.3.5.1.1.
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
Endpoint / Variables

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
Model Specification

The endpoint of 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 will be 
analysed using the Modified Intent-to-Treat population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI
Model Results Presentation

The percentage will be reported for the single treatment group along with a 95% confidence 
interval (CI) for the percentage, calculated using the exact binomial distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the primary composite estimand display, an observed data 
display with no imputation may be presented if a substantial amount (10% of the total 
population) of participants do not answer ease of use questionnaire. This display will include 
the number of puffs question completers only.


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7.3.5.1.2.
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.
Endpoint / Variables

The percentage of participants 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.
Model Specification

The endpoint of the percentage of participants 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 will be analysed using the Modified Intent-to-Treat population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI
Model Results Presentation

The percentage will be reported for the single treatment group along with a 95% confidence 
interval (CI) for the percentage, calculated using the exact binomial distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the primary composite estimand display, an observed data 
display with no imputation may be presented if a substantial amount (10% of the total 
population) of participants parents/guardians do not answer ease of use questionnaire. This 
display will include the number of doses question completers only.

It is required for the parent/guardian who attends visit 2 to have also attended visit 1. A 
sensitivity analysis may be presented if a substantial amount (10% of the total population) of 
participants parents/guardians who attend visit 2 are not the same as those who attended visit 
1. This display will only include the results of those parents/guardians who attended both study 
visits.
7.3.5.1.3.
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.
Endpoint / Variables

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.
Model Specification

The endpoint of the 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 will be analysed using the Modified 


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Intent-to-Treat population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI
Model Results Presentation

The percentage will be reported for the single treatment group along with a 95% confidence 
interval (CI) for the percentage, calculated using the exact binomial distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the primary composite estimand display, an observed data 
display with no imputation may be presented if a substantial amount (10% of the total 
population) of participants parents/guardians do not answer ease of use questionnaire. This 
display will include the current daily inhaled medication question completers only.

It is required for the parent/guardian who attends visit 2 to have also attended visit 1. A 
sensitivity analysis may be presented if a substantial amount (10% of the total population) of 
participants parents/guardians who attend visit 2 are not the same as those who attended visit 
1. This display will only include the results of those parents/guardians who attended both study 
visits.
7.3.5.1.4.
Percentage of participants from each stratum who demonstrate correct 
use after the study period at V2 with assistance from parents/guardians
Endpoint / Variables

The percentage of participants from each stratum who demonstrate correct use after the study 
period at V2 with assistance from parents/guardians.
Model Specification

The endpoint of the participants from each stratum who demonstrate correct use after the 
study period at V2 with assistance from parents/guardians will be analysed using the Modified 
Intent-to-Treat population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI
Model Results Presentation

The percentage will be reported for the single treatment group along with a 95% confidence 
interval (CI) for the percentage, calculated using the exact binomial distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the composite estimand display, an observed data display with 
no imputation may be presented if a substantial amount (10% of the total population) of 
participants do not complete the correct use demonstration. This display will include the correct 
use demonstration completers only.

It is required for the parent/guardian who attends visit 2 to have also attended visit 1. A 
sensitivity analysis may be presented if a substantial amount (10% of the total population) of 
participants parents/guardians who attend visit 2 are not the same as those who attended visit 


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1. This display will only include the results of those parents/guardians who attended both study 
visits.
7.3.5.1.5.
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.
Endpoint / Variables

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.
Model Specification

The endpoint of the participants from each stratum who made at least one critical error during 
use of the ELLIPTA DPI after the study period at V2 will be analysed using the Modified Intent-
to-Treat population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI
Model Results Presentation

The percentage will be reported for the single treatment group along with a 95% confidence 
interval (CI) for the percentage, calculated using the exact binomial distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the composite estimand display, an observed data display with 
no imputation may be presented if a substantial amount (10% of the total population) of 
participants do not complete the correct use demonstration. This display will include the correct 
use demonstration completers only.
7.3.5.1.6.
Percentage of participants who made at least one critical error during 
use of the ELLIPTA DPI after initial training from HCP at V1.
Endpoint / Variables

The percentage of participants who made at least one critical error during use of the ELLIPTA 
DPI after initial training from HCP at V1.
Model Specification

The endpoint of the participants who made at least one critical error during use of the ELLIPTA 
DPI after initial training from HCP at V1 will be analysed using the Modified Intent-to-Treat 
population.

This endpoint will be analysed using the exact binomial distribution to calculate the 
95% CI
Model Results Presentation

The percentage will be reported for the single treatment group along with a 95% confidence 


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interval (CI) for the percentage, calculated using the exact binomial distribution.
Sensitivity and Supportive Analyses

Observed analyses: Along with the composite estimand display, an observed data display with 
no imputation may be presented if a substantial amount (10% of the total population) of 
participants do not complete the correct use demonstration. This display will include the correct 
use demonstration completers only.
8.
SAFETY ANALYSES
The safety analyses will be based on the ITT population, unless otherwise specified.
8.1.
Adverse Events
Adverse events analyses including summaries of adverse events (AEs), serious adverse 
events (SAEs) and any other significant AE’s will be based on the GSK Core Data 
Standards. 
Considering this is a placebo only ELLIPTA DPI study and no active drug is being 
prescribed, the summaries will be presented for all participants combined regardless of 
their randomised questionnaire version. The details of the planned analyses are provided 
in Appendix 10: List of Data Displays
A summary of the following AEs and SAEs will be provided:

Any AE or SAE (pre-treatment (SAE only), on-treatment or post-treatment)]

Any on-treatment drug related AE

Any on-treatment non-serious AE

Any AE (pre-treatment or on-treatment) leading to permanent discontinuation of 
study treatment or withdrawal from the study

Any fatal AE

Any non-fatal SAE

Any on-treatment non-fatal drug related SAE

Any on-treatment fatal drug related SAE
The numbers and percentage of participants will all AEs (regardless of causality) will be 
summarised by system organ class (SOC) and preferred term (PT). The ordering of the 
SOCs and PTs will be in descending order of total incidence. A SOC will not be 
presented if the overall incidence for AE within the particular system. If the total 
incidence for any two or more AEs is equal, the events will be presented in alphabetical 
order. 
8.2.
Adverse Events of Special Interest Analyses
No AE of special interest analysis will be performed as no active drug is prescribed in 
this study.


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9.
REFERENCES
GlaxoSmithKline Document Number 2017N346371_00 Study ID 206924. 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. 
Report Date 23-Jan-2018.


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10.
APPENDICES
10.1.
Appendix 1: Protocol Deviation Management
The full list of protocol deviations collected on the eCRF is in the Protocol Deviation 
Management Plan (PDMP). Please refer to this document for current guidance. 
10.1.1.
Exclusions from Per Protocol Population
There is no Per Protocol population in this study.


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10.2.
Appendix 2: Schedule of Activities
10.2.1.
Protocol Defined Schedule of Events
Procedure
Visit 0-
Screeni
ng 
(up to 
30 days 
before 
Day 1)
Treatment Period
Notes
Visit 1 
(can 
occur on 
same day 
as 
screenin
g)
Early 
Withdra
wal
Visit 2
Study Day
-30
1
29 ± 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 in 
the Protocol).
Questionnaires and Assessments
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.


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Procedure
Visit 0-
Screeni
ng 
(up to 
30 days 
before 
Day 1)
Treatment Period
Notes
Visit 1 
(can 
occur on 
same day 
as 
screenin
g)
Early 
Withdra
wal
Visit 2
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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10.3.
Appendix 3: Assessment Windows
10.3.1.
Definitions of Assessment Windows for Analyses
Study day 29 ± 2 (Visit 2, 28 days after Visit 1) is defined as the day of randomisation to 
an ease of use questionnaire.
Analysis Set 
/ Domain
Parameter      
(if applicable)
Target 
Analysis Window
Analysis 
Timepoint
Beginning 
Timepoint
Ending 
Timepoint
All
1
-30
1
Visit 0
All
1
1
1
Visit 1
All
29
27
31
Visit 2
NOTES:

Visit 1 can occur on same day as screening visit (Visit 0)


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10.4.
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events
10.4.1.
Study Phases
Assessments and events will be classified according to the time of occurrence relative to 
study treatment start and stop dates.
Study Phase
Definition
Pre-Treatment 
Date < Study Treatment Start Date
On-Treatment
Study Treatment Start Date ≤ Date ≤ Study Treatment Stop Date + 1
Post-Treatment
Date > Study Treatment Stop Date + 1
10.4.1.1.
Study Phases for Concomitant Medication
Treatment phases for summaries of Asthma and Non-Asthma concomitant medications 
will be defined as follows:
Definition
Treatment Phase
Pre-Treatment
On-Treatment
Post-Treatment
Subject did not take study treatment (e.g, 
screening failures) and conmed stop date > 
date of Screening or variable that asks if 
conmed is on-going (refer hereafter as 
ongoingmed) is “yes”
Y
(Conmed start date < treatment start date or 
variable that asks if medication taken prior to 
study is ”yes”(refer hereafter as priormed)) and 
date of Screening < conmed stop date 
<treatment start date
Y
(Conmed start date < treatment start date or 
priormed is yes) and (treatment start date 
conmed stop date treatment stop date)
Y
Y
(Conmed start date < treatment start date or 
priormed is yes) and (conmed stop date >
treatment stop date or ongoingmed is “yes”)
Y
Y
Y
(Treatment start date conmed start date <
treatment stop date and treatment start date 
conmed stop date treatment stop date) or 
(Treatment start date = conmed start date =
conmed stop date = treatment stop date)
Y
(Treatment start date conmed start date <
treatment stop date) or (Treatment start date =
conmed start date = treatment stop date) and
(conmed stop date > treatment stop date or 
ongoingmed is Yes)
Y
Y


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Definition
Treatment Phase
Pre-Treatment
On-Treatment
Post-Treatment
Conmed start ≥treatment stop date and 
treatment start date ≠ treatment stop date
Y
NOTES: 

A concomitant medication will be classed in every period of the study in which it was taken (e.g., run-in, on- treatment 
or post-treatment).  

See Section 10.7.2.1 for handling of partial dates.

If the study treatment stop date is missing, it will be imputed as described in Section 10.7.

Medications that stopped prior to Screening will not be assigned a treatment phase and will not be summarized.
10.4.2.
Treatment Emergent Flag for Adverse Events
Flag
Definition
Treatment 
Emergent

If AE onset date is on or after Visit 1 start date & on or before Visit 2 stop date.

(Visit 1 Start Date ≤ AE Start Date ≤ Visit 2 Stop Date + 1 day).
NOTES: 

If the study treatment stop date is missing, then the AE will be considered to be On-Treatment.


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10.5.
Appendix 5: Data Display Standards & Handling 
Conventions
10.5.1.
Reporting Process
Software

The currently supported versions of SAS software will be used.
Reporting Area
HARP Server
: UK1SALX00175
HARP Compound
: GSK2285997
QC Spreadsheet
: gsk2285997/mid206924/final_01/documents
Analysis Datasets 

Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.2 & ADaM IG 
Version 1.0.
Generation of RTF Files

RTF files will be generated for use in writing the CSR.
10.5.2.
Reporting Standards
General

The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx):

4.03 to 4.23: General Principles

5.01 to 5.08: Principles Related to Data Listings

6.01 to 6.11: Principles Related to Summary Tables

7.01 to 7.13: Principles Related to Graphics 

Do not include subject level listings in the main body of the GSK Clinical Study Report. All subject level 
listings should be located in the modular appendices as ICH or non-ICH listings
Formats

GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for reporting of 
data based on the raw data collected, unless otherwise stated.

Numeric data will be reported at the precision collected on the eCRF.
Planned and Actual Time

Reporting for tables, figures and formal statistical analyses:

Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated.

The impact of any major deviation from the planned assessment times and/or scheduled visit days 
on the analyses and interpretation of the results will be assessed as appropriate.

Reporting for Data Listings: 

Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1).

Unscheduled or unplanned readings will be presented within the subject’s listings. 
Unscheduled Visits

Unscheduled visits will not be included in summary tables and/or figures.

All unscheduled visits will be included in listings.


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Descriptive Summary Statistics
Continuous Data
Refer to IDSL Statistical Principle 6.06.1
Categorical Data
N, n, frequency, %
Graphical Displays

Refer to IDSL Statistical Principals 7.01 to 7.13.


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10.6.
Appendix 6: Derived and Transformed Data
10.6.1.
General
Study Day

Calculated as the number of days from First Dose Date:

Ref Date = Missing              → Study Day = Missing 

Ref Date < First Dose Date → Study Day = Ref Date – First Dose Date

Ref Data ≥ First Dose Date → Study Day = Ref Date – (First Dose Date) + 1    
10.6.2.
Study Population
Treatment Compliance

For ELLIPTA inhaler, the number of doses of study inhaler taken by each subject will be calculated from 
the dose counter start and stop counts for each inhaler prescribed during the 4-week study period (take 
home period). The derivation for treatment compliance during the 4-week study period is defined as the 
sum of (Dose Counter Start-Dose Counter Stop) over all inhalers dispensed to the participant and 
returned during the 4-week study period. If a dose counter start count is missing, then it will be 
assumed to be 30. If dose counter stop count is non-missing, then the percentage compliance will be 
calculated as:
Where 
is the total number of doses taken from all 
ELLIPTA DPI placebo inhalers in the 4-week study period, and 
and 
are the earliest treatment start date and the latest treatment stop date 
recorded for all of the inhalers used in the calculation.

If the dose counter stop count is missing for the subject, then the treatment compliance will be set to 
missing for that subject.
Extent of Exposure

Number of days of exposure to study drug will be calculated based on the formula:  
Duration of Exposure in Days = Treatment Stop Date – (Treatment Start Date) + 1

Participants who successfully complete the Visit 1 assessments but did not report a treatment start date 
will be categorised as having zero days of exposure. 

If there are any treatment breaks during the study, exposure data will be adjusted accordingly.
10.6.3.
Efficacy
Correct Use Checklist
Demonstrate Correct Use
For a participant to have demonstrated correct use, they need to have a “Yes” to all the correct use checklist 
items recorded:

Participant slides the cover completely down to expose the mouthpiece until a “click” is heard.

Participant does not shake the inhaler

Participant breathes out (exhales) while holding the inhaler away from their mouth

Participant does not breathe into the mouthpiece

Participant places mouthpiece between lips, and closes lips firmly around it.

Participant takes one long steady deep breath in through their mouth


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Correct Use Checklist

Participant does not block air vent with fingers.

Participant removes inhaler from his/her mouth and holds his/her breath

Participant breathes out slowly and gently

Participant closes the inhaler completely
Critical Errors
If a participant has recorded a “No” to any of the following in the correct use checklist items, this is then 
considered a critical error for the ELLIPTA DPI:

Participant slides the cover completely down to expose the mouthpiece until a “click” is heard.

Participant does not shake the inhaler

Participant does not breathe into the mouthpiece

Participant places mouthpiece between lips, and closes lips firmly around it.
Ease of Use Questionnaire
Number of Doses Remaining
The number of participant’s parents/guardians who answer the number of doses question in their respective 
versions of the questionnaire as “Easy” or “Very easy” will be summarised together and presented such as:

Very easy

Easy

Difficult

Very difficult

Very easy/Easy
The 95% confident intervals will be calculated for all the responses listed above using the exact binomial 
distribution. 
Current Inhaled Asthma Medication
The number of participant’s parents/guardians who answer the current inhaled asthma medication question 
in their respective versions of the questionnaire as “Likely” or “Very likely” will be summarised together and 
presented such as:

Very likely

Likely

Unlikely

Very unlikely

Very likely/Likely
The 95% confident intervals will be calculated for all the responses listed above using the exact binomial 
distribution. 
10.6.4.
Safety
Safety is only summarised in this study – no derivations or transformations are required.


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10.7.
Appendix 7: Reporting Standards for Missing Data
10.7.1.
Premature Withdrawals
Element
Reporting Detail
General

Subject study completion (i.e. as specified in the protocol) was defined as one who has 
completed all phases of the study (Visit 0 through Visit 2).

Withdrawn subjects will not be replaced in the study.

All available data from participants who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, unless 
otherwise specified.

Withdrawal visits will be slotted as per Appendix 3: Assessment Windows or will be 
summarised as withdrawal visits.
10.7.2.
Handling of Missing Data
Element
Reporting Detail
General

Missing data occurs when any requested data is not provided, leading to blank fields on 
the collection instrument:
o
These data will be indicated by the use of a “blank” in subject listing displays. 
Unless all data for a specific visit are missing in which case the data is excluded 
from the table. 
o
Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such.
Outliers

Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report.
10.7.2.1.
Handling of Missing and Partial Dates
Element
Reporting Detail
General

Partial dates will be displayed as captured in subject listing displays.
Adverse 
Events

The eCRF allows for the possibility of partial dates (i.e., only month and year) to be 
recorded for AE start and end dates; that is, the day of the month may be missing. In 
such a case, the following conventions will be applied for calculating the time to onset 
and the duration of the event:
o
Missing Start Day: First of the month will be used unless this is before the start 
date of study treatment; in this case the study treatment start date will be used and 
hence the event is considered On-treatment as per Appendix 4: Study Phases and 
Treatment Emergent Adverse Events.
o
Missing Stop Day: Last day of the month will be used, unless this is after the stop 
date of study treatment; in this case the study treatment stop date will be used.

Completely missing start or end dates will remain missing, with no imputation applied. 
Consequently, time to onset and duration of such events will be missing.

Start or end dates which are completely missing (i.e. no year specified) will remain 
missing, with no imputation applied.
Concomitant 
Medications/
Medical 
History

Partial dates for any concomitant medications recorded in the CRF will be imputed 
using the following convention:
o
If the partial date is a start date, a '01' will be used for the day and 'Jan' will be 
used for the month.


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Element
Reporting Detail
o
If the partial date is a stop date, a '28/29/30/31' will be used for the day (dependent 
on the month and year) and 'Dec' will be used for the month.

The recorded partial date will be displayed in listings.


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10.8.
Appendix 8: Values of Potential Clinical Importance
10.8.1.
Vital Signs
Height, weight, gestational age and gestational weight will be collected and presented in 
this study.
As this is a placebo only ELLIPTA DPI study, there are no values of potential clinical 
importance.


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10.9.
Appendix 9: Abbreviations & Trade Marks
10.9.1.
Abbreviations
Abbreviation
Description
ADaM
Analysis Data Model
AE
Adverse Event
ASE
All Subjects Enrolled
A&R
Analysis and Reporting 
CDISC
Clinical Data Interchange Standards Consortium
CI
Confidence Interval
CS
Clinical Statistics
CSR
Clinical Study Report
DBF
Database Freeze
DBR
Database Release
DOB
Date of Birth
DP
Decimal Places
DPI
Dry Powder Inhaler
eCRF
Electronic Case Record Form
GSK
GlaxoSmithKline
ICF
Informed Consent Form
ICH
International Conference on Harmonization
IDMC
Independent Data Monitoring Committee 
IDSL
Integrated Data Standards Library
IMMS
International Modules Management System
IP
Investigational Product
ITT
Intent-To-Treat
MITT
Modified Intent-to-Treat
PDMP
Protocol Deviation Management Plan
QC
Quality Control
RAP
Reporting & Analysis Plan
RAMOS
Randomization & Medication Ordering System 
SAC
Statistical Analysis Complete
SDTM
Study Data Tabulation Model
SOP
Standard Operation Procedure
TA
Therapeutic Area
TFL
Tables, Figures & Listings 
10.9.2.
Trademarks
Trademarks of the GlaxoSmithKline 
Group of Companies
Trademarks not owned by the 
GlaxoSmithKline Group of Companies
ELLIPTA
SAS


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10.10.
Appendix 10: List of Data Displays
10.10.1.
Data Display Numbering
The following numbering will be applied for RAP generated displays:
Section
Tables
Figures
Study Population
1.1 to 1.29
N/A
Efficacy
2.1 to 2.16
2.1 to 2.4
Safety
3.1 to 3.16
N/A
Section
Listings
ICH Listings
1 to 20
Other Listings
21 to 32
10.10.2.
Mock Example Shell Referencing
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in Appendix 11: Example Mock Shells for Data Displays 
Section
Figure
Table
Listing
Study Population
N/A
POP_Tn
POP_Ln
Efficacy
EFF_Fn
EFF_Tn
EFF_Ln
Safety
N/A
SAFE_Tn
SAFE_Ln
NOTES: 

Non-Standard displays are indicated in the ‘IDSL /  Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’
10.10.3.
Deliverables
Delivery [Priority] [1]
Description
Dry Run [1]
Dry Run Deliverable before DBR
SAC [2]
Final Statistical Analysis Complete
NOTES: 
1.
Indicates priority (i.e. order) in which displays will be generated for the reporting effort


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10.10.4.
Study Population Tables
Study Population Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.1.
ASE
SP1
Summary of Study Populations
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.2.
ASE
ES6
Summary of Screening Status and Reasons for Screen Failure
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.3.
ASE
NS1
Summary of Number of Participants by Country and Site ID
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.4.
ITT
Non-standard 
POP_T1
Summary of Attendance at Each Clinical Visit
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.5.
ITT
SD1
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.6.
ITT
ES1
Summary of End of Study Record
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.7.
ITT
ES4
Summary of Participant Disposition at Each Epoch
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
Protocol Deviations
1.8.
ASE
DV1
Summary of Important Protocol Deviations – All Subjects 
Enrolled Population
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.9.
ASE
IE1
Summary of Inclusion/Exclusion/Randomisation Criteria
Deviations – All Subjects Enrolled Population
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.10.
ITT
DV1
Summary of Important Protocol Deviations – Intent-to-Treat 
Population
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]


CONFIDENTIAL
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54
Study Population Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
1.11.
ITT
IE1
Summary of Inclusion/Exclusion/Randomisation Criteria 
Deviations - Intent-to-Treat Population
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
Population Analysed
1.12.
ITT
SP2
Summary of Exclusions from the Modified Intent-to-Treat 
Population
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
Demographic and Baseline Characteristics
1.13.
ITT
DM1 
Summary of Demographic Characteristics
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.14.
ASE
DM11
Summary of Age Ranges
Present Total Column only
Dry Run[1]
SAC[2]
1.15.
ITT
DM5
Summary of Race and Racial Combinations
Present Total Column only
Dry Run[1]
SAC[2]
1.16.
ITT
DM6
Summary of Race and Racial Combinations Details
Present Total Column only
Dry Run[1]
SAC[2]
1.17.
ITT
Non-standard 
POP_T5
Summary of Subgroups
Present by 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
Medical Conditions & Concomitant Medications
1.18.
ITT
MH4
Summary of Current Medical Conditions
Present Total Column only
Dry Run[1]
SAC[2]
1.19.
ITT
MH4
Summary of Past Medical Conditions
Present Total Column only
Dry Run[1]
SAC[2]


CONFIDENTIAL
206924
55
Study Population Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
1.20.
ITT
Non-standard 
POP_T2
Summary of Duration of Asthma and Asthma Exacerbation 
History at Screening
Present Total Column only
Dry Run[1]
SAC[2]
1.21.
ITT
CM1
Summary of Pre-Treatment Asthma Concomitant Medications
Present 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.22.
ITT
CM1
Summary of Pre-Treatment Non-Asthma Concomitant 
Medications
Present 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.23.
ITT
CM1
Summary of On-Treatment Asthma Concomitant Medications
Present 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.24.
ITT
CM1
Summary of On-Treatment Non-Asthma Concomitant 
Medications
Present 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.25.
ITT
CM1
Summary of Post-Treatment Asthma Concomitant Medications
Present 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.26.
ITT
CM1
Summary of Post-Treatment Non-Asthma Concomitant 
Medications
Present 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
Exposure and Treatment Compliance
1.27.
ITT
Non-standard 
POP_T3
Summary of Exposure to Study Treatment
Present 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]
1.28.
ITT
Non-standard 
POP_T4
Summary of Study Compliance
Present 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]


CONFIDENTIAL
206924
56
Study Population Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Summary of Intercurrent Events
1.29.
ITT
Non-standard 
POP_T6
Summary of Intercurrent Events
Present 5-7 year, 8-11 year, Total 
columns
Dry Run[1]
SAC[2]


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57
10.10.5.
Efficacy Tables
Efficacy: Tables
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Correct Use
2.1.
ITT
EFF_T1
Summary of the Number of Completers of the Correct Use 
Demonstration at Visit 1
Dry Run [1]
SAC [2]
2.2.
ASE
EFF_T11
Summary of Number of Attempts to Demonstrate Correct Use of 
ELLIPTA at Visit 1 – All Subjects Enrolled
Present 5-7 year, 8-11 year, Total 
columns
Note: Attempts 1, 2 and 3 the 
Healthcare Professional trains the 
participant in correct use of the 
ELLIPTA DPI. Attempts 4 and 5 the 
parents/guardians assist the participant 
in demonstrating correct use of the 
ELLIPTA DPI.
Programming Note: Percentages are 
based on the subjects who attempted to 
demonstrate correct use, not Big N.
Dry Run [1]
SAC [2]
2.3.
ITT
EFF_T11
Summary of Number of Attempts to Demonstrate Correct Use of 
ELLIPTA at Visit 1 – Intent-to-Treat Population
Present 5-7 year, 8-11 year, Total 
columns
Note: Attempts 1, 2 and 3 the 
Healthcare Professional trains the 
participant in correct use of the 
ELLIPTA DPI. Attempts 4 and 5 the 
parents/guardians assist the participant 
in demonstrating correct use of the 
ELLIPTA DPI.
Programming Note: Percentages are 
based on the subjects who attempted to 
demonstrate correct use, not Big N.
Dry Run [1]
SAC [2]


CONFIDENTIAL
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Efficacy: Tables
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.4.
ITT
EFF_T2
Summary of Correct Use at Visit 1
Repeat for attempts 2 to 5.
Dry Run[1]
SAC [2]
2.5.
ITT
EFF_T10
Summary of Critical Errors at Visit 1
Repeat for attempts 2 to 5.
Dry Run[1]
SAC [2]
2.6.
MITT
EFF_T1
Summary of the Number of Completers of the Correct Use 
Demonstration at Visit 2
Dry Run [1]
SAC [2]
2.7.
MITT
EFF_T2
Summary of Correct Use at Visit 2
Repeat for attempt 2
Dry Run [1]
SAC [2]
2.8.
ITT
EFF_T10
Summary of Critical Errors at Visit 2
Repeat for attempt 2
Dry Run [1]
SAC [2]
2.9.
MITT
EFF_T11
Summary of Number of Attempts to Demonstrate Correct Use of 
ELLIPTA at Visit 2
Present 5-7 year, 8-11 year, Total 
columns
Programming Note: Only include 
Number of Attempts: 1, 2 or Did not 
perform correct use after 2 attempts.
Note: Attempt 1 the participant attempts 
to demonstrate correct use of the 
ELLIPTA DPI. Attempt 2 the 
parents/guardians assist the participant 
in demonstrating correct use of the 
ELLIPTA DPI.
Programming Note: Percentages are 
based on the subjects who attempted to 
demonstrate correct use, not Big N.
Dry Run [1]
SAC [2]
Ease of Use at Visit 2
2.10.
MITT
EFF_T9
Summary of the Number of Completers of the Ease of Use 
Questionnaire at Visit 2
Dry Run [1]
SAC [2]


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206924
59
Efficacy: Tables
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.11.
MITT
EFF_T3
Summary of Participants Ease of Use at Visit 2
Present by: “Questionnaire: Overall, 
Version A, Version B”
Dry Run [1]
SAC [2]
2.12.
MITT
EFF_T4
Summary of Parent/Guardians Ease of Use at Visit 2
Present by: “Questionnaire: Overall, 
Version A, Version B”
Dry Run [1]
SAC [2]
Protocol Defined Endpoints for Correct Use and Ease of Use
2.13.
MITT
EFF_T5
Summary of Protocol Defined Endpoints for Correct Use and 
Ease of Use at Visit 2 by Age Stratum
Dry Run [1]
SAC [2]
2.14.
MITT
EFF_T6
Summary of Protocol Defined Endpoints for Correct Use and 
Ease of Use at Visit 2
Dry Run [1]
SAC [2]
2.15.
ITT
EFF_T7
Summary of Protocol Defined Endpoints for Correct Use at End 
of Visit 1 by Age Stratum
Dry Run [1]
SAC [2]
2.16.
ITT
EFF_T8
Summary of Protocol Defined Endpoints for Correct Use at End 
of Visit 1
Dry Run [1]
SAC [2]


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60
10.10.6.
Efficacy Figures
Efficacy: Tables
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Correct Use
2.1.
ITT
EFF_F1
Summary of Correct Use at Visit 1
Present Age Stratum: 5-7 Year Old, 8-
11 Year Old on one page, and Total 
Population on the second page
Note: Attempts 1, 2 and 3 the 
Healthcare Professional trains the 
participant in correct use of the 
ELLIPTA DPI. Attempts 4 and 5 the 
parents/guardians assist the participant 
in demonstrating correct use of the 
ELLIPTA DPI.
Dry Run [1]
SAC [2]
2.2.
MITT
EFF_F1
Summary of Correct Use at Visit 2
Present Age Stratum: 5-7 Year Old, 8-
11 Year Old on one page, and Total 
Population on the second page
Present only Attempts “Overall”, “1” and 
“2”
Note: Attempt 1 the participant attempts 
to demonstrate correct use of the 
ELLIPTA DPI. Attempt 2 the 
parents/guardians assist the participant 
in demonstrating correct use of the 
ELLIPTA DPI.
Dry Run [1]
SAC [2]


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61
Efficacy: Tables
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.3.
MITT
EFF_F2
Summary of Participant’s Ease of Use at Visit 2
Present Age Stratum: 5-7 Year Old, 8-
11 Year Old on one page, and Total 
Population on the second page
Replace “Number of Doses” and 
“Request the ELLIPTA” with “Ease of 
Use” and Number of Puffs”.
Include footnotes:
Ease of Use: Responder is defined as 
the number of participants who rate the 
use of ELLIPTA as easy
Number of Puffs: Responder is defined 
as the number of participants who rate 
the ability to tell how many doses are 
remaining in the ELLIPTA as easy
Dry Run [1]
SAC [2]
2.4.
MITT
EFF_F2
Summary of Parent/Guardian’s Ease of Use at Visit 2
Present Age Stratum: 5-7 Year Old, 8-
11 Year Old on one page, and Total 
Population on the second page.
Dry Run [1]
SAC [2]


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10.10.7.
Safety Tables
Safety: Tables
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events
3.1.
ITT
AE13
Adverse Event Overview
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.2.
ITT
AE1
Summary of Adverse Events by System Organ Class and 
Preferred Term
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.3.
ITT
AE1
Summary of On-Treatment Adverse Events by System Organ 
Class and Preferred Term
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.4.
ITT
AE1
Summary of Drug-Related Adverse Events
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.5.
ITT
AE1
Summary of Non-Serious Drug Related Adverse Events
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.6.
ITT
AE3
Summary of Common (>=3%) Adverse Events by Overall 
Frequency
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.7.
ITT
AE15
Summary of Common (>=3%) On-Treatment Non-Serious 
Adverse Events by Overall Frequency (Number of Subjects and 
Occurrences)
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.8.
ITT
AE15
Summary of Common (>=3%) Non-Serious Adverse Events by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences)
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]


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63
Safety: Tables
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.9.
ITT
AE15
Summary of Common (>=3%) On-Treatment Drug Related 
Adverse Events by Overall Frequency (Number of Subjects and 
Occurrences)
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.10.
ASE
AE16
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Subjects and Occurrences)
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.11.
ITT
AE16
Summary of On-Treatment Serious Adverse Events by System 
Organ Class and Preferred Term (Number of Subjects and 
Occurrences)
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.12.
ITT
AE1
Summary of Serious Drug Related Adverse Events
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.13.
ITT
AE1
Summary of On-Treatment Adverse Events Leading to
Permanent Discontinuation of Study Drug or Withdrawal
from the Study
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.14.
ITT
AE15
Summary of Common (>=3%) On-Treatment Serious Adverse 
Events by Overall Frequency (Number of Subjects and 
Occurrences)
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
3.15.
ITT
AE1
Summary of Fatal Adverse Events
Present Total column only
Note: All participants received placebo 
only ELLIPTA DPI Inhalers.
Dry Run [1]
SAC [2]
Exacerbations
3.16.
ITT
SAFE_T1
Summary of On-Treatment Asthma Exacerbations
Present Total column only
If more than 10 Asthma exacerbations 
are recorded, then present the 
summary, otherwise present listing 
only.
Dry Run [1]
SAC [2]


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10.10.8.
ICH Listings
ICH Listings
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Study Population
Subject Disposition
1.
ASE
ES7
Listing of Reasons for Screen Failure
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
2.
ITT
ES2
Listing of Reasons for Study Withdrawal
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
3.
ITT
SD2
Listing of Reasons for Study Treatment Discontinuation
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
4.
MITT
TA1
Listing of Planned and Actual Ease of Use Questionnaire
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
Protocol Deviations
5.
ITT
DV2
Listing of Important Protocol Deviations
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
6.
ITT
IE3
Listing of Inclusion/Exclusion/Randomisation Criteria Deviations
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]


CONFIDENTIAL
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65
ICH Listings
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
7.
ASE
SP3
Listing of Participants Excluded from the Modified Intent-to-Treat 
Population
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
Demography
8.
ASE
DM2
Listing of Demographic Characteristics
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column.
Programming Note: Include gestational 
age, gestational weight and country as 
the optional measurements.
Dry Run [1]
SAC [2]
9.
ITT
DM9
Listing of Race
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column.
Dry Run [1]
SAC [2]
Exposure
10.
ITT
EX3
Listing of Exposure Data
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column.
Dry Run [1]
SAC [2]
Concomitant Medications
11.
ITT
CM3
Listing of Concomitant Medications
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column.
Include columns: “Pre-Treatment” “On-
Treatment” “Post-Treatment”
Dry Run [1]
SAC [2]


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66
ICH Listings
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Safety
Adverse Events
12.
ITT
AE8
Listing of All Adverse Events
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
13.
ITT
AE7
Listing of Subject Numbers for Individual Adverse Events
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
14.
ITT
AE2
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
15.
ITT
AE8
Listing of Adverse Events Leading to Permanent Discontinuation 
of Study Treatment or Withdrawal from Study
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
16.
ITT
AE8
Listing of All Serious Adverse Events
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
17.
ITT
AE8
Listing of Fatal Serious Adverse Events
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]


CONFIDENTIAL
206924
67
ICH Listings
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
18.
ITT
AE8
Listing of Non-Fatal Serious Adverse Events
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
19.
ITT
AE8
Listing of Reasons for Considering as a Serious Adverse Event
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]
20.
ITT
AE8
Listing of Other Significant Adverse Events
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column. 
Dry Run [1]
SAC [2]


CONFIDENTIAL
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68
10.10.9.
Non-ICH Listings
Non-ICH Listings
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Study Population
Subject Disposition
21.
ASE
Non-Standard 
POP_L4
Listing of Participants by Country and Site IDs
Dry Run [1]
SAC [2]
Compliance
22.
ITT
Non-Standard 
POP_L1
Listing of Treatment Compliance
Dry Run [1]
SAC [2]
Medical Conditions & Concomitant Medications
23.
ITT
MH2
Listing of Medical Conditions
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column.
Dry Run [1]
SAC [2]
24.
ITT
CM6
Relationship between ATC Level 1, Ingredient and Verbatim text
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column.
Dry Run [1]
SAC [2]
25.
ITT
Non-Standard 
POP_L2
Listing of Asthma History and Asthma Exacerbation History
Dry Run [1]
SAC [2]
Correct Use at Visit 1
26.
ITT
Non-Standard 
POP_L3
Listing of Correct Use at Visit 1
Dry Run [1]
SAC [2]


CONFIDENTIAL
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69
Non-ICH Listings
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Safety
Adverse Events
27.
ITT
Non-Standard 
SAFE_L1
Listing of Asthma Exacerbations
Dry Run [1]
SAC [2]
28.
ITT
Non-Standard 
SAFE_L2
Listing of Deaths
Programming Note: If IDSL shell 
includes a treatment column, replace 
treatment column with “Age Stratum” 
column.
Dry Run [1]
SAC [2]
Efficacy
Correct Use at Visit 2
29.
MITT
Non-standard 
EFF_L1
Listing of Correct Use at Visit 2
Dry Run [1]
SAC [2]
Ease of Use
30.
MITT
Non-standard 
EFF_L2
Listing of Ease of Use at Visit 2
Dry Run [1]
SAC [2]
31.
MITT
Non-standard 
EFF_L2
Listing of Parent/Guardian Ease of Use at Visit 2
Footnote:
Q1: How easy or difficult (difficult or 
easy) was it for you to tell how many 
doses were left in the 
ELLIPTA inhaler?
Q2: 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?
Dry Run [1]
SAC [2]


CONFIDENTIAL
206924
70
10.11.
Appendix 11: Example Mock Shells for Data Displays
Example:    POP_T1
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 1.x
Summary of Attendance at Each Clinical Visit
                                                  
5-7 Year        8-11 Year 
Stratum
Stratum
Total
Visit                                                               (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Visit 0 Screening (Can occur on same day as V1)
xxx (xx%)
xxx (xx%)
xxx (xx%)
Visit 1 Assessment (Can occur on same day as V0)
xxx (xx%)
xxx (xx%)
xxx (xx%)
Visit 2 Last Visit/End of Study/Early Withdrawal
xxx (xx%)
xxx (xx%)
xxx (xx%)


CONFIDENTIAL
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71
Example:    POP_T2
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 1.xx
Summary of Asthma History and Asthma Exacerbation History at Screening
                                                  
5-7 Year        8-11 Year 
Stratum
Stratum
Total
                                                                    (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Duration of Asthma
n
xxx
xxx
xxx
< 1 year
xxx (xx%)
xxx (xx%)
xxx (xx%)
>= 1 year to < 3 years
xxx (xx%)
xxx (xx%)
xxx (xx%)
>= 3 years to < 5 years
xxx (xx%)
xxx (xx%)
xxx (xx%)
>= 5 years
xxx (xx%)
xxx (xx%)
xxx (xx%)
Number of exacerbations that required Oral/Systemic 
Corticosteroids and/or antibiotics in the past 12 months
n
xxx
xxx
xxx
0
xxx (xx%)
xxx (xx%)
xxx (xx%)
1
xxx (xx%)
xxx (xx%)
xxx (xx%)
2
xxx (xx%)
xxx (xx%)
xxx (xx%)
>2
xxx (xx%)
xxx (xx%)
xxx (xx%)
Number of exacerbations that required hospitalisation in the
past 12 months
n
xxx
xxx
xxx
0
xxx (xx%)
xxx (xx%)
xxx (xx%)
1
xxx (xx%)
xxx (xx%)
xxx (xx%)
2
xxx (xx%)
xxx (xx%)
xxx (xx%)
>2
xxx (xx%)
xxx (xx%)
xxx (xx%)


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Example:    POP_T3
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 1.xx
Summary of Exposure
                                                  
5-7 Year        8-11 Year 
Stratum
Stratum
Total
                                                                    (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Exposure (days)
n
xxx
xxx
xxx
Mean
xx.x
xx.x
xx.x
SD
xx.xx
xx.xx
xx.xx 
Median
xx.x
xx.x
xx.x
Min.
xx
xx
xx
Max.
xx
xx
xx
Range of exposure (days)
n
xxx
xxx
xxx
< 14
xxx (xx%)
xxx (xx%)
xxx (xx%)
>= 14
xxx (xx%)
xxx (xx%)
xxx (xx%)


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Example:    POP_T4
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 1.xx
Summary of Study Compliance
                                                  
5-7 Year        8-11 Year 
Stratum
Stratum
Total
                                                                    (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Compliance (%)
n
xxx
xxx
xxx
Mean
xx.x
xx.x
xx.x
SD
xx.xx
xx.xx
xx.xx 
Median
xx.x
xx.x
xx.x
Min.
xx
xx
xx
Max.
xx
xx
xx
Compliance category
n
xxx
xxx
xxx
<80%
xxx (xx%)
xxx (xx%)
xxx (xx%)
>=80% to <95%
xxx (xx%)
xxx (xx%)
xxx (xx%)
>=95% to <=105%
xxx (xx%)
xxx (xx%)
xxx (xx%)
>105% to <=120%
xxx (xx%)
xxx (xx%)
xxx (xx%)
>120%
xxx (xx%)
xxx (xx%)
xxx (xx%)
Non-calculable
xxx (xx%)
xxx (xx%)
xxx (xx%)


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Example:    POP_T5
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 1.xx
Summary of Subgroups
                                                  
5-7 Year        8-11 Year 
Stratum
Stratum
Total
                                                                    (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Country
n
  xxx
xxx
  xxx
United States
  xxx (xx%)
xxx (xx%)
  xxx (xx%)
Canada
  xxx (xx%)
xxx (xx%)
  xxx (xx%)
Main Current Asthma Therapy
n
  xxx
xxx
  xxx
Maintenance with/without Rescue
  xxx (xx%)
xxx (xx%)
  xxx (xx%)
Rescue Only
  xxx (xx%)
xxx (xx%)
  xxx (xx%)
Main Current Asthma Therapy Device Type
n
  xxx
xxx
  xxx
DPI
  xxx (xx%)
xxx (xx%)
  xxx (xx%)
MDI
  xxx (xx%)
xxx (xx%)
  xxx (xx%)
Other [1]
  xxx (xx%)
xxx (xx%)
  xxx (xx%)
[1] Other includes ‘device’ types such as Nebuliser, Pill/Tablet etc.


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Example:    POP_T6
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 1.xx
Summary of Intercurrent Events
5-7 Year 
Stratum
8-11 Year 
Stratum
Total
Intercurrent events, n (%)
(N=xxx)
(N=xxx)
(N=xxx)
Any intercurrent event
   n
xx
xx
xx
   Participant not fully completing the correct use demonstration
   at Visit 1
xx (xx%)
xx (xx%)
xx (xx%)
   Participant not fully completing the correct use demonstration
   at Visit 2
xx (xx%)
xx (xx%)
xx (xx%)
   Participant not fully completing the ease of use questionnaire
xx (xx%)
xx (xx%)
xx (xx%)
   Participant’s parents/guardians not fully completing the ease  
   of use questionnaire
xx (xx%)
xx (xx%)
xx (xx%)
   Early discontinuation of study ELLIPTA DPI placebo during the 4 
   week period
xx (xx%)
xx (xx%)
xx (xx%)
   Participant changed their standard Asthma therapy inhaler to 
   one contained in ELLIPTA DPI
xx (xx%)
xx (xx%)
xx (xx%)


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Example:    EFF_T1
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 2.1
Summary of the Number of Completers of the Correct Use Demonstration at Visit 1
Attempt: 1
                                        
5-7 Year        8-11 Year 
Stratum
Stratum
Total
                                                                    (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Number of participants who attempted to demonstrate correct
  xxx
xxx
   xxx
use of the ELLIPTA DPI [1]
Number of participants who completed the ELLIPTA correct
  xxx (xx%)
xxx (xx%)
   xxx (xx%)          
use demonstration [2]
Number of participants who did not fully complete the 
  xxx (xx%)
xxx (xx%)
   xxx (xx%)          
ELLIPTA DPI correct use demonstration [3]
Note: Attempts 1, 2 and 3 the Healthcare Professional trains the participant in correct use of the ELLIPTA 
DPI. Attempts 4 and 5 the parents/guardians assist the participant in demonstrating correct use of the ELLIPTA 
DPI.
[1] The participants who attempted to demonstrate correct use of the ELLIPTA DPI at that attempt.
[2] The participants who completed the correct use demonstration whether they correctly demonstrated or not.
[3] The participants who did not fully perform the correct use demonstration. These participants will be 
assumed to have not demonstrated correct use. 
Programming Note: Repeat for Attempt: 2 to 5.


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Example:    EFF_T2
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 2.2
Summary of Correct Use at Visit 1
Attempt: 1                                                  
5-7 Year        8-11 Year 
Stratum
Stratum
Total
                                                                    (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Number of participants who demonstrated correct use
xxx (xx%)
xxx (xx%)
xxx (xx%)
Number of participants who did not demonstrate correct use
xxx (xx%)
xxx (xx%)
xxx (xx%)
Reasons for incorrect use [1]:
Participant did not slide the cover completely down to expose the 
xxx (xx%)
xxx (xx%)
xxx (xx%)
  mouthpiece until a ‘click’ is heard
Participant did shake the inhaler
xxx (xx%)
xxx (xx%)
xxx (xx%)
Participant did not breathe out (exhales) while holding the inhaler
xxx (xx%)
xxx (xx%)
xxx (xx%)
  away from their mouth
Participant did breathe into the mouthpiece
xxx (xx%)
xxx (xx%)
xxx (xx%)
Participant did not place mouthpiece between lips, and closes 
xxx (xx%)
xxx (xx%)
xxx (xx%)
  firmly around it
Participant did not take one long steady breath in through their 
xxx (xx%)
xxx (xx%)
xxx (xx%)
  mouth
Participant did block the air vent with fingers
xxx (xx%)
xxx (xx%)
xxx (xx%)
Participant did not remove inhaler from his/her mouth and holds 
xxx (xx%)
xxx (xx%)
xxx (xx%)
  his/her breath
Participant did not breathe out slowly and gently
xxx (xx%)
xxx (xx%)
xxx (xx%)
Participant did not close the inhaler completely
xxx (xx%)
xxx (xx%)
xxx (xx%)
Note: Attempts 1, 2 and 3 the Healthcare Professional trains the participant in correct use of the ELLIPTA 
DPI. Attempts 4 and 5 the parents/guardians assist the participant in demonstrating correct use of the ELLIPTA 
DPI.
Note: Participants can be counted more than once depending on the reasons for incorrect use.
[1] Percentage for individual incorrect use reasons are calculated based on number of participants who did not
demonstrate correct use.
Programming note: Repeat for attempts 2 to 5. 


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Example:    EFF_T3
                 Page 1 of n
Protocol:     206924
Population: Modified Intent-to-Treat
Table 2.7
Summary of Participants Ease of Use at Visit 2
Questionnaire: Overall
                                                  
5-7 Year        8-11 Year 
Stratum
Stratum
Total
                                                                    (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Is it easy or hard to use the ELLIPTA inhaler?
n
xxx
xxx 
xxx
Easy
xxx (xx%)
xxx (xx%)
xxx (xx%)
Hard
xxx (xx%)
xxx (xx%)
xxx (xx%)
Is it easy or hard to tell how many puffs are 
n
xxx
xxx 
xxx
left in the ELLIPTA inhaler?
Easy
xxx (xx%)
xxx (xx%)
xxx (xx%)
Hard
xxx (xx%)
xxx (xx%)
xxx (xx%)
Programming note: Repeat for “Questionnaire: Version A, Version B”


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Example:    EFF_T4
                 Page 1 of n
Protocol:     206924
Population: Modified Intent-to-Treat
Table 2.x
Summary of Parent/Guardians Ease of Use at Visit 2
Questionnaire: Overall
                                                  
5-7 Year        8-11 Year 
Stratum
Stratum
Total
                                                                    (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Number of parents who attended the final
n
xxx
xxx 
xxx 
visit also present during the initial
training in Correct Use?
How easy or difficult was it for you to
n
xxx
xxx 
xxx
tell how many doses were left in the 
ELLIPTA inhaler?
Very easy
xxx (xx%)
xxx (xx%)
xxx (xx%)
Easy
xxx (xx%)
xxx (xx%)
xxx (xx%)
Difficult
xxx (xx%)
xxx (xx%)
xxx (xx%)
Very difficult
xxx (xx%)
xxx (xx%)
xxx (xx%)
Very easy/Easy
xxx (xx%)
xxx (xx%)
xxx (xx%)
If your child’s current inhaled asthma 
n
xxx 
xxx
medication was available in the ELLIPTA 
inhaler, how likely would you be to request
the ELLIPTA inhaler from your child’s doctor? Very Likely
xxx (xx%)
xxx (xx%)
xxx (xx%)
Likely
xxx (xx%)
xxx (xx%)
xxx (xx%)
Unlikely
xxx (xx%)
xxx (xx%)
xxx (xx%)
Very unlikely
xxx (xx%)
xxx (xx%)
xxx (xx%)
Very likely/Likely
xxx (xx%)
xxx (xx%)
xxx (xx%)
Programming note: Repeat for “Questionnaire: Version A, Version B”


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Example:    EFF_T5
                
Protocol:     206924
Population: Modified Intent-to-Treat
Table 2.xx
Summary of Protocol Defined Endpoints for Correct Use and Ease of Use at Visit 2 by Age Stratum
                                                                     5-7 Year Stratum    8-11 Year Stratum
                                                                              (N=xxx)              (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Number of participants who demonstrate correct use at Visit 2
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%)
without assistance from their parents/guardians (Attempt #1)
Number of participants who rate the use of ELLIPTA as
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%)
easy, among those who demonstrate correct use of the
inhaler at Visit 2 [1]
Number of participants who rate the ability to tell how many
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%)
doses are remaining in the ELLIPTA as easy at Visit 2
Number of participant’s parents/guardians who rate the ability
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%)
to tell how many doses are remaining in the ELLIPTA as easy
or very easy at Visit 2
Number of participant’s parents/guardians who would be likely or
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%)
very likely to ask their doctor for the ELLIPTA inhaler if the
participants current daily inhaled medication(s) were available
in the ELLIPTA inhaler
Number of participants who demonstrate correct use at Visit 2
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%)
with assistance from their parents/guardians (Attempt #2)
Number of participants who demonstrate correct use at Visit 2
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%)
with or without assistance from their parents/guardians
(Attempt #1 or Attempt #2)


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Number of participants who made at least one critical error
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%)
during the use of the ELLIPTA at Visit 2
[1] The percentage is calculated as “number of participants who rate the ELLIPTA as easy” divided by “number 
of participants who demonstrate correct use at Visit 2 (Attempt #1)” x 100
Note: The 95% CI for the percentages are calculated using the exact binomial distribution.
Programming Note: Please include the following footnotes if any of the composite intercurrent events detailed 
in the body of the RAP occurred during the study:
For correct use endpoints:
[#] Denominator used to calculate percentage and precision intervals includes participants who did not fully 
complete the correct use demonstration and have been deemed as not demonstrating correct use.
For questionnaire endpoints:
[#] Denominator used to calculate percentage and precision include participants who did not answer the 
question and have been deemed as [not rating the ease of use as easy/not rating the ability to tell how many 
doses are remaining in the ELLIPTA as easy/ not rating the ability to tell how many doses are remaining in the 
ELLIPTA as Very easy/easy/ not very likely/likely requesting the participant’s current daily inhaled 
medication in the ELLIPTA inhaler]. [Select the ones that apply and write a new footnote for each one].
For critical error endpoint:
[#] Denominator used to calculate percentage and precision includes participants who did not fully complete 
all the critical error items in the correct use demonstration and have been deemed as performing a critical 
error.


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Example:    EFF_T6
                 Page 1 of n
Protocol:     206924
Population: Modified Intent-to-Treat
Table 2.15
Summary of Protocol Defined Endpoints for Correct Use and Ease of Use at Visit 2
                                                                     
    
Total
                                                                                             
(N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Number of participants who demonstrate correct use at Visit 2
xx (xx%) (xx%, xx%)
without assistance from their parents/guardians (Attempt #1)
Number of participants who rate the use of ELLIPTA as
xx (xx%) (xx%, xx%)
easy, among those who demonstrate correct use of the
inhaler at Visit 2 [1]
Number of participants who rate the ability to tell how many
xx (xx%) (xx%, xx%)
doses are remaining in the ELLIPTA as easy at Visit 2
Number of participant’s parents/guardians who rate the ability
xx (xx%) (xx%, xx%)
to tell how many doses are remaining in the ELLIPTA as easy
or very easy at Visit 2
Number of participant’s parents/guardians who would be likely or
xx (xx%) (xx%, xx%)
very likely to ask their doctor for the ELLIPTA inhaler if the
participants current daily inhaled medication(s) were available
in the ELLIPTA inhaler
Number of participants who demonstrate correct use at Visit 2
xx (xx%) (xx%, xx%)
with assistance from their parents/guardians (Attempt #2)
Number of participants who demonstrate correct use at Visit 2
xx (xx%) (xx%, xx%)
with or without assistance from their parents/guardians
(Attempt #1 or Attempt #2)


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Number of participants who made at least one critical error
xx (xx%) (xx%, xx%)
during the use of the ELLIPTA at Visit 2
[1] The percentage is calculated as “number of participants who rate the ELLIPTA as easy” divided by “number 
of participants who demonstrate correct use at Visit 2 (Attempt #1)” x 100
Note: The 95% CI for the percentages are calculated using the exact binomial distribution.
Programming Note: Please include the following footnotes if any of the composite intercurrent events detailed 
in the body of the RAP occurred during the study:
For correct use endpoints:
[#] Denominator used to calculate percentage and precision intervals includes participants who did not fully 
complete the correct use demonstration and have been deemed as not demonstrating correct use.
For questionnaire endpoints:
[#] Denominator used to calculate percentage and precision include participants who did not answer the 
question and have been deemed as [not rating the ease of use as easy/not rating the ability to tell how many 
doses are remaining in the ELLIPTA as easy/ not rating the ability to tell how many doses are remaining in the 
ELLIPTA as Very easy/easy / not very likely/likely requesting the participant’s current daily inhaled 
medication in the ELLIPTA inhaler]. [Select the ones that apply and write a new footnote for each one].
For critical error endpoint:
[#] Denominator used to calculate percentage and precision includes participants who did not fully complete 
all the critical error items in the correct use demonstration and have been deemed as performing a critical 
error.


CONFIDENTIAL
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Example:    EFF_T7
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 2.xx
Summary of Protocol Defined Endpoints for Correct Use at End of Visit 1 by Age Stratum
                                                                     5-7 Year Stratum    8-11 Year Stratum
                                                                              (N=xxx)               (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Number of participants who demonstrate correct use of the
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%) 
ELLIPTA DPI after initial training from the HCP at Visit 1
(Attempt #1)
Number of participants who demonstrate correct use of the
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%) 
ELLIPTA DPI at Visit 1 (Attempt #1 - #5)
Number of participants who made at least one critical error
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%)
during use of the ELLIPTA DPI after initial training from
HCP at Visit 1 (Attempt #1)
Number of participants who made at least one critical error
xx (xx%) (xx%, xx%)
xx (xx%) (xx%, xx%)
during use of the ELLIPTA DPI at Visit 1 (Attempt #1 - #5)
Note: Attempts 1, 2 and 3 the Healthcare Professional trains the participant in correct use of the ELLIPTA 
DPI. Attempts 4 and 5 the parents/guardians assist the participant in demonstrating correct use of the ELLIPTA 
DPI.
Note: The 95% CI for the percentages are calculated using the exact binomial distribution.
Programming Note: Please include the following footnotes if any of the composite intercurrent events detailed 
in the body of the RAP occurred during the study:
For correct use endpoints:
[#] Denominator used to calculate percentage and precision intervals includes participants who did not fully 
complete the correct use demonstration and have been deemed as not demonstrating correct use.
For critical error endpoint:


CONFIDENTIAL
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[#] Denominator used to calculate percentage and precision includes participants who did not fully complete 
all the critical error items in the correct use demonstration and have been deemed as performing a critical 
error.


CONFIDENTIAL
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Example:    EFF_T8
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 2.xx
Summary of Protocol Defined Endpoints for Correct Use at End of Visit 1
                                                                     
Total
                                                                              
(N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Number of participants who demonstrate correct use of the
xx (xx%) (xx%, xx%) 
ELLIPTA DPI after initial training from the HCP at Visit 1
(Attempt #1)
Number of participants who demonstrate correct use of the
xx (xx%) (xx%, xx%) 
ELLIPTA DPI at Visit 1 (Attempt #1 - #5)
Number of participants who made at least one critical error
xx (xx%) (xx%, xx%)
during use of the ELLIPTA DPI after initial training from the
HCP at Visit 1
Number of participants who made at least one critical error
xx (xx%) (xx%, xx%)
during use of the ELLIPTA DPI at Visit 1 (Attempt #1 - #5)
Note: Attempts 1, 2 and 3 the Healthcare Professional trains the participant in correct use of the ELLIPTA 
DPI. Attempts 4 and 5 the parents/guardians assist the participant in demonstrating correct use of the ELLIPTA 
DPI.
Note: The 95% CI for the percentages are calculated using the exact binomial distribution.
Programming Note: Please include the following footnotes if any of the composite intercurrent events detailed 
in the body of the RAP occurred during the study:
For correct use endpoints:
[#] Denominator used to calculate percentage and precision intervals includes participants who did not fully 
complete the correct use demonstration and have been deemed as not demonstrating correct use.
For critical error endpoint:


CONFIDENTIAL
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[#] Denominator used to calculate percentage and precision includes participants who did not fully complete 
all the critical error items in the correct use demonstration and have been deemed as performing a critical 
error.


CONFIDENTIAL
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Example:    EFF_T9
                 Page 1 of n
Protocol:     206924
Population: Modified Intent-to-Treat
Table 2.xx
Summary of the Number of Completers of the Ease of Use Questionnaire at Visit 2
Questionnaire: Overall
5-7 Year        8-11 Year 
Stratum
Stratum
Total
                                                                    (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Number of participants randomised to an Ease of Use Questionnaire    xxx
xxx
   xxx
   Number of participants who answered the Ease of Use 
   xxx (xx%)
xxx (xx%)
   xxx (xx%)
   question
   Number of participants who did not answer the Ease of Use
   xxx (xx%)
xxx (xx%)
   xxx (xx%)
   question
   Number of participants who answered the number of puffs 
   xxx (xx%)
xxx (xx%)
   xxx (xx%)
   question
   Number of participants who did not answer the number of puffs
   xxx (xx%)
xxx (xx%)
   xxx (xx%)
   question
   Number of participants parents/guardians who answered the
   xxx (xx%)
xxx (xx%)
   xxx (xx%)
   number of doses question
   Number of participants parents/guardians who did not answer
   xxx (xx%)
xxx (xx%)
   xxx (xx%)
   the number of doses question
   Number of participants parents/guardians who answered the
   xxx (xx%)
xxx (xx%)
   xxx (xx%)
   current daily inhaled medication question 
   Number of participants parents/guardians who did not answer
   xxx (xx%)
xxx (xx%)
   xxx (xx%)
   the current daily inhaled medication question
Programming note: Repeat for Questionnaire: Version A and Version B


CONFIDENTIAL
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Example:    EFF_T10
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 2.x
Summary of Critical Errors at Visit 1
Attempt: 1                                                  
5-7 Year        8-11 Year 
Stratum
Stratum
Total
                                                                    (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Number of participants who performed a critical error
xxx (xx%)
xxx (xx%)
xxx (xx%)
Number of participants who did not perform a critical error
xxx (xx%)
xxx (xx%)
xxx (xx%)
Critical errors performed [1]:
Participant did not slide the cover completely down to expose the 
xxx (xx%)
xxx (xx%)
xxx (xx%)
mouthpiece until a ‘click’ is heard
Participant did shake the inhaler
xxx (xx%)
xxx (xx%)
xxx (xx%)
Participant did breathe into the mouthpiece
xxx (xx%)
xxx (xx%)
xxx (xx%)
Participant did not place mouthpiece between lips, and closes 
xxx (xx%)
xxx (xx%)
xxx (xx%)
  firmly around it
Note: Attempts 1, 2 and 3 the Healthcare Professional trains the participant in correct use of the ELLIPTA 
DPI. Attempts 4 and 5 the parents/guardians assist the participant in demonstrating correct use of the ELLIPTA 
DPI.
Note: Participants can be counted more than once depending on the reasons for critical errors performed.
[1] Percentage for individual critical errors performed are calculated based on number of participants who 
performed a critical error.
Programming note: Repeat for attempts 2 to 5.


CONFIDENTIAL
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Example:    EFF_T11
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 2.xx
Summary of Number of Attempts to Demonstrate Correct Use at Visit 1
                                                  
5-7 Year        8-11 Year 
Stratum
Stratum
Total
                                                                    (N=xxx)         (N=xxx)        (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Number of participants who
n
xxx
xxx
xxx
demonstrated correct use
Number of participants who
n
xxx
xxx
xxx
did not demonstrate correct use
Number of attempts to
n
xxx
xxx
xxx
demonstrate correct use:
1
xxx (xx%)
xxx (xx%)
xxx (xx%)
2
xxx (xx%)
xxx (xx%)
xxx (xx%)
3
xxx (xx%)
xxx (xx%)
xxx (xx%)
4
xxx (xx%)
xxx (xx%)
xxx (xx%)
5
xxx (xx%)
xxx (xx%)
xxx (xx%)
Did not demonstrate correct use
xxx (xx%)
xxx (xx%)
xxx (xx%)
after 5 attempts
Note: Attempts 1, 2 and 3 the Healthcare Professional trains the participant in correct use of the ELLIPTA 
DPI. Attempts 4 and 5 the parents/guardians assist the participant in demonstrating correct use of the ELLIPTA 
DPI.


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Example:    EFF_F1
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 2.xx
Summary of Correct Use at Visit 1
Note: Attempts 1, 2 and 3 the Healthcare Professional trains the participant in correct use of the ELLIPTA 
DPI. Attempts 4 and 5 the parents/guardians assist the participant in demonstrating correct use of the ELLIPTA 
DPI.
Programming Note: Present Age Stratum: 5-7 Year Old, 8-11 Year Old on one page, and Total Population on the 
second page.


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Example:    EFF_F2
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 2.xx
Summary of 
Parent/Guardian’s 
Ease of Use at Visit 2
Number of Puffs: Responder is defined as the participant’s parents/guardians who rate the ability to tell how 
many doses are remaining in the ELLIPTA as easy or very easy.
Request the ELLIPTA: Responder is defined as the participant’s parents/guardians who would be likely or very 
likely to ask their doctor for the ELLIPTA inhaler if the participants current daily inhaled medication(s) 
were available in the ELLIPTA inhaler.
Programming Note: Present Age Stratum: 5-7 Year Old, 8-11 Year Old on one page, and Total Population on the 
second page.


CONFIDENTIAL
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Example:    SAFE_T1
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 3.x
Summary of On-Treatment Asthma Exacerbations
                                                       
    Total
                                                                    
      
   (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Number of participants with an Asthma exacerbation
xxx
Total number of Asthma exacerbations per participant
n
xxx
0
xxx (xx%)
1
xxx (xx%)
2
xxx (xx%)
>=3
xxx (xx%)
Total number of Asthma exacerbations 
Total number of exacerbations
xxx
Total number of exacerbations leading to a withdrawal from study
xxx
Treatment [1][2]
Took oral/systemic corticosteroids
xxx (xx%)
Took antibiotics
xxx (xx%)
Visited emergency room
xxx (xx%)
Hospitalised
xxx (xx%)
Intubated
xxx (xx%)
Outcome [1]
Resolved
xxx (xx%)
Fatal
xxx (xx%)
Not resolved
xxx (xx%)


CONFIDENTIAL
206924
94
Example:    SAFE_T1
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Table 3.x
Summary of On-Treatment Asthma Exacerbations
                                                       
   Total
                                                                    
      
   (N=xxx)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Duration of asthma exacerbation (days)
n
xxx
mean
xx.x
SD
xx.xx
median
xx.x
Min.
xx
Max.
xx
[1] Percentages calculated using the total number of Asthma exacerbations as the denominator.
[2] More than one treatment may be selected for a given exacerbation.


CONFIDENTIAL
206924
95
Example:    POP_L1
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Listing x
Listing of Treatment Compliance
Site ID/
Age Stratum
Compliance
Date Placebo
Date Placebo
Dose counter
Total doses    
Unique
(%)
Dispensed
Returned
start/stop
Taken   
Subject ID.   
   
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
xxxxxx/
   5-7 Year Old
xx.x
    DDMMMYYYY
DDMMMYYYY      30/xx
        xx
xxxxxx
.....


CONFIDENTIAL
206924
96
Example:    POP_L2
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Listing x
Listing of Asthma History and Asthma Exacerbation History
                                                    Number of exacerbations in the last 12 months that:
                                              
        Required
             Unique
               oral/systemic corticosteroid    Required
    Site ID  Subject ID.  Age Stratum    Asthma Duration     and/or antibiotics [1]          hospitalisation
    ----------------------------------------------------------------------------------------------------
         xxxxxx
xxxxxx         5-7 Year Old
< 1 year
x
x
.....
[1] Not involving hospitalisation


CONFIDENTIAL
206924
97
Example:    POP_L3
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Listing x
Listing of Correct Use at Visit 1
  
Site ID/
Unique 
Subject ID.
Age Stratum
Date of 
Assessment/
Study Day
Attempt
Demonstrate 
Correct Use?
Reasons for not demonstrating correct use
Xxxxxx/
Xx
5-7 Year-Old
DDMMYYYY/
1
1
Y
None
Xxxxxx/
Xx
5-7 Year-Old
DDMMYYYY/
1
1
2
N
Y
Participant blocked air vent with fingers
None
.....


CONFIDENTIAL
206924
98
POP_L4
Protocol: 206924                             
                                            Page 1 of x
Population: All Subjects Enrolled
Listing xx
Listing of Participants by Country and Site IDs
Country
Site ID.
Investigator
Name
Subject 
Age Stratum
United States
Hoek
5-7 Years Old
Canada
Baker
PPD
PPD


CONFIDENTIAL
206924
99
Example:    EFF_L1
                 Page 1 of n
Protocol:     206924
Population: Modified Intent-to-Treat
Listing x
Listing of Correct Use at Visit 2
Site ID/
Unique 
Subject 
ID.
Age 
Stratum
Date of 
Assessment/
Study Day
Questionnaire 
Version
Attempt
Demonstrate 
Correct 
Use?
Reasons for not 
demonstrating correct use
Xxxxxx/
Xx
5-7 
Year-Old
DDMMYYYY/
27
Version A
1
Y
None
Xxxxxx/
Xx
5-7 
Year-Old
DDMMYYYY/
29
Version B
1
2
N
Y
Participant blocked air 
vent with fingers
None


CONFIDENTIAL
206924
100
Example:    EFF_L2
                 Page 1 of n
Protocol:     206924
Population: Modified Intent-to-Treat
Listing x
Listing of Ease of Use at Visit 2
Site ID
Unique 
Subject ID.
Age 
Stratum
Visit
Date of 
Assessment
Study Day
Questionnaire 
Version
Q1
Q2
Xxxxxx
xxx
5-7 
Year-Old
Day 28
DDMMYYYY
27
Version A
Easy
Easy
Xxxxxx
xxx
5-7 
Year-Old
Day 28
DDMMYYYY
29
Version B
Easy
Hard
Q1: How easy or difficult (difficult or easy) is it to use the ELLIPTA inhaler?
Q2: How easy or difficult (difficult or easy) is it to tell how many puffs are left in the ELLIPTA inhaler?


CONFIDENTIAL
206924
101
Example:    SAFE_L1
                 Page 1 of n
Protocol:     206924
Population: Intent-to-Treat
Listing x
Listing of Asthma Exacerbations
Site ID/
Unique 
Subject ID.
Age Stratum
Date of 
Onset/
Study Day
Date of 
Resolution/
Duration(days)
Severity/
Outcome
Withdrawn due 
to 
Exacerbation
Systemic or Oral 
Corticosteroid/
Antibiotics
Hospitalised/
Emergency 
Room/
Intubated/
X-ray 
performed
Xxxxxx/
xxxx.xxxx
5-7 Year-Old
DDMMMYYY/
xx
DDMMMYY/
xx
Moderate/
Recovered/
Resolved
N
Y/N
N/N/N/N


CONFIDENTIAL
206924
102
Example: SAFE_L2
Protocol: 206924                                                                           Page 1 of 1
Population: Intent-to-Treat
                                                 Listing x
                                             Listing of Deaths
                      Age                                                                          Time
    Site Id./         (YEARS)/                                                         Date of     From
    Unique Subject    Sex/                                                             Death/      Last
    Id.               Race      Primary Cause of Death     Subreason  Specify          Study Day   Dose
    ----------------------------------------------------------------------------------------------------
   
 58/       HAEMORRHAGE                           GASTROINTESTINEL 2015
 9d
   
 M/                                              BLEEDING         210
                      WHITE
PPD
PPD