Establishing Outcomes of Once-Daily ICS/LABA/LAMA Plus PRN Respiratory Therapy Treatments in Hospitalized Patients With COPD Exacerbations (SUNDIAL-COPD)
Phase: PHASE4
Conditions: Copd
Sponsor: Baylor Research Institute

IRB 021-182 
Sundial COPD 
PI Dr. Millard 
 
 
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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
Study Title: 
 
Establishing Outcomes of Once-Daily ICS/LABA/LAMA Plus PRN Respiratory Therapy Treatments in 
Hospitalized Patients with COPD Exacerbations (SUNDIAL-COPD) 
ORIGINAL PROTOCOL Version 1.4 
Dated   
 
 
8 March 2023 
Protocol History 
Original Protocol  
 
12 May 2021; Version 1.0  
 
 
 
 
20 October 2021; Version 1.1 
 
 
 
 
21 June 2022; Version 1.2 
 
Amendment 1  
 
9 December 2022; Version 1.3 
Amendment 2  
 
08 March 2023 Version 1.4 
 
Site Location:  
 
Baylor University Medical Center 
 
 
 
 
3500 Gaston Avenue 
 
 
 
 
Dallas, TX 75246 
Center for Advanced Heart and Lung Disease / 
Annette C. & Harold C. Simmons Transplant Institute 
3410 Worth St., Suite 250, Dallas, Texas 75246 
Phone: 214-820-6856 
Fax: 214-820-1474 
 
Principal Investigator:  
Mark W. Millard, MD 
 
 
 
 
 
Sub (Co)-Investigators:  
Susan Mathai, MD 
 

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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
 
  
 
PROTOCOL SIGNATURE PAGE 
Study Title:  Establishing Outcomes of Once-Daily ICS/LABA/LAMA Plus PRN Respiratory Therapy 
Treatments in Hospitalized Patients with COPD Exacerbations (SUNDIAL-COPD)  
 
Protocol Number:  N/A 
 
IRB Number: 021-182 
 
I have read this protocol and agree to adhere to the requirements outlined within. I will provide copies of 
this protocol and all pertinent information to the study personnel under my supervision. I will review and 
discuss this material with them and ensure they are fully informed regarding the requirements of this 
protocol. I will also ensure that this study is conducted in compliance with this protocol, Good Clinical 
Practice (GCP), and all applicable regulatory agencies and their requirements. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Investigator (Printed Name) 
 
_________________________________                                     ___________________________ 
Clinical Investigator (Signature) 
 
 
 
 
 
Date 
 
 

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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
PROTOCOL AMENDMENT HISTORY TABLE 
Protocol # 
Version Date 
Section 
(Section & page #) 
Language 
Added/Revised/Deleted 
Rationale 
V1.1 
Header 
IRB number added 
 
 
Section 9.3 
A telephone call will be made by an 
authorized study research staff 
member to assess if the subject was 
readmitted within 30 days of 
discharge. 
Detail added 
V1.2 
Section 5.2.3, 5.2.5 
Adding St. George questionnaire-
short version to enrollment. And 
adding short version term to 5.2.5 
Questionnaire name.  
 
Amendment 1 
9 December 2022 
Section 4 b i 
Page 20 
Inclusion criteria 
Diagnosis of COPD 
inspiratory flow rate  
Diagnosis of COPD (per 
investigator’s discretion by 
prior spirometry results or 
by spirometry assessment at 
screening visit) 
Acronym has been added 
(PIFR) 
Amendment 1 
9 December 2022 
Section 5.2.2, section 
5.2.3 
Page 23-22 
Change in the procedures during the 
screening visit section and 
enrollment section 
The procedures during the 
screening visit will include: 
1. Assignment of 
screening number 
2. Spirometry (FEV1, 
FVC, FEV1/FVC) 
3. Demographics 
4. Medical History 
5. Decision by 
investigator to 
enroll subject or to 

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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
declare screen 
failure. 
 
Amendment 1 
9 December 2022 
Section 5.2.4 
Page 24 
Change in the time of treatment 
administration  
Treatments will be 
administered by a respiratory 
therapist daily in the 
morning between 06:00 AM 
and 12:00 PM.   
Amendment 1 
9 December 2022 
Section 5.2.5 
Page 25 
A schedule a follow-up with the 
subject in the research clinic  
To obtain the missed 
assessments. 
Amendment 1 
9 December 2022 
Section 16.1 
Pages 37-38 
Gilead Science is deleted  
The sponsor is 
GlaxoSmithKline plc. (GSK) 
Amendment 1 
9 December 2022 
Section 16.2 
Page 39 
FDA Form 1572 is deleted from the 
Essential Documents list 
Invalid 
Amendment 2 
8 March 2023 
Section 1, Page 14 
Section 4, Page 20 
Section 8.7, Page 32 
9-month enrollment duration 
removed 
Updated enrollment 
timeline. 
 
 
 
 
 

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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
Table of Contents 
LIST OF ABBREVIATIONS .................................................................................................................................... 8 
1. 
SYNOPSIS ........................................................................................................................................................... 9 
2. 
OBJECTIVES & ENDPOINTS ...................................................................................................................... 15 
a. 
Primary Objective..................................................................................................................................... 15 
b. 
Secondary Objectives ............................................................................................................................... 15 
c. 
Exploratory Objectives ............................................................................................................................. 15 
d. 
Study Endpoints ........................................................................................................................................ 15 
3. 
BACKGROUND ............................................................................................................................................... 16 
a. 
Disease ........................................................................................................................................................ 16 
b. 
Therapy/Agent .......................................................................................................................................... 16 
c. 
Rationale for study.................................................................................................................................... 17 
4. 
PATIENT POPULATION ............................................................................................................................... 18 
a. 
Enrollment Goal ........................................................................................................................................ 19 
b. 
Eligibility Criteria ..................................................................................................................................... 19 
i. 
Inclusion Criteria .............................................................................................................................. 19 
ii. 
Exclusion Criteria ............................................................................................................................. 19 
5. 
STUDY VISITS AND ACTIVITIES ............................................................................................................... 21 
5.1 
DESIGN ..................................................................................................................................................... 21 
5.2 
STUDY VISITS ......................................................................................................................................... 21 
5.2.1 
PRE-SCREENING ........................................................................................................................... 21 
5.2.2 
SCREENING (+ 24 hours) ............................................................................................................... 21 
5.2.3 
ENROLLMENT (within 24 hours of admission) ........................................................................... 22 
5.2.4 
TREATMENT (Enrollment to Discharge) ..................................................................................... 23 
5.2.5 
DISCHARGE .................................................................................................................................... 23 

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5.2.6 
30 DAY POST DISCHARGE/WITHDRAWAL FOLLOW-UP .................................................. 24 
6. 
SAFETY & EVENT REPORTING ................................................................................................................ 24 
6.1 
ADVERSE EVENTS ................................................................................................................................ 25 
Table 1 Adverse Event Severity and Relationship to Study Drug ................................................................ 25 
6.2 
SERIOUS ADVERSE EVENTS .............................................................................................................. 26 
6.3 
DEVICE INCIDENTS REPORTING..................................................................................................... 27 
6.4 
COVID-19 CONSIDERATIONS ............................................................................................................ 28 
6.5 
PREGNANCY REPORTING .................................................................................................................. 28 
7. 
CONCOMITANT MEDICATION ................................................................................................................. 29 
7.1 
Data Collection .......................................................................................................................................... 29 
7.2 
Disallowed Medications ............................................................................................................................ 29 
8. 
PROTOCOL DEVIATIONS ........................................................................................................................... 29 
9. 
STATISTICAL ANALYSIS & DATA MANAGEMENT ............................................................................. 30 
8.1. 
Measurement of Safety ............................................................................................................................. 30 
8.2. 
Measurement of Efficacy .......................................................................................................................... 30 
8.3. 
Response Criteria ...................................................................................................................................... 30 
8.4. 
Data Reporting .......................................................................................................................................... 30 
8.5. 
Regulatory Requirements ........................................................................................................................ 31 
8.6. 
Multicenter Guidelines ............................................................................................................................. 31 
8.7. 
Statistical Considerations ......................................................................................................................... 31 
9 
ETHICS AND GOOD CLINICAL PRACTICE ............................................................................................ 32 
9.1 
Institutional Review Board/Independent Ethics Committee ................................................................ 32 
9.2 
Informed Consent ..................................................................................................................................... 33 
9.3 
Declaration of Helsinki ............................................................................................................................. 33 

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Protocol No. 021-182 
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10. 
COMPENSATION ....................................................................................................................................... 34 
11. 
COSTS ........................................................................................................................................................... 34 
12. 
SAFETY MONITORING ............................................................................................................................ 34 
13. 
DATA SAFETY MONITORING COMMITTEE (DSMC) ...................................................................... 34 
14. 
RISK AND BENEFITS TO PARTICIPANTS ........................................................................................... 34 
14.1 
POTENTIAL BENEFITS ........................................................................................................................ 35 
14.2 
POTENTIAL RISKS ................................................................................................................................ 35 
14.2.1 
Drug Adverse events ......................................................................................................................... 35 
14.2.2 
Physical Risks .................................................................................................................................... 35 
14.2.3 
Psychosocial & Privacy Risks .......................................................................................................... 35 
14.2.4 
Reproductive Risks and Contraception Guidelines ....................................................................... 36 
15. 
RISK/BENFIT ASSESSMENT ................................................................................................................... 36 
16. 
Protocol amendment procedures and data retention ................................................................................ 37 
16.1 
PROTOCOL AMENDMENTS AND OTHER CHANGES IN STUDY CONDUCT ............................ 37 
16.2 
RECORDING OF DATA, DOCUMENTATION, AND RETENTION OF DOCUMENTS ............. 38 
16.3 Auditing Procedures ..................................................................................................................................... 39 
17. 
Publication of Results ................................................................................................................................... 39 
18. 
DISCLOSURE AND CONFIDENTIALITY .............................................................................................. 39 
19. 
DATA SHARING ......................................................................................................................................... 41 
20. 
STUDY DISCONTINUATION ................................................................................................................... 41 
21. 
REFERENCES.............................................................................................................................................. 41 
22. 
APPENDICES ............................................................................................................................................... 42 
 
 
 
 

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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
 
Adverse event 
 
Ab 
Ag 
 
Antibody 
Antigen 
 
CRF 
Case report form 
FDA 
Food and Drug Administration 
HIPAA 
Health Insurance Portability and Accountability Act of 
1996 
IHC 
Immunohistochemistry  
IL-1R 
IR 
Interleukin-1 Receptor 
Increased risk 
IRB 
Institutional Review Board 
ITT 
Intent to treat 
IV 
Intravenous  
PHI 
Protected health information 
PI 
Principal Investigator 
PRN 
Pro re nata-as need arises 
SAE 
Serious adverse event 
SOP 
Standard operating procedure 
 
 
 
 

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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
1. SYNOPSIS 
Summary/Rational:  
This phase IV, post market approval single-center, open-label 
study will be used evaluate to a more standardized open-label 
protocol which would allow for a more accurate assessment of 
intervention outcomes when a combination LABA/LAMA/ICS 
inhaler is used as the primary scheduled daily inhaled therapy.  
Study Objectives: 
Primary objective:  
1. To establish the requirements for PRN respiratory therapy 
treatments in patients hospitalized with the diagnosis of 
COPD exacerbation receiving once-daily ICS/LABA/LAMA 
(fluticasone furoate/umeclidinium/vilanterol) therapy. 
Secondary objectives: 
1. To measure the distribution of inspiratory flow rates with an 
InCheck Dial device set on measuring PIF using the medium low 
resistance setting in patients admitted with COPD exacerbations 
at Baylor University Medical Center, Dallas TX at the time of 
enrollment and day of discharge 
2. To determine the hospital length of stay for patients admitted 
with the diagnosis of COPD exacerbation 
3. To monitor and report any side effects from using once-daily 
ICS/LABA/LAMA or PRN therapy. 
4. To evaluate the transition of care in delivering respiratory 
therapy medications from hospital to home 
5. To compare the number of PRN treatments, length of hospital 
stay, and rate of readmissions with findings in a previously 

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Protocol No. 021-182 
Version 1.4 
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analyzed historical cohort of 60 patients in our healthcare 
system. 
Exploratory Objectives 
To determine the cost of respiratory care for patients hospitalized 
with the diagnosis of COPD exacerbation. 
Study Design: 
Phase IV, post market approval, single-center, open-label study 
Number of Subjects:  Up to 120 subjects will be enrolled out of which approximately 
80 will be TRELEGY ELLIPTA Treated Subjects; this allows 
for an anticipated acceptance rate of 2/3 
Inclusion Criteria: 
A patient will be eligible for inclusion in this study if he or she 
meets all the following criteria:  
1. Willing and capable of providing written informed 
consent. 
2. Subjects aged 18 years or older at time of enrollment 
3. Diagnosis of COPD with or without asthma for ≥12 
months 
4. Hospitalized ≤24 hours prior to enrollment and currently 
hospitalized for COPD exacerbation with or without 
asthma.  
5. Able to properly use the Ellipta medication delivery 
device. 
6. Able to generate ≥ 30 L/min inspiratory flow at 
screening, measured with an InCheck DIAL adjusted to 
medium low resistance, to document a subject’s ability to 

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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
effectively inhale medication delivered via an Ellipta 
device. 
Exclusion Criteria: 
1. Clinically significant lung disease other than COPD with or 
without asthma 
2. Positive SARS-CoV-2 test at the time of ED or hospital 
admission, or any time between admission and enrollment. 
3. History of severe hypersensitivity to milk proteins or 
demonstrated hypersensitivity to fluticasone furoate, 
umeclidinium, vilanterol, or any of the excipients 
4. Unable to perform inspiratory flow or spirometry procedures. 
5. Critically ill patients, or patients with rapidly deteriorating or 
life-threatening episodes of COPD or asthma including: 
• Patients in critical care unit or transferred from critical 
care unit. 
o Patients who are transferred to critical care after 
enrollment will be withdrawn from the study and 
continue to receive care according to institutional 
standard practice. 
• Patients who initiate Bilevel Positive Airway Pressure 
(BiPAP) after hospitalization. 
o Patients who use BiPAP at baseline (prior to COPD 
exacerbation) may be included if BiPAP settings 
remain consistent with pre-exacerbation settings.  
Patients will be withdrawn if BiPAP settings are 
changed after enrollment. 

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Protocol No. 021-182 
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6. Pregnant or lactating women or women of child-bearing 
potential (WOCBP).  Women must meet the non-productive 
potential definition below to be eligible. 
➢ Non-reproductive potential is defined as: 
• Pre-menopausal females with one of the following: 
o Documented tubal ligation. 
o Documented hysteroscopic tubal occlusion procedure 
with follow-up confirmation of bilateral tubal 
ligation. 
o Hysterectomy. 
o Documented Bilateral Oophorectomy. 
• Postmenopausal defined as 12 months of spontaneous 
amenorrhea with an appropriate clinical profile (e.g., age 
appropriate, >45 years, in the absence of hormone 
replacement therapy). In questionable cases for women <60 
years of age, a blood sample with simultaneous follicle 
stimulating hormone and estradiol falling into the central 
laboratory’s postmenopausal reference range is confirmatory. 
Females under 60 years of age, who are on HRT and whose 
menopausal status is in doubt, are required to use a highly 
effective method to avoid pregnancy if they wish to continue 
their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal 
status prior to study enrolment. For most forms of HRT, at 
least 2 to 4 weeks will elapse between the cessation of 
therapy and the blood draw; this interval depends on the type 
and dosage of HRT. Following confirmation of their post-
menopausal status, subjects can resume use of HRT during 

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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
the study without use of a highly effective method to avoid 
pregnancy. 
 
Sponsor: 
GlaxoSmithKline plc. (GSK)-Only provide the drug. 
Baylor Scott and White Research Institute (BSWRI) 
Principal 
Investigators: 
Mark W Millard MD 
Primary Study 
Site/Data Center: 
Annette C. & Harold C. Simmons Transplant Institute 
3410 Worth St., Suite 250, Dallas, Texas 75246 
Phone: 214-820-6856 
Fax: 214-820-1474 
Medication: 
TRELEGY ELLIPTA (fluticasone furoate 100 mcg, 
umeclidinium 62.5 mcg, and vilanterol 25 mcg inhalation 
powder) 
Medication Delivery 
Device: 
ELLIPTA 
 
 

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Protocol No. 021-182 
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Efficacy 
Assessments: 
➢ Number of in-hospital PRN respiratory therapy treatments 
with PRN nebulized albuterol 2.5mg. 
➢ Time in between PRN respiratory therapy.  
➢ Change in respiratory inspiratory flow rate measured by 
InCheck DIAL at medium resistance from baseline to 
discharge.  
➢ Length of stay.  
➢ At-home drug compliance. 
➢ 30-day re-admissions (all-cause and COPD exacerbation), 
30-day survival, cost of in-hospital respiratory therapy, 
response to a patient satisfaction questionnaire (QOL 
questionnaire). 
Safety Assessments: 
• Vital signs and vital status. 
• Concomitant medication use. 
• Reporting of adverse events. 
• Pregnancy test (women of childbearing potential). 

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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
2. OBJECTIVES & ENDPOINTS 
 
a. Primary Objective 
1. To establish the requirements for PRN respiratory therapy treatments in patients 
hospitalized with the diagnosis of COPD exacerbation receiving once-daily 
ICS/LABA/LAMA (fluticasone furoate/umeclidinium/vilanterol) therapy. 
 
b. Secondary Objectives 
1. To measure the distribution of inspiratory flow rates with an InCheck Dial device set on 
measuring PIF using the medium low resistance setting in patients admitted with COPD 
exacerbations at Baylor University Medical Center, Dallas TX at the time of enrollment 
and day of discharge. 
2. To determine the hospital length of stay for patients admitted with the diagnosis of COPD 
exacerbation. 
3. To monitor and report any side effects from using once-daily ICS/LABA/LAMA or PRN 
therapy. 
4. To evaluate the transition of care in delivering respiratory therapy medications from 
hospital to home. 
5. To compare the number of PRN treatments, length of hospital stay, and rate of 
readmissions with findings in a previously analyzed historical cohort of 60 patients in our 
healthcare system. 
 
c. Exploratory Objectives 
To determine the cost of respiratory care for patients hospitalized with the diagnosis of COPD 
exacerbation. 
 
d. Study Endpoints 

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Protocol No. 021-182 
Version 1.4 
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To attain these objectives, the following study endpoints will be evaluated. Primary and 
secondary endpoints include the number of in-hospital PRN respiratory therapy treatments, 
time in between PRN respiratory therapy, change in peak inspiratory flow rate from baseline 
to discharge, length of stay, at-home drug compliance, 30-day re-admissions (all-cause and 
respiratory), 30-day survival, cost of respiratory therapy, QOL score, and safety measures 
(AEs and SAEs; Section 5). See section 8.7 on analytical methods to evaluate these endpoints. 
 
 
 
 
3. BACKGROUND 
a. Disease 
The disease under study is Chronic Obstructive Pulmonary Disease (COPD), a group of 
progressive chronic inflammatory diseases that cause obstruction of airflow in the lungs. COPD 
affects 16 million people in the United States, and its death rate is approximately 40 per 100,000.1 
Symptoms include breathing difficulty, cough, mucus/sputum production, and wheezing. The 
main cause of COPD in the United States is tobacco smoking. COPD may co-occur with asthma. 
 
b. Therapy/Agent 
TRELEGY ELLIPTA is supplied as a disposable light grey and beige plastic inhaler containing 2 
foil strips, each with 30 blisters. One strip contains fluticasone furoate (100 mcg per blister), and 
the other strip contains a blend of umeclidinium and vilanterol (62.5 mcg and 25 mcg per blister, 
respectively). A blister from each strip is used to create one dose. The inhaler is packaged within 
a moisture-protective foil tray with a desiccant and a peelable lid.   
 
It will be stored at room temperature between 68°F and 77°F (20°C and 25°C); excursions 
permitted from 59°F to 86°F (15°C to 30°C). It will be stored in a dry place away from direct heat 
or sunlight. 

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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
 
Subjects will be given TRELEGY ELLIPTA once daily at the same time every day (± 2 hours). 
TRELEGY ELLIPTA will be initiated the morning of enrollment if feasible, or the morning 
following hospital enrollment otherwise.  It will be administered as 1 inhalation by the orally 
inhaled route only. 
 
Although FDA approved, TRELEGY ELLIPTA is seldom prescribed to hospitalized COPD 
patients by treating physicians. Study participants will be consented prior to being prescribed 
TRELEGY ELLIPTA as part of this study. 
 
c. Rationale for study 
 
When exacerbations of COPD that require hospitalization occur, short-acting bronchodilators 
(both beta agonists and anticholinergics) are routinely prescribed as part of a comprehensive 
regimen that includes supplemental oxygen, parenteral corticosteroids, antibiotics (usually), and if 
severe, non-invasive positive pressure ventilation.  
 
According to GOLD 2018 recommendations,2 long-acting bronchodilators are to be introduced as 
soon as possible prior to discharge from the hospital if not continued during hospitalization. 
However, the recommendation to use short-acting bronchodilators as a primary therapeutic 
inhalant is based on grade C level of evidence, suggesting a paucity of data to support that 
position. Primarily related to pharmacy-driven cost considerations, the exclusive use of short-
acting bronchodilators has become the standard of care in treating hospitalized patients with 
COPD exacerbations, with the introduction of long-acting inhalants only upon discharge, by a 
number of institutions including Ben Taub Hospital in Houston (Nicola Hanania MD: personal 
communication), and throughout the Baylor Scott and White Healthcare System in Texas. This 
therapeutic substitution of short-acting for long-acting bronchodilators has been estimated to 
result in a cost savings of ~$400k at Baylor University Medical Center alone (personal 

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Protocol No. 021-182 
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communication: director of pharmacy services). Even so, few if any studies have evaluated the 
length of stay, in-hospital adverse events (nocturnal awakenings related to respiratory symptoms 
that occur beyond the window of pharmacologic efficacy of short-acting medications), respiratory 
therapy utilization or the potential impact upon re-hospitalizations with this paradigm shift of 
care. Sanford Hospital System in North Dakota recently published a study comparing a once daily 
long-acting combination with compared with a twice-daily combination and saw minimal cost 
savings and no real change in outcomes.3 This same system had previously studied substitution of 
twice daily beta agonist and once daily anticholinergic bronchodilators for combination short-
acting bronchodilators and found improved outcomes and cost savings but reported their results in 
a non-peer reviewed journal in (AARC Times, November 2011). 
 
Results of an analysis of 60 patient charts randomly selected after hospitalization at Baylor 
University Medical Center for an exacerbation of underlying airways disease (>90% with COPD) 
showed tremendous variation in practice patterns; with 30% of patients receiving short-acting 
beta-antagonists and muscarinic agonists (SABA/SAMA) only, 70% receiving long-acting beta-
antagonists (LABA) with PRN SABA/SAMA, and only 42% receiving a long-acting muscarinic 
agonist (LAMA), despite practice guidelines encouraging the use of SABA/SAMA only 
(typically 4 times daily and as needed). 
 
It is this large variability that renders the evaluation and interpretation of institution-specific 
outcomes difficult. The main impetus for the proposed study is therefore to establish a more 
standardized open-label protocol which would allow for a more accurate assessment of 
intervention outcomes. As one of several secondary goals of this study, we aim to compare key 
outcomes (including, number of PRN treatments, length of hospital stay, and rate of readmission) 
with those from the historical cohort described above, when a combination LABA/LAMA/ICS 
inhaler is used as the primary scheduled daily inhaled therapy. 
 
4. PATIENT POPULATION 

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Protocol No. 021-182 
Version 1.4 
Dated 8 MARCH 2023 
a. Enrollment Goal  
This study aims to enroll 80 subjects. With an anticipated acceptance rate of 2/3, this means we will 
approach 120 eligible candidates over that period. We estimate we will be able to achieve 30-day 
follow-up in 80% of enrolled patients. 
 
b. Eligibility Criteria 
i.   Inclusion Criteria  
a. Willing and capable of providing written informed consent. 
b. Subjects aged 18 years or older at time of enrollment. 
c. Diagnosis of COPD (per investigator’s discretion by prior spirometry results or by 
spirometry assessment at screening visit) with or without asthma for ≥12 months. 
d. Hospitalized ≤24 hours prior to enrollment and currently hospitalized for COPD 
exacerbation with or without asthma. 
e. Able to properly use the Ellipta medication delivery device. 
f. Able to generate ≥ 30 L/min inspiratory flow rate (PIFR) at screening, measured with 
an InCheck DIAL adjusted to medium low resistance, to document a subject’s ability 
to effectively inhale medication delivered via an Ellipta device. 
ii.   Exclusion Criteria 
a. Clinically significant lung disease other than COPD with or without asthma. 
b. Positive SARS-CoV-2 test at the time of ED or hospital admission, or any time 
between admission and enrollment. 
c. History of severe hypersensitivity to milk proteins or demonstrated hypersensitivity to 
fluticasone furoate, umeclidinium, vilanterol, or any of the excipients. 
d. Unable to perform inspiratory flow or spirometry procedures. 
e. Critically ill patients, or patients with rapidly deteriorating or life-threatening episodes 
of COPD or asthma including: 
• Patients in critical care unit, or transferred from critical care unit. 

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Protocol No. 021-182 
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• Patients who are transferred to critical care after enrollment will be 
withdrawn from the study and continue to receive care according to 
institutional standard practice. 
• Patients who initiate Bilevel Positive Airway Pressure (BiPAP) after 
hospitalization. 
o Patients who use BiPAP at baseline (prior to COPD exacerbation) may 
be included if BiPAP settings remain consistent with pre-exacerbation 
settings.  Patients will be withdrawn if BiPAP settings are changed after 
enrollment. 
f. Pregnant or lactating women or women of child-bearing potential (WOCBP).  Women 
must meet the non-productive potential definition below to be eligible. 
➢ Non-reproductive potential is defined as: 
o Pre-menopausal females with one of the following: 
▪ Documented tubal ligation. 
▪ Documented hysteroscopic tubal occlusion procedure with follow-
up confirmation of bilateral tubal ligation. 
▪ Hysterectomy. 
▪ Documented Bilateral Oophorectomy. 
o Postmenopausal defined as 12 months of spontaneous amenorrhea with an 
appropriate clinical profile (e.g., age appropriate, >45 years, in the absence 
of hormone replacement therapy). In questionable cases for women <60 
years of age, a blood sample with simultaneous follicle stimulating hormone 
and estradiol falling into the central laboratory’s postmenopausal reference 
range is confirmatory. Females under 60 years of age, who are on HRT and 
whose menopausal status is in doubt, are required to use a highly effective 
method to avoid pregnancy if they wish to continue their HRT during the 
study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status prior to study enrolment. For most forms of HRT, at 

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least 2 to 4 weeks will elapse between the cessation of therapy and the 
blood draw; this interval depends on the type and dosage of HRT. 
Following confirmation of their post-menopausal status, subjects can 
resume use of HRT during the study without use of a highly effective 
method to avoid pregnancy. 
 
5.   STUDY VISITS AND ACTIVITIES 
 
5.1 DESIGN 
This is a single-center, phase IV, post market approval prospective, open-label study evaluating 
outcomes of TRELEGY ELLIPTA (fluticasone furoate 100 mcg, umeclidinium 62.5 mcg, and 
vilanterol 25 mcg inhalation powder) on PRN nebulized short-acting beta agonist (SABA) 
treatment in hospitalized subjects with COPD with or without asthma.   
Approximately 80 adult subjects with COPD with or without asthma will take part in this study at 
Baylor University Medical Center. Subjects will be given TRELEGY ELLIPTA, using the Ellipta 
device, placed on a consistent short-term systemic corticosteroid therapy, and followed until 30 
days post hospital discharge. This study will not include patients with rapidly deteriorating or 
potentially life-threatening episodes of COPD or asthma. 
 
5.2 STUDY VISITS  
 
5.2.1 PRE-SCREENING 
The inpatient hospital team will identify and refer the potential subject to the study team. 
The study team will verify that all inclusion criteria and none of the exclusion criteria are 
met.  
 
5.2.2 SCREENING (+ 24 hours) 

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Subjects will be identified from the inpatient hospital team. Prior to participation in the 
study, each subject will be given an opportunity to ask questions and to understand the 
details of study participation, including risks and benefits. The consent process will be 
documented in the subject’s source documents.  
 
Assessments and procedures at screening 
• Informed consent  
• Assignment of screening number 
• Inspiratory Flow Rate (PIFR) evaluation, with InCheck DIAL device set to 
measure medium low resistance. The best of 3 maximum inspiratory flow 
measurements, taken from RV will be recorded. 
▪ Spirometry (FEV1, FVC, FEV1/FVC) 
• Inclusion/Exclusion Criteria 
• Demographics 
▪ Medical History 
• Decision by investigator to enroll subject or to declare screen failure. 
 
5.2.3 ENROLLMENT (within 24 hours of admission) 
The following procedures/assessments will be done the morning or following morning of 
admission into study: 
• Concomitant Medications 
• Adverse Events (AE) Assessment 
• Patient Satisfaction Questionnaire (St George’s Respiratory questionnaire-short 
version) 
 
In addition, data from the specified assessments will be collected when available, and 
entered the case report forms (CRFs): 
• Vital signs 

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• Physical Exam 
 
5.2.4 TREATMENT (Enrollment to Discharge) 
TRELEGY ELLIPTA (fluticasone furoate 100 mcg, umeclidinium 62.5 mcg, and 
vilanterol 25 mcg inhalation powder) will be initiated on the morning of enrollment if 
feasible, or the morning after enrollment otherwise.  Treatment will continue daily until 
discharge.  Treatments will be administered by a respiratory therapist daily in the morning 
between 06:00 AM and 12:00 PM.  Patients will receive nebulized short-acting beta-2 
agonist (SABA) treatments of albuterol sulfate (2.5mg) as needed during hospitalization.  
Patients will receive prednisone 40 mg PO daily for the first 7 days from enrollment, 
subtracting 1 day for each consecutive day the patient received systemic corticosteroid 
treatment prior to enrollment. 
 
Treatment procedures/assessments include:  
• Concomitant Medications 
• AE Assessment 
• TRELEGY administration 
 
Data from the following specified assessments will be collected daily, when available, and 
entered the case report forms (CRFs): 
• Vital Signs 
• Short-acting beta agonist (SABA) therapy: number and time of treatments  
 
5.2.5 DISCHARGE 
Upon discharge, patients will receive a full TRELEGY ELLIPTA inhaler containing 30 
doses with instructions to take 1 puff daily in the morning for 30 days. The in-hospital use 
TRELEGY ELLIPTA used by the patient will be discarded. 
 

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The following procedures/assessments will be done prior to hospital discharge: 
• Spirometry (FEV1, FVC, FEV1/FVC) 
• Peak inspiratory flow rate, measured by the InCheck Dial set at medium resistance. 
• Concomitant Medications 
• Adverse Events (AE) Assessment 
• Patient Satisfaction Questionnaire (St George’s Respiratory questionnaire, short 
version) 
 
 
 
In addition, data from the specified assessments will be collected when available, and 
entered the case report forms (CRFS): 
• Vital signs 
• Withdrawal from protocol 
 
If for any reason, some of the research assessments at discharge are not performed, the 
study team may (at investigator’s discretion) schedule a follow-up with the subject in the 
research clinic to obtain the missed assessments. 
 
 
5.2.6 30 DAY POST DISCHARGE/WITHDRAWAL FOLLOW-UP 
Subjects will receive a follow-up phone call from a study coordinator and Medical Charts 
will be reviewed to assess if the subject was readmitted within 30 days of discharge.  
Follow-up phone call and Medical Chart review will instead occur 30 days after 
withdrawal for patients who are withdrawn prior to discharge.  
 
 
6. SAFETY & EVENT REPORTING 

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6.1 ADVERSE EVENTS 
An AE is any untoward sign, symptom or medical condition occurring at any time after the 
subject receives his/her first dose of study drug, even if the event is not considered to be 
related to the study drug. Information about all AEs whether volunteered by the subject, 
discovered by Investigator questioning, or detected through physical examination, 
laboratory test, or other means, will be collected, and recorded on the AE CRF and 
followed as appropriate. 
 
Abnormal laboratory values or test results constitute AEs only if they induce clinical signs 
or symptoms, and are considered clinically significant, or require therapy. They will be 
recorded on the AE CRF under signs, symptoms, or diagnosis associated with them.  
 
As far as possible, each AE will be described by: 
• Its duration (start and end dates) 
• The severity grade (mild, moderate, severe) 
• Its relationship to the study drug (suspected/not suspected) 
• The action (s) taken and as relevant 
• The outcome 
 
Criteria for determining the severity of an AE and its relationship to the study drug are 
shown below in Table 5-1. These criteria are guidelines. It is the responsibility of the 
Investigator to decide of severity and whether or not a relationship to study drug is 
suspected. 
 
Table 1 Adverse Event Severity and Relationship to Study Drug 
AE Severity 
Mild 
Awareness of sign or symptom but easily tolerated 

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Moderate 
Discomfort sufficient to cause interference with normal 
activities 
Severe 
Incapacitating, with inability to perform normal activities 
AE Relationship 
 
Suspected 
A clinical event, including laboratory test abnormality, with a 
reasonable time sequence to drug administration, which might 
or might not be also explained by concurrent disease or other 
drugs or chemicals 
Not Suspected 
A clinical event, including laboratory test abnormality, judged 
to be clearly and incontrovertibly due to extraneous causes 
(diseases, environment, etc.), or with a temporal relationship 
to drug administration which makes a causal relationship 
improbable, and/or for which other drugs, chemicals or 
underlying disease provide a much more plausible explanation 
Adverse events (including serious adverse events) will be monitored and reported from 
enrollment to discharge. 
 
 
6.2 SERIOUS ADVERSE EVENTS 
All Serious Adverse Events (SAEs) will be reported to the sponsor within 24 hours of 
awareness of the event.  An AE will be considered serious if it meets any of the following 
criteria: 
• Events resulting in death. 
• Life-threatening events 
• Events requiring hospitalization or prolongation of existing hospitalization. 
• Events resulting in persistent or significant disability/incapacity. 

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• Events not meeting any of the above criteria deemed to be serious by the 
Investigator. 
 
6.3 DEVICE INCIDENTS REPORTING 
Study drug administered via the ELLIPTA device is a drug/device combination product. All 
device incidents should be notified to the sponsor. 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 and a Serious Adverse Device Effect (SADE) that has 
resulted in any of the consequences characteristic of a serious adverse event and any device 
deficiency that might have led to an SAE if appropriate action had not been taken, intervention 
had not occurred, or circumstance had been less fortunate. Not all incidents lead to death or 
serious deterioration in health. The non-occurrence of such a result might have been due to 
other fortunate circumstances or to the intervention of health care personnel. It is sufficient 
that: an incident associated with a device happened; and the incident was such that, if it 
occurred again, it might lead to death or serious deterioration in health. 
 
Device incidents should be reported as outlined below, and not as a safety event. 
 
It is possible for a reportable safety event to occur at the same time as a device incident. Safety 
events are reported as described in Section 5.1 and should be reported in parallel as an 
AE/SAE as appropriate. 
 
If a device incident is detected, the following process should be followed: 
o Report the incident to the sponsor using the Combination Product with Device 
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o Arrange for a new device to be provided if not already done so by a pharmacy/ 
prescription. 
 
 
6.4 COVID-19 CONSIDERATIONS 
 
It is standard practice for patients admitted with respiratory symptoms to receive SARS-CoV-2 
testing at the time of admission.  The study will not require additional testing but will record 
results of any additional SARS-CoV-2 testing that occurs during hospitalization. 
 
Patients with positive SARS-CoV-2 test at the time of admission or in the time between 
admission and enrollment will be excluded from the study.  Patients with positive SARS-CoV-
2 test after the time of enrollment will be withdrawn from the study and will continue to 
receive care according to institutional standard practice. 
 
 
 
6.5 PREGNANCY REPORTING 
If pregnancy occurs in a female participant, the pregnancy should be reported as outlined 
below. 
• Details of all pregnancies in female participants will be collected after the start of 
study intervention and until the safety follow-up visit. 
• If a pregnancy is reported, the investigator will record pregnancy information on 
the appropriate form and submit it to the sponsor within 24 hours of learning of the 
pregnancy.  While pregnancy itself is not considered to be an AE or SAE, any 
pregnancy complication or elective termination of a pregnancy for medical reasons 
will be reported as an AE or SAE. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
as such. 

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• The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate, 
and the information will be forwarded to the sponsor. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section. 
• 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 in the study will 
discontinue study intervention but may remain in the study (if consent is not 
withdrawn). 
 
7. CONCOMITANT MEDICATION 
7.1 Data Collection 
Concomitant medications will be assessed from Enrollment to Discharge. The stop and start date, 
dose, brand name, generic name, and indication for each concomitant medication will be 
documented in source documents and on CRFs. 
 
7.2 Disallowed Medications 
Subjects will be prohibited from taking the following medications during the study: 
• Inhaled short-acting muscarinic antagonist (SAMAs), such as ipratropium bromide. 
• Inhaled therapies other than TRELEGY ELLIPTA containing any of the following:  
ICS, LAMA, or LABA. 
 
8. PROTOCOL DEVIATIONS 
Any event, whether planned or not, where the procedures as outlined in the documents approved by 
the IRB are not followed. Record all protocol deviations in the CRFs. 
 

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Report all unplanned deviations that involve a potential for increased risk to the subjects to the IRB 
within 10 days of occurrence or becoming aware of the occurrence. Report all unplanned deviations 
that do not involve increased risk to the subjects to the IRB at the next continuing review.  
 
9. STATISTICAL ANALYSIS & DATA MANAGEMENT 
Continuous variables will be reported as means ± standard deviations or medians [quartile 1, quartile 3], if 
skewed. Categorical variables will be reported as frequencies and percentages.  
8.1.Measurement of Safety 
Safety will be assessed by monitoring vital signs, body weight, concomitant medication use, adverse 
events (AE), and serious adverse events (SAE). 
8.2.Measurement of Efficacy 
Efficacy will be assessed by the number of in-hospital PRN respiratory therapy treatments with PRN 
nebulized albuterol 2.5mg, time in between PRN respiratory therapy, change in respiratory inspiratory 
flow rate measured by InCheck DIAL at medium resistance  from baseline to discharge, length of 
stay, at-home drug compliance, 30-day re-admissions (all-cause and COPD exacerbation), 30-day 
survival, cost of in-hospital respiratory therapy, and response to a patient satisfaction questionnaire 
(QOL questionnaire).  
Drug compliance at home will be assessed through follow-up phone call at 30-day post-discharge. 
Compliance will be calculated as the difference between 100 and the percentage of doses left on the 
TRELEGY ELLIPTA inhaler out of 30. 
8.3.Response Criteria 
N/A 
8.4.Data Reporting 

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It is intended that the results of the study will be published in at least one abstract for a scientific 
meeting and one manuscript. 
8.5.Regulatory Requirements 
All subject records will only be identified by a unique screening number. Subjects’ names are not to 
be transmitted to the Sponsor. The Investigator or designated site personnel will keep a master subject 
list containing the patient identification number, full name, date of birth, and hospital (or other) 
identification number of each subject. 
8.6.Multicenter Guidelines 
This is a single-center study. 
8.7.Statistical Considerations  
a. Study Design Endpoints 
Primary and secondary endpoints include the number of in-hospital PRN respiratory therapy 
treatments, time in between PRN respiratory therapy, change in peak inspiratory flow rate 
measured with an InCheck DIAL through medium low resistance from baseline to discharge, 
length of stay, at-home drug compliance, 30-day re-admissions (all-cause and respiratory), 30-
day survival, cost of respiratory therapy, and QOL score. 
b. Sample Size & Accrual Rate 
Enrollment of 80 patients. 
c. Analysis of Primary Endpoint 
The number of PRN respiratory treatments during hospitalization will be reported as the 
median [quartile 1, quartile 3] and as the average number of PRN respiratory treatments per-
inpatient day ± standard deviation. A comparison between patients who were and were not 
readmitted within 30-days will be made using a Wilcoxon signed rank test for the number of 
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day PRN treatments will be estimated using a robust Poisson regression model comparing 
patients who were readmitted within 30-days to those who were not. 
d. Analysis of Secondary Endpoints 
Time (in days) in between PRN treatments, change in respiratory inspiratory flow rate from 
baseline to discharge, length of stay, at-home drug compliance, 30-day readmissions (all-cause 
and COPD/Asthma exacerbation), and 30-day survival will be compared between patients who 
were and were not readmitted using t-tests or chi-square tests (or Wilcoxon Rank Sum tests 
and Fisher’s Exact tests), as appropriate. 
The efficacy of the treatment protocol in the study cohort compared to the historical cohort 
will be assessed by comparing (1) the average number of PRN treatments per patient day while 
hospitalized estimated using a robust Poisson regression model (2) length of stay in the 
hospital, and (3) the rate of rehospitalization, using the Wilcoxon Rank sum test.  
e. Reporting and Exclusions 
Missing data will not be imputed or carried forward in any of the analyses.  
The sample size for continuous variables will be the number of subjects with non-missing 
data; in the summary of categorical variables, subjects with missing data will be excluded in 
the calculation of percentages. 
 
9 ETHICS AND GOOD CLINICAL PRACTICE 
9.1 Institutional Review Board/Independent Ethics Committee 
The Investigator will submit this protocol and ICF for IRB approval prior to starting the study. 
The Investigator will not begin any study subject activities until approval from the IRB has 
been documented and provided as a letter to the Investigator. Before implementation, the 
Investigators will submit to and receive documented approval from the IRB of any 
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after initial IRB approval, except for those necessary to reduce immediate risk to study 
subjects.  
 
9.2 Informed Consent 
The investigator or delegated person must explain to each subject the nature of the study, its 
purpose, the procedures involved and any discomfort it may entail. Each subject must be 
informed that participation in the study is voluntary, that he/she may withdraw from the study 
at any time, and that withdrawal of consent will not affect his/her subsequent medical 
treatment or relationship with the treating physician.  
 
The informed consent should be given by means of a standard written statement, written in 
nontechnical language. The subject should read and consider the statement before signing and 
dating it and should be given a copy of the signed document. No subject can enter the study 
before his/her informed consent has been obtained. The ICF must be submitted by the 
Investigator for IRB approval. 
 
There will also be an option to do electronic consenting and electronic signatures by using study 
approved methods such as hospital telehealth system, patient iPad, telephone calls/telephone 
video conferencing. Documents will be sent electronically to the email address you provide for 
you to review the documents and sign off on.   
 
A telephone call will be made by an authorized study research staff member to assess if the 
subject was readmitted within 30 days of discharge. 
 
9.3 Declaration of Helsinki   
The Investigator must conduct the study in accordance with the principles of the current 
version of the Declaration of Helsinki. Copies of the Declaration of Helsinki and 

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amendments will be provided upon request or can be accessed via the website of the World 
Medical Association at http://www.wma.net/en/30publications/10policies/b3/index.html 
 
10. COMPENSATION 
 
Participants will not receive any compensation for participating in this study. 
 
11. COSTS 
Participants will not incur any additional costs due to study participation. Patient or their insurance 
company will be required to pay for all expenses related to regular care including hospital care. 
 
12. SAFETY MONITORING 
Safety will be assessed by monitoring the following:  
• Vital signs, 
• height,  
• body weight,  
• concomitant medication use,  
• AEs, SAEs,  
• Pregnancy testing for women of childbearing potential, as determined by the study PI 
 
 
 
13. DATA SAFETY MONITORING COMMITTEE (DSMC) 
It has been determined that this study does not need a DSMB as the study drug has full FDA 
approval. 
 
14. RISK AND BENEFITS TO PARTICIPANTS 
 

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14.1 POTENTIAL BENEFITS 
There may or maynot be be any direct benefit to the patients who participate in this study.  
 
14.2 POTENTIAL RISKS 
14.2.1 Drug Adverse events 
• COPD: Most common adverse reactions (incidence ≥1%) are upper respiratory 
tract infection, pneumonia, bronchitis, oral candidiasis, headache, back pain, 
arthralgia, influenza, sinusitis, pharyngitis, rhinitis, dysgeusia, constipation, 
urinary tract infection, diarrhea, gastroenteritis, oropharyngeal pain, cough, and 
dysphonia. (6.1) 
• Asthma: Most common adverse reactions (incidence ≥2%) are 
pharyngitis/nasopharyngitis, upper respiratory tract infection/viral upper 
respiratory tract infection, bronchitis, respiratory tract infection/viral respiratory 
tract infection, sinusitis/acute sinusitis, urinary tract infection, rhinitis, 
influenza, headache, and back pain. (6.2) 
14.2.2 Physical Risks 
The Ellipta oral inahler may cause a bad taste, soreness or irritation of the mouth and 
throat. 
 
14.2.3 Psychosocial & Privacy Risks 
Any time information is collected there is a potential for loss of confidentiality. Every effort 
will be made to keep participant’s information confidential, however this cannot be 
guaranteed.  
 
Participation in research study may make participants feel uncomfortable.  
 
Participants will be informed that they may refuse to participate or stop their participation at 
any time without effect on future medical treatment or relationship with the treating physician. 

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14.2.4 Reproductive Risks and Contraception Guidelines   
Women must meet the non-productive potential definition below to be eligible. 
Non-reproductive potential is defined as: 
➢ Pre-menopausal females with one of the following: 
• Documented tubal ligation. 
• Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of 
bilateral tubal ligation. 
• Hysterectomy 
• Documented Bilateral Oophorectomy 
➢ Postmenopausal defined as: 
12 months of spontaneous amenorrhea with an appropriate clinical profile (e.g., age 
appropriate, >45 years, in the absence of hormone replacement therapy). In questionable cases 
for women <60 years of age, a blood sample with simultaneous follicle stimulating hormone 
and estradiol falling into the central laboratory’s postmenopausal reference range is 
confirmatory. Females under 60 years of age, who are on HRT and whose menopausal status is 
in doubt, are required to use a highly effective method to avoid pregnancy if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status prior to study enrolment. For most forms of HRT, at 
least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this 
interval depends on the type and dosage of HRT. Following confirmation of their post-
menopausal status, subjects can resume use of HRT during the study without use of a highly 
effective method to avoid pregnancy. 
 
15. RISK/BENFIT ASSESSMENT 
There may be no direct benefit to the subjects.  However, the information obtained may help to 
advance the understanding of COPD disease and improve treatment protocols, may thus be of 
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no cost from participating in this study.  They are also not paid for their participation. As, except 
for the study drug, all other medical care will be part of routine care, they are still responsible for 
the costs of the hospitalization, clinic visit, and any clinical labs ordered by their doctors.   
 
16. Protocol amendment procedures and data retention 
16.1 PROTOCOL AMENDMENTS AND OTHER CHANGES IN STUDY CONDUCT 
Protocol Amendments  
Any substantive changes will be made as formal amendments to the protocol and will be 
submitted for appropriate review by an institutional review board (IRB), and to regulatory 
authorities. 
Any change or addition to this protocol requires a written protocol amendment that must be 
approved by GlaxoSmithKline plc. (GSK)and the Investigator before implementation. 
Amendments affecting the safety of subjects, the scope of the investigation, or the scientific 
quality of the study require additional approval by the IRB. Examples of amendments requiring 
such approval are: 
1. 
A significant change in the study design (e.g., addition or deletion of a control group) 
2. 
An increase in the number of invasive procedures to which subjects are exposed 
3. 
Addition or deletion of a test procedure for safety monitoring 
These requirements for approval should in no way prevent any immediate action from being taken 
by the Investigator to ensure the safety of all subjects included in the study. If an immediate 
change to the protocol is deemed necessary by the Investigator and is implemented by him/her for 
safety reasons, GlaxoSmithKline plc. (GSK)should be notified, and the IRB should be informed 
within 10 working days. 
Protocol changes affecting only administrative aspects of the study do not require formal protocol 
amendments or IRB approval, but the IRB must be kept informed of such administrative changes.  

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16.2 RECORDING OF DATA, DOCUMENTATION, AND RETENTION OF 
DOCUMENTS 
Data will be stored and evaluated in such a way as to guarantee subject confidentiality in 
accordance with the legal stipulations applying to confidentiality of data. All study records must 
be available for inspection by the Sponsor, its authorized representatives, the FDA, and other 
regulatory authorities. 
 
Data on subjects collected on CRFs during the study will be documented in an anonymous fashion 
and the subject will only be identified by the study number and by initials if also required. If, as an 
exception, it is necessary for safety or regulatory reasons to identify the subject, both Gilead 
Sciences, Inc. and the Investigator are bound to keep this information confidential.  
 
The Investigator must maintain source documents for each subject in the study, consisting of all 
demographic and medical information, and must keep a copy of the signed ICF. The subject’s 
clinical source documents (usually defined by the project in advance to record key efficacy/safety 
parameters independent of the CRFs) would include but are not limited to the subject’s 
hospital/clinic records, physicians’ and nurses’ notes, appointment book, original laboratory 
reports, ECG, pathology, and special assessment reports and signed ICFs. All information on the 
CRFs must be traceable to these source documents in the subject's file. Data without a written or 
electronic record will be defined before study start and will be recorded directly on the CRFs, 
which will be documented as being the source data.  
 
Essential documents defined in the ICH Guidance on Good Clinical Practice (ICH E6) and listed 
below, must be retained by the Investigator for as long as needed to comply with national and 
international regulations. The Sponsor will notify the Investigator(s)/institution(s) when the study-
related records are no longer required. The Investigator agrees to adhere to the document retention 
procedures by signing the protocol.  
 

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Essential documents include: 
1. 
IRB approvals for the study protocol and all amendments 
2. 
All source documents and laboratory records 
3. 
CRF copies  
4. 
Subjects' ICFs (with study number and title of study) 
5. 
Country-specific regulatory documents 
16.3 Auditing Procedures 
 
Investigator understands that source documents for this study must be made available to 
appropriately qualified personnel from the Sponsor or its designees, to the IRB, and/or to 
health authority inspectors after appropriate notification. The verification of the CRF data 
must be by direct inspection of source documents. The Sponsor conducts audits of clinical 
research activities in accordance with internal SOPs to evaluate compliance with the 
principles of GCP. A regulatory authority may also wish to conduct an inspection (during the 
study or even after its completion). If an inspection is requested by a regulatory authority, the 
Investigator must immediately inform the Sponsor that this request has been made. 
 
17. Publication of Results 
An integrated clinical and statistical report will be prepared at the completion of the treatment 
period. However, it is intended that the results of the study will be included on 
http://clinicaltrials.gov and published and/or presented at scientific meetings. 
 
18. DISCLOSURE AND CONFIDENTIALITY 
By signing this protocol, the Investigator agrees to keep all information provided by 
GlaxoSmithKline plc. in strict confidence and to request similar confidentiality from his/her staff 
and the IRB. The information provided by GlaxoSmithKline plc. to the Investigator may not be 
disclosed to others without direct written authorization from GSK, except to the extent necessary 
to obtain informed consent from subjects who wish to participate in the study. 

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All information will be kept private. The Investigator will assure that subjects’ anonymity will be 
maintained and that their identities are protected from unauthorized parties. The Investigator 
should keep a subject enrollment log relating codes to the names of subjects. The Investigator 
should maintain documents not for submission to the Sponsor, (e.g., subjects’ signed consent 
forms), in strict confidence. 
 
If scientific reports, publications, or educational materials are written using information from the 
database, patients within the database will not be identified by name, and data will be present only 
in aggregate form. They will be given a subject identification number.   
 
Access to this database will be restricted by a database manager and will be password protected.  
The only individuals who will be able to see patient identifiers, like name, date of birth, date of 
surgery will be the Principal Investigator, research coordinators, recruiters, and the database 
managers.  Other investigators will have different passwords that will provide restricted access to 
the database.  Those with restricted access will be able to query the database for scientific 
information/variables but will not be able to view information on patient identifiers such as name, 
address, and social security number.  If investigators with restricted access want to conduct studies 
which require them to obtain patient identifiers so that patients can be contacted for follow-up 
information/follow-up visits, these investigators will have to submit a separate protocol to IRB to 
get permission to obtain patient identifiers and contact patients.   
 
The information in the database will help study pulmonary disease and lung transplant.  These 
studies will require authorization by the Principal Investigator.  Any approved study run by an 
investigator must be approved by an Institutional Review Board.   
 

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All personnel that are involved with this protocol or that will have access to the Biobank have 
passed the IRB certifying examination.  The personnel will only include faculty and staff 
employed at the recruitment site (BUMC). 
 
19. DATA SHARING 
Data generated from this study may be shared with the study sponsor.  No information that can 
directly identify participants will be shared outside the study site/study team.   
 
Information that may be released to institutional study researchers may include, but is not limited 
to medical information, age, sex, ethnic background, family history, imaging data, blood samples, 
and blood sample products.  Identifiers, like names, addresses, and social security numbers, will 
not be released, except if patients need to be contacted again for specific purposes in new IRB-
approved studies.  All efforts will be made to keep true identities confidential.   
 
20. STUDY DISCONTINUATION 
The study site reserves the right to discontinue the study at any time. The sponsor reserves the 
right to terminate the study in its entirety or at the study center at any time and as specified in the 
clinical study agreement. 
 
21. REFERENCES 
 
1. Centers for Disease Control and Prevention. Chronic Obstructive Pulmonary 
Disease (COPD). Department of Health and Human Services; 2018 
[Available from: https://www.cdc.gov/copd/index.html. 
2. Global Initiative for Chronic Obstructive Lung Disease. Global trategy for the 
diagnosis, management, and prevention of chronic obstructive pulmonary 
disease (2019 Report). Global Initiative for Chronic Obstructive Lung 
Disease, Inc.; 2019 [Available from: https://goldcopd.org/gold-reports/. 

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3. Chapin TW, Mann MA, Brown GL, Leitheiser TL, Anderson B, Leedahl DD. 
Effectiveness of Umeclidinium-Vilanterol for Protocolized Management of 
Chronic Obstructive Pulmonary Disease Exacerbation in Hospitalized 
Patients: A Sequential Period Analysis. Chronic Obstr Pulm Dis 
2018;5(1):38-45. 
 
 
22. APPENDICES 
TRELEGY-ELLIPTA-PI-PIL-IFU (9/2020) (attachment)