The Primary Symptoms of GERD in Chinese Outpatients in Gastroenterology Department: A Cross-sectional Investigation
Conditions: Gastroesophageal Reflux
Sponsor: First Affiliated Hospital, Sun Yat-Sen University

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
Clinical Study Protocol  
Drug Substance 
Esomerprozole 
Study Code 
D9612L00157 
Edition Number 
2.0 
Date 
Jun 8 2018 
The primary symptoms of GERD in Chinese outpatients in Gastroenterology 
department: A cross-sectional investigation 
Sponsor:  
The following Amendment(s) and Administrative Changes have been made to this protocol since the date of 
preparation: 
Amendment No. 
Date of Amendment 
Local Amendment No: 
Date of Local Amendment 
Administrative 
Change No. 
Date of Administrative 
Change 
Local Administrative 
Change No. 
Date of Local 
Administrative Change 
 
 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
PROTOCOL SYNOPSIS 
 
The primary symptoms of GERD in Chinese outpatients in Gastroenterology department: A 
cross-sectional investigation 
 
 
Principal Investigator 
Minhu Chen  
Study site(s) and number of subjects planned 
One site 
Study period 
 
Estimated date of first subject enrolled 
Aug 2015 
Estimated date of last subject completed 
Sep 2018 
 
Study design 
Cross-sectional investigation 
Objectives 
 
Primary Objective: 
Outcome Measure: 
To define the primary symptom of GERD in 
Chinese outpatients in Gastroenterology 
department 
The primary symptoms of GERD in Chinese 
outpatients in Gastroenterology department defined 
by 24-hour impedance-pH monitoring, upper 
endoscopy or proton pump inhibitor test. 
 
 
 
 
 
 
 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
Secondary Objective: 
Outcome Measure : 
1. To investigate the symptom distribution of 
paitents who present with symptoms originated 
from upper gastrointestinal tract and have 
pathologic esophageal reflux established by 
24-hour impedance-pH monitoring, upper 
endoscopy, or proton pump inihibitor test. 
2. To evaluate the life quality of patients with 
atypical GERD symptoms (symptoms except 
heartburning and regurgitation) 
3. To investigate the diagnostic value of proton 
pump inhibitor trial to diagnose GERD with 
atypical reflux symptoms 
4. To investigate the predictive value of Gerd 
Q to diagnose GERD with atypical reflux 
symptoms with heartburn or regurgitation 
1. The percentage of each symptom of GERD in the 
symptom questionnaire in Chinese outpatients in 
Gastroenterology department 
2. The measurement of SF-36 questionnaire of GERD 
patients with atypical symptoms before PPI test 
3. The sensitivity and specificity of positive PPI test in 
patients with atypical reflux symptom 
4. The concordance rate of Gerd Q with 24-hour pH 
monitoring in GERD patients with atypical reflux 
symptoms with heartburn or regurgitation 
 
 
 
Target subject population 
 Consecutive patients aged 18–65 years who go to the gastroenterology clinic presented with 
upper gastrointestinal discomfort, such as the following symptoms: heartburn, regurgitation, 
dysphagia, substernal pain, epigastric pain,epigastric burning, early satiety, postprandial 
fullness. 
Duration of treatment 
4-8 weeks  
Investigational product, dosage and mode of administration 
Esomeprazole, 20mg bid, p.o    
4-8 weeks 
Statistical methods 
Assuming the prevalence of GERD is 30%, 400 completed patients provides a precision (half 
width of 95% CI) of 0.045 for the estimate of two-sided 95% confidence interval of the 
primary endpoint. All patients underwent upper endoscopy or an ambulatory 24-h pH 
monitoring. Pathologic esopheal acid reflux was defined as the percentage total time for which 
a pH value < 4 was >4.2 % in the distal esophagus. Then, patients were treated with 
esomeprazole 20 mg twice daily for 28 days. The symptom scores were measured by the 
frequency score multiplied by the severity scores of the predominant symptom before and at 
the end of the treatment, and the “ PPI test ” was defined as positive if the overall scores of the 
predominant dyspeptic symptom in the fourth week decreased by >50 % compared with those 
of the baseline. 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
GERD is defined by either 24-hour impedance-pH monitoring or positive PPI test or positive 
result from endoscopy. The percentage of each symptom of GERD in the symptom 
questionnaire in Chinese outpatients in Gastroenterology department will be calculated. The 
symptom of the highest percentage will be the primary symptom.  
 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
TABLE OF CONTENTS 
PAGE 
 
TITLE PAGE ........................................................................................................... 1 
PROTOCOL SYNOPSIS ......................................................................................... 2 
TABLE OF CONTENTS ......................................................................................... 5 
1. 
INTRODUCTION ................................................................................................... 7 
1.1 
Background and rationale for conducting this study ............................................... 7 
1.2 
Rationale for study design, doses and control groups .............................................. 8 
1.3 
Study Design ............................................................................................................ 9 
2. 
STUDY OBJECTIVES .......................................................................................... 10 
2.1 
Primary objective ................................................................................................... 10 
2.2 
Secondary objectives .............................................................................................. 10 
2.3 
Safety objectives .................................................................................................... 10 
3. 
SUBJECT SELECTION, ENROLMENT, RANDOMISATION, 
RESTRICTIONS, DISCONTINUATION AND WITHDRAWAL ...................... 10 
3.1 
Inclusion criteria .................................................................................................... 11 
3.2 
Exclusion criteria ................................................................................................... 11 
3.3 
Subject enrolment and randomization .................................................................... 11 
3.4 
Methods for assigning treatment groups ................................................................ 11 
3.5 
Methods for ensuring blinding ............................................................................... 11 
3.6 
Criteria for withdrawal ........................................................................................... 12 
3.7 
Discontinuation of the study .................................................................................. 12 
4. 
STUDY PLAN AND TIMING OF PROCEDURES ............................................. 12 
4.1 
Enrolment/screening period ................................................................................... 15 
4.2 
Treatment period .................................................................................................... 15 
4.3 
Follow-up period .................................................................................................... 15 
5. 
SAFETY REPORTING AND MEDICAL MANAGEMENT .............................. 15 
5.1  Definition ......................................................................................................................... 15 
Adverse Events ....................................................................................................................... 15 
Serious Adverse Event............................................................................................................ 15 
Adverse Drug Reaction (ADR) .............................................................................................. 16 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
5.2   Reporting of Serious Adverse Events ............................................................................. 16 
Investigators are responsible for meeting all regulatory reporting requirements. .................. 16 
The investigator should report SAEs associated with AstraZeneca study drug 
Esomerprozole to AstraZeneca Patient Safety data entry site within 24 
hours of initial awareness, whether or not considered causally related to the 
AstraZeneca investigational product. ..................................................................... 16 
5.3  Reporting of Non-serious Adverse Drug Reactions ........................................................ 16 
All non-serious ADRs which are suspected to be related to AstraZeneca 
investigational Product should be reported to AstraZeneca. .................................. 16 
If any non-serious ADR occurs in the course of the study, the investigator should 
report it to AstraZeneca Patient Safety data entry site within 24 hours of 
initial awareness. .................................................................................................... 16 
AstraZeneca Patient Safety data entry site contact information: ............................................ 16 
E-mail: AEMailboxClinicalTrialTCS@astrazeneca.com....................................................... 16 
6. 
INVESTIGATIONAL PRODUCT AND OTHER TREATMENTS .................... 16 
7. 
STATISTICAL ANALYSES ................................................................................ 16 
7.1 
Sample size estimate .............................................................................................. 16 
7.2 
Definitions of analysis sets .................................................................................... 16 
7.2.1 
Efficacy analysis set ............................................................................................... 16 
7.3 
Outcome measures for analyses ............................................................................. 17 
7.4 
Methods for statistical analyses ............................................................................. 17 
7.4.1 
Analysis of the primary variable(s) ........................................................................ 17 
7.4.2 
Analysis of the secondary variable(s) .................................................................... 17 
8. 
DATA COLLECTION .......................................................................................... 17 
9. 
ETHICS .................................................................................................................. 18 
9.1 
Ethical conduct of the study ................................................................................... 18 
9.2 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ............. 18 
9.3 
Subject information and Informed consent ............................................................ 18 
10. 
LIST OF REFERENCES ....................................................................................... 18 
 
 
 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
1. 
INTRODUCTION 
1.1 
Background and rationale for conducting this study 
Gastroesophageal reflux disease (GERD) is a condition which develops when the reflux 
of stomach contents cause troublesome symptoms and/or complication. It is one of the most 
common gastrointestinal diseases in the West countries and imposes a heavy burden on the 
population. It was reported that the prevalence of GERD has increased greatly since 1995, 
particularly in North America and East Asia. GERD has been believed to be a major risk 
factor for esophageal adenocarcinoma, especially in Barrett's esophagus. Thus it is important 
to confirm the diagnosis of GERD and give the subsequent therapy for the patient to lower 
down the risk for esophageal adenocarcinoma.  
According to the global consensus issued in 2006, GERD could be diagnosed simply by 
typical reflux symptoms.Heartburn and acid regurgitaiton are the primary symptoms of 
gatroesophageal reflux disease. These two symptoms are derived from the studies performed 
in western countries. And using the 24-hour esophageal pH monitoring as “gold standard”, the 
sensitivity and specificity of reflux symptoms are moderate. The current prevalence of 
heartubrn and/or regurgitation in China was 6.2% weekly and there is an increasing trend in 
the prevalence of GERD. It is reported that the prevalence of GERD is much lower in China 
than that in other western countries.. This might be due to the diet culture in China, where a 
lower fat intake is introduced. Another common reason is about the understanding of GERD 
symptoms. The primary symptom of GERD is heartburn as confirmed in the Montreal 
consensus, which is defined as the burning sensation in the retrosternal area. However, there is 
no equivalent word for heartburn in Chinese, many Chinese pateints came to the hospital with 
the complaint of “burning in the stomache”, thus the questionaire which focus on the 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
heartburn symptoms would underestimate the prevalence of GERD. The last and also the most 
important reason might lie in that the symptoms which indicate reflux were different in 
Chinese population. In other words, heartburn might not be the primary reflux symptom in 
China. For example, more symptoms oiginated from the upper gastrointestinal tract was 
described as reflux symptom when patients went to see docotors in China. According to the 
investigation in our own center, about one third of dyspepsia patients without reflux syptoms 
presented pathologic esophageal acid reflux in our clinic. Thus heartburn was not understood 
as well as in other western countries, the symptoms of GERD might distribute differently in 
China compared to other western countries. So it is necessary to investigate the primary 
symptoms and spectrum of GERD in Chinese population in order to better define and 
diagnose GERD. 
1.2 
Rationale for study design, doses and control groups 
The symptom spectrum of GERD has been studied in the western population using the 
24-hour esophageal pH monitoring as the gold standard, heartburn and regurgitation has been 
advocated as the primary symptoms of GERD according to these studies. However, the 
current studies on GERD in China referred to these western studies and took it for granted that 
heartburn and regurgitation were also the primary symptoms of GERD. Our clinical practise 
indicated that a lot of Chinese patients who came to the hospital seeking for therapy of 
symptoms originated from the upper GI tract including epigastric pain, epigastric burning 
sensation et al turned out to be GERD. Thus the primary symptoms of GERD might differ 
from that in the western counties. It is necessary to find out the primary symptoms and 
symptoms spectrum in Chinese population, which might be useful in our clinical management. 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
All the included patients who do not have positive finding during 24 hour esophageal pH 
monitoring would be administered with esomeprazole 20mg bid for 4 weeks which would be a 
complement for GERD diagnosis of pH monitoring. 
Benefit/risk and ethical assessment 
The study might be helpful in the understanding of symptom spectrum of GERD in Chinese 
population and promote the GERD study in China. There won’t be any risk and ethical issue 
in the current study.   
1.3 
Study Design  
Figure 1 
Study flow chat 
 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
2. 
STUDY OBJECTIVES 
2.1 
Primary objective 
Primary Objective: 
Outcome Measure: 
To define the primary symptom of GERD in 
Chinese outpatients in Gastroenterology 
department 
The primary symptoms of GERD in Chinese 
outpatients in Gastroenterology department defined 
by 24-hour impedance-pH monitoring,upper 
endoscopy or proton pump inhibitor test. 
 
 
2.2 
Secondary objectives 
Secondary Objective: 
Outcome Measure : 
1. To investigate the symptom distribution of 
paitents who present with symptoms originated 
from upper gastrointestinal tract and have 
pathologic esophageal reflux established by 
24-hour impedance-pH monitoring, upper 
endoscopy or proton pump inihibitor test. 
2. To evaluate the life quality of patients with 
atypical GERD symptoms (symptoms except 
heartburning and regurgitation) 
3. To investigate the diagnostic value of proton 
pump inhibitor trial to diagnose GERD with 
atypical reflux symptoms 
4. To investigate the predictive value of Gerd 
Q to diagnose GERD with atypical reflux 
symptoms with heartburn or regurgitation 
1. The percentage of each symptom of GERD in the 
symptom questionnaire in Chinese outpatients in 
Gastroenterology 
department 
2. The measurement of SF-36 questionnaire of GERD 
patients with atypical symptoms before PPI test 
3. The sensitivity and specificity of positive PPI test in 
patients with atypical reflux symptom 
4. The concordance rate of Gerd Q with 24-hour pH 
monitoring in GERD patients with atypical reflux 
symptoms with heartburn or regurgitation 
 
 
2.3 
Safety objectives 
NA 
3. 
SUBJECT SELECTION, ENROLMENT, RANDOMISATION, 
RESTRICTIONS, DISCONTINUATION AND WITHDRAWAL  
 The study  will be done in the outpatient clinic, department of Gastroenterology, first 
affiliated hospital, sun yet-sen university.  

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
3.1 
Inclusion criteria 
1. Consecutive patients aged 18–65 years who go to the gastroenterology clinic presented with 
upper gastrointestinal discomfort, such as the following symptoms: heartburn, regurgitation, 
dysphagia, substernal pain, epigastric pain, epigastric burning, early satiety, postprandial 
fullness. 
2. The previous symptoms should last for at least 3 months. 
3. The frequency of the previous symptoms should be at least 3 days per weekwith at least  
moderate. 
4. All the previous symptoms would be evaluated in the questionaires (see attachment). 
3.2 
Exclusion criteria 
1.Patients with gastric or duodenal ulcers, upper GI neoplasms on upper endoscopy 
2.Patients with severe cardiac or pulmonary diseases, diabetes or rheumatic diseases 
3.Patients with a history of operations in the upper GI tract 
4.Patients with renal failure or abnormal liver function 
5. Patients with use of non-steroidal anti-inflammatory drugs (NSAIDs) 
6. Patients who are allergy to esomeprazole 
7. Pregnancy or lactating mother 
3.3 
Subject enrolment and randomization 
Consecutive patients who met the inclusion criteria in the Gastroenterology clinic in the first 
affiliated hospital will be enrolled in the study. There will not be any randomization in the 
study.  
3.4 
Methods for assigning treatment groups 
All the patients who were endoscopy negative, with esophagatitis or Barrett’s esophagus 
would be given esomeprazole 20mg bid for 4- 8 weeks. 
3.5 
Methods for ensuring blinding 
Not applicable. This is a cross-sectional study. 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
3.6 
Criteria for withdrawal  
Patients would be withdraw from the current study if  their symptoms do not meet the 
inclusion criteria, they could no tolerate any procedure of the study, they could not finish the 
esomeprazole therapy part. 
 
3.7 
Discontinuation of the study 
Those patients who  had not symptom relief after four weeks of esomeprazole would 
discontinue this study. 
4. 
STUDY PLAN AND TIMING OF PROCEDURES  
The study includes screening and treatment period. The screen period would be 7 days, during 
this stage all the  procedure including questionaires, upper endoscopy and MII-pH monitoring 
need to be finished. The treatment period  would be 4 to 8 weeks according to the findings 
under upper endoscopy. For patients with esophagitits, this period would be 8 weeks; for 
patients with normal findings, this period would be 4 weeks.

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
Table 1 Study Plan detailing the procedures for patients with esophagitis 
Visit 
Visit window 
  Days –7 to 0 for Visit 1 
  ±0 day for Visit 2  
  ±1 day for Visits 3 and 
4  
  ±5 days starting at Visi t 
5 
1  
Screening 
2 
3 
4 
5 
6 
7 
Week 
 
0 
1 
2 
4 
8 
12   
Day 
- 
0 
7 
14 
28 
56 
84 
Written informed consent 
(including tissue samples, 
pharmacogenetics) 
X 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
Physical examination, 
height, and weight 
X 
 
 
 
 
 
 
Medical/surgical history 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
Treatment 
dispensed/returned 
 
X 
 
 
 
 
X 
Concomitant medication  
X 
X 
X 
X 
X 
X 
X 
GERD questionaire 
 
X 
X 
X 
X 
X 
X 
 
 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
Table 2 Study Plan detailing the procedures for endoscopy negative patients 
Visit 
Visit window 
  Days –7 to 0 for Visit 1 
  ±0 day for Visit 2  
  ±1 day for Visits 3 and 
4  
  ±5 days starting at Visit 
5 
1  
Screening 
2 
3 
4 
5 
6 
 
Week 
 
0 
1 
2 
4 
8 
 
Day 
- 
0 
7 
14 
28 
56 
 
Written informed consent 
(including tissue samples, 
pharmacogenetics) 
X 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
Physical examination, 
height, and weight 
X 
 
 
 
 
 
 
Medical/surgical history 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
Treatment 
dispensed/returned 
 
X 
 
 
 
 
 
Concomitant medication  
X 
X 
X 
X 
X 
X 
 
GERD questionaire 
 
X 
X 
X 
X 
X 
 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
4.1 
Enrolment/screening period 
Seven days 
4.2 
Treatment period 
Four to eight weeks 
4.3 
Follow-up period 
Four weeks 
5. 
SAFETY REPORTING AND MEDICAL MANAGEMENT 
The Principal Investigator is responsible for ensuring that all staff involved in the study are 
familiar with the content of this section. 
5.1  Definition 
Adverse Events 
An adverse event is the development of an undesirable medical condition or the deterioration 
of a pre-existing medical condition following or during exposure to a pharmaceutical product, 
whether or not considered causally related to the product.  An undesirable medical condition 
can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver) or the 
abnormal results of an investigation (e.g., laboratory findings, electrocardiogram).  In clinical 
studies, an AE can include an undesirable medical condition occurring at any time, including 
run-in or washout periods, even if no study treatment has been administered. 
The term AE is used to include both serious and non-serious AEs. 
Serious Adverse Event 
A serious adverse event is an AE occurring during any study phase (i.e., run-in, treatment, 
washout, follow-up), that fulfils one or more of the following criteria: 
 
Results in death 
 
Is immediately life-threatening 
 
Requires in-patient hospitalisation or prolongation of existing 
hospitalisation  
 
Results in persistent or significant disability/incapacity or substantial 
disruption of the ability to conduct normal life functions 
 
Is a congenital abnormality or birth defect 
 
Is an important medical event that may jeopardise the subject or may 
require medical intervention to prevent one of the outcomes listed above. 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
Adverse Drug Reaction (ADR) 
An ADR is a response to a medicinal product which is noxious and unintended. A response in 
this context means that a causal relationship between the medicinal product and an AE is at 
least a reasonable possibility. 
5.2   Reporting of Serious Adverse Events 
Investigators are responsible for meeting all regulatory reporting requirements.  
The investigator should report SAEs associated with AstraZeneca study drug Esomerprozole 
to AstraZeneca Patient Safety data entry site within 24 hours of initial awareness, whether or 
not considered causally related to the AstraZeneca investigational product. 
For fatal or life-threatening adverse events where important or relevant information is missing, 
active follow-up is undertaken immediately. Investigator should inform AstraZeneca of any 
follow-up information on a previously reported SAE within one calendar day when he or she 
becomes aware of it.  
5.3  Reporting of Non-serious Adverse Drug Reactions  
All non-serious ADRs which are suspected to be related to AstraZeneca investigational 
Product should be reported to AstraZeneca. 
If any non-serious ADR occurs in the course of the study, the investigator should report it to 
AstraZeneca Patient Safety data entry site within 24 hours of initial awareness. 
AstraZeneca Patient Safety data entry site contact information: 
E-mail: AEMailboxClinicalTrialTCS@astrazeneca.com  
 
6. 
INVESTIGATIONAL PRODUCT AND OTHER TREATMENTS 
Esomeprazole MUPS, 20 mg, bid, Astrazeneca, 4- 8 weeks  
7. 
STATISTICAL ANALYSES  
7.1 
Sample size estimate 
Assuming the prevalence of GERD is 30%, 400 completed patients provides a precision (half 
width of 95% CI) of 0.045 for the estimate of two-sided 95% confidence interval of the 
primary endpoint.. 
7.2 
Definitions of analysis sets 
7.2.1 
Efficacy analysis set 
All the patients complete the study per protocol. 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
7.3 
Outcome measures for analyses 
Pathologic esopheal acid reflux was defined as the percentage total time for which a pH value 
< 4 was >4.2 % in the distal esophagus. Then, patients were treated with esomeprazole 20 mg 
twice daily for 28 days. The symptom scores were measured by the frequency score multiplied 
by the severity scores of the predominant symptom before and at the end of the treatment, and 
the “ PPI test ” was defined as positive if the overall scores of the predominant dyspeptic 
symptom in the fourth week decreased by >50 % compared with those of the baseline. 
GERD is defined by 24-hour impedance-pH monitoring, upper endoscopy or positive PPI test.  
7.4 
Methods for statistical analyses 
7.4.1 
Analysis of the primary variable(s) 
The percentage of each symptom of GERD in the symptom questionnaire in Chinese 
outpatients in Gastroenterology department will be calculated. The symptom of the highest 
percentage will be the primary symptom. 
7.4.2 
Analysis of the secondary variable(s) 
The percentage of each symptom of GERD in the symptom questionnaire in Chinese 
outpatients in Gastroenterology department will be calculated. 
The life quality of GERD patients with atypical symptoms before PPI test will be measured 
via SF-36 questionnaire. 
Receiver operating characteristic (ROC) curves will be constructed to identify the sensitivity 
and speicificity of either GERD Q or 4-week PPI test against positive 24-hour pH monitoring 
or positive endoscopy result in GERD patients with atypical reflux symptoms 
 
8. 
DATA COLLECTION 
To enable evaluations and/or audits from regulatory authorities, the investigator agrees to 
keep records, including the identity of all participating subjects (sufficient information to link 
records), all original signed informed consent forms, source documents, and detailed records 
of treatment disposition, and adequate documentation of relevant correspondence (eg, letters, 
meeting minutes, telephone calls reports).  The records should be retained by the investigator 
as specified in the Clinical Study Agreement. 
If the investigator becomes unable for any reason to continue to retain study records for 
the required period (eg, retirement, relocation), First Affiliated Hospital of Sun Yat-sen 
University should be prospectively notified.  The study records must be transferred to a 
designee acceptable to First Affiliated Hospital of Sun Yat-sen University, such as another 
investigator, another institution, or to an independent third party arranged by First Affiliated 
Hospital of Sun Yat-sen University.  The investigator must obtain written permission from 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
First Affiliated Hospital of Sun Yat-sen University before disposing of any records, even if 
retention requirements have been met. 
9. 
ETHICS 
9.1 
Ethical conduct of the study 
The study will be conducted in accordance with legal and regulatory requirements, as well 
as the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences 2002), Guidelines for Good Clinical Practice (International Conference on 
Harmonization 1996), and the Declaration of Helsinki (World Medical Association 2008).  
In addition, the study will be conducted in accordance with the protocol, the International 
Conference on Harmonisation guideline on Good Clinical Practice, and applicable local 
regulatory requirements and laws. 
 
9.2 
Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) 
It is the responsibility of the investigator to have prospective approval of the study 
protocol, protocol amendments, informed consent forms, and other relevant documents, e.g., 
recruitment advertisements, if applicable, from the IRB/IEC.  All correspondence with the 
IRB/IEC should be retained in the Investigator File.  Copies of IRB/IEC approvals should be 
forwarded to study sites. 
 
9.3 
Subject information and Informed consent 
All parties will ensure protection of subject personal data and will not include subject 
names on any forms, reports, publications, or in any other disclosures, except where required 
by laws.  
The informed consent form must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements. 
The informed consent form used in this study, and any changes made during the course of 
the study, must be prospectively approved by the IRB/IEC before use. 
The investigator must ensure that each study subject, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible risks 
associated with participation.  The investigator, or a person designated by the investigator, 
will obtain written informed consent from each subject or the subject's legally acceptable 
representative before any study-specific activity is performed.  The investigator will retain the 
original of each subject's signed consent form. 
 
10. 
LIST OF REFERENCES 
1. Xiao YL, Peng S, Tao J, Wang AJ, Lin JK, Hu PJ, Chen MH.Prevalence and symptom 
pattern of pathologic esophageal acid reflux in patients with functional dyspepsia based on 

Clinical Study Protocol 
Drug Substance Esomerprozole 
Study Code D9612L00157 
Edition 2.0 
Date Jun 8 2018 
the Rome III criteria. Am J Gastroenterol. 2010 Dec;105(12):2626-31. 
2. Dent J, Vakil N, Jones R, Bytzer P, Schöning U, Halling K, Junghard O, Lind T.Accuracy 
of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump 
inhibitor treatment: the Diamond Study.Gut. 2010 Jun;59(6):714-21. 
3. Nimish Vakil, F.A.C.G., Sander V. van Zanten, et al. The Montreal Definition and 
Classification of Gastroesophageal Reflux Disease: A Global Evidence-Based Consensus. 
Am J Gastroenterol 2006;101:1900–1920. 
4. Gallup Organization. A Gallup Organization National Survey:Heatburn across 
American.Princeton,NJ:The Gallup Organization,1998. 
5. CHEN Minhu, XIONG Lishou, CHEN Huixin, et al. Prevalence, risk factors and impact 
of gastroesophageal reflux disease: a population-based study in South China. Scand J 
Gastroenterol, 2005;40(7):759-767. 
6. Addition of Esophageal Impedance Monitoring to pH Monitoring Increases the Yield of 
Symptom Association Analysis in Patients off PPI Therapy. Albert J. Bredenoord, Bas 
L.A.M. Weusten, Robin Timmer, et al. Am J Gastroenterol,2006;101:453–459. 
7. Fass R, Fennerty MB, Vakil N. Non-erosive reflux disease – current concepts and 
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