Clinical trial NCT05535972
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: TRELEGY ELLIPTA Single Inhaler Fluticasone Furoate Umeclidinium Bromide Vilanterol FF/UMEC/VI
Sponsor: GlaxoSmithKline
Start date: 2022-10-14; Completion date: 2023-09-25
Enrollment: 463 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The primary objective of this study is to evaluate the effectiveness of TRELEGY ELLIPTA on health status in participants with symptomatic COPD. The secondary objective is to evaluate the effectiveness of TRELEGY ELLIPTA on dyspnea and lung function in participants with symptomatic COPD. TRELEGY and ELLIPTA are trademarks of the GlaxoSmithKline group of companies.

Detailed description:

Arms: arm 1: Participants will receive FF/UMEC/VI, inhalation powder, once daily, in a single device (TRELEGY ELLIPTA) for 12 weeks.
Interventions: intervention 1: FF/UMEC/VI
Intervention descriptions: intervention 1: FF/UMEC/VI will be administered in a single inhaler Trelegy Ellipta.

Protocol documents:
Prot_000.pdf: 
Protocol Amendment 1
Study ID:  217658
Official Title of Study: A 12-week, Prospective, Open Label, Single Cohort 
Study to Evaluate the Real-world Effectiveness of Fluticasone Furoate/
Umeclidinium Bromide/Vilanterol in a Single Inhaler (Trelegy Ellipta) in 
Symptomatic Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT ID: NCT05535972
Date of Document: 27-Jan-2023


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GlaxoSmithKline group of companies 
 
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CLINICAL STUDY PROTOCOL 
UNIQUE IDENTIFIER 
217658 
TITLE 
A 12-week, prospective, open label, single cohort study 
to evaluate the real-world effectiveness of Fluticasone 
Furoate/Umeclidinium Bromide/Vilanterol in a single 
inhaler (Trelegy Ellipta) in symptomatic chronic 
obstructive pulmonary disease (COPD) patients. 
STUDY ACCOUNTABLE 
PERSON 
CONTRIBUTING 
AUTHORS 
ASSET ID 
GSK2834425 
GSK ASSET 
Trelegy Ellipta 
INDICATION 
COPD 
PHASE OF 
DEVELOPMENT 
Phase IV 
 
Sponsor Name and Legal Registered Address: 
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
SPONSOR SIGNATORY: 
David Slade 
Senior Clinical Development Director 
Approval Date:  27 Jan 2023 
 
Copyright 2023 the GSK group of companies. All rights reserved.  Unauthorized copying 
or use of this information is prohibited 
PPD
PPD


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Amendment 1 
27 Jan 2023 
TMF-15637673 
Original Protocol 
02 February 2022. 
TMF-14425986 
 
Amendment 1:  
This amendment is considered non-substantial based on the criteria defined in EU 
Clinical Trial Regulation No 536/2014 of the European Parliament and the Council of the 
European Union. 
Overall Rationale for Amendment 1: The protocol is amended mainly to 1) add an 
additional analysis for license renewal to have the flexibility to provide data as a 
supporting document to agency to meet Trelegy licence renewal timeline, 2) eligibility 
criteria are adjusted to reflect real world clinical practice and add flexibility in 
recruitment, 3) inverse-probability weighted mixed model for repeated measures will be 
employed in the primary analysis, 4) others include correcting typo errors and 
inconsistencies. Protocol changes are described in the table below. 
Section # and Name Description of Change 
Brief Rationale 
Title 
Correct the spelling error of ‘Trelegy’ 
Correction 
Study accountable 
person 
is taking the role of Study 
accountable person and replaces
personnel change  
Contributing authors 
is taking the role of study 
statistician and replaces 
Personnel change 
PPD
PPD
PPD
PPD
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Section # and Name Description of Change 
Brief Rationale 
Section 2: objective 
Add ‘to evaluate the proportion of 
patients achieving health status response 
with Trelegy.’ as the third secondary 
objective   
Add an additional secondary outcome to 
see CAT score change at week 4 
Align with study 
endpoints 
 
Align with study 
objectives 
 
 
Section 3.2.1. 
Withdrawal from 
Trelegy or the Study 
Add ‘Any female participant who 
becomes pregnant while participating 
will be withdrawn from the study.’ 
For clarification 
Section 3.3 study 
population 
Update study site to 30 
Replace ‘Based on local market research 
data, the proportion of participants taking 
free combination of triple therapy and 
with LAMA/LABA at baseline will be no 
more than 25% of all enrolled 
participants to reflect the real-world 
status of COPD maintenance treatment 
pattern in China.’ with ‘Based on local 
market research data, the proportion of 
participants with different baseline 
maintenance treatments in this study may 
be adjusted during enrolment stage to 
reflect the real-world status of COPD 
maintenance treatment pattern in China.’ 
Update. 
Remove threshold 
for baseline pre-
existing treatment 
to add flexibility in 
recruitment. 
Section 3.4.1 
inclusion criteria 
replace ‘who have been prescribed it 
continually for at least 12 weeks’ with 
‘with no minimum treatment duration’ 
To accommodate 
to real world 
clinical practice 
and add flexibility 
in recruitment 
Section 3.4.2: 
Exclusion criteria 
Modify exclusion criteria 2 to ‘Treated 
with Trelegy within 3 months prior to 
screening (Visit 1).’ 
Replace ‘prescribed’ to ‘treated’ 
Reduce the timeframe to 3 months 
To ensure the 
alignment with 
inclusion criteria 6 
and avoid 
confusion. 
To reduce the 
timeframe to 3 
months to add 
flexibility in 
recruitment. 


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Section # and Name Description of Change 
Brief Rationale 
Section 3.4.2: 
Exclusion criteria 
Remove original exclusion criteria 10 
 
Not applicable 
based on current 
China COVID-19 
management 
policy. 
Section 3.6.1.3: 
Pulmonary function 
test (spirometry) for 
Pre-dose FEV1, 
FVC, FEF25-75, IC 
Remove ‘Participants who are unable to 
perform spirometry could still have an 
inhaler error assessment and are not 
excluded from the study.’ 
 
Not applicable in 
the study. 
Section 3.6.2.4: 
Electrocardiogram 
Remove ‘and a repeated recording used 
for analysis’ 
Correction.  
No recording will 
be used for analysis 
in this study. 
Section 3.7.2: 
Sample size 
consideration 
Change Table 2 to Table 3 
Correction. 
Section 5.2:  
Reporting of 
pregnancy exposures 
Remove ‘and/ or GSK medical affairs’ 
Correction. 
No GSK medical 
affairs will be 
involved in this 
procedure. 
Section 3.8.2.1  
Primary endpoint/ 
estimand 
Primary analysis will be conducted using 
an inverse-probability weighted mixed 
model for repeated measures (MMRM) 
for the change from baseline in CAT 
score under the missing at random 
assumption to handle missingness which 
may occur during the data collection.  
The MMRM may 
provide additional 
insights to the 
primary endpoint.   
Section 3.8.3: 
Additional analysis 
for license renewal 
Add section of additional analysis for 
license renewal 
To add flexibility 
to provide data for 
license renewal. 
Section 6 
Add ‘whole study’ 
For clarification. 
Whole study data 
will be reported. 
(rather than after 
the additional 
analysis for license 
renewal) 
Throughout 
Minor editorial and document formatting 
revisions 
Minor therefore 
have not been 
summarized. 
 
 


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TABLE OF CONTENTS 
1. 
BACKGROUND AND RATIONALE .......................................................................... 9 
2. 
OBJECTIVES ......................................................................................................... 11 
3. 
RESEARCH METHODOLOGY .............................................................................. 12 
3.1. 
Study Design ................................................................................................. 12 
3.2. 
Data Source / Data Collection ........................................................................ 12 
3.2.1. 
Withdrawal from Trelegy or the Study .......................................... 19 
3.2.2. 
Lost to Follow Up ......................................................................... 19 
3.3. 
Study Population ............................................................................................ 19 
3.4. 
Eligibility Criteria ............................................................................................ 19 
3.4.1. 
Inclusion Criteria .......................................................................... 19 
3.4.2. 
Exclusion Criteria ......................................................................... 20 
3.5. 
Treatment ...................................................................................................... 21 
3.5.1. 
Treatment Administered ............................................................... 21 
3.5.2. 
Concomitant Therapy................................................................... 22 
3.6. 
Study Assessments and Procedures ............................................................. 22 
3.6.1. 
Effectiveness Assessments ......................................................... 22 
3.6.2 
Safety Assessments .................................................................... 23 
3.7 
Sample Size Calculations .............................................................................. 25 
3.7.1 
Statistical assumptions ................................................................ 25 
3.7.2 
Sample size consideration ........................................................... 25 
3.7.3 
Sensitivity assessments ............................................................... 25 
3.8 
Data Analysis Considerations ........................................................................ 28 
3.8.1 
Population for Analysis ................................................................ 28 
3.8.2 
Statistical Analysis ....................................................................... 28 
3.8.3 
Additional Analysis for License Renewal ...................................... 30 
4 
LIMITATIONS ......................................................................................................... 30 
5 
STUDY CONDUCT, MANAGEMENT & ETHICS .................................................... 30 
5.1 
AEs, Study treatment related AEs and SAEs ................................................. 31 
5.2 
Reporting of pregnancy exposures ................................................................ 31 
5.3 
Medical Device .............................................................................................. 31 
6 
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY 
RESULTS .............................................................................................................. 32 
7 
REFERENCES ....................................................................................................... 33 
8 
APPENDIX 1: QUESTIONNAIRES AND MEASURE .............................................. 35 
8.1 
Appendix 1-1 CAT Assessment ..................................................................... 35 
8.2 
Appendix 1-2  The mMRC.............................................................................. 36 
9 
APPENDIX 2: STUDY GOVERNANCE CONSIDERATIONS ................................. 37 
10 APPENDIX 3: AES AND SAES: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ........................... 41 
10.1 
Definition of AE .............................................................................................. 41 
10.2 
Definition of SAE ............................................................................................ 43 
10.3 
Definition of Study treatment related AEs ....................................................... 44 


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10.4 
Recording and Follow-Up of AE and SAE ...................................................... 44 
10.5 
Reporting of SAE to GSK ............................................................................... 46 
11 APPENDIX 4: COLLECTION OF PREGNANCY INFORMATION ........................... 47 


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ABBREVIATIONS AND TRADEMARK INFORMATION 
AE 
Adverse Event 
CAT 
COPD Assessment Test 
CDE 
Center for Drug Evaluation in China 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
COPD 
chronic obstructive pulmonary disease 
CRA 
clinical research assistant 
CSR 
clinical study report 
DPI 
Dry Powder Inhaler 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
E.D. 
early discontinuation / withdrawal 
EHR 
Electronic Health Records 
FAS 
Full Analysis Set 
FEF25-75 
Forced Expiratory Flow at the 25 and 75% 
FEV1 
Forced expiratory volume in 1 second 
FF 
fluticasone furoate 
FVC 
Forced Vital Capacity 
GCP 
Good clinical practice 
HIPAA 
Health Insurance Portability and Accountability Act  
HRQoL 
health related quality of life 
IC 
Inspiratory Capacity 
ICF 
informed consent form 


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ICMJE 
International Committee of Medical Journal Editors 
ICS 
Inhaled Corticosteroids 
IEC 
Independent Ethics Committee 
LABA 
Long-Acting Beta-2-Agonists 
LAMA 
Long-Acting Muscarinic Antagonist 
MCID 
minimum clinical meaningful difference 
MedDRA 
Medicinal Dictionary for Regulatory Activities 
mMRC 
Modified Medical Research Council 
NDA 
New Drug Application 
PK 
Pharmacokinetic 
PFT 
Pulmonary function test 
RCT 
Randomized controlled trial 
SAE 
Serious Adverse Event 
SD 
standard deviation 
SMPC 
Summary of Product Characteristics 
SoA 
Schedule of Activities 
SRM 
Study Reference Manual 
WOCBP 
Woman of Childbearing Potential  
UMEC 
umeclidinium 
VI 
vilanterol 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
Ellipta 
 
NONE 
Trelegy 
 
 
 
 
 


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1. 
BACKGROUND AND RATIONALE 
Trelegy [fluticasone furoate (FF)/ umeclidinium (UMEC)/ vilanterol (VI) (100 µg/62.5 
µg/25 µg)] in a single inhaler (TRELEGY ELLIPTA) provides a recently approved 
treatment option for the management of patients with advanced Chronic obstructive 
pulmonary disease (COPD) the aim of reducing exacerbation frequency and burden of 
polypharmacy, improving lung function, health related quality of life (HRQoL) and 
symptom control, while providing a more convenient treatment option for patients 
compared with established dual/monotherapies.  
Trelegy 100/62.5/25 µg was approved in China on 04 November 2019 for a maintenance 
treatment in adult patients with COPD. Data from two phase Ⅲ studies and one 
Pharmacokinetic (PK) study supported the New Drug Application (NDA) approval in 
China. In the two phase Ⅲ studies [Lipson, 2018; Lipson, 2017], Trelegy showed 
significantly better improvement in the primary and secondary endpoints, including 
Forced expiratory volume in 1 second (FEV1), exacerbation reduction and symptoms 
compared with Inhaled Corticosteroids (ICS)/ Long-Acting Beta-2-Agonists (LABA) or 
Long-Acting Muscarinic Antagonist (LAMA)/LABA in the overall population.  
COPD refers to a progressive deterioration of lung function and a series of mental and 
physical comorbidities. It is one of the leading causes of morbidity and mortality 
worldwide, inducing substantial economic, social, and health-care burden [GOLD, 2021]. 
COPD is the fifth leading cause of death in China with a reported prevalence of 13.7% in 
people aged 40 years or older [GBD, 2017]. It is essential to provide appropriate 
treatments for COPD patients according to guidelines. 
GOLD guideline recommends one of the goals of treatment of stable COPD is the 
reduction of symptoms which includes three components, i.e., to reduce symptoms, 
improve exercise tolerance and improve health status [GOLD, 2021]. Triple therapy 
(ICS/LABA/LAMA) is recommended as step-up therapy in patients with COPD whose 
symptoms or exacerbations are not controlled by ICS/LABA or LAMA/LABA, or with 
high level of blood eosinophils or comorbid with asthma [GOLD, 2021]. 
As high symptom burden is one of the key unmet medical needs for COPD patients even 
among those under the treatment of maintenance therapies, the main goal of this single-
armed study is to collect the real-life effectiveness data focusing on symptoms of COPD 
in patients treated with Trelegy for 12 weeks, by comparison to baseline data which can 
reflect the benefits of patients who remain symptomatic with their prior maintenance 
treatment and switch to Trelegy under the discretion of their physicians. Based on 
previous results [Marth, 2021; Bansal, 2021], a decrease over 2 unit [minimum clinical 
meaningful difference (MCID)] of COPD Assessment Test (CAT) score and MCID 
change (over 100 ml) of forced expiratory volume in one second (FEV1) were observed 
CCI


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for triple therapy after 12-week treatment. Therefore, a 12-week duration is considered to 
be enough to observe a clinical meaningful change from baseline of the study outcomes, 
i.e., CAT and FEV1.  
The CAT score is defined as primary outcome because it is recommended by guideline 
[GOLD, 2021] as the tool for assessment of disease severity and usually leveraged by 
physicians in daily practice to evaluate the patient’s response to treatment. A decrease of 
2 unit compared to baseline is considered as the MCID [Kon, 2014]. Other outcomes 
including lung function and dyspnea can provide data from different dimensions on 
effectiveness which are also clinically relevant to the evaluation of the response of 
patients to treatment. 
 
 


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2. 
OBJECTIVES 
Primary Objective 
Primary Outcome 
The primary objective of this study is to 
evaluate the effectiveness of Trelegy on health 
status in patients with symptomatic COPD at 
week 12. 
• 
Change from baseline of CAT score at 
week 12 
Secondary Objectives 
Secondary Outcomes 
to evaluate the effectiveness of Trelegy on 
dyspnea in patients with symptomatic COPD 
at week 12. 
to evaluate the effectiveness of Trelegy on 
lung function in patients with symptomatic 
COPD at week 12. 
to evaluate the proportion of patients achieving 
health status response with Trelegy.  
to evaluate the effectiveness of Trelegy on 
health status in patients with symptomatic 
COPD at week 4. 
• 
Change from baseline of Modified 
Medical Research Council (mMRC) at 
week 12 
• 
Change from baseline of pre-dose FEV1 
at week 12 
• 
Proportion of CAT responder (defined as 
≥ 2 unit decrease from baseline) at week 
12  
• 
Change from baseline of CAT score at 
week 4 
 
Exploratory Objectives 
Exploratory Outcomes 
to evaluate the effectiveness of Trelegy on 
lung function in patients with symptomatic 
COPD 
• 
Change from baseline of Forced Vital 
Capacity (FVC), Forced Expiratory Flow 
at the 25 and 75% (FEF25-75) , Inspiratory 
Capacity (IC) at week 12 
Safety Objective 
Safety Outcomes 
The safety objective is to collect the safety 
information of participants using Trelegy. 
• 
Trelegy related AEs 
• 
SAEs 
• 
AEs that lead to the discontinuation of 
Trelegy 
 


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3. 
RESEARCH METHODOLOGY 
3.1. 
Study Design 
This is a 12-week, prospective, open label, single cohort study. The enrolled participants 
will be those who are symptomatic under COPD maintenance treatments, and newly 
prescribed with Trelegy under the discretion by clinical physicians.  
The study applies a single cohort design to evaluate the effectiveness following 12-week 
treatment with Trelegy by comparison to baseline data, which can reflect the benefits 
(i.e., CAT score and FEV1, etc.) of patients who remain symptomatic with their prior 
maintenance treatment. The decision to prescribe Trelegy shall be independent to the 
study with medical records providing documentation of a Trelegy prescription.  
The prospective data collection starts from Visit 1 when Trelegy is taken by patients for 
the first dose (see Figure 1 below). The participants will complete the CAT score at Visit 
1, Visit 2 and Visit 3 or early discontinuation/withdrawal visit (E.D.), and the mMRC at 
Visit 1 and Visit 3 or E.D. The participants’ pulmonary function test will be assessed at 
Visit 1 and Visit 3 or E.D.. The investigators will record Trelegy-related adverse events 
(AEs), serious adverse events (SAEs) and AEs that lead to withdrawal from Trelegy.  
Figure 1 
The Schematic diagram for this study 
 
 
3.2. 
Data Source / Data Collection 
The investigators will enroll participants by assessing the inclusion/exclusion criteria. 
The patients will be enrolled at visit 1 and will be followed up prospectively for 12 
weeks.  


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During this trial the following information and measurements will be collected, and the 
details are listed in Table 1:  
To be completed at Visit 1: 
• 
Patient demographics (including sex, age, height, weight)  
• 
Patient past medical history and co-morbid diseases  
• 
Patient smoking history [never a smoker, former smoker (previously smoked ≥10 
pack year and has not smoked for at least 6 months prior to Visit 1), current smoker 
(10 pack year and smoked within 6 months prior to Visit 1); the number of pack 
years for former smoker and current smoker should be calculated (round up to the 
nearest integer)]  
• 
Patient concomitant medication  
• 
Pregnancy status 
• 
Oxygen saturation 
• 
Patient vital signs and Electrocardiogram (ECG) 
• 
CAT score  
• 
mMRC 
• 
Pulmonary function test (spirometry): pre-dose FEV1, FVC, FEF25–75 and IC  
• 
Trelegy related AEs 
• 
AEs that lead to the discontinuation of Trelegy 
• 
SAEs 
To be completed at Visit 2:  
• 
Patient concomitant medication  
• 
Pregnancy status 
• 
Number of doses of Trelegy taken   
• 
CAT score  
• 
Trelegy related AEs 
• 
AEs that lead to the discontinuation of Trelegy 
• 
SAEs 


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To be completed at Visit 3 or E.D.:  
• 
Patient concomitant medication  
• 
Pregnancy status 
• 
Number of doses of Trelegy taken   
• 
Patient vital signs 
• 
CAT score  
• 
mMRC  
• 
Pulmonary function test (spirometry): Pre-dosed FEV1, FVC, FEF25–75 and IC 
• 
Trelegy related AEs 
• 
AEs that lead to the discontinuation of Trelegy 
• 
SAEs 
 


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Table 1 
Visit flow chart and data collection schedule  
Procedure 
Conse
nting 
Treatment and Observation 
Period (Days) 
 
Notes 
E.D. = early discontinuation / withdrawal  (within 7 days of 
study discontinuation) 
Study visit 
V01 
Pre-
Scree
ning 
V1 
Screen, 
enroll & 
baseline 
(Day 1) 
V2 
(Day 28) 
V3 
End of 
Study 
(Day 84) 
E.D. 
 
Time Window Allowed 
(days) 
 
 
±7 
±10 
 
 
Informed consent2 
X 
 
 
 
 
 
Inclusion / exclusion 
criteria 
 
X 
 
 
 
 
Demography 
 
X 
 
 
 
 
Full physical 
examination including 
height and weight 
 
X 
 
 
 
 
Smoking History 
 
X 
 
 
 
 


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Procedure 
Conse
nting 
Treatment and Observation 
Period (Days) 
 
Notes 
E.D. = early discontinuation / withdrawal  (within 7 days of 
study discontinuation) 
Medical history: past 
and current medical 
conditions  
 
X 
 
 
 
 
Vital signs 
 
X 
 
X 
X 
 
Oxygen saturation 
 
X 
 
 
 
 
ECG 
 
X 
 
 
 
 
Trelegy Taken 
worksheet 
 
 
X 
X 
X 
Number of doses of Trelegy taken should be documented 
weekly by the patients, and the investigators will review and 
record in EDC 
CAT score2 
 
X 
X 
X 
X 
 
mMRC3 
 
X 
 
X 
X 
 
Spirometry4 
 
X 
 
X 
X 
 


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Procedure 
Conse
nting 
Treatment and Observation 
Period (Days) 
 
Notes 
E.D. = early discontinuation / withdrawal  (within 7 days of 
study discontinuation) 
Review of Study 
treatment related AEs  
 
X 
X  
X 
X 
Clinical judgment should be used to determine whether there is 
a relationship between study treatment and each occurrence of 
each AE/SAE. 
Study treatment related adverse events must be recorded from 
V1. 
Where a causality relationship is determined, this must be 
recorded as a study treatment related AE. 
AEs not related to either study treatment or discontinuation 
from study treatment are not recorded, unless classified as 
SAE. 
 
Review of AEs that lead 
to the discontinuation of 
Trelegy 
 
X 
X 
X 
X 
All AEs that lead to discontinuation from study treatment, 
whether judged related to study treatment or not, should be 
recorded. 
All AEs that lead to withdrawal from the study whilst the 
participant is on study treatment, whether judged related to 
study treatment or not, should be recorded. 


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Procedure 
Conse
nting 
Treatment and Observation 
Period (Days) 
 
Notes 
E.D. = early discontinuation / withdrawal  (within 7 days of 
study discontinuation) 
SAEs review 
 
X 
X  
X 
X 
All SAEs are recorded from the start of using Trelegy. 
Clinical judgment should be used to determine the relationship 
between study treatment and each occurrence of each 
AE/SAE. 
Where a causality relationship is determined, this must be 
recorded as a study treatment related SAE. 
Pregnancy status 
 
X 
X  
X 
X 
 
Concomitant medication 
review 
 
X 
X  
X 
X 
 
1. V0 and V1 could occur on the same day, and V1 should be completed ≤7 days after V0.  
2. If a participant is unable to attend to the clinic for Visit 2  under certain situation (e.g. COVID-19 impact or lockdown), it’s acceptable to carry out the CAT 
assessment by telephone or other remote approaches. 
3. mMRC: assessed by both patients and physicians will be collected, refers to 3.6.1.2. 
4. Pre-dose FEV1 , FVC, FEF25-75 and IC will be entered into eCRF. 
 


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3.2.1. 
Withdrawal from Trelegy or the Study 
Participants that permanently stop Trelegy are not required to withdraw from the study. If 
for any reason a participant must permanently stop Trelegy, every effort should be made 
by the Investigator/delegate to keep the participant in the study to collect all the 
effectiveness and safety data of the subsequent visits per the Schedule of Activities (SoA) 
after the Trelegy discontinuation. 
Any female participant who becomes pregnant while participating will be withdrawn 
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, or 
administrative reasons. If a participant withdraw from the study, he/she has to complete 
the E.D. visit per SoA (Table 1), and no more extra data will be collected after E.D. visit. 
3.2.2. 
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. 
If a participant fails to return to the clinic for Visit 2 or Visit 3, the site should attempt to 
contact 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) and 
reschedule the missed visit as soon as possible. If a participant is completely unreachable, 
they are considered to have withdrawn from the study with a primary reason of lost to 
follow-up.  
3.3. 
Study Population 
This study plans to enrol 460 patients with symptomatic COPD (details in sample size 
estimation in Section 3.7). In this study, patients will be recruited from approximately 30 
centres in China. The study sites will be selected from different regions and tiers of 
hospitals around China to ensure the patients could be representative. Based on local 
market research data, the proportion of participants with different baseline maintenance 
treatments in this study may be adjusted during enrolment stage to reflect the real-world 
status of COPD maintenance treatment pattern in China. 
3.4. 
Eligibility Criteria 
3.4.1. 
Inclusion Criteria 
AGE 
1. Participant must be 40 years or above of age inclusive, at the time of signing 
the informed consent. 
TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS  
2. Participants with a documented physician diagnosis of COPD;  


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3. CAT ≥ 10; 
4. Existing COPD Maintenance Treatment. Patients currently receiving one of the 
maintenance therapies listed below with no minimum treatment duration prior 
to screening (Visit 1): 
• 
ICS/LABA (single or multiple inhalers) 
• 
LAMA/LABA (single or multiple inhalers) 
• 
Free combination of ICS, LAMA, LABA  
5. Current or former cigarette smokers with a history of cigarette smoking 
history≥10 pack-years at screening.  
6. Trelegy is prescribed under the discretion of clinical physicians with medical 
records providing documentation of a Trelegy prescription in daily practice. 
 
INFORMED CONSENT 
7. Capable of giving signed informed consent which includes compliance with the 
requirements and restrictions listed in the informed consent form (ICF) and in 
this protocol. 
3.4.2. 
Exclusion Criteria 
Women of childbearing potential 
1. Women who are pregnant or lactating or are planning on becoming pregnant 
during the study. 
 
PRIOR/CONCOMITANT THERAPY 
2. Treated with Trelegy within 3 months prior to screening (Visit 1). 
3. Patients who, in the opinion of the treating investigator, are chronic users of 
oral corticosteroids for respiratory or other indications (if unsure discuss with 
the medical monitor prior to screening). Chronic use is defined as more than 14 
days’ continuous use during the 12 weeks prior to Visit 1. 
 
MEDICAL CONDITIONS 
4. Patients with any life-threatening condition i.e. low probability, in the opinion 
of the investigator, of 3-month survival due to severity of COPD or comorbid 
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MEDICAL CONDITIONS 
5. Patients with unstable COPD. Patients with resolution of an exacerbation less 
than 2 weeks prior to Visit 1. Patients may be rescreened 2 weeks after 
resolution of exacerbation (exacerbation is defined as: requiring treatment with 
antibiotics and/or systemic steroids or hospitalisation; resolution is defined as: 2 
weeks after all symptoms have resolved and any medicines to treat the 
exacerbation have finished). 
6. Patients who need more than 3 L/min supplemental oxygen at rest at screening. 
7. Other diseases/abnormalities: Patients with historical or current evidence of 
uncontrolled or clinically significant disease. 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 efficacy or 
safety analysis if the disease/condition exacerbated during the study. 
 
PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE 
8. Participation received any investigational drug in other clinical trial within four 
weeks or 5 half-lives prior to this study whichever is longer. 
 
OTHER EXCLUSIONS 
9. Any conditions or illnesses listed in the section of contraindications in the 
Summary of Product Characteristics (SmPC) of Trelegy, i.e., hypersensitivity 
to the active substances of Trelegy Ellipta; 
10. Inability to read: In the opinion of the Investigator, any participant who is 
unable to read and/or would not be able to complete study related materials. 
3.5. 
Treatment 
3.5.1. 
Treatment Administered 
All patients will receive Trelegy (FF/UMEC/VI ELLIPTA 100/62.5/25 µg) according to 
the local SmPC. Participants are expected to inhale one dose in the morning from the 
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3.5.2. 
Concomitant Therapy 
Any medication or vaccine for the treatment of a respiratory condition that the participant 
receives at the time of consent or receives during the study should be recorded along 
with: 
• dates of administration including start and end dates 
• dosage information including dose and frequency 
 
3.6. 
Study Assessments and Procedures  
3.6.1. 
Effectiveness Assessments 
3.6.1.1. 
The COPD Assessment Test (CAT) 
The COPD Assessment Test (CAT) is a validated 8-item questionnaire developed for use 
in routine clinical practice to measure the health status of patients with COPD [Jones, 
2009; Jones, 2012]. Participants rate their experience on a 6-point scale (Protocol 8.1 
Appendix 1-1), ranging from 0 (no impairment) to 5 (maximum impairment) with a 
scoring range of 0-40. Higher scores indicated greater disease impact.  
The questionnaire is completed on paper prior to the study treatment and before any 
procedures or assessments are performed (to avoid influencing the participant’s 
response). To avoid biasing responses, the participant is not to be told the results of any 
diagnostic tests prior to completing the CAT questionnaire. Questionnaires are to be 
administered at Visit 1, Visit 2 and Visit 3/E.D. 
A change of 2 unit compared to baseline is considered as the MCID [Jones, 2012]. 
3.6.1.2. 
Modified Medical Research Council (mMRC) 
The mMRC was developed in 1960 [Behrman S, 1960], and it’s considered adequate for 
assessment of symptoms, as it relates well to other measures of health status and predicts 
future mortality risk [GOLD, 2021]. 
The mMRC (Patient Version and Physician Version) will be used to assess the 
breathlessness state of the patient before and after the treatment (Protocol 8.2 Appendix 
1-2). With it, patients are scored on a scale of 0-4 depending on their disability due to 
shortness of breath from 0 (no impact) to 4 (worst possible impact). 
The mMRC (Patient Version) will be completed by each patient firstly, without 
supervision, after CAT. The investigator should check whether the patient has completed 
the mMRC adequately but cannot assist in completing it. Then, the investigators will 
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3.6.1.3. 
Pulmonary function test (spirometry) for Pre-dose FEV1, FVC, FEF25-75 , 
IC 
Pre-dose FEV1, FVC, FEF25-75 and IC are all measured through a pulmonary function test 
(spirometry). Pre-dose FEV1 and FVC are basic items of COPD’s pulmonary function 
test (PFT). FEV % of predicted value is a good indicator to assess moderate to severe 
airflow limitation [GOLD, 2021]. It’s used clinically as a predictor of exacerbation or 
mortality in patients with COPD [CMA, 2018]. FEF25-75 is one of the standard results 
provided in spirometry reports too, low FEF25-75 is well known indicator of small airway 
obstruction [GOLD, 2021]. IC is measured as you exhale casually followed by a maximal 
inhalation. The calculation for IC is tidal volume plus inspiratory reserve volume. The 
decrease of IC is associated with an increase at the end of expiration, it can be used as a 
simple assessment of lung volume changes in COPD [GOLD, 2021]. 
Spirometry for assessment of pulmonary function is to be performed as described in 
Table 1 in all participants at Visit 1and Visit 3/E.D.  
All sites will use their own spirometry equipments for pulmonary function test. For Pre-
dose FEV1, FVC, FEF25-75 and IC determination, at least 3 acceptable spirometry efforts 
(no more than 8) need to be obtained. To facilitate pre-dose spirometry, participants are 
encouraged to time their COPD maintenance therapy so that they are due for their next 
dose at the time of the study visit, which should be in the morning.  
Each spirometry should be performed prior to the day’s dose of usual care/ study 
treatment. The largest Pre-dose FEV1 , FVC, FEF25-75 and IC from the 3 acceptable 
efforts are recorded, even if not from the same effort. If it is not possible to withhold 
usual care/study treatment and/or short-acting beta-agonists or anti-cholinergic for ≥4 
hours, spirometry is still measured and recorded along with the most recent use of COPD 
maintenance treatment/ study treatment.  
3.6.2 Safety Assessments 
The following safety events will be collected during the study: 
- All Trelegy related AEs 
- All SAEs 
- AEs that lead to the discontinuation of Trelegy 
COPD exacerbation is a disease-related event. Because exacerbations are typically 
associated with the disease under study, an exacerbation will not to be reported as an 
SAE unless, in the investigator’s opinion, the event is of greater intensity, frequency, or 
duration than expected for the individual participant, or the investigator considered that 
there is a reasonable possibility that event is related to study treatment. 
The investigator or site staff are responsible for detecting, documenting and reporting 
events that meet the definition of an AE or SAE. The following information on AEs will 
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• Patient’s coded data  
• Treatment’s data 
• Reporter’s data 
• Duration (start and stop dates). 
• Severity (mild, moderate, severe). 
• Causality (reasonable possibility yes/no). 
• Actions taken and outcome. 
The detailed definitions and procedures for recording, evaluating, follow-up, and 
reporting of the AEs, study treatment related AEs and SAEs are listed in APPENDIX 3. 
3.6.2.1       Physical examination 
A complete 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. 
3.6.2.2        Vital signs 
Vital signs (Body Temperature, Pulse Rate, Blood Pressure) will be performed at the time 
points specified in Visit 1 and Visit 3/E.D. prior to conducting spirometry and prior to 
taking the morning dose of study treatment. Blood pressure (systolic and diastolic) and 
pulse rate will be measured in the sitting position after approximately 5 minutes rest. A 
single set of values will be collected and recorded in the source documentation and 
eCRF. 
3.6.2.3        Oxygen saturation 
The oxygen saturation of participants is evaluated by pulse oximetry, to ensure whether 
they need supplemental oxygen or not. Patients who need more than 3 L/min 
supplemental oxygen at rest at screening are excluded. 
3.6.2.4        Electrocardiogram  
12-lead resting ECG will be conducted at Visit 1. All ECG measurements will be made 
with the participant in a supine position having rested in this position for approximately 5 
minutes before each reading. The investigator or a designee will evaluate whether the 
ECG is normal or abnormal. ECGs may be repeated for quality reasons . Dated and 
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3.7 Sample Size Calculations 
3.7.1 Statistical assumptions 
INTREPID study [study 206854 China CSR GSK Document Number 2019N418769_00] 
showed that in the real world setting 19% participants had early withdrawn from the 
Trelegy treatment prior to week 24. Considering the difference in the China clinical 
practice and study designs, it is assumed that 79% enrolled participants would complete 
12 weeks of Trelegy treatment with no intercurrent events, 20% would have the 
intercurrent event of receiving a new COPD maintenance therapy, 1% would have the 
intercurrent event of treatment discontinuation.  
Based on results from a few studies, i.e., IMPACT [Lipson, 2018; study CTT116855 
China CSR GSK Document Number 2018N356723_00], INTREPID [study 206854 
China CSR GSK Document Number 2019N418769_00]  and one randomized controlled 
trial (RCT) [Bansal, 2021], it is assumed that a decrease of 2 in the primary endpoint at 
week 12 will be observed in this study with a common standard deviation of 7 (Table 2).  
Table 2 
Assumptions for the primary endpoint 
Proportion of each type of participants 
Primary endpoint 
Mean 
Standard 
deviation 
Participants with no intercurrent events 
79% 
-2 
7 
Participants receiving other COPD maintenance therapy 
20% 
-2 
7 
Participants with treatment discontinuation 
1% 
0  
7 
Total 
100% 
-1.98  
7.003 
3.7.2 Sample size consideration 
A sample size of 460 is planned. With the aforementioned assumptions in Table 1, the 
sample size would be able to provide a half-width ranging from 0.64 to 0.73 for the 95% 
confidence interval (CI) of the inverse probability weighted mean of the change from 
baseline in CAT score at week 12 in the primary analysis under different missingness 
scenarios (Table 3).  
3.7.3 Sensitivity assessments 
The half-width of confidence interval are assessed when the sample size varies under 
different missingness scenarios (Table 3). Scenario 1 is the ideal situation where no 
missingness occurs, which results a half-width of 0.64 for the 95% confidence interval 
for the inverse probability weighted mean of the primary endpoint with the sample size of 
460. Scenario 2 represents a situation with the moderate missingness, which results a 


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half-width of 0.69 for the 95% confidence interval of the primary endpoint with the 
sample size of 460. Scenario 3 represents the worst missingness situation, which results a 
half-width of 0.73 for the 95% confidence interval of the primary endpoint with the 
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Table 3 
Sample size versus the half-width of the 95% CI for the primary 
endpoint 
Sample 
size 
Data 
availability 
status 
Proportion of missing data at week 12 
Expected 
inverse 
probability 
weighted 
mean 
Half 
width 
of  
95% CI 
Participants 
with no 
intercurrent 
events 
Participants 
receiving other 
COPD maintenance 
therapy 
Participants with 
treatment 
discontinuation 
280 
Scenario 1 
No missing 
No missing 
No missing 
-1.98 
0.82 
 
Scenario 2 
5% missing 
30% missing 
50% missing 
-1.98 
0.87 
 
Scenario 3 
10% missing 
50% missing 
70% missing 
-1.98 
0.94 
340 
Scenario 1 
No missing 
No missing 
No missing 
-1.98 
0.74 
 
Scenario 2 
5% missing 
30% missing 
50% missing 
-1.98 
0.79 
 
Scenario 3 
10% missing 
50% missing 
70% missing 
-1.98 
0.85 
400 
Scenario 1 
No missing 
No missing 
No missing 
-1.98 
0.69 
 
Scenario 2 
5% missing 
30% missing 
50% missing 
-1.98 
0.73 
 
Scenario 3 
10% missing 
50% missing 
70% missing 
-1.98 
0.78 
460 
Scenario 1 
No missing 
No missing 
No missing 
-1.98 
0.64 
 
Scenario 2 
5% missing 
30% missing 
50% missing 
-1.98 
0.69 
 
Scenario 3 
10% missing 
50% missing 
70% missing 
-1.98 
0.73 
With the planned sample size of 460, the half-width of the 95% confidence interval for 
the inverse probability weighted mean for the primary endpoint is also assessed when the 
standard deviation varies (Table 4).  


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Table 4 
The half-width of the 95% CI versus standard deviations when N=460 
Standard 
deviation 
Data 
availability 
status 
Proportion of missing data at week 12 
Expected 
inverse 
probability 
weighted 
mean 
Half 
width 
of  
95% CI 
Participants 
with no 
intercurrent 
events 
Participants 
receiving other 
COPD maintenance 
therapy 
Participants with 
treatment 
discontinuation 
6.5 
Scenario 1 
No missing 
No missing 
No missing 
-1.98 
0.60 
 
Scenario 2 
5% missing 
30% missing 
50% missing 
-1.98 
0.64 
 
Scenario 3 
10% missing 
50% missing 
70% missing 
-1.98 
0.68 
7 
Scenario 1 
No missing 
No missing 
No missing 
-1.98 
0.64 
 
Scenario 2 
5% missing 
30% missing 
50% missing 
-1.98 
0.69 
 
Scenario 3 
10% missing 
50% missing 
70% missing 
-1.98 
0.73 
7.5 
Scenario 1 
No missing 
No missing 
No missing 
-1.98 
0.69 
 
Scenario 2 
5% missing 
30% missing 
50% missing 
-1.98 
0.73 
 
Scenario 3 
10% missing 
50% missing 
70% missing 
-1.98 
0.79 
 
3.8 Data Analysis Considerations 
3.8.1 Population for Analysis 
Full Analysis Set (FAS) The Full Analysis Set will consist all participants who enrol in 
the study and take at least one dose of Trelegy. Unless otherwise specified the data will 
be analysed based on the Full Analysis Set. 
3.8.2 Statistical Analysis 
3.8.2.1 
Primary endpoint/estimand 
Primary estimand 
The primary clinical question of interest is: what is the change from baseline in CAT 
score at week 12, regardless of receiving a new COPD maintenance therapy or treatment 
discontinuation. 
The estimand is described by the following attributes: 
• 
Population: Symptomatic Chinese COPD participants who are receiving COPD 
maintenance treatment 
• 
Treatment condition: Trelegy (FF/UMEC/VI ELLIPTA 100/62.5/25 µg) one dose 
daily, inhaled 
• 
Variable: change from baseline of CAT score at week 12. 
• 
Intercurrent events: 


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• 
Receiving other COPD maintenance therapy is addressed by the treatment 
policy strategy.  
• 
Treatment discontinuation due to any reason is addressed by the treatment 
policy strategy.  
• 
Summary measure: average change from baseline in CAT score at week 12.  
Rationale: Interest lies in the treatment effect at week 12 in the real-world setting, maybe 
confounded by other COPD maintenance therapies or the event of treatment 
discontinuation due to any reason. Therefore, treatment policy strategy is employed to 
handle the intercurrent events of receiving a new COPD maintenance therapy and 
treatment discontinuation due to any reason as it reflects the clinical practice. 
Primary analysis 
Primary analysis will be conducted using an inverse-probability weighted mixed model 
for repeated measures (MMRM) for the change from baseline in CAT score under the 
missing at random assumption to handle missingness which may occur during the data 
collection. 
The missingness of the change from baseline in CAT score at week 12 will be modelled 
using a logistic regression model [Seaman SR and White IR, 2011], with the covariates 
of age, gender,  years of COPD, smoker history, pre-dose FEV1 at baseline, COPD 
maintenance treatment at baseline, CAT score at baseline, the change from baseline in 
CAT score at week 4, intercurrent event status, duration of treatment exposure. The 
missingness of the change from baseline in CAT score at week 4 will be modelled 
analogously with the covariates collected before week 4. 
The change from baseline in CAT score will be analysed using the MMRM model (in 
which each observation is weighted with the inverse probabilities derived from the above 
logistic regression models) with the covariates of smoking history, CAT score at baseline, 
visit, the interaction of CAT score at baseline*visit [Protocol No. CTT116855]. 
Sensitivity analysis will be conducted using the arithmetic mean. Missing data will be 
imputed using multiple imputation under missing at random assumption, for participants 
with no intercurrent events, receiving other COPD maintenance therapy, with treatment 
discontinuation, separately if data permits, otherwise may be imputed for the pooled 
groups.   
Subgroup analyses of the primary endpoint will be further investigated across the CAT 
score at baseline: moderate impact [CAT 10-20], severe impact [CAT 21-30], very severe 
impact [31-40]. 
3.8.2.2 
Secondary and exploratory endpoints/estimands 
Similar estimands as the primary estimand will be employed for secondary endpoints and 
exploratory endpoints, except the variable is changed to the corresponding endpoint.  
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• 
Summary measure is the proportion of participants having ≥ 2 unit decrease from 
baseline at week 12. The response status of a participant at a visit is set to missing if 
his/her CAT score at baseline or at the visit is missing. 
The statistical analyses will be analogous to the primary endpoint.  
Safety Analysis 
AE terms will be coded using Medicinal Dictionary for Regulatory Activities (MedDRA) 
dictionary. The number and percentage of participants experiencing at least one Trelegy-
related AE, SAEs, AE leading to discontinuation of Trelegy will be provided. 
3.8.3 Additional Analysis for License Renewal 
The study is designed to support the license renewal of Trelegy 100/62.5/25 µg in adult 
patients with COPD. If the study report is unlikely to be completed before the license 
renewal submission period due to the evolving COVID-19 situation and the competing 
enrolment environment, an additional analysis may be performed with the early available 
study data (i.e. the data in participants who are enrolled by 29 May 2023 and at the time 
when they all have completed the study or withdrawn from study). This analysis is 
exclusively for the license renewal purpose and will not have any impact on the study 
design and other study criteria. The whole study data will be analyzed when all the 
participants have completed the study or withdrawn from study. 
4 
LIMITATIONS 
One main limitation arises from the single cohort design of this study with no control 
group and no blinding or randomisation, which may lead to difficulties to interpret the 
study results.  
Another limitation could lie in the lack of representativeness of the enrolled patients to 
the overall COPD population treated with Trelegy in China. The study sites will be 
selected from different regions and tiers of hospitals around China to minimize this 
limitation although this could be influenced by a few factors, e.g., hospital listing status 
of Trelegy, willingness of participation in the study by sites and qualification of sites, etc. 
5 
STUDY CONDUCT, MANAGEMENT & ETHICS  
This study will be conducted in accordance with GCP and all applicable legal 
requirements including subject privacy requirements. The investigator shall obtain proper 
consent from the study subjects which enables GSK’s access and processing of the study 
data containing their personal information possibly for purpose of this study and shall 
ensure the protocol, the site’s informed consent form, and any other information that will 
be presented to the study subjects are reviewed and approved by the appropriate 
Independent Ethics Committee (IEC). GSK will provide the investigator with needed 
documents for IEC. The detailed study governance considerations refer to Appendix 2. 
All clinical safety data will be collected as outlined in the electronic Case Report Form 
(eCRF). Under ICH GCP and all applicable local regulations and legal requirements, the 


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Sponsor, is responsible for, and undertakes to, assess all clinical safety information 
arising during the Study (including, but not limited to, that listed in the APPENDIX 3 in 
order to generate all safety reports as required).  
5.1 
AEs, Study treatment related AEs and SAEs 
All AEs and SAEs will be collected from the start of using Trelegy. For AEs/SAEs 
identified before study treatment discontinuation, it will be followed up. The subject 
should be followed until the event is resolved, stabilized with appropriate diagnostic 
evaluation or reasonably explained, or until the subject is lost to follow-up. Planned time 
points for safety assessments are provided in the Table 1. 
5.2 
 Reporting of pregnancy exposures 
To ensure subject safety, each pregnancy must be reported to the sponsor within 24 hours 
of learning of its occurrence. The pregnancy must be followed up to determine outcome 
(including premature termination) and status of mother and child, which must also be 
reported to the sponsor. Pregnancy complications and elective terminations for medical 
reasons must be reported. 
 Investigators will be provided with necessary “pregnancy exposure” and “pregnancy 
follow up” forms and supported by clinical research assistant (CRA) in complying with 
pregnancy reporting procedures. The Collection of Pregnancy Information is listed in 
Section 11 APPENDIX 4. 
5.3 
Medical Device 
The definition of a Medical Device Deficiency is an inadequacy of a medical device with 
respect to its identity, quality, durability, reliability, safety, or performance. Device 
deficiencies include malfunctions, use errors, and information supplied by the 
manufacturer. 
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 9. 
A medical device is any instrument, apparatus, appliance, material or other article, 
whether used alone or in combination, including the software necessary for its proper 
application intended by the manufacturer to be used for human beings for the purpose of: 
• 
diagnosis, prevention, monitoring, treatment or alleviation of disease; 
• 
diagnosis, monitoring, treatment, alleviation of or compensation for an injury or 
handicap; 
• 
investigation, replacement or modification of the anatomy or of a physiological 
process; 
• 
control of conception and which does not achieve its principle action in or on the 
human body by pharmacological, immunological or metabolic means, but may be 
assisted in its function by such means. 


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A medical device incident is any malfunction or deterioration in the characteristics and/or 
performance of a device, as well as any inadequacy in the labelling or the instructions for 
use which, directly or indirectly might lead to or might have led to the death of a patient, 
or user or of other persons or to a serious deterioration in their state of health. 
Not all delivery systems are considered “medical devices”. However, some GSK 
investigational products are considered “drug/device combination products” and incidents 
of device malfunction must be reported to GSK from the investigative site. Examples of 
GSK drug/device combination products include, but are not limited to: albiglutide 
lyophylized pen injector, albiglutide liquid autoinjector, ELLIPTA (Dry Powder Inhaler, 
DPI) inhaler, and Breezhaler inhaler. 
GSK must be notified if any GSK device or Drug/Device combination product fails to 
function properly. Incidents should be reported as a device malfunction and not as a 
safety event. 
It is possible for a reportable safety event to occur at the same time as a device 
malfunction. Safety events are reported as described in Section 5.1. 
If a device malfunction is reported to the investigator site, the following process should 
be followed:  
• 
report the malfunction. 
• 
customer/consumer can call GSK hotline 400 991 1165 or mail to China Hub 
(cn.customer-relations@consumerrelations-mail.gsk.com) to report complaint, and 
China hub will log the complaint in system and assign to relevant department. 
• 
Non-GSK medical device incidents should be reported to the appropriate 
manufacturer as per usual local practice. 
6 PLANS FOR DISSEMINATING AND COMMUNICATING STUDY 
RESULTS 
Any publication of the results from this study must be consistent with GSK’s publication 
policy and guided by Uniform Requirements for Manuscripts Submitted to Biomedical 
Journals: Writing and Editing for Biomedical Publication of the International Committee 
of Medical Journal Editors (ICMJE).  
A publication would be generated once the whole study results are ready, and it will be 
submitted to the academic conferences and published in peer-reviewed journals. 


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7 
REFERENCES 
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tiotropium monotherapy in patients with COPD. NPJ Prim Care Respir Med. 2021 May 
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Behrman S. John LIZARS. Centenary of a forgotten pioneer of the surgery of trigeminal 
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Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and 
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Jones PW, Harding G, Wiklund I, Berry P, Tabberer M, Yu R, et al. Tests of the 
responsiveness of the COPD assessment test following acute exacerbation and pulmonary 
rehabilitation. Chest. 2012 Jul;142(1):134-140. 
Kon SS, Canavan JL, Jones SE, Nolan CM, Clark AL, Dickson MJ, et al. Minimum 
clinically important difference for the COPD Assessment Test: a prospective analysis. 
Lancet Respir Med. 2014 Mar;2(3):195-203. 


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Lipson DA, Barnhart F, Brealey N, Brooks J, Criner GJ, Day NC, et al. Once-Daily 
Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med 
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Lipson DA, Barnacle H, Birk R, Brealey N, Locantore N, Lomas DA, et al. FULFIL 
Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary 
Disease. Am J Respir Crit Care Med. 2017;196:438–446 
Marth K, Renner A, Pohl W. TRICOP - A Real-world effectiveness study with a single-
inhaler extrafine triple therapy over 52 weeks in Austrian patients with COPD. Respir 
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Seaman SR, White IR. Review of inverse probability weighting for dealing with missing 
data. Statistical methods in medical research. 2011;22(3):278-295.  
The Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy 
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Disease,, 2021 Report. Available from: http://www. goldcopd.org/ 


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8 APPENDIX 1: QUESTIONNAIRES AND MEASURE 
8.1 
Appendix 1-1 CAT Assessment 
 


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8.2 
Appendix 1-2  The mMRC 
The Modified Medical Research Council Grading System (mMRC)- Patient  
Check the box that best describes how breathless you are: 
 0 “I only get breathless with strenuous exercise” 
 1 “I get short of breath when hurrying on the level or walking up a slight 
hill” 
 2 “I walk slower than people of the same age on the level because of 
breathlessness or have to stop for breath when walking at my own pace on the 
level” 
 3 “I stop for breath after walking about 100 yards or after a few minutes on 
the level” 
 4 “I am too breathless to leave the house” or “I am breathless when 
dressing” 
MODIFIED MEDICAL RESEARCH COUNCIL (mMRC) DYSPNEA SCALE – 
PHYSICIAN COMPLETED (OBSERVER) 
Select the one best response to describe the patient’s shortness of breath 
[0] 
 
Not troubled by breathlessness except with strenuous exercise 
[1] 
 
Troubled by shortness of breath when hurrying on level ground or walking up a slight hill 
[2] 
 
Walks slower than people of the same age on level ground because of breathlessness or 
has to stop for breath when walking at own pace on level ground 
[3] 
 
Stops for breath after walking about 100 yards or after a few minutes on level ground 
[4] 
 
Too breathless to leave the house or breathless when dressing or undressing 


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9 
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 ICH Good Clinical Practice (GCP) Guidelines  
• 
Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, 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 IRB/IEC 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/IEC 
• 
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 Regulations (CFR), ICH guidelines, the 
IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), and 
all other applicable local regulations 
Financial Disclosure 
If required, 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. 
Informed Consent Process 
• 
The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorised representative and answer all questions 
regarding the study. 
• 
Participants must be informed that their participation is voluntary. Participants or 
their legally authorised representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 


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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 authorised 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 
authorised representative. 
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 authorised personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
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 multicentre studies only in their entirety and 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 (CSR). The investigator will be 
provided reasonable access to statistical tables, figures, and relevant reports and will have 


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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 participants, as 
appropriate. 
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 
• 
Participant data relating to the study will be recorded on printed or electronic CRF 
unless transmitted to the sponsor or designee electronically [e.g., Electronic Health 
Records (EHR)]. The investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the CRF. 
• 
The investigator must maintain accurate documentation (source data) that supports 
the information entered in the CRF. 
• 
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 CRF by authorised 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 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 reported on the CRF or 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. 


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Definition of what constitutes source data can be found in the Study Reference Manual 
(SRM). 
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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10 
APPENDIX 3: AES AND SAES: DEFINITIONS AND 
PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW-UP, AND REPORTING 
10.1 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 intervention, whether or not considered related to 
the study intervention. 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 intervention. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECG, 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 intervention administration even 
though it may have been present before the start of the study.  
• 
• Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention 
interaction.  
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention 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/selfharming intent. Such overdoses should be reported regardless of 
sequelae.  
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, 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.  
• 
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. "Lack of 
efficacy" or "failure of expected pharmacological action" also constitutes an AE or 
SAE. 


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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.  
• 
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. 


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10.2 Definition of SAE 
An SAE is defined as any serious adverse event 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 admitted (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 or significant 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. Is a suspected transmission of any infectious agent via an authorised medicinal product 
g. Other situations:  
• 
Possible Hy’s Law case: ALT≥3xULN AND total bilirubin ≥2xULN (>35% direct bilirubin) 
or international normalized ratio (INR) >1.5 must be reported as SAE  
• 
Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations such as significant medical 
events that 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 for 
allergic bronchospasm, blood dyscrasias, convulsions, or development of intervention 
dependency or intervention abuse. 


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10.3 Definition of Study treatment related AEs 
It may also be referred to as Adverse Drug Reaction (ADR).  
Study treatment related AE Definition 
A response to a medicinal product which is noxious and unintended.  
Response in this context means that a causal relationship between a medicinal product and an 
adverse event is at least a reasonable possibility.  
An adverse reaction, in contrast to an adverse event, is characterized by the fact that a causal 
relationship between a medicinal product and an occurrence is suspected. 
10.4 Recording and Follow-Up of 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.  
• 
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 required form.  
• 
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 sufficient 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.  


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• 
• 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. 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 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 intervention 
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 submitted documents.  


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• 
The investigator will submit any updated SAE data to GSK within 24 hours of receipt of 
the information. 
 
 
10.5 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 
tool.  
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) 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 [X/medical monitor/SAE coordinator] by telephone.  
• 
Mail to Qwy11935@gsk.com to report SAE. 
 
SAE Reporting to GSK via Paper Data Collection Tool 
• 
• Facsimile transmission of the SAE paper data collection tool is the preferred method to 
transmit this information to the [X/medical monitor or the SAE coordinator].  
• 
• In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service.  
• 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE data collection tool within the designated reporting time 
frames.  
• 
• Mail to Qwy11935@gsk.com to report SAE 
 
 


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11 
APPENDIX 4: COLLECTION OF PREGNANCY 
INFORMATION 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with ONE of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
Note: Documentation can come from the site personnel’s review of participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. 
• 
Females on HRT must have physician confirmation of postmenopausal status 
prior to study enrolment. 
Female Participants who become pregnant 
• 
Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study. 
• 
Information will be recorded on the appropriate form and submitted to GSK 
within 24 hours of learning of a participant's pregnancy. 
• 
Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on participant and neonate, which 
will be forwarded to GSK. 
• 
Generally, follow-up will not be required for longer than 6 to 8 weeks beyond 
the estimated delivery date. 
• 
Any termination of pregnancy will be reported, regardless of foetal status 
(presence or absence of anomalies) or indication for procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
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A spontaneous abortion is always considered to be an SAE and will be reported as such. 
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to 
GSK as described in Section 5.2. While the investigator is not obligated to 
actively seek this information in former study participants, he or she may learn 
of an SAE through spontaneous reporting. 
Any female participant who becomes pregnant while participating will be withdrawn 
from the study. 


Signature Page for  217658 TMF-15637673 v2.0
Signature Page for TMF-15637673 v2.0
Reason for signing: Approved
Name:
Role: Approver
Date of signature: 27-Jan-2023 13:03:21 GMT+0000
PPD

SAP_001.pdf: 
Statistical Analysis Plan
Study ID:  217658
Official Title of Study: A 12-week, Prospective, Open Label, Single Cohort 
Study to Evaluate the Real-world Effectiveness of Fluticasone Furoate/
Umeclidinium Bromide/Vilanterol in a Single Inhaler (Trelegy Ellipta) in 
Symptomatic Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT ID: NCT05535972
Date of Document: 10-November-2023


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Page 1 of 20 
Information Type: 
Statistical Analysis Plan (SAP) 
 
TITLE PAGE 
Protocol Title: 
A 12-week, prospective, open label, single cohort study to evaluate the 
real-world effectiveness of Fluticasone Furoate/Umeclidinium 
Bromide/Vilanterol in a single inhaler (Trelegy Ellipta) in symptomatic 
chronic obstructive pulmonary disease (COPD) patients. 
Study Number: 
217658  
Compound Number: 
GSK2834425 
Abbreviated Title: 
Phase IV study of GSK2834425 in symptomatic COPD patients 
 
Sponsor Name: GlaxoSmithKline Research & Development Limited  
Regulatory Agency Identifier Number(s)  
 
Registry 
 
ID 
Chinadrugtrials.org.cn 
CTR20222010 
Clintrials.gov  
NCT05535972 
 
 
 
 
 
 
 
 
 
 
 
 
Copyright 2023 the GlaxoSmithKline group of companies. All rights reserved.  Unauthorised 
copying or use of this information is prohibited. 
 


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XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021  
Page 2 of 20 
TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
TABLE OF CONTENTS .................................................................................................. 2 
VERSION HISTORY ....................................................................................................... 4 
1. 
INTRODUCTION ...................................................................................................... 6 
1.1. 
Objectives, Estimands and Endpoints ........................................................... 6 
1.2. 
Study Design ................................................................................................ 8 
2. 
STATISTICAL HYPOTHESES ................................................................................. 8 
2.1. 
Multiplicity Adjustment .................................................................................. 8 
3. 
ANALYSIS SETS ..................................................................................................... 9 
4. 
STATISTICAL ANALYSES ....................................................................................... 9 
4.1. 
General Considerations ................................................................................ 9 
4.1.1. 
General Methodology .................................................................... 9 
4.1.2. 
Baseline Definition ......................................................................... 9 
4.2. 
Primary Endpoint Analyses ......................................................................... 10 
4.2.1. 
Definition of estimand .................................................................. 10 
4.2.2. 
Main analytical approach ............................................................. 10 
4.2.3. 
Sensitivity analyses ..................................................................... 11 
4.3. 
Secondary Endpoints Analyses .................................................................. 12 
4.3.1. 
Secondary endpoints ................................................................... 12 
4.4. 
Exploratory Endpoints Analyses ................................................................. 13 
4.5. 
Safety Analyses .......................................................................................... 13 
4.5.1. 
Adverse Events............................................................................ 13 
4.5.2. 
Vital Signs and Others ................................................................. 13 
4.6. 
Other Analyses ........................................................................................... 14 
4.6.1. 
Subgroup analyses ...................................................................... 14 
4.6.2. 
Other variables and/or parameters............................................... 14 
4.7. 
Sequence of Planned Analyses .................................................................. 14 
4.8. 
Changes to Protocol Defined Analyses ....................................................... 14 
5. 
SAMPLE SIZE DETERMINATION ......................................................................... 14 
6. 
SUPPORTING DOCUMENTATION ....................................................................... 15 
6.1. 
Appendix 1 Study Population Analyses ....................................................... 15 
6.1.1. 
Participant Disposition ................................................................. 15 
6.1.2. 
Demographic and Baseline Characteristics .................................. 15 
6.1.3. 
Protocol Deviation ........................................................................ 16 
6.1.4. 
Prior and Concomitant Treatments .............................................. 16 
6.1.5. 
Trelegy Exposure and Compliance .............................................. 16 
6.2. 
Appendix 2 Data Derivations Rule .............................................................. 17 
6.2.1. 
Study Period ................................................................................ 17 
6.3. 
Appendix 3 Assessment Windows .............................................................. 17 
6.3.1. 
General ........................................................................................ 17 


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Page 3 of 20 
6.3.2. 
E.D. Data ..................................................................................... 17 
6.4. 
Appendix 4 Handling of Missing or Partial Dates ......................................... 18 
6.5. 
References ................................................................................................. 19 
 


CONFIDENTIAL 
XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021  
Page 4 of 20 
Version history 
SAP 
Version 
Approval Date 
Protocol 
Version 
(Date) on 
which SAP 
is Based 
Change 
Rationale 
SAP 1.0 
10 Nov 2023 
Original 
(02Feb2022) 
Not Applicable 
Original 
version 
SAP 
amendmen
t 1.0 
10 Nov 2023 
Amend  
(27Jan2023) 
Add ‘to evaluate 
the proportion of 
patients achieving 
health status 
response 
with Trelegy.’  as 
the third secondary 
objective. 
Add an additional 
secondary outcome 
to see CAT score 
change at week 4. 
To align with 
Protocol 
Amendment. 
SAP 
amendmen
t 1.0 
10 Nov 2023 
Amend  
(27Jan2023) 
Remove Interim 
analysis in the 
section of ‘1.2 
study design’. 
Change the name 
of the Interim 
Analysis section to 
additional analysis 
for license renewal. 
To add 
flexibility to 
provide data 
for license 
renewal. 
SAP 
amendmen
t 1.0 
10 Nov 2023 
Amend 
(27Jan2023) 
Inverse-probability 
weighted mixed 
model for repeated 
measures 
(MMRM) was 
updated and written 
into the primary 
analysis. 
The MMRM 
may provide 
additional 
insights to the 
primary 
endpoint. 


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Page 5 of 20 
SAP 
Version 
Approval Date 
Protocol 
Version 
(Date) on 
which SAP 
is Based 
Change 
Rationale 
SAP 
amendmen
t 1.0 
10 Nov 2023 
Amend 
(27Jan2023) 
Update the baseline 
and post-baseline 
covariates for the 
primary analysis.  
Further 
specification 
of covariates 
used in IPW 
and MMRM. 
SAP 
amendmen
t 1.0 
10 Nov 2023 
Amend 
(27Jan2023) 
Delete the 
description of the 
process of filtering 
covariates. Update 
the description of 
using MMRM 
model to analyze 
the change from 
baseline in CAT 
score. Add the 
description that the 
week 4 and week 
12 may have 
different IPW 
weights. 
For 
clarification 
SAP 
amendmen
t 1.0 
10 Nov 2023 
Amend 
(27Jan2023) 
Update the 
description of 
sensitivity analysis 
and indicate the 
covariates included 
in the model. 
The 
description of 
the mothed of 
primary 
analysis 
changes. 
SAP 
amendmen
t 1.0 
10 Nov 2023 
Amend 
(27Jan2023) 
Delete the 
exploratory 
endpoint ‘Change 
from baseline of 
FEV1/FVC ratio at 
week 12’. 
Correction. 
 


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1. 
INTRODUCTION 
The purpose of this SAP is to describe the planned analyses to be included in the CSR for 
Study 217658. It describes the rules and conventions to be used in the analysis and 
presentation of data, the data to be summarised and analysed, including specificities of 
the statistical analyses to be performed. 
1.1. 
Objectives, Estimands and Endpoints 
Objectives 
Endpoints 
Primary 
 
• The primary objective of this study 
is to evaluate the effectiveness of 
Trelegy on health status in patients 
with symptomatic COPD at week 
12. 
• Change from baseline of CAT 
score at week 12  
Secondary 
 
• to evaluate the effectiveness of 
Trelegy on dyspnea in patients with 
symptomatic COPD at week 12. 
• to evaluate the effectiveness of 
Trelegy on lung function in 
patients with symptomatic COPD 
at week 12. 
• to evaluate the proportion of 
patients achieving health status 
response with Trelegy. 
• to evaluate the effectiveness of 
Trelegy on health status in patients 
with symptomatic COPD at week 
4. 
• Change from baseline of 
Modified Medical Research 
Council (mMRC) at week 12 
• Change from baseline of pre-dose 
FEV1 at week 12 
• Proportion of CAT responder 
(defined as ≥ 2 unit decrease from 
baseline) at week 12 
• Change from baseline of CAT 
score at week 4 
Exploratory 
 
• to evaluate the effectiveness of 
Trelegy on lung function in 
patients with symptomatic COPD  
• Change from baseline of Forced 
Vital Capacity (FVC), Forced 
Expiratory Flow at the 25 and 
75% (𝐹𝐸𝐹25−75), Inspiratory 
Capacity (IC) at week 12 


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Objectives 
Endpoints 
Safety 
 
• The safety objective is to collect 
the safety information of 
participants using Trelegy. 
• Trelegy related AEs 
• SAEs 
• AEs that lead to the 
discontinuation of Trelegy 
 
 
Primary estimand refers to Section 4.2.1. 


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1.2. 
Study Design 
Overview of Study Design and Key Features 
Design Features This is a 12-week, prospective, open label, single cohort study. The 
enrolled participants will be those who are symptomatic under COPD 
maintenance treatments, and newly prescribed with Trelegy under the 
discretion by clinical physicians.  
The study applies a single cohort design to evaluate the effectiveness 
following 12-week treatment with Trelegy by comparison to baseline data, 
which can reflect the benefits (i.e., CAT score and FEV1, etc.) of patients 
who remain symptomatic with their prior maintenance treatment. The 
decision to prescribe Trelegy shall be independent to the study with 
medical records providing documentation of a Trelegy prescription. 
The prospective data collection starts from Visit 1 when Trelegy is taken 
by patients for the first dose. The participants will complete the CAT score 
at Visit 1, Visit 2 and Visit 3 or early discontinuation/withdrawal visit 
(E.D.), and the mMRC at Visit 1 and Visit 3 or E.D. The participants' 
pulmonary function test will be assessed at Visit 1 and Visit 3 or E.D.. The 
investigators will record Trelegy-related adverse events (AEs), serious 
adverse events (SAEs) and AEs that lead to withdrawal from Trelegy. 
Study 
Treatment 
 
All patients will receive Trelegy (FF/UMEC/VI ELLIPTA 100/62.5/25 μg) 
according to the local SmPC. Participants are expected to inhale one dose 
in the morning from the Trelegy Ellipta at approximately the same time 
each day for 12 weeks after enrolment.  
 
 
2. 
STATISTICAL HYPOTHESES  
The primary objective of this study is to evaluate the effectiveness following 12-week treatment 
with Trelegy by comparison to baseline data. There are no formal hypothesis tests associated 
with this objective and no formal significance tests. 
2.1. 
Multiplicity Adjustment 
Not applicable. 


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3. 
ANALYSIS SETS 
For purposes of analysis, the following populations are defined: 
Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Screened  
All participants who were prescreened or screened, 
i.e. those having signed the informed consent.  
Disposition 
Enrolled 
All participants who entered the study, i.e. those 
having passed the screening procedure.  
Disposition 
Full 
Analysis Set 
(FAS) 
All participants who enrolled into the study and take 
at least one dose of Trelegy 
 
• Disposition 
• Demographic and 
baseline characteristic 
• All effectiveness 
analyses 
• All safety analyses 
 
4. 
STATISTICAL ANALYSES 
4.1. 
General Considerations 
4.1.1. 
General Methodology 
Unless otherwise specified, continuous data will be summarized using descriptive statistics: n, 
mean, standard deviation (std), median, minimum and maximum. Categorical data will be 
summarized as the number and percentage of participants in each category. 
Confidence intervals will use 95% confidence levels unless otherwise specified.  
4.1.2. 
Baseline Definition 
For all endpoints, the baseline value will be the latest pre-dose of Trelegy 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, and values at 
scheduled visit have higher priority than the ones at the unscheduled visits if the two records are 
on the same day.  
Unless otherwise stated, if baseline data is missing, no derivation and/or imputation will be 
performed and baseline will be set as missing. 
All baseline values will be referred to as ‘Baseline’ in the summary outputs. 


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4.2. 
Primary Endpoint Analyses 
4.2.1. 
Definition of estimand 
The primary clinical question of interest is: what is the change from baseline in CAT score at 
week 12, regardless of receiving a new COPD maintenance therapy or treatment discontinuation. 
The estimand is described by the following attributes:  
• 
Population: Symptomatic Chinese COPD participants who are receiving COPD 
maintenance treatment  
• 
Treatment condition: Trelegy (FF/UMEC/VI ELLIPTA 100/62.5/25 µg) one dose daily, 
inhaled  
• 
Variable: change from baseline of CAT score at week 12.  
• 
Intercurrent events: 
o Receiving other COPD maintenance therapy is addressed by the treatment policy 
strategy.   
o Treatment discontinuation due to any reason is addressed by the treatment policy 
strategy.   
• 
Summary measure: average change from baseline in CAT score at week 12.   
Rationale: Interest lies in the treatment effect at week 12 in the real-world setting, maybe 
confounded by other COPD maintenance therapies or the event of treatment discontinuation due 
to any reason. Therefore, treatment policy strategy is employed to handle the intercurrent events 
of receiving a new COPD maintenance therapy and treatment discontinuation due to any reason 
as it reflects the clinical practice. 
The COPD Assessment Test (CAT) is a validated 8-item questionnaire developed for use in 
routine clinical practice to measure the health status of patients with COPD [Jones, 2009; Jones, 
2012]. Participants rate their experience on a 6-point scale (Protocol Appendix 1-1), ranging 
from 0 (no impairment) to 5 (maximum impairment) with a scoring range of 0-40. Higher scores 
indicated greater disease impact.  
In the derivation of CAT total score, the score of an item at a visit is set as the average of the 
other non-missing items when only this item is missing at that visit.   
4.2.2. 
Main analytical approach 
Primary analysis will be conducted using an inverse-probability weighted mixed model for 
repeated measures (MMRM) for the change from baseline in CAT score under the missing at 
random (MAR) assumption to handle missingness which may occur during the data collection.  
The inverse probability weighting (IPW) method can reduce the selection bias caused by the 
missingness, by weighting the participants whose change from baseline of CAT score is 
observed at week 12 using the inverse probability of completeness in the endpoint. The key 
assumption for the IPW method is MAR which means that the missingness mechanism of the 
primary endpoint could be modelled using the observed factors, i.e. the baseline covariates and 
the post-baseline covariates by the time of missingness, and no unmeasured confounders are 
involved in the missingness mechanism.  


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To estimate the probability of the completeness of the primary endpoint, a logistic model is 
constructed to model its missingness mechanism with the missingness status as the dependent 
variable (status=observed, status=missing as the reference group). The following baseline and 
post-baseline covariates will be considered for the missingness of change from baseline in CAT 
score at week 12:  
• 
Age, 
• 
Gender,  
• 
Years of COPD,  
• 
Smoking history: smoking status and number of pack years,  
• 
Pre-dose FEV1 at baseline,  
• COPD maintenance treatment at baseline, 
• 
CAT score at baseline,  
• 
The change from baseline in CAT score at week 4,  
• 
Intercurrent event status: no intercurrent events, received other COPD maintenance 
therapy, Trelegy discontinued due to other reason.  
The subjects receiving other COPD maintenance therapy are those who have 
discontinued their Trelegy therapy and switched to other COPD maintenance therapy. 
• Duration of Trelegy 
 
The right tail of estimated weights may be truncated by its appropriate percentile if deemed 
necessary.  
The change from baseline in CAT score will be analysed using the MMRM model with the 
covariates of smoking status, CAT score at baseline, visit, the interaction of CAT score at 
baseline*visit,  in which each observation is weighted with the inverse probabilities derived from 
the above logistic regression models.  
 
If a covariate is with missing values, the missing values in the covariate may be imputed if 
deemed necessary using appropriate imputation models with information by the time of its 
missingness. If any imputed covariate is used, the multiple imputation process will be employed 
to ensure the variability in the missingness of covariates are considered. At least 1000 datasets 
will be generated which include both observed and imputed values for the covariates. The 
inverse-probability weighted MMRM estimates,the corresponding standard errors and 95% 
confidence intervals from each dataset will be combined using the Rubin’s rule. 
Descriptive statistics will be summarized using the observed data.  
  
4.2.3. 
Sensitivity analyses 
Sensitivity analysis will be conducted using a MMRM with the covariates of smoking status, 
CAT score at baseline, visit, the interaction of CAT score at baseline*visit to derive the point 
estimate and the standard error of change from the baseline in the CAT score, but in which the 


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missing data in the primary endpoint will be imputed using monotone linear regression multiple 
imputation under missing at random assumption, for participants with no intercurrent events, 
receiving other COPD maintenance therapy, with treatment discontinuation, separately if data 
permits, otherwise may be imputed for the pooled groups, using the observed factors, i.e. the 
baseline covariates and the post-baseline covariates by the time of missingness.  
The missing values in the covariate may be imputed with information by time of its missingness 
if deemed necessary. 
At least 1000 datasets will be generated which include both observed and imputed values for the 
covariates. The MMRM estimates for the primary endpoint as well as the corresponding standard 
errors from each complete dataset will be combined using the Rubin’s rule. 
 
4.3. 
Secondary Endpoints Analyses 
4.3.1. 
Secondary endpoints 
The analysis approach for the below secondary endpoints is analogous to the primary analysis 
and the sensitivity analyses for the primary endpoint:  
• 
Change from baseline of Modified Medical Research Council (mMRC) at week 12  
• 
Change from baseline of pre-dose FEV1 at week 12  
• 
Proportion of CAT responder (defined as ≥ 2 unit decrease from baseline) at week 12  
• Change from baseline of CAT score at week 4 
 
In the analysis for the proportion of CAT responder (defined as ≥ 2 unit decrease from baseline) 
at week 12, the considerations follow:  
• 
Summary measure is the proportion of participants having ≥ 2 unit decrease from 
baseline at week 12.  
• 
The response status of a participant at a visit is set to missing if his/her CAT score at 
baseline or at the visit is missing. 
• 
The IPW weights used for primary endpoint were applied here to estimate the proportion 
of CAT responder at Week 12.  
 
 
The missingness of the change from baseline in CAT score at week 4 will be modelled 
analogously as the primary analysis but with the covariates collected before week 4. The missing 
values in the covariates may be imputed with information by time of its missingness. The IPW 
weights are applied at the observation level, thus the observations for a same subject with 
available change from baseline in CAT score values at the week 4 and week 12 may have 
different weights. 
 


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4.4. 
Exploratory Endpoints Analyses 
The analysis approaches for the below exploratory endpoints are analogous to the primary 
analysis and the sensitivity analyses for the primary endpoint: 
• 
Change from baseline of Forced Vital Capacity (FVC) at week 12 
• 
Change from baseline of Forced Expiratory Flow at the 25% and 75% (𝐹𝐸𝐹25−75) at 
week 12 
• 
Change from baseline of Inspiratory Capacity (IC) at week 12 
 
4.5. 
Safety Analyses 
The safety analyses will be based on the Full Analysis Set, unless otherwise specified. 
4.5.1. 
Adverse Events  
AE terms will be coded using Medicinal Dictionary for Regulatory Activities (MedDRA) 
dictionary.  
The number and percentage of participants experiencing at least one AE of below category will 
be summarized:  
• Overview of AEs 
• On-treatment AEs will be summarized by system organ class (SOC) and preferred term 
(PT) for:  
o Trelegy related non-serious AE  
o SAEs  
o Trelegy related SAEs 
o AE leading to discontinuation of Trelegy  
o Trelegy related AE leading to discontinuation of Trelegy  
• Post-treatment AEs will be summarized for: 
o SAEs by SOC and PT 
4.5.2. 
Vital Signs and Others 
 
Body Temperature, Pulse Rate, and Blood Pressure (systolic and diastolic) will be summarized at 
the scheduled time points specified in Visit 1 and Visit 3.  
Pregnancy status will be listed if any. 
 


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4.6. 
Other Analyses 
4.6.1. 
Subgroup analyses 
Subgroup analyses of the primary endpoint will be further investigated across the CAT score at 
baseline:  
• Moderate impact [CAT 10-20],  
• Severe impact [CAT 21-30],  
• Very severe impact [31-40]. 
4.6.2. 
Other variables and/or parameters 
Not applicable. 
4.7. 
Sequence of Planned Analyses 
To support the license renewal, an additional analysis may be performed with the early available 
study data (i.e. the data in participants who are enrolled by 29 May 2023 and at the time when 
they all have completed the study or withdrawn from study). This analysis is exclusively for the 
license renewal purpose and will not have any impact on the study design and other study 
criteria.  
 
The whole study data will be analysed when all the participants have completed the study or 
withdrawn from study.  
4.8. 
Changes to Protocol Defined Analyses 
Protocol defined that sensitivity analysis will be conducted using the arithmetic mean and 
missing data will be imputed using multiple imputation under missing at random assumption. 
The change is that sensitivity analysis will employ a mixed model for repeated measures 
(MMRM) to estimate the treatment effect. By employing the MMRM model, although the 
estimate of mean will not change, its standard error may be reduced due to the information from 
covariates, and the MMRM model provides additional insight to the impact of covariates. 
5. 
SAMPLE SIZE DETERMINATION 
INTREPID study [study 206854 China CSR GSK Document Number 2019N418769_00] 
showed that in the real world setting 19% participants had early withdrawn from the Trelegy 
treatment prior to week 24. Considering the difference in the China clinical practice and study 
designs, it is assumed that 79% enrolled participants would complete 12 weeks of Trelegy 
treatment with no intercurrent events, 20% would have the intercurrent event of receiving a new 
COPD maintenance therapy, 1% would have the intercurrent event of treatment discontinuation. 
 
Based on results from a few studies, i.e., IMPACT [Lipson, 2018; study CTT116855 China CSR 
GSK Document Number 2018N356723_00], INTREPID [study 206854 China CSR GSK 
Document Number 2019N418769_00] and one randomized controlled trial (RCT) [Bansal, 


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2021], it is assumed that a decrease of 2 in the primary endpoint at week 12 will be observed in 
this study with a common standard deviation of 7. 
 
A sample size of 460 is planned. With the assumptions in Table 1 of the protocol, the sample size 
would be able to provide a half-width ranging from 0.64 to 0.73 for the 95% confidence interval 
(CI) of the inverse probability weighted mean of the change from baseline in CAT score at week 
12 in the primary analysis under different missingness scenarios. 
6. 
SUPPORTING DOCUMENTATION 
6.1. 
Appendix 1 Study Population Analyses 
Unless otherwise specified, the study population analyses will be based on the Full Analysis Set.  
6.1.1. 
Participant Disposition 
A summary of the number of participants in each of the participant level analysis set will be 
provided. 
 
The participant disposition will be summarized for: 
• Number of withdrawals leading to the screening failure, number of subjects in the 
screening, number of subjects having failed the screening, based on the Screened 
Analysis Set. 
• Trelegy conclusion and the primary reason of the Trelegy discontinuation 
• 
Study conclusion and the primary reason of the Study discontinuation 
6.1.2. 
Demographic and Baseline Characteristics 
The following demographic characteristics will be summarized:  
• Age: continuous and also in the category of 18-<40, 40-<65, 65-<85 and >=85 ages.  
Age is derived using the date of the informed consent date. Day and Month of birth are 
imputed as 30 June. 
• Sex: male, female 
• Height: continuous 
• 
Weight: continuous 
• Body Mass Index (BMI): continuous, calculated as weight (kg)/[height (m)]2. 
 
The following baseline characteristics will be summarized:  
• COPD History:  
o Year of COPD, derived using the date of the informed consent date, continuous 
and also in the category of <6 months, >=6 months to <1 year, >=1 to <5 years, 
>=5 to <10 years, >=10 to <15 years, >=15 to <20 years, >=20 to <25 years and  
>=25 years. 
o Number of severe COPD Exacerbation during the Past Year,  
o Number of moderate COPD Exacerbation during the Past Year, 
o Number of moderate/severe COPD Exacerbation during the Past Year, continuous 
and also in the category of 0, 1 and >=2.  


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• 
Existing COPD Maintenance Treatment: ICS/LABA, LAMA/LABA, Free combination 
of ICS, LAMA, LABA 
• Medical history 
o The number and percentage of participants with each medical history condition  
• Smoking history 
o Smoking status 
o Year of smoking 
o Average Number of Units Consumed Per Day 
o Number of Pack Years 
• Physical examination: Normal, Abnormal - Not Clinically Significant, Abnormal - 
Clinically Significant 
• Electrocardiogram (ECG): Normal, Abnormal - Not Clinically Significant, Abnormal - 
Clinically Significant 
6.1.3. 
Protocol Deviation 
Important protocol deviations will be summarized. 
Protocol deviations will be tracked by the study team throughout the conduct of the study. These 
protocol deviations will be reviewed to identify those considered as important as follows: 
• Data will be reviewed prior to freezing the database to ensure all important deviations are 
captured and categorised in the protocol deviations dataset.  
• This dataset will be the basis for the summaries of important protocol deviations. 
 
6.1.4. 
Prior and Concomitant Treatments 
Prior and concomitant medication tables will be summarized by Anatomical Therapeutic 
Chemical (ATC) level 1 and ingredient for: 
• 
Pre-treatment COPD Medications 
• 
On-treatment COPD Medications 
• 
Post-treatment COPD Medications 
• 
Prior and Concomitant Non-COPD Medications 
Multi-ingredient medications will be presented according to their combination ATC 
classification rather than the classification of the ingredients. 
Prior and Concomitant Non-Drug Treatments will be summarized. 
6.1.5. 
Trelegy Exposure and Compliance 
The duration of Trelegy, the actual dose will be summarized.  


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A summary of overall compliance for Trelegy based on the exposure data will be produced. 
Overall compliance will be summarized using descriptive statistics as well as the categories 
<80%, 80%-105%, and >105%.  
Trelegy Compliance (%) = [Total cumulative actual dose / Total cumulative scheduled dose] 
*100. 
Number of subjects with treatment switch will be summarized. 
6.2. 
Appendix 2 Data Derivations Rule 
6.2.1. 
Study Period 
Assessments and events will be classified according to the time of occurrence relative to the 
study intervention period.  
Pre-treatment is defined as time prior to the first dose of Trelegy. 
On-treatment is defined as time from first dose to last date of Trelegy.  
Post-treatment is defined as any time post on-intervention window, i.e. > last dose date of 
Trelegy. 
For AE, if the study period cannot be determined due to partial or missing data, the study period 
would be classified as “on-treatment”, unless the end date of the AE rules out this probability. 
Trelegy-related AEs are classified as “on-treatment”. 
For COPD medications, a COPD medication may be classified into one or multiple categories of 
“pre-treatment”, “on-treatment” and “post-treatment” medication. If the study period cannot be 
determined due to partial or missing data, the medication would be classified into one or multiple 
categories of “pre-treatment”, “on-treatment” and “post-treatment” if it might satisfy the study 
period definition(s).  
 
6.3. 
Appendix 3 Assessment Windows 
6.3.1. 
General 
In general, data will be reported according to the nominal time of clinic visits and assessments as 
specified in the protocol. 
6.3.2. 
E.D. Data 
To make full use of effectiveness outcomes data, the effectiveness measurements collected at 
E.D. including CAT score, mMRC and Pulmonary function test (Pre-dosed FEV1, FVC, FEF25–75 
and IC) will be used according to the following rules: 


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• If E.D. date of the participant is before Day 55 (<=55), the participant’s value of week 12 
related endpoints will be treated as missing and its analysis approach can be found in 
Section 4. Otherwise, the participant’s value of week 12 related endpoints will be mapped 
to E.D. results. 
• If E.D. date of the participant is before Day 12 (<=12), the participant’s value of week 4 
related endpoints will be treated as missing and its analysis approach can be found in 
Section 4. Otherwise, the participant’s value of week 4 related endpoints will be mapped 
to E.D. results, if E.D. date of the participant is before Day 21 (<=20). 
 
6.4. 
Appendix 4 Handling of Missing or Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant 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 day of the month will be used, respectively, 
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 Section 6.2.1: Study Period. 
• 
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. 
Concomitant 
Medications/
Medical 
History 
• 
Partial dates for any concomitant medications or medical history recorded in 
the CRF will be imputed using the following convention: 
o If the partial date is start date, a ‘01’ will be used for the day and ‘Jan’ 
will be used for the month. 
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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6.5. 
References 
Bansal S, Anderson M, Anzueto A, Brown N, Compton C, Corbridge TC, et al. Single-inhaler 
fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus tiotropium 
monotherapy in patients with COPD. NPJ Prim Care Respir Med. 2021 May 25;31(1):29. 
China Clinical Study Report for study CTT116855 - A phase III, randomized, double-blind study 
comparing the efficacy, safety and tolerability of the Trelegy with the fixed dose dual 
combinations of FF/VI and UMEC/VI in subjects with COPD [GlaxoSmithKline Document 
Number 2018N356723_00] 
China Clinical Study Report for study 206854 - The Clinical Effectiveness of Fluticasone 
Furoate/Umeclidinium Bromide/Vilanterol in a Single Inhaler (TRELEGY TM ELLIPTA TM ) 
when Compared with Non-ELLIPTA Multiple Inhaler Triple Therapies in COPD Patients within 
a Usual Care Setting [GlaxoSmithKline Document Number 2019N418769_00] 
Clinical Study Protocol for study CTT116855 - A phase III, 52 week, randomized, double-blind, 
3-arm parallel group study, comparing the efficacy, safety and tolerability of the fixed dose triple 
combination FF/UMEC/VI with the fixed dose dual combinations of FF/VI and UMEC/VI, all 
administered once-daily in the morning via a dry powder inhaler in subjects with chronic 
obstructive pulmonary disease [GlaxoSmithKline Document Number 2013N176913_05] 
Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first 
validation of the COPD Assessment Test. Eur Respir J. 2009. 34(3):648-54. 
Jones PW, Harding G, Wiklund I, Berry P, Tabberer M, Yu R, et al. Tests of the responsiveness 
of the COPD assessment test following acute exacerbation and pulmonary rehabilitation. Chest. 
2012 Jul;142(1):134-140. 
Lipson DA, Barnhart F, Brealey N, Brooks J, Criner GJ, Day NC, et al. Once-Daily Single-
Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med 2018;378: 1671-80. 
 


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TRADEMARKS 
Trademarks of the GlaxoSmithKline Group 
of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
ELLIPTA 
 
MedDRA 
Trelegy 
 
SAS