Conditions: Gastroesophageal Reflux Disease
Keywords: Gastroesophageal Reflux Disease GERD Acid reflux Compound Sodium Alginate Double Action Chewable Tablet Gaviscon Double Action Tablets
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 45
Healthy volunteers: no

Brief summary:
This study is being conducted to assess the effectiveness of the Compound Sodium Alginate Double Action Chewable Tablets compared to placebo on acidic reflux events into the esophagus in patients diagnosed with Gastroesophageal Reflux Disease (GERD).

Detailed description:

Arms:
arm 1: 4 Compound Sodium Alginate Double Action Chewable Tablets administered as a single dose, followed by 7 days of Compound Sodium Alginate Double Action Chewable Tablets (two tablets four times daily), then a single dose of 4 Placebo tablets arm 2: Single dose of 4 Placebo tablets, followed by 7 days of Compound Sodium Alginate Double Action Chewable Tablets (two tablets four times daily), then a single dose of 4 Compound Sodium Alginate Double Action Chewable Tablets

Interventions: intervention 1: Sodium Alginate Double Action Chewable Tablets intervention 2: Placebo
Intervention descriptions: intervention 1: 4 tablets as a single dose intervention 2: 4 tablets as a single dose

Protocol document:
Prot_000.pdf: 
Study Title: A Multi-centred, Randomised, Open Label, Placebo-controlled, Two-period 
Crossover Study to Evaluate 4-hour Esophageal pH Change in GERD Patients After 
Administration of Compound Sodium Alginate Double Action Tablets or Placebo Tablets   
 
ClinicalTrials.gov ID: NCT01872897 
 
 
 
Final Protocol, dated 01-Mar-2013 
 
Amendment 1, dated 04-Jun-2013 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 1 of 76 
Reckitt Benckiser 
 
1 
STUDY PROTOCOL TITLE PAGE 
CTA (China) 
Number: 
2010L02452 
Study Number: 
GA1202 
Project Name: 
Shanghai 
Study Phase: 
III 
Study Country: 
China 
Indication: 
Gastro-esophageal reflux disease (GERD) 
Test Product(s): 
Compound Sodium Alginate Double Action Chewable Tablet. 
Reference 
Product(s): 
Placebo Matching Compound Sodium Alginate Double Action Chewable Tablet. 
Study Title: 
A multi-centred, randomised, open label, placebo-controlled, two-period 
crossover study to evaluate 4-hour esophageal pH change in GERD patients 
after administration of Compound Sodium Alginate Double Action Chewable 
Tablets or matching placebo tablets 
Short Study 
Title: 
Compound Sodium Alginate Double Action Chewable Tablets 4-hour esophageal 
pH study in GERD patients 
Protocol Date: 
1 March 2013 
Protocol 
Version: 
Final version 2 
Confidentiality 
Statement: 
The information contained in this document is privileged and confidential. 
Do not copy, circulate or otherwise distribute without written authority from 
the Reckitt Benckiser Clinical Project Manager function. 
 
 
 
 
 
 
 
 
 


Investigational Study Protocol Template 
Study No: GA 1202 
f Reckitt 
Benckiser 
SOP 00365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
2 
PROTOCOL APPROVAL 
Reviewed and Agreed by: 
Statist c an: 
Clinical Project Manager 
Reckitt Benckiser Healthcare 
(UK) Limited 
Reviewed and Approved by: 
R&D Manager - Clinical (Healthcare): 
Senior Statistician 
Reckitt Benckiser Healthcare 
(UK) Limited 
Global Medical Director: 
Reviewed and Accepted by: 
Co-ordinating Principal Investigator: 
Chief Department of 
Gastroenterology, 
Ruijin Hospital, 
 
 
 
 
China 
Study Sponsor: Reck1tt Benckiser Healthcare (UK) Ltd, Dansom Lane, HUB 70S; Telephone No: +44 {0) 1482 
326151 ; Fax No: +44 (0) 1482 582172 
Template vs_ 4.0, 23-Jan-2013 
Page 2 of 76 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 3 of 76 
3 
PROTOCOL SYNOPSIS 
3.1 
Rationale 
This study is being conducted to assess the effectiveness of the Compound Sodium Alginate 
Double Action Chewable Tablets compared to placebo on acidic reflux events into the 
esophagus in patients diagnosed with GERD. 
 
3.2 
Objective(s) 
The primary objective of this study is to compare the time during the 4 hour post dosing 
period where the pH is below pH 4 for Compound Sodium Alginate Double Action Chewable 
Tablets versus matching placebo tablets. 
The secondary objectives of this study are to determine and compare the number of 
occasions and percentage of time during the 1 and 4 hour post dosing period when pH falls 
below pH 4 and pH 5.  Other secondary objectives include comparing the longest reflux time 
and DeMeester scores during the 4 hour period. 
 
3.3 
Primary Endpoint 
The primary efficacy endpoint will be the percentage of time during the 4 hour post dosing 
period with pH below pH 4 for Compound Sodium Alginate Double Action Chewable Tablets 
versus matching placebo tablets. 
 
3.4 
Secondary Endpoints 
The following secondary endpoints will also be evaluated: 
• 
Percentage of time during the 4 hour post dosing period with pH below pH 5 
• 
Number of occasions during the 4 hour post dosing period when pH falls below pH 4 
• 
Number of occasions during the 4 hour post dosing period when pH falls below pH 5 
• 
Number of reflux episodes during the 4 hour post dosing period with pH below pH 4 
for at least 5 minutes 
• 
Percentage of time during the first hour post dosing with pH below pH 4 
• 
Percentage of time during the first hour post dosing with pH below pH 5 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 4 of 76 
• 
Number of occasions during the first hour post dosing when pH falls below pH 4 
• 
Number of occasions during the first hour post dosing when pH falls below pH 5 
• 
The longest reflux time during the 4 hour post dosing period (i.e. the longest period 
with pH below pH 4) 
• 
The DeMeester scores during the 4 hour post dosing period  
 
3.5 
Design Summary 
This is a multi-centre, randomised, open-label, placebo-controlled, two-period crossover 
study.  After signing a written informed consent, patients will undergo a screening period of 
up to 10 days.  Patients who satisfy the study entry requirements within 10 days of consent, 
will be randomised to receive either four Compound Sodium Alginate Double Action 
Chewable Tablets or four matching placebo tablets following placement of a pH electrode 
and a standardised refluxogenic meal.  
Upon completion of the 4-hour post-dose pH monitoring period patients will be instructed to 
begin taking supplied Compound Sodium Alginate Double Action Chewable Tablets (two 
tablets four times daily) for 7 days. Patients will return after the 7 day period for repeat 
catheter insertion and pH monitoring, receiving the alternative randomised treatment. 
 
3.6 
Sample Size 
The number of patients enrolled for this study has been derived from experience of previous 
pH monitoring studies conducted with other Gaviscon® formulations. It is anticipated that 36 
evaluable patients will be required to complete the study. In order to achieve this, 44 patients 
will be enrolled in this study. 
 
3.7 
Anticipated Study Timings 
It is estimated that the clinical phase of this study will commence in May 2013 and last a 
period of 6-9 months. 
The duration of each patient’s participation in the study will be a maximum of 19 days (from 
screening visit to end of treatment visit) and involve 3 visits. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 5 of 76 
3.8 
Inclusion Criteria 
Only patients to whom all of the following conditions apply will be included: 
1. Informed consent has been obtained. 
2. Age: ≥ 18 years to ≤ 65 years. 
3. Sex: male or female. 
4. Primary diagnosis: meet the diagnostic criteria for GERD with a GERD history of 
frequent episodes of GERD-related symptoms during the last 2 months prior to study 
screening.  The patient must also meet the following criteria:  
a. The only or main symptom is heartburn (burning feeling back of breast bone) 
and/or acid reflux. Symptoms persists or have occurred repeatedly for more 
than 2 months; 
b. As assessed by the Investigator at screening by questioning of the patient, 
the frequency of occurrence of heartburn is ≥ 3 days/week and the score of 
severity of heartburn in general is ≥ Level 2 within 3 weeks before screening. 
The severity of heartburn will be evaluated as follows: 
Level 0  
no heartburn  
 
Level 1  
heartburn is mild in severity and is not obvious  
Level 2  
heartburn is moderate, or it is obvious when it occurs, the 
patient experiences discomfort  
Level 3  
heartburn is severe and significant, seriously interferes with 
daily activities  
The frequency of heartburn will be evaluated as number of days /week that heartburn 
is suffered (0, 1, 2, 3, 4, 5, 6 or 7 days). 
5. Status: Patients will be patients at the clinic or members of the public who respond to 
an advertisement or via their doctor. 
6. Patients who have not taken any antacids within 24 hours before randomisation (Visit 
2) and be instructed not to take antacids, other than the Compound Sodium Alginate 
Double Action Chewable Tablets provided, throughout the remainder of the study. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 6 of 76 
7. Patients taking mucous membrane protection drugs or prokinetics may enter the 
study provided that these are discontinued for at least 5 days before screening and 
throughout the remainder of the study. 
8. Systemic glucocorticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs, 
except for low dose aspirin which can be given for cardioprotection) can only be taken 
for up to 3 consecutive days in the 28 days prior to screening. 
9. Absence of relevant abnormalities in the physical examination, endoscopy, ECG and 
laboratory safety results. 
10. Patients who are willing to consume the entire standard refluxogenic test meal.  
Patients cannot be vegetarian. 
 
3.9 
Exclusion Criteria 
Patients to whom any of the following conditions apply must be excluded: 
1. Patients who have a history of drug, solvent or alcohol abuse (weekly alcohol intake ≥ 
140g). 
2. Patients who have suffered cardiac chest pain within the last year. 
3. Patients who have suffered a recent, significant unexplained weight loss of more than 
6 Kg in the last 6 months. 
4. Female patients of childbearing potential who, for the duration of the study, are either 
unwilling or unable to take adequate contraceptive precautions (as defined in 
Section 10.3) or are unwilling to be sexually abstinent (as defined in Section 10.3).  
5. Pregnancy or lactating mother.  
6. Patients with a history and/or symptom profile suggestive of the following:  any other 
gastrointestinal (GI) disease, erosive GERD (Los Angeles [LA] classification grades 
C-D), Barrett’s esophagus, acute peptic ulcer and/or ulcer complications, Zollinger-
Ellison syndrome, gastric carcinoma, pyloric stenosis, oesophageal or gastric surgery, 
intestinal obstruction, current pernicious anaemia, indication for H-pylori eradication 
therapy, known gastro-intestinal bleeding (hematochezia or hematemesis) within the 
last 3 months, and severe diseases of other major body systems. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 7 of 76 
7. Patients who are observed at screening to have a hiatus hernia with a diameter which 
exceeds 3cm. 
8. Patients who have taken anti-cholinesterase drugs, traditional Chinese medicines for 
treating gastrointestinal disease, ulcerlmin or misoprostol preparations within 7 days 
prior to screening or throughout the study. 
9. Patients who have taken PPIs during the 10 days prior to screening, prokinetics or H2 
antagonists during the 5 days prior to screening or systemic glucocorticosteroids, non-
steroidal anti-inflammatory drugs (NSAIDs, except for low dose aspirin which can be 
given for cardioprotection) on more than 3 consecutive days or PPI-based triple or 
quadruple therapy for eradication of H-pylori during the last 28 days. 
10. Patients taking or requiring to take macrolide antibiotics, such as erythromycin, 
azithromycin, from the day before screening. 
11. Patients with difficulty in swallowing. 
12. Patients with known hypophosphataemia, phenylketonuria or hypercalcaemia. 
13. Patients with severe constipation, or history of intestinal obstruction. 
14. In the opinion of the Investigator, patients with damaged heart or kidney function and 
patients who require a low sodium diet. 
15. Patients either with any co-existing condition which, in the opinion of the Investigator, 
would be likely to compromise patient safety or interfere with assessment of efficacy; 
or with any clinically significant abnormal laboratory values; or in the Investigator’s 
view to unable to comply fully with the study requirements. 
16. Any previous history of allergy or known intolerance to any of the IMP’s or following 
formulation constituents: macrogol 20,000, mannitol (E421), copovidone, acesulfame 
K, aspartame (E951), mint flavour, carmoisine lake (E122), magnesium stearate, 
xylitol DC (contains carmellose sodium) or the following formulation constituents: 
sodium alginate, calcium carbonate, sodium bicarbonate. 
17. Previously randomised into the study. 
18. Employee at study site. 
19. Partner or first-degree relative of the Investigator. 
20. Patients who failed screening will not be allowed to re-enter the study. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 8 of 76 
21. Participation in a clinical study in the previous 6 months or participation in a previous 
Compound Sodium Alginate Double Action Chewable Tablet study.  
22. Unable in the opinion of the Investigator to comply fully with the study requirements.  
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 9 of 76 
3.10 
Methodology 
Schedule of Assessments 
 
Items 
Visit 1 
(Screening 
Visit) 
Visit 2 
0-10 days 
after Visit 
1 
Visit 3 
7 + 2 days 
after Visit 2 
Early 
Termination 
(ET) Visit 
Assess patient's suitability to enter study 
X 
X 
 
 
Issue patient information sheet and obtain 
informed consent 
X 
 
 
 
Assess concomitant medications  
X 
X 
X 
X 
Medical history 
X 
X 
 
 
Physical examination 
X 
 
X 
X 
Blood samples for haematology & clinical 
chemistry, urine pregnancy tests 
X 
 
X 
X 
Vital signs 
X 
 
X 
X 
12-lead ECG  
X 
 
 
 
Endoscopy 
X 
 
 
 
Assess Adverse Events 
 
X 
X 
X 
Administer refluxogenic test meal (after 
fast) 
 
X 
X 
 
Administer single randomised dose of four  
Compound Sodium Alginate Double Action 
Chewable Tablets or four matching placebo 
tablets 30 min after completion of test meal 
 
X 
X 
 
4-hour pH monitoring (from 30 min prior to 
dosing to 4 hours post dosing) 
 
X 
X 
 
Collect and record time pH data obtained 
 
X 
X 
 
Dispense one week NIMP Compound 
Sodium Alginate Double Action Chewable 
Tablets  (2 tablets 4 times daily) 
 
X 
 
 
Make appointment for next visit 
X 
X 
 
 
Collect returned unused & used medication 
(IMP & NIMP) 
 
 
X 
X 
End of study Assessments 
 
 
X 
X 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 10 of 76 
 
pH Monitoring 
 
Visit 
Time 
First Dosing Visit Procedures 
2 
• 
Ensure patient has not taken symptomatic treatment for GERD (antacids etc) 
in the 24 hours prior to pH monitoring 
• 
Ensure the patient has abstained from alcohol for 24 hours prior to the test 
meal. 
• 
Ensure the patient has fasted for a minimum of 4 hours prior to insertion of 
manometry probe. 
• 
Insert manometry probe to aid positioning of esophageal pH sensor (prior to 
consuming test meal). 
• 
Record pH from 30 minutes prior to dosing to 4 hours post dosing. 
-4 hours 
Abstain from food. 
-60 min 
Eat test meal. 
-30 min 
End of test meal. Start recording pH measurement. 
0  
Administer four Compound Sodium Alginate Double Action 
Chewable Tablets or four matching placebo tablets (as 
randomised). 
4 hours 
End of esophageal pH measurement. 
2 
 
Prior to departure 
Question for adverse events.   
Leave Unit. 
Visit 
Time 
Second Dosing Visit Procedures 
3 
• 
Ensure patient has not taken symptomatic treatment for GERD (antacids etc), 
including Compound Sodium Alginate Double Action Chewable Tablets, in the 
24 hours prior to pH monitoring 
• 
Ensure the patient has abstained from alcohol for 24 hours prior to the test 
meal. 
• 
Ensure the patient has fasted for a minimum of 4 hours prior to insertion of 
manometry probe. 
• 
Insert manometry probe to aid positioning of esophageal pH sensor (prior to 
consuming test meal). 
• 
Record pH from 30 minutes prior to dosing to 4 hours post dosing. 
-4 hours 
Abstain from food. 
-60 min 
Eat test meal. 
-30 min 
End of test meal. Start recording pH measurement. 
0  
Administer four Compound Sodium Alginate Double Action 
Chewable Tablets or four matching placebo tablets (as 
randomised). 
3 
 
4 hours 
End of esophageal pH measurement. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 11 of 76 
Prior to departure 
Question for adverse events.  
Follow-up assessments.   
Leave Unit. 
 
3.11 
Statistics 
All statistical tests will be conducted using two-tailed tests at the 5% significance level. 
The null hypothesis at all times will be the equality of the fixed effect being compared from 
the model. 
The primary endpoint will be analysed primarily using an ANOVA of variance model with 
treatment, dosing visit treatment sequence as fixed effects and patient nested within 
treatment sequence as a random effect. The difference between treatment least square 
means will be used to represent the treatment differences. The effects for dosing visit and 
treatment sequence will also be assessed. A residual analysis will be performed. If there is a 
major departure from the assumptions of normality, independence or heteroscedasticity of 
residuals, then further analysis using transformed data will be used to support the original 
model results. If such assumptions still do not hold following an appropriate transformation 
then Wilcoxon Rank-Sum test will be used to compare the dosing visit difference (dosing 
visit 1 – dosing visit 2) between treatment sequence groups to represent the treatment 
comparison. 
All secondary endpoints will be analysed identically to the primary endpoint. 
All secondary endpoints and sensitivity or alternate analyses for the primary endpoint will 
serve as supportive evidence for the primary analysis only and therefore no adjustment for 
multiple comparisons will be made. 
If less than 2 hours post-dosing monitoring data is available, for whatever reason, (or less 
than 1 hour post-dosing data within the first hour for parameters based on the first hour post-
dosing) the derived parameters will be considered missing.  If 2 or more hours post-dosing 
monitoring data is available, the parameters will be derived using the data available, and will 
be adjusted, where necessary, by multiplying by the factor (4 hours / time with data 
available).  Any data recorded more than 4 hours post-dosing will be ignored when deriving 
these parameters. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 12 of 76 
4 
TABLE OF CONTENTS 
1 
STUDY PROTOCOL TITLE PAGE..................................................................... 1 
2 
PROTOCOL APPROVAL ................................................................................... 2 
3 
PROTOCOL SYNOPSIS .................................................................................... 3 
3.1 
Rationale ........................................................................................................ 3 
3.2 
Objective(s) .................................................................................................... 3 
3.3 
Primary Endpoint............................................................................................ 3 
3.4 
Secondary Endpoints ..................................................................................... 3 
3.5 
Design Summary............................................................................................ 4 
3.6 
Sample Size ................................................................................................... 4 
3.7 
Anticipated Study Timings .............................................................................. 4 
3.8 
Inclusion Criteria............................................................................................. 5 
3.9 
Exclusion Criteria............................................................................................ 6 
3.10 
Methodology................................................................................................... 9 
3.11 
Statistics....................................................................................................... 11 
4 
TABLE OF CONTENTS.................................................................................... 12 
4.1 
List of Tables and Figures Contained in the Body of the Protocol................. 17 
4.2 
List of Appendices ........................................................................................ 18 
4.3 
List of Abbreviations ..................................................................................... 18 
5 
INVESTIGATORS AND ADMINISTRATIVE STUCTURE ................................. 19 
5.1 
Reckitt Benckiser Details.............................................................................. 19 
5.2 
Investigational Sites...................................................................................... 20 
5.3 
Laboratories ................................................................................................. 20 
6 
INTRODUCTION.............................................................................................. 21 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 13 of 76 
7 
STUDY RATIONALE ........................................................................................ 22 
8 
STUDY OBJECTIVES ...................................................................................... 22 
8.1 
Primary Objective ......................................................................................... 23 
8.2 
Secondary Objective(s) ................................................................................ 23 
9 
STUDY DESIGN............................................................................................... 23 
9.1 
Study Endpoints ........................................................................................... 23 
9.1.1 
Primary Endpoint ...................................................................................... 23 
9.1.2 
Secondary Endpoints................................................................................ 23 
9.2 
Design Summary.......................................................................................... 24 
9.3 
Discussion of Study Design.......................................................................... 24 
9.4 
Number of Patients....................................................................................... 25 
9.5 
Study Duration.............................................................................................. 25 
9.6 
Patient Commitment to the Study ................................................................. 26 
9.6.1 
Duration of Patient Participation................................................................ 26 
9.6.2 
Invasive Procedures ................................................................................. 27 
9.6.3 
General and Dietary Restrictions .............................................................. 27 
9.7 
End of Study................................................................................................. 27 
10 
STUDY POPULATION ..................................................................................... 28 
10.1 
Inclusion Criteria........................................................................................... 28 
10.2 
Exclusion Criteria.......................................................................................... 29 
10.3 
Patients of Reproductive Potential................................................................ 31 
11 
STUDY METHODOLOGY ................................................................................ 32 
11.1 
Recruitment of Study Patients ...................................................................... 32 
11.2 
Study Visits/Assessments............................................................................. 32 
11.3 
Baseline Visit................................................................................................ 35 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 14 of 76 
11.3.1 
Screening/Enrolment Procedures ............................................................. 35 
11.3.1.1 
Clinical Assessments Performed at Baseline (Visit 1, Screening Visit).. 35 
11.3.2 
Clinical Assessments Performed After Baseline ....................................... 37 
11.3.2.1 
Clinical Assessments at Visit 2.............................................................. 37 
11.3.2.2 
Clinical Assessments at Visit 3.............................................................. 39 
11.3.2.3 
Clinical Assessments at Early Termination (ET) Visit (only if required for 
patient early terminations)..................................................................... 40 
11.4 
Study Variables and Methods of Assessment............................................... 42 
11.4.1 
Efficacy Variables ..................................................................................... 42 
11.4.1.1 
Overview of Efficacy Variables.............................................................. 42 
11.4.1.2 
Methods of Assessment of Efficacy Variables....................................... 42 
11.4.2 
Appropriateness of Measurements ........................................................... 42 
11.5 
Study Specific Supplies ................................................................................ 43 
11.6 
Unscheduled Visits....................................................................................... 43 
11.7 
Patient Withdrawal and Replacement Criteria............................................... 43 
11.7.1 
Patient Withdrawal.................................................................................... 43 
11.7.2 
Replacement of Patients........................................................................... 44 
11.8 
Additional Care of Study Patients Following Completion of the Study........... 44 
11.9 
Treatment Compliance ................................................................................. 44 
11.10 
Premature Termination of the Study ............................................................. 44 
12 
STUDY TREATMENTS .................................................................................... 45 
12.1 
Identity of Investigational Medicinal Products ............................................... 45 
12.2 
Identity of Non-Investigational Medicinal Products........................................ 46 
12.3 
Randomisation and Treatment Allocation ..................................................... 47 
12.3.1 
Randomisation.......................................................................................... 47 
12.3.2 
Blinding..................................................................................................... 47 
12.3.3 
Emergency Unblinding Procedures........................................................... 47 
12.3.4 
IMP allocation for Replacement Patients .................................................. 47 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 15 of 76 
12.4 
Dosage Instructions...................................................................................... 47 
12.5 
Standard Test Meal ...................................................................................... 48 
12.6 
Packaging .................................................................................................... 48 
12.7 
Labelling....................................................................................................... 49 
12.7.1 
Investigational Medicinal Product(s) ......................................................... 49 
12.7.2 
Patient Carton........................................................................................... 49 
12.7.3 
Patient Pack ............................................................................................. 49 
12.7.4 
Non-Investigational Medicinal Products .................................................... 49 
12.8 
Accountability of Investigational and Non-Investigational Medicinal Product(s)
..................................................................................................................... 50 
12.9 
Disposal of Unused Investigational and Non-Investigational Medicinal 
Product(s)..................................................................................................... 50 
12.10 
Concomitant Therapies ................................................................................ 51 
12.11 
Prohibited Therapies .................................................................................... 51 
13 
SAFETY ASSESSMENTS................................................................................ 52 
13.1 
Adverse Events ............................................................................................ 52 
13.1.1 
Adverse Event Definitions......................................................................... 52 
13.1.2 
Observation Period for Adverse Event Reporting...................................... 54 
13.1.3 
Information to be Collected on Adverse Events ........................................ 54 
13.1.4 
Procedure for Reporting Adverse Events.................................................. 57 
13.1.5 
Procedure for Reporting Serious Adverse Events..................................... 57 
13.1.6 
Reporting to Regulatory Authorities .......................................................... 59 
13.1.7 
Follow-up of Patients Experiencing Adverse Events upon Completion of the 
Study or Withdrawal from the Study.......................................................... 60 
13.1.8 
Procedures for Patients Experiencing Onset of Adverse Events after End of 
the Study .................................................................................................. 60 
13.2 
Overdose...................................................................................................... 60 
13.3 
Pregnancy .................................................................................................... 60 
13.4 
Clinical Laboratory Investigations ................................................................. 61 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 16 of 76 
13.4.1 
Collection of Laboratory Samples ............................................................. 62 
13.4.2 
Labelling of Laboratory Samples............................................................... 62 
13.4.3 
Reference Ranges.................................................................................... 62 
13.4.4 
Laboratory Results Review....................................................................... 62 
13.4.5 
Good Clinical Laboratory Practice (GCLP) Compliance ............................ 63 
13.5 
Vital Signs, Physical Findings and other Observations Related to Safety ..... 63 
14 
STATISTICAL CONSIDERATIONS.................................................................. 63 
14.1 
Sample Size Justification.............................................................................. 63 
14.2 
Data to be Analysed ..................................................................................... 64 
14.3 
Patient Disposition and Characteristics......................................................... 64 
14.4 
Efficacy Analyses ......................................................................................... 65 
14.4.1 
Primary Efficacy Analysis Endpoint........................................................... 65 
14.4.2 
Secondary Efficacy Endpoints .................................................................. 65 
14.4.3 
Statistical Methods for Efficacy Analyses.................................................. 66 
14.5 
Safety Analyses............................................................................................ 66 
14.5.1 
Adverse Events ........................................................................................ 67 
14.5.2 
Laboratory Data........................................................................................ 67 
14.5.3 
Vital Signs ................................................................................................ 68 
14.5.4 
Other Variables Related to Safety............................................................. 68 
14.6 
Interim Analyses........................................................................................... 68 
15 
QUALITY CONTROL AND QUALITY ASSURANCE AUDIT............................. 68 
15.1 
Monitoring .................................................................................................... 68 
15.2 
Source Document Verification ...................................................................... 69 
15.3 
Audit............................................................................................................. 70 
15.4 
RB Policy on Fraud in Clinical Studies.......................................................... 70 
16 
ETHICS ............................................................................................................ 70 
16.1 
Independent Ethics Committee/Institutional Review Board Review .............. 70 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 17 of 76 
16.2 
Patient Information and Consent .................................................................. 71 
16.3 
Informing General Practitioners .................................................................... 71 
17 
REGULATORY REQUIREMENTS ................................................................... 72 
17.1 
Competent Authority Authorisation ............................................................... 72 
17.2 
Curriculum Vitae........................................................................................... 72 
18 
DATA HANDLING AND RECORD KEEPING ................................................... 72 
18.1 
Case Report Forms (CRFs).......................................................................... 72 
18.2 
Retention of Essential Documentation.......................................................... 73 
18.3 
Protocol Amendments .................................................................................. 73 
19 
CLINICAL TRIAL AGREEMENT....................................................................... 74 
20 
COMPENSATION, INDEMNITY AND INSURANCE......................................... 74 
20.1 
Compensation .............................................................................................. 74 
20.2 
Indemnity...................................................................................................... 74 
20.3 
Insurance ..................................................................................................... 75 
21 
REPORTING, PUBLICATION AND PRESENTATION...................................... 75 
22 
REFERENCES................................................................................................. 75 
23 
APPENDICES .................................................................................................. 76 
 
4.1 
List of Tables and Figures Contained in the Body of the Protocol 
Table 4-1 List of Abbreviations............................................................................................ 18 
Table 5-1 Reckitt Benckiser Details..................................................................................... 20 
Table 11-1 Schedule of Assessments................................................................................. 33 
Table 13-1 Table of Information to be Collected on Adverse Events ................................... 55 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 18 of 76 
Figure 13-1 Procedure for Reporting SAEs......................................................................... 59 
 
4.2 
List of Appendices 
There are no appendices. 
 
4.3 
List of Abbreviations 
Table 4-1 List of Abbreviations 
Abbreviation 
Abbreviation in Full 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
ANOVA 
Analysis of Variance 
AR 
Adverse Reaction 
CA 
Competent Authority 
CIOMS 
Council for International Organizations of Medical Sciences 
CPM 
Clinical Project Manager 
CRF 
Case Report Form 
CRO 
Contract Research Organisation 
CTA 
Clinical Trial Application 
CV 
Curriculum Vitae 
DSO 
RB Drug Safety Officer 
eCRF 
Electronic Case Report Form 
GCP 
Good Clinical Practice 
GCLP 
Good Clinical Laboratory Practice 
GERD 
Gastro-esophageal reflux disease 
GMP 
Good Manufacturing Practice 
GVG 
Global Vigilance Group 
IB 
Investigators Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 19 of 76 
Abbreviation 
Abbreviation in Full 
NCR 
No Carbon Required  
NERD 
Nonerosive Esophageal Reflux Disease 
NIMP 
Non-investigational Medicinal Product 
NSAID 
Non Steroidal Anti-Inflammatory Drug 
OTC 
Over-the-counter 
PFDA 
Provincial Food and Drug Administration in China 
PPI 
Proton pump inhibitor 
QA 
Quality Assurance 
R&D 
Research and Development 
RB 
Reckitt Benckiser 
SAE 
Serious Adverse Event 
SDV 
Source Data Verification 
SFDA 
State Food and Drug Administration in China 
SOP 
Standard Operating Procedure 
UK 
United Kingdom (of Great Britain and Northern Ireland) 
 
5 
INVESTIGATORS AND ADMINISTRATIVE STUCTURE 
5.1 
Reckitt Benckiser Details 
The following RB personnel are responsible for the conduct of the study: 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 20 of 76 
Table 5-1 Reckitt Benckiser Details 
Name 
Position 
Address and Contact Number 
Clinical Project Manager  
Reckitt Benckiser Healthcare (UK) 
Ltd, Dansom Lane, Hull, HU8 7DS. 
UK. 
Global Medical Director  
Reckitt Benckiser Healthcare (UK) 
Ltd, Dansom Lane, Hull, HU8 7DS. 
UK. 
Senior Statistician 
Reckitt Benckiser Healthcare (UK) 
Ltd, Dansom Lane, Hull, HU8 7DS. 
UK. 
 
The names and addresses of the 
 Study Monitors will be provided in the Initiation 
Visit Report.  
 
5.2 
Investigational Sites 
This is a multi-centre, hospital based study in China.  This study will be conducted at two or 
more hospital sites. 
The Co-ordinating Principal Investigator is 
 
 
China. 
 
5.3 
Laboratories 
Local hospital site laboratories will be used for this study. The names and addresses of all 
laboratories involved in the study for safety analyses will be documented in the Initiation Visit 
Reports for each site.  


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 21 of 76 
 
6 
INTRODUCTION 
Gastro-esophageal reflux disease (GERD) is a condition that develops when the backward 
movement of stomach contents into the esophagus causes troublesome symptoms and/or 
complications. The troublesome symptoms of GERD can have significant impact on health-
related quality of life and work productivity [1-4].  GERD is believed to be the most common 
upper gastro-intestinal condition, affecting between 10% and 20% of the Chinese population 
and the prevalence of GERD in Asia is reported to be approximately 5% [5]. 
Dyspepsia (sometimes referred to by the non-medical term indigestion) is defined as pain or 
discomfort centred in the upper abdomen. It is often described as a feeling of fullness, 
bloating, nausea, heartburn or gassy discomfort in the chest or abdomen. 
Heartburn and regurgitation are the two most predominant clinical manifestations of GERD 
[6]. The pain is usually burning in character and felt retrosternally, rising from the epigastrium 
towards or into the throat.   
The over-the-counter (OTC) preparations for treatment of heartburn in China include 
antacids, proton pump inhibitors (PPIs) and histamine H2-receptor antagonists as well as 
traditional Chinese medicines.  While PPIs are effective in acid-related conditions, they offer 
limited benefit for patients with functional dyspepsia and/or functional heartburn [6-8]. 
Compound Sodium Alginate Double Action Chewable Tablets (also known as Gaviscon® 
Double Action Tablets) are a combination of two antacids (calcium carbonate and sodium 
bicarbonate) and an alginate. On ingestion, the product reacts rapidly with gastric acid to 
form a raft of alginic acid gel having a near neutral pH and which floats on the stomach 
contents effectively impeding gastro-esophageal reflux. 
Calcium carbonate neutralises gastric acid to provide fast relief from indigestion and 
heartburn. This effect is increased by the addition of sodium bicarbonate which also has a 
neutralising action. The total neutralising capacity of four tablets is approximately 20 mEqH+. 
A similar study was previously conducted in China to demonstrate the effect of Gaviscon® 
Original Liquid on esophageal pH in GERD patients [9]. No clinical studies have been 
performed with Compound Sodium Alginate Double Action Chewable Tablets to 
demonstrate the effect on esophageal pH in patients with GERD.  This study is being 
conducted to provide evidence for inclusion in applications to regulatory authorities that 
Compound Sodium Alginate Double Action Chewable Tablets are effective for the treatment 
of reflux in patients diagnosed with GERD. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 22 of 76 
The potential risks to patients taking part in the present study are considered to be low.  
Endoscopy and placement of the pH catheter can cause discomfort but the risks associated 
with these procedures are considered to be low.  The adverse reactions that occur very 
rarely (<1/10,000) as a result of taking Gaviscon® products are allergic manifestations such 
as urticaria or bronchospasm, anaphylactic or anaphylactoid reactions as a result of a 
patient being sensitive to any of the active substances (sodium alginate, sodium bicarbonate 
and calcium carbonate) or any of the excipients.  Other adverse reactions include:  
1. Sodium bicarbonate – increased plasma sodium levels especially for those with renal 
and cardiovascular conditions on a highly restricted salt diet. 
2. Calcium carbonate – high doses of calcium may cause alkalosis, hypercalcaemia, 
acid rebound, milk alkali syndrome or constipation. 
For this reason, the risk benefit balance for the current study is considered to be acceptable. 
This study will be conducted in accordance with the principles set out in the Declaration of 
Helsinki. It will comply with International Conference on Harmonisation (ICH) Good Clinical 
Practice (GCP) and applicable regulatory requirements. 
 
7 
STUDY RATIONALE 
This study is being conducted to assess the effectiveness of the Compound Sodium Alginate 
Double Action Chewable Tablets compared to placebo on acidic reflux events into the 
esophagus in patients diagnosed with GERD. 
 
8 
STUDY OBJECTIVES 
The objective of this study is to demonstrate that Compound Sodium Alginate Double Action 
Chewable Tablets are statistically significantly superior to matching placebo tablets in the 
suppression of gastric reflux provoked by a standard refluxogenic meal in GERD patients. 
Gastric reflux will be assessed by ambulatory esophageal pH monitoring over 4 hours. 
The purpose of this study is to compare esophageal pH profiles monitored during the 
4-hours after ingestion of a refluxogenic test meal, followed by a single dose of study 
medication. Patients recruited to the study will attend the clinic on two occasions separated 
by 7 days, and at each visit they will consume a refluxogenic meal; 30 minutes later the 
patient will be randomised to receive either a dose of either four Compound Sodium Alginate 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 23 of 76 
Double Action Chewable Tablets or four matching placebo tablets. On each occasion 
esophageal pH will be monitored for 4 hours post dosing.  Each patient will be his/her own 
control. Between the pH monitoring visits, patients will take Compound Sodium Alginate 
Double Action Chewable Tablets, two tablets 4 times daily for 7 days, to provide ongoing 
symptom relief.  
 
8.1 
Primary Objective 
The primary objective of this study is to compare the time during the 4 hour post dosing 
period where the pH is below pH 4 for Compound Sodium Alginate Double Action Chewable 
Tablets versus matching placebo tablets. 
 
8.2 
Secondary Objective(s) 
The secondary objectives of this study are to determine and compare the number of 
occasions and percentage of time during the 1 and 4 hour post dosing period when pH falls 
below pH 4 and pH 5.  Other secondary objectives include comparing the longest reflux time 
and DeMeester scores during the 4 hour period. 
 
9 
STUDY DESIGN 
9.1 
Study Endpoints 
9.1.1 
Primary Endpoint 
The primary efficacy endpoint will be the percentage of time during the 4 hour post dosing 
period with pH below pH 4 for Compound Sodium Alginate Double Action Chewable Tablets 
versus matching placebo tablets. 
 
9.1.2 
Secondary Endpoints 
The following secondary endpoints will also be evaluated: 
• 
Percentage of time during the 4 hour post dosing period with pH below pH 5 
• 
Number of occasions during the 4 hour post dosing period when pH falls below pH 4 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 24 of 76 
• 
Number of occasions during the 4 hour post dosing period when pH falls below pH 5 
• 
Number of reflux episodes during the 4 hour post dosing period with pH below pH 4 
for at least 5 minutes 
• 
Percentage of time during the first hour post dosing with pH below pH 4 
• 
Percentage of time during the first hour post dosing with pH below pH 5 
• 
Number of occasions during the first hour post dosing when pH falls below pH 4 
• 
Number of occasions during the first hour post dosing when pH falls below pH 5 
• 
The longest reflux time during the 4 hour post dosing period (i.e. the longest period 
with pH below pH 4) 
• 
The DeMeester scores during the 4 hour post dosing period  
 
9.2 
Design Summary 
This is a multi-centre, randomised, open-label, placebo-controlled, two-period crossover 
study.  After signing a written informed consent, patients will undergo a screening period of 
up to 10 days.  Patients who satisfy the study entry requirements within 10 days of consent, 
will be randomised to receive either four Compound Sodium Alginate Double Action 
Chewable Tablets or four matching placebo tablets following placement of a pH electrode 
and a standardised refluxogenic meal.  
Upon completion of the 4-hour post-dose pH monitoring period patients will be instructed to 
begin taking supplied Compound Sodium Alginate Double Action Chewable Tablets (two 
tablets four times daily) for 7 days. Patients will return after the 7 day period for repeat 
catheter insertion and pH monitoring, receiving the alternative randomised treatment.   
 
9.3 
Discussion of Study Design 
Esophageal pH monitoring is a well validated and accepted technique for diagnosis of 
gastro-esophageal reflux disease (GERD). It provides direct physiologic measurement of 
acid in the esophagus and can assess the response of the disease to treatment.   In this 
study it is being used to assess and compare the effects of Compound Sodium Alginate 
Double Action Chewable Tablets and matching placebo tablets on pH over a 4 hour post-
dose period 30 minutes after a refluxogenic meal. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 25 of 76 
A crossover design is used for this study where the patient has pH measurement for four 
hours after four Compound Sodium Alginate Double Action Chewable Tablets and four 
matching placebo tablets on two separate occasions.  A 7-day washout period occurs 
between each pH monitoring visit; all patients will receive standardised treatment consisting 
of Compound Sodium Alginate Double Action Chewable Tablets (two tablets four times 
daily) for their symptoms of GERD during during this washout period between pH monitoring 
visits. 
 
9.4 
Number of Patients 
The number of patients enrolled for this study has been derived from experience of previous 
pH monitoring studies conducted with other Gaviscon formulations. It is anticipated that 36 
evaluable patients will be required to complete the study. In order to achieve this, 44 patients 
will be enrolled in this study. 
Further details are provided in Section 14.1. 
 
9.5 
Study Duration 
It is estimated that the clinical phase of this study will commence in May 2013 and last a 
period of 6-9 months. 
The duration of each patient’s participation in the study will be a maximum of 19 days (from 
screening visit to end of treatment visit) and involve 3 visits. 
Patients can enter the study, if eligible, as soon as all screening results are available 
following informed consent at Visit 1. A maximum of 10 days will be allowed to screen a 
patient at Visit 1. If eligible, the patient will be randomised and will commence the first pH 
monitoring period at Visit 2 (Day 0).  The patients will be randomised to receive either four 
Compound Sodium Alginate Double Action Chewable Tablets or four matching placebo 
tablets 30 minutes after a refluxogenic meal with pH monitored and recorded for a 4-hour 
period post-dose. 
All patients will then receive Compound Sodium Alginate Double Action Chewable Tablets 
(two tablets four times daily) as Non-investigational Medicinal Product (NIMP) for 
symptomatic treatment.  Patients will stop Compound Sodium Alginate Double Action 
Chewable Tablets 24 hours prior to returning for Visit 3 which occurs 7 ± 2 days later. The 
patient will receive the alternate treatment after a refluxogenic meal with pH monitored and 
recorded for a 4-hour period post-dose. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 26 of 76 
The anticipated overall duration of study conduct will be between 6 and 9 months.  
 
9.6 
Patient Commitment to the Study 
The duration of each patient’s participation in the study will be up to 19 days (from screening 
visit to final visit). The initial screening visit (Visit 1) will be followed by two visits (Visits 2 and 
3) at which the patient will consume a refluxogenic meal, followed 30 minutes later by a dose 
of either four Compound Sodium Alginate Double Action Chewable Tablets or four matching 
placebo tablets (as randomised); esophageal pH will be monitored continuously from 30 
minutes prior to dosing to 4 hours post dosing.  The study will be completed with post-study 
assessments after the second pH monitoring visit. 
 
9.6.1 
Duration of Patient Participation 
Up to 10 days will be allowed to screen a patient at Visit 1 following informed consent. The 
pre-study procedures will consist of a medical history and physical examination, 12-lead 
ECG, endoscopy diagnostic examination (endoscopy’s conducted prior to consent may be 
used if patients were examined within 28 days of giving consent if the examination was 
conducted at the same hospital), haematology and clinical chemistry and urine pregnancy 
test for female patients of child-bearing potential. 
Visit 2 (Day 0) will take place immediately after all screening results are available and within 
10 days after Visit 1. Patients meeting the entry criteria will be randomised to receive either 
four Compound Sodium Alginate Double Action Chewable Tablets or four matching placebo 
tablets administered following placement of a pH electrode (using manometry to position the 
pH electrode) and 30 minutes after a standardised refluxogenic meal. pH will be measured 
for 4 hours post-dose. 
The patient will then be issued with Compound Sodium Alginate Double Action Chewable 
Tablets (two tablets four times daily) to take for 7 + 2 days, stopping dosing at least 24 hours 
prior to Visit 3. 
At Visit 3, End of treatment period (Day 7 ± 2 days), unused investigational medicinal 
product (IMP) will be collected.  The patient will receive the alternate treatment following 
placement of a pH electrode and 30 minutes after a standardised refluxogenic meal.  pH will 
be measured for 4 hours post-dose followed by a final assessment for safety (AEs, 
haematology and clinical chemistry with urine pregnancy test for female patients and 
physical examination).  


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 27 of 76 
Further details on the timing of study visits are provided in Section 11.2. 
 
9.6.2 
Invasive Procedures 
Blood samples will be taken for haematology and clinical chemistry at Visit 1 and Visit 3.  
The total volume of blood samples will not exceed 30 ml. 
An endoscopy will be performed at screening or results may be used if conducted prior to 
consent within 28 days of giving consent if the examination was conducted at the same 
hospital. 
pH reflux monitoring for a period of 4.5 hours will take place on two occasions.  This requires 
placement of the pH monitoring probe via one nostril, down the back of the throat, and into 
the esophagus as the patient swallows. Esophageal manometry is used to guide the 
accurate placement of the pH electrodes. 
Further details on the study assessments are provided in Section 11.2. 
 
9.6.3 
General and Dietary Restrictions 
Patients will be instructed to follow their routine meal pattern, avoiding food not normally 
consumed, such as excessively spicy food. There should be an interval of at least three 
hours between meals. 
The patient will be asked to abstain from alcohol 24 hours prior to each test meal and to fast 
for a minimum of 4 hours prior to placement of the pH electrodes. 
The patient will be asked not to take any treatment for GERD symptoms for 24 hours prior to 
each test meal. 
 
9.7 
End of Study 
The end of the study is defined as the last visit of the last patient undergoing the study. 
 will notify SFDA within 90 days of the end of the study (within 15 days if the study is 
terminated prematurely). 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 28 of 76 
The Investigator will notify the IEC within 90 days of the end of the study (within 15 days if 
the study is terminated prematurely). 
 
10 
STUDY POPULATION 
10.1 
Inclusion Criteria 
Only patients to whom all of the following conditions apply will be included: 
1. Informed consent has been obtained. 
2. Age: ≥ 18 years to ≤ 65 years. 
3. Sex: male or female. 
4. Primary diagnosis: meet the diagnostic criteria for GERD with a GERD history of 
frequent episodes of GERD-related symptoms during the last 2 months prior to study 
screening.  The patient must also meet the following criteria:  
a. The only or main symptom is heartburn (burning feeling back of breast bone) 
and/or acid reflux. Symptoms persists or have occurred repeatedly for more 
than 2 months; 
b. As assessed by the Investigator at screening by questioning of the patient, 
the frequency of occurrence of heartburn is ≥ 3 days/week and the score of 
severity of heartburn in general is ≥ Level 2 within 3 weeks before screening; 
The severity of heartburn will be evaluated as follows: 
Level 0  
no heartburn  
 
Level 1  
heartburn is mild in severity and is not obvious  
Level 2  
heartburn is moderate, or it is obvious when it occurs, the 
patient experiences discomfort  
Level 3  
heartburn is severe and significant, seriously interferes with 
daily activities  
The frequency of heartburn will be evaluated as number of days /week that heartburn 
is suffered (0, 1, 2, 3, 4, 5, 6 or 7 days). 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 29 of 76 
5. Status: Patients will be patients at the clinic or members of the public who respond to 
an advertisement or via their doctor. 
6. Patients who have not taken any antacids within 24 hours before randomisation (Visit 
2) and be instructed not to take antacids, other than the Compound Sodium Alginate 
Double Action Chewable Tablets provided, throughout the remainder of the study. 
7. Patients taking mucous membrane protection drugs or prokinetics may enter the 
study provided that these are discontinued for at least 5 days before screening and 
throughout the remainder of the study. 
8. Systemic glucocorticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs, 
except for low dose aspirin which can be given for cardioprotection) can only be taken 
for up to 3 consecutive days in the 28 days prior to screening. 
9. Absence of relevant abnormalities in the physical examination, endoscopy, ECG and 
laboratory safety results. 
10. Patients who are willing to consume the entire standard refluxogenic test meal.  
Patients cannot be vegetarian. 
 
10.2 
Exclusion Criteria 
Patients to whom any of the following conditions apply must be excluded: 
1. Patients who have a history of drug, solvent or alcohol abuse (weekly alcohol intake ≥ 
140g). 
2. Patients who have suffered cardiac chest pain within the last year. 
3. Patients who have suffered a recent, significant unexplained weight loss of more than 
6 Kg in the last 6 months. 
4. Female patients of childbearing potential who, for the duration of the study, are either 
unwilling or unable to take adequate contraceptive precautions (as defined in 
Section 10.3) or are unwilling to be sexually abstinent (as defined in Section 10.3).  
5. Pregnancy or lactating mother.  


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 30 of 76 
6. Patients with a history and/or symptom profile suggestive of the following:  any other 
gastrointestinal (GI) disease, erosive GERD (Los Angeles [LA] classification grades 
C-D), Barrett’s esophagus, acute peptic ulcer and/or ulcer complications, Zollinger-
Ellison syndrome, gastric carcinoma, pyloric stenosis, oesophageal or gastric surgery, 
intestinal obstruction, current pernicious anaemia, indication for H-pylori eradication 
therapy, known gastro-intestinal bleeding (hematochezia or hematemesis) within the 
last 3 months, and severe diseases of other major body systems. 
7. Patients who are observed at screening to have a hiatus hernia with a diameter which 
exceeds 3cm. 
8. Patients who have taken anti-cholinesterase drugs, traditional Chinese medicines for 
treating gastrointestinal disease, ulcerlmin or misoprostol preparations within 7 days 
prior to screening or throughout the study. 
9. Patients who have taken PPIs during the 10 days prior to screening, prokinetics or H2 
antagonists during the 5 days prior to screening or systemic glucocorticosteroids, non-
steroidal anti-inflammatory drugs (NSAIDs, except for low dose aspirin which can be 
given for cardioprotection) on more than 3 consecutive days or PPI-based triple or 
quadruple therapy for eradication of H-pylori during the last 28 days. 
10. Patients taking or requiring to take macrolide antibiotics, such as erythromycin, 
azithromycin, from the day before screening. 
11. Patients with difficulty in swallowing. 
12. Patients with known hypophosphataemia, phenylketonuria or hypercalcaemia. 
13. Patients with severe constipation, or history of intestinal obstruction. 
14. In the opinion of the Investigator, patients with damaged heart or kidney function and 
patients who require a low sodium diet. 
15. Patients either with any co-existing condition which, in the opinion of the Investigator, 
would be likely to compromise patient safety or interfere with assessment of efficacy; 
or with any clinically significant abnormal laboratory values; or in the Investigator’s 
view to unable to comply fully with the study requirements. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 31 of 76 
16. Any previous history of allergy or known intolerance to any of the IMP’s or following 
formulation constituents: macrogol 20,000, mannitol (E421), copovidone, acesulfame 
K, aspartame (E951), mint flavour, carmoisine lake (E122), magnesium stearate, 
xylitol DC (contains carmellose sodium) or the following formulation constituents: 
sodium alginate, calcium carbonate, sodium bicarbonate. 
17. Previously randomised into the study. 
18. Employee at study site. 
19. Partner or first-degree relative of the Investigator. 
20. Patients who failed screening will not be allowed to re-enter the study. 
21. Participation in a clinical study in the previous 6 months or participation in a previous 
Gaviscon study.  
22. Unable in the opinion of the Investigator to comply fully with the study requirements.  
 
10.3 
Patients of Reproductive Potential 
Woman of childbearing potential must take adequate contraceptive precautions for the entire 
duration of study participation. Adequate contraceptive precautions include oral or injectable 
contraceptives; approved hormonal implants or topical patches; intrauterine devices; barrier 
methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with 
spermicidal foam/gel/film/cream/suppository; true abstinence (true abstinence: when this is 
in line with the preferred and usual lifestyle of the patient. Periodic abstinence e.g., calendar, 
ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable 
methods of contraception. Should the patient become sexually active while participating in 
the study, she must agree to use a double barrier method or condoms/diaphragms with 
spermicidal foam/gel/film/cream/suppository). Patients are to be informed that a female 
condom and male condom should not be used together as friction between the two can 
result in either product failing. A woman of childbearing potential is defined as any female 
who is less than 2 years post-menopausal or who has not undergone a hysterectomy or 
surgical sterilisation, e.g. bilateral tubal ligation, bilateral ovariectomy (oophorectomy). 
The procedures to be followed if a patient becomes pregnant while enrolled in the study are 
described in Section 13.3. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 32 of 76 
11 
STUDY METHODOLOGY 
11.1 
Recruitment of Study Patients 
Patients will be recruited from the hospital clinics, hospital database or by advertisement.  
Patients suffering from mild to moderate symptoms of GERD will be given the opportunity by 
the investigator to participate in the study. Patients will be recruited according to the 
Investigator’s standard procedures at the study site. 
 
11.2 
Study Visits/Assessments 
A patient is enrolled into a study when he or she (or a legal representative as defined 
in Section 16.2) has signed the informed consent form, i.e. prior to any study-specific 
assessments being performed.  
 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 33 of 76 
Table 11-1 Schedule of Assessments 
 
Items 
Visit 1 
(Screening 
Visit) 
Visit 2 
0-10 days 
after Visit 
1 
Visit 3 
7 + 2 days 
after Visit 2 
Early 
Termination 
(ET) Visit 
Assess patient's suitability to enter study 
X 
X 
 
 
Issue patient information sheet and obtain 
informed consent 
X 
 
 
 
Assess concomitant medications  
X 
X 
X 
X 
Medical history 
X 
X 
 
 
Physical examination 
X 
 
X 
X 
Blood samples for haematology & clinical 
chemistry, urine pregnancy tests 
X 
 
X 
X 
Vital signs 
X 
 
X 
X 
12-lead ECG  
X 
 
 
 
Endoscopy 
X 
 
 
 
Assess Adverse Events 
 
X 
X 
X 
Administer refluxogenic test meal (after 
fast) 
 
X 
X 
 
Administer single randomised dose of four  
Compound Sodium Alginate Double Action 
Chewable Tablets or four matching placebo 
tablets 30 min after completion of test meal 
 
X 
X 
 
4-hour pH monitoring (from 30 min prior to 
dosing to 4 hours post dosing) 
 
X 
X 
 
Collect and record time pH data obtained 
 
X 
X 
 
Dispense one week NIMP Compound 
Sodium Alginate Double Action Chewable 
Tablets  (2 tablets 4 times daily) 
 
X 
 
 
Make appointment for next visit 
X 
X 
 
 
Collect returned unused & used medication 
(IMP & NIMP) 
 
 
X 
X 
End of study Assessments 
 
 
X 
X 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 34 of 76 
pH Monitoring 
The time course for pH monitoring is summarised in the following table: 
Table 11-2 Schedule for pH monitoring 
 
Visit 
Time 
First Dosing Visit Procedures 
2 
• 
Ensure patient has not taken symptomatic treatment for GERD (antacids etc) 
in the 24 hours prior to pH monitoring 
• 
Ensure the patient has abstained from alcohol for 24 hours prior to the test 
meal. 
• 
Ensure the patient has fasted for a minimum of 4 hours prior to insertion of 
manometry probe. 
• 
Insert manometry probe to aid positioning of esophageal pH sensor (prior to 
consuming test meal). 
• 
Record pH from 30 minutes prior to dosing to 4 hours post dosing. 
-4 hours 
Abstain from food. 
-60 min 
Eat test meal. 
-30 min 
End of test meal. Start recording pH measurement. 
0  
Administer four Compound Sodium Alginate Double Action 
Chewable Tablets or four matching placebo tablets (as 
randomised). 
4 hours 
End of esophageal pH measurement. 
2 
 
Prior to departure 
Question for adverse events.   
Leave Unit. 
Visit 
Time 
Second Dosing Visit Procedures 
3 
• 
Ensure patient has not taken symptomatic treatment for GERD (antacids etc), 
including Compound Sodium Alginate Double Action Chewable Tablets, in the 
24 hours prior to pH monitoring 
• 
Ensure the patient has abstained from alcohol for 24 hours prior to the test 
meal. 
• 
Ensure the patient has fasted for a minimum of 4 hours prior to insertion of 
manometry probe. 
• 
Insert manometry probe to aid positioning of esophageal pH sensor (prior to 
consuming test meal). 
• 
Record pH from 30 minutes prior to dosing to 4 hours post dosing. 
-4 hours 
Abstain from food. 
-60 min 
Eat test meal. 
-30 min 
End of test meal. Start recording pH measurement. 
3 
 
0  
Administer four Compound Sodium Alginate Double Action 
Chewable Tablets or four matching placebo tablets (as 
randomised). 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 35 of 76 
4 hours 
End of esophageal pH measurement. 
Prior to departure 
Question for adverse events.  
Follow-up assessments.   
Leave Unit. 
 
11.3 
Baseline Visit 
11.3.1 
Screening/Enrolment Procedures 
Potential patients will be provided with the patient information sheets and given ample time 
to read and decide whether they are interested in taking part in the study. If the patient is 
interested, she/he will speak to the investigator or person delegated by the investigator to 
take consent who will explain more about the study and answer any questions. If the patient 
feels fully informed and willing to participate in the study they will complete, sign and date 
the informed consent form (ICF). The ICF will then be counter signed and dated by the 
investigator or person delegated by the investigator  to take consent. A copy of the ICF and 
patient information sheet will be provided to the patient for their personal records. 
All patients will be given a 4-digit screening number once they have provided consent. The 
first two digits will refer to the centre number and the second two digits to the number of 
patients screened at that centre. For example, screening numbers at centre 01 will start 
0101, 0102 etc.  
The screening process can take up to a maximum of ten days after informed consent. 
 
11.3.1.1 
Clinical Assessments Performed at Baseline (Visit 1, 
Screening Visit) 
The following baseline assessments (Visit 1, screening visit) will be conducted: 
Review of primary inclusion and exclusion criteria  
Assessment of symptoms 
The severity of heartburn will be evaluated as follows: 
Level 0  
no heartburn  
 
Level 1  
heartburn is mild in severity and is not obvious  


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 36 of 76 
Level 2  
heartburn is moderate, or it is obvious when it occurs, the patient experiences 
discomfort  
Level 3  
heartburn is severe and significant, seriously interferes with daily activities  
The frequency of heartburn will be evaluated as number of days / week that heartburn is 
suffered (0, 1, 2, 3, 4, 5, 6 or 7 days) 
The primary inclusion criteria will be based on the symptom of heartburn only. 
Demographic data: 
• 
Sex 
• 
Race (categorised as: Caucasian, Asian, Afro-Caribbean and Other) 
• 
Date of birth 
• 
Height (cm)  
• 
Weight (kg)  
• 
Smoking/alcohol/drugs of abuse history/use 
Laboratory safety data: 
• 
Haematology 
• 
Clinical chemistry 
Vital signs: 
• 
Blood pressure (after sitting for 5 minutes; mmHg) 
• 
Heart rate (radial pulse counted for 30 seconds after resting for 5 minutes; beats/minute) 
12-lead ECG 
Medical history and current status: 
• 
Primary diagnosis 
• 
Duration of disease 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 37 of 76 
• 
Medical history and current status 
Medication and therapy history: 
• 
Current therapy (including any OTC or traditional Chinese medicines) 
• 
Therapy in the previous 30 days (including any OTC or traditional Chinese medicines) 
Endoscopy examination: 
• 
A standard hospital endoscopy examination will be conducted to indicate whether the 
patient meets inclusion/exclusion criteria.  
 
• 
Endoscopy diagnosis examinations conducted prior to consent may be used if patients 
were examined within 28 days of giving consent, only if the examination was conducted 
at the same hospital and if the endoscopy results are available for study monitoring 
purposes. 
Physical examination 
• 
A standard physical examination 
Pregnancy testing  
• 
Women of child-bearing potential will undergo urine pregnancy testing.   
 
11.3.2 
Clinical Assessments Performed After Baseline 
11.3.2.1 
Clinical Assessments at Visit 2 
Visit 2 will take place up to 10 days after Visit 1. It can be the same day as Visit 1 but will 
only occur on the same day as Visit 1 if the patient meets all criteria with respect to use of 
concomitant medication, abstention from alcohol, fasting etc.  
At Visit 2 patients will return to the clinic to have any medical history changes during the 
screening period and concomitant medications recorded; any adverse events noted during 
the pH monitoring session will be recorded. If the patient fulfils the eligibility criteria for 
randomisation, a unique 3-digit randomisation number will be allocated and study medication 
dispensed (001, 002 etc.). The randomisation number will be pre-printed on the medication 
assigned to that patient. Randomisation numbers will not be site-specific. The numbers 
available at a site have to be allocated to the patients in consecutive order.  


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 38 of 76 
Eligible patients will undergo the following pH monitoring procedure: 
4-hour pH monitoring 
1) Patients will be required to fast for a minimum period of 4 hours prior to insertion 
of the manometric probe used to transfer the pH electrode. 
2) The basic equipment requirements for ambulatory esophageal pH studies are a 
portable data logger for data storage, a pH electrode, a computer and software for 
analysis of pH data. 
3) The probe and pH electrode will be passed through a nostril; manometry will be 
used to ensure the pH electrode is correctly positioned 5 cm above the superior 
margin of the lower esophageal sphincter (LES) and then taped to the face to hold 
it in place. 
4) 30 minutes after the procedure patients will receive a standardised reflux 
provoking meal (Section 12.5); patients will be allowed 30 minutes to consume the 
entire meal. After consumption of the meal the pH monitoring data logger will be 
activated and recording will continue until 4 hours post-dose. 
5) 30 minutes after completing the meal patients will receive their randomised single 
dose of study medication, either four Compound Sodium Alginate Double Action 
Chewable Tablets or four matching placebo tablets.  
6) Patients will remain in the clinic for the duration of the pH monitoring period, under 
supervision. They will be allowed to sit or stand during the pH monitoring period 
but will be encouraged not to lie down.  
7) Volunteers will not be permitted to eat or drink anything other than the test meal 
from the start of the fasting period until the end of the first dosing visit. 
8) Upon completion of the monitoring period patients will be given a prescribing card 
which they will use to collect their symptom control medication, Compound 
Sodium Alginate Double Action Chewable Tablets, from a dispensing unit.  
Sufficient medication will be dispensed to allow 8 days usage. Patients will be 
instructed to begin taking their Compound Sodium Alginate Double Action 
Chewable Tablets later that same day (typically the evening of Visit 2) and 
continue until their last dose 24 hours prior to their next visit. Patients will be 
instructed to follow their routine meal pattern, avoiding food not normally 
consumed, such as excessively spicy food. There should be an interval of at least 
three hours between meals. They will be instructed to take bring all medication 
with them to the clinic when they return for Visit 3. 
9) Patients will be questioned about adverse events ("How have you been feeling 
today?").  Any adverse events reported in response to this question or otherwise 
spontaneously reported by the volunteer or observed by the study personnel at 
any point during study procedures will be recorded in the patient’s CRF. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 39 of 76 
On completion of the visit, an appointment will be made for the next visit, 7 + 2 days later.  
Patients will be instructed to stop taking Compound Sodium Alginate Double Action 
Chewable Tablets 24 hours prior to the next visit and fast from food and liquids for 4 hours 
prior to the next visit. 
Emergency cards will be issued to patients before they leave the centre. The emergency 
card will be the size of a credit card and will contain the following information: 
• 
Study number.  
• 
Patient (randomisation) number. 
• 
Statement that patient is participating in a clinical trial. 
• 
Statement that the patient is taking two Compound Sodium Alginate Double Action 
Chewable Tablets four times per day. 
• 
Instructions to non-investigator staff to ring a 24-hour telephone number in case of 
emergency. 
 
11.3.2.2 
Clinical Assessments at Visit 3 
Patients will arrive at the hospital 7 + 2 days after the last visit.  At Visit 3 the Investigator 
will: 
1) Record any concomitant medications and adverse events occurring since the last 
visit; 
2) The Investigator will conduct 4-hour pH monitoring (see section 11.3.2.1 4-hour 
pH monitoring for procedure and fasting requirements). At this second dosing 
visit, the patient will receive the alternate randomised study treatment (four 
Compound Sodium Alginate Double Action Chewable Tablets or four matching 
placebo tablets).  
3) 4-hour pH monitoring data will be collected from Visit 3. The Investigator will 
record any additional adverse events and concomitant medications at the end of 
the visit.  
4) All medication, used and unused blister packs, will be returned to the drug 
dispensing unit. 
Post study Follow Up Assessments (visit 3) 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 40 of 76 
The following examinations and investigations will be conducted after the pH monitoring data 
has been collected (on the same day as the pH monitoring visit): 
Vital Signs  
• 
Blood pressure (after sitting for 5 minutes; mmHg). 
• 
Heart rate (radial pulse counted for 30 seconds after resting for 5 minutes; 
beats/minute). 
 
Concomitant Medication 
• 
All concomitant medication usage including any OTC medications and tradional 
Chinese medications  will be recorded. 
 
Adverse Events 
• 
All adverse events will be recorded. 
 
Physical examination 
• 
A standard physical examination will be conducted. 
 
Laboratory investigations (haematology and clinical chemistry) 
• 
Details are listed in section 13.4. 
 
Pregnancy testing  
• 
Women of child-bearing potential will undergo urine pregnancy testing. 
 
11.3.2.3 
Clinical Assessments at Early Termination (ET) Visit (only if 
required for patient early terminations) 
If the investigator withdraws the patient from the study for any reason after Visit 2 the patient 
will complete the study at this early termination visit and the following will be completed. 
Vital Signs  


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 41 of 76 
• 
Blood pressure (after sitting for 5 minutes; mmHg). 
• 
Heart rate (radial pulse counted for 30 seconds after resting for 5 minutes; 
beats/minute). 
 
Concomitant Medication 
• 
All concomitant medication usage including any OTC medications and traditional 
Chinese medications will be recorded. 
 
Adverse Events 
• 
All adverse events will be recorded. 
 
Physical examination 
• 
A standard physical examination will be conducted. 
 
Laboratory investigations (haematology and clinical chemistry) 
• 
Details are listed in section 13.4. 
 
Pregnancy testing  
• 
Women of child-bearing potential will undergo urine pregnancy testing 
 
Early Study Termination 
• 
The investigator will assess the reason for early termination: AE; lack of efficacy; lost 
to follow-up; no further need for IMP; protocol violation; death; withdrawal of consent; 
other. 
• 
The patient will return unused NIMP 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 42 of 76 
11.4 
Study Variables and Methods of Assessment 
11.4.1 
Efficacy Variables 
11.4.1.1 
Overview of Efficacy Variables 
The primary and some secondary efficacy variables are derived from the 4-hour pH 
monitoring sessions following four Compound Sodium Alginate Double Action Chewable 
Tablets or four matching placebo tablets. 
 
11.4.1.2 
Methods of Assessment of Efficacy Variables 
Efficacy is assessed by esophageal pH monitoring following a standard refluxogenic test 
meal.  A single dose of the study treatment is administered 30 minutes after completion of 
the meal and pH measurements recorded for 4 hours post-dose.  Patients will be 
randomised to receive four Compound Sodium Alginate Double Action Chewable Tablets or 
four matching placebo tablets and one week later will receive the alternate treatment. 
 
11.4.2 
Appropriateness of Measurements 
Esophageal pH monitoring is a well validated and accepted technique for diagnosis of 
gastro-esophageal reflux disease (GERD). It provides direct physiologic measurement of 
acid in the esophagus and can assess the response of the disease to treatment. In this study 
it is being used to assess and compare the effects of four Compound Sodium Alginate 
Double Action Chewable Tablets and four matching placebo tablets on pH over a 4 hour 
post-dose period 30 minutes after a refluxogenic meal. 
A crossover design is used for this study where the patient has pH measurement after 
Compound Sodium Alginate Double Action Chewable Tablets and matching placebo tablets 
on two separate occasions.  A 7-day washout period occurs between each pH monitoring 
visit; all patients will receive standard treatment, Compound Sodium Alginate Double Action 
Chewable Tablets (two tablets four times daily), for their symptoms of GERD during this 
washout period between pH monitoring visits. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 43 of 76 
11.5 
Study Specific Supplies 
Not applicable 
 
11.6 
Unscheduled Visits 
If unscheduled visits occur, the Investigator must record the following in the patient’s CRF: 
• 
Reason for unscheduled visit 
• 
Any AEs. 
• 
Concomitant therapy changes. 
• 
Withdrawal (if deemed appropriate). 
• 
Any clinical assessments deemed appropriate for the clinical care of the patient. 
If the dosage regimen of study medication has been changed, the Investigator must contact 
the RB Clinical Project Manager in order to determine if the patient should be withdrawn 
from the study or may be allowed to continue. The Clinical Project Manager will advise the 
Investigator of how information should be recorded on the CRF. 
Unscheduled visits should not alter the timing of the routine study schedule. 
 
11.7 
Patient Withdrawal and Replacement Criteria 
11.7.1 
Patient Withdrawal 
The Investigator may withdraw the patient from the study at any time. Reasons for removing 
a patient from the study include, but are not limited to: 
• 
AEs that in the judgement of the Investigator may cause severe or permanent harm 
(significant clinical deterioration is an AE). 
• 
Violation of the study protocol. 
• 
In the Investigator’s judgement, it is in the patient’s best interest. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 44 of 76 
• 
Patient declines further study participation. 
The primary reason for withdrawal will be documented as one of the following: AE; lack of 
efficacy; lost to follow-up; no further need for IMP (unless this is a study endpoint); protocol 
violation; death; withdrawal of consent; other. The Investigator must make reasonable 
attempts to contact patients who are lost to follow-up - a minimum of 2 documented 
telephone calls or a letter is considered reasonable. 
In the event of early withdrawal the patient should have the assessments listed in Section 
11.3.2.3 completed. 
 
11.7.2 
Replacement of Patients 
Patients who withdraw from the study will not be replaced. 
 
11.8 
Additional Care of Study Patients Following Completion of the 
Study 
Patients who experience AEs at the end of the study, or experience the onset of an AE after 
the end of the study, will be followed up as described in Sections 13.1.7 and 13.1.8. 
No other additional care of study patients will take place following the end of the study. The 
treatment of the patient’s condition will follow normal clinical practice. 
 
11.9 
Treatment Compliance 
The IMP will be administered at the study site under the supervision of the Investigator or his 
or her delegate. 
 
11.10 
Premature Termination of the Study 
RB may prematurely terminate the conduct of the study specific study sites or the entire 
study.  Reasons for early termination include, but are not limited to: 
• 
Inability to recruit or slow recruitment of patients 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 45 of 76 
• 
Unacceptable data quality 
• 
Concerns regarding the risk/benefit ratio 
• 
Withdrawal of CA or IEC approval 
• 
Recall of a batch of IMP where replacement medication will not be provided 
• 
Results from an interim statistical or safety analysis 
• 
Inability to remedy a clinical hold or suspension 
• 
Unresolved non-compliance with GCP or the protocol that compromises patient rights 
or safety or the study data 
The CPM will inform all investigators in writing at specific study sites relevant to the decision.  
A suitable course of action will be agreed for existing patients.  The investigator will inform 
the IEC/IRB in writing and provide a copy to RB for filing in the TMF.  
 will inform the 
SFDA within 15 days of the date of termination and file a copy of the correspondence in 
TMF. 
 
12 
STUDY TREATMENTS 
12.1 
Identity of Investigational Medicinal Products 
The following medication will be supplied. 
 
Compound Sodium Alginate Double Action Chewable Tablets.  
 
Matching placebo tablets.  
Compound Sodium Alginate Double Action Chewable Tablets will be manufactured to Good 
Manufacturing Practice (GMP) by Reckitt Benckiser Healthcare (UK) Limited, Dansom Lane, 
Hull, HU8 7DS, UK (Product Licence 00063/0157).  The matching placebo tablets will be 
manufactured to Good Manufacturing Practice (GMP) by 
 
 for RB. 
The active and placebo treatment will be shipped to 
 
 where both 
active and placebo will be blister packed.  The blister packs will be shipped to the 
Investigational Material Supplies Unit (IMSU), Reckitt Benckiser Healthcare UK Ltd, Dansom 
Lane, Hull, HU8 7DS UK. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 46 of 76 
The supplies will be assembled and labelled to GMP standards by the Investigational 
Material Supplies Unit (IMSU), Reckitt Benckiser Healthcare UK Ltd, Dansom Lane, Hull, 
HU8 7DS.  They will be shipped directly from IMSU to be distributed to the investigator sites 
from a distribution centre in China. 
For the open-label single dose treatments, labels will identify which of the two treatments 
(active or placebo) the patient’s pack contains. 
 
12.2 
Identity of Non-Investigational Medicinal Products 
Each patient will be instructed to take Compound Sodium Alginate Double Action Chewable 
Tablets as a multiple dose regimen for the 7-day period between each pH monitoring visit. 
Prior to dosing, all patients will be instructed by the Investigator on how they will take the 
medication, ie, chew and swallow two tablets on each dosing occasion. Patients will be 
instructed to start taking their medication on the same day following the first pH monitoring 
visit (usually the evening dose). Two tablets will be chewed and swallowed four times a day: 
30 minutes after breakfast, 30 minutes after lunch, 30 minutes after dinner and immediately 
before lying down for bed.  
Compound Sodium Alginate Double Action Chewable Tablets will be used for treatment of 
the symptoms of GERD between the pH monitoring visits and not for experimental purposes. 
Compound Sodium Alginate Double Action Chewable Tablets will be manufactured to Good 
Manufacturing Practice (GMP) by Reckitt Benckiser Healthcare (UK) Limited, Dansom Lane, 
Hull, HU8 7DS, UK (Product Licence 00063/0157).   
The active treatment will be shipped to 
 
, where the Compound 
Sodium Alginate Double Action Chewable Tablets will be blister packed.  The blister packs 
will be shipped to the Investigational Material Supplies Unit (IMSU), Reckitt Benckiser 
Healthcare UK Ltd, Dansom Lane, Hull, HU8 7DS UK. 
The supplies will be assembled and labelled to GMP standards by the Investigational 
Material Supplies Unit (IMSU), Reckitt Benckiser Healthcare UK Ltd, Dansom Lane, Hull, 
HU8 7DS.  They will be shipped directly from IMSU to be distributed to the investigator sites 
from a distribution centre in China. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 47 of 76 
12.3 
Randomisation and Treatment Allocation 
12.3.1 
Randomisation 
Drug supplies for the two single doses per patient will be randomised by the RB IMSU, 
according to a computer-produced randomisation schedule. On randomisation, patients will 
be allocated a unique patient number in numerical sequence. Issue of the IMP in this 
sequence will ensure randomisation.   
The IMSU will hold the master code for the randomisation schedule.   
This study is not blinded. 
 
12.3.2 
Blinding 
This study is not blinded. 
 
12.3.3 
Emergency Unblinding Procedures 
This study is not blinded. 
 
12.3.4 
IMP allocation for Replacement Patients 
Patients will not be replaced. 
 
12.4 
Dosage Instructions 
For the open-label, single dose treatment at each of the pH monitoring visits, patients will be 
administered four Compound Sodium Alginate Double Action Chewable Tablets or four 
matching placebo tablets. 
All patients will be instructed by the Investigator on how they will take the medication, ie, 
thoroughly chew then swallow each tablet.  
Medication errors may result in this study, from the administration or consumption of the 
wrong drug, by the wrong patient, at the wrong time, or at the wrong dosage strength.  Such 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 48 of 76 
medication errors occurring to a study participant will be captured on the adverse event (AE) 
page of the CRF and on a SAE form as appropriate.  In the event of medication dosing error, 
the sponsor should be notified immediately. 
Medication errors are reportable to RB irrespective of the presence of an associated 
AE/SAE, including: 
• 
Medication errors involving patient exposure to a medicinal product  
• 
Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the participating patient. 
Whether or not the medication error is accompanied by an AE/SAE, as determined by the 
investigator, the medication error and any associated AE/SAEs will be captured on an AE 
CRF page /SAE form (refer to Adverse Event Reporting section 13.1 for further details).  
 
12.5 
Standard Test Meal 
In addition to the study medications, during the pH monitoring period, all the patients are 
required to consume a standard test meal on two separate occasions. This will comprise the 
following from McDonalds:  
The Standardised Meal will consist of the following: 
Medium sized McDonalds Big Mac   
Portion of Medium size fries 
Medium sized Fanta Orange Drink 
 
This meal has a total calorific value of 990 kcal and contains protein 31 g, fat 40 g and 
carbohydrate 124 g.   
 
12.6 
Packaging 
Sufficient drug supplies will be packaged and labelled for 100 patients for the single dose 
crossover.  


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 49 of 76 
Each patient’s open-label, single dose pack will contain two blister packs each pack 
containing 4 tablets. Four tablets are to be taken from the first blister pack at the first pH 
monitoring visit and four tablets are to be taken from the second blister pack at the second 
pH monitoring visit.   
Each patient’s complete pack for the study will consist of:  
• 
One blister pack containing 4 Compound Sodium Alginate Double Action Chewable 
Tablets 
• 
One blister pack containing 4 matching placebo tablets  
 
12.7 
Labelling 
12.7.1 
Investigational Medicinal Product(s) 
Supplied IMP(s) will be labelled according to GCP and GMP requirements and any other 
applicable national/state legislation. 
Each patient pack and each patient carton will be labelled and each blister pack will be 
labelled.  
12.7.2 
Patient Carton  
The blister packs containing the single dose study treatments will be contained in an outer 
carton. 
 
12.7.3 
Patient Pack 
The patient pack will contain one open label treatment carton containing 8 blister packs of 
NIMP Compound Sodium Alginate Double Action Chewable Tablets and one single dose 
IMP carton containing the two single dose, open-label packs for to be administered at pH 
monitoring visits.  
 
12.7.4 
Non-Investigational Medicinal Products 
Supplied NIMP will be labelled according to GCP and GMP requirements and any other 
applicable national/state legislation. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 50 of 76 
Each blister pack, patient pack and each patient carton will be labelled.  
The patient will be asked to complete a NIMP return form noting the number of tablets 
returned. 
 
12.8 
Accountability of Investigational and Non-Investigational 
Medicinal Product(s) 
The Investigator will keep all IMP(s) and NIMP(s) in a pharmacy or a secure storage facility, 
accessible only to those individuals authorised by the Investigator to dispense the 
medication. 
The Investigator or designated individual will maintain an inventory. This will include the 
description and quantity of IMP(s) and NIMP(s) received during the course of this study, as 
well as a record of the materials that are dispensed and returned (how much, to whom, and 
when). This inventory (“Drug Dispensing Log”) will be subject to review by the study monitor 
during monitoring visits. 
The Investigator agrees not to supply IMP(s) and NIMP(s) to any person except study 
personnel and patients enrolled in this study. 
All IMP(s) and NIMP(s) should be stored between 4°C and 30°C. Temperatures must be 
monitored using a minimum / maximum thermometer and recorded in a temperature log on 
working days. 
 
12.9 
Disposal of Unused Investigational and Non-Investigational 
Medicinal Product(s) 
The Investigator agrees to conduct a drug supply inventory, to record the results of this 
inventory (“IMP/NIMP Removal from Site” form) and to return it and all original IMP/NIMP 
containers, whether empty or containing IMP or NIMP, to 
 at the end of the study or 
in stages during the course of the study. 
 and RB will arrange for the appropriate and timely destruction of all returned IMP(s) 
and NIMP(s) following the end of the study (on finalisation of the study report).  
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 51 of 76 
12.10 
Concomitant Therapies 
Concomitant therapies are defined as prescribed medications, physical therapies, and over-
the-counter preparations, including herbal preparations licensed for medicinal use, other 
than IMP(s) and NIMP(s) that the patient receives during the course of the study. 
The Investigator will record any medications given for treatment of AEs on the concomitant 
medication page in the patient’s CRF. Any medication taken by the patient from the time of 
giving informed consent through to the end of the study should also be recorded in the CRF. 
Any changes in concomitant therapy during the study will be documented, including 
cessation of therapy, initiation of therapy, and dose changes. 
 
12.11 
Prohibited Therapies 
The use of the following therapies will not be permitted: 
 
PPIs during the 10 days prior to screening and throughout the study. 
 
Prokinetics or H2 antagonists during the 5 days prior to screening and throughout the 
study. 
 
Systemic glucocorticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs except 
low dose aspirin given for cardioprotection) on more than 3 consecutive days in the 28 
days prior to screening and are not allowed throughout the study. 
 
PPI-based triple or quadruple therapy for eradication of H-pylori during the 28 days prior 
to screening and throughout the study. 
 
Mucous membrane protection drugs for 5 days prior to screening and throughout the 
study. 
 
Patients who have taken anti-cholinesterase drugs, traditional Chinese medicines for 
treating gastrointestinal disease, ulcerlmin or misoprostol preparations within 7 days prior 
to screening or throughout the study. 
 
Macrolide antibiotics, such as erythromycin, azithromycin, from the day before screening 
and throughout the study. 
 
Any antacids within 24 hours before randomisation (Visit 2) and throughout the 
remainder of the study.  Compound Sodium Alginate Double Action Chewable Tablets 
will be provided for symptom relief at the end of Visit 2 but must be stopped 24 hours 
prior to Visit 3. 
 
Patients who use any of these above medications during the study will be withdrawn. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 52 of 76 
The Investigator Brochure indicates that due to the presence of calcium carbonate which 
acts as an antacid, a time-interval of 2 hours should be considered between Compound 
Sodium Alginate Double Action Chewable Tablet intake and the administration of other 
medicinal products, especially H2-antihistaminics, tetracyclines, digoxine, fluoroquinolone, 
iron salt, ketoconazole, neuroleptics, thyroxine, penicilamine, beta-blockers (atenolol, 
metoprolol, propranolol), glucocorticoid, chloroquine and diphosphonates.  
 
13 
SAFETY ASSESSMENTS 
13.1 
Adverse Events 
13.1.1 
Adverse Event Definitions 
Adverse Event (AE): Any untoward medical occurrence in a patient participating in a clinical 
study administered an IMP, which does not necessarily have a causal relationship with 
administration of the IMP. 
Comment: An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of an 
IMP, whether or not considered related to the IMP. 
AEs do not include the following: 
• 
Medical or surgical procedures; the condition requiring a medical or surgical procedure is 
an AE. 
• 
Elective surgery or pre-existing conditions requiring planned procedures outside the 
scope of the study. 
Adverse Reaction (AR) to an IMP: All untoward and unintended responses to an IMP 
related to any dose administered. 
Comment: All AEs judged by either the Investigator or the sponsor as having a reasonable 
causal relationship to an IMP qualify as ARs. The expression “reasonable causal 
relationship” means to convey in general that there is evidence or argument to suggest a 
causal relationship. 
Serious Adverse Event (SAE): Any untoward medical occurrence (i.e. AE) that at any 
dose: 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 53 of 76 
• 
Results in death. 
• 
Is life-threatening. 
• 
Requires hospitalisation or prolongation of existing hospitalisation. 
• 
Results in persistent or significant disability/incapacity. 
• 
Is a congenital anomaly/birth defect. 
• 
Is otherwise considered to be medically significant. 
Comments: Life-threatening in the definition of an SAE or serious AE refers to an event in 
which the patient was at risk of death at the time of the event; it does not refer to an event 
which hypothetically might have caused death if it were more severe. 
Medical judgement should be exercised in deciding whether an AE or AR is otherwise 
considered to be medically significant. Important AEs or ARs that are not immediately life-
threatening or do not result in death or hospitalisation but may jeopardise the patient or may 
require intervention to prevent 1 of the other outcomes listed in the definition above should 
also be considered serious. 
Examples of such medically significant events are: 
• 
Intensive treatment in an emergency room or at home for allergic bronchospasm. 
• 
Blood dyscrasias or convulsions that do not result in hospitalisation. 
• 
Development of drug dependency or drug abuse. 
Unexpected Adverse Reaction: An AR, the nature or intensity of which is not consistent 
with the applicable product information (e.g. Investigator Brochure for an unauthorised IMP 
or SmPC for an authorised IMP). 
Comment: When the outcome of the AR is not consistent with the applicable product 
information this AR should be considered as unexpected. 
Suspected Unexpected Serious Adverse Reaction (SUSAR): An SAE considered to have 
a causal relationship with administration of the IMP, and the nature or intensity of which is 
not consistent with the applicable product information (e.g. Investigator brochure for an 
unauthorised IMP or SmPC for an authorised IMP). 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 54 of 76 
Intensity:  The term “severe” is often used to describe the intensity (severity) of a specific 
event.  This is not the same as “serious”, which is based on patient/event outcome or action 
criteria. 
 
13.1.2 
Observation Period for Adverse Event Reporting 
The observation period for an individual patient will start after giving informed consent and 
will finish at the last visit defining the end of the study for the given individual patient.  
Any SAEs occurring after Informed Consent must be reported. 
Any untoward medical events occurring after Informed Consent but prior to IMP 
administration should be recorded in the patient’s medical history and not reported as an AE. 
 
13.1.3 
Information to be Collected on Adverse Events 
Each AE will be recorded according to the criteria given below. “Relationship to IMP” must 
be determined by the Investigator (if medically qualified) or by a medically qualified Co-
Investigator. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 55 of 76 
Table 13-1 Table of Information to be Collected on Adverse Events 
Variable 
Category 
Definition 
AE reported 
term 
 
Any untoward medical occurrence in a patient 
administered an IMP and which does not 
necessarily have to have a causal relationship with 
this treatment. 
An AE can therefore be any unfavourable and 
unintended sign (including an abnormal laboratory 
finding, for example), symptom, or disease 
temporally associated with the use of a medicinal 
product, whether or not considered related to the 
IMP. 
Date AE 
started 
 
The date on which the AE started. 
Date of 
change in 
severity of AE 
 
The date on which the AE changed in severity. 
This date equates to the finish date of the old 
severity and the onset date of the new severity. 
Intensity 
 
Intensity will be determined by the Investigator. For 
symptomatic AEs the following definitions will be 
applied, but medical experience and judgement 
should also be used in the assessment of intensity. 
 
Mild 
The AE does not limit usual activities; the patient 
may experience slight discomfort. 
 
Moderate 
The AE results in some limitation of usual 
activities; the patient may experience significant 
discomfort. 
 
Severe 
The AE results in an inability to carry out usual 
activities; the patient may experience intolerable 
discomfort or pain. 
Actions taken 
None 
No action was taken in relation to this AE. 
 
IMP dose changed 
The dose of IMP was changed due to this AE, i.e. 
increase, decrease, or temporary discontinuation. 
 
IMP permanently 
discontinued 
The IMP was permanently discontinued due to this 
AE. 
 
Symptomatic therapy 
Symptomatic therapy was added or changed due 
to this AE. 
 
Patient hospitalised 
or hospitalisation 
prolonged 
The patient was hospitalised or hospitalisation was 
prolonged due to this AE. 
 
Other action (specify)
Other action was taken due to this AE, e.g. 
diagnostic tests, laboratories and procedures. 
Relationship 
to IMP 
Unassessable/ 
Unclassifiable 
Insufficient information to be able to make an 
assessment. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 56 of 76 
Variable 
Category 
Definition 
 
Conditional/ 
Unclassified 
Insufficient information to make an assessment at 
present (causality is conditional on additional 
information). 
 
Unrelated 
No possibility that the AE was caused by the IMP. 
 
Unlikely 
Slight, but remote, chance that the AE was caused 
by the IMP, but the balance of judgment is that it 
was most likely not due to the IMP. 
 
Possible 
Reasonable suspicion that the AE was caused by 
the IMP. 
 
Probable 
Most likely that the AE was caused by the IMP. 
 
Certain 
The AE was definitely caused by the IMP. 
Is the AE 
serious? 
Results in death 
Life-threatening 
Requires or prolongs 
hospitalisation  
Results in persistent 
or significant 
disability/incapacity  
Congenital 
anomaly/birth defect 
Otherwise 
considered to be 
medically significant 
See Section 13.1.1. 
Date resolved 
 
The date on which the AE ceased to be present.  
Outcome 
Not recovered/not 
resolved 
The AE still persists. 
 
Recovered/resolved 
The AE is resolved. 
 
Recovered/resolved 
with sequelae 
The patient is stabilised, but with sequelae from 
this AE. 
 
Recovering/resolving 
The patient is recovering from this AE/this AE is 
resolving. 
 
Fatal 
The patient died whilst this AE was ongoing or as a 
result of it. 
 
Unknown 
The outcome of this AE is not known. 
Has the 
patient ever 
experienced 
this AE 
before? 
Yes/No 
A query confirming whether the patient has a 
previous medical history of the AE at any time 
before entering into the study. If the patient has 
experienced this AE before, brief details should be 
given under additional information. 
Additional 
information 
 
Additional information regarding the AE. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 57 of 76 
 
13.1.4 
Procedure for Reporting Adverse Events 
All AEs that arise after the patient has had IMP administered will be recorded in the patient’s 
CRF. AEs can be reported spontaneously by the patient or in response to non-leading 
questioning or observation by the Investigator, or be a significant laboratory abnormality. 
The Investigator will ask the patient: “Are you experiencing any symptoms or complaints?” at 
the baseline visit and “Have you had any symptoms or complaints since the last visit?” 
during the study.  
Assessments of the relationship of AEs to IMP must be made by the Investigator (if 
medically qualified) or by a medically qualified Co-Investigator. 
 
13.1.5 
Procedure for Reporting Serious Adverse Events 
In the event of a Serious Adverse Event (SAE), the Investigator should telephone the Clinical 
Project Manager (CPM) within 24 hours of knowledge of the event. The name and contact 
number of the CPM will be provided to the Investigator in the study protocol and/or at the 
Study Initiation Visit. To allow timelines to be met the Investigator can report the event to the 
Global Vigilance Group (GVG) simultaneously by contacting GVG by email: 
. 
The CPM will also forward any SAE information/forms to the RB Global Vigilance Group 
within the same day using the email address: 
.  
Out of hours emergency contacts will be provided to the Investigator in the study protocol 
and/or at the Study Initiation Visit. If notification is via telephone the CPM will ensure that a 
SAE Form is completed but the Investigator will be requested to make a detailed written 
report by sending a follow-up SAE Form as soon as possible. The CPM will be responsible 
for reporting the event to the Global Vigilance Group (
). All the SAE forms will 
be provided to the CPM function via email, and a copy filed in the TMF. Any inconsistencies 
in the information received from the Investigator will be clarified using the Adverse Event 
Data Clarification Form.  
If the case does require reporting, a CIOMS (Council for International Organizations of 
Medical Sciences) form will be produced. A copy of this will be sent to the RB Drug Safety 
Officer (DSO) in China who will complete the SFDA SAE Form in Chinese and submit to the 
SFDA within 7 days for fatal or life-threatening events, or 15 days for all events. 
If the event requires expedited reporting (event classified as a SAE): 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 58 of 76 
1. The IEC/IRB, SFDA and PFDA will be notified by the Investigator within 24 hours of 
awareness 
2. All other investigators participating in the study will be informed by the CPM 
The Investigator will be instructed to retain a copy of all the SAE Forms in the Investigator 
Site File, and must inform his/her local ethics committee/institutional review board of all 
SAEs occurring in the study. 
The Investigator should not break the randomisation code except when it is necessary to do 
so in order to ensure the patient receives appropriate medical care (see Section 12.2). 
The overall procedure for reporting SAEs is illustrated in the flowchart below. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 59 of 76 
Figure 13-1 Procedure for Reporting SAEs 
 
 
13.1.6 
Reporting to Regulatory Authorities 
SAEs and non-serious AEs will be reported to the appropriate regulatory authorities by RB, 
in accordance with the authorities’ requirements. 
 
 
GVG database event  
SAE
 
Not SAE
Fatal or life 
threatening 
Not Fatal or life 
threatening 
Request to CPM for 
additional information if 
required
SAE Form signed 
copy filed in the 
TMF
No further action 
details kept on record. 
Listing of drug related 
SAEs to CA and EC as 
part of annual safety
report  
Expedited Reporting within 7 
days of knowledge of the event
 
and follow-up information 
within an additional 8 days 
Expedited Reporting within 15 
days of knowledge of the event
Investigator informs EC, SFDA, PFDA, CPM
& GVG  within 24 hours 
Additional/follow up 
information 
AE Identified 
Investigator records 
AE in patient CRF 
Is the event serious? 
No  
Final AE listings 
to 
 
 
GVG
Yes 
 
SAE form filed in Site File 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 60 of 76 
13.1.7 
Follow-up of Patients Experiencing Adverse Events upon 
Completion of the Study or Withdrawal from the Study 
All SAEs, and all AEs that cause premature withdrawal of the patient from the study, that 
have not resolved by the end of the study will be followed up by the Investigator until 
resolution or until the Investigator believes there will be no further change. This may involve 
the patient making additional visits to the site. 
All other AEs will be followed up where possible to resolution or until the Investigator 
believes there will be no further change, whichever is the earlier.  
The minimum data required are the final outcome and date, which may be obtained by the 
Investigator in a documented telephone conversation with the patient or patient’s medical 
practitioner. 
 
13.1.8 
Procedures for Patients Experiencing Onset of Adverse Events 
after End of the Study 
As the active study drug in this study is not absorbed, a serious adverse event that occurs 
within a day of the final dose of study medication should be reported and followed to 
resolution or until the Investigator believes there will be no further change. 
 
13.2 
Overdose 
Overdoses are reportable to RB irrespective of the presence of an associated AE/SAE. The 
overdose and any associated AE/SAE will be captured on an AE CRF page/SAE form. 
 
13.3 
Pregnancy 
If a patient is found to be pregnant after being dosed with IMP: 
• 
Promptly notify RB (i.e. Clinical Project Manager) or CRO monitor (if CRO is 
Investigator’s first port of call for reporting SAEs).  
• 
Withdraw the patient from the study. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 61 of 76 
• 
Perform study completion assessments. 
• 
Collect details of due date, etc.  
Pregnancy follow-up will be conducted by RB GVG personnel as part of their drug safety 
monitoring responsibilities and will not form part of the study dataset.  
Pregnancy should be reported to RB as AE. 
 
13.4 
Clinical Laboratory Investigations 
All blood samples will be collected and prepared according to the standard procedures of the 
hospital laboratory conducting the analyses at each of the study sites. Laboratory safety 
parameters will be analysed using standard validated methods. 
The following investigations will be made: 
Haematology 
• 
Haemoglobin 
• 
Red blood cells 
• 
Mean cell haemoglobin concentration 
• 
White blood cells 
• 
Platelet count 
 
Biochemistry 
• 
Electrolytes: sodium, potassium, calcium 
• 
Urea 
• 
Creatinine 
• 
Uric acid 
• 
Glucose 
• 
Inorganic phosphorous 
• 
Alanine transaminase 
• 
Aspartate transaminase 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 62 of 76 
 
Pregnancy testing  
• 
Women of child-bearing potential will undergo urine pregnancy testing (positive or 
negative). 
The total volume of blood expected to be sampled for clinical laboratory safety investigations 
from an individual patient in the course of the study is not expected to exceed 30 ml. 
 
13.4.1 
Collection of Laboratory Samples 
Blood samples will be collected and labelled in tubes provided by the local laboratory.  
Urine samples will be collected mid-stream. 
 
13.4.2 
Labelling of Laboratory Samples 
The site’s standard labels will be used. 
 
13.4.3 
Reference Ranges 
Up-to-date reference ranges for the above investigations must be obtained for each site 
performing analyses prior to the start of the study and be updated as appropriate during the 
course of the study. 
 
13.4.4 
Laboratory Results Review 
The Investigator will review the results and comment, on the laboratory results sheet, upon 
all abnormal values, identifying those that are clinically significantly abnormal. The 
Investigator will sign and date the laboratory results sheet, to indicate that the review has 
taken place. 
A copy of these results will be provided to the 
 monitor. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 63 of 76 
13.4.5 
Good Clinical Laboratory Practice (GCLP) Compliance 
Confirmation of compliance with GCLP will be required from the laboratories involved prior to 
the start of the study. 
The laboratories will be requested to provide documented evidence of GCLP compliance. 
This may be a statement of compliance issued by the appropriate national authority, or 
details of accreditation by a recognised organisation. 
An independent inspection of the laboratories by 
 or RB may be conducted. 
 
13.5 
Vital Signs, Physical Findings and other Observations Related to 
Safety 
Vital signs and physical examinations will be conducted at baseline and final or early 
termination visits. A 12-lead ECG and endoscopy will be conducted and the results will be 
reviewed by the investigator at baseline as part of the screening procedures. Patients will be 
asked about adverse events at follow-up visits. 
 
14 
STATISTICAL CONSIDERATIONS 
The statistical analysis will be undertaken in collaboration with Quintiles. 
A detailed Statistical Analysis Plan will be finalised before the database is locked and prior to 
analysis of the study being carried out.  
Any deviations from the analyses described below will be included in the Statistical Analysis 
Plan, which will form Appendix 16.1.9 of the clinical study report. 
 
14.1 
Sample Size Justification 
No statistical justification for the sample size in this study was performed because the 
variance of the response is not known for Compound Sodium Alginate Double Action 
Chewable Tablets. 
The number of patients enrolled for this study has been derived from experience of previous 
pH monitoring studies conducted with other Gaviscon® formulations.. It is anticipated that 36 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 64 of 76 
evaluable patients will be required to complete the study. In order to achieve this, 44 patients 
will be enrolled in this study. 
 
14.2 
Data to be Analysed 
Definition of the analysis populations: 
• 
Full Analysis Set (FAS): All patients enrolled in the study; 
• 
Safety (Safety) population: All patients who are subjected to any invasive procedures 
and/or  take at least one dose of study medication;  
• 
Intention to treat (ITT) population: All patients who take at least one dose of study 
medication and have evaluable pH monitoring data for at least 1 hour post-dosing;  
• 
Per protocol (PP) population: The criteria for inclusion in the PP population will be 
confirmed during data checking, but will at least include the following: patients who 
adhered to the inclusive/exclusive criteria; did not take any prohibited medication 
which would interfere with evaluation of drugs in the study period; attended visits 
within the specified visit windows and had complete pH monitoring data for 4 hour 
post-dosing for both pH monitoring visits. 
The ITT population and safety population are the primary populations for evaluation of 
efficacy and safety, respectively. The PP population will be used for a secondary evaluation 
of the primary endpoint only. 
 
14.3 
Patient Disposition and Characteristics 
Descriptive summary statistics will be provided for demographic characteristics and baseline 
data for each treatment sequence group and all patients. For continuous parameters, mean, 
standard deviation, median, minimum, and maximum will be provided. For categorical 
parameters, the cell frequencies and percentage of patients in each category will be 
provided. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 65 of 76 
14.4 
Efficacy Analyses 
Results will be summarised by treatment for each dosing visit and overall (Compound 
Sodium Alginate Double Action Chewable Tablets, matching placebo tablets) using n, mean, 
standard deviation, median, minimum and maximum values. 
If less than 2 hours post-dosing monitoring data is available, for whatever reason, (or less 
than 1 hour post-dosing data within the first hour for parameters based on the first hour post-
dosing) the derived parameters will be considered missing.  If 2 or more hours post-dosing 
monitoring data is available, the parameters will be derived using the data available, and will 
be adjusted, where necessary, by multiplying by the factor (4 hours / time with data 
available).  Any data recorded more than 4 hours post-dosing will be ignored when deriving 
these parameters. 
 
14.4.1 
Primary Efficacy Analysis Endpoint 
The primary efficacy parameter will be the percentage of time during the 4 hour post dosing 
period with pH below pH 4. 
14.4.2 
Secondary Efficacy Endpoints 
The secondary endpoints will be: 
• 
Percentage of time during the 4 hour post dosing period with pH below pH 5 
• 
Number of occasions during the 4 hour post dosing period when pH falls below pH 4 
• 
Number of occasions during the 4 hour post dosing period when pH falls below pH 5 
• 
Number of reflux episodes during the 4 hour post dosing period with pH below pH 4 
for at least 5 minutes 
• 
Percentage of time during the first hour post dosing with pH below pH 4 
• 
Percentage of time during the first hour post dosing with pH below pH 5 
• 
Number of occasions during the first hour post dosing when pH falls below pH 4 
• 
Number of occasions during the first hour post dosing when pH falls below pH 5 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 66 of 76 
• 
The longest reflux time during the 4 hour post dosing period (i.e. the longest period 
with pH below pH 4)  
• 
The DeMeester scores during the 4 hour post dosing period. 
 
14.4.3 
Statistical Methods for Efficacy Analyses 
SAS 9.1 (or later) will be used for statistical analysis. 
All statistical tests will be conducted using two-tailed tests at the 5% significance level. 
The null hypothesis at all times will be the equality of the fixed effect being compared from 
the model. 
The primary endpoint will be analysed primarily using an ANOVA of variance model with 
treatment, dosing visit treatment sequence as fixed effects and patient nested within 
treatment sequence as a random effect. The difference between treatment least square 
means will be used to represent the treatment differences. The effects for dosing visit and 
treatment sequence will also be assessed. A residual analysis will be performed. If there is a 
major departure from the assumptions of normality, independence or heteroscedasticity of 
residuals, then further analysis using transformed data will be used to support the original 
model results. If such assumptions still do not hold following an appropriate transformation 
then Wilcoxon Rank-Sum test will be used to compare the dosing visit difference (dosing 
visit 1 – dosing visit 2) between treatment sequence groups to represent the treatment 
comparison. 
All secondary endpoints will be analysed identically to the primary endpoint. 
All secondary endpoints and sensitivity or alternate analyses for the primary endpoint will 
serve as supportive evidence for the primary analysis only and therefore no adjustment for 
multiple comparisons will be made. 
14.5 
Safety Analyses 
Withdrawals will be listed in the Clinical Study Report (CSR) Appendices and summarised by 
reason for withdrawal. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 67 of 76 
Adverse events will be listed on a patient by patient basis in the CSR Appendices. The 
number of adverse events will be summarised by body system and preferred term, 
relationship to study medication and severity. The number of patients experiencing adverse 
events will also be summarised in the same manner. 
14.5.1 
Adverse Events 
All AEs will be coded using the most up-to-date version of MedDRA. For an individual 
patient, AEs that began prior to the first dose of IMP or more than one day after the final 
dose of IMP will not be included in the analysis.  
The incidence of AEs (number and percent of patients reporting each type of AE at least 
once during the study) will be summarised for all AEs, by investigator attribution of 
relationship to IMP and by severity. The incidence of AEs will be compared among 
(between) treatment groups using McNemar’s Test for all AEs, for those AEs classified by 
the Investigator as possibly, probably or certainly related to IMP and for severe AEs. 
 
14.5.2 
Laboratory Data 
For the purpose of analysing laboratory data, “baseline” is defined as the baseline 
assessments at Visit 1, screening and “last visit” is defined as the final visit, Visit 3 or the 
Early Termination Visit. 
Each pre-study baseline laboratory value will be categorised as low, normal, or high based 
on the reference range. Each post-baseline value will be classified in a similar manner, 
producing a 3 x 3 table for each treatment group at each post-baseline visit. Scores of “1” 
will be assigned to low values, “2” to normal values, and “3” to high values. Using these 
scores, shifts from baseline will also be assigned a score. For example, a laboratory value 
that shifts from low to high will be assigned a score of 2, whilst a laboratory value that 
remains at a low value will be assigned a score of 0. Shifts between these categories 
between baseline and subsequent timepoints will be compared using the Wilcoxon Signed-
Rank test within each treatment group. Statistical testing will be performed at last visit. 
At each visit, summary statistics for the absolute laboratory value and the changes from 
baseline will be presented by treatment group. The significance of changes from baseline 
will be assessed using the Wilcoxon Signed-Rank Test.  
Scatter plots of end of treatment values versus baseline values will be provided for all 
laboratory tests. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 68 of 76 
14.5.3 
Vital Signs 
At each visit, summary statistics for the absolute vital sign value and the changes from 
baseline will be presented by treatment group. The significance of changes from baseline 
will be assessed at the last visit, using the Wilcoxon Signed-Rank Test.  
 
14.5.4 
Other Variables Related to Safety 
No further variables related to safety will be analysed. 
 
14.6 
Interim Analyses 
No interim analysis is planned for this study. 
 
15 
QUALITY CONTROL AND QUALITY ASSURANCE AUDIT 
15.1 
Monitoring 
The study will be monitored by site visits and meetings with the Investigator and co-
workers(s) at intervals agreed with the Investigator. The anticipated monitoring frequency will 
be stated in the Monitoring Plan. Monitoring will also involve, as appropriate, 
correspondence and telephone contacts. 
The Investigator, or a designated member of the Investigator’s staff, must be available at 
some time during the monitoring visit to review the data and resolve any queries and to allow 
direct access to the patient’s records for source data verification. 
At a site visit the CRFs forms should be made available in order that the accuracy of their 
completion may be checked. Each completed set of CRFs for each visit must be signed and 
dated by the Investigator, or a designated member of the Investigator’s medical staff, to 
verify the data and statements submitted. Similarly all alterations must be initialled and dated 
by the Investigator or a designated person, explained as necessary, with the original mistake 
left legible. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 69 of 76 
15.2 
Source Document Verification 
On-site monitoring will also include source document verification (SDV). SDV is the 
procedure whereby the data contained in the CRFs are compared with the primary source 
data (e.g. patient notes, original recordings from automated instruments, X-ray films, ECG 
tracings, laboratory results) contained in the patient records held at the investigational site, 
and thereby verified as accurate. 
The Investigator must be aware that: 
• 
SDV is a part of the normal monitoring process. It will be carried out by designated study 
personnel and will be done in such a way as to preserve patient confidentiality, taking 
into account all ethical and legislative requirements. 
• 
SDV will be carried out by direct comparison of entries made in the CRF with appropriate 
source data. Direct access to source data requires that the patient gives written, 
documented consent to this.  
• 
Where source data are in the form of a computer print-out (e.g. medical records, ECG 
tracings) they will be made available by the Investigator to the monitor. Each will be 
signed and dated by the Investigator or a designated person, confirming that the print-out 
is a true and faithful record of the data for that patient. These print-outs will be filed in the 
CRF. 
• 
The 
 Clinical Project Manager/Study Monitor will write an SDV Plan, specifying 
which data require SDV and what constitutes source data. This plan will also include the 
identification of any data to be recorded directly on the CRF and therefore considered 
source data. The Plan will be agreed with the Investigator and documented in the 
Initiation Visit Report.  For all patients, patient identity (date of birth, sex, initials and 
patient number), record of entry into the study and signature of informed must be verified 
from source documents as a minimum. In addition the following will be verified (add as 
appropriate): 
• 
pH monitoring data 
• 
Diagnosis of the condition under investigation and eligibility criteria 
• 
Laboratory reports  
• 
Details of adverse events 
• 
Concomitant medications 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 70 of 76 
o Details of SAEs. 
 
It is important that the patient’s notes record important details about their participation in the 
study. The Investigator or designated person will agree, as a minimum requirement, to 
record the following information in the patient’s notes: 
• 
Study number, brief description or title of study. 
• 
Date that the patient gave written consent. 
• 
All visit dates. 
• 
All SAEs. 
• 
All concomitant medications. 
 
15.3 
Audit 
In accordance with the standards defined in ICH GCP, clinical studies sponsored by RB may 
be subject to an independent audit at the study site which will be conducted by personnel 
from an appropriate Quality Assurance Unit. Full consultation with the Investigator will be 
made prior to and during such audit, which will be conducted according to Quality Assurance 
Unit Standard Operating Procedures. 
 
15.4 
RB Policy on Fraud in Clinical Studies 
In accordance with GCP, it is RB’s policy always to follow up suspected cases of fraud. 
 
16 
ETHICS 
16.1 
Independent Ethics Committee/Institutional Review Board Review 
Written approval of the study by an independent and appropriately constituted IEC/IRB must 
be obtained and a copy provided to RB before any protocol-related procedures that do not 
form part of the patient’s normal clinical treatment are performed. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 71 of 76 
The approval letter must contain: 
• 
Name and address of the IEC/IRB. 
• 
Date of meeting. 
• 
Sufficient information to identify the version of both the protocol and patient 
information/informed consent. 
• 
Sufficient information to identify the version of other documents reviewed. 
The investigator must also provide RB with a list of IEC/IRB members that includes each 
member’s name, sex, and institutional affiliation. 
The Investigator must submit all protocol amendments to the IEC/IRB for approval and notify 
them of any administrative changes. 
 
16.2 
Patient Information and Consent 
Prior to entering the study, the Investigator or designated assistant will explain to each 
patient or legally acceptable representative, the nature of the study, its purpose, procedures, 
expected duration, alternative therapy available, and the benefits and risks involved in study 
participation. Patients will be given information and consent documents and the opportunity 
to ask questions. They will be informed of their right to withdraw from the study at any time 
without prejudice. After this explanation and before any study-specific procedures have been 
performed, the patient, or legally acceptable representative, will voluntarily sign and date the 
informed consent form. The person conducting the informed consent discussion and 
providing the information to the patient will also sign and date the consent form. Prior to 
participation in the study, the patient will receive copies of the written information and their 
signed and dated consent document, plus any other written information provided to them. 
 
16.3 
Informing General Practitioners 
Not applicable. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 72 of 76 
17 
REGULATORY REQUIREMENTS 
17.1 
Competent Authority Authorisation 
This study proposal was submitted to the SFDA and approved on 4 June 2010.   The 
approval number is 2010L02452. 
 
17.2 
Curriculum Vitae 
A current curriculum vitae (CV) will be obtained from all personnel with significant study 
responsibilities, i.e. the Investigator and those to whom he or she has delegated some of 
his/her responsibilities as well as those whose names appear on the signature and 
delegation of duties forms (see below).  
The CV will contain as a minimum the following information: name, current work address, 
qualifications, current position and previous positions. It will be signed and dated within 2 
years of the start of the study. The CVs will be maintained on file by RB. 
The Investigator and individuals to whom the Investigator has delegated some of his or her 
responsibilities as an investigator will be asked to provide sample signatures. The duties 
delegated to them will also be recorded on the signature and delegation of duties forms. 
 
18 
DATA HANDLING AND RECORD KEEPING 
18.1 
Case Report Forms (CRFs) 
Electronic CRFs (eCRFs) will not be used in this study. The Investigator is responsible for 
the quality of the data recorded in the CRF. The data recorded should be a complete and 
accurate account of the patient’s record collected during the study. The Investigator and 
study monitor will identify any data that will be recorded directly on the CRF such that the 
CRF will be considered the source document (i.e. no prior written or electronic record of the 
data). The study monitor will document this on the Initiation Visit Report. 
The Investigator and other staff who have been delegated responsibility for entering data 
into the CRF at each visit will be trained in the use of the paper/No carbon required (NCR) 
CRFs before the first patient at that site is enrolled. The Investigator must review all entries 
for completeness and correctness. When changes or corrections are made on any 
paper/NCR CRF, the Investigator or authorised persons must draw a single line through the 
error then initial and date the correction, as well as stating the reason for the error, except 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 73 of 76 
when due to a transcription error. The original entry should not be obscured. Data 
management will be conducted by Quintiles. The paper CRF / NCR CRF system will keep an 
audit trail of all changes made after the CRF pages are initially completed and submitted. 
The Investigator agrees to complete and sign the CRFs in a timely fashion after completion 
of each patient and make them available to the study monitor for full inspection. In addition, 
any data queries prepared after the original CRF has been completed should be answered 
promptly. Following monitoring of each patient’s paper CRF / NCR CRF, the investigator will 
sign the CRF. Re-signature by the Investigator may be required prior to database lock after 
resolution of interim data queries. 
Before acceptance, the study monitor will review the CRFs for completeness and adherence 
to the protocol. If a paper CRF is being used, the top copy will be submitted to the 
organisation responsible for data management and a second copy will be retained by the 
Investigator in the Study Site File.  
 
18.2 
Retention of Essential Documentation 
The Investigator should retain all essential documents (as defined in ICH E6 or according to 
other national and international regulations) until at least 5 years after the completion of the 
study. These documents should be retained for a longer period, however, if required by the 
applicable regulatory requirements or by an agreement with RB. It is the responsibility of RB 
to inform the Investigator when these documents no longer need to be retained. 
Patient files and other source data must be kept for the maximum period of time permitted by 
the hospital, institution or private practice. The Investigator must notify RB if his/her 
institution’s policy is to retain documents for a shorter period of time. 
 
18.3 
Protocol Amendments 
The investigator must abide by the agreed protocol as approved by the IEC/IRB. 
No change will be made to the agreed protocol without the prior written approval of the 
Investigator, the Clinical Project Manager, the R&D Manager Clinical (Healthcare) and the 
Global Medical Director, except in circumstances where the immediate safety of the patient 
is at risk. Written approval will also be obtained from other functions if appropriate, for 
example the Statistician if the amendment relates to a change in endpoints. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 74 of 76 
All substantial protocol amendments require IEC/IRB and regulatory approval. Protocol 
amendments will be submitted to the same IEC/IRB and regulatory authority as the study 
protocol. 
 
19 
CLINICAL TRIAL AGREEMENT 
Before the study commences, a Clinical Trial Agreement be will signed in which financial 
aspects of the study (including financial disclosure) as well as responsibilities and obligations 
are described. This will take the form of: 
• 
A contract between 
 and the Investigator/healthcare organisation. 
 
20 
COMPENSATION, INDEMNITY AND INSURANCE 
20.1 
Compensation 
Appropriate treatment and/or compensation will only be provided and/or paid to the patient 
by the Sponsor to the extent that a patient suffers injury or death directly attributable to 
participation in the study without: 
• 
Fault on the part of the investigator or the CRO or its employees or agents. 
• 
The investigator or the CRO failing to comply with the protocol. 
• 
The investigator or the CRO failing to notify the Sponsor of the claim or denying the 
Sponsor full conduct of the claim.  
In any event, such compensation and treatment shall only be provided by the Sponsor to the 
extent required by the applicable law. 
 
20.2 
Indemnity 
RB will provide appropriate indemnity for the Investigator and staff who conduct part or all of 
this study, upon request. The request must be received before the first patient is recruited. 
 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 75 of 76 
20.3 
Insurance 
If required, and in accordance with applicable regulatory and legal requirements, RB will take 
out appropriate insurance policies on behalf of the Investigator and staff who conduct part or 
all of this study, and/or on behalf of the patients participating in the study. 
 
21 
REPORTING, PUBLICATION AND PRESENTATION 
A clinical study report will be prepared according to ICH E3 (Structure and Content of 
Clinical Study Reports) as part of RB’s commitment to Good Clinical Practice. The report will 
be a record of the total study conduct and findings, and will be subject to approval by the Co-
ordinating Investigator who will sign the final report. 
The study data will be owned by RB. RB retains the right to publish the data independently 
of the Investigator. RB agrees that before it publishes the results, it will provide the 
Investigator with at least 30 days for full review prior to submission of the manuscript to the 
publisher. The Investigator must submit any proposed manuscript to RB for approval prior to 
submission for publication. 
Any publication must state that it is a part of a multicentre study. Where it would be 
impractical to send the manuscript to every Investigator in a multicentre study, a copy will be 
sent to the Co-ordinating Investigator. In such a study, RB may wish to publish the results of 
the study and this may be done without all participants having the opportunity to review the 
manuscript. 
 
22 
REFERENCES 
1. Vakil N, Veldhuyzen van Zanten S, Kahrilas P, Dent J, Jones R. The Montreal definition 
and classification of gastro-esophageal reflux disease (GERD)- a global evidence-based 
concensus. Am J Gastrolenterol 2006, 101: 1900-1920.  
2. Armstrong D. Systematic review: persistence and severity in gastroesophageal reflux 
disease. Aliment Pharmacol Ther 2008, 28: 841-853. 
3. Liker H, Hungin AP, Wiklund I. Management of reflux disease in primary care: the 
subject perspective. J Am Boar Fam Pract 2005, 18: 393-400. 
4. Wahqvist P, Reilly M, Barkun AN. Systematic review: the impact of gastro-oesophageal 
reflux disease on work productivity. Aliment Pharmacol Ther 2006, 24: 259-272. 


Investigational Study Protocol Template 
Study No: GA1202 
 
SOP D0365585, Version 4.0 
Protocol Version: Final version 2.0, 01 Mar 
2013 
 
 
Study Sponsor: Reckitt Benckiser Healthcare (UK) Ltd, Dansom Lane, HU8 7DS; Telephone No: +44 (0) 1482 
326151; Fax No: +44 (0) 1482 582172 
Template vs_4.0, 23-Jan-2013                             Page 76 of 76 
5. Dent J, El-Serag HB, Wallander MA, Johansson S. Epidemiology of gastro-oesophageal 
reflux disease: a systematic review. Gut 2005, 54: 710-717. 
6. Kahrilas PJ, Howden CW, Hughes, N. Response of Regurgitation to Proton Pump 
Inhibitor Therapy in Clinical Trials of Gastroesophageal Reflux Disease. Am J 
Gastroenterol 2011, 106:1419–1425. 
7. Moayyedi P, Delaney BC, Vakil N, Forman D, Talley NJ. The efficary of proton pump 
inhibitors in nonulcer dyspepsia: A systematic review and economic analysis. 
Gastroenterology 2004, 127: 1329-1337. 
8. Fass R, Tougas G. Functional heartburn: The stimulus, the pain, and the brain. Gut 
2002, 51: 885-892. 
9. GA0916 data on file 
 
23 
APPENDICES 
There are no appendices. 
 
 


:,, 
Reckitt 
Benckiser 
Non Substantial Amendment Form 
SOP D0365585, Version 4.0, Page 1 of 5 
Reckitt Benckiser 
PROTOCOL NON SUBSTANTIAL AMENDMENT NUMBER [ 11 
PRINCIPAL INVESTIGATOR: 
 
 
 
 
 
 
China 
DETAILS OF PROTOCOL AMENDMENT: 
1. Section(s) to be Changed: 
Section 5.1, Table 5.1 - Reckitt Benckiser Details, page 18 
From: 
Name 
Position 
Address and Contact Number 
Clinical Project Manager 
Reckitt 
Benckiser 
Healthcare 
(UK) Ltd, Dansom Lane, Hull, 
HUB 70S. UK. 
Global Medical Director 
Reckitt 
Benckiser 
Healthcare 
(UK) Ltd, Dansom Lane, Hull, 
HUB 7DS. UK. 
Senior Statistician 
Reckitt 
Benckiser 
Healthcare 
(UK) Ltd, Dansom Lane, Hull, 
Study No~ GA1202 
, 
Protocol Final Version: FINAL (version 2•1noorporating amendment 4) 
Template vs_ 4.0, 23-Jan-2013 
Reckitt Benckiser Confidential 
08044044 


,
=" Reckitt 
Non Substantial Amendment Form 
Benckiser 
SOP D0365585, Version 4.0, Page 2 of 5 
ttUt.ftt • lt'tt:ittH( • ttOMC 
Revised Paragraphs: 
Name 
Reason for Change: 
Position 
Clinical Project Manager 
Reckitt Benckiser Medical 
Officer 
Statistical Manager 
Address and Contact Number 
Reckitt Benckiser Healthcare 
(UK) Ltd, Dansom Lane, Hull, 
~ e  
No: 
Reckitt Benckiser Healthcare 
(UK) Ltd, Dansom Lane Hull 
HUB 7D8. 
Reckitt Benckiser Healthcare 
(UK) Ltd, Dansom Lane, Hull 
HU87DS. Tel 
Change of the person responsible at the Sponsor Company for medical cover of the 
study. 
2. Section(s) to be Changed: 
pH Monitoring table footnote in Section 3.10, page 8 and Section 11.2, page 34 
From: 
Revised Paragraphs: 
Addition of the following words "The timings in this table are for guidance only. For 
full details see GA 1202 pH Monitoring Guidelines" as a footnote to the pH monitoring 
table. 
Reason for Change: 
Clarification that the timings for pH monitoring procedures are only used for 
guidance. The pH monitoring guidelines provide full details of the methods. 
·" • ··Study No:-GA1'202-
Protocol Final Version: FINAL (version 2 lncorporallng'Smendment-4) 
Template vs_ 4.0, 23-Jan-2013 
Reckitt Benckiser Confidential 
08044044 


:,, 
Reckitt 
Benckiser 
HtAf..TH • tffV,1ftf[ • t!Of.tt: 
Non Substantial Amendment Form 
SOP D03655B5, Version 4.0, Page 3 of 5 
3. Section(s) to be Changed: 
Section 12.2, Identity of Non-lnvestigational Medicinal Products, page 45 
From: 
Compound Sodium Alginate Double Action Chewable Tablets will be manufactured 
to Good Manufacturing Practice (GMP) by Reckitt Benckiser Healthcare (UK) 
Limited, Dansom Lane, Hull, HUB 7DS, UK (Product Licence 00063/0157). 
The active treatment will be shipped to 
 
, where the 
Compound Sodium Alginate Double Action Chewable Tablets will be blister packed. 
The blister packs will be shipped to the lnvestigational Material Supplies Unit (IMSU), 
Reckitt Benckiser Healthcare UK Ltd, Dansom Lane, Hull, HUB 7DS UK. 
Revised Paragraphs: 
Compound Sodium Alginate Double Action Chewable Tablets will be manufactured 
and blister packed to Good Manufacturing Practice (GMP) by Reckitt Benckiser 
Healthcare (UK) Limited, Dansom Lane, Hull, HUB 7DS, UK (Product Licence 
00063/0157). 
The blister packs will be shipped to the lnvestigational Material Supplies Unit (IMSU), 
Reckitt Benckiser Healthcare UK Ltd, Dansom Lane, Hull, HUB 7OS UK. 
Reason for Change: 
The NIMP was to be manufactured at 
 but this was 
switched to Reckitt Benckiser Healthcare (UK) Ltd to utilise standard Gaviscon blister 
packs. 
Study No: GA 1202··' ., 
Protocol Final Version:·FINAL ·(versioo 2 incorporating amendment 1)· • ·' 
Template vs_4.0, 23-Jan-2013 
D8044044 
Reckitt Benckiser Confidential 


CTA(China) 
Number: 
Trial Number: 
f 
Reckitt 
Benckiser 
2010L02452 
GA1202 
Non Substantial Amendment Form 
SOP D0365585, Version 4.0, Page 4 of 5 
Protocol Title: 
A multi-centred, randomised, open label, placebo-controlled, two-
period crossover study to evaluate 4-hour esophageal pH change in 
GERO patients after administration of Compound Sodium Alginate 
Double Action Chewable Tablets or matching placebo tablets 
Protocol 
Amendment Date: 
4 Jun 2013 
Version: 
Phase: 
Final Version 2, Amendment 1 
Ill 
Reviewed and Agreed by: 
Clinical Project Manager 
Reckitt Benckiser 
Healthcare (UK) Limited 
Reviewed and Approved by: 
R&D Senior Manager (Health), Clinical: 
Reckitt Benckiser Medical Officer: 
Reckitt Benckiser Healthcare 
(UK) Limited 
',, Study'No: GA1202 ,_,,.. 
Protocol·Final Version: FINAL (version·21noorporating'amendmenMt 
Template vs_ 4.0, 23-Jan-2013 
Reckitt Benckiser Confidential 
D8044044 


l ,, 
Reckitt 
Benckiser 
HULTII • HVGlfNr • HOU£ 
Reviewed and Accepted by: 
• 
• 
• 
I -: 
I • 
• 
I 
I 
• 
I 
:. 
• -: 
• 
 
 
 
 
 
 
 
 
China 
Non Substantial Amendment Form 
SOP D0365585, Version 4.0, Page 5 of 5 
Protocol Final Version: FINAL (version 2 incorporatfng·amendment,1) 
Template vs_ 4.0, 23-Jan-2013 
D8044044 
Reckitt Benckiser Confidential 

SAP_001.pdf: 
Study Title: A Multi-centred, Randomised, Open Label, Placebo-controlled, Two-period 
Crossover Study to Evaluate 4-hour Esophageal pH Change in GERD Patients After 
Administration of Compound Sodium Alginate Double Action Tablets or Placebo Tablets 
 
ClinicalTrials.gov ID: NCT01872897 
 
 
 
Final Statistical Analysis Plan, dated 25-Feb-2014 
 
Changes to Planned Statistical Analyses Form, dated 19-Mar-2014 
 
Changes to Planned Statistical Analyses Form, dated 08-May-2014 
 
Changes to Planned Statistical Analyses Form, dated 17-Jul-2014 


 
Document: 
Reckitt Benckiser GA1202 Statistical Analysis Plan
Author: 
 
Version Number: 
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Version Date: 
[25Feb2014] 
Template No:  CS_TP_BS016 – Revision 3 
Effective Date: 01May2012 
                  Reference:  CS_WI_BS005 
                                        Page 1 of 29 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
GA1202 
A MULTI-CENTRED, RANDOMISED, OPEN LABEL, PLACEBO-CONTROLLED, TWO-
PERIOD CROSSOVER STUDY TO EVALUATE 4-HOUR ESOPHAGEAL PH CHANGE IN 
GERD PATIENTS AFTER ADMINISTRATION OF COMPOUND SODIUM ALGINATE 
DOUBLE ACTION CHEWABLE TABLETS OR MATCHING PLACEBO TABLETS 
 
 
 
 
 
AUTHOR: 
 
VERSION NUMBER AND DATE: V5.1(FINAL), 25FEB2014 
 
 
 


~~eckltt 
Q QUINTILES. 
Benckiser 
ST ATISTICAl ANAl YSIS PLAN: PROTOCOL GA1202 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
Statistical Analysis Plan Final VS.l (Date 25Feb2014) for Protocol «GA1202 >> Dated 01Mar2013 
Author: 
Position: 
• 
Company: 
Name -
Manager, Biostatistics 
Quintiles 
Upon review of this document, the undersigned approves this version of the Statistical Analysis Plan, authorizing 
that the content is acceptable for the reporting of this study. 
Name 
Approved By: -
Position: 
Statistical Manager 
Company: 
Reckitt Benckiser Brands Limited 
Document: 
Reckitt Benckiser GA 1202 Statistical Analysis Plan 
Author: 
Template No: CS_TP _8S016- Revision 3 
Effective Date: 01May2012 
Version Number: 
Version Date: 
Final 5.1 
[25Feb2014J 
Rererence: CS_WI_BSOOS 
Page 2 or 29 


 
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Version Number: 
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Effective Date: 01May2012 
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                                        Page 3 of 29 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
MODIFICATION HISTORY 
 
Unique 
Identifier 
for 
this 
Version 
Date of the 
Document 
Version 
Author 
Significant 
Changes 
from  
Previous Authorized Version 
0.1 
16Apr2013 
Not Applicable – First Version 
0.2 
30Jul2013 
Update per internal comments 
0.3 
16Aug2013 
Update per internal comments 
0.4 
19Aug2013 
Update per internal comments 
0.5 
20Aug2013 
Update per internal comments 
1.0 
20Aug2013 
Update to draft version 1.0 and sent to 
sponsor for review 
1.1 
02SEP2013 
Update per sponsor’s comment 
1.2 
06Sep2013 
Update per internal review comment 
2.0 
06Sep2013 
Update to draft version 2.0 and sent to 
sponsor for review 
3.0 
21Oct2013 
Update per sponsor’s comment 
3.1 
23Oct2013 
Update per sponsor’s comment 
4.0 
25Oct2013 
Update to final version 4.0 
5.0 
10Jan2014 
Update 
to 
present 
the 
concomitant 
medication by ATC level.  
5.1 
25Feb2014 
Update FAS definition 
Change listings (16.2.3.1-16.2.3.8) to be 
presented on FAS instead of all patients.  
Updated list of tables and listings per 
sponsor’s comments. 
 
 
 


 
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STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE 
Adverse event 
ANOVA 
Analysis of Variance 
ATC 
Anatomical Therapeutic Chemical 
BLQ 
Below the lower limit of quantification 
CI 
Confidence Interval 
CRF 
Case report form 
FAS 
Full analysis set 
GERD 
Gastro-esophageal reflux disease 
IMP 
Investigational medicinal product 
ITT 
Intention-to-Treat  
MedDRA 
Medical Dictionary for Regulatory Activities 
NIMP 
Non-investigational medicinal product 
PP 
Per protocol 
PT 
Preferred term 
SAE 
Serious adverse event 
SOC 
System organ class 
SAP 
Statistical analysis plan 
SI 
International System 
ULQ 
Upper limit of quantification 
WHO 
World Health Organization 


 
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STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
TABLE OF CONTENTS 
1. 
INTRODUCTION ............................................................................................................................ 8 
2. 
STUDY OBJECTIVES ..................................................................................................................... 8 
2.1. 
Primary Objective..................................................................................................................................... 8 
2.2. 
Secondary Objectives ............................................................................................................................... 8 
3. 
STUDY DESIGN .............................................................................................................................. 9 
3.1. 
General Description .................................................................................................................................. 9 
3.2. 
Schedule of Events ................................................................................................................................... 9 
4. 
FINAL ANALYSIS ........................................................................................................................... 9 
5. 
ANALYSIS SETS .............................................................................................................................. 9 
5.1. 
Full Analysis Set [FAS]............................................................................................................................... 9 
5.2. 
Safety Population ................................................................................................................................... 10 
5.3. 
Intent-to-treat [ITT] Population .............................................................................................................. 10 
5.4. 
Per Protocol [PP] Population .................................................................................................................. 10 
6. 
GENERAL CONSIDERATIONS ................................................................................................. 10 
6.1. 
Reference Start Date and Study Day ....................................................................................................... 10 
6.2. 
Baseline ................................................................................................................................................. 11 
6.3. 
Retests, Unscheduled Visits and Early Termination Data ......................................................................... 11 
6.4. 
Statistical Tests ...................................................................................................................................... 11 
6.5. 
Common Calculations ............................................................................................................................. 11 
6.6. 
Software Version .................................................................................................................................... 12 


 
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STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
7. 
STATISTICAL CONSIDERATIONS .......................................................................................... 12 
7.1 
Adjustments for Covariates and Factors to be Included in Analyses ......................................................... 12 
7.1. 
Multicenter Studies ................................................................................................................................ 12 
7.2. 
Missing data ........................................................................................................................................... 12 
7.3. 
Examination of Subgroups ...................................................................................................................... 12 
7.4. 
Multiple Comparisons/ Multiplicity ........................................................................................................ 13 
8. 
OUTPUT PRESENTATIONS ..................................................................................................... 13 
9. 
DISPOSITION AND WITHDRAWALS .................................................................................... 13 
10. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ...................................... 13 
10.1. 
Derivations ......................................................................................................................................... 14 
11. 
MEDICAL HISTORY ................................................................................................................... 14 
12. 
CONCOMITANT ILLNESSES ..................................................................................................... 14 
13. 
PRIOR AND CONCOMITANT MEDICATION AND THERAPIES ...................................... 15 
14. 
STUDY MEDICATION EXPOSURE & COMPLIANCE .......................................................... 15 
14.1. 
Derivations ......................................................................................................................................... 16 
15. 
EFFICACY OUTCOMES .............................................................................................................. 16 
15.1. 
Primary Efficacy .................................................................................................................................. 16 
15.1.1. 
Primary Efficacy Variable ..........................................................................................................................16 
15.1.2. 
Missing Data Methods for Primary Efficacy Variable ...............................................................................16 
15.1.3 
Primary Analysis of Primary Efficacy Variable ..........................................................................................16 
15.1.4 
Sensitivity Analysis of Primary Efficacy Variable .......................................................................................17 
15.2. 
Secondary Efficacy .............................................................................................................................. 17 
15.2.1 
Secondary Efficacy Variables ....................................................................................................................17 
15.2.2 
Missing Data Methods for Secondary Efficacy Variables ..........................................................................18 


 
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STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
15.2.3 
Analyses of Secondary Efficacy Variables .................................................................................................19 
15.2.4 
Sensitivity Analyses of Secondary Efficacy Variables ................................................................................19 
16 
SAFETY OUTCOMES .................................................................................................................. 19 
16.2 
Adverse Events ....................................................................................................................................... 19 
16.2.1 
Adverse Events .........................................................................................................................................20 
16.2.1.1 
Severity .............................................................................................................................................21 
16.2.1.2 
Relationship to Study Medication ....................................................................................................21 
16.2.2 
Adverse Events leading to Dose Change or Discontinuation of Study Medication ..................................21 
16.2.3 
Serious Adverse Events .............................................................................................................................21 
16.2.4 
Adverse Events Leading to Death .............................................................................................................21 
16.3 
Death ..................................................................................................................................................... 21 
16.4 
Laboratory Evaluations ........................................................................................................................... 22 
16.5 
ECG Evaluations ..................................................................................................................................... 22 
16.6 
Vital Signs .............................................................................................................................................. 23 
16.7 
Physical Examination .............................................................................................................................. 23 
16.8 
References ............................................................................................................................................. 23 
17 
LIST OF TABLES ......................................................................................................................... 23 
18 
LIST OF LISTINGS ...................................................................................................................... 25 
APPENDIX 1 LIST OF LABORATORY ASSESSMENTS ................................................................. 26 
 
 


 
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STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
1. INTRODUCTION 
This document describes the rules and conventions to be used in the presentation and analysis of efficacy and 
safety data for Protocol GA1202. It describes the data to be summarized and analyzed, including specifics of the 
statistical analyses to be performed.  
This statistical analysis plan (SAP) is based on protocol version 2, amendment 1, dated 4Jul2013. 
2. STUDY OBJECTIVES 
2.1. PRIMARY OBJECTIVE 
The primary objective is to compare the time during the 4 hour post dosing period where the pH is below pH 4 for 
Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets. 
2.2. SECONDARY OBJECTIVES 
The following secondary endpoints will also be evaluated: 
 
• 
Percentage of time during the 4 hour post dosing period with pH below pH 5 
• 
Number of occasions during the 4 hour post dosing period when pH falls below pH 4 
• 
Number of occasions during the 4 hour post dosing period when pH falls below pH 5 
• 
Number of reflux episodes during the 4 hour post dosing period with pH below pH 4 for at least 5 minutes 
• 
Percentage of time during the first hour post dosing with pH below pH 4 
• 
Percentage of time during the first hour post dosing with pH below pH 5 
• 
Number of occasions during the first hour post dosing when pH falls below pH 4 
• 
Number of occasions during the first hour post dosing when pH falls below pH 5 
• 
The longest reflux time during the 4 hour post dosing period (i.e. the longest period with pH below pH 4) 
• 
The DeMeester scores during the 4 hour post dosing period. 
 


 
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STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
3. STUDY DESIGN 
3.1. GENERAL DESCRIPTION 
This is a multi-centre, randomised, open-label, placebo-controlled, two-period crossover study.  Forty - four (44) 
patients are planned to be enrolled in this study to ensure that thirty six (36) patients complete it. After signing a 
written informed consent, patients will undergo a screening period up to 10 days. Patients who satisfy the study 
entry requirements within 10 days of consent, will be randomised to receive either four Compound Sodium 
Alginate Double Action Chewable Tablets or four matching placebo tablets following placement of a pH electrode 
and a standardised refluxogenic meal. 
Upon completion of the 4-hour post-dose pH monitoring period patients will be instructed to begin taking 
supplied Compound Sodium Alginate Double Action Chewable Tablets (two tablets four times daily) for 7 days. 
Patients will return after the 7 day period for repeat catheter insertion and pH monitoring, receiving the 
alternative randomised treatment.  
3.2. SCHEDULE OF EVENTS 
Schedule of assessments can be found in Section 3.10 of the protocol.  
4. 
FINAL ANALYSIS  
All final, planned analyses identified in this SAP will be performed by Quintiles Biostatistics following Reckitt 
Benckiser’s Authorization of this SAP, Database Lock and Sponsor Authorization of Analysis Sets. 
 
5. ANALYSIS SETS 
Agreement and authorization of patients included/excluded from each analysis set will be conducted at data 
review meeting before database lock.  
5.1. FULL ANALYSIS SET [FAS] 
All patients enrolled (e.g. those assigned randomization number) in the study will be included in full analysis set 
(FAS). 


 
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STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
5.2. SAFETY POPULATION 
All patients who are subjected to any invasive procedures and/or take at least one dose of study medication will 
be included in safety population.   
5.3. INTENT-TO-TREAT [ITT] POPULATION 
All patients who take at least one dose of study medication and have evaluable pH monitoring data for at least 1 
hour post-dosing will be included into intent-to-treat (ITT) population. 
5.4. PER PROTOCOL [PP] POPULATION 
The inclusion/exclusion from per protocol (PP) population will be confirmed during data review meeting, but will 
include patients who satisfied following criteria and did not experience any major protocol violations in ITT 
population: patients who adhered to the inclusive/exclusive criteria; did not take any prohibited medication 
which would interfere with evaluation of drugs in the study period; attended visits within the specified visit 
windows and had complete pH monitoring data for 4 hour post-dosing for both pH monitoring visits.   
A major violation of the protocol is defined as any violation of the protocol that is considered to affect the 
efficacy results and may include the following:  
• 
When a randomization error or administration of the wrong study medication occurred; 
• 
When the patient did not satisfy the inclusion/exclusion criteria; 
• 
When the patient had taken prohibited concomitant medications; 
• 
When the patient failed to attend visit at specified visit windows; 
• 
When the efficacy (4 hour post-dosing monitoring) evaluation was not completed for either monitoring visits. 
Protocol violations will be categorized before database lock and will be summarized (by treatment sequence 
group and overall) and listed. 
6. 
GENERAL CONSIDERATIONS 
6.1. REFERENCE START DATE AND STUDY DAY 
Study Day will be calculated from the reference start date, and will be used to show start/stop day of 
assessments and events.  
Reference start date (Day 0) is defined as the day of first dose of study medication.  


 
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STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
• 
Study Day = (date of event – reference start date). 
In the situation where the event date is partial or missing, Study Day, and any corresponding durations will 
appear partial or missing in the listings. 
Randomization date will be considered as the same date of randomization visit, that is, visit 2.  
6.2. BASELINE 
Unless otherwise specified, baseline value refers to the tests or measurements recorded at Visit 1, screening 
visit. If a particular test or measurement was repeated after Visit 1, screening visit, then the baseline value is 
defined as the last non-missing measurement taken prior to Visit 2, Day 0 (including unscheduled assessments). 
In the case where the last non-missing measurement and the reference start date coincide, that measurement 
will be considered pre-baseline, but Adverse Events (AEs) and medications commencing on the reference start 
date will be considered post-baseline. 
For patients randomized but not treated, baseline is defined as the last non-missing measurement taken on or 
before the baseline visit date. 
6.3. RETESTS, UNSCHEDULED VISITS AND EARLY TERMINATION DATA 
In general, for by-visit summaries, data recorded at the nominal visit will be presented. Unscheduled 
measurements will not be included in by-visit summaries. In the case of a retest (same visit number assigned), 
the latest available measurement for that visit will be used for by-visit summaries.  
Early termination data will be mapped to the next available visit number for by-visit summaries. 
Listings will include scheduled, unscheduled, retest and early discontinuation data. 
6.4. STATISTICAL TESTS 
The default significant level will be (5%); confidence intervals (CIs) will be 95% and all tests will be two-sided, 
unless otherwise specified in the description of the analyses. 
6.5. COMMON CALCULATIONS 
For quantitative measurements, change from baseline will be calculated as: 
 
• 
Test Value at Visit X – Baseline Value 
Log transformed (natural logarithm) of efficacy data (or another transformation) might be used in the statistical 
models if after inspection of the data it is considered necessary.  This decision will be undertaken in collaboration 
with the sponsor. 


 
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STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
6.6. SOFTWARE VERSION 
All analyses will be conducted using SAS version 9.2 or higher.  
7. STATISTICAL CONSIDERATIONS 
7.1 ADJUSTMENTS FOR COVARIATES AND FACTORS TO BE INCLUDED IN ANALYSES 
The following factors are used in the analyses. For details of their inclusion in the models, see section 15.1.3. 
• 
Treatment (Study medication and matching placebo tablets) 
• 
Dose visit (Visit 2 and Visit 3) 
• 
Subject 
• 
Treatment sequence (Group A: Patients take study medication at Visit 2 and matching placebo tablets and Visit 
3. Group B: Patients take study medication at Visit 3 and matching placebo tablets at Visit 2.  
7.1. MULTICENTER STUDIES 
This study will be conducted at two or more hospital sites. The 4-hour pH endpoints will be summarized 
separately for each center. Center will not be included as a factor in any of the statistical models because the 
study has a cross-over design 
7.2. MISSING DATA 
Patients who withdraw from the study will not be replaced.  
Unless otherwise specified, all analysis will be based on the number of non-missing observations, i.e. patients 
with missing information will not be included in the denominator when calculating percentages. If relevant for 
categorical tabulations, missing values will be treated as another category, so that all tabulations involving this 
variable will also include a row or column as appropriate to indicate the number of patients for whom the 
variable was recorded as a missing value.  
For AEs, partial or missing dates and times will not be imputed, and this will be listed as originally reported in the 
Case Report Form (CRF). 
7.3. EXAMINATION OF SUBGROUPS 
No subgroup analyses will be performed for this study. 


 
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7.4. MULTIPLE COMPARISONS/ MULTIPLICITY 
Since there is only one primary analysis, no multiple comparison adjustments will be used. 
8. OUTPUT PRESENTATIONS 
The table and listing templates provided with this SAP describe the conventions for presentation of data in 
outputs, and presentations for this study and therefore the format and content of the summary tables, figures 
and listings to be provided by Quintiles Biostatistics.  
9. DISPOSITION AND WITHDRAWALS 
The number of patients who provided informed consent, as well as those who were eligible at Visit 1 and Visit 2 
(met all inclusion criteria and not met all exclusion criteria) will be summarized overall. The number of patients 
who completed the study, the number of patients who withdrew prematurely from the study, the reasons for 
withdrawals and the number of patients in the FAS, Safety, ITT and PP population (see Section 4 for population 
definitions) will be summarized for each treatment sequence group and overall. Listings on patient 
completion/withdrawal information, as well as eligibility details will be reported  
Major protocol violations will be summarized by treatment sequence group and overall. Furthermore the 
number of patients to be excluded from each population together with reasons of exclusion will be summarized. 
Details on major protocol violations as well as population classification information will be listed. 
10. DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic data and other baseline characteristics will be summarized by treatment sequence group and 
overall for all patients in FAS. 
No statistical testing will be carried out for demographic or other baseline characteristics. 
The following demographic and other baseline characteristics will be reported for this study:  
• 
Age (years) – calculated relative to date of consent  
• 
Race 
• 
Sex 
• 
Height 
• 
Weight 
Counts and percentages will be displayed for patients with smoking habits (no, yes, former), alcohol/drug use 
(no, yes) and drugs of abuse history; summary statistics (mean, median, minimum, maximum and standard 
deviation) will be provided for the continuous variables including height, weight, age, smoking/drinking years and 
amount.  These data will also be listed. 


 
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Summary statistics will be presented for patients’ baseline Gastro-esophageal reflux disease (GERD) symptoms, 
including the severity and frequency of heartburn. In addition, 12 lead ECG and a standard hospital endoscopy 
examination will be conducted at baseline as part of the screening procedures. The following Information on ECG 
and endoscopy will be presented by summary statistics:  
ECG: 
Whether ECG is performed  
Interpretation of ECG results 
Endoscopy: 
Whether endoscopy performed  
Whether local anaesthetic throat spray administered  
Whether a sedative administered 
Any abnormalities presented in endoscopy 
If the patient has erosive GERD 
If the patient have hiatus hernia and diameter of the hernia 
Other baseline characteristics such as laboratory evaluations, vital signs, and physical examination are specified 
in section 16.3, 16.5 and 16.6 respectively.  
10.1. DERIVATIONS 
Age = Date of Informed Consent – Date of Birth (rounded down to the nearest whole year)  
11. MEDICAL HISTORY 
Medical History conditions are defined as those conditions which stopped prior to or at screening visit. Medical 
history information will be coded using version 16.0 of Medical Dictionary for Regulatory Activities (MedDRA) 
coding dictionary and presented for all patients in FAS by system organ class (SOC) and preferred term (PT), for 
each treatment sequence group and overall.  
12. CONCOMITANT ILLNESSES 
Concomitant illnesses are conditions other than GERD which are ongoing before or on the day of last dose of 
Investigational Medicinal Product (IMP), or stopped after screening visit but before or on the day of last dose of 
IMP. Concomitant Illnesses will be captured from Medical History and Current Status form in CRF, and will be 
coded using MedDRA version 16.0 and presented for all patients in safety population by SOC and PT, for each 
treatment sequence group and overall.  


 
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13. PRIOR AND CONCOMITANT MEDICATION AND THERAPIES  
Medications will be coded using World Health Organization (WHO) Drug Dictionary Enhanced version dated 
01Mar2013 and tabulated using the Anatomical Therapeutic Chemical (ATC) classification system, under Level 3 
and Level 4 for the FAS (for prior and concomitant medications separately) 
• 
‘Prior’ medications are medications which started and stopped prior to first dose of study medication.  
• 
‘Concomitant’ medications are medications which:  
o 
started prior to, on or after first dose of study medication 
o 
AND ended on or after first dose of study medication or were ongoing at the end of the study. 
14. STUDY MEDICATION EXPOSURE & COMPLIANCE 
At each of the pH monitoring visits, patients will be administered four Compound Sodium Alginate Double Action 
Chewable Tablets or four matching placebo tablets under the supervision of the Investigator or his or her 
delegate. No measurement on medication compliance will be performed.  
In addition, all patients will then receive Compound Sodium Alginate Double Action Chewable Tablets (two 
tablets four times daily) as Non-investigational Medicinal Product (NIMP) for symptomatic treatment. The 
number of tablets dispensed and returned will be recorded in CRF and presented by table and listing.  
The following information regarding whether the patients fulfill each requirement prior to pH monitoring and the 
time interval from each procedure to taking treatment will be summarized by treatment sequence group: 
Requirement prior to pH monitoring: 
Not taken symptomatic treatment for GERD (antacids etc) in the 24 hours prior to pH monitoring  
Abstain from alcohol 24 hours prior to the test meal  
Fast for a minimum of 4 hours prior to insertion of manometry probe  
Insert manometry probe to aid positioning of esophageal pH sensor prior to consuming test meal  
Consume the entire reflux provoking meal  
Record pH from 30 minutes prior to dosing to 4 hours post dosing  
Time interval from each procedure to taking treatment: 
Position pH electrode (90 mins before treatment) 
Eat test meal (60 mins before treatment) 
Activate pH monitoring data logger and Record (30 mins before treatment) 
Stop pH monitoring (4 hour post dose) 
The calculation of time interval is provided in section 14.1 


 
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14.1. DERIVATIONS  
Time interval from each procedure to taking treatment (minutes) is calculated by 
• 
Time of the procedure – Time when patient takes treatment 
15. EFFICACY OUTCOMES  
15.1. PRIMARY EFFICACY 
15.1.1. PRIMARY EFFICACY VARIABLE  
The primary efficacy endpoint is the percentage of time during the 4 hour post dosing period with pH below pH 4 
for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets. This variable is 
collected on the “Results of 4-hour pH Monitoring” page in CRF. 
15.1.2. MISSING DATA METHODS FOR PRIMARY EFFICACY VARIABLE 
If less than 2 hours post-dosing monitoring result for this variable is available, for whatever reason, the derived 
variable will be considered missing. If 2 or more hours post-dosing monitoring data is available, the parameter will 
be derived by multiplying by the factor (4 hours / time with data available). Any data recorded more than 4 hours 
post-dosing will be ignored when deriving these parameter. 
The table below shows the implementation of adjustment rules under different monitoring duration scenarios.  
Monitoring 
Duration(End of pH 
monitoring – taking 
treatment) 
Percentage of time 
with pH<4 during the 
monitoring 
period 
(data directly from 
database) 
Number of hours 
with pH<4  during 
the 
monitoring 
period 
Adjustment 
factor  
Adjusted 
percentage with 
pH<4 
over 
4 
hours 
240 mins (4 hours) 
80.0% 
240 mins 
1 
80.0% 
230 mins (<4 hours) 
80.0% 
230*80%  mins 
240/230 
230*80%*240/23
0/240=80.0% 
90 mins (<2 hours) 
20.0%  
90*20% mins 
NA 
missing 
15.1.3 PRIMARY ANALYSIS OF PRIMARY EFFICACY VARIABLE 
The primary endpoint will be analysed primarily using a linear mixed model with treatment, dosing visit and 


 
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STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
treatment sequence as fixed effects and patient nested within treatment sequence as a random effect. The 
primary analysis is to test the null hypothesis that there is no difference between treatment, Least square means 
(with 95% CI) corresponding to the two treatments will be presented. Descriptive statistics will also be presented 
for the primary endpoint by treatment for each dosing visit and overall. The effects for dosing visit and treatment 
sequence will also be assessed.  
The following SAS core code will be used. 
proc mixed data=XXX method=REML; 
  class treatment visit sequence subID; 
  model Y= treatment visit sequence /ddfm=kenwardroger; 
  random subID(sequence); 
  lsmeans treatment/diff cl; 
run; 
SAS output from Mixed procedure will be sent to the sponsor to assist with the model assumptions review. 
The linear mixed model for the primary endpoint is based on the assumption that the percentage of time with 
pH<4 within each treatment sequence group is normally distributed. To test this assumption, a qualitative 
residual analysis will be performed. If there is a major departure from the assumptions of normality or 
heteroscedasticity of residuals, then further analysis using transformed data might be performed if deemed 
necessary. If the analysis based on the transformed data still rises reasonable concerns about validity of the tests 
then the  Wilcoxon Rank-Sum test will be used to compare the dosing visit difference (dosing visit 1 – dosing visit 
2) between treatment sequence groups to represent the treatment comparison. 
The primary efficacy analysis will be performed for the ITT population using adjusted 4-hour data based on the 
imputation rule specified in section 15.1.2. 
15.1.4 SENSITIVITY ANALYSIS OF PRIMARY EFFICACY VARIABLE 
A sensitivity analysis will be conducted on the primary endpoint using the PP population. 
If the percentage of missing data for the primary endpoint is greater than 10% (data from > 10% patients is not 
recorded exactly at 4 hours (+/- 5 minutes), an additional complete case sensitivity analysis will be conducted, 
using only the observed 4-hour (+/- 5 minutes) data. 
15.2. SECONDARY EFFICACY 
15.2.1 SECONDARY EFFICACY VARIABLES  
The secondary endpoints are:  
Percentage of time during the 4 hour post dosing period with pH below pH 5 
Number of occasions during the 4 hour post dosing period when pH falls below pH 4 
Number of occasions during the 4 hour post dosing period when pH falls below pH 5 


 
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STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
Number of reflux episodes during the 4 hour post dosing period with pH below pH 4 for at least 5 minutes 
Percentage of time during the first hour post dosing with pH below pH 4 
Percentage of time during the first hour post dosing with pH below pH 5 
Number of occasions during the first hour post dosing when pH falls below pH 4 
Number of occasions during the first hour post dosing when pH falls below pH 5 
The longest reflux time during the 4 hour post dosing period (i.e. the longest period with pH below pH 4) 
The DeMeester scores during the 4 hour post dosing period. 
The secondary efficacy analyses will be performed for the ITT population. 
15.2.2 MISSING DATA METHODS FOR SECONDARY EFFICACY VARIABLES 
Missing data for the percentage of time during the 4 hour post dosing period with pH below pH 5 due to early 
termination of recording will be derived in the same way as for the primary efficacy variable. 
For the following secondary efficacy variables: 
• 
Number of occasions during the 4 hour post dosing period when pH falls below pH 4 
• 
Number of occasions during the 4 hour post dosing period when pH falls below pH 5 
• 
Number of reflux episodes during the 4 hour post dosing period with pH below pH 4 for at least 5minutes 
If less than 2 hours post-dosing monitoring result for these variables is available, for whatever reason, the derived 
variable will be considered missing.  If 2 or more hours post-dosing pH data is available then the variable will be 
multiplied by 4 / (hours of post-dosing pH data available). Any data recorded more than 4 hours post-dosing will be 
ignored when deriving these parameters. 
The table below shows the implementation of adjustment rules (take number of occasions as an example) under 
different monitoring duration scenarios.  
Monitoring 
Duration(End of pH 
monitoring – taking 
treatment) 
Number of occasions with 
pH<4 during the monitoring 
period (data directly from 
database) 
Adjustment 
factor 
Adjusted occasion with 
pH<4 over 4 hours 
240 mins (4 hours) 
2 
1 
2 
230 mins (<4 hours) 
2 
240/230 
2*240/230=2.09 
90 mins (<2 hours) 
1 
NA 
missing 
 
Missing data for other secondary endpoints due to early termination of recording will not be derived.  


 
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15.2.3 ANALYSES OF SECONDARY EFFICACY VARIABLES 
The analysis methods for all secondary endpoints will be identically to those described for the primary endpoint 
in 15.1.3. 
15.2.4 SENSITIVITY ANALYSES OF SECONDARY EFFICACY VARIABLES 
Sensitivity analyses will be conducted on the secondary endpoints using the PP population. 
If the percentage of missing data for the secondary variables listed in section 15.2.2 is greater than 10% (data 
from > 10% patients is not recorded exactly at 4 hours +/- 5 minutes), an additional complete case sensitivity 
analysis will be conducted, using only the observed 4-hour (+/- 5 minutes) data. 
16 SAFETY OUTCOMES 
All outputs for safety outcomes will be based on the Safety Population. 
16.2 ADVERSE EVENTS 
Adverse Events (AEs) will be coded using MedDRA version 16.0. For an individual patient, only adverse events 
commencing after first dose of IMP and no later than last dose of IMP+1day will be included in the AE and 
serious adverse event (SAE) summaries. AEs that began prior to the first dose of IMP or more than one day after 
the final dose of IMP will not be included in the analysis. Where an AE start date is partially or completely 
missing, and it is unclear using partial dates as to whether the AE is treatment-emergent, it will be assumed that 
it is.  


 
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16.2.1 ADVERSE EVENTS 
An overall AE summary presenting the number and percentage of patients within the following categories by 
treatment sequence group and total will be provided.  
• 
Total number of AEs (each patient might be counted more than once within this item) 
• 
Patients with AEs 
• 
Patients with SAEs 
• 
Patients with AEs with a relationship to IMP as “Possible”, “Probable” and “Certain” 
• 
Patients with severe AEs 
• 
Patients with AEs leading to IMP dose change 
• 
Patient with AEs leading to IMP permanently discontinued 
In addition, an analysis using McNemar's test to compare the AE incidence during the 4-hour post dosing period 
between treatments will be presented for the following categories: 
• 
Total number of AEs (note that for this item only the total numbers will be presented, no comparison on 
McNemar’s test will be performed) 
• 
Patients with AEs 
• 
Patients with SAEs 
• 
Patients with AEs with a relationship to IMP as “Possible”, “Probable” and “Certain” 
• 
Patients with severe AEs 
In addition, following tables will be reported by treatment sequence group:  
• 
AEs, by SOC, PT and severity 
• 
Related AEs, by SOC, PT and severity 
The tables above will be repeated for adverse events occur during the 4 hour post dosing period by treatment. 
Individual listings on adverse events, related adverse events (see definition in section 16.1.1.2), serious adverse 
events, adverse events leading to dose change/study discontinuation and death will be reported.  


 
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16.2.1.1 
Severity 
Severity is classified as mild/ moderate/ severe. AEs with a missing severity will be counted in a separate missing 
category. If a patient reports an AE more than once within that SOC/ PT, the AE with the worst case severity will be 
used in the corresponding severity summaries. 
16.2.1.2 
Relationship to Study Medication 
Relationship, as indicated by the Investigator, is classed as “Unassessable/Unclassified”, “Conditional/Unclassified”, 
“Unrelated”, “Unlikely”, “Possible”, “Probable”, and “Certain”. Adverse events with a relationship of “Possible”, 
“Probable” and “Certain” to IMP will be considered as related to study medication. AEs with a missing relationship 
to study medication will be counted in a separate missing category. If a patient reports the same AE more than 
once within that SOC/ PT, the AE with the worst case relationship to study medication will be used in the 
corresponding relationship summaries.  
16.2.2 ADVERSE EVENTS LEADING TO DOSE CHANGE OR DISCONTINUATION OF STUDY MEDICATION 
If the action taken for an AE is recorded as “IMP permanently discontinued” on AE page of the CRF it will be 
considered as an AE leading to permanent discontinuation. If the action taken for an AE is recorded as “IMP dose 
changed” on AE page of the CRF it will be considered as an AE leading to dose change. These will be summarized by 
SOC and PT by treatment sequence group and also listed. 
16.2.3 SERIOUS ADVERSE EVENTS 
SAEs are those events recorded as “Serious” on the Adverse Events page of the CRF. A summary of SAEs by SOC, PT 
and severity, as well as a summary of related SAEs by SOC, PT, and severity will be reported by treatment sequence 
group. The tables will be repeated for serious adverse events during the 4 hour post doing period. Summaries will 
also be provided for SAEs leading to dose change as well as study discontinuation. These data will also be listed. 
16.2.4 ADVERSE EVENTS LEADING TO DEATH 
AEs leading to Death are those events with outcome reported as “Fatal” in the Adverse Events page of the CRF. A 
summary of AEs leading to death by SOC and PT will be prepared. This information will also be listed. 
 
16.3  DEATH 
As only AEs leading to death are recorded for this study, please refer to Section 16.1.4. 


 
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16.4 LABORATORY EVALUATIONS 
Clinical assessments on hematology and clinical chemistry are to be measured at Visit 1 and Visit 3 (Early 
Termination Visit).  A list of laboratory assessments to be included in the outputs is provided in appendix 1. 
Local laboratories will be used for the assessment of hematology and clinical chemistry data and these data will 
be converted to the International System (SI) of units by Data Management Team using standard conversion 
factors. Quantitative laboratory measurements reported as “< X”, i.e. below the lower limit of quantification 
(BLQ), or “> X”, i.e. above the upper limit of quantification (ULQ), will be converted to X for the purpose of 
quantitative summaries, but will be presented as recorded, i.e. as “< X” or “> X” in the listings. 
At each visit, summary statistics for the absolute laboratory value and the changes from baseline will be 
presented by treatment sequence group and overall. The significance of changes from baseline will be assessed 
using the Wilcoxon Signed-Rank Test within each sequence group and overall.  
Each pre-study baseline laboratory value will be categorised as low, normal, or high based on the reference 
range:  
Low: Below the lower limit of the laboratory reference range.  
Normal: Within the laboratory reference range (upper and lower limit included). 
High: Above the upper limit of the laboratory reference range. 
Each post-baseline value will be classified in a similar manner, producing a 3 x 3 table for each treatment 
sequence group at each post-baseline visit. Scores of “1” will be assigned to low values, “2” to normal values, and 
“3” to high values. Using these scores, shifts from baseline will also be assigned a score. For example, a 
laboratory value that shifts from low to high will be assigned a score of 2, whilst a laboratory value that remains 
at a low value will be assigned a score of 0. Shifts between these categories between baseline and Visit 3 (Early 
Termination Visit) will be compared using the Wilcoxon Signed-Rank test within each treatment sequence group 
and overall. Statistical testing will be performed at last visit.  
In addition to the high and low quantitative laboratory assignments (as identified by means of the laboratory 
reference ranges), clinically significant quantitative laboratory assessments will be identified by investigator and 
the result will be recorded in the CRF. The number and percentage of patients with abnormal or clinically 
significant results will be tabulated by treatment sequence groups by visit. The results will also be listed.  
Women of child-bearing potential will undergo urine pregnancy testing (positive or negative). The results will be 
listed. 
16.5  ECG EVALUATIONS 
A 12-lead ECG examination will be conducted at baseline. The results will be listed and summarised as per 
Section 10. 


 
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16.6 VITAL SIGNS  
Vital signs will be conducted at baseline and final or early termination visits. The following Vital Signs 
measurements will be reported: 
Systolic and diastolic blood pressure (after sitting for 5 minutes; mmHg) 
Heart rate (radial pulse counted for 30 seconds after resting for 5 minutes; beats/minute) 
At each visit, summary statistics for the absolute vital sign value and the changes from baseline will be presented 
by treatment sequence group and overall. The significance of changes (within each sequence separately and 
overall) from baseline will be assessed at the last visit, using the Wilcoxon Signed-Rank Test.  
A complete listing on all patients’ vital sign result will be presented.  
16.7 PHYSICAL EXAMINATION  
A physical examination is to be performed at Visit 1 and Visit 3 or early termination visit. The following 
summaries will be provided for physical examination data: 
Incidence of clinically significant abnormalities at screening 
Incidence of clinically significant abnormalities at Visit 3 (early termination visit) 
A shift table on clinically significant abnormalities between baseline and Visit 3 (Early Termination Vist) will be 
presented, and P- values from McNemar’s test will be reported within each sequence group and overall.  
A listing on clinical significant abnormalities will be reported.  
16.8 REFERENCES  
1. Reckitt Benckiser GA1202 Study Protocol Final Version 2.0, Amendment 1, 4Jun2013.  
17 LIST OF TABLES 
14.1.1 Patient Disposition and Withdrawals – All Patients 
14.1.2 Protocol Deviations/Violations – Full Analysis Set   
14.1.3 Summary of Patiens Excluded from Analysis Populations – Full Analysis Set 
14.1.4 Demographic and Baseline Characteristics – Full Analysis Set 
14.1.5 Smoking habits and Alcohol/Drug Use – Full Analysis Set 
14.1.6 GERD Status at Baseline – Full Analysis Set 
14.1.7 12-Lead ECG Examination – Full Analysis Set 
14.1.8 Endoscopy Examination – Full Analysis Set 
14.1.9.1  Medical History – Full Analysis Set 
14.1.9.2 Concomitant Illnesses – Full Analysis Set 


 
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14.1.10.1 Prior Medications and Therapies  - Full Analysis Set 
14.1.10.2 Concomitant Medications and Therapies  – Full Analysis Set 
14.1.11 NIMP Accountability – Safety Population 
14.1.12 4-Hour Monitoring Procedure – Intent-to-treat Population 
 
14.2.1.1  Summary of 4-hour pH Monitoring Results based on Adjusted 4-hour Data – Intent-to-treat Population 
14.2.1.2 Summary of 4-hour pH Monitoring Results based on Adjusted 4-hour Data by Center – Intent-to-treat 
Population 
14.2.2.1 Analysis of Treatment Difference during the 4-hour Post Dosing Period based on Adjusted 4-hour Data – 
Intent-to-treat Population 
14.2.2.2 Analysis of Treatment Difference during the 4-hour Post Dosing Period – Per protocol Population 
14.2.2.3 Analysis of Treatment Difference during the 4-hour Post Dosing Period based on Log Transformed Adjusted 
4-hour Data – Intent-to-treat Population 
 
14.2.3.1 Analysis of Visit and Sequence Difference during the 4-hour Post Dosing Period – Intent-to-treat 
Population 
14.2.3.2 Analysis of Visit and Sequence Difference during the 4-hour Post Dosing Period – Per Protocol Population 
 
14.3.1.1 Summary of All Adverse Events – Safety Population 
14.3.1.2 Comparison of Adverse Events during the 4-hour Post Dosing Period – Safety Population 
14.3.2.1 Overall Adverse Events by System Organ Class, Preferred Term and Intensity – Safety Population  
14.3.2.2 Overall Related Adverse Events by System Organ Class, Preferred Term and Intensity – Safety Population 
14.3.2.3 Overall Serious Adverse Events by System Organ Class, Preferred Term and Intensity – Safety Population 
14.3.2.4 Overall Related Serious Adverse Events by System Organ Class, Preferred Term and Intensity – Safety 
Population 
14.3.2.5 Adverse Events during the 4-hour Post Dosing Period by System Organ Class, Preferred Term and Intensity 
– Safety Population 
14.3.2.6 Related Adverse Events during the 4-hour Post Dosing Period by System Organ Class, Preferred Term and 
Intensity – Safety Population 
14.3.2.7 Serious Adverse Events during the 4-hour Post Dosing Period by System Organ Class, Preferred Term and 
Intensity – Safety Population 
14.3.2.8 Related Serious Adverse Events during the 4-hour Post Dosing Period by System Organ Class, Preferred 
Term and Intensity – Safety Population 
14.3.2.9 Adverse Events Leading to Dose Change by System Organ Class and Preferred Term – Safety Population 
14.3.2.10 Adverse Events Leading to Study Discontinuation by System Organ Class and Preferred Term – Safety 
Population 
14.3.2.11 Adverse Events Leading to Death - Safety Population 
14.3.2.12 Serious Adverse Events Leading to Dose Change by System Organ Class and Preferred Term – Safety 
Population 
14.3.2.13 Serious Adverse Events Leading to Study Discontinuation – Safety Population 
 
14.3.3.1   Hematology: Observed Values – Safety Population 
14.3.3.2   Hematology: Change from Baseline at Visit 3 – Safety Population 
14.3.3.3   Clinical Chemistry: Observed Values – Safety Population 
14.3.3.4   Clinical Chemistry: Change from Baseline at Visit 3 – Safety Population 


 
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14.3.3.5   Abnormal Results in Hematology – Safety Population 
14.3.3.6   Abnormal Results  in Clinical Chemistry – Safety Population 
14.3.3.7   Clinically Significant Results in Hematology – Safety Population 
14.3.3.8   Clinically Significant Results in Clinical Chemistry – Safety Population 
14.3.3.9   Shift Table for Hematology – Safety Population 
14.3.3.10 Shift Table for Clinical Chemistry – Safety Population 
 
 
14.3.4.1 Vital Signs: Observed Values – Safety Population 
14.3.4.2 Vital Signs: Change from Baseline at Visit 3 – Safety Population 
14.3.5.1   Summary of Physical Examination Results – Safety Population 
14.3.5.2  Shift Table for Physical Examination – Safety Population 
18   LIST OF LISTINGS   
16.2.1.1  Patient Completion Information  - All Patients  
16.2.1.2  Inclusion/Exclusion Criteria Eligibility - All Patients 
16.2.1.3  Population Classification - Full Analysis Set  
 
16.2.2.    Major Protocol Deviations/Violations - Full Analysis Set  
16.2.3.1 Demographic Data - Full Analysis Set  
16.2.3.2  Medical History – Full Analysis Set  
16.2.3.3  Concomitant Illnesses - Full Analysis Set 
16.2.3.4  Smoking Habits and Alcohol/Drug Use - Full Analysis Set  
16.2.3.5  GERD Status at Baseline - Full Analysis Set 
16.2.3.6.1    Prior Medication and Therapies – Full Analysis Set 
16.2.3.6.2 Concomitant Medications and Therapies – Full Analysis Set 
16.2.3.7 Pregnancy Test Results  - Full Analysis Set 
16.2.3.8 12-lead ECG at Baseline – Full Analysis Set 
16.2.3.9 Endoscopy Examination – Full Analysis Set 
16.2.3.10 NIMP Accountability – Safety Population 
16.2.4.1   4-hour pH Monitoring Procedure – Full Analysis Set  
16.2.4.2   4-hour pH Monitoring Results – Full Analysis Set 
 
16.2.5.1   Adverse Events - Safety Population 
16.2.5.2   Related Adverse Events - Safety Population  
16.2.5.3   Serious Adverse Events - Safety Population  
16.2.5.4   Severe Adverse Events – Safety Population 
16.2.5.5   Adverse Events Leading to Dose Change - Safety Population 
16.2.5.6   Adverse Events Leading to Study Discontinuation – Safety Population 
16.2.5.7   Serious Adverse Events Leading to Dose Change – Safety Population 
16.2.5.8   Serious Adverse Events Leading to Study Discontinuation – Safety Population 
16.2.5.9   Death – Safety Population 


 
Document: 
Reckitt Benckiser GA1202 Statistical Analysis Plan
Author: 
Version Number: 
Final 5.1 
 
 
Version Date: 
[25Feb2014] 
Template No:  CS_TP_BS016 – Revision 3 
Effective Date: 01May2012 
                  Reference:  CS_WI_BS005 
                                        Page 26 of 29 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
 
16.2.6.1   Hematology Results - Safety Population 
16.2.6.2   Clinically Significant Hematology Results - Safety Population 
16.2.6.3   Clinical Chemistry Results - Safety Population 
16.2.6.4   Clinically Significant Chemistry Results – Safety Population 
 
16.2.7.1   Vital Signs – Safety Population 
16.2.7.2   Physical Examinations – Safety Population 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
APPENDIX 1 LIST OF LABORATORY ASSESSMENTS 
Site 01 


 
Document: 
Reckitt Benckiser GA1202 Statistical Analysis Plan
Author: 
Version Number: 
Final 5.1 
 
 
Version Date: 
[25Feb2014] 
Template No:  CS_TP_BS016 – Revision 3 
Effective Date: 01May2012 
                  Reference:  CS_WI_BS005 
                                        Page 27 of 29 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
Assessment 
Normal Range  
SI Unit 
Haematology 
 
Haemoglobin 
113-151 for female, 131-172 for male
g/L 
Red blood cells 
3.68-5.13 for female, 4.09-5.74 for male
10^12/L 
Mean cell haemoglobin concentration 
322-362 for female, 320-355 for male
g/L 
White blood cells 
3.69-9.16 for female, 3.97-9.15 for male
10^9/L 
Platelet count 
101-320 for female, 85-303 for male
10^9/L 
Clinical chemistry 
 
Sodium 
130-147
mmol/L 
Potassium 
3.5-5.1
mmol/L 
Calcium 
2-2.75
mmol/L 
Urea 
2.5-7.1
mmol/L 
Creatinine 
53-97 for female, 62-115 for male
µmol/L 
Uric Acid 
160-430
µmol/L 
Glucose 
3.9-6.1
mmol/L 
Inorganic phosphorous
0.8-1.6
mmol/L 
Alanine transaminase 
10-64
U/L 
Aspartate transaminase 
8-40
U/L 
 
 
 
 
Site 02 
Assessment 
Normal Range  
SI Unit 


 
Document: 
Reckitt Benckiser GA1202 Statistical Analysis Plan
Author: 
 
Version Number: 
Final 5.1 
 
 
Version Date: 
[25Feb2014] 
Template No:  CS_TP_BS016 – Revision 3 
Effective Date: 01May2012 
                  Reference:  CS_WI_BS005 
                                        Page 28 of 29 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
Haematology 
 
Haemoglobin 
110-170
g/L 
Red blood cells 
4.09-5.74
10^12/L 
Mean cell haemoglobin concentration 
320-355
g/L 
White blood cells 
3.97-9.15
10^9/L 
Platelet count 
85-303
10^9/L 
Clinical chemistry 
 
Sodium 
135-145
mmol/L 
Potassium 
3.5-5.5
mmol/L 
Calcium 
2-2.5
mmol/L 
Urea 
1.7-8.3
mmol/L 
Creatinine 
40-110
µmol/L 
Uric Acid 
119-428
µmol/L 
Glucose 
3.6-6.1
mmol/L 
Inorganic phosphorous
1-1.6
mmol/L 
Alanine transaminase 
0-75
U/L 
Aspartate transaminase 
0-40
U/L 
 
 
 
 
 
 
Site 03 


 
Document: 
Reckitt Benckiser GA1202 Statistical Analysis Plan
Author: 
Version Number: 
Final 5.1 
 
 
Version Date: 
[25Feb2014] 
Template No:  CS_TP_BS016 – Revision 3 
Effective Date: 01May2012 
                  Reference:  CS_WI_BS005 
                                        Page 29 of 29 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN: PROTOCOL GA1202 
Assessment 
Normal Range  
SI Unit 
Haematology 
 
Haemoglobin 
110-150 for female, 120-160 for male
g/L 
Red blood cells 
3.5-5 for female, 4-5.5 for male
10^12/L 
Mean cell haemoglobin concentration 
310-350
g/L 
White blood cells 
4-10
10^9/L 
Platelet count 
100-300
10^9/L 
Clinical chemistry 
 
Sodium 
135-148
mmol/L 
Potassium 
3.5-5.5
mmol/L 
Calcium 
2.15-2.62
mmol/L 
Urea 
2.5-6.5
mmol/L 
Creatinine 
50-110
µmol/L 
Uric Acid 
150-420
µmol/L 
Glucose 
3.6-6.1
mmol/L 
Inorganic phosphorous
0.82-1.62
mmol/L 
Alanine transaminase 
0-64
U/L 
Aspartate transaminase 
0-64
U/L 
 


O
ou1NTILES 
Changes to Planned Statistical Analyses Form 
Customer: 
RB Healthcare 
Protocol No.: 
GAl202 
QVA96908 
19/MAR/2014 
Project Code: 
Date: 
The timing of the change(s) was: 
[2l 
After unblinding (or database lock for an open-label study) but before completion of the 
final ~tatistical Report/Clinical Study Report 
After completion of the final Statistical Report/Clinical Study Report 
The tenn "Full Analysis Set" is to be renamed lhe "All Patient Population" 
Describe the rocess used to decide on the chan e s and who was involved: 
Page 1 of 1 
The RB Statistical Manager (
) was made aware ofa comment made by the SFDA on a previous 
submitted RB study stating that RB had used lhe term Full Analysis Set (FAS) inappropriately. 
According to the "Technical Guidelines of the Biostatistics for the Clinical Trials of Chemical Drugs and 
Biological Products" the FAS should be represented as follows: "The data set is obtained after excluding the 
examinees in the minimal and reasonable approach from all the randomized examinees". However the FAS 
in GA1202 represent all randomised patients. Therefore RB request that the Full Analysis Set (FAS) in this 
study is to be renamed the All Patient Population (APP). As listings currenlly including screen failures are 
headed 'All patients', this heading will now be headed 'All Screened Patients' lo prevent confusion with the 
new definition. 
In the final GA1202 SAP the FAS according lo the guidance is represented by the Intent lo Treat (ITT) 
o ulation so no chan 
• 
• 
ulation. 
The rou s res onsible for the chan e s and im lications for the stud 
The RB Statistical Manager 
) is responsible for requesting this change and Quintile 
Statisticians are responsible or up atmg the TFLs and ensuring appropriate documentation and 
explanation in the Statistical and Clinical Reports. 
This change is purely a wording issue and does not affect lhc conduct or interpretation of the planned study 
anal ses 
Fonn completed by: 
Title 
0 II 
I I 
4 
• 
0 
Mgr, Biostatistics 
Form approved by: 
Title 
Dir, Biostatistics 
Form approved by Customer Representative (if applicable): 
Title 
Name 
Si 
Statistical Manager 
Form No: CS_FM_BS006 - Revision 4 
Effective Date: 01 Feb2010 
Copyright© 2010 Quintiles TransnaUonal Corp. All rights reserved. 
Reference: CS_Wl_BSOOS 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction Is strictly prohibited. 


J QUINTILES 
Changes to Planned Statistical Analyses Form 
Customer: 
Protocol No.: 
RB Healthcare 
GA1202 
QVA96908 
08/MAY/2014 
Project Code: 
Date: 
The timing of the change(s) was: 
t8l 
After unblinding (or database lock for an open-label study) but before completion of the 
linarstatistical Report/Clinical Study Report 
After completion of the final Statistical Report/Clinical Study Report 
1. Additional analyses in which erosive/non-erosive GERO factor and its interaction with 
treatment are added to the primary analysis model. 
Page 1 of 1 
2. Fl ure of the rima 
and oint ITT o ulation result showin the lot of DADA v lacebo. 
Describe the rocess used to decide on the chan ""e""s4.;;;;a.ccn.;;;d_w,;,,;h,;;.o;..w...c,.;.;a.;;.s..;..inc..v:..:o;.;;.lv"--e:..:d:.;.: _________ 
Requested by RB Statistical Manager 
to provide informative additional exploratory analyses 
not planned in the analyses and also a grap 1ca representation of the primary endpoint result. 
The rou s res onslble for the chan e s and im licatioos for the stud : 
The RB Statistical Manager 
is responsible for requesting this change and Quintile 
Statisticians are responsible for producing the requested output and ensuring appropriate documentation 
and explanation in the Statistical and Clinical Reports. 
Fonn completed by: 
Title 
Name 
Signature 
Mgr, Biostafotics 
Fon11 approved by: 
Title 
Dir, Biostatistics 
Forni approved by Customer Representative (if applicable): 
Title 
Name 
Signature 
Statistical Manager 
Form No: CS FM 8S006 - Revision 4 
Effective Date: 01 Feb2010 
Date 
Date 
Reference: CS_WI_BS005 
Copyright © 2010 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited. 


Q
OUINTILES 
Changes to Planned Statistical Analyses Form 
Customer: 
Protocol No.: 
RB Healthcare 
GAl202 
QVA96908 
Project Code: 
Date: 
I 7/JUL/2014 
The timing of the change(s) was: 
IZI 
After unblinding {or database lock for an open-label study) but before completion of the 
final 'Statistical Report/Clinical Study Report 
After completion of the final Statistical Report/Clinical Study Report 
Additional listing on minor protocol deviation is to be added. 
Describe the orocess used to decide on the chan2e(s) and who was involved: 
Page 1 of 1 
During the preparation of the Clinical Study Report, the Quintiles Medical Writer ( 
and team 
noticed that Table 14.1 .2 includes an analysis of the minor protocol deviation, yet the listing referred to 
(Listing 16.2.2) only covers the major deviation. 
According lo the ICH GCP guidance, it was interpreted that only major deviation need to be reported hence 
only major protocol d-
· 
• • 
as included in the SAP. 
solve the anomaly in the CSR, 
RB Clinical Manager 
and Statistical Manager ~
) requested to have another 
listing added to display the minor deviation. 
Thus, Listing l 6.2.2 will become 16.2.2.1, and a new listing 16.2.2.2 will present all minor protocol 
deviation. Table 14.1.2 wi II reference both listings. 
The rou s res onsible for the chan e s and im licatlons for the stud : 
The RB Clinical Manager 
and RB Statistical Manager 
) are responsible for 
requesting this change and 
um I e 
a 1s 1cians are responsible for providing the additional listing and 
ensuring appropriate documentation and explanation in the Statistical and Clinical Reports. 
Form completed by: 
Title 
AD, Biostatistics 
Form approved by: 
Title 
Dir, Biostatistics 
Form approved by Custom 
• 
• 
• 
• 
Title 
Statistical Manager 
Form No: CS_FM_BS006 - Revision 4 
Effective Date: 01 Feb2010 
Copyright © 2010 Quintiles Transnational Corp. All rights reserved. 
Reference: CS_WI_BS00S 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.