Clinical trial NCT02905825
Conditions: Helicobacter Pylori Infection
Sponsor: Meridian Bioscience, Inc.
Start date: 2017-05-18; Completion date: 2017-11-05
Enrollment: 54 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Clinical Study to Confirm Safety and Accuracy in Detection of H. pylori with 13C-Urea Breath Test using the BreathID® Hp and BreathID® Hp Lab Systems in the Pediatric Population

Detailed description:
Pediatric subjects with indication for H.pylori testing, will be tested with both stool antigen as a reference standard and a urea breath test using the BreathID® Hp and BreathID® Hp Lab Systems. The BreathID® Hp system continuously measures breath via a nasal cannula and the BreathID® Hp Lab System measures breath collection bags before and after ingestion of a solution with enriched carbon 13 urea and citric acid. The stool sample will be provided within a week of the breath tests and will be analyzed by a central laboratory. Safety and overall efficacy will be assessed.

Arms: arm 1: Walk in basis: any pediatric subjects with indication for Helicobacter pylori testing will be enrolled if they meet study eligibility criteria and will perform stool test and urea breath test within a week of each other.
Interventions: intervention 1: BreathID® Hp System intervention 2: BreathID® Hp Lab System intervention 3: Stool Test
Intervention descriptions: intervention 1: Breath will be analyzed for change in carbon 13 content in breath after ingestion of carbon 13 enriched urea intervention 2: Breath will be analyzed for change in carbon 13 content in breath after ingestion of carbon 13 enriched urea intervention 3: Each subject was asked to perform a stool test in parallel to the breath test.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
Clinical Study to Confirm Safety and Accuracy in Detection of H. 
pylori with 13C-Urea Breath Test using the BreathID® Hp and  
BreathID® Hp Lab Systems in the Pediatric Population 
 
Protocol No. PED-HP-0616B 
Document No.: CSD00092 
Total Pages: 59 
Protocol version: 2.0 
Last update on: Mar 12, 2017 
 
 
Name 
Position 
Author 
Avraham Hershkowitz 
Clinical Trials Manager 
Reviewed by 
Gil Guggenheim 
Clinical Research Development Manager 
Reviewed by 
Michal Brunner 
Clinical Trials Manager 
Approved by 
Melina Arazy, MD 
VP of Clinical Affairs 
Electronic signatures and approvals, effective information and Lifecycle Status can be 
obtained by accessing the system generated approval page associated with this document.  
The system generated approval page can be retrieved from the PDM system. 
This publication, in whole or in part, may not be reproduced, disclosed, translated into any 
language or computer language or distributed without the prior written consent of: 
Exalenz Bioscience Ltd. 4 Ha’Maayan St. Modiin, Israel 7177872 
Versions Control: 
Version 
Date 
Responsible Person 
Description of Change 
1 
20 Sep 2016 
Avraham Hershkowitz  Initial Release Israel MOH Stool 
and EGD 
1.1 
19 Sep 2016 
Michal Brunner 
Internal version – administrative 
changes, Stool and EGD (not 
released) 
1.2 
20 Sep 2016 
Michal Brunner 
Initial US Release for IDE 
1.3 
13 Nov 2016 
Avraham Hershkowitz Minor changes due to IDE 
conditional approval- 
2.0 
12 Mar 2017 
Gil Guggenheim 
Clarifying the Blinding of PI and 
minor edits (Post Pre-Submission 
Comments Q170072) 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  2 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
TABLE OF CONTENTS 
Abbreviations ........................................................................................................................................ 5 
1. 
Protocol Synopsis .......................................................................................................................... 7 
2. 
Visit Schedule Overview ............................................................................................................. 19 
3. 
Study Sponsor .............................................................................................................................. 20 
4. 
Background ................................................................................................................................. 21 
4.1. 
Helicobacter pylori (H. pylori) Infections in Pediatrics ...................................................... 21 
4.2. 
Comparator Details .............................................................................................................. 22 
4.3. 
The 13C-Urea Breath Test .................................................................................................... 23 
4.4. 
Breath Analyzing Devices and Breath Collection Methods ................................................ 24 
4.4.1. 
Exalenz’ BreathID® Hp System (K130524) .................................................................... 24 
4.4.2. 
Exalenz’ BreathID® Hp Lab System (K162150) ............................................................. 25 
4.5. 
Rationale of performing UBT with two methods of breath collection ................................ 26 
5. 
Intended Use BreathID® Hp System ............................................................................................ 26 
6. 
Intended Use BreathID® HP LAB System ................................................................................... 27 
7. 
BreathID® Hp System – Description ........................................................................................... 27 
8. 
BreathID® Hp LAB System test – Description and components ................................................ 29 
9. 
Study Design ............................................................................................................................... 32 
10. 
Breath testing procedure .......................................................................................................... 32 
10.1. 
Collecting the Breath Samples ........................................................................................ 32 
10.2. 
Measuring Bags ............................................................................................................... 35 
11. 
Study Objectives ...................................................................................................................... 35 
11.1. 
Primary Objective: Safety ............................................................................................... 35 
11.2. 
Secondary Objectives: Confirmation of Efficacy ............................................................ 35 
12. 
Subject Selection ..................................................................................................................... 36 
12.1. 
Inclusion Criteria ............................................................................................................. 36 
12.2. 
Exclusion Criteria ............................................................................................................ 37 
12.3. 
Exclusion Criteria for Day of Urea Breath Test .............................................................. 37 
12.4. 
Consenting ....................................................................................................................... 37 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  3 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
12.5. 
Termination of Subjects .................................................................................................. 38 
12.6. 
Early Withdrawal from the Study .................................................................................... 38 
12.7. 
Expected Duration of Recruitment .................................................................................. 38 
13. 
Study Assessments and procedures ......................................................................................... 38 
13.1. 
Study Visits ..................................................................................................................... 38 
13.1.1. 
Screening Visit (can be done up to 37 days prior to the breath test) ............................... 39 
13.1.2. 
Baseline Visit Day 1 ........................................................................................................ 39 
13.1.3. 
Stool sample collection visit (Day 1 +/- 7 days) ............................................................. 40 
13.1. 
Schedule of activities and evaluations ............................................................................. 41 
13.2. 
Screen failure Re-screening and dropout ......................................................................... 41 
13.3. 
Study assessments ........................................................................................................... 42 
13.3.1. 
Stool Test ......................................................................................................................... 42 
13.3.2. 
Breath Test....................................................................................................................... 42 
13.4. 
Investigational Product Handling .................................................................................... 42 
13.5. 
Investigational Product Accountability ........................................................................... 43 
14. 
Statistical Considerations ........................................................................................................ 43 
14.1. 
Study Design and Objectives ........................................................................................... 43 
14.2. 
Endpoints ......................................................................................................................... 44 
14.2.1. 
Primary Endpoint: Safety ................................................................................................ 44 
14.2.2. 
Secondary Endpoints: Efficacy ....................................................................................... 44 
14.2.3. 
Study Hypotheses ............................................................................................................ 44 
14.3. 
Sample Size ..................................................................................................................... 44 
14.4. 
Randomization ................................................................................................................. 45 
14.5. 
Analysis Sets ................................................................................................................... 45 
14.5.1. 
Full Analysis Set (FA) ..................................................................................................... 45 
14.5.2. 
Per Protocol Analysis Set (PP) ........................................................................................ 45 
14.6. 
Analysis set and their statistical analysis ......................................................................... 45 
14.7. 
Statistical Analysis .......................................................................................................... 46 
14.7.1. 
General Considerations ................................................................................................... 46 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  4 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
14.7.2. 
Demographic and Other Baseline Characteristics ........................................................... 46 
14.7.3. 
Disposition of Subjects .................................................................................................... 46 
14.7.1. 
Safety Analysis ................................................................................................................ 46 
14.7.2. 
Confirmatory Efficacy Analyses ..................................................................................... 47 
14.7.3. 
Handling of Missing Data ............................................................................................... 47 
15. 
Ethics & Regulatory Considerations ....................................................................................... 47 
16. 
Investigator Responsibilities ................................................................................................... 48 
17. 
Safety Considerations .............................................................................................................. 48 
17.1. 
Adverse Event Definitions .............................................................................................. 48 
17.2. 
Serious Adverse Event (SAE), Unanticipated Adverse Device Effect (UADE) and 
Suspected Unexpected Serious Adverse Reactions (SUSAR) ........................................................ 49 
17.3. 
Relationship to Study Medical Product ........................................................................... 50 
17.4. 
Adverse Event Severity ................................................................................................... 50 
17.5. 
Adverse Event Reporting ................................................................................................ 51 
18. 
Access to Source Data and Documents ................................................................................... 52 
18.1. 
Availability of Source Data and Documents ................................................................... 52 
18.2. 
Subject Confidentiality .................................................................................................... 52 
19. 
Monitoring and Quality Assurance ......................................................................................... 52 
19.1. 
Data Collection and Monitoring ...................................................................................... 52 
20. 
Publication Policy and Finance ............................................................................................... 52 
21. 
Financial Aspects..................................................................................................................... 53 
22. 
Study termination .................................................................................................................... 53 
References ........................................................................................................................................... 54 
Appendix A - Protocol Approval Signature Page ............................................................................... 56 
Appendix B – Stool Antigen Test KIT and Procedure ........................................................................ 57 
 
 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  5 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
ABBREVIATIONS 
ACG 
American College of Gastroenterology 
AE 
Adverse Event 
CDER 
Center for Drug Evaluation and Research 
CDRH 
Center for Devices and Radiological 
CFR  
Code of Federal Regulation 
CP 
Conditional Power 
CRF 
Case Report Form 
DOB  
Delta over Baseline 
EC 
Ethics Committee  
EGD 
Esophagogastroduodenoscopy 
EIA 
Enzyme ImmunoAssay test 
ELISA 
Enzyme-linked immunosorbent assay 
FA 
Full Analysis (cohort) 
FAT 
Fecal Antigen Test 
FDA 
Food and Drug Administration 
GCP  
Good Clinical Practice 
GERD 
Gastroesophageal Reflux Disease 
GI 
Gastrointestinal 
H. pylori 
Helicobacter pylori 
HP 
Helicobacter pylori 
ICA 
Immuno-Chromatographic Assays 
ICF 
Informed Consent Form 
ICH 
International Conference of Harmonization 
IDE  
Investigational Device Exemption 
IEC 
Independent Ethics Committee  
IND 
Investigational New Drug 
IRB  
Institutional Review Board 
IVD  
In Vitro Diagnostics 
MD 
Medical Doctor 
NDA 
New Drug Application 
 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  6 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
PP 
Per Protocol  
PPI 
Proton Pump Inhibitor 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SF 
Screen Failure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
UADE 
Unanticipated Adverse Device Effect 
UBT 
¹³C-Urea Breath Test  
US 
United States (of America) 
USA 
United States of America 
 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  7 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
1. PROTOCOL SYNOPSIS 
Protocol Title: 
Clinical Study to Confirm Safety and Accuracy in Detection  
of H. pylori with 13C-Urea Breath Test using the 
BreathID® Hp and BreathID® Hp Lab Systems in the 
Pediatric Population 
Short Title: 
Pediatric Hp study 
Protocol Reference #: 
PED-HP-0616B 
Version and Date: 
Protocol v 2.0, March 12, 2017 
 
Phase of Development: 
Phase III 
 
 
Sponsor and Study 
Monitor: 
Exalenz Bioscience Ltd. 
4 Ha’Maayan Street 
Modi'in, Israel 7177872 
Tel: +972-8-9737500 
Fax: +972-8-9737501 
Investigated Disease: 
Helicobacter pylori infection 
Study Start Date: 
Q2 2017 
Duration of Study: 
Approximately 6 months 
Investigational 
Products (IP): 
BreathID® Hp System (K130524) and BreathID® Hp Lab 
System (K162150) 
IP Details: 
 
1. The BreathID® Hp System (K130524) that uses the 
approved test kit IDkit:Hp™ One in adults, comprised of 
a nasal cannula and the approved 13C-urea/citric acid 
reagent (NDA-21-314).  
2. The BreathID® Hp Lab System (K162150) that uses 
thecleared test kit IDkit:Hp™ Two, comprised of two 
breath sample bags and the approved 13C-urea/citric acid 
reagent (NDA-21-314).  
 
 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  8 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
Study Goal and 
Rationale: 
The goal of this study is to expand the use of the breath test to 
the pediatric population for safety at the dose being tested, 
and effectiveness, to gain indication of the test kits in 
pediatrics. Also, this study will address CDER's request for 
expansion of the use of the 13C-urea and citric acid that is the 
subject of NDA-21-314, to the pediatric population (ages 3-
181). 
Based on a recent guidance document released by the FDA on 
June 21, 2016: Leveraging Existing Clinical Data for 
Extrapolation to Pediatric Uses of Medical Devices, the 
BreathID® Hp System and the BreathID® Hp Lab System, 
meet the main criteria needed for extrapolation of the efficacy 
of clinical data for Pediatric Use: 
a) Relevancy of Adult Data and Similarity of Response: 
The breath test, its kits and the contained test substrate are 
all well established in the adult population (K130524 and 
K162150) using the biopsy composite reference method 
as the gold standard. The H. pylori infection is the same in 
children and adults as H. pylori colonize the stomach in 
humans of all ages. In fact, infection is commonly spread 
to children in the family. The mechanism of detection for 
this breath test is by measuring the activity of the H. 
pylori organisms that split urea and are only present in the 
human stomach. Positive breath testing is indicative of H. 
pylori activity in the subject's stomach, independently of 
the subject's age. This has been confirmed by individual 
investigators and other companies (PMA# P1000254) 
utilizing the composite reference standard(1-3).  
b) Quality of Safety and Effectiveness Data: The clinical 
data collected for the clearance of the BreathID® Hp 
                                                     
1 Subjects 18 years of age and older will not be included in this study.  The age range of 18-21 wasincluded in 
the framework of the adult protocols (any adult over 18) to support this cleared indication in the adult 
population.   


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  9 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
System and the BreathID® Hp Lab System breath tests 
(K130524 and K162150 respectively), were collected in 
accordance 
with 
the 
ethical 
principles 
under 
Investigational Review Board (IRB) approval consistent 
with Good Clinical Practice (GCP) and with the 
applicable regulatory requirements. 
This approach was confirmed by FDA through Pre-Sub 
Q170072. 
This study is thus primarily aimed to confirm tolerance and 
safety of the dose used for the pediatric population. The 
13C-urea and citric acid (NDA-21-314) are contained in 
IDkit:Hp™ One in the BreathID® Hp System (K130524) 
and IDkit:Hp™ Two in the BreathID® Hp Lab System 
(K162150). Additionally the respective means of breath 
collection, the nasal cannula and breath collection bags 
contained in the respective kits, will be confirmed for 
pediatric use. 
Although it is believed that the efficacy of the test can be 
fully extrapolated from the adult data, subject's H. pylori 
status will also be collected as part of this study in order to 
further support and confirm the efficacy of the breath test in 
the pediatric population. 
The safety of the specific drug substance in children at the 
dose utilized in the test setting remains to be established in 
this study. The dose has been proven to be both safe and 
effective in adults in clinical trials as well as in routine 
clinical use in more than 150,000 subjects. 
Upper endoscopy - Esophagogastroduodenoscopy (EGD) is 
generally not standard of care for evaluation of children with 
symptoms associated with H. pylori infection. As such, it is 
difficult to justify performing the procedure which requires 
sedation only for the research purpose. Children are evaluated 
for H. pylori infection most commonly with stool antigen 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  10 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
testing. Therefore, this study proposes to test the drug and its 
dosing in symptomatic children suspected of having H. pylori 
who will undergo both a breath test and an FDA cleared stool 
test. The stool test has a sensitivity and specificity ranging 
from 90 to 97%, and comparing the breath test to the stool 
test results will confirm that the use of this test is reasonable 
in the target population. 
This study will enroll all-comers whether for initial diagnosis 
or 
post-eradication 
testing. 
It 
will 
predominantly 
(approximately 2/3) enroll children under the age of 12 to 
confirm drug/dose tolerance and confirm its efficacy. Older 
children between 12 and 18 years are similar to adults and no 
more than a third (approximately 1/3) will be enrolled from 
this age group. 
Description of Test:  
The ¹³C-Urea Breath Test is performed using a test kit that 
contains 75mg of non-radioactive 13C-urea and citric acid to 
be dissolved in tap water ("solution").  
Exhaled breath will be collected using: 
(1) a nasal cannula for continual passive collection of breath 
samples from the nose before and after ingestion of the 
solution, and/or 
(2) two breath sample bags (orally and actively exhaled 
breath) obtained at two defined time points, before and after 
ingestion of the solution. 
Both exhaled breath collection methods will be performed in 
parallel, and the subject will ingest the solution only once 
after baseline breath collection. 
The subject’s exhaled breath is analyzed and the ratio 
between 13CO2 and 12CO2 is computed. 
The 
BreathID® 
Hp 
System 
using 
the 
cleared 
IDkit:Hp™ One collects breath passively from the subject's 
nostrils via a nasal cannula whose other end is connected to 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  11 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
the device via a luer lock connector.  
The BreathID® Hp Lab System is a modified version of the  
BreathID® Hp System, using IDkit:Hp™ Two enabling up to 
10 pairs of bags (i.e., 2 bags each from 10 separate patient 
sampling events, resulting in 10 tests) to be measured 
consecutively and automatically by means of attaching the 
bags to a dedicated Auto Sampler unit. The bags will be 
collected and measured by the BreathID® Hp Lab System 
within 14 days from the time of collection. 
When using breath sample bags, the initial sample, collected 
immediately before ingesting the 13C-urea/citric acid solution, 
defines the baseline ratio of 13CO2 to 12CO2. The second 
sample, collected 15 to 20 minutes following the 
13C-urea/citric acid solution ingestion, is analyzed to 
determine changes in the 13CO2/12CO2 ratio.  
For both the BreathID® Hp System and the BreathID® Hp 
Lab System, the patient is considered H. pylori positive when 
the difference between the ratios exceeds a predefined and 
previously cleared threshold (in adults) of 5 delta over 
baseline (DOB).  
 
Comparator Details: 
Efficacy of the test can be fully extrapolated from the adult 
data (as confirmed with FDA through Pre-Submission 
Q170072). The goal of this study is thus primarily aimed to 
support expansion of the use of the 13C-urea and citric acid 
that is the subject of NDA-21-314, to the pediatric population 
(ages 3-18) and to confirm tolerance of the dose used for this 
target population. The 13C-urea and citric acid is contained in 
IDkit:Hp™ One (K130524) in the BreathID® Hp System 
and IDkit:Hp™ Two (K162150) in the BreathID® Hp Lab 
System. In addition to safety data that is collected for this 
study, their H. pylori status using the stool antigen test will 
also be collected as a comparator in order to further support 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  12 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
and confirm the efficacy of the breath test. 
As mentioned above, EGD is not standard of care for 
evaluation of children with symptoms associated with H. 
pylori infection. They are evaluated for H. pylori infection 
most commonly with stool antigen testing. This study 
proposes to test the drug and its dosing in symptomatic 
children suspected of having H. pylori who will undergo both 
a breath test and an FDA cleared stool test. This population is 
chosen as they are the target population for the breath test and 
therefore drug use, and their evaluation with the stool test, 
will confirm that the use of this test is reasonable in the target 
population. Stool testing detects H. pylori antigen in stool 
specimens and can be used for diagnosis, therapeutic 
monitoring, and proof of eradication post treatment. 
This study will use the Premier Platinum HpSA PLUS 
(K053335) Enzyme Immunoassay test kit for the detection of 
H. pylori antigen in human stool specimens (Appendix B). It 
will be tested in a central clinical laboratory. 
The stool enzyme immunoassay employs a mixture of 
monoclonal anti-H. pylori antibodies as capture antibody and 
a mixture of peroxidase-conjugated monoclonal anti-H. pylori 
antibodies as detection antibody. Based on the intensity of 
color developed, results are reported as H. pylori antigen 
detected, not detected, or indeterminate. 
A positive result (antigen detected) is indicative of H. pylori 
infection. A negative result (antigen not detected) indicates 
absence of H. pylori or an antigenic level below the assay 
limit of detection.  
Study Design: 
Multi-center, non-randomized, open label study, designed to 
confirm the safety and the efficacy of 13C-urea breath test 
using the BreathID® Hp and BreathID® Hp Lab Systems, as 
appropriate, in pediatric subjects and confirm the efficacy of 
the respective means of breath collection, the nasal cannula 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  13 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
and breath collection bags, in this population compared to  
stool antigen testing. A central lab will analyze the stool 
specimens. Children that cannot inflate the breath collection 
bags adequately may perform the UBT only with nasal 
cannula. All children will be exposed to the same dose of the 
non-radioactive 13C-urea and citric acid. 
Subjects will be enrolled on a walk-in basis. Subjects will be 
treated only based on the established methods used in the 
local routine clinical practice. No patient management 
decisions should be made based on the investigational 
BreathID® Hp and/or BreathID® Hp Lab System test 
outcomes and the investigator and treating physician will 
remain blinded to the BreathID® Hp and/or BreathID® Hp 
Lab System test results until the end of the study. 
Study Population: 
Consecutive pediatric subjects aged between 3 and 18 years 
evaluated by the physician, or presented by referral from 
other institutions or physicians who are clinically indicated to 
undergo H. pylori testing and meet study criteria will be 
enrolled. Distribution of subject's ages will be monitored to 
assure all age ranges are represented, while predominantly 
(approximately 2/3) enrolling children under the age of 12 to 
confirm drug/dose tolerance and confirm its efficacy. 
Consent to participate in the study and to undergo the breath 
test 
procedures 
must 
be 
obtained 
from 
the 
legal 
representative/guardian of every subject following a thorough 
explanation of the study, including the benefits and risks (if 
any). The majority (approximately 2/3) of the subjects will be 
from US centers. Assent will also be obtained from those 
subjects above the age that local regulations require 
consenting/assenting of the child. 
Sites: 
Up to 8 US sites will participate in this study. Non-US sites 
may be included.  


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  14 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
Primary Endpoint: 
Safety Endpoint: 
Adverse event rate: The safety of the 13C-urea/citric acid 
solution has been previously established in adults and in 
children in literature(1-3). Any adverse event (whether related 
or not) will be recorded. There are no safety concerns and no 
adverse events anticipated for the breath test or the stool 
antigen test beyond those already listed in the respective 
labels.  
Secondary Endpoint: 
Efficacy Endpoints: 
I. Overall agreement in diagnosis (presence/absence of H. 
pylori) between the BreathID® Hp System results where 
breath is collected using IDkit:Hp™ One via a nasal 
cannula applying the 5 DOB threshold and stool antigen 
outcome in the pediatric population. 
II. Overall agreement in diagnosis (presence/absence of H. 
pylori) between the BreathID® Hp Lab System results 
when analyzing IDkit:Hp™ Two breath sample bags 
using the 5 DOB threshold and the stool antigen outcome 
in the pediatric population.  
Inclusion Criteria: 
To be eligible to participate in this study, subjects must meet 
the following inclusion criteria: 
• Be older than 3 and younger than 18 years of age 
• Present with a clinical indication compatible with H. 
pylori based on the judgement of the treating 
physician (such as abdominal pain, nausea, diarrhea, 
reflux, peptic ulcer, dyspepsia, etc., or following 
treatment for H.pylori) 
• Subject/Legal 
guardian 
(and 
subject 
whenever 
relevant) 
is 
willing 
to 
sign 
the 
Informed 
Consent/Assent Form 
• Naïve to H. pylori treatment in the past 6 weeks 
 
Exclusion Criteria: 
To be eligible to participate in this study, subjects must NOT 
meet any of the following exclusion criteria: 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  15 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
• Participation in other interventional trials 
• PPI or H2 blockers within two (2) weeks prior to 
breath test/stool antigen test 
• Pregnant or breastfeeding female 
• Allergy to test substrates 
• Antibiotics (not related to H. pylori eradication) 
and/or Bismuth preparations within four (4) weeks 
prior to breath test 
• Exposure to any type of anesthesia, analgesics or 
sedation 24 hours prior to the breath test. 
• Exposure to any 13C-enriched substance 24 hours 
prior to the breath test. 
• Children 12 years and older – to be excluded after a 
written notification from the sponsor is received at the 
site that the limit of 1/3 of the sample size was 
achieved for this group 
• Subjects outside US - to be excluded after a written 
notification from the sponsor is received at the site 
that the limit of 1/3 of the sample size was achieved 
for this group 
 
Exclusion on the day of 
the UBT: 
Subject did not fast for the last hour prior to the UBT 
Statistical 
Considerations: 
This study is designed to confirm safety for the use of the 
13C-urea/citric acid solution used in the cleared Exalenz UBT 
testing using the IDkit:Hp™ One and/or IDkit:Hp™ Two as 
part of BreathID® Hp System and/or BreathID® Hp Lab 
System and to confirm that they have performance measures 
in the pediatric population similar to that of adults. Due to the 
fact that esophagogastroduodenoscopy (EGD) is uncommon 
in pediatrics, the comparator to be used in this trial is stool 
antigen testing, a common test method used to diagnose 
and/or confirm eradication of H. pylori infection in 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  16 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
pediatrics.  
Sample Size: 
The sample size for this study of pediatric subjects with 
indications for H. pylori testing is calculated to allow 
confirmation of both, the primary and secondary study 
endpoints. For the safety assessment, with no related SAE's 
expected, a sample size of 35 evaluable subjects would 
provide an upper confidence limit with less than or equal to 
10% for the 95% two sided confidence limit. In order to 
support the efficacy endpoints a sample size is calculated 
through the width of the two-sided 95% confidence interval 
of the percent overall agreement, such that the lower limit of 
the confidence interval will be greater than or equal to 75% 
with a point estimate of 90%. 
A total of at least 40 evaluable subjects with no less than 5 
positive subjects will be accrued for both breath collection 
methods. If the minimum of 5 positive subjects is not reached 
within the first 40 subjects enrolled, enrolment will continue 
until this minimal number of positive subjects is reached 
(with evaluable UBT results for both breath collection 
methods). 
This will be sufficient to confirm the safety and the utility of 
the BreathID® Hp System and BreathID® Hp Lab System in 
detecting H. pylori infection in pediatric subjects. 
Distribution of subject's ages will be monitored to assure all 
age ranges are represented, while at least two thirds (2/3) of 
the enrolled children will be under the age of 12. 
Site Termination: 
A study site may be terminated after appropriate consultation 
between the study sponsor and the principal investigator. 
Conditions warranting termination include, but are not 
limited to: 
• Failure of the investigator to enroll subjects at an 
acceptable rate 
• Insufficient adherence to protocol requirements 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  17 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
• Decision by the study sponsor to suspend or discontinue 
development of the device and/or kit 
• Failure to adhere to GCP 
• Sponsor decision 
Regulatory 
Considerations: 
The current clinical study will require an IDE as the subject 
receives a drug substance approved for adults but not yet 
approved for those under 18 years of age.  
Study Procedure: 
The clinical study will be conducted in compliance with this 
protocol and in accordance with the ethical principles under 
Investigational Review Board (IRB) and Ethics Committee 
(EC) approvals consistent with Good Clinical Practice (GCP) 
and with the applicable regulatory requirements. 
• The investigator(s) at each site will sign a Protocol 
Approval Page (Appendix A). 
• Patient management will not be affected by the 
BreathID® Hp and/or BreathID® Hp Lab System test 
results and will be based only on the common clinical 
method used. The investigator and treating physician 
will remain blinded to the breath test results until the 
end of the study. 
• Physical examination of the subject and recording of 
demographic data will be completed. 
• The stool antigen test will be performed for each 
subject after at least 2 weeks of refraining from proton 
pump 
inhibitors, 
antimicrobials 
and 
bismuth 
preparations. The test procedure is described in 
Appendix B. 
• Within 1 week before or after the stool antigen test 
and after refraining at least 2 weeks from proton pump 
inhibitors and 4 weeks from antimicrobials and 
bismuth preparations, the subjects will perform the 
UBT by filling two IDkit:Hp™ Two breath collection 
bags, one at each time point (pre-ingestion and 15-20 
minutes post-test solution ingestion) and by having 
breath collected via the IDkit:Hp™ One nasal 
cannula. Subjects unable to fill the breath collection 
bags will perform the breath test with the nasal 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  18 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
cannula only. 
 
• All bags will be analyzed by a BreathID® Hp Lab 
System within 14 days of collection by unmasked 
personnel at the site or by a selected central lab.  
• The breath collected via nasal cannula will be 
analyzed continually by an on-site BreathID® Hp 
System by unmasked personnel. 
• Stool specimens will be sent to a central lab. The site 
coordinator will provide each subject with all supplies 
needed for collection of the stool specimen. The 
specimen will be either collected on-site, brought back 
to the site, brought to a local approved stool collection 
facility or it may be sent directly to a central 
laboratory from the subject’s residence. A requisition 
form will be completed. After confirming that each 
stool antigen sample was sent to the central lab, the 
study coordinator will complete an entry line in a log 
documenting the shipment. 
• An electronic Case Report Form (CRF) will be 
completed for each subject. Any additional diagnostic 
testing performed for the subjects will be recorded. 
• Breath test results will remain non-accessible to the 
investigator. Unmasked site personnel will be trained 
to assure results are not shared. 
 
 


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Screening
ͻ Informed Consent Process
ͻ Screening process
ͻ Verification of Inclusion/Exclusion Criteria
Day 0-7
UBT 1
ͻ Perform Pregnancy test, if applicable
ͻ Perform Urea Breath Test: All subjects will also perform 
continuous breath test via nasal cannula. If subject can inflate 
the breath collection bags, one pair of breath collection bags 
will be collected.  
ͻ Within a week (before or after), perform the stool antigen 
testing
Recording 
Results
ͻ Complete CRF and include all clinical assessments and treatment 
decisions
Sample 
Testing
ͻ Bags will be sent to a central laboratory or on-site and will be tested 
within 14 days from collection
ͻ Stool specimens will be sent to a central lab


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  20 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
3. STUDY SPONSOR  
Exalenz Bioscience Ltd. 
Address: 4 Ha`Maayan St., Modi'in, 7177872, Israel 
Tel: +972−8−9737500 
Fax: +972−8−9737501 
Email: contact@exalenz.com 
US Address: 
Exalenz Bioscience Inc. 
Attn: Raffi Werner, CEO 
35 Colby Ave. Suite #9 
Manasquan, NJ 08736, USA 
Tel: 732-722-8736 
Fax: 732-722-8738 
Email: raffiw@exalenz.com  
 
Each Investigator will sign the protocol approval page (see Appendix A) before study 
initiation at their respective site. 
 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  21 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
4. BACKGROUND  
Helicobacter pylori (H. pylori) infections remain a prevalent chronic problem worldwide. 
Although the prevalence of this infection appears to be decreasing in many parts of the 
world, H. pylori remains an important factor linked to the development of peptic ulcer 
disease, gastric malignancy and dyspeptic symptoms.(4) Whether to test for H. pylori in 
subjects with functional dyspepsia, gastro-esophageal reflux disease (GERD), subjects 
taking non-steroidal anti-inflammatory drugs, with iron deficiency anemia, or who are at 
greater risk of developing gastric cancer remains controversial. According to the American 
College of Gastroenterology (ACG) Guidelines(4) H. pylori can be diagnosed by endoscopic 
or non-endoscopic methods. A variety of factors including the need for endoscopy, pretest 
probability of infection, local availability of testing, and an understanding of the 
performance characteristics and cost of the individual tests influences the choice of 
evaluation in a given patient. Testing to prove eradication should be performed in subjects 
who receive eradication therapy for H. pylori for peptic ulcer disease, individuals with 
persistent dyspeptic symptoms despite the test-and-treat strategy, those with H. pylori-
associated mucosa-associated lymphoid tissue (MALT) lymphoma, and individuals who 
have undergone resection of early gastric cancer.(4) 
Children differ from adults with respect to H. pylori infection in terms of the prevalence of 
the infection, the complication rate, the near-absence of gastric malignancies, age-specific 
problems with diagnostic tests and drugs, and a higher rate of antibiotic resistance2. None 
of these differences are related to the basis of the breath testing. The pathophysiology of the 
infection is the same, colonization of the stomach, and the organisms are the same. 
The clinical study will be conducted in accordance with the ethical principles that have 
their origin in the Declaration of Helsinki, and that are consistent with Good Clinical 
Practices(5) (GCP) and with the applicable regulatory requirements. The clinical protocol 
will be reviewed and approved by the Institutional Review Board/Ethical Committee 
(IRB/EC) at each participating institution or by a central IRB/EC. 
4.1. Helicobacter pylori (H. pylori) Infections in Pediatrics 
Exact estimates of the incidence and prevalence rates of H. pylori infection in children less 
than 18 years of age in the USA are not known at this time. There is evidence that early 
childhood is the critical period of Helicobacter pylori infection, since clustering of the 
                                                     
2 http://emedicine.medscape.com/article/929452-overview  


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  22 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
infection within families suggests a major role of interfamilial transmission(6). However, it is 
well known that the prevalence of peptic ulcer disease in childhood is extremely low. 
Generally, if there is a suspicion of a duodenal ulceration, an esophagogastroduodenoscopy 
(EGD) is performed to confirm the existence of this condition. Large pediatric endoscopy 
centers report an incidence of 5 to 7 children with peptic ulcer disease per year(7). Since 
almost all peptic ulcers in children are located in the duodenum, it is safe to conclude that 
the majority of gastric ulcers (which are extremely rare in children) are usually secondary to 
drugs, Crohn’s disease, cystic fibrosis, etc. Due to the low prevalence of gastric ulcers in 
children, no significant studies have been done to evaluate any possible association between 
gastric ulcers and H. pylori infection in children. 
However, a strong correlation has been shown between duodenal ulceration and H. pylori 
gastritis in children(8). In fact, H. pylori gastritis has been found in 90% to 100% of pediatric 
subjects with duodenal ulcer disease(9). Thus, finding a duodenal ulcer in children in the 
absence of H. pylori gastritis is extremely rare. 
Although the gold standard for H. pylori testing is EGD and biopsy, the most accepted 
method of testing for H .pylori infection in the pediatric population is stool antigen testing. 
Breath testing is also common, but requires specialized laboratories for analysis and active 
breathing into breath collection bags is not always possible in young children. 
In this study, breath testing with a nasal cannula will be performed for all children. This 
method (use of nasal cannula as part of IDkit:Hp™ One) has been used in previous 
pediatric studies with the Exalenz BreathID device(3, 10, 11) and will be further confirmed in 
this study. Those children who can follow the instructions and breathe effectively into breath 
collection bags will also be tested using the IDkit:Hp™ Two breath collection bags.  
4.2. Comparator Details 
Due to the fact that esophagogastroduodenoscopy (EGD) is extremely uncommon in 
pediatrics, the comparator used in this trial is a standard test method used to diagnose H. 
pylori infection in pediatrics; that is: stool antigen testing as assessed by a central pathology 
laboratory. Fecal antigen tests detect antigens in stool samples. Enzyme-linked 
immunosorbent assay (ELISA) formats comprising monoclonal antibodies against H. pylori 
proteins showed improved results compared to polyclonal approaches(12). The current 
guideline evaluates the use of the stool antigen test as equivalent to the UBT if a validated 
laboratory-based monoclonal antibody is used (13). Korkmaz et al. (14) compared the 
diagnostic accuracy of five different stool antigen tests in adult dyspeptic subjects 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  23 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
comparing 
monoclonal 
enzyme 
immunoassay 
tests 
(EIA) 
and 
rapid 
immunochromatographic assays (ICA). The sensitivity and specificity of the tests analyzed 
had a high variation between 48.9%–92.2% and 88.9%–94.4%, respectively, depending on 
the test format. Best results were obtained for Premier Platinum HpSA Plus (which will be 
used in this study) with sensitivity and specificity of 92.2% and 94.4%, respectively. They 
conclude that EIA tests are more accurate compared to the currently available ICA-based 
test, that are fast and easy to use but provide less reliable results(14). A recent meta-analysis 
conducted by Zhou and colleagues analyzed forty-five studies, including 5931 subjects, and 
evaluated the test performance of a H. pylori stool antigen test in children. The average 
sensitivity and specificity was 92.1% and 94.1%, respectively(15). In a study conducted in 
South Korea on 515 subjects comparing the stool antigen test to histology, RUT, 13C-Urea 
breath test and serology, the accuracy of the stool antigen test ranged from 93% to 96%(16). 
Furthermore, the available stool antigen tests have been shown to be able to distinguish 
infected from treated subjects(17, 18), enabling the confirmation of treatment. Degradation of 
antigens in the intestine and consequent disintegration of epitopes might lead to false 
negative results. Moreover, the process of sample handling could be difficult for subjects. 
False negative results may occur when the bacterial load is low, due to proton-pump 
inhibitors or the recent use of antibiotics or bismuth(19, 20). As such, there are limitations in 
eligibility criteria and study procedures in order to reduce the possibility of any potential 
effect by these factors(10).  
4.3. The 13C-Urea Breath Test 
The ¹³C-Urea Breath Test (UBT) is a non-invasive test for detecting the presence of 
Helicobacter pylori (H. pylori) infection by the organism's urease activity. In the presence of 
H. pylori, the ingestion of urea, labeled with the non-radioactive isotope 13C, results in 
production of labeled 13CO2, which can be quantified in exhaled breath.  
A solution containing 13C-urea is given orally. 13C (read as ‘carbon 13’) is a stable, non-
radioactive isotope. In the presence of H. pylori infection, bacterial urease splits the urea to 
produce 13CO2 and ammonia. The 13CO2 diffuses rapidly into the bloodstream and is 
excreted by the lungs. The increase of 13CO2 in breath can be measured and detected by 
specific analyzers (e.g., the BreathID® Hp device). 
Because the normal human stomach is devoid of urease, any gastric urease activity is 
considered to be derived from H. pylori. Therefore, demonstration of urease activity in the 
stomach is a reliable surrogate marker of active H. pylori infection(21). The test aims at 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  24 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
giving reliable results without need for an invasive procedure. UBTs have high accuracy and 
reproducibility because they are functional tests that essentially “sample” the entire stomach; 
they are not prone to the same level of sampling error as biopsy-based tests may be. False 
positive results are uncommon with UBTs(22). The sensitivity and specificity of the breath 
test ranges from 90% to 100%, while in most cases it is above 95%(21, 23-26). Upper 
esophagogastroduodenal (EGD) endoscopy is considered the reference (or gold standard) 
method for the diagnosis of H. pylori infection, as well as UBT(4, 27, 28). For the pediatric 
population, EGD is usually avoided and breath tests or stool antigen tests are generally used. 
Although not pleasant, stool antigen testing is widely used due to the ease and availability of 
the test and its relatively high accuracy (approximately 95%). 
4.4. Breath Analyzing Devices and Breath Collection Methods 
Metabolism of the labeled compound (13C-urea) is assessed by measuring the ratio of 
13CO2/12CO2 in exhaled breath. In order to assess this ratio the breath needs to be collected 
before ingestion of the labeled substrate and after ingestion. Continuous breath collection 
utilizes a nasal cannula connected to a measuring device and is cleared for use in adults 
based on Premarket Notification (K011668, K130524). This method can be especially useful 
in children as the device automatically collects the breath via nasal cannula and does not 
require the child blow forcefully into bags or tubes. When using breath collection bags, the 
two breath samples are collected and then analyzed later by the BreathID® Hp Lab System. 
Systems using this method have been already cleared by the FDA (e.g. K974322, K000316, 
K013371). The method of using breath sample bags in the diagnosis of H. pylori is common 
in the US and in other countries (23), but it requires more subject cooperation in order to fill 
the breath collection bags with adequate breath samples, which can be difficult for young 
children. 
4.4.1. 
Exalenz’ BreathID® Hp System (K130524) 
Exalenz’ established and marketed BreathID® Hp System (K130524) includes the 
BreathID® Hp device, an in vitro diagnostic (IVD) Class I (product code MSQ, 
Microbiology) which is used with the test kit IDkit:Hp™ One cleared in adults.  
The BreathID® Hp device is a modification of the BreathID® System that was originally 
cleared by the FDA in July 2001 (K011668) and utilizes the same test kit, IDkit:Hp™ One. 
This portable device senses CO2 in exhaled breath, and analyzes its different isotopes in 
real-time based on specific optical-radiation emission and absorption by 13CO2 and 12CO2 
gases. The device calculates the change in the 13CO2/12CO2 ratio from exhaled breath1 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  25 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
before and after ingestion of 13C labeled urea and produces a Delta-over-Baseline (DOB3) 
value that is printed out on an automatic printout. The procedure uses a nasal cannula that 
samples the subject’s breath continually and provides an immediate answer within 10 –
 30 minutes for the overall procedure including the ingestion of the 13C labeled substrate. 
Over 150,000 subjects have been assessed worldwide using the BreathID® and BreathID® 
Hp Systems with its test kit - IDkit:Hp™ One. 
Three studies were published using the BreathID device with nasal cannula and 75mg 13C-
urea in over 100 pediatric subjects(2, 10, 11). Furthermore, a similar product has been approved 
for marketing in the pediatric population (PMA# P1000254). As such and as confirmed with 
FDA (Q170072), the UBT with the data obtained for adults can be extrapolated for 
pediatrics and a confirmatory trial is deemed sufficient. 
 
4.4.2. 
Exalenz’ BreathID® Hp Lab System (K162150) 
Exalenz’ recently extended the panel of breath collection methods by establishing and 
obtaining clearance for marketing of the BreathID® Hp Lab System (K162150) to satisfy 
marketing requirements and enable the use of Exalenz 13C-Urea Breath Test with low capital 
costs. The BreathID® Hp System (K130524) was modified to enable breath testing and the 
calculations based on two breath sample bags collected at specified times, instead of using 
the nasal cannula, thereby enabling off site testing when a device is not available for online 
measurements. The test kit, IDkit:Hp™ Two, contains the same 13C-urea/citric acid reagent 
(NDA-21-314) as in the original IDkit:Hp™ One, but instead of a nasal cannula it contains 
two breath sample bags. The bags are specially designed to store the exhaled breath samples 
until analysis for up to 14 days from the time of collection.  
The analyzer unit, the BreathID® Hp device, was modified with software enabling the bag 
measurements. Together with the IDkit:Hp™ Two, an Auto Sampler, and the 
BreathID® Hp Lab Application installed on a standard computer, these components form 
the BreathID® Hp Lab System. The BreathID® Hp Lab System allows consecutive and 
automatic analysis of the IDkit:Hp™ Two breath collection bags. The first sample, collected 
immediately before ingesting the 13C-urea/citric acid solution, defines the baseline ratio of 
                                                     
3 Delta Over Baseline (DOB) is defined as: [(13CO2(n)/ 12CO2(n) - 13CO2(0)/ 12CO2(0) )*1000]/ (13CO2(PDB)/ 12CO2(PDB)), where 
PDB is the standard 13C/12C isotope ratio (=1.1273%);  (0) is the base line measurement and (n) is the measurement of 
interest. DOB ≥ 5 indicate H. pylori infection 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  26 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
13CO2/12CO2. The second sample, collected 15-20 minutes following the 13C-urea/citric acid 
solution ingestion, is analyzed to determine changes in the 13CO2/12CO2 ratio. 
 
4.5. Rationale of performing UBT with two methods of breath collection 
Although 13C-urea breath tests have been in use for over three decades, most testing has been 
with breath collection bags or test tubes. The procedure using the BreathID® and BreathID® 
Hp Systems with a nasal cannula (IDkit:Hp™ One) where the subject’s breath is 
continually collected has the advantage of providing an immediate answer within 10 –
 20 minutes. This is also advantageous in children who have difficulty exhaling actively into 
breath collection bags. To facilitate testing in clinics that cannot accommodate a BreathID® 
Hp System on site, and allow higher volumes of testing, Exalenz has developed an 
additional test kit, the IDkit:Hp™ Two, that incorporates the same 13C-labeled urea tablet 
and citric powder (approved under NDA-21-314) as IDkit:Hp™ One, but instead of using a 
nasal cannula for breath collection, a pair of breath sample bags are used. The bags are 
specially designed to store the exhaled breath samples until analysis for up to 14 days from 
the time of collection.  
The pair of filled breath sample bags will be analyzed using the BreathID® Hp Lab System.  
5. INTENDED USE BREATHID® HP SYSTEM 
The Exalenz BreathID® Hp System is intended for use to continually and non-invasively 
measure changes in the 13CO2/12CO2 ratio of exhaled breath, which may be indicative of 
increased urease production associated with active Helicobacter pylori (H. pylori) infection 
in the stomach. The Exalenz BreathID® Hp System is indicated for use as an aid in the 
initial diagnosis and post treatment monitoring of H. pylori infection in adult and pediatric 
patients. The Exalenz BreathID® Hp System consists of the IDkit: Hp™ One and the 
BreathID® Hp test device. 
The device is for use by trained health care professionals. To be administered under a 
physician’s supervision. 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  27 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
6. INTENDED USE BREATHID® HP LAB SYSTEM 
The Exalenz BreathID® Hp Lab System is intended for use to non-invasively measure 
changes in the 13CO2/12CO2 ratio of exhaled breath, which may be indicative of increased 
urease production associated with active H. pylori infection in the stomach. The Exalenz 
BreathID® Hp Lab System is indicated for use as an aid in the initial diagnosis and post 
treatment monitoring of H. pylori infection in adult and pediatric patients. The Exalenz 
BreathID® Hp Lab System consists of the IDkit: Hp™ Two kits, and the BreathID® Hp 
device, Auto Sampler and Lab Application.  
The device is suitable for use in both point of care and clinical laboratory settings. To be 
administered by trained personnel as ordered by a licensed healthcare practitioner. 
7. BREATHID® HP SYSTEM – DESCRIPTION  
The BreathID® Hp System is a stand-alone table top device for real-time breath testing. The 
device includes custom imbedded software specifically for use with the intended application. 
The user screen provides self-explanatory messages that lead the user through the test 
procedure. The operation is via a touch screen and the subject is connected to the device 
with a nasal cannula. This device provides a printout with the final DOB result automatically 
when the test is completed after a maximum of 20 minutes. A detailed description of the 
device and its operation appear in the Operator Manual. 
Figure 1: The BreathID® Hp System 
 
 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  28 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
The device elements are summarized in the following table:  
Element 
Description 
Device Display 
The device display is located on the front panel and is the user interface of 
the BreathID® Hp. All BreathID® Hp controls, instructions, and 
messages appear on this screen. Controls may be selected by touching the 
screen. 
IDcircuit/Input 
Connector 
The IDcircuit or Bag Adaptor is connected here. The IDcircuit/Input 
Connector has a protective cover that covers the breath entry port when 
the BreathID® Hp is not in use. 
Printer 
The printer is located to the right of the screen. 
BreathID® Hp LED 
Indicator 
There is a Green indicator LED located on the front panel of the 
BreathID® Hp. 
USB Port 
The USB port is located on the front panel (above the screen) and is used 
for connecting the Exalenz Flash Drive to the BreathID® Hp. 
Power ON/OFF 
Switch 
This switch is located on the back of the device.  
AC Connector 
The AC Connector is located on the back panel of the BreathID® Hp. 
The AC power cord is attached to this connector.  
Printer LED 
Indicators 
There are two indicator LEDs located on the printer. 
Printer Controls 
There are two controls located on the printer. One is used to advance the 
paper feed, and one is used to cut the printer paper. 
Printer Open Button 
Pressing this button opens the printer compartment cover. 
 
The BreathID® Hp System is used with the IDkit:Hp™ One. The following materials are 
included in this kit:  
• One 75 mg tablet 13C-enriched urea 
• One packet of granulated Citrica (4 gram of artificially sweetened citric acid powder) 
• One stirring and drinking straw 
• One Package insert for the breath test 
• IDcircuit (nasal cannula)  


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  29 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
Required materials not provided: 
• Drinking cup 
• Tap water 
8. BREATHID® HP LAB SYSTEM TEST – DESCRIPTION AND 
COMPONENTS 
The BreathID® Hp Lab System (P/N VS01082) is suitable for Clinical Laboratory settings. 
It is to be administered by trained personnel as ordered by a licensed healthcare practitioner.  
As previously mentioned, the BreathID® Hp Lab System consists of the IDkit:Hp™ Two 
kits and the BreathID® Hp Lab device, Auto Sampler and Lab Application. The 
components of the BreathID® Hp Lab System are described below: 
1. BreathID® Hp Lab device - a table top device weighing approximately 33 lbs (15kg) 
(Figure 1). The user screen on the device is inactive, and the user interface is on the 
screen of the computer on which the BreathID® Hp Lab Application is installed. 
The device includes custom embedded software specifically for use with the 
intended application.  
Figure 2: The BreathID® Hp Lab device 
 
2. Auto Sampler - a free standing module connected to the device with 20 ports for 
loading up to 10 sets of breath collection bags (Figure 3). The breath sample transfer 
to the BreathID® Hp device is controlled and synchronized by the Lab Application.  


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  30 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
Figure 3: The BreathID® Hp - Auto Sampler 
 
 
3. BreathID® Hp Lab Application/Work station - a personal computer that contains 
specialized software that controls the entire system and provides a touch - sensitive 
user screen for the operator. The Lab Application controls and synchronizes between 
the Auto Sampler and the BreathID® Hp Lab device. The Lab Application also 
instructs the user on performing bag tests and displays the results obtained from the 
device.  
4. IDkit:Hp™ Two breath sample bags - The entire list of components of this kit will 
be described in the next section. The breath sample bags are part of the 
IDkit:Hp™ Two and are used to collect the subject’s breath at baseline, before 
ingestion of the test drink, and 15 minutes (and no more than 20 minutes) post 
ingestion. They can be measured at a later time up to 14 days following collection 
and at any location with the equipment described above.  
 
 
Figure 4: IDkit:Hp™ Two breath sample bags 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  31 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
5. Components of IDkit:Hp™ Two 
The IDkit:Hp™ Two  kit components: 
a. Two breath sample bags4 (baseline and post ingestion) 
b. One 75 mg tablet 13Cenriched urea 
c. One packet of granulated Citrica (4 gram of artificially sweetened citric acid 
powder) 
d. One stirring/ drinking straw  
e. One large sample transport bag provided to store/ship both breath sample 
bags 
f. One Quick User Guide showing the basic steps of administering the test 
 
Figure 5: Components of the IDkit:Hp™ Two 
 
Required materials not provided: 
• Drinking cup 
• Tap water 
• Timer 
 
Note: In this study, IDkit:Hp™ Two will be used, with the addition of a nasal cannula 
(part of IDkit:Hp One). 
                                                     
 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  32 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
9. STUDY DESIGN  
Multi-center, non-randomized, open label study, designed to confirm the safety and the 
efficacy of 13C-urea breath test using the BreathID® Hp and the BreathID® Hp Lab 
Systems in pediatric subjects and confirm the efficacy of the respective means of breath 
collection, the nasal cannula and breath collection bags, in this population compared to stool 
antigen testing. A central lab will analyze the stool specimens. Children, that cannot inflate 
the breath collection bags, may perform UBT only with nasal cannula. All children will be 
exposed to non-radioactive 13C-urea and citric acid. 
Subjects will be enrolled on a walk-in basis. Subjects will be treated only based on the 
established methods used in clinical practice. No patient management decisions should be 
made based on the investigational BreathID® Hp and/or BreathID® Hp Lab Systems test 
outcomes and the investigator and treating physician will remain blinded to the 
BreathID® Hp and/or BreathID® Hp Lab System test results until the end of the study. 
Appropriate measures will be taken to maintain blinding. 
A minimum of 40 evaluable, with at least 5 infected, subjects will be accrued. If the 
minimum of 5 positive subjects is not reached within the first 40 subjects enrolled, 
enrollment will continue until this minimal number of positive subjects is reached (with 
evaluable UBT results for both breath collection methods). The actual number of recruited 
subjects may be slightly higher due to parallel recruiting in multiple sites. The main 
eligibility criteria for the trial are subjects that have a clinical indication for H. pylori testing 
and are naïve to H. pylori treatment in the past 6 weeks. 
10. BREATH TESTING PROCEDURE  
10.1. 
Collecting the Breath Samples 
Prior to filling the bags, complete all fields including the subject number and initials (except 
for filling times that will be written immediately after filling the bags) on the bag 
identification label (blue BASELINE and gray POST INGESTION breath bags) and write 
subject’s number and initials on both bags.  
All subjects will undergo the breath test using the IDkit:Hp One nasal cannula. The 
unmasked study personnel will perform this test and the print out will be kept in a separate 
binder with no access for the investigator and/or treating physician. Subjects that can and are 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  33 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
willing to exhale into IDkit:Hp™ Two breath collection bags, will breathe into them in 
parallel as described below.  
I. 
Bag filling of baseline breath sample (only for those subject able to fill the 
breath collection bags): 
Ask the subject to take a deep breath, wait 4 - 5 seconds and then exhale into the blue 
BASELINE breath bag. Ascertain that the cap of the bag is returned securely into place 
until it clicks, after filling the breath collection bag. 
II. 
Beginning test on the BreathID® Hp System: 
Connect the IDcircuit (nasal cannula) using the following procedure: 
 
 
 
                            
 
1. Slide the tubing sleeve down and place the cannula tips gently into the subject’s 
nostrils, with the lip guards placed on the upper lip. Place the cannula tubing over 
the ears. 
2. Slide the tubing sleeve up toward the neck to fit comfortably under the chin. 
3. Twist one orange connector clockwise securely into the device as shown.  
4. Verify that the IDcircuit is not twisted or kinked, and that the cannula tips are in 
the nostrils. 
Note: Subject should breathe normally throughout the test and refrain from talking.  
5. Press the Start button on the device to proceed and measure baseline. This will 
usually take 2 minutes but may take up to 12 minutes when calibration is 
necessary. 
 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  34 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
III. 
Preparation and Administration of the Test Drink  
Note: Administer the test drink within two hours of preparation, as this is the maximal 
time for maintaining solution stability. 
1. Empty the contents of the packets with Citrica and with 13C-enriched urea tablet 
in 150 to 200 ml (5.1 to 6.8 oz) of tap water in a single drinking cup of at least 
236 ml (8 oz.) in capacity. 
2. Stir thoroughly with the provided straw for a few minutes until the Citrica 
powder and the 13C-urea tablet are completely dissolved. Keep the stirring straw 
in the cup to serve for drinking. 
Note: Tiny particles may remain visible after thorough mixing. However, if more 
substantial particulate matter is still present after five minutes, discard the 
solution and repeat the procedure with a new kit. 
3. Administer solution to the subject when Citrica powder and urea tablet are 
completely dissolved and begin measuring 15 minutes.  
4. Record the time of ingestion on the blue BASELINE breath bag. 
IV. 
Collecting Breath samples after ingestion of the test substrate  
1. Immediately after the subject finishes drinking the solution, press the Start button 
on the BreathID® Hp System screen to proceed. 
2. At least 15 minutes after the administration of the test drink (but not later than 
20 minutes after administration), ask the subject to take a deep breath, wait 4-5 
seconds and then exhale into the gray POST INGESTION breath bag. Ascertain 
that the cap of the bag is returned securely into place until it clicks.  
3. Record the actual time filled on the gray breath POST INGESTION bag. 
4. Once the BreathID® Hp System has completed the measurement it will prompt 
the user to disconnect the cannula. Please remove it from the subject's nostrils 
and twist the orange connector counterclockwise removing it from the device. 
The used cannula should be discarded according to local operating procedures for 
disposal of medical waste. 
V. 
Storage of Bags for future measurement 
Assure that all fields are complete on the breath sample bag labels, for future 
identification. The bags should be stored until they are tested at room temperature in a 
safe place where they will not get destroyed or be exposed to high pressure. 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  35 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
10.2. Measuring Bags 
The bags will be measured by the BreathID® Hp Lab System whose operators will be 
trained prior to performing measurements of the bags by authorized Exalenz personnel 
according to the BreathID® Hp Lab System Operator Manual. 
The bags should be measured within 14 days.  
After testing, although the bags were not designed for re-testing, all bags should be stored 
under the same conditions for potential collection by the sponsor for research purposes. 
When instructed by the Sponsor in writing, they may be discarded.  
11. STUDY OBJECTIVES  
This study is primarily designed to confirm tolerance of the dose used for the pediatric 
population. The 13C-urea and citric acid (NDA-21-314) are contained in IDkit:Hp™ One in 
the BreathID® Hp System (K130524) and IDkit:Hp™ Two in the BreathID® Hp Lab 
System (K162150). Additionally the efficacy of the respective means of breath collection, 
the nasal cannula contained in IDkit:Hp™ One and breath collection bags contained in 
IDkit:Hp™ Two, will be confirmed to be similar in the pediatric population as that of 
adults. 
Three studies were published using the BreathID device with nasal cannula and 75mg 13C-
urea in over 100 pediatric subjects(2, 10, 11). As such, the UBT with the data obtained for 
adults can be extrapolated for pediatrics (as confirmed with FDA through Q170072) and a 
confirmatory trial is deemed sufficient.  
11.1. 
Primary Objective: Safety 
The safety of the 13C-urea/citric acid solution has been previously established in adults and 
in children in literature.(1-3)Any adverse event (whether related or not) will be recorded. 
There are no safety concerns and no adverse events anticipated for the breath test or the stool 
antigen test beyond those already listed in the respective labels..  
11.2. 
Secondary Objectives: Confirmation of Efficacy 
1. To confirm overall agreement measures with lower 95% confidence limit ≥75% 
for the BreathID® Hp System where breath is collected via a IDkit:Hp™ One 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  36 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
nasal cannula using the 5 DOB threshold in pediatric subjects (presence/absence 
of H. pylori) compared to stool antigen testing. 
2. To confirm overall agreement measures with lower 95% confidence limit > 75% 
for the BreathID® Hp Lab System when analyzing IDkit:Hp™ Two breath 
sample bags using the 5 DOB threshold in pediatric subjects (presence/absence 
of H. pylori) compared to stool antigen testing.  
12. SUBJECT SELECTION 
Consecutive pediatric subjects aged between 3 and 18 years of age evaluated by the 
physician, or presented by referral from other institutions or physicians who are clinically 
indicated to undergo H. pylori testing and meet study criteria will be enrolled. Distribution 
of subject's ages will be monitored to assure all age ranges are represented. To confirm 
safety and performance of the tests in younger children, this study will predominantly 
(approximately 2/3) enroll children under the age of 12 to confirm drug/dose tolerance and 
safety and confirm its efficacy. 
Consent to participate in the study and to undergo the breath test procedures must be 
obtained from the legal representative/guardian of every subject following a thorough 
explanation of the study, including the benefits and risks (if any). The majority 
(approximately 2/3) of the subjects will be from US centers. Assent will also be obtained 
from those subjects above the age that local regulations require consenting of the child. 
All subjects screened will be documented in a screening log, regardless of subsequent entry 
into the study. Reasons for non-inclusion will be recorded. 
12.1. 
Inclusion Criteria  
To be eligible to participate in this study, subjects must meet all of the following inclusion 
criteria: 
• Be older than 3 and younger than 18 years of age 
• Present with clinical indication compatible with H. pylori based on the 
judgement of the treating physician (such as abdominal pain, nausea, 
diarrhea, reflux, peptic ulcer, dyspepsia, etc., or following treatment for 
H.pylori) 
• Subject/Legal guardian (and subject when relevant) is willing to sign the 
Informed Consent/Assent Form 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  37 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
• Naïve to H. pylori treatment in the past 6 weeks 
12.2. 
Exclusion Criteria  
To be eligible to participate in this study, subjects must not meet any of the following 
exclusion criteria: 
• Participation in other interventional trials 
• PPI or H2 blockers within two (2) weeks prior to breath test/stool antigen test 
• Pregnant or breastfeeding female 
• Allergy to test substrates 
• Antibiotics (not related to H. pylori eradication) and/or Bismuth preparations 
within four (4) weeks prior to breath test 
• Exposure to any type of anesthesia, analgesics or sedation 24 hours prior to 
the breath test. 
• Exposure to any 13C-enriched substance 24 hours prior to the breath test. 
• Children 12 years and older – to be excluded after a written notification from 
the sponsor is received at the site that the limit of 1/3 of the sample size was 
achieved for this group 
• Subjects outside US – to be excluded after a written notification from the 
sponsor is received at the site that the limit of 1/3 of the sample size was 
achieved for this group 
12.3. 
Exclusion Criteria for Day of Urea Breath Test 
• Subject did not fast for the hour prior to the UBT 
12.4. 
Consenting 
Subject's legal guardian(s) will sign a consent form prior to study participation.  
Subjects, old enough according to local regulations, to understand and sign an assent will do 
so prior to study participation. 
The consent/assent will include willingness to share pertinent blood, clinical and imaging 
data that appear in the subject's health record and incorporate all data from time of 
enrollment until the subject's termination of the study. 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  38 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
12.5. 
Termination of Subjects  
The study subject may be terminated in an individual case by the subject or his/her legal 
guardian if for some reason after giving written consent/assent, the subject or his/her legal 
guardian wishes to withdraw and/or discontinue his/her participation in the study. This will 
not have any effect on the treatment that he/she receives. 
12.6. 
Early Withdrawal from the Study 
Subjects, their relatives, their representatives or the subjects’ physician may withdraw the 
subject from the study at any time if they feel the study is not in the subjects’ best interest, 
or they may be withdrawn by the investigator or sponsor for safety, compliance issues, or 
administrative reasons. All withdrawals will be fully documented as to time and cause. 
If the subject or his/her legal guardian withdraws from the study and also withdraws consent 
for the disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. This will not have any effect on the treatment that the 
subject receives. The subject’s data that have been collected until the time of withdrawal 
will be retained and analyzed. 
12.7. 
Expected Duration of Recruitment 
The study is planned for a duration of approximately 6 months.  
13. STUDY ASSESSMENTS AND PROCEDURES 
13.1. 
Study Visits 
The clinical study will be conducted in compliance with this protocol and in accordance 
with the ethical principles under Investigational Review Board (IRB) or Helsinki 
committee approval consistent with Good Clinical Practice (GCP) and with the 
applicable local regulatory requirements. 
The investigator(s) at each site will sign a Protocol Approval Page (Appendix A). 
Screening and Baseline can be performed at the same visit 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  39 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
13.1.1. Screening Visit (can be done up to 37 days prior to the 
breath test) 
1. The legal guardian (and subject if applicable) will sign the consent/assent form 
prior to performing any study related procedures. The child will sign the assent 
form if, based on his age, local regulations require the child to sign the form. 
2. The investigator(s), co-investigator(s) or study coordinator will record: 
•  Demographic information. 
• Medical history including information regarding H. pylori results. 
• Concomitant medications (starting 6 weeks prior to the planned breath 
test/stool test)  
This will be performed for each subject in order to establish compliance with the 
inclusion and exclusion criteria. 
13.1.2. Baseline Visit Day 1 
1. The investigator(s), co-investigator(s) or study coordinator will record any 
changes from screening visit in medical history including changes in concomitant 
medications (starting 6 weeks prior to the breath test/stool test) for each subject 
to establish compliance with the inclusion and exclusion criteria. 
2. Physical examination including height and weight of the subject will be 
performed. 
3. A urine pregnancy test will be performed for females of childbearing potential 
who did not have a pregnancy test within 7 days prior to the breath test. 
4. Inclusion and exclusion criteria will be checked. 
5. Only once the subject’s eligibility has been confirmed, and after refraining at 
least 2 weeks from proton pump inhibitors and 4 weeks from antimicrobials and 
bismuth preparations, the subjects will perform the UBT (according to the 
procedure described in Section 10 above) by filling two IDkit:Hp™ Two breath 
collection bags, one at each time point (pre-ingestion and 15-20 minutes post-test 
solution ingestion) and by having breath collected via the IDkit:Hp™ One nasal 
cannula. Subjects unable to fill the breath collection bags will perform the breath 
test with the nasal cannula only.  


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  40 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
6. Adverse events will be recorded, accounting for the rules of assessment and 
documentation (see Section 17 below). 
7. Breath collection bags will be analyzed by the BreathID® Hp Lab System within 
14 days of collection either on site or at a central laboratory. When relevant, the 
site coordinator will arrange shipment of the breath collection bags to a central 
laboratory, including a completed requisition form. The name and the address for 
the central laboratory service provider can be found in the respective 
documentation.  
8. The investigator and treating physician will remain blinded until the end of the 
study and patient management will not be affected by the breath test results. 
 
This visit can be combined with screening visit and performed on the same day. 
13.1.3. Stool sample collection visit (Day 1 +/- 7 days) 
1. The stool antigen test will be performed within 7 days before or after the UBT 
and after at least 2 weeks of refraining from proton pump inhibitors & H2 
blockers and 4 weeks of refraining from antimicrobials and bismuth preparations. 
The test procedure is described in Appendix B. 
 
2. Stool specimens will be sent to a central lab. The site coordinator will provide 
each subject with all supplies needed for collection of the stool specimen. The 
specimen will be either collected on-site, brought back to the site, brought to a 
local approved stool collection facility or it may be sent directly to a central 
laboratory from the subject’s residence. A requisition form will be completed.  
After confirming that each stool antigen sample was sent to the central lab, the 
study coordinator will complete an entry line in a log documenting the shipment. 
The name and the address for the central laboratory service provider can be 
found in the respective documentation 
 
3. Adverse events will be recorded, according to rules of assessment and 
documentation defined in Section 17 below). 
The visit can be combined with the Breath Test visit and/or with the 
Screening visit and performed on the same day. 
For each subject tested, an individual set of electronic Case Report Forms (CRFs) will be 
completed. 
The Sponsor will notify the sites when to commence and stop recruitment. 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  41 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
13.1. 
Schedule of activities and evaluations 
Visit 
Screening 
Baseline Day 1 
Stool Testing 
Day 
Up to 37 days 
prior to the 
breath test 
0-7 
UBT +/- 7 days 
Informed consent 
Including Assent if applicable  
X 
 
 
Inclusion & exclusion criteria  
X 
X 
X 
Demographic information 
X 
 
 
Medical history 
information regarding previous H. pylori results 
X 
X 
 
Prior and concomitant medications (starting 6 
weeks prior to the Stool Test/UBT) 
X 
X 
X 
Physical examination including height and weight  
 
X 
 
Urine pregnancy test 
 
X 
 
Adverse event assessment  
 
X 
X 
UBT - ¹³C-Urea Breath Test (cannula & bags) 
 
X 
 
Stool Testing 
 
 
X 
Note:  
Screening visit can be combined with Day 1 visit and performed on the same day. 
Stool test visit can be combined with Day 1 visit or screening visit and performed on the same day. 
Breath collection bags will be tested within 14 days after UBT visit. 
13.2. 
Screen failure Re-screening and dropout 
Every subject for whom an Inform Consent/Assent Form was signed and withdrew from the study 
for any reason prior to the UBT or stool test will be defined as a Screen Failure. 
Re-screening will be allowed once for each subject. 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
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Every subject for whom  an Inform Consent/Assent Form was signed and withdrew from the study 
for any reason after UBT and/or stool testing started will be defined as dropout/early termination. 
The cause of each such case will be recorded. 
13.3. 
Study assessments 
13.3.1. 
Stool Test  
The stool specimens will be sent to a central lab. The site coordinator will provide each 
subject with all supplies needed for collection. The specimen will be either collected on-site, 
brought back to the site, brought to a local approved stool collection facility or it may be 
sent directly to a central laboratory from the subject’s residence. A requisition form will be 
completed. After confirming that each stool antigen sample was sent to the central lab, the 
study coordinator will complete an entry line in a log documenting the shipment. The central 
lab will proceed in the analysis of the specimen according to the stool test manufacturer's 
instructions. 
13.3.2. 
Breath Test 
The results from the BreathID® Hp System will be printed out immediately after the test and 
will serve as source data for the CRF completion. Appropriate measures will be taken to 
maintain blinding of the investigator and treating physician to the breath test results. The 
breath test collection bags will be measured within 14 days of collection using the 
BreathID® Hp Lab System according to the respective User Manual. 
13.4. 
Investigational Product Handling  
The Investigator and/or Research Pharmacist (as appropriate per site) will be provided with 
guidance regarding the packaging and labeling requirements, receipt of investigational 
product, dispensing and accountability procedures, preparation instructions, storage and 
stability of Investigational product, Disposition of Investigational Product, with the 
following forms required: Proof of receipt form, Temperature logs, Accountability logs, 
Investigational product and material transfer/disposition form and pharmacy staff 
identification log (if applicable).  
The kits containing the substrate should be stored at room temperature (15-30°C, 59-86°F), 
in a restricted area or cabinet, and will be inaccessible to unauthorized personnel. The 
sponsor should be notified regarding any temperature excursion on site, and the substrate 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
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should be kept in quarantine until a written approval from the sponsor that the substrate can 
be used has been received.  
Local forms may be authorized for use after being approved by the Sponsor or his assigned 
representative. 
13.5. 
Investigational Product Accountability 
The Investigator or their designee, are responsible for ensuring that all study supplies 
received at the site are inventoried and accounted for throughout the study. The dispensing 
of study test kits for the individual subject must be documented in the respective 
accountability form. The study Investigational Product must be handled in strict accordance 
with the protocol, GCP and GMP requirements, and the container label and will be stored in 
a limited access area or in a locked cabinet under appropriate environmental conditions. 
Unused study materials must be available for verification by the sponsor’s site monitor 
during on-site monitoring. Used packages of the substrate should also be kept for 
accountability purposes and will be destroyed at the site only after accountability is 
completed by the sponsor. The destruction of unused study materials (both, expired or 
unexpired) will be documented on the return/disposition form. The Sponsor will authorize 
destruction of excess supplies on site according to local policy. In this case, before 
proceeding, the site must seek written authorization from the Sponsor using the 
return/destruction form and this must also be documented on the Study Supply Return Form. 
Study test solutions should be dispensed under the supervision of the investigator, a 
qualified member of the investigational staff, or by the hospital clinical pharmacist. 
14. STATISTICAL CONSIDERATIONS 
14.1. 
Study Design and Objectives 
The study is designed as multi-center, open label study, designed to confirm the safety and 
the efficacy of 13C-urea breath test using the BreathID® Hp and BreathID® Hp Lab 
Systems in pediatric subjects and confirm the efficacy of the respective means of breath 
collection, the nasal cannula and breath collection bags, in this population compared to  stool 
antigen testing. A central lab will analyze the stool specimens. Children, that cannot inflate 
the breath collection bags, may perform UBT only with IDkit:Hp One nasal cannula. All 
children will be exposed to non-radioactive 13C-urea and citric acid. Subjects will be 
enrolled on a walk-in basis. Subjects will be treated only based on the established methods 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  44 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
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used in the local routine clinical practice and the investigator and treating physician will 
remain blinded to the breath test results until the end of the study. 
14.2. 
Endpoints 
14.2.1. 
Primary Endpoint: Safety 
Adverse event rate: The safety of the 13C-urea/citric acid solution has been previously 
established in adults and in children in literature(1-3). Any adverse event (whether related or 
not) will be recorded. There are no safety concerns and no adverse events anticipated for the 
breath tests.  
14.2.2. 
Secondary Endpoints: Efficacy 
1. Overall agreement in diagnosis (presence/absence of H. pylori) between the 
BreathID® Hp System results where breath is collected using IDkit:Hp™ One 
via a nasal cannula applying the 5 DOB threshold in pediatric subjects and stool 
antigen outcome or biopsy results in the pediatric population. 
2. Overall agreement in diagnosis (presence/absence of H. pylori) between the 
BreathID® Hp Lab System results when analyzing IDkit:Hp™ Two breath 
sample bags using the 5 DOB threshold in pediatric subjects and the stool antigen 
outcome or biopsy results in the pediatric population.  
14.2.3. 
Study Hypotheses 
In this study, the following two sets of hypotheses will be evaluated for both the IDkit:Hp 
One used with the BreathID® Hp System and IDkit:Hp™ Two used with the BreathID® 
Hp Lab System. 
• H0: Overall agreement < 75% 
• H1: Overall agreement ≥ 75% 
14.3. 
Sample Size 
The sample size for this study of pediatric subjects with indications for H. pylori testing is 
calculated to allow confirmation of both, the primary and secondary study endpoints. For the 
safety assessment, with no related SAE's expected, a sample size of 35 evaluable subjects 
would provide an upper confidence limit with less than or equal to 10% for the 95% two 
sided confidence limit. In order to support the efficacy endpoints a sample size is calculated 
through the width of the two-sided 95% confidence interval of the percent overall 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  45 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
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agreement, such that the lower limit of the confidence interval will be greater than or equal 
to 75% with a point estimate of 90%. 
A total of at least 40 evaluable subjects with no less than at least 5 positive subjects will be 
accrued for both breath collection methods. If the minimum of 5 positive subjects is not 
reached within the first 40 subjects enrolled, enrolment will continue until this minimal 
number of positive subjects is reached (with evaluable UBT results for both breath 
collection methods).  
This will be sufficient to confirm the safety and the utility of the BreathID® Hp System and 
BreathID® Hp Lab System in detecting H.pylori infection in pediatric subjects. 
Distribution of subject's ages will be monitored to assure all age ranges are represented, 
while predominantly (approximately 2/3) enrolling children under the age of 12. 
14.4. 
 Randomization 
The study is an open label study, and is not randomized. 
14.5. 
Analysis Sets 
14.5.1. 
Full Analysis Set (FA) 
The Full Analysis (FA) set includes all subjects who were enrolled and underwent study 
tests (BreathID® Hp System when using IDkit:Hp™ One nasal cannula and/or 
BreathID® Hp Lab System when using IDkit:Hp™ Two breath sample bags and stool 
antigen testing). 
14.5.2. 
Per Protocol Analysis Set (PP) 
The Per-Protocol (PP) analysis set includes all subjects from the FA analysis set without any 
major protocol deviation.  
14.6. 
Analysis set and their statistical analysis 
The FA analysis set will serve as the analysis set for performance and safety assessments. 
The confirmatory performance assessment will also be performed on the PP analysis set.  


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  46 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
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14.7. 
Statistical Analysis  
14.7.1. 
General Considerations 
Statistical analyses will be performed using SAS® v9.4 (SAS Institute, Cary NC, USA). 
If any statistical tests are performed, they will be two-sided. The required significance level 
of findings will be equal to or lower than 5%. Where confidence limits are appropriate, the 
confidence level will be 95%. 
Baseline values are defined as the last valid value prior to study start. 
All statistical analyses of safety and performance measures will be descriptive in nature. 
Continuous variables will be summarized by a mean, standard deviation, minimum, median 
and maximum, and categorical variables by a count and percentage. Confidence intervals 
will be provided where relevant.  
If multiple measurements are taken in a single subject, statistics described below will be 
appropriately modified to accommodate the within subject correlation.  
14.7.2. 
Demographic and Other Baseline Characteristics 
Demographic, medical and clinical history variables will be tabulated. Continuous variables 
will be summarized by a mean, standard deviation, minimum, median and maximum, and 
categorical variables by a count and percentage. 
14.7.3. 
Disposition of Subjects 
The numbers of subjects who were enrolled will be provided, as well as the reasons for all 
enrollment discontinuations, grouped by major reason (e.g., lost to follow-up, adverse event, 
poor compliance). A list of discontinued subjects, protocol deviations, and subjects excluded 
from the efficacy analysis will be provided as well. 
14.7.1. 
Safety Analysis 
Any events related to study drug and/or device AE’s rate will be presented along with a 95% 
exact binomial two sided 95% confidence interval. The analysis of all adverse events will 
include incidence tables and will include analyses by severity, relationship to device or drug 
and baseline variables. 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  47 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
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14.7.2. 
Confirmatory Efficacy Analyses 
A 2x2 table of the results comparing the positive/negative results obtained from the 
BreathID® Hp System and for the results of the BreathID® Hp Lab System applying the 5 
DOB threshold and the stool antigen test results will be presented (each system compared 
separately to the stool antigen testing).  
The confirmatory efficacy analysis will present the estimation of overall agreement (% on 
diagonal) with its two-sided 95% exact confidence intervals. If the lower limits of the two 
sided 95% confidence interval of the overall agreement are greater than or equal to 75%, the 
null-hypotheses will be rejected and we will have shown the breath test to be effective for 
the diagnosis of H. pylori. This will be performed for each breath collection method 
individually. 
Positive and negative percent agreement will also be presented together with respective 95% 
confidence intervals. 
Poolability of the data from the study sites will be assessed. 
14.7.3. 
Handling of Missing Data 
Measurements with unknown values or unavailable estimates will be treated as missing 
values and excluded from the analysis. No imputation of missing data will be performed. 
15. ETHICS & REGULATORY CONSIDERATIONS 
The study will be conducted in compliance with the principles of the Declaration of Helsinki 
(1996), the principles of GCP and in accordance with all applicable regulatory requirements 
including but not limited to the Code of Federal Regulations and FDA guidance documents. 
This protocol and related documents will be submitted for review to all relevant IRBs or EC 
delegated to approve the study at their respective sites. Any amendment to the protocol may 
be proposed by the principal investigator. The amendment must be submitted to the relevant 
IRB or EC. When applicable, the implementation of the amendment will take place only 
once approved by the appropriate ethics committee. 
Annual progress and safety reports and a final report at conclusion of the study will be 
submitted by Exalenz Bioscience (or on behalf of the Sponsor), to the FDA and the IRB/EC 
within the timelines defined in the Regulations. 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  48 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
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16. INVESTIGATOR RESPONSIBILITIES 
The investigator is responsible for ensuring that the clinical study is performed in 
accordance with the protocol, current ICH guidelines on GCP, US-GCP and applicable 
regulatory requirements. GCP is an international ethical and scientific quality standard for 
designing, conducting, recording, and reporting studies that involve the participation of 
human subjects. Compliance with this standard provides public assurance that the rights, 
safety, and well-being of study subjects are protected, consistent with the principles that 
originated in the Declaration of Helsinki, and that the clinical study data are credible. 
The investigational devices and substrate accountability will be filed in the Investigator’s 
Study File. Study supplies logged in will be kept by the investigator or the delegated persons 
in a secure place. All supplies (device, substrate / kits) will be used for this study only. After 
completion of the study, the device, kits and all unused accessories must be returned to 
Exalenz Bioscience Ltd. as per their request or alternatively, destroyed according to local 
regulations after receiving explicit authorization by Exalenz to do so and provide Exalenz 
with a confirmation. 
The Principal Investigator will act as custodian for the study data. Subject data will be 
pseudonymized and it will be stored on password protected media. All data will be 
compliant with CFR and GCP. 
17. SAFETY CONSIDERATIONS 
17.1. 
Adverse Event Definitions  
An adverse event (AE) is any undesirable or unintentional event that occurs in a patient or 
clinical investigation subject, whether or not considered related to the investigational 
product; this includes clinically significant changes in laboratory values. As this study is not 
therapeutic in nature, there will be no therapeutic failures to report.  
Regardless of severity or relationship to the study investigational product, all diagnoses, 
symptom(s), sign(s) or finding(s) with a start date after the first study test has begun (Breath 
test/stool test) and until the last study procedure is being completed will be documented, 
assessed 
by 
the 
investigator 
and 
recorded 
in 
the 
subject's 
CRF.  
A surgical procedure that was planned prior to the first study test by any physician treating 
the subject should not be recorded as an AE. 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
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Exalenz Bioscience Ltd.    2016 
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17.2. 
 Serious Adverse Event (SAE), Unanticipated Adverse Device 
Effect (UADE) and Suspected Unexpected Serious Adverse Reactions 
(SUSAR) 
A serious adverse event (SAE) is an event that is either: 
a) Fatal 
b) Life-threatening 
Life threatening is defined as an event in which the patient is at risk of death at the time 
of the event. It does not refer to an event that hypothetically might have caused death if it 
was more severe.  
c) Results in persistent or significant disability/incapacity  
Disability is defined as a substantial disruption of a person’s ability to conduct normal 
life functions.  
d) Requires or prolongs inpatient hospitalization 
e) A congenital anomaly or birth defect. 
f) Another serious or important medical event as judged by the investigator. 
An Unanticipated Adverse Device Effect (UADE) or a Suspected Unexpected Serious 
Adverse Reactions (SUSAR) is an SAE, related to the investigational product, for which the 
nature or severity is not consistent with the expected outcomes of the treatment/testing being 
offered. 
An unexpected adverse event is one that has not been previously observed, or one that is of a 
specificity or severity not consistent with the current investigator brochure. 
As with every procedure risks and discomforts may occur with relations to the Breath ID 
test. The potential risks/complications and discomforts which may be associated with all 
study procedures are listed below.  
• Allergic and/or other reactions to BreathID reagent 
• Aspiration (inhaling) of food or fluids into the lungs 
• Discomfort  


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
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When an adverse event occurs, the following information and assessments should be 
documented in the subject’s file and reported in the adverse event section of the CRF: 
• The signs, symptoms, or diagnosis of the event if available 
• The date and time of onset of the event using the 24 hour clock where midnight is 
00:00 and noon is 12:00 
• The adverse event severity using the criteria outlined below  
• The relationship of the event to the study medical device or drug as outlined below 
• Describe any action taken regarding study medical device or drug disposition  
• List any required therapy, medication, treatment, or diagnostic procedure. 
17.3. 
Relationship to Study Medical Product 
An investigator, who is a qualified physician, should assess the relationship to the study 
medical device and the substrate, based on all information available at the time of 
assessment.   
The following definitions should be used: 
• Not Related:  
1. The event is clearly related to other factors such as the patient's clinical state, 
therapeutic interventions or concomitant drugs.  
2. There is a highly likely alternative explanation. 
• Related:  
1. The event AE is reasonably associated with the use of the investigational product 
(device or substrate). 
17.4. 
Adverse Event Severity 
• Mild Adverse Events 
A mild adverse event is one that the symptoms are barely noticeable to the patient. It does 
not influence performance, require drug treatment or prevent the patient from carrying on 
with normal life activities. 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  51 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
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• Moderate Adverse Events 
A moderate adverse event is one that the symptoms make the patient uncomfortable and 
causes some impairment to normal life activities. Treatment for symptom(s) may be 
required. 
• Severe Adverse Events 
A severe adverse event is one that the symptoms cause severe discomforts to the patient and 
severely limits the patient’s normal daily activities. Treatment for symptom(s) is given.  
Note: Serious and severe are not synonymous. A serious adverse event must fulfill the 
requirements listed in the definition above.  
17.5. 
Adverse Event Reporting 
The investigator should report all adverse events in the case report form. The investigator is 
responsible for the appropriate medical management of all adverse events.  
The investigator must report any serious adverse event to the sponsor immediately, within 
24 hours of awareness, via email. Full details of the event, severity, outcome (if available) 
and an assessment of the relationship to the study investigational product must be provided 
in the report.  
All SAEs must be followed up until resolution or stabilization by submission of updated 
reports. Follow-up SAE reports will be reported according to the same timelines as initial 
reports, as soon as new significant information becomes available.  
All SAEs that fulfill UADE or SUSAR definitions will be reported to the relevant 
authorities by expedited means. 
Notification of the IECs/IRBs and regulatory authorities 
Notification to the IECs/IRBs about all relevant events (e.g. SAEs, UADEs, SUSARs) will 
be performed by the sponsor and/or by the investigator according to all applicable 
regulations. 
The processing and reporting of all relevant events to the regulatory authorities will be done 
by the sponsor according to all applicable regulations. 
If unexpected safety issues are identified, specific amendments will be implemented. 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  52 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
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18. ACCESS TO SOURCE DATA AND DOCUMENTS 
18.1. 
Availability of Source Data and Documents 
The Investigator will permit study-related monitoring, audits, IRB/EC review, and 
regulatory inspections (where appropriate) by providing direct access to source data and 
other documents (i.e. subjects’ case sheets, blood test reports, histology reports etc.). 
18.2. 
Subject Confidentiality 
The subject’s name and personal data will remain confidential and will not be published in 
any way. All data will be coded and stored in locked offices or on password protected 
media. 
19. MONITORING AND QUALITY ASSURANCE 
Monitoring of this study will be to ensure compliance with GCP, local regulations and 
scientific integrity and will be managed and oversight retained by Exalenz Bioscience (the 
Sponsor) or its assigned representative.  
 
19.1. 
Data Collection and Monitoring 
A set of electronic Case Report Forms (eCRF) will be completed for each subject. All case 
report forms will be filled out completely and will be reviewed for accuracy during 
monitoring.  
The Investigator or designee will be responsible for recording study data into the eCRF 
provided by the Sponsor. It is the Investigator’s responsibility to ensure the accuracy of the 
data entered into the eCRFs. The Sponsor or designee will be responsible for data 
processing, in accordance with data management procedures. Database lock will occur once 
monitoring and quality assurance procedures have been completed. 
The eCRF will be managed based on CFR 21 Part 11 and EU's Annex 11.  
20. PUBLICATION POLICY AND FINANCE 
It is intended that the results of the study will be reported and disseminated at international 
conferences and in peer-reviewed scientific journals. The policy regarding publications 
appears in the non-disclosure agreement signed by each study investigator prior to signing of 
the study contract. 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  53 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
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21. FINANCIAL ASPECTS  
The device and compound will be provided by the Sponsor. Funding for regulatory 
approvals and administration will also be provided by the Sponsor. Funding will also be 
provided for one study support staff at local sites. 
22. STUDY TERMINATION 
The study may be terminated after appropriate consultation between the study sponsor and 
the principal investigator and co investigators. Conditions warranting termination include, 
but are not limited to: 
• Failure of the investigator to enroll subjects at an acceptable rate 
• Insufficient adherence to protocol requirements 
• Failure to adhere to GCP 
• Decision by the study sponsor to suspend or discontinue development of the 
device or kit 
 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  54 of 59 
 
 
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Canete A, Abunaji Y, Alvarez-Calatayud G, DeVicente M, Gonzalez-Holguera JA, Leralta 
M, Pajares JM, et al. Breath test using a single 50-mg dose of 13C-urea to detect 
Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr 2003;36:105-111. 
2. 
Levine A, Shevah O, Miloh T, Wine E, Niv Y, Bujanover Y, Avni Y, et al. Validation of a 
novel real time 13C urea breath test for rapid evaluation of Helicobacter pylori in children 
and adolescents. J Pediatr 2004;145:112-114. 
3. 
Guarner J, Kalach N, Elitsur Y, Koletzko S. Helicobacter pylori diagnostic tests in children: 
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Chey WD, Wong BC. American College of Gastroenterology guideline on the management 
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ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice. J Postgrad 
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Brenner H, Bode G, Adler G, Rothenbacher D. Does maternal smoking hinder mother-child 
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Drumm B, Rhoads JM, Stringer DA, Sherman PM, Ellis LE, Durie PR. Peptic ulcer disease 
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Drumm B, Perez-Perez GI, Blaser MJ, Sherman PM. Intrafamilial clustering of 
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Kilbridge PM, Dahms BB, Czinn SJ. Campylobacter pylori--associated gastritis and peptic 
ulcer disease in children. Am J Dis Child 1988;142:1149-1152. 
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Hino B, Eliakim R, Levine A, Sprecher H, Berkowitz D, Hartman C, Eshach-Adiv O, et al. 
Comparison of invasive and non-invasive tests diagnosis and monitoring of Helicobacter 
pylori infection in children. J Pediatr Gastroenterol Nutr 2004;39:519-523. 
11. 
Beg MB, LeLeiko NS. Evaluation of the BreathID™ System for the Diagnosis of 
Helicobacter pylori Infection in Children. Journal of Pediatric Gastroenterology 2004;39 
(Supplement I). 
12. 
Paimela HM, Oksala NK, Kaariainen IP, Carlson PJ, Kostiala AA, Sipponen PI. Faecal 
antigen tests in the confirmation of the effect of Helicobacter eradication therapy. Ann Med 
2006;38:352-356. 
13. 
Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, et 
al. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus 
Report. Gut 2012;61:646-664. 
14. 
Korkmaz H, Kesli R, Karabagli P, Terzi Y. Comparison of the diagnostic accuracy of five 
different stool antigen tests for the diagnosis of Helicobacter pylori infection. Helicobacter 
2013;18:384-391. 
15. 
Zhou X, Su J, Xu G, Zhang G. Accuracy of stool antigen test for the diagnosis of 
Helicobacter pylori infection in children: a meta-analysis. Clin Res Hepatol Gastroenterol 
2014;38:629-638. 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  55 of 59 
 
 
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16. 
Choi J, Kim CH, Kim D, Chung SJ, Song JH, Kang JM, Yang JI, et al. Prospective 
evaluation of a new stool antigen test for the detection of Helicobacter pylori, in 
comparison with histology, rapid urease test, (13)C-urea breath test, and serology. J 
Gastroenterol Hepatol 2011;26:1053-1059. 
17. 
Gisbert JP, Cabrera Md Mdel M, Pajares JM. [Stool antigen test for initial Helicobacter 
pylori diagnosis and for confirmation of eradication after therapy]. Med Clin (Barc) 
2002;118:401-404. 
18. 
Weingart V, Russmann H, Koletzko S, Weingart J, Hochter W, Sackmann M. Sensitivity of 
a novel stool antigen test for detection of Helicobacter pylori in adult outpatients before and 
after eradication therapy. J Clin Microbiol 2004;42:1319-1321. 
19. 
Bravo LE, Realpe JL, Campo C, Mera R, Correa P. Effects of acid suppression and bismuth 
medications on the performance of diagnostic tests for Helicobacter pylori infection. Am J 
Gastroenterol 1999;94:2380-2383. 
20. 
Manes G, Balzano A, Iaquinto G, Ricci C, Piccirillo MM, Giardullo N, Todisco A, et al. 
Accuracy of the stool antigen test in the diagnosis of Helicobacter pylori infection before 
treatment and in patients on omeprazole therapy. Aliment Pharmacol Ther 2001;15:73-79. 
21. 
Atherton JC. Non-endoscopic tests in the diagnosis of Helicobacter pylori infection. 
Aliment Pharmacol Ther 1997;11 Suppl 1:11-20. 
22. 
Howden CW, Hunt RH. Guidelines for the management of Helicobacter pylori infection. 
Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. 
Am J Gastroenterol 1998;93:2330-2338. 
23. 
Gisbert JP, Pajares JM. Review article: 13C-urea breath test in the diagnosis of 
Helicobacter pylori infection -- a critical review. Aliment Pharmacol Ther 2004;20:1001-
1017. 
24. 
Graham DY, Klein PD. Accurate diagnosis of Helicobacter pylori. 13C-urea breath test. 
Gastroenterol Clin North Am 2000;29:885-893, x. 
25. 
Perri F. Diagnosis of Helicobacter pylori infection: which is the best test? The urea breath 
test. Dig Liver Dis 2000;32 Suppl 3:S196-198. 
26. 
Chey WD. Accurate diagnosis of Helicobacter pylori. 14C-urea breath test. Gastroenterol 
Clin North Am 2000;29:895-902. 
27. 
Hellinger A, Rauen U, de Groot H, Erhard J. [Auxiliary liver transplantation for acute liver 
failure after intake of 3,4-methylenedioxymethamphetamine ("Ecstasy")]. Dtsch Med 
Wochenschr 1997;122:716-720. 
28. 
Pereira SP, McCarthy M, Ellis AJ, Wendon J, Portmann B, Rela M, Heaton N, et al. 
Auxiliary partial orthotopic liver transplantation for acute liver failure. J Hepatol 
1997;26:1010-1017.


 
 
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 CONFIDENTIAL AND PROPRIETARY 
 
APPENDIX A - PROTOCOL APPROVAL SIGNATURE PAGE 
 
Protocol No: 
PED- HP- 0616B 
 
Protocol Title: 
Clinical Study to Confirm Safety and Accuracy in Detection of H. 
pylori with 13C-Urea Breath Test using the BreathID® Hp and 
BreathID® Hp Lab Systems in the Pediatric Population  
 
Version:   
2.0 
 
 
Date of Protocol: March 12, 2017 
 
 
Site Name: _____________ 
 
 
 
 
 
Principal Investigator: __________________  
 
 
 
             Print name 
 
I have read this protocol and agree to conduct the study as outlined herein and as per 
GCP and local regulations. 
 
 
 
 
 
Principal/ Chief Investigator____________________ Date_____________________ 
 
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  57 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
APPENDIX B – STOOL ANTIGEN TEST KIT AND PROCEDURE  
The Premier Platinum HpSA PLUS enzyme immunoassay (EIA) is an in vitro qualitative 
procedure for the detection of Helicobacter pylori antigens in human stool.  Test results are 
intended to aid in the diagnosis of H. pylori infection and to monitor response during and 
post-therapy in patients.  Accepted medical practice recommends that testing by any current 
method, to confirm eradication, be done at least four weeks following completion of therapy. 
 
Premier Platinum HpSA PLUS is a microwell-based enzyme immunoassay that detects H. 
pylori antigens present in human stool. No calculations are required and the visual color 
change makes the interpretation of results objective and simple. In addition, the HpSA test 
permits assessment of established or novel anti-H. pylori treatment during and post-therapy 
to monitor for treatment effectiveness, relapse or eradication.  Premier Platinum HpSA 
PLUS is a modification of Premier Platinum HpSA that provides increased signal strengths 
with positive test results and better discrimination between low positive and negative tests. 
 
The Premier Platinum HpSA PLUS test utilizes a plurality of monoclonal anti-H. pylori 
capture antibodies adsorbed to microwells. (Plurality is defined as a mixture of monoclonal 
antibodies.)  Diluted patient samples and a conjugate (peroxidase conjugated to a plurality of 
monoclonal antibodies) are added to the wells and incubated for one hour at room 
temperature.  A wash is performed to remove unbound material.  Substrate is added and 
incubated for ten minutes at room temperature.  Color develops in the presence of bound 
enzyme.  Stop Solution is added and the results are interpreted visually or 
spectrophotometrically. 
 
Procedure 
The doctor or hospital laboratory usually will provide written instructions on how to collect a stool 
sample. If instructions aren't provided, here are tips for collecting a stool sample from your child: 
 
• Be sure to wear protective gloves and wash your hands and your child's hands 
afterward. 
• Some young kids can't always let a parent know in advance when a bowel movement 
is coming. So a hat-shaped plastic lid is used to collect the stool specimen. This 
catching device can be quickly placed over a toilet bowl, or under your child's 
bottom, to collect the sample. Using a catching device can prevent contamination of 
the stool by water and dirt. Another way to collect a stool sample is to loosely place 
plastic wrap over the seat of the toilet. Then place the stool sample in a clean, 
sealable container before taking it to the lab. 
• Plastic wrap can also be used to line the diaper of an infant or toddler who isn't yet 
using the toilet. The wrap should be placed so that urine runs into the diaper, not the 
wrap. Stools shouldn't be allowed to touch the inside of disposable diapers because 
the lining usually has antibacterial properties that can interfere with the test results. 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  58 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
• Your child shouldn't urinate into the container. If possible, have your child empty his 
or her bladder before a bowel movement. 
• The stool should be collected into clean, dry plastic jars with screw-cap lids. Your 
child may be asked to provide a stool sample one or more times. For best results, the 
stool should be brought to the lab right away. If this isn't possible, the stool should be 
refrigerated and then taken to the lab as soon as possible. 
• Alternatively, a doctor or nurse may collect a small stool sample by inserting a swab 
into your child's rectum. 
 
Getting the Results 
In general, the result of the H. pylori stool test is reported in 1-4 days. 
 
Interpretation of Results; 
The following interpretations apply to both initial diagnosis and monitoring of anti- H. 
pylori therapy. 
Visual Reading 
Negative = colorless to faint yellow 
Positive   = definite yellow color 
To be called positive, a faint yellow color must be confirmed by a spectrophotometric 
reading.  If a spectrophotometer is not available, the cut-off must be determined by an 
alternative method. 
Spectrophotometric Single Wavelength (450 nm) 
Negative:  < 0.140 
Positive:  ≥ 0.140 
Negative Control: < 0.140 
Positive Control: ≥ 0.640 
Spectrophotometric Dual Wavelength (450/630 nm) 
Negative: < 0.100 
Positive:  ≥ 0.100 
Negative Control: < 0.100 
Positive Control: ≥ 0.600 
If a Negative Control is < 0.000, reblank the plate reader to air and reread the plate.   
 


Exalenz Bioscience Ltd. 
Last update on: Mar. 12, 2017 
Study Title: Clinical Study to Confirm Safety and 
Accuracy in Detection of H. pylori with 13C-Urea 
Breath Test using the BreathID® Hp and BreathID® 
Hp Lab Systems in the Pediatric Population 
Protocol Number: 
    PED-HP-0616B 
    Version 2.0 
Document No.: CSD00092 
Page  59 of 59 
 
 
Exalenz Bioscience Ltd.    2016 
 CONFIDENTIAL AND PROPRIETARY 
 
Reporting of Results: 
A positive result indicates the presence of H. pylori antigens.  A negative result indicates the 
absence of H. pylori antigens, or that the level of antigens is below what can be detected by 
the assay. The magnitude of the OD above the cut-off is not indicative of the severity or 
extent of H. pylori infection, nor can it be correlated to an endpoint titer.  Extremely strong 
positive reactions may yield a purple precipitate within a few minutes of stopping the 
reaction. 
Risks 
No risks are associated with collecting stool samples. 
 
Helping Your Child 
 
Collecting a stool sample is painless. Tell your child that collecting the stool won't hurt, but 
it has to be done carefully. A child who's old enough might be able to collect the sample 
alone to avoid embarrassment. Tell your child how to do this properly. If the sample is 
collected by swabbing, your child may feel slight pressure in his or her rectum during the 
procedure.