Presence or Absence of Blood in the GI Lumen - Correlating a HemoPill Acute Measurement With a Subsequent Endoscopic Finding
Phase: NA
Conditions: Upper GI Bleeding
Sponsor: NYU Langone Health

Official Title: 
Presence or Absence of Blood in the GI Lumen - Correlating a HemoPill 
Acute Measurement With a Subsequent Endoscopic Finding  
NCT Number:
NCT05415124
Study Number:
22-00387 
Document Type:
Protocol and Statistical Analysis Plan
Date of the 
Document: 
 
February 10, 2023 

Page i
Tool Revision History:
Version Number
Version Date
Summary of Revisions Made
1.0
April 3, 2022
Original Version (initial submission to IRB)
  2.0
            February 8, 2023   modified version

Page ii
Presence or Absence of blood in the GI lumen – Correlating a HemoPill 
acute measurement with a subsequent endoscopic finding
Principal Investigator:
Melissa Latorre, MD
Division of Gastroenterology and Hepatology 
550 1st Avenue, New York, NY 10016 
Melissa.latorre@nyulangone.org 
212-263-7300
Additional Investigators:
Gregory B. Haber, MD
Seth Gross, MD
Tamas Gonda, MD
Lauren Khanna, MD
Scott Smukalla, MD 
Eileen Janec, MD
NYULMC Study Number:
s22-00387
Funding Sponsor: 
Ovesco Endoscopy USA, Inc.
James B. Potts
120 Quade Drive, Cary, NC 27513 
919 651 9449
Regulatory Sponsor
Melissa Latorre, MD
Division of Gastroenterology and Hepatology 
550 1st Avenue, New York, NY 10016
Study Product:
HemoPill acute
HemoPill Receiver
Study Product Provider: 
Ovesco Endoscopy USA, Inc.
Regulatory Status
Abbreviated IDE
Abbreviated IDE holder: Melissa Latorre, MD
ClinicalTrials.gov Number    Include the National Clinical Trial (NCT) Number assigned once the 
trial is registered on the ClinicalTrials.gov.
Initial version: 03/18/2022 
Modified: 02/08/2023

Study number: s22-00387
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Statement of Compliance
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 as applicable, any other applicable 
US government research regulations, and institutional research policies and procedures. The International 
Conference on Harmonisation (“ICH”) Guideline for Good Clinical Practice (“GCP”) (sometimes referred 
to as “ICH-GCP” or “E6”) will be applied only to the extent that it is compatible with FDA and DHHS 
regulations. The Principal Investigator will assure that no deviation from, or changes to the protocol will 
take place without prior agreement from the sponsor and documented approval from the Institutional 
Review Board (IRB), except where necessary to eliminate an immediate hazard(s) to the trial participants. 
All personnel involved in the conduct of this study have completed Human Subjects Protection Training. 
 

Study number: s22-00387
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Table of Contents 
 
STATEMENT OF COMPLIANCE ....................................................................................................... III 
LIST OF ABBREVIATIONS .............................................................................................................. VIII 
PROTOCOL SUMMARY ......................................................................................................................... 1 
SCHEMATIC OF STUDY DESIGN......................................................................................................... 5 
1 
KEY ROLES ....................................................................................................................................... 6 
2 
INTRODUCTION, BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ..... 6 
2.1 
BACKGROUND INFORMATION AND RELEVANT LITERATURE......................................................6
2.1.1 
Study importance ..................................................................................................................... 8 
2.2 
NAME AND DESCRIPTION OF THE INVESTIGATIONAL AGENT ..................................................... 8 
2.2.1 
HemoPill acute capsule ........................................................................................................... 9 
2.1.2 
Operating principle ............................................................................................................... 13 
2.1.3 
Clinical application ............................................................................................................... 15 
2.2.2 
Device Category .................................................................................................................... 16 
2.2.3 
Non-significant risk rationale ............................................................................................... 17 
2.2.4 
Preclinical Data .................................................................................................................... 17 
2.2.5 
Clinical Data to Date ............................................................................................................ 22 
2.3 
RATIONALE................................................................................................................................ 23 
2.3.1 
Epidemiology ......................................................................................................................... 23 
2.3.2 
Scoring systems ..................................................................................................................... 24 
2.4 
POTENTIAL RISKS & BENEFITS.................................................................................................. 27 
2.4.1 
Known Potential Risks .......................................................................................................... 27 
2.4.2 
Known Potential Benefits ...................................................................................................... 29
3 
OBJECTIVES AND PURPOSE ..................................................................................................... 29 
3.1 
PRIMARY OBJECTIVE ................................................................................................................. 29 
4 
STUDY DESIGN AND ENDPOINTS ............................................................................................ 30 
4.1 
DESCRIPTION OF STUDY DESIGN...............................................................................................30
4.2 
STUDY ENDPOINTS^.......................................................................................................................  
 
31 
4.2.1 
Primary Study Endpoints ...................................................................................................... 31 
4.2.2 
Secondary Study Endpoints ................................................................................................... 31 
4.2.3 
Exploratory Endpoints .......................................................................................................... 31 
5 
STUDY ENROLLMENT AND WITHDRAWAL ........................................................................ 31 
5.1 
INCLUSION CRITERIA ................................................................................................................. 31 
5.2 
EXCLUSION CRITERIA................................................................................................................ 31 
5.3 
VULNERABLE SUBJECTS............................................................................................................ 32 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION.................................................................... 32 
5.4.1 
Use of DataCore/Epic Information for Recruitment Purposes Error! Bookmark not defined. 
5.5 
DURATION OF STUDY PARTICIPATION....................................................................................... 32 
5.6 
TOTAL NUMBER OF PARTICIPANTS AND SITES .......................................................................... 32 
5.7 
PARTICIPANT WITHDRAWAL OR TERMINATION ........................................................................ 32 
5.7.1 
Reasons for Withdrawal or Termination ............................................................................... 32 
5.7.2 
Handling of Participant Withdrawals or Termination .......................................................... 33 

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5.8
PREMATURE TERMINATION OR SUSPENSION OF STUDY............................................................ 33 
6 
STUDY AGENT (STUDY DRUG, DEVICE, BIOLOGIC, VACCINE ETC.) AND/OR 
PROCEDURAL INTERVENTION ........................................................................................................ 33 
6.1 
STUDY AGENT AND CONTROL DESCRIPTION ..................... ERROR! BOOKMARK NOT DEFINED.
6.1.1 
Acquisition............................................................................................................................. 33 
6.1.2 
Formulation, Appearance, Packaging, and Labeling ........................................................... 34 
6.1.3 
Product Storage and Stability ............................................................................................... 34 
6.1.4 
Preparation ........................................................................................................................... 34 
6.1.5 
Dosing and Administration ................................................................................................... 35 
6.1.6 
Route of Administration ........................................................................................................ 35 
6.1.7 
Starting Dose and Dose Escalation Schedule ....................................................................... 35 
6.1.8 
Dose Adjustments/Modifications/Delays ............................................................................... 35 
6.1.9 
Duration of Therapy .............................................................................................................. 35 
6.1.10 
Tracking of Dose ............................................................................................................... 36 
6.1.11 
Device Specific Considerations ........................................................................................ 36 
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES ....................................................................... 36 
6.3 
STUDY BEHAVIORAL OR SOCIAL INTERVENTION(S) .......... ERROR! BOOKMARK NOT DEFINED.
6.3.1 
Administration of Intervention ................................................ Error! Bookmark not defined.
6.3.2 
Procedures for Training Interventionalists and Monitoring Intervention Fidelity ........ Error! 
Bookmark not defined. 
6.3.3 
Assessment of Subject Compliance with Study Intervention ... Error! Bookmark not defined. 
6.4 
STUDY PROCEDURAL INTERVENTION(S) DESCRIPTION............................................................. 36 
6.4.1 
Administration of Procedural Intervention ........................................................................... 36 
6.4.2 
Procedures for Training of Clinicians on Procedural Intervention ...................................... 37 
6.4.3 
Assessment of Clinician and/or Participant Compliance with Study Procedural Intervention
 
37 
7 
STUDY PROCEDURES AND SCHEDULE ................................................................................. 37 
7.1 
STUDY PROCEDURES/EVALUATIONS ......................................................................................... 37 
7.1.1 
Study Specific Procedures ..................................................................................................... 37 
7.1.2 
Standard of Care Study Procedures ...................................................................................... 37 
7.2 
LABORATORY PROCEDURES/EVALUATIONS ...................... ERROR! BOOKMARK NOT DEFINED.
7.2.1 
Clinical Laboratory Evaluations ............................................. Error! Bookmark not defined.
7.2.2 
Other Assays or Procedures .................................................... Error! Bookmark not defined. 
7.2.3 
Specimen Preparation, Handling, and Storage....................... Error! Bookmark not defined. 
7.2.4 
Specimen Shipment .................................................................. Error! Bookmark not defined. 
7.3 
STUDY SCHEDULE......................................................................................................................37 
7.3.1 
Screening ...............................................................................................................................37 
7.3.2 
Enrollment .............................................................................................................................38 
7.3.3 
Intermediate Visits .................................................................. Error! Bookmark not defined. 
7.3.4 
Final Study Visit ...................................................................... Error! Bookmark not defined. 
7.3.5 
Withdrawal/Early Termination Visit ....................................... Error! Bookmark not defined. 
7.3.6 
Unscheduled Visit .................................................................... Error! Bookmark not defined. 
7.4 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURESERROR! BOOKMARK 
NOT 
DEFINED.
7.5 
JUSTIFICATION FOR SENSITIVE PROCEDURES ..................... ERROR! BOOKMARK NOT DEFINED.
7.5.1 
Precautionary Medications, Treatments, and Procedures ...... Error! Bookmark not defined. 
7.6 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURESERROR!
BOOKMARK 
NOT 
DEFINED.

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7.7
PROPHYLACTIC MEDICATIONS, TREATMENTS, AND PROCEDURESERROR! BOOKMARK 
NOT 
DEFINED.
7.8 
RESCUE MEDICATIONS, TREATMENTS, AND PROCEDURES ERROR! BOOKMARK NOT DEFINED.
7.9 
PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSUREERROR!
BOOKMARK 
NOT 
DEFINED.
8 
ASSESSMENT OF SAFETY .......................................................................................................... 38 
8.1 
SPECIFICATION OF SAFETY PARAMETERS .................................................................................38
8.1.1 
Definition of Adverse Events (AE) ........................................................................................ 38 
8.1.2 
Definition of Serious Adverse Events (SAE).......................................................................... 38 
8.1.3 
Definition of Unanticipated Problems (UP) ......................................................................... 39 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT ................................................................................. 39 
8.2.1 
Severity of Event .................................................................................................................... 39 
8.2.2 
Relationship to Study Agent .................................................................................................. 39 
8.2.3 
Expectedness ......................................................................................................................... 40 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP........................... 40 
8.4 
REPORTING PROCEDURES – NOTIFYING THE IRB ..................................................................... 41 
8.4.1 
Adverse Event Reporting ....................................................................................................... 41 
8.4.2 
Serious Adverse Event Reporting .......................................................................................... 41 
8.4.3 
Unanticipated Problem Reporting ........................................................................................ 41 
8.4.4 
Reporting of Pregnancy ........................................................................................................ 41 
8.5 
REPORTING PROCEDURES – NOTIFYING THE STUDY SPONSOR ................................................. 41 
8.6 
REPORTING PROCEDURES – NOTIFYING THE FDA ............ ERROR! BOOKMARK NOT DEFINED.
8.7
REPORTING PROCEDURES – PARTICIPATING INVESTIGATORSERROR!
BOOKMARK 
NOT 
DEFINED.
8.8 
STUDY HALTING RULES ............................................................................................................ 42 
8.9 
SAFETY OVERSIGHT................................................................................................................... 42 
9 
CLINICAL MONITORING ........................................................................................................... 43 
10 
STATISTICAL CONSIDERATIONS ............................................................................................ 43 
10.1 
STATISTICAL AND ANALYTICAL PLANS (SAP) ......................................................................... 43 
10.2 
STATISTICAL HYPOTHESES ........................................................................................................ 43 
10.3 
ANALYSIS DATASETS ................................................................................................................ 43 
10.4 
DESCRIPTION OF STATISTICAL METHODS ................................................................................. 44 
10.4.1 
General Approach ............................................................................................................. 44 
10.4.2 
Analysis of the Primary Efficacy Endpoint(s) ................................................................... 44 
10.4.3 
Analysis of the Secondary Endpoint(s) ............................................................................. 45 
10.4.4 
Safety Analyses ................................................................................................................. 45 
10.4.5 
Adherence and Retention Analyses ................................................................................... 45 
10.4.6 
Baseline Descriptive Statistics .......................................................................................... 45 
10.4.7 
Planned Interim Analysis .................................................................................................. 45 
10.4.8 
Additional Sub-Group Analyses ........................................................................................ 45 
10.4.9 
Multiple Comparison/Multiplicity .................................................................................... 45 
10.4.10 
Tabulation of Individual Response Data .......................................................................... 45 
10.4.11 
Exploratory Analyses ........................................................................................................ 45 
10.5 
SAMPLE SIZE .............................................................................................................................. 46 
10.6 
MEASURES TO MINIMIZE BIAS .................................................................................................. 46
10.6.1 
Enrollment/Randomization/Masking Procedures ............................................................. 46 
10.6.2 
Evaluation of Success of Blinding ..................................................................................... 46 
10.6.3 
Breaking the Study Blind/Participant Code ...................................................................... 46 

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11
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ...................... 43 
12 
QUALITY ASSURANCE AND QUALITY CONTROL ............................................................. 47 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ..................................................................... 47 
13.1 
ETHICAL STANDARD .................................................................................................................. 47 
13.2 
INSTITUTIONAL REVIEW BOARD ...............................................................................................47
13.3 
INFORMED CONSENT PROCESS.................................................................................................. 48 
13.3.1 
Consent/Assent and Other Informational Documents Provided to Participants ....... Error! 
Bookmark not defined. 
13.3.2 
Consent Procedures and Documentation ........................... Error! Bookmark not defined. 
13.4 
POSTING OF CLINICAL TRIAL CONSENT FORM................... ERROR! BOOKMARK NOT DEFINED.
13.5 
PARTICIPANT AND DATA CONFIDENTIALITY.............................................................................48 
13.5.1 
Research Use of Stored Human Samples, Specimens, or DataError! 
Bookmark 
not 
defined. 
13.6 
FUTURE USE OF STORED SPECIMENS .................................ERROR! BOOKMARK NOT DEFINED.
14 
DATA HANDLING AND RECORD KEEPING .......................................................................... 49 
14.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES..................................................... 49 
14.2 
STUDY RECORDS RETENTION.................................................................................................... 50 
14.3 
PROTOCOL DEVIATIONS ............................................................................................................ 50 
14.4 
PUBLICATION AND DATA SHARING POLICY .............................................................................. 50 
15 
STUDY FINANCES ......................................................................................................................... 51 
15.1 
FUNDING SOURCE...................................................................................................................... 51 
15.2 
COSTS TO THE PARTICIPANT ............................................... ERROR! BOOKMARK NOT DEFINED.
15.3 
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ...................................................................... 51
16 
STUDY ADMINISTRATION .......................................... ERROR! BOOKMARK NOT DEFINED. 
16.1 
STUDY LEADERSHIP ............................................................ ERROR! BOOKMARK NOT DEFINED.
17 
CONFLICT OF INTEREST POLICY .......................................................................................... 51
18 
REFERENCES ................................................................................................................................. 52 
19 
ATTACHMENTS.............................................................. ERROR! BOOKMARK NOT DEFINED. 
20 
SCHEDULE OF EVENTS ............................................... ERROR! BOOKMARK NOT DEFINED. 
 
 
 
 

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List of Abbreviations 
 
AE
Adverse Event/Adverse Experience
CFR
Code of Federal Regulations
CRF
Case Report Form
CSOC
Clinical Study Oversight Committee
DCC
Data Coordinating Center
DHHS
Department of Health and Human Services
DSMB
Data and Safety Monitoring Board
FFR
Federal Financial Report
FWA
Federalwide Assurance
GCP
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HI
HemoPill Index
ICF 
Informed Consent Form 
ICH
International Conference on Harmonisation
IRB
Institutional Review Board 
ISM 
Independent Safety Monitor
MOP 
Manual of Procedures 
N
Number (typically refers to participants)
NIH 
National Institutes of Health 
OHRP
Office for Human Research Protections
OHSR
Office of Human Subjects Research
PI 
Principal Investigator 
QA 
Quality Assurance
QC 
Quality Control 
SAE
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
UGIB 
Upper Gastrointestinal Bleeding 
US
United States 

Study number:
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Protocol Summary
Title 
Presence or Absence of blood in the GI lumen – Relation between 
a HemoPill acute measurement with a subsequent endoscopic 
finding
Short Title
PROOF (Presence or Absence of blood in the GI lumen – Relation 
between a HemoPill acute measurement with a subsequent 
endoscopic finding) 
Brief Summary 
Patients scheduled for endoscopy on the basis of suspected UGIB 
are generally eligible for inclusion into the trial. After patient 
screening, information and obtaining informed consent, a patient is 
enrolled into the trial. Shortly before the scheduled endoscopy is 
performed, the patient ingests a HemoPill acute. Endoscopy is 
performed as scheduled. Blood within the GI lumen is identified if 
present and pictures are taken. Pathologies, if found, are treated as 
per clinical standard. The HemoPill acute measurement regarding 
presence or absence of blood in the GI lumen is compared to 
observations made during endoscopy. For statistical validity, 43 
patients are required. Considering dropouts, a recruitment goal of 
50 patients is defined. 
Phase 
N.A. 
Objectives 
The objective of the study is to determine the clinical relation 
between the detection of blood in the GI lumen using the HemoPill 
acute (trial procedure) with the detection of bleeding / a bleeding 
source during an endoscopic examination (control procedure).
Methodology 
Intraindividual comparison of HemoPill acute measurement to 
endoscopic work up. 

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Endpoint 
Effectiveness Endpoints:
-
Technical effectiveness endpoint
Technical success, defined as: 
Successful data transmission of the HemoPill acute to the HemoPill 
Receiver 
 
- 
Clinical effectiveness endpoint 
Result accuracy: Clinical relation between HemoPill acute 
measurement (trial procedure) and endoscopic findings (control 
procedure) according to defined events for true positive, true 
negative, false positive, false negative.
Safety Endpoints: 
- 
Adverse events / complications associated with trial or 
control procedure, such as: 
Trial procedure: 
o Aspiration of the capsule on ingestion 
o Delayed excretion, or failure to excrete the capsule 
(capsule retention) 
o Obstruction of the digestive tract 
o Injury to tissue structures during the passage of the 
HemoPill acute through the digestive tract. In 
particular, this may involve: 
 
Injury to the mucosa 
 
Bleeding, e.g., variceal bleeding 
 
Perforations 
Control procedure: 
o Cardiopulmonary adverse events 
o Infection 
o Perforation 
o Bleeding (iatrogenic) 
Study Duration 
March 18, 2022 to July 31st, 2022
Participant Duration 
Single visit, patient participation ends with conclusion of 
endoscopy
Population 
Adult subjects (meeting inclusion criteria) with suspected UGIB 
due to clinical and / or laboratory findings and therefore scheduled 
for endoscopy
Study Sites 
NYU Langone Health
550 First Avenue 
New York, NY 10016
Number of participants 
Recruitment goal: 50 Patients; Statistical validity reached at 43 
Patients w/o dropouts. 

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Description 
of 
Study 
Agent/Procedure
HemoPill acute: 
A capsule equipped with a photometric sensor for the detection of 
blood or hematin in the gastrointestinal tract. The capsule can be 
ingested and travels through the gastrointestinal tract naturally. For 
approximately 9 hours, the photometric sensor measures the 
absorption of light at specific wavelengths through the contents of 
the gastrointestinal lumen. Blood and hematin have a specific 
absorption behavior for the defined wavelengths used. The 
HemoPill acute capsule makes a measurement every 12 seconds and 
wirelessly transmits data to the HemoPill Receiver that displays the 
HemoPill acute data.  
HemoPill Receiver: 
Handheld device that displays HemoPill acute data. The HemoPill 
Receiver displays the data in a graphical form as well as the current 
value and the highest measured value. The threshold value for 
confirmation of presence of blood or hematin is displayed for 
reference.  
Reference Therapy 
Endoscopy 
Key Procedures 
Diagnostic procedures used leading to a suspicion of UGIB are not 
within the scope of this trial as these procedures are necessary 
irrespective of trial participation. A suspicion of UGIB, however 
justified, is a prerequisite for trial participation.  
Endoscopy and associated procedural steps are omitted as 
endoscopy is scheduled for trial participants irrespective of trial 
participation. 
Provide patient information and obtain informed consent. Screen by 
inclusion and exclusion criteria, document. 
Activation of the HemoPill acute by the investigator as per 
instructions for use. 
Ingestion of HemoPill acute capsule by the trial participant with a 
minimal amount of water. 
Data collection on the HemoPill Receiver from ingestion of the 
HemoPill acute capsule until conclusion of endoscopy.
Statistical Analysis 
Relation between HemoPill acute measurements and endoscopic 
findings along the lines of the following definitions for “true 
positive”, “true negative”, “false positive”, “false negative”: 
True Positive 
HemoPill acute measurement 
indicates presence of blood; 
Endoscopy 
identifies 
fresh 
blood or hematin in the GI 
lumen. 

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True Negative 
HemoPill acute measurement 
does not indicate presence of 
blood; Endoscopy does not 
identify fresh blood or hematin 
in the GI lumen in quantities > 
20 mL; Minimum latency of 20 
minutes achieved.
False Positive 
HemoPill acute measurement 
indicates presence of blood; 
Endoscopy does not identify 
fresh blood or hematin in the GI 
lumen. 
False Negative 
HemoPill acute measurement 
does not indicate presence of 
blood 
in 
the 
GI 
lumen; 
Endoscopy 
identifies 
fresh 
blood or hematin in the GI 
lumen in quantities > 20 mL; 
Minimum latency of 20 minutes 
achieved. 
 

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Schematic of Study Design
Total N: Obtain informed consent. Screen potential subjects by inclusion and exclusion 
criteria; obtain history, documentation.
50 Subjects
Investigator explains the subject device HemoPill to the trial participant. HemoPill acute 
capsule is activated and linked to the HemoPill Receiver as described in the 
Instructions for Use. 
Ingestion of activated HemoPill acute by the trial participant with a small amount of 
water.
Endoscopy is performed as scheduled. Pathologies found are treated as per clinical 
standard. HemoPill acute measurements are stored on the HemoPill Receiver
The further clinical course of the patient is determined based on the overall result of the 
endoscopic work up and clinical presentation
Relation of endoscopic findings and HemoPill 
acute measurements along the lines of defined 
“true positive”, “true negative”; “false positive”, 
and “false negative” scenarios
Prior to 
endoscopy
Prior to 
Enrollment
20 to 60 
minutes before 
endoscopy
During 
endoscopy
After 
endoscopy
Data 
analysis

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1
Key Roles
Principal Investigator 
Melissa Latorre, MD 
NYU Langone Health 
550 1st Avenue, New York, NY 10016 
212-263-7300 
melissa.latorre@nyulangone.org 
Site Investigators 
Gregory B. Haber, MD 
Seth Gross, MD 
Tamas Gonda, MD 
Lauren Khanna, MD 
Scott Smukalla, MD 
Eileen Janec, MD 
 
Clinical Safety Monitor: 
Jennifer Katz, MD 
 
Clinical Research Coordinator: 
Philip Burkhard 
 
Study Site Monitor 
Sofie Yuen, MD, MBA 
 
Industry Partner 
James B. Potts 
Vice President of Sales 
Ovesco Endoscopy USA, Inc. 
585-944-2515 
jpotts@ovesco-usa.com 
 
 
2 
Introduction, Background Information and Scientific Rationale 
 
2.1 
Background Information and Relevant Literature 
Gastrointestinal hemorrhage is the 19th most common diagnosis for hospital admissions. A total of 86 % 
of patients with gastrointestinal hemorrhage are admitted to the hospital. However, when 
esophagoduodenoscopy is performed in the emergency department (ED), 30 % to 46 % of ED patients with 
acute UGIBs can be safely discharged. Risk stratification in the ED presents a logistic issue because 
gastroenterologists are frequently unavailable to conduct ED-based esophagoduodenoscopies. As a result, 
many patients with benign diseases are admitted to the hospital only to have a negative endoscopy result 
(Meltzer AC et al., 2013). The HemoPill has the potential to provide information on the presence or absence 
of blood in the GI-lumen which is a valuable information on the urgency of a situation if viewed in the 
general clinical context of a given patient. The HemoPill is a CE-marketed device and has been on the 
European market since 2019. Since market entry, the following literature on the use of the HemoPill has 
been published: 

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Telemetric capsule-based upper gastrointestinal tract – blood detection – first multicentric 
experience
Brunk and colleagues presented results from an observational study on the use of the HemoPill in terms of 
safety and usability under real-life conditions from experiences in 12 hospitals (Brunk T et al., 2021). The 
use of the HemoPill in 61 patients was retrospectively analyzed. Indications for HemoPill application were 
clinical suspicion of UGIB, suspected small bowel bleeding after uneventful esophagoduodenoscopy 
(EGB) and colonoscopy if symptoms persisted, or exclusion of rebleeding after hemostasis. Primary 
endpoints were technical success and bleeding detection/exclusion. Secondary endpoints included adverse 
events and change of clinical course. Complete baseline characteristics were available in 49 of 61 patients 
(80.3 %). Mean age was 70 (± 10.7) years, 41 % were female. Mean hemoglobin level at admission to the 
emergency department was 8.1 g/dL (± 1.6). Over signs of bleeding such as melaena and/or hematochezia 
were present in 27 patients (55 %). Median Glasgow-Blatchford score (GBS) was 10 (range 0 – 19). 46 
patients (94 %) had a GBS > 1. 61 patients received the HemoPill; in 45 patients (74 %), the capsule was 
administered due to the suspicion of UGIB, in 12 patients (20 %), the capsule was used for detection of a 
suspected small intestinal bleeding and in 4 patients (7 %), HemoPill was used as a “second look” tool after 
primary hemostasis in the upper GI-tract. One patient was excluded as data transfer was stopped after 10 
minutes of recording. Of the remaining 60 patients, 35 (58 %) had a positive capsule signal while 25 (42 %) 
had a negative HemoPill result. In 20 of 35 patients (57 %) with a positive HemoPill signal, evidence of 
bleeding was seen in a subsequent endoscopic work up. The bleeding sources were angiodysplasia (n = 10), 
peptic ulcer (n = 5), Dieulafoy lesion (n = 1), esophageal varices (n = 1), esophagitis (n = 1), erosive 
gastritis (n = 1), unknown as only blood was seen (n = 1). In 15 of 35 patients with a positive HemoPill 
signal, no bleeding source was detected, yet only in 11 of these 15 patients an EGD was performed.  
 
In 20 of 25 HemoPill negative patients, endoscopy was performed and did not reveal a bleeding source or 
blood/hematin. Until discharge, no clinically relevant bleeding was detected in HemoPill negative patients. 
 
The authors state that all endoscopically confirmed bleedings had been detected by the HemoPill and no 
HemoPill negative patients showed an endoscopically or clinically proven bleeding site. In HemoPill 
negative patients (25 / 60), the further clinical course was changed in 18 cases (72 %). Change from urgent 
to elective regarding timing of endoscopy was reported in 40 % of cases (10 / 25). Small bowel enteroscopy 
was avoided in 5 / 25 patients (20 %) and EGD was avoided in 3 / 25 patients (12 %). In 7 / 25 patients, no 
change of the clinical course occurred. Brunk T et al. conclude that HemoPill is a promising tool for real-
time blood detection to aid stratification of patients with UGIB (Brunk T et al., 2021).  
 
Potential use of a novel telemetric sensor capsule in patients with suspected gastrointestinal bleeding 
during the COVID-19 pandemic 
Elsayed and colleagues evaluated the HemoPill acute in three patients with confirmed or suspected COVID-
19 (Elsayed I et al., 2021). Case 1 was a patient with COVID-19, congestive heart failure, and severe obesity 
who reported melena and had a drop of hemoglobin from 14.6g/dL to 11.3g/dL. The maximum HI value 
was 1.0 after 89 minutes. Endoscopy subsequently showed a gastric ulcer with a non-bleeding visible 
vessel. Patient 2 suffered from dyspnea and anemia (hemoglobin 4.3g/dL) with possible gastrointestinal 
bleeding. She was routinely tested for SARS-CoV-2 and isolated until receipt of her result. The maximum 
HI value was 0.2. Her endoscopy, which showed no evidence of gastrointestinal bleeding, was postponed 
for 48 hours until receipt of negative test results. Patient 3 suffered from COVID-19 and was therefore 
receiving anti-coagulant therapy. He underwent endoscopic retrograde cholangioscopy with papillotomy 
because of biliary pancreatitis; here ported a single episode of hematochezia 1 week after the endoscopy 

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and his hemoglobin had dropped by 4.5 g/dL to 7.9 g/dL. His maximum HI value was 0.8 and no endoscopy 
was performed. No further episodes of bleeding were reported, and the patient’s hemoglobin remained 
stable. 
The authors concluded that the sensor capsule might aid in decision-making during the COVID-19 
pandemic. In patients with as yet unavailable COVID-19 test results, it might aid in determining the 
appropriate time-point for endoscopy. In patients who are positive for COVID-19 with suspected 
gastrointestinal bleeding, it could help in deciding whether to perform an endoscopy or not and thereby 
potentially help minimizing risk of disease transmission (Elsayed I et al., 2021). 
 
Detection of mid-gastrointestinal bleeding caused by Meckel’s diverticulum using a novel telemetric 
sensor capsule in a non-fasting patient
Wiedbrauck and colleagues used the HemoPill acute to provide further assessment of an acute bleeding 
situation (Wiedbrauck D et al., 2021). A 52-year-old male patient presented with anemia (hemoglobin 9.9 
g/dL) due to episodes of severe hematochezia. He underwent esophagogastroduodenoscopy, colonoscopy 
and CT-angiography, however, none of these procedures could identify the source of bleeding. After these 
procedures, the patient was stable and had eaten. Several hours later, his hemoglobin dramatically dropped 
(6.4 g/dL) and VCE was not possible. Therefore, the authors administered the HemoPill acute which 
detected blood after 6 h 58 min (HI = 1.1). The time of blood detection indicated a bleeding source at the 
level of the ileum/terminal ileum. Subsequent video capsule endoscopy revealed a bleeding Meckel’s 
diverticulum. The patient underwent segmental ileal resection. Wiedbrauck and colleagues concluded that 
this case shows that the HemoPill may serve as an add-on pre-diagnostic tool for detecting and localizing 
gastrointestinal bleeding in a non-fasting patient (Wiedbrauck D et al., 2021). 
 
2.1.1 
Study importance 
As described in the above-mentioned publications, further tools for risk stratification in patients with 
suspected UGIB are in demand to identify high risk patients and adequately allocate resources. The clinical 
data on the use of the HemoPill in Europe is generally positive and promising. As Brunk T et al. conclude, 
thus far no HemoPill negative patient developed a clinically significant GI bleeding until discharge and 
every endoscopically confirmed bleeding pathology was associated with a previously positive HemoPill 
measurement. The proposed study further investigates the safety and performance profile of the HemoPill 
by controlling and limiting latency to endoscopy. HemoPill may prove to be a valuable tool for the US 
healthcare system by reliably providing information on the presence or absence of blood in the GI tract. 
HemoPill does not require patient preparation and measurement data is displayed in a way that allows for 
immediate, real-time interpretation. Thus far, HemoPill has a high technical success rate and is well 
tolerated by patients. Only patients who are already scheduled for endoscopy for suspected UGIB are 
eligible for participation in the study and endoscopy is neither delayed nor prolonged by the study protocol. 
The potential benefits for the US healthcare system are already highlighted in publications describing the 
use of the subject device in Europe. 
 
2.2 
Name and Description of the Investigational Agent 
The investigational device is the HemoPill, consisting of an ingestible capsule (HemoPill acute), and a 
wireless data receiver module (HemoPill Receiver) that displays and stores data. 
 

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2.2.1
HemoPill acute capsule
The HemoPill acute is an active medical device. It is a wireless, battery-powered ingestible capsule 
containing an optical sensor, electronics, radio link and software. The electronic assembly (as a stack of 
three electronic boards) contains software for measurement data acquisition and signal transmissions. These 
components are encapsulated into a transparent epoxy resin that is coated with Parylene C.
The signals of the HemoPill acute sensor correlate with the presence of blood in the measuring slot of the 
capsule and are transmitted wirelessly to the HemoPill Receiver. 
Figure 1: Components of the HemoPill acute
Figure 2: Dimensions of the HemoPill acute
The operating mode of the optical sensor is based on alternating screening of the measuring slot using 
wavelength of 415 nm (violet) and 700 nm (red). The optical sensor measures the absorption of light by the 
medium inside the measuring slot for each wavelength separately. The ratio of red to violet light intensity, 
that has not been absorbed is, calculated. Measurement data is transmitted by radio to the HemoPill 
Receiver. A more detailed description is provided in chapter 2.1.2.
The HemoPill acute is activated by exposing the activation area to light. The light intensity required for 
activation is higher than normal environmental light (day light or room light), therefore the exposure to a 
light-source at close distance is required. The HemoPill Receiver includes a light source for activating the 
HemoPill acute. The procedure of capsule activation using the activation light source of the HemoPill 
Receiver is shown in Figure 2-3. In order to ensure sterility, the capsule remains in the blister packaging 
for activation.
After activation, the capsule conducts one measurement approximately every twelve seconds for at least 
nine hours. Subsequently, the device changes into a second mode to facilitate monitoring the presence of 
the device in the patient using the HemoPill Receiver. During this second period, no measurements are 
conducted, but data packages are transmitted until at least 21 days after activation.

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Figure 3: Blister package of HemoPill acute (activation area is marked by triangle, (1) and (2)) 
 
Table 1: Specifications of the HemoPill acute 
Dimensions and weight 
Product dimensions 
26.3 mm x 7.0 mm
Weight
Approx. 2 g
Energy source 
Battery type 
Silver oxide 
Version 
Software version
02.xx.yy 
Electronics version
01.xx.xx 
CAD version
12
Wireless specification 
Frequency range 
433.05 MHz to 434.79 MHz 
Send frequency 
434.42 MHz 
Send bandwidth
100 kHz 
Send rate 
0.083Hz 
Transmission period 
< 10ms
Modulation
GFSK 
ERP
-24 dBm
Range
Short range
Application related specifications
General specifications
Single use
EO sterilized
Latex-free 
Shelf life 
21 months
Technical characteristics 
General characteristics 
Unidirectional data transmission
MR conditional
Environmental conditions for operation, transport and storage
Operation 
Storage
Transport 
Temperature
+20 °C to +40 °C
+10 °C to +30 °C 
-10 °C to +50 °C
Relative humidity 
20% to 90% RH; 
non-condensing
20% to 85% RH;  
non-condensing
20% to 90% RH; 
non-condensing
Air pressure 
785 to 1060 hPa
700 to 1060 hPa
700 to 1060 hPa
Max. operating height
 
-
-

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2.1.1.1
HemoPill Receiver
The HemoPill Receiver (Figure 2-4) is an accessory (wireless, handheld device) to the HemoPill acute. The 
HemoPill acute and the HemoPill Receiver can only be used together. The HemoPill Receiver is designed 
to receive data from the HemoPill acute via the radio link and display this data to the user. 
Figure 4: Components of the HemoPill Receiver
The HemoPill Receiver features and is operated by a touch-sensitive color display. After activation of the 
HemoPill Receiver using the power button, the user controls the device via the touch display. Furthermore, 
the HemoPill Receiver features an USB-interface to connect to the HemoPill Printer for printing 
measurement results for documentation, a LED light source for activation of the HemoPill acute, and an 
indicator LED for data reception and charge level of the internal secondary battery (Figure 2-4). The internal 
secondary battery can be charged via the DC connection using the supplied external power supply (Figure 
2-5). Normal operation of the device is possible also during battery charging. The Receiver power supply 
is included in the scope of delivery.
The HemoPill Receiver contains a software for displaying the values measured and transmitted by the 
HemoPill acute. The HemoPill Receiver receives and saves the measured values. The values are displayed 
numerically and as a curve diagram on the display of the HemoPill Receiver. 
The HemoPill receiver can be disinfected using alcohol-based cleaning agents and disinfectants.
Figure 5: Connecting the HemoPill Receiver to the power supply

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Table 2: Specifications of the HemoPill Receiver 
Dimensions and weight 
Product dimensions (W x H x D)
96 x 145 x 37 mm
Net weight
262 g
Packaging information/dimensions (W x H x D) 
Case 465 x 350 x 110 mm
Gross weight 
approx. 
4.4 
kg 
(including 
accessories 
and 
packaging)
Version 
Software version
02.xx.yy
Device version
1.xx
Receiver power supply
Power input
100 V – 240 V AC
Supply voltage
220 V – 240 V AC
100 V – 120 V AC
Max. power consumption  
5 W / 12 VA 
5 W / 16 VA
5 W / 8 VA 
5 W / 10 VA
Supply frequency
50/60 Hz
50/60 Hz 
DC output voltage
5 V
Max. output current
5 A
Overcurrent protection (power input) 
2 A
Wireless specification 
Operational Frequency band  
433.05 MHz to 434.79 MHz 
Reception frequency
434.42 MHz
Reception bandwidth 
100 kHz
Modulation
GFSK
Receiver category
2
Application related specifications 
General specifications 
Reusable 
Non-sterile 
Environmental conditions for operation, transport and storage
Operation
Storage
Transport
Temperature
+10 °C to +40 °C
+10 °C to +40 °C
-10 °C to +50 °C
Relative humidity 
20% to 80% RH; 
non-condensing
20% to 90% RH; 
non-condensing
20% to 90% RH; 
non-condensing
Air pressure 
785 to 1060 hPa
700 to 1060 hPa 
700 to 1060 hPa
Max. operating height
 
- 
- 
2.1.1.2 
HemoPill Printer
The HemoPill Printer serves to document values measured by the HemoPill Receiver. It is designed solely 
for use with the HemoPill Receiver. It may only be connected to the HemoPill Receiver using the USB 
cable supplied. The accessories of the HemoPill Printer furthermore contain the power supply (rated output: 
9.0 VDC. 4A) as well as the paper reels for the printer. 
 
HemoPill printer is not a medical device. It must not be used in the patient environment. 

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Figure 6: HemoPill printer
2.1.2
Operating principle
The HemoPill acute has been specifically developed for detection of blood. The operating principle of the 
HemoPill acute relies on an optical sensor for alternating screening of the measuring gap in two different 
wavelengths emitted from LEDs (bicolor) on the other side of the measuring gap, opposite the sensor: red 
light at 700 nm and violet light at 415 nm (Figure 2-8). The optical sensor measures separately transmitted 
light intensity that passes the measuring gap, and the ratio of red to violet light transmission is calculated. 
The intensity of the measured light depends on the absorption characteristics of the medium in the 
measuring gap (e.g. blood). The measurement data is transmitted to the HemoPill Receiver via a radio link 
at a frequency of 434.42 MHz. 
Figure 7: Sensor principle; A: Red and violet light source, B: sensor/measuring gap, C: Light sensor
Figure 8: Sensor principle (side view)
2.1.2.1
Sensor principle
The transmission effects depend on the respective digestive tract content in the measuring gap. The two 
wavelengths being emitted by the bicolor LED have been selected to create a high sensitivity of the sensor 

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to the presence of blood inside the measuring gap. Blood shows a minimum light transmission rate 
(maximum light absorption rate) around 415 nm, and a maximum light transmission rate (minimum light 
absorption rate) around 700 nm (from about 650 nm into the infrared-range). These two wavelengths have 
been selected for the bicolor LED. Undiluted blood (venous, arterial) or hematin absorbs violet light at 415 
nm approx. 1,000-times more strongly than red light at 700 nm. The light sensor has a comparable 
sensitivity at both of these wavelengths. 
The sensor operation follows a fixes sequence: 
- 
First, the red LED (700 nm) is activated, and the resulting voltage signal at the light sensor, 
indicating the grade of absorption of red light, is digitalized (Ired) and stored. The red LED is 
deactivated subsequently. 
- 
Second, the violet LED (415 nm) is activated, and the resulting voltage signal at the light sensor, 
indicating the grade of absorption of violet light, is digitalized (Ivio) and stored. The violet LED is 
deactivated subsequently. 
- 
Third, the sensor value Q is calculated on the board of the HemoPill acute capsule and transmitted 
to the HemoPill Receiver via radio link. 
2.1.2.2 
Sensor value calculation 
The light sensor is translating the light intensity into a voltage, which is digitalized with a resolution of 10 
bit. Therefore, the intensities Ired and Ivio are given as an integer value on a scale from 0 to 1023.
 
The actual sensor value Q is calculated on the basis of these intensity values and further a correction factor 
for compensation of gain and offset errors of the intensity measurement. The correction factor is determined 
during production for each HemoPill acute capsule individually and stored in the non-volatile memory of 
the capsules. The correction factors are K for the gain error, and Ileak,red  and Ileak,vio fo the offset errors of the 
two LED wavelengths. 
 
A gain error can be caused by e.g. variances in the characteristics curves of the LEDs, the resistors or the 
voltage supply of the HemoPill acute capsule as well as variance of the surface structure of the 
encapsulation in the area of the measuring gap. An offset error can be caused by variances in the gap 
manufacturing that might allow light to reach the light sensor without passing the measuring gap, e.g. if the 
depth of the gap does not reach the printed circuit board (PCB) which is covered by a light blocking layer.  
 
The sensor value Q determines the ration between the grade of absorption of violet light and the grade of 
absorption of red light be the medium or fluid within the measuring gap. For example, if the absorption of 
violet light is ten times higher than the grade of absorption of the red light, the sensor value Q is 10. A 
detailed description of the calculation method of is given in the document “002_OVE_HP_Quotient 
calculation_Rev03_2018-04-06” in Volume 002. 
 
 
Q = Icorr2,red / Icorr2,via 
On the display of the HemoPill receiver the HI-value (short for HemoPill Indicator) is presented to the user. 
The sensor value Q is not appropriate for usability reasons, as the quotient requires a logarithmic scale to 
be read and interpreted in a way that it is clinically useful. Therefore, the HI-value, which ranges between 
0 and 1.5 on a linear scale, is used. It is calculated as follows: 
 
 
HI = 0.5 x log10(Q) 
 

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The resulting decimal values are rounded down to have one decimal number (e.g. 0.88 = 0.8, 1.31 = 1.3). 
by rounding down, the HI-value has the same clinical significance as the quotient (e.g. a quotient of Q = 99 
corresponds to a HI-value of HI = 0.9, therefore both are not crossing 100 and 1.0, respectively).
If the measuring gap is filled with blood, violet light can be almost completely blocked, while red light 
passes through the sensor gap almost entirely unimpeded. In this case, the HI-value can reach its maximum 
of 1.5.
Other foodstuffs can return a HI-value of up to 0.7 in individual cases. In empty stomachs the sensor can 
come into contact with undiluted bile as it passes through the stomach passage. This can lead to a HI-value 
of approx. 1.0. Several substances have been tested in an animal study, see Volume 005.
2.1.3
Clinical application
For intended examination, the detection of blood in the upper gastrointestinal tract, the patient swallows 
the HemoPill acute capsule (after activation) ((1) in Figure 2-9). The capsule must be taken with at least 
100 ml water, which aids swallowing and promotes the suspension of blood. The HemoPill acute 
continuously sends measurement data which are received and recorded by the HemoPill Receiver ((2) in 
Figure 2-9). Measurement data are displayed on the HemoPill Receiver for interpretation by the user ((3) 
in Figure 2-9). After the data acquisition procedure, the data can be printed using the HemoPill Printer.
Figure 9: Operation principle of the HemoPill acute system
The HemoPill acute continuously send approx. 5 measured values per minute to the HemoPill Receiver. 
The duration of the measurement is approx. 9 hours from activation of the HemoPill acute. The values 
measured by the capsule are displayed numerically and as a curve diagram on the display of the HemoPill 
Receiver (Figure 2-10). Furthermore, the capsule ID, which is individual for each individual capsule, is 
shown on the display, ensuring an allocation to the patient. The capsule ID is indicated directly on the blister 
packaging of the capsule. The separately enclosed patient labels (four stickers) serve the document in the 
patient file and do also include the capsule ID.
The numerical display shows the maximum HI value (MAXHI) (see (1) in Figure 2-10) and the last measured 
value (LASTHI) (see (2) in Figure 2-10)). The respective measuring time is located below. LASTHI is updated 
with each measured value received (about 5 times per minute). MAXHI updates every minute during the first 
hour, after the first hour until the 9th hour about every 8 minutes. The MAXHI value is also plotted as a curve 
over time (Figure 2-10). By pressing the information button (see (3) in Figure 2-10) information on 
interpreting the HI values are shown.

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Figure 10: Information on the display of the HemoPill Receiver
For interpretation of the HI values the following procedure is recommended:
1.
First, interpret the maximum HI value within 10 minutes from swallowing the HemoPill acute, see 
Table 3.
2.
Then interpret, independently of this, the maximum HI value in the further course of the 
Table 4.
Table 3: Interpretation of the HI value within 10 minutes after swallowing
HI
Within 10 minutes after swallowing 
< 0.8
Negative 
Liquid blood (or hematin) was not detected. 
NOTE: Blood may still be present but may be highly diluted or exist in unsuspended, 
adherent coagula.
Positive 
Liquid blood (or hematin) was detected. 
Table 4
HI
> 10 minutes after swallowing 
< 1.0
Negative 
Liquid blood (or hematin) was not detected. 
NOTE: Blood may still be present but may be highly diluted or exist in an unsuspended, 
adherent coagula. 
Positive 
Liquid blood (or hematin) was detected. 
The HemoPill is excreted through being passed naturally by the patient. To check that this has occurred, 
the transmission function of the capsule is active for at least 21 days. 
2.2.2
Device Category
The subject device is currently part of a DeNovo classification request. Thus, the specific device category 
is not yet established. If the DeNovo request is granted, a product code is assigned. 

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2.2.3
Non-significant risk rationale
Under 21 CFR 812.3(m), a significant risk device means an investigational device that: 
- 
Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare 
of a subject. 
NSR Rationale: The subject device is not an implant. 
- 
Is purported or represented to be for use supporting or sustaining human life and presents a potential 
for serious risk to the health, safety, or welfare of a subject. 
NSR Rationale: The subject device is not intended for supporting or sustaining human life. 
- 
Is for use of substantial importance in diagnosing, curing, mitigating, or treating disease, or 
otherwise preventing impairment of human health and presents a potential for serious risk to health, 
safety, or welfare of a subject 
NSR Rationale: Within the context of this clinical trial, any eligible trial participant is already 
scheduled for endoscopy based on the individual clinical presentation. The HemoPill acute is 
ingested prior to endoscopy and does not disrupt the clinical course of the trial participant. 
HemoPill acute data is retrospectively analyzed and compared to endoscopic findings. The data is 
however not used for risk stratification and does not influence the further clinical course of a given 
trial participant. The subject device is therefore not of substantial importance in diagnosing, curing, 
mitigating, or treating disease. The subject device does not further prevent impairment of human 
health and does not present a potential for serious risk to health, safety, or welfare of a subject. 
 
- 
Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject. 
NSR Rationale: The subject device does not present a serious risk to the health, safety, or welfare 
of a subject. Results from prior studies are provided in chapter 2.1. The described publications 
report on a total of 65 patients. Within these publications, no HemoPill acute capsule related 
complications were reported. One patient described discomfort while swallowing the HemoPill 
acute capsule (Brunk T et al., 2021).  
2.2.4 
Preclinical Data 
Ovesco performed various bench tests on the HemoPill acute which are briefly described in Table 7.  
 
Ovesco further conducted a volunteer trial and animal testing to investigate HemoPill performance. These 
are described in the following in more detail: 
 
2.2.4.1 
Volunteer trial 
Prior to market entry in Europe, feasibility testing was performed in a volunteer trial to evaluate the 
following aspects (Table 5): 
 
Table 5: Aspects and acceptance criteria of the volunteer trial 
No.
Aspect
Acceptance criteria
1
Direct, reproducible proof of presence of 
blood in stomach 
The measures sensor value during the course of 
the test must react specifically and sensitively to 
the presence of blood 
2
Quasi-continuous 
collection 
of 
measurement data 
Data transmission from the capsule to the 
receiver unit must be quasi-continuous at a 
measurement frequency > 1/min. 

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No.
Aspect
Acceptance criteria
3
Operating time
The passage duration and therefore the 
operating time of the capsule must be at least 4 
hours.
4
Introduction of capsule by swallowing
Capsule must be able to be swallowed without 
any problems. 
The aspects described in Table 5 were investigated through a series of 8 tests. Before testing started the test 
subject had an empty stomach (no ingestion of food or drink in at least 4 hours before start of the test). 
Three different meal scenarios ((1) empty stomach, (2) breakfast, (3) dinner) were planned and the capsule 
was swallowed a few minutes after the respective meal and blood ingestion (with different concentrations). 
The dose of blood ingested consisted of autologous blood from the vein of the respective test subject. No 
additives were added to the blood, which was ingested immediately after it was drawn.  
The data was acquired over the time period from the swallowing of the capsule to its expulsion.  
Results summary 
All capsules were expelled naturally from the test subject’s body. Passage duration was in average 79h 01 
min (standard deviation: 32h 17min; Max: 129h 58min; Min: 51h 25 min). The minimum measurement 
duration required (4 hours) was vastly exceeded in all tests. 
Several observations were made for the different scenarios. In general, it was shown that the amount of 
food in the stomach influences the blood detection. In all scenarios with blood ingestion, the presence of 
blood was shown by the HemoPill acute.  
In all 8 tests, swallowing of the capsule was possible without any problems. There were no complications. 
Bearing in mind that only one test subject was included in the test, it can be stated that neither size nor form 
of the capsule lead to any limitations with regards to swallowability of complications. 
The measurement interval was set to about 1 measurement every 4 seconds. Reception quality was 
adequate, so that essentially all measured values were recorded. Quasi-continuous collection of 
measurement data was achieved during all 8 tests. 
 
All acceptance criteria were met. 
 
2.2.4.2 
Animal trial 
The purpose of the pre-clinical animal study was to assess the sensitivity and specificity of the HemoPill in 
detection of upper digestive bleeding by means of an elaborate and realistic bleeding model (feasibility 
study). 
 
Since bleeding cannot be spontaneously induced in the animal by any means, a pre-operated model (pig) 
was used. Within the animals’ stomach, an artificial bleeding site was created: A small laparotomy was 
performed, a silicone tube was inserted into the gastric cavity and fixated to ensure it remained in place. 
The end of the tube was tunneled through the subcutaneous tissue of the animal to the area of the pig’s 
neck. This setting allowed the administration of blood from outside into the gastric cavity with variable 
parameters with regard to blood amount and speed of flow. 
 

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The study comprised 10 animals (4 animals for the pilot phase and 6 animals for the main trial) and was 
performed from October 2011 until August 2014.
The animal trial for the HemoPill has been conducted over a longer period during the development of the 
HemoPill acute capsule. Therefore, the HemoPill acute capsule and the receiver used for this animal study 
were prototypes. However, the sensor principle (red vs. violet wavelength, distance between the optical 
components, position of the measuring gap, as well as the potting material and coating) is unchanged in the 
final HemoPill capsule compared to the one used in the animal study. Therefore, the differences of the 
HemoPill acute capsule and Receiver have no negative impact on the quality of this animal study.
In clinical practice the HemoPill acute is swallowed by the patient. However, for this animal study, the 
HemoPill acute capsule stayed in the stomach for multiple episodes to maximize the data collection. For 
attaching the HemoPill capsule to the gastric wall for a period of 14 days, the HemoPill acute capsule was 
fixed to an OTSC clip prior to the intervention and implanted into the stomach endoscopically. Measured 
data was transferred to the receiver.
Each individual experiment started with endoscopic implantation of the HemoPill, and laboratory animals 
received the tube for bleeding simulation in the same session. In each animal two HemoPill capsules were 
implanted at two different locations in the gastric cavity, one in the closer proximity of the gastric bleeding 
site (entry of the bleeding tube) and one in the gastric antrum. The purpose was to evaluate if sensitivity 
varies by location. After implantation of the HemoPill the animal was followed and during an observational 
period of 14 days bleedings were simulated twice a day in order to evaluate the detectability of blood.
The influence of different modalities of food intake (fasting, noodle soup, potato mash and premade mash 
for infants, occasionally, in the pilot phase of study, high-caloric Fresubin was added to the food) on the 
detectability of blood by the HemoPill was investigated. The different food types were chosen to simulate 
liquid food (noodle soup) or more solid food (mashed potatoes, intending to imitate chewed food). For each 
animal, the feeding and bleeding test followed a specific test set-up. The test set-up und animal preparation 
are depicted in Figure 11.
Figure 11: Experimental set up for simulating gastric bleeding in a porcine model

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Total amount of bleeding tests is described in the following Table 6: 
Table 6: Total number of bleeding tests during the animal trial by type of food and simulated bleeding 
intensity. 
12 ml/hour 
60 ml/hour 
300 ml/hour 
No food 
19 
19 
--
Noodle soup 
19 
20 
15
Potato mash
17
16
15
The study demonstrates the capability of the HemoPill sensor to detect blood with high sensitivity and 
specificity values (typically > 80 %). The prototypical HemoPill was robust against food artifacts. 
Evaluation metrics of true positive, true negative, false positive, and false negative are to be clinically 
established by the proposed clinical trial at NYU Langone. 
2.2.4.3 
Bench testing 
In the following, performance testing conducted with the HemoPill is briefly described: 
 
Table 7: Performance testing conducted with the HemoPill 
Title and objective
Acceptance criteria
Results 
Lifetime test 
Confirmation of a minimum runtime of 
21 days in a physiological environment 
and minimum measurement time of 9 
hours. 
- The 
HemoPill 
capsule sends data 
packets for at least 
21 days. 
- A runtime of 21 
days, after two-year 
storage time can be 
derived 
from 
the 
storage 
time 
and 
electrical 
characteristics (test 
method: 
exploration). 
- The 
measurement 
time 
(active 
application mode 1) 
is at least 9 hours. 
The average HemoPill acute runtime 
were 36.77 days (standard deviation: 
2.48 days). Thereby, the minimum 
average 
runtime 
after 
two-year 
storage could be calculated and 
resulted in a minimum average 
runtime of 34.86 days. The test results 
showed an average measurement time 
(active application mode 1) of 28.1 
hours 
(standard 
deviation: 
0.55 
hours). 
All acceptance criteria were met 
Sensor performance 
Each HemoPill capsule (n = 22) was 
submerged into a blood solution 
(6.25 %). In order to generate a dark 
environment, the lid of the cup was 
closed as soon as possible. The capsule 
(in production made) performed ten 
measurements and transmitted the data 
- A blood solution of 
6.25 % leads to a 
signal (quotient) of 
at least 41. 
- In the defined dark 
environment, 
the 
The results showed a mean maximum 
quotient 
of 
423 
(standard 
deviation = 174,8) 
and 
a 
mean 
maximum external light (ELmax) of 1 
(standard 
deviation = 0.2). 
All 
acceptance criteria were met. 

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to the measurement computer, where 
the data was recorded by the sensor 
performance test software. The quotient 
was calculated based on the recoded 
data using the quotient calculation 
according to the specifications.
extraneous light is 
< 3.
Chemical resistance after shelf life 
test was performed to verify the 
chemical resistance of the HemoPill 
acute capsule in a worst-case scenario 
at the end of the shelf life. 
The test was performed with the final 
HemoPill capsule with 11 samples. 
Initial sensor performance testing was 
followed 
by 
a 
45 
-day 
acidic 
environment test. Then, a second sensor 
performance test was conducted. Initial 
performance 
testing 
served 
as 
reference. 
The 
quotient 
resulting from the 
measurement of a 
6.25 % blood dilution 
(in water) reaches 41 
or more after the 
capsule was chemical 
stressed in total for 45 
days (pH 1.1 – 1.3). 
All 
capsules 
showed 
a 
signal 
(quotient) > 41 when exposed to a 
blood-water dilution of 6.25 %, before 
and after chemical stress. 
Chemical resistivity Parylene C 
The chemically inert properties of 
Parylene C on the actual subject device 
in a simulated intended use (worst case: 
pH 1.0 – 1.3 for up to 60 days) were 
investigated. Three capsules were 
subjected to simulated gastric fluid for 
60 days, three capsules for 30 days and 
three capsules were not submerged in 
gastric fluid as reference. 
- After the simulated 
gastric 
fluid 
treatment, no visible 
damages or changes 
on 
the 
capsule 
surface are visible. 
- The thickness of the 
Parylene C layer is 
within the specified 
range 
of 
12 
µm ± 20 % on the 
analyzed position.
Within the chosen methodology, no 
difference between capsules that were 
exposed to chemical stress according 
to a worst case scenario and reference 
capsules from the same batch without 
exposure have been observed. 
Chemical reliability
Capsules implanted in pigs for the 
animal trial described in chapter 2.2.4.2
were explanted after the trial had 
concluded. 
Microscopic 
and 
macroscopic analysis of the capsule 
surface was performed.  
- No 
damage 
of 
capsule surface, e.g., 
scratches, 
notches, 
holes, splitting.  
- No capsule staining 
through 
the 
penetration 
of 
liquids inside of the 
capsule. 
The test shows that the HemoPill 
acute is able to operate safely in the 
harsh chemical environment of the 
stomach. The capsules showed no 
discoloration that would alter the 
sensor performance, nor did any 
defects on the encapsulation appear. 
The acceptance criteria were met for 
all 17 samples, thus the chemical 
resistance of all 17 capsuled could be 
verified. 
Mechanical strength
Capsule structural integrity against 
chewing. Exposure to 300 N chewing 
simulation with a genuine tooth, which 
is twice the normal human chewing 
Set Up 1 “Tooth”: 
No 
disintegrating 
damages 
to 
the 
HemoPill 
after 
Relevant damage to the capsule or 
exposure of electronic components 
due to biting / chewing is improbable 
since, even when assuming a high bite 
force of 300 N for a human molar, no 

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force. Second set up with metal wedge 
and force increase until complete 
disintegration 
applying 300 N five 
times.
Set Up 2 “Wedge”: 
No disintegration of 
the HemoPill below 
600 N 
damage that would comprise the 
capsule integrity was observed in this 
test. Regular voluntary bite force in 
humans is at about 70 to 150 N. 
Disintegration in set up 2 occurred at 
application of 1,800 N. 
Intestinal passage 
Simulated 
GI-passage: 
Simulated 
stomach milieu for 41 hours; simulated 
intestinal milieu for 653 hours. Visual 
inspection and functional testing after 
exposure. 
The integrity of the 
capsule measured by 
the appearance of any 
alterations 
of 
the 
encapsulation 
(defects, 
discolorations, etc.) is 
uncompromised. The 
capsules must also be 
successfully 
activated to confirm 
normal operability of 
the device after the 
stress test. 
The safety of the device is maintained 
throughout the entire passage of the 
GI tract and the exposure to the 
different environments. Furthermore, 
all capsules were fully operational, 
thus, the passage did not lead to any 
alterations of the encapsulation. 
Argon Plasma Coagulation stress test
Investigation of HemoPill material 
behavior in case high frequency 
hemostasis is performed in close 
proximity to the HemoPill. Test 
performed ex vivo in a porcine 
stomach. 
Insulation 
material 
does not deteriorate 
when HF-hemostasis 
procedure takes place 
in close proximity to 
the capsule. 
No damages to the insulation of the 
capsule could be observed. There 
were no signs of perforation or 
discoloration. 
The 
acceptance 
criterion was met. 
2.2.5 
Clinical Data to Date 
Publications of clinical data on the use of HemoPill in Europe is described in chapter 2.1. Prior to market 
entry in the EU, a clinical trial was conducted which is described in the following: 
 
Ovesco conducted a prospective non-randomized, single-center, open-label study to investigate feasibility 
and safety of the HemoPill acute in patients with symptoms of UGIB. The primary aim of the study was to 
investigate feasibility and safety of the device in a clinical setting. All patients underwent endoscopy within 
12 hours after capsule ingestion. Sensor data from the capsule within 10 minutes after ingestion were 
compared with endoscopic findings. 
 
From April 2015 to February 2016, 30 consecutive patients with symptoms of acute UGIB were included. 
 
Objective and clinical endpoints of the investigation were: 
- 
Safety of the capsule 
- 
Feasibility of bleeding detection 
- 
Evaluation of threshold values for the sensor capsule data 
- 
Sensitivity and specificity of the sensor capsule data 
 

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The clinical investigation population were patients with indications on esophagogastroduodenoscopy 
(ESG) and with suspected upper GI bleeding. Inclusion criteria were: 
- 
Clinical suspicion based on anamnestic statements of clinical symptoms such as hematemesis, tarry 
stools/melena 
- 
Alert and conscious patient 
- 
Written informed consent 
- 
 
 
The capsule was swallowed by the patient and an external study receiver recorded the capsule sensor data 
for 4 consecutive hours. Patients underwent endoscopy within 12 hours after capsule ingestion. Afterwards, 
the endoscopic findings (endoscopy pictures and patient’s endoscopy record) were compared to the sensor 
capsule data results. Capsule excretion was monitored for up to 4 days. If excretion was not recorded during 
that time, a follow up examination of the patient would have been conducted after 10 days.  
 
30 consecutive patients with symptoms of acute UGIB were included; 28 were eligible for analysis. All 
together the HemoPill acute was found to be feasible and safe. 
 
Only n=1 serious adverse event occurred during the study which, according to physicians, had no causal 
relationship to the use of the investigational device. Capsule ingestion was well tolerated in all patients. 
Passage and excretion of the HemoPill acute was observed without any adverse events or complaints by the 
patients. Furthermore, no adverse device effects or device deficiencies could be observed during the trial, 
thus the sensor capsule and the study receiver can be considered as safe devices that performed as expected 
in all n=30 subjects. 
 
n=1 human failure occurred during the read-out procedure of the sensor capsule data from the study receiver 
and was due to the wrong order in manual program execution. This failure is not relevant for the final 
receiver device because the read-out procedure was automated for the final device. 
Sensitivity and specificity assessment of the HemoPill acute in detecting the presence of blood in the upper 
GI tract proved to be favorable in patients with > 20 ml of blood: sensitivity = 100 % (95 % confidence 
interval (CI), 54 to 100 %) and specificity = 83 % (95 % CI, 60 to 95 %). However, comparatively wide 
95 % confidence intervals must be considered due to the low subject number included in the analysis. 
2.3 
Rationale 
Gastrointestinal bleeding is common. Its clinical spectrum ranges from anemia, which can only be detected 
in laboratory tests, to fulminant bleeding with shock. Gastrointestinal bleeding requires a differentiated 
approach from the first suspicion to acute care and prevention of renewed bleeding. A number of endoscopic 
(EGD, colonoscopy, device-assisted enteroscopy, and capsule endoscopy) as well as non-endoscopic 
procedures (CT angiography, angiography, scintigraphy) are available to localize the source of bleeding.  
2.3.1 
Epidemiology 
Upper gastrointestinal bleeding (UGIB) is defined as intraluminal bleeding derived from a source proximal 
to the Treitz ligament (Franco MC et al., 2015). Acute UGIB is a common condition worldwide, with an 
estimated annual incidence of 40 to 150 cases per 100,000 population. Acute UGIB frequently leads to 
hospital admission (more than 300,000 inpatient admissions in the US annually) and is associated with 
significant morbidity and mortality, in particular in the elderly (Chuang CH et al., 2020; Cai JX et al., 2018; 
Gralnek IM et al., 2015). The annual incidence of UGIB indicates that there are great geographical 
variations, which can be explained due to various factors including the different definitions of UGIB, 
population characteristics, different prevalence of drug-induced ulcers and Helicobacter pylori infection 

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(ISG, 2014). However, bleeding from the small intestine is a relatively rare event with 5 – 10 % of all GI 
bleedings (Gerson LB et al., 2015).  
 
The severity of UGIB is positively correlated with the amount of blood loss. Mixing of blood with gastric 
contents and feces, in addition to incomplete discharge of accumulated blood, makes it difficult to 
accurately judge the amount of blood loss according to the volume of hematemesis or melena. Therefore, 
the volume of blood loss is often determined based on clinical composite indexes such as peripheral 
circulatory changes caused by hypovolemia (e.g., heart rate, blood pressure) and the shock index rate (heart 
rate/systolic blood pressure), which are important indicators to determine the volume of blood loss (Bai Y 
and Li ZS, 2016). 
 
The 2015 German AWMF S2 consensus-based guideline on the quality requirements in gastrointestinal 
endoscopy (German: S2k Leitlinie Qualitätsanforderungen in der gastrointestinalen Endoskopie, 2015 
“Guideline: Quality specifications in gastrointestinal endoscopy”) by Denzer and colleagues states that 
predictive factors for severe UGBI are an underlying tumor disease or liver cirrhosis, hematemesis, 
hypovolemia and hypotension, as well as shock and an Hb < 8 g/dl. Further, with a strong consensus, the 
guideline recommends that severe UGIB and increased mortality must be taken into account if certain 
factors are present, such as additional comorbidities (such as heart, liver, tumor disease), limited clinical 
and laboratory parameters (Hb < 8 g / dl, INR < 1.5, albumin < 
al., 2015). 
 
The use of risk scores has been recommended to stratify patients into those at higher or lower risk of poor 
outcomes. Those at very low risk may be managed as outpatients (Stanley A and Laine L, 2019). A primary 
goal of initial assessment is to determine whether the patient requires urgent intervention, e.g., endoscopy, 
surgical intervention or transfusion, or can undergo delayed endoscopy or even be discharged to outpatient 
management (Hwang JH et al., 2012). Elderly age, multiple comorbidities and hemodynamic instability 
indicate aggressive treatment (ISG, 2014). In geriatric patients, great care must be taken to obtain a thorough 
medical history and identify comorbidities. Determination of the etiology and severity of UGIB should be 
a high priority in light of current diagnostic and therapeutic advances, with consideration given to geriatric-
specific causes. Lab tests that should be obtained in patients with acute UGIB include complete blood count 
(CBC), serum chemistries, liver function tests and lactic acid and coagulation studies. An increased 
BUN/serum creatinine ratio is often identified in patients with UGIB. In addition, serial electrocardiograms 
and cardiac enzymes may be indicated in patients who are at risk for a myocardial infarction (Stowlow E 
et al., 2021). 
2.3.2 
Scoring systems 
A number of scoring tools have been developed for predicting outcomes following acute UGIB, with the 
Rockall Score and the Glasgow-Blatchford Score being the most widely evaluated and adopted. However, 
no single tool has been shown to excel at predicting all relevant outcomes in UGIB, including re-bleeding, 
need for intervention and mortality (Gralnek IM et al., 2015; Al Dhahab H et al., 2013; Ramaekers R et al., 
2016). 
The Rockall Score was primarily developed for the assessment of mortality after 30 days of UGIB (Franco 
MC et al., 2015). The Rockall score can be calculated using both pre-endoscopic (clinical Rockall) and 
post-endoscopic data. The full Rockall Score incorporates both pre- and post-endoscopic parameters. It 
predicts the risk of re-bleeding and mortality using age, the presence of shock (systolic blood pressure < 100 
mmHG and heart rate > 100 beat/min), comorbidities and endoscopic diagnosis along with endoscopic 
findings, such as blood in stomach, adherent clot, visible vessel, spurting vessel, pigmented spot or no 
stigmata (Table 23). The Rockall Score ranges from 0 to 11. Patients with risk scores of 0 and 1 have a low 

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incidence of re-bleeding and no associated mortality, allowing the identification of patients at low risk for 
complications and for early discharge (Al Dhahab H et al., 2013).
Table 8: The full (post-endoscopy) Rockall Scoring System (for a patient with acute upper gastrointestinal 
bleeding, add up scores at the top of the columns for each of the variables to derive the total risk score*) 
(Dworzynski K et al., 2012).
The Glasgow Blatchford Score (GBS) was developed to identify a patient’s need for treatment in order 
to assist the clinical management of patients presenting with UGIB. The GBS ranges from 0 to 23 and uses 
data on blood urea and hemoglobin levels, systolic blood pressure, pulse, presentation with melena, 
presentation with syncope, history of hepatic disease and history of heart failure (Table 9; Hwang JH et al., 
2012). A GBS of 0 predicts a 0.5 % risk for needing subsequent intervention, thus, early discharge and 
outpatient follow-up (Al Dhahab HA et al., 2013). The European Society of Gastrointestinal Endoscopy 
(ESGE) recommends the use of the GBS for pre-endoscopic risk stratification (Gralnek IM et al., 2015).
Table 9: Glasgow-Blatchford Score (GBS) (Gralnek IM et al., 2015).

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The AIMS-65 scoring system provides a more geriatric-adjusted score and may be a useful addition to the 
risk-stratification approach in identifying high-risk patients. AIMS-65 assigns one point for each of the 
following: albumin < 3 g/dl, international normalized ratio (INR) > 1.5, alteration in mental status, systolic 
blood pressure (SBP) 
90 mmHg, and age 
65 years. These values are readily obtainable from patient 
monitoring and labs in the emergency department. Recent studies suggest that this system may provide a 
more accurate prediction of in-hospital mortality, need for ICU admission, and length of hospital stay. As 
referenced by Stolow and colleagues, Robertson et al. found that a score > 3 was considered high risk with 
a mortality of 12.1 % compared with 1.6 % in the lower risk group (p < 0.001). As referenced by Stolow 
and colleagues, Kawaguchi et al. showed mortality to be as high as 33 % in patients scoring 4 - 5. Directed 
therapeutics should be based on the evaluation of etiology, comorbidities, and risk. While the International 
Consensus Group (ICG) did not recommend the use of the AIMS-65 score for risk assessment, its 
recommendation was based on low quality of evidence, and therefore, more prospective studies are needed 
to determine its true utility in the geriatric population (Table 25, Stolow E et al., 2021).
Table 10: The AIMS-65 scoring system. Score 1 point for each of the categories. Add the points recorded 
to find the total score. The in-hospital mortality rates by score are: 0: 0.3 %, 1: 1.2 %, 2: 5.3 %, 4: 16.5 % 
5 24.5 % (source: Stolow E et al., 2021).
2.3.3
Summary
While the above-mentioned scoring systems and general clinical presentation of a patient are considered, 
approximately one third of all endoscopic interventions for suspected UGIB are inconclusive. This is 
deemed acceptable as patient risks from endoscopy are known and rare. Conducting an endoscopy on a 
patient that does not require one is considered safer than potentially missing a patient who would have 
needed endoscopic work up. HemoPill is designed to provide information on the acute presence or absence
of blood/hematin in the gastrointestinal lumen. This piece of information has been shown to be valuable in 
the further risk stratification in patients with suspected UGIB. As described by Brunk T et al., a negative 
HemoPill measurement influenced the further clinical course of patients in 72 % of cases, mostly by shifting 
from emergency/urgent endoscopy to elective endoscopy. All HemoPill negative patients who did receive 
endoscopic work up did not show bleeding stigmata. The proposed clinical value of the HemoPill is that 
allocation of endoscopic resources can be more adequately planned which is a considerable financial benefit 
to the patient as well as the health care system. That being said, HemoPill is not intended to replace 
endoscopic procedures. Endoscopy does require patient preparation but has ultimately various curative 
possibilities in case pathologies are found. HemoPill solely provides information on the acute presence of 
blood/hematin in an otherwise unprepared patient in a real time fashion – no more, no less. The reliability 
of the measurement could already be shown in real-world use of the subject device in the EU. The value of 
the information on the presence or absence of blood/hematin in the GI lumen needs to be assessed within 
the context of the broader clinical presentation of a given patient and thus may differ from case to case.

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Hypothesis: 
Relation between HemoPill measurements to subsequent endoscopic findings show an adequate sensitivity 
and specificity for the HemoPill measurement regarding presence or absence of blood in the GI lumen. 
 
Justification for route of administration and selection of study population: 
Only patients already scheduled for an endoscopy on the basis of suspected UGIB are eligible for trial 
participation. HemoPill ingestion is embedded into the already fixed schedule for endoscopy. Endoscopy 
is not delayed by trial participation. HemoPill measurements do not influence the clinical course of a trial 
participant. Thus, no risks from false (e.g., false negative or false positive) measurements arise. 
 
Rational for endoscopy as a control measure: 
While there are differences between the function principle of the HemoPill and endoscopy, endoscopy is 
the most suitable control measure. UGIBs are volatile events as activity of a bleeding can be spontaneous. 
HemoPill is able to detect fresh blood and hematin within the GI lumen, thus solely requires presence of 
blood or hematin which can stem from a currently inactive pathology.  
 
Endoscopy is able to identify blood or hematin as well as associated pathologies. Thus, relation between a 
HemoPill measurement and endoscopic findings is generally possible. Even more so if latency between 
HemoPill ingestion and endoscopy is a controlled parameter. 
 
The aim of this clinical trial is to further investigate HemoPill’s capacity to determine presence or absence 
of blood/hematin in a clinical setting by comparing a HemoPill measurement with endoscopic findings. 
Patients eligible for trial participation are already scheduled for endoscopy for suspicion of UGIB. Thus, 
the HemoPill measurement is not considered for further risk stratification and only put in relation to 
endoscopic findings after the fact. To allow for a reasonable comparison of HemoPill measurement and 
endoscopic findings, latency between the two is controlled. However, as scheduling for endoscopy is 
already in place as a prerequisite for trial participation, planning of HemoPill ingestion is embedded into 
endoscopy schedule – thus, no delay to endoscopy is introduced. The patient always receives endoscopy as 
planned, regardless of trial participation.  
 
2.4 
Potential Risks & Benefits 
2.4.1 
Known Potential Risks 
As the subject device is already marketed in the EU, foreseeable risks and complications provided in the 
instructions for use are: 
- 
Aspiration of the capsule on ingestion 
- 
Delayed excretion, or failure to excrete the capsule (capsule retention) 
- 
Obstruction of the digestive tract 
- 
Injury to tissue structures during the passage of the HemoPill acute through the digestive tract. In 
particular: 
o Injury to the mucosa 
o Bleeding, e.g., variceal bleeding 
o Perforations 
 
The above-mentioned risks are generally associated with capsule endoscopy. So far, no case of harm to a 
patient from the use of the HemoPill has been reported.  
 
Risks to participants by virtue or trial participation 

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- 
Immediate risks 
o Aspiration of the capsule on ingestion 
o Obstruction of the digestive tract 
o Injury to tissue structures during the passage of the HemoPill acute through the digestive 
tract. In particular: 
 
Injury to the mucosa 
 
Bleeding, e.g., variceal bleeding 
 
Perforations 
- 
Long-range risks 
o Obstruction of the digestive tract 
o Delayed excretion, or failure to excrete the capsule (capsule retention) 
 
- 
Necessity of exposing human participants to above-mentioned risks 
The above-mentioned risks are generally associated with capsule endoscopy, e.g., video capsule 
endoscopy. As of today, no incidence of patient harm from use of HemoPill has been reported. 
Within the trial context, HemoPill is ingested in a closely supervised setting. Within the trial 
context, a HemoPill measurement does not influence the clinical course of a given trial participant. 
Thus, any hypothetical risks from false negative or false positive measurements are avoided.  
 
On the other hand, investigating HemoPill’s capacity for reliably providing information on the 
presence or absence of blood in the GI lumen has the potential to better understand the clinical 
applicability of the device and provide information on the proposed clinical benefit. In case 
HemoPill shows to be a reliable and effective tool, it can be safely introduced into clinical routine 
and unfold its then identified potential. 
 
- 
Value of the information to be gained outweighs the risks involved 
So far, HemoPill use has not resulted in any harm to a patient. The known risks are controllable 
and generally associated with capsule endoscopy. A risk from a potential false negative or false 
positive measurement does not apply within the context of the trial as the HemoPill measurement 
is disregarded in patient assessment. The value of a side-by-side comparison to endoscopy however 
further distinguishes the performance profile of the subject device. Scientifically sound 
determination of accuracy parameters is achievable with the proposed trial design. With these 
accuracy parameters adequately determined, the use of the HemoPill (once legally marketed) as 
well as interpretation of HemoPill measurement is tremendously facilitated. Introducing HemoPill 
into the clinical routine for risk stratification of suspected UGIB patients facilitates adequate 
allocation of emergency resources and potentially avoids unnecessary endoscopies altogether, as 
Brunk T. et al have shown.  
 
- 
Rationale: Exclusion of alternative procedures 
HemoPill is compared to an endoscopy already scheduled regardless of trial participation. Ultimate 
goal of the trial is establishing accuracy parameters of the HemoPill measurement to provide data 
needed for an adequate risk evaluation. The HemoPill measurement is however disregarded for 
further patient evaluation. Thus, no alternative procedure is required as it would also not influence 
the further clinical course of a trial participant. The control method endoscopy is already indicated 
and scheduled as per NYU protocol and neither delayed nor prolonged by trial participation.  

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2.4.2
Known Potential Benefits
With regard to trial participation, no immediate potential benefits are expected for a trial participant. Long 
range potential benefits stem from an introduction of HemoPill into the US market. On the basis of then 
established accuracy parameters, adequate consideration of HemoPill measurements for risk stratification 
will potentially lead to avoidance of endoscopic procedures if overall clinical presentation permits, which 
is a considerable benefit to a patient. Improving risk stratification precision by taking HemoPill 
measurements into consideration introduces benefits the health care system in general as decision for urgent 
or elective endoscopies are made on the basis of additional relevant and previously unavailable information 
on the presence or absence of blood/hematin in the GI lumen. 
HemoPill is designed to provide information on the presence or absence of blood or hematin in the 
gastrointestinal lumen. The measurement data is depicted graphically and numerically in real time and 
allows for immediate data evaluation based on the introduced measurement value threshold. Ingestion of 
the HemoPill acute capsule does not require patient preparation and usability testing as well as clinical use 
in Europe indicates easy use and data assessment. The information on the presence or absence of blood in 
suspected UGIB patients is usually only available from nasogastric tube aspiration. However, this procedure 
has major deficiencies and is associated with a mediocre sensitivity and specificity as well as discomfort to 
the patient. HemoPill acute ingestion on the other hand has not caused any such discomfort. The value of 
the information on presence or absence of blood or hematin in a patient with suspected UGIB has to be 
assessed within the context of the overall clinical presentation of said patient, e.g., scoring systems, blood 
samples, Hb value, blood pressure etc.  
 
The real-world clinical benefit from HemoPill use is best described by Brunk T et al (see chapter 2.1). Here, 
a negative HemoPill measurement influenced the further clinical course of patients in 72 %: 40 % of 
patients were rescheduled from urgent to elective endoscopy, in 20 %, small bowel enteroscopy could be 
avoided and in 12 %, EGD could be avoided. No HemoPill negative patient has a clinically significant 
bleeding until discharge. In HemoPill positive patients, median time to EGD was 3 h 18 minutes (range: 12 
min – 64 h 52 min), whereas median time to EGD (if performed) was 19 h 52 min (range: 1 h 45 min – 146 
h 10 min), which beautifully presents the influence of a HemoPill measurement within the broader context 
of risk stratification in patients with suspected UGIB.  
 
Further benefits from availability of the HemoPill were reported within the context of risk stratification 
under COVID-19 pandemic conditions. Elsayed I et al. report on three cases as described in chapter 2.1. 
The authors conclude that the sensor capsule might aid in decision-making during the COVID-19 pandemic. 
In patients with as yet unavailable COVID-19 test results, HemoPill might aid in determining the 
appropriate time for endoscopy. In patients who are positive for COVID-19 with suspected UGIB, 
HemoPill could help on deciding whether to perform an endoscopy or nor and thereby help minimizing risk 
of disease transmission.  
 
3 
Objectives and Purpose 
3.1 
Primary Objective 
The objective of the study is to determine the clinical relation between the detection of blood in the GI 
lumen using the HemoPill acute (trial procedure) with the detection of bleeding / a bleeding source during 
an endoscopic examination (control procedure). The study is an intra-case control procedure. 

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4
Study Design and Endpoints
4.1 
Description of Study Design 
Patients are included according to the defined inclusion criteria and prepared for endoscopy. At the latest 
possible time before endoscopy, a HemoPill acute capsule is administered with a minimal amount of water. 
The HemoPill receiver is stored in a carrying bag. The transparent part of the bag over the display of the 
receiver is covered with tape. The LED light is left uncovered, so a successful signal transmission can be 
checked at any times. The investigator is unaware of the HemoPill acute measurement result until 
endoscopy has concluded. After a latency of minimum 20 minutes, maximum 60 minutes, endoscopy is 
performed as scheduled, identifying blood within the GI lumen, if present. A minimum latency is introduced 
to ensure HemoPill acute is able to make a measurement without interference from endoscopy, e.g., 
insufflation or endoscopic light. 
 
The amount of blood identified in endoscopy is visually analyzed and pictures are taken. For the estimation 
of the amount of blood present in a patient, comparative images are provided. Assessment categories are: 
x < 20 mL and x > 20 mL. The detection threshold is introduced to provide a point of reference for the 
HemoPill acute detection rate.  
 
Pathologies, if found, are treated as per clinical standard. HemoPill acute measurements regarding presence 
or absence of blood are put in relation to endoscopic findings. 
 
Endoscopic images are further analyzed to determine the digestive state of the blood found as HemoPill 
acute is capable of detecting fresh blood or hematin. Blood digested to a point beyond hematin is no 
indicator for an acute bleeding pathology. The following foreseeable combination of events are described 
and allocated to “True Positive”, “False Positive”, “True Negative”, and “False Negative”. 
- 
True positive: 
HemoPill acute measurement indicates presence of blood; Endoscopy identifies fresh blood or 
hematin in the GI lumen 
- 
False positive: 
HemoPill acute measurement indicates presence of blood; Endoscopy does not identify fresh blood 
or hematin in the GI lumen. 
- 
True negative: 
HemoPill acute measurement does not indicate presence of blood; Endoscopy does not identify 
fresh blood or hematin in the GI lumen in quantities > 20 mL; Minimum latency of 20 minutes 
achieved. 
- 
False negative: 
HemoPill acute measurement does not indicate presence of blood in the GI lumen; Endoscopy 
identifies fresh blood or hematin in the GI lumen in quantities > 20 mL; minimum latency of 20 
minutes achieved.  
 
Patient recruitment goal is set at 50 patients as derived from statistical planning, including potential 
dropouts. The proposed clinical trial is a single-arm, single-center clinical trial. The control procedure 
endoscopy is applied in all trial participants as an intra-case relation of HemoPill measurement and 
endoscopic evaluation is performed. 

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4.2
Study Endpoints
4.2.1 
Primary Study Endpoints 
Clinical effectiveness endpoint 
- 
Result Accuracy: Clinical relation between HemoPill acute measurement (trial procedure) and 
endoscopic findings (control procedure) according to the defined scenarios for “true positive”, 
“false positive”, “true negative”, “false negative” (see above, chapter 4.1). 
4.2.2 
Secondary Study Endpoints 
Technical effectiveness endpoint 
Technical success, defined as: 
- 
Successful data transmission of the HemoPill acute to the HemoPill Receiver. 
 
Safety endpoints: 
Adverse events / complications associated with trial or control procedure, such as: 
Trial procedure: 
- 
Aspiration of the capsule on ingestion 
- 
Delayed excretion, or failure to excrete the capsule (capsule retention) 
- 
Obstruction of the digestive tract 
- 
Injury to tissue structures during the passage of the HemoPill acute through the digestive tract. 
 
Control procedure: 
- 
Cardiopulmonary adverse events 
- 
Infection 
- 
Perforation  
- 
Bleeding (iatrogenic) 
 
These secondary endpoints were chosen as they potentially provide meaningful information on the safety 
(number and type of adverse events / complications) and performance (successful data transmission) of the 
subject device. 
4.2.3 
Exploratory Endpoints 
Not applicable. 
5 
Study Enrollment and Withdrawal 
5.1 
Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Patient is scheduled for endoscopy due to suspicion of UGIB based on clinical and / or laboratory 
findings 
2. Signed informed consent 
3. 
 
4. Willingness and ability to participate in the study procedure 
5.2 
Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. The inclusion criteria cannot be met  

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2.
Contraindications to the use of the HemoPill acute, such as:
a. Known gastrointestinal obstruction, stricture, fistula, or diverticula 
b. Dysphagia or other swallowing disorders 
c. Pregnancy 
d. Incapacity to provide informed consent  
e. In patients with cardiac pacemakers and other implanted medical devices 
5.3 
Vulnerable Subjects 
No vulnerable subjects are to be included in the clinical trial.  
5.4 
Strategies for Recruitment and Retention 
The patient may be recruited from both inpatient and outpatient setting. Patient will be identified by our 
gastroenterology inpatient consult team when a consult for upper gastrointestinal bleeding has been 
suspected on admission or by an outpatient provider that is part of the study when they see the patient in 
their perspective clinics. Patients for suspected upper GI bleed will be asked by a study member of his/her 
willingness to participate in the study. The target number for subject recruitment is 50. The study team will 
not be using Epic as part of the recruitment process.  
 
All subjects will be recruited from the PI and sub-investigators’ practices or under their care in the inpatient 
setting. Potential subjects will be approached at one of their clinic visits by the PI, sub-investigator or 
research coordinator. Potential subjects will be approached after suspicion of a GI bleed led to the 
scheduling of endoscopy. Patient will be consented prior to scheduled endoscopy and sedation. Time 
between approaching potential subjects and onset of study procedures may vary as this depends on the 
scheduling of endoscopy. Scheduling for endoscopy is influenced by, e.g., urgency of the patient’s situation 
and availability. It is not influenced by willingness or unwillingness to participate in the study. No 
recruitment materials are needed for this process. 
5.5 
Duration of Study Participation 
From screening a likely trial participant to enrollment and to conclusion of the endoscopic procedure, 
usually 1 hours to 3 days elapse. Screening of a potential trial participant occurs after a NYU patient is 
scheduled for endoscopy for a suspected UGIB. Scheduling of endoscopy is at the attending physician’s 
discretion and not within the scope of the trial. If patient screening is successful and informed consent is 
obtained, the study intervention phase starts approximately 20 minutes to 1 hour prior to endoscopy. The 
study intervention phase finishes with conclusion of endoscopy. No trial related follow-up is required. 
Scheduling further appointments to follow-up on endoscopic findings are not within the scope of the clinical 
trial. 
 
5.6 
Total Number of Participants and Sites  
Recruitment will end when approximately 50 participants are enrolled. It is expected that approximately 50 
participants will be enrolled in order to produce 43 evaluable participants. Enrollment will take place solely 
at NYU Langone Health- Tisch Hospital. 
 
5.7 
Participant Withdrawal or Termination 
5.7.1 
Reasons for Withdrawal or Termination 
Participants are free to withdraw from participation in the study at any time upon request. An investigator 
may terminate participation in the study if: 

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Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
 
The participant meets an exclusion criterion (either newly developed or not previously recognized) 
that precludes further study participation 
 
Decision for conducting endoscopy is reversed for any reason 
 
5.7.2 
Handling of Participant Withdrawals or Termination 
Participant withdrawal or termination does not affect subject safety. If a patient withdraws from 
participating in the clinical trial, scheduling of endoscopy is not affected. He or she will continue to be 
scheduled for endoscopy regardless of trial participation and therefore receive appropriate clinical care. 
Participation may be terminated by an investigator. As the trial procedure does not provide any immediate 
clinical benefits for a participant (see chapter 2.4.2), he or she is not negatively affected by termination. As 
the trial uses an intra-case relation of HemoPill measurement and endoscopy, any trial participant is 
evaluated on the basis of his or hers HemoPill measurement and endoscopic findings. Withdrawal or 
termination does therefore not require replacement of any individual participant for intra-individual 
comparison. The total number of participants is determined based on statistical considerations. 
 
5.8 
Premature Termination or Suspension of Study 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. 
Written notification, documenting the reason for study suspension or termination, will be provided by the 
suspending or terminating party to investigator, and regulatory authorities. If the study is prematurely 
terminated or suspended, the PI will promptly inform the IRB and will provide the reason(s) for the 
termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
Determination of unexpected, significant, or unacceptable risk to participants 
 
Demonstration of efficacy that would warrant stopping 
 
Insufficient compliance to protocol requirements 
 
Data that are not sufficiently complete and/or evaluable 
 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, data quality are addressed and satisfy 
the sponsor, IRB and/or FDA. 
 
6 
Study Agent (Study drug, device, biologic, vaccine etc.) and/or Procedural Intervention  
 
6.1.1 
Acquisition 
Subject device 
The HemoPill acute and HemoPill Receiver are Ovesco Endoscopy AG products, CE-labeled and marketed 
in the European Union. The HemoPill acute is provided sterile with a shelf life of 2 years. The HemoPill 
Receiver is provided non-sterile and is neither required nor intended to be sterilized. Packaging, sterilization 
and shipping of the HemoPill acute and HemoPill Receiver follow established and verified processes as 
required for medical devices in the EU. These processes are not altered for the devices provided for clinical 
trial purposes. The final, finished devices are supplied to NYU by Ovesco USA Inc.  

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Control product 
The control procedure is endoscopy. Endoscopes and associated devices and accessories are chosen as per 
site protocol, physician’s discretion and provided by NYU. 
6.1.2 
Formulation, Appearance, Packaging, and Labeling 
Subject device 
HemoPill acute capsules are provided sterile in a transport carton containing single blister packaging and 
instructions for use. The HemoPill Receiver is provided non-sterile in a transport carton containing blister 
packaging and instructions for use. The subject device is provided by Ovesco USA Inc. Ovesco Endoscopy 
AG is the legal manufacturer of the subject device for the European market. For trial purposes, the subject 
device is to be considered as an investigational device. The subject device is available for human use in the 
EU and does not require alterations to meet the trial plan. 
 
Control product 
The control procedure is endoscopy. Endoscopes and associated devices and accessories are chosen as per 
site protocol, physician’s discretion and provided by NYU. 
6.1.3 
Product Storage and Stability 
Subject device 
The HemoPill acute capsules are provided sterile in single blister packaging. As marketed devices, 
sterilization validation, transport simulation, aging etc. has been conducted. The sterile HemoPill acute 
capsule has a shelf life of two years. Information on storage conditions is provided on device labeling and 
used visuals are described in the instructions for use. The HemoPill acute capsules should be stored between 
10°C and 30°C and protected from direct solar radiation. Relative humidity during storage should be 
between 20 % and 85 %, non-condensing. 
The HemoPill Receiver is provided non-sterile. It has a service life of 10 years. Storage conditions should 
be: 
- 
Temperature: between – 10°C and + 50°C 
- 
Relative humidity: 20 % to 90 %, non-condensing 
- 
Air pressure: 700 to 1,060 hPa 
 
While storage temperatures may be as low as – 10°C, the HemoPill Receiver needs to acclimatize to room 
temperature is stored below + 10°C. Further information is provided in the instructions for use. 
 
Control product 
The control procedure is endoscopy. Endoscopes and associated devices and accessories are chosen as per 
site protocol, physician’s discretion and provided by NYU. Respective storage conditions apply as indicated 
on the device labeling. 
6.1.4 
Preparation 
Subject device 
In the following the stepwise clinical use of the HemoPill acute is described 
- 
Switching on the HemoPill Receiver 
- 
Activation of the HemoPill acute using the HemoPill Receiver 
- 
Establishment of a data connection between HemoPill acute and HemoPill Receiver 
- 
Handing the activated HemoPill acute to the patient in the blister 
- 
Swallowing of the HemoPill acute with a small amount of water 

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-
Receiving and reading of measurement data (HI values) using the HemoPill Receiver
- 
Interpretation of the measured values by the user based on the information provided in the IFUs of 
the HemoPill acute and HemoPill Receiver (document A01) 
- 
At the end of measurement, deactivation of the data connection with the HemoPill Receiver 
- 
Natural excretion of the HemoPill acute by the patient 
 
A detailed description on the handling of the HemoPill Receiver can be found in the respective instructions 
for use, provided as a separate document. 
 
Control product 
The control procedure is endoscopy. Endoscopes and associated devices and accessories are chosen as per 
site protocol, physician’s discretion and provided by NYU. Use of endoscopy is clinically established, as 
are requirements for preparation. 
6.1.5 
Dosing and Administration 
Subject device 
The HemoPill acute capsule is switched on using the HemoPill Receiver as described in the instructions for 
use. A data connection between the HemoPill acute capsule and the HemoPill Receiver is established. Every 
trial participant receives a single, sterile, switched on HemoPill acute capsule for ingestion with a minimal 
amount of water. The HemoPill acute capsule is not to be chewed. Ingestions is timed under consideration 
of endoscopy scheduling. Minimum latency to endoscopy should be 20 minutes, maximum latency to 
endoscopy should be one hour. The HemoPill Receiver is operated by the investigators. 
Control product 
Application of endoscopy as per clinical standard. Scheduling of endoscopy follows NYU protocol and 
suspected urgency of a given patient’s situation. 
 
6.1.6 
Route of Administration 
Subject device 
Administered orally by ingestion.
Control device 
Oral introduction of endoscope. 
6.1.7 
Starting Dose and Dose Escalation Schedule 
Not applicable. 
 
6.1.8 
Dose Adjustments/Modifications/Delays 
Not applicable. 
 
6.1.9 
Duration of Therapy 
From HemoPill acute capsule ingestion to start of endoscopy, a maximum of 60 minutes elapse. Duration 
of endoscopy depends on presence or absence of pathologies and time needed for treating pathologies if 
found.  
 

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6.1.10 Tracking of Dose
Not applicable. 
 
6.1.11 Device Specific Considerations 
Subject device 
- 
Device size:  
- 
Length: 26.3 mm 
- 
Maximum diameter: 7 mm 
- 
Weight: 2 g 
- 
Device model 
- 
HemoPill acute capsule: Software version 02.xx.yy 
- 
HemoPill Receiver: Software version 02.xx.yy 
- 
Device settings and programming 
- 
HemoPill acute capsule: No settings or adjustments can be made during the trial. Software 
version 02.02.xx is implemented. 
- 
HemoPill Receiver: The HemoPill Receiver is used for activating a HemoPill acute 
capsule, for establishing a data connection between a HemoPill acute capsule and for 
displaying HemoPill acute measurements. Up to 50 data sets can be stored on the HemoPill 
Receiver. The HemoPill Receiver can be used to display, store, and delete data sets. The 
HemoPill Receiver cannot be used to alter or manipulate data sets. 
- 
Frequency of exposure 
- 
HemoPill acute capsule: Once, duration of exposure from ingestion to excretion 
- 
HemoPill Receiver: Once, from establishing a data connection to a HemoPill acute capsule 
to conclusion of the measurement. 
 
6.2 
Study Agent Accountability Procedures 
The subject devices are provided to NYU by Ovesco. Distribution of HemoPill acute capsule is within the 
responsibility of the investigators. For trial purposes, at least 50 HemoPill acute capsules and minimum 2 
HemoPill Receivers will be provided to NYU. Requirements for adequate and safe handling are provided 
by described storage conditions. Unused products are returned to Ovesco Endoscopy AG. 
 
6.3 
Study Procedural Intervention(s) Description 
Within the scope of the proposed trial, HemoPill acute capacity for providing information on the presence 
or absence of blood in the GI lumen is controlled by relation to an endoscopic intervention. Latency to 
endoscopy is controlled. The trial procedure HemoPill acute introduces ingestion of the HemoPill acute 
capsule by the patient as a procedural intervention. Endoscopy however is not a procedural intervention in 
the sense that a patient is subjected to endoscopy for trial purposes. Endoscopy is already scheduled for the 
trial participant to further investigate the suspicion of UGIB and for treatment of lesions if identified.  
6.3.1 
Administration of Procedural Intervention 
The investigator activates the HemoPill acute capsule by using the HemoPill Receiver. A data connection 
to the HemoPill Receiver is established. The activated HemoPill acute, still within the blister, is handed to 
the trial participant for ingestion with a minimal amount of water. Ingestion is timed under consideration 
of the previously established scheduling for endoscopy. Between HemoPill acute ingestion and start of 

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endoscopy, a minimum of 20 minutes should have elapsed. No more than 60 minutes between HemoPill 
acute ingestion and start of endoscopy should elapse. A trial participant is subjected to one intervention.  
6.3.2 
Procedures for Training of Clinicians on Procedural Intervention 
Investigators are trained in the use of the HemoPill acute capsule and HemoPill Receiver. Adequate training 
material is available. As the subject device is already marketed in the EU, usability data and user feedback 
are available, indicating a safe and easy use. For endoscopy, no additional training is provided. Investigators 
are however instructed to document finding of blood and/or hematin in the GI lumen if identified. A single 
investigator trained for estimating amounts of blood and/or hematin on the basis of endoscopic images will 
assess the amount of blood/hematin found. He or she will be provided reference images. He or she will be 
unaware of respective HemoPill acute measurements.  
6.3.3 
Assessment of Clinician and/or Participant Compliance with Study Procedural Intervention 
Not applicable.  
7 
Study Procedures and Schedule 
7.1 
Study Procedures/Evaluations 
7.1.1 
Study Specific Procedures 
Trial specific procedures are only related to the use of the HemoPill acute. With relevance to the patient is 
HemoPill acute capsule ingestion. While endoscopy is performed as per clinical standard, additionally, 
images of blood or hematin are taken.  
 
Only patients scheduled for endoscopy for suspicion of UGIB are eligible for trial participation. Suspicion 
of UGIB is established as per site protocol and/or physician’s preference. After suspicion of UGIB is 
established and endoscopy scheduled, eligible patients are approached. Adequate patient information is 
provided. Only if informed consent is acquired, inclusion criteria are met and no exclusion criteria apply, 
may a patient enter into the trial as a trial participant. 
 
7.1.2 
Standard of Care Study Procedures 
Standard of care procedures are: 
- 
Clinical and laboratory evaluations as per standard of care, including but not limited to, complete 
blood count, and initial consultation 
- 
Endoscopy: As a diagnostic as well as curative tool for UGIBs, endoscopy is applied in all patients 
to investigate a suspicion of UGIB. If a pathology is found, it is treated as per clinical standard. If 
blood or hematin are found, images are taken for later volume evaluation. 
7.2 
Study Schedule 
7.2.1 
Screening  
In the following, procedures and evaluations necessary for assessing whether a participant meets eligibility 
criteria are described: 
- 
In case a physician’s patients is suspected of having a UGIB and endoscopy is scheduled, an 
investigator is contacted and introduced to the patient. A physician might also be an investigator. 
- 
Patient information is provided. Any questions a patient may have, are answered. Informed patient 
consent is obtained. The patient is made aware that he or she may withdraw from trial participation 
at any time.  

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-
Inclusion and exclusion criteria are applied to further investigate a patient’s eligibility for trial 
participation. 
- 
Screening is concluded and the patient is enrolled. 
7.2.2 
Enrollment 
If a patient is successfully screened and informed consent obtained, he or she is enrolled into the trial.  
As endoscopy is already scheduled, a trial participant likely stays at the hospital. Approximately 20 to 60 
minutes prior to endoscopy, the HemoPill acute capsule is activated by the investigator and a data 
connection to the HemoPill Receiver is established. Then, the HemoPill acute capsule is ingested by the 
trial participant with a minimal amount of water. 
8 
Assessment of Safety 
8.1 
Specification of Safety Parameters  
Safety parameters are identical to the safety endpoints defined in chapter 4.2.2: 
Adverse events / complications associated with trial or control procedure, such as: 
Trial procedure: 
- 
Aspiration of the capsule on ingestion 
- 
Delayed excretion, or failure to excrete the capsule (capsule retention) 
- 
Obstruction of the digestive tract 
- 
Injury to tissue structures during the passage of the HemoPill acute through the digestive tract. 
 
Control procedure: 
- 
Cardiopulmonary adverse events 
- 
Infection 
- 
Perforation  
- 
Bleeding 
 
8.1.1 
Definition of Adverse Events (AE) 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
results in study withdrawal
 is associated with a serious adverse event 
 is associated with clinical signs or symptoms 
 leads to additional treatment or to further diagnostic tests 
 is considered by the investigator to be of clinical significance 
8.1.2 
Definition of Serious Adverse Events (SAE) 
Serious Adverse Event 
Adverse events are classified as serious or non-serious. A serious adverse event is any AE that is:  
 fatal 
 life-threatening 
 requires or prolongs hospital stay 
 results in persistent or significant disability or incapacity 
 an important medical event 
 

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Important medical events are those that may not be immediately life threatening, but are clearly of major 
clinical significance. They may jeopardize the subject, and may require intervention to prevent one of the 
other serious outcomes noted above. For example, drug overdose or abuse, a seizure that did not result in 
in-patient hospitalization, or intensive treatment of bronchospasm in an emergency department would 
typically be considered serious.  
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious adverse 
events.  
 
8.1.3 
Definition of Unanticipated Problems (UP) 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
Unexpected in nature, severity, or frequency (i.e. not described in study-related documents such as 
the IRB-approved protocol or consent form, the investigators brochure, etc) 
 Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research)
 Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
This definition could include an unanticipated adverse device effect, any serious adverse effect on health 
or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects (21 CFR 812.3(s)). 
8.2 
Classification of an Adverse Event 
8.2.1 
Severity of Event 
For AEs not included in the protocol defined grading system, the following guidelines will be used to 
describe severity. 
 
 Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
 Moderate – Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 
 Severe – Events interrupt a participant’s usual daily activity and may require systemic drug therapy 
or other treatment. Severe events are usually potentially life-threatening or incapacitating. 
 
 
8.2.2 
Relationship to Study Agent 
The clinician’s assessment of an AE's relationship to subject device is part of the documentation process, 
but it is not a factor in determining what is or is not reported in the study. If there is any doubt as to whether 
a clinical observation is an AE, the event should be reported. All AEs must have their relationship to subject 
device assessed. In a clinical trial, the study product must always be suspect. To help assess, the following 
guidelines are used. 

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 Related – The AE is known to occur with the subject device, there is a reasonable possibility that 
the subject device caused the AE, or there is a temporal relationship between the subject device and 
event. Reasonable possibility means that there is evidence to suggest a causal relationship between 
the subject device and the AE. 
 Not Related – There is not a reasonable possibility that the use of the subject device caused the 
event, there is no temporal relationship between the subject device and event onset, or an alternate 
etiology has been established. 
8.2.3 
Expectedness 
Expected adverse reactions known to occur for capsule endoscope devices and complications associated 
with the control procedure endoscopy are: 
Trial procedure: 
- 
Aspiration of the capsule on ingestion 
- 
Delayed excretion, or failure to excrete the capsule (capsule retention) 
- 
Obstruction of the digestive tract 
- 
Injury to tissue structures during the passage of the HemoPill acute through the digestive tract. In 
particular, this may involve: 
- 
Injury to the mucosa 
- 
Bleeding, e.g., variceal bleeding 
- 
Perforations 
 
Control procedure: 
- 
Cardiopulmonary adverse events 
- 
Infection 
- 
Perforation  
- 
Bleeding 
 
Dr. Melissa Latorre will be responsible for determining whether an AE is expected or unexpected. An AE 
will be considered unexpected if the nature, severity, or frequency of the event is not consistent with the 
risk information previously described for the subject device. 
8.3 
Time Period and Frequency for Event Assessment and Follow-Up 
AEs and SAEs from trial procedure: 
- 
Aspiration of the capsule on ingestion 
Immediate identification through extensive coughing. Localization and retrieval with 
bronchoscope.  
- 
Delayed excretion, or failure to excrete the capsule (capsule retention) 
Identification  
- 
Obstruction of the digestive tract 
- 
Injury to tissue structures during the passage of the HemoPill acute through the digestive tract. In 
particular, this may involve: 
- 
Injury to the mucosa 
- 
Bleeding, e.g., variceal bleeding 
- 
Perforations 

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8.4
Reporting Procedures – Notifying the IRB 
8.4.1 
Adverse Event Reporting 
SAEs as defined above, and any adverse events related to the study device (AI) should be reported within 
24 hours of the Investigator’s knowledge of the event to Sponsor as well as IRB department. Reporting to 
the IRB will be performed by the Investigator 
8.4.2 
Serious Adverse Event Reporting 
All SAEs, unless otherwise specified in the protocol and approved by the IRB, require expedited reporting 
by the Principal Investigator to the study's safety monitoring bodies. An expedited report of an SAE can be 
submitted by telephone, fax, or email and must be reported to the independent safety monitoring body 
within 24 hours of the event being reported to the Investigator. The expedited report should be followed by 
a detailed, written SAE report as soon as possible. Follow up information may be required and asked for 
by the independent safety monitoring body directly. If a second serious event occurs, the study will be 
halted.  
8.4.3 
Unanticipated Problem Reporting 
Unexpected risks will be evaluated throughout the research study and any modifications, based on serious 
and unexpected adverse events occurring and reported in these submitted reports and not previously 
identified in this research study, would be implemented by the study team on an ongoing basis. Any serious 
or unexpected adverse event related to HemoPill will necessitate review with modification of the protocol 
to address the specific adverse event. 
Incidents or events that meet the OHRP criteria for UPs require the creation and completion of an UP report 
form. It is the site investigator’s responsibility to report UPs to their IRB and Dr. Jennifer Kats. The UP 
report will include the following information: 
 
 Protocol identifying information: protocol title and number, PI’s name, and the IRB project number; 
 A detailed description of the event, incident, experience, or outcome; 
 An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP; 
 A description of any changes to the protocol or other corrective actions that have been taken or are 
proposed in response to the UP. 
8.4.4 
Reporting of Pregnancy 
Pregnant women are excluded from trial participation. As from enrollment to trial intervention merely hours 
elapse, change in pregnancy status of an enrolled patient is highly unlikely. However, if pregnancy is 
discovered after trial enrollment, trial participation is terminated. 
8.5 
Reporting Procedures – Notifying the Study Sponsor 
The study clinician will complete a SAE Form within the following timelines: 
 
 All deaths and immediately life-threatening events, whether related or unrelated, will be recorded 
on the SAE Form and submitted to the IRB office and Dr. Jennifer Katz within 24 hours of site 
awareness. See Section 1, Key Roles for contact information. 
 Other SAEs regardless of relationship will be submitted to the Dr. Katz within 72 hours of site 
awareness. 

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All SAEs will be followed until satisfactory resolution or until the site investigator deems the event to be 
chronic or the adherence to be stable. Other supporting documentation of the event may be requested by 
the Dr. Katz and should be provided as soon as possible.  
As a follow-up to the initial report, within the following 48 hours of awareness of the event, the investigator 
shall provide further information, as applicable, on the unanticipated event or the unanticipated problem in 
the form of a written narrative.  This should include a copy of the completed Unanticipated Problem form, 
and any other diagnostic information that will assist the understanding of the event.  Significant new 
information on ongoing unanticipated adverse effects shall be provided promptly to the study sponsor. 
The study investigator shall complete an Unanticipated Adverse Device Effect Form and submit to the 
study sponsor and to the reviewing IRB as soon as possible, but in no event later than 10 working days after 
the investigator first learns of the effect. The study sponsor contact information is provided in Section 1, 
Key Roles. 
 
As a follow-up to the initial report, within the following 48 hours of awareness of the event, the investigator 
shall provide further information, as applicable, on the unanticipated event or the unanticipated problem in 
the form of a written narrative.  This should include a copy of the completed Unanticipated Problem form, 
and any other diagnostic information that will assist the understanding of the event.  Significant new 
information on ongoing unanticipated adverse effects shall be provided promptly to the study sponsor. 
The PI is responsible for conducting an evaluation of an unanticipated adverse device effect and shall report 
the results of such evaluation the reviewing IRB and participating investigators within 10 working days 
after the sponsor first receives notice of the effect. Thereafter the sponsor shall submit such additional 
reports concerning the effect as IRB requests. 
8.6 
Study Halting Rules 
Use of subject device will be halted when three grade 3 AEs determined to be “probably related” are 
reported to the, Dr. Jennifer Katz. Dr. Katz will notify the study sponsor and investigators immediately 
when the third grade 3 event is reported and enrollment screens will stop accepting new study participants. 
The study sponsor will inform the DSMB members within 24 hours of this occurrence and will provide the 
DSMB with AE listing reports. The DSMB will convene an ad hoc meeting by teleconference or in writing 
as soon as possible. The DSMB will provide recommendations for proceeding with the study to the study 
sponsor. 
8.7 
Safety Oversight 
Data Safety Monitoring will be conducted by Dr. Jennifer Katz, who is a board-certified gastroenterologist 
trained in endoscopic procedures including upper endoscopy. Data safety monitoring will be done after 
each cohort of 10 patients is enrolled.  
 
SAE and AE are defined as: 
- 
Aspiration of the capsule on ingestion 
Immediate identification through extensive coughing. Localization and retrieval with 
bronchoscope.  
- 
Delayed excretion, or failure to excrete the capsule (capsule retention) 
Identification  
- 
Obstruction of the digestive tract 

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-
Injury to tissue structures during the passage of the HemoPill acute through the digestive tract. In 
particular, this may involve: 
- 
Injury to the mucosa 
- 
Bleeding, e.g., variceal bleeding 
- 
Perforations 
Furthermore, unexpected events are classified as SAE or AE under consideration of the respective 
definitions provided in chapter 8.1.1 and chapter 8.1.2 
9 
Clinical Trial Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of the trial 
is in compliance with the currently approved protocol/amendment(s), with GCP, and with applicable 
regulatory requirement(s). 
 
The PI will monitor the study. In addition to completed medical records, the procedure report, and any 
additional supporting documents will be made available for review and verification during each monitoring 
visit.  
 
Study monitoring will be conducted routinely throughout the study. The monitors will confirm that the 
study is being conducted according to the protocol. 
10 Statistical Considerations 
10.1 Statistical and Analytical Plans (SAP) 
No additional formal SAP is provided. 
10.2 Statistical Hypotheses 
Formal hypotheses are only specified for the primary clinical effectiveness endpoint, the detection of blood 
in the gastrointestinal lumen with both measurements1.
 
The assumed null hypothesis is that the accuracy of the HemoPill acute measurement in comparison with 
endoscopic finding is 50%, equaling a random distribution and no relation between these measurements. 
As the alternative hypothesis, it is assumed that the accuracy is equal or higher to 75%. This concrete 
accuracy value is derived from previous results of Brunk et al. (2021), see section 2.1. 
10.3 Analysis Datasets 
All patients with full study protocol participation are included in the analysis dataset, i.e. with results on 
both measurements, the subjective device (HemoPill acute capsule) and the control product (endoscopy). 
Therefore, only patient withdrawal or termination by the investigator can lead to exclusion from the analysis 
dataset (described in detail in section 5.7). 
No further (sub-)analysis datasets are planned. 
 

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10.4
Description of Statistical Methods
10.4.1 General Approach 
This study has a double blinded, prospective diagnostic case-control design. This prototypic design of 
diagnostic accuracy study is a consecutive series of individuals in whom the target condition is suspected, 
here GI lumen bleeding. The index test, here HemoPill acute, is performed first in all participants. 
Subsequently, the presence of the target condition is also measured in all participants with the reference 
standard, in this case endoscopy (Rutjes et al. 2005). 
In more detail, this study is performed: 
 
on one sample: the study is conducted on a single sample (single-arm) at a single center 
double blinded: neither the patients nor the investigators are aware of the result of the subjective 
device, the HemoPill acute capsule, during the examination of the control product, the endoscopy. 
 
with repeated measurement: all patients are measured with the subjective device and additionally 
with the control product
 
case-control design: the status of a patient with positive endoscopy result equals as classification 
in the case group, the status of a patient with negative endoscopy result equals as classification in 
the control group. This classification is determined after the study process, during the statistical 
analysis to ensure double blindness. 
 
The categorical variables (such as positive or negative test results) will be summarized with subject counts, 
respectively frequency, and percentages. 
-of-fit test of a 2 x 2 contingency table with two tailed p-
.05 will be used. 
-of-fit test, a required minimal expected cell size of 5, will be 
controlled (and is a priori controlled in the power analysis, see section 10.5). The dichotomous data level 
of the two factors, results of subjective device and results of control product, are transformed into a cell 
count, observed cases, in the 2 x 2 contingency table. 
10.4.2 Analysis of the Primary Efficacy Endpoint(s) 
The original continues data level of the subject device, HemoPill acute, the so-called HI-value, is 
transformed during the study process by the investigator in dichotomous values, negative or positive for GI 
lumen bleeding, i.e. negative or positive output results (described in detail in section 2.1.2.2). 
The qualitative visual data of the control product, the endoscopy, is also transformed during the study 
process by the investigator in dichotomous values, negative or positive for GI lumen bleeding, i.e. negative 
or positive output results (described in section 4.1).  
 
After the study process the values of these two factors (HemoPill acute: negative or positive, endoscopy: 
negative or positive) are combined in a 2 x 2 contingency table with four possible results: 
 
True positive: HemoPill acute measurement positive; Endoscopy measurement positive 
 
False positive: HemoPill acute measurement positive; Endoscopy measurement negative 
 
True negative: HemoPill acute measurement negative; Endoscopy measurement negative 
 
False negative: HemoPill acute measurement negative; Endoscopy measurement positive 
(for detailed description see section 4.1) 
 
From this 2 x 2 contingency table the summary three test indices are calculated accuracy (ACC, = (TP + 
TN) / pop), sensitivity (true positive rate) and specificity (true negative rate). 
-of-fit test of a 2 x 2 contingency 
table with two tailed p-
 

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-of-fit test, a required minimal expected cell size of 5, will be 
controlled. After the inference analysis the 95% confidence intervals of the test indices can be calculated. 
If either of both measurement results is missing for a patient, the whole subject is omitted from the data 
analysis. 
10.4.3 Analysis of the Secondary Endpoint(s) 
Secondary study endpoints as described in chapter 4.2.2 are technical and safety endpoints. These are solely 
documented, and their respective prevalence is calculated and described in relation to the total number of 
participants. Presentation in study reporting will either be as a percentage value (e.g., “in 2 % of 
patients, …”), as a number of occurrences as a fraction of total number of patients or a subgroup thereof 
(e.g., “in 4 of 50 patients, …”; “in 3 of the 22 patients with an endoscopically identified bleeding pathology). 
10.4.4 Safety Analyses 
Among the secondary endpoints, safety endpoints are defined (see chapter 4.2.2). Occurrences are 
documented, and their respective prevalence is calculated and described in relation to the total number of 
participants. Safety oversight measures are described in chapter 8.7. The Study will be halted after two 
SAEs (see chapter 8.4.2). 
10.4.5 Adherence and Retention Analyses 
The successful consumption of the subjective device, the HemoPill acute capsule, is controlled by the 
administering investigator (see section 6.3.1). No further adherence analyses are planned. Retention 
analyses are not applicable in this study design. 
10.4.6 Baseline Descriptive Statistics 
Baseline demographic, clinical and procedural data will be summarized using descriptive statistics. 
For continuous variables (such as age), results will be summarized with the numbers of observations, 
minimums, maximums, means, and standard deviations and where specified in table or figure conventions 
with quartiles. 
For categorical variables (such as gender) results will be summarized with subject counts and percentages. 
Inferential statistics are not planned for the baseline statistics, because no subgroups are compared within 
the sample, nor comparisons with epidemiolocal or demographic data are planned. 
10.4.7 Planned Interim Analysis 
Not applicable. 
10.4.8 Additional Sub-Group Analyses 
No analyses of based on age, sex, race/ethnicity or other demographic characteristics are planned. 
10.4.9 Multiple Comparison/Multiplicity 
Not applicable. 
10.4.9.1 Tabulation of Individual Response Data 
The individual participant data will be listed by subject with measurement result and time point for each 
subject. 
10.4.9.2 Exploratory Analyses 
No exploratory analyses are planned. 

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10.5
Sample Size
The study will enroll in total n = 50 participants: 
 
at least 43 eligible for statistical analyses 
 
plus 7 as highest expectable dropout count. 
 
sensitivity and specificity). The calculation was based on the previous clinical study of Burk et al. (2021) 
which provide an accuracy of 75% (sensitivity of 100% and specificity of 63%) equaling an assumed effect 
-
or higher than .90. 
 
Based on the previous studies dropout ratios between 2% (Burk et al., 2021) and 7% (Caca & Zimmermann, 
2017) could be expected. By reason of clinical judgement, a maximal dropout ratio of 14% was assumed 
(which equals two times the maximal previous dropout ratio). An assumed maximal dropout of 14% equals 
7 additional participants (when targeting at least 43 participants eligible for statistical analyses). 
 
effect size. The power analysis was conducted with the computer program G*Power 3.1 (Faul et al., 2009). 
10.6 Measures to Minimize Bias 
10.6.1 Enrollment/Randomization/Masking Procedures 
While the study is an intra-individual relation between a HemoPill acute measurement and an endoscopic 
examination and thus not randomized, masking is achieved by application of the following considerations: 
- 
Patient: Sedated during endoscopy. Does not know how to interpret information displayed by the 
HemoPill Receiver. He or she does not provide an interpretation of measurements.  
- 
Endoscopist: While aware of the endoscopic presentation of the patient as it unfolds, the 
investigator is unaware of the HemoPill acute measurement. The relation between the HemoPill 
acute measurement and endoscopic findings is investigated after endoscopy has concluded.  
- 
Blood quantification: A third person quantifies the amount of blood depicted on endoscopic images. 
This person is unaware of the respective HemoPill acute measurement. A relation to the HemoPill 
acute measurement is made only after the quantification of blood depicted has been made. 
10.6.2 Evaluation of Success of Blinding 
Success of blinding cannot retrospectively be evaluated in this study. 
10.6.3 Breaking the Study Blind/Participant Code 
In this study, the HemoPill acute measurement is blinded to the investigator who is conducting the 
endoscopy as not to influence the evaluation of endoscopic findings. After endoscopy has concluded, 
blinding is no longer required here. As for the quantification of blood from endoscopic images, the evaluator 
is unaware of the respective HemoPill acute measurement. As soon as the quantification process has 
concluded, blinding is no longer required. 
11 Source Documents and Access to Source Data/Documents 
Source data is all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial.  Source data are contained in source 
documents.  Examples of these original documents, and data records include: hospital records, clinical and 
office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing 

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records, recorded data from automated instruments, copies or transcriptions certified after verification as 
being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, 
subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments 
involved in the clinical trial. It is acceptable to use CRFs as source documents. If this is the case, it should 
be stated in this section what data will be collected on CRFs and what data will be collected from other 
sources. 
 
The study case report form (CRF) is the primary data collection instrument for the study.  All data requested 
on the CRF must be recorded.  All missing data must be explained.  If a space on the CRF is left blank 
because the procedure was not done or the question was not asked, write “N/D”.  If the item is not applicable 
to the individual case, write “N/A”.  All entries should be printed legibly in black ink.  If any entry error 
has been made, to correct such an error, draw a single straight line through the incorrect entry and enter the 
correct data above it.  All such changes must be initialed and dated.  DO NOT ERASE OR WHITE OUT 
ERRORS.  For clarification of illegible or uncertain entries, print the clarification above the item, then 
initial and date it. 
 
Access to study records will be limited to IRB-approved members of the study team. The investigator will 
permit study-related monitoring, audits, and inspections by the IRB/EC, the sponsor, government regulatory 
bodies, and University compliance and quality assurance groups of all study related documents (e.g. source 
documents, regulatory documents, data collection instruments, study data etc.).  The investigator will ensure 
the capability for inspections of applicable study-related facilities (e.g. pharmacy, diagnostic laboratory, 
etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable University compliance and quality assurance offices. 
12 Quality Assurance and Quality Control 
QC procedures will be implemented beginning with the data entry system and data QC checks that will be 
run on the database will be generated. Any missing data or data anomalies will be communicated to the site 
for clarification/resolution. 
 
Following written SOPs, the monitors will verify that the clinical trial is conducted and data are generated, 
documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory 
requirements (e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)). 
 
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory 
authorities. 
13 Ethics/Protection of Human Subjects 
13.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 
and/or the ICH E6. 
13.2 Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must be 

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obtained before any participant is enrolled. Any amendment to the protocol will require review and approval 
by the IRB before the changes are implemented to the study. All changes to the consent form will be IRB 
approved; a determination will be made regarding whether previously consented participants need to be re-
consented. 
13.3 Informed Consent Process 
The consent form will be submitted for approval by the IRB and contain all elements required by federal, 
state, local, and institutional regulations or requirements. The study procedures, risks and benefits, and 
voluntary nature of involvement must be completely explained to every study subject. Each subject found 
to be eligible for the study must voluntarily provide written informed consent on the form approved by the 
IRB and also provide written authorization for use, collection, and disclosure of PHI information. Each 
subject must be allowed adequate time to consider the potential risks and benefits associated with his or her 
participation in the study. Informed consent must be in language understandable to the subjects. 
 
It will be the responsibility of the investigator to provide each subject with full and adequate verbal and 
written information using the IRB approved informed consent document, including the objective and 
procedures of the study and the possible risks involved before inclusion in the study. Informed consent must 
be obtained prior to performing any study-related procedures. A copy of the signed informed consent must 
be given to the study subject. 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study 
and continues throughout the individual’s study participation. Extensive discussion of risks and possible 
benefits of participation will be provided to the participants and their families. Consent forms will be IRB-
approved and the participant will be asked to read and review the document. The investigator will explain 
the research study to the participant and answer any questions that may arise. All participants will receive 
a verbal explanation in terms suited to their comprehension of the purposes, procedures, and potential risks 
of the study and of their rights as research participants. Participants will have the opportunity to carefully 
review the written consent form and ask questions prior to signing. The participants should have the 
opportunity to discuss the study with their surrogates or think about it prior to agreeing to participate. The 
participant will sign the informed consent document prior to any procedures being done specifically for the 
study. The participants may withdraw consent at any time throughout the course of the trial. A copy of the 
signed informed consent document will be given to the participants for their records. The rights and welfare 
of the participants will be protected by emphasizing to them that the quality of their medical care will not 
be adversely affected if they decline to participate in this study. 
 
A copy of the signed informed consent document will be stored in the subject’s research record. The consent 
process, including the name of the individual obtaining consent, will be thoroughly documented in the 
subject’s research record. Any alteration to the standard consent process (e.g. use of a translator, consent 
from a legally authorized representative, consent document presented orally, etc.) and the justification for 
such alteration will likewise be documented. 
13.4 Participant and Data Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
signed subject authorization informing the subject of the following:  
 What protected health information (PHI) will be collected from subjects in this study 
 Who will have access to that information and why 
 Who will use or disclose that information  
 The rights of a research subject to revoke their authorization for use of their PHI.  

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In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains 
the ability to use all information collected prior to the revocation of subject authorization.  For subjects that 
have revoked authorization to collect or use PHI, attempts should be made to obtain permission to collect 
at least vital status (i.e. that the subject is alive) at the end of their scheduled study period. 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. Therefore, the study protocol, documentation, data, and all other information 
generated will be held in strict confidence. No information concerning the study or the data will be released 
to any unauthorized third party without prior written approval of the sponsor. 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or 
pharmaceutical company supplying study product may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) and 
pharmacy records for the participants in this study. The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as long 
a period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be 
transmitted to and stored at NYU Langone Medical Center. This will not include the participant’s contact 
or identifying information. Rather, individual participants and their research data will be identified by a 
unique study identification number. The study data entry and study management systems used by clinical 
sites and by NYU Langone Medical Center research staff will be secured and password protected. At the 
end of the study, all study databases will be de-identified and archived at the NYU Langone Medical Center. 
14 Data Handling and Record Keeping 
14.1 Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site PI. 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data. Black ink is required to ensure clarity of reproduced copies. When making changes or corrections, 
cross out the original entry with a single line, and initial and date the change. DO NOT ERASE, 
OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for 
recording data for each participant enrolled in the study. Data reported in the eCRF derived from source 
documents should be consistent with the source documents or the discrepancies should be explained and 
captured in a progress note and maintained in the participant’s official electronic study record. 
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered into TrialMaster, a 21 CFR Part 11-compliant data capture system. The data 
system includes password protection and internal quality checks, such as automatic range checks, to identify 
data that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the 
source documents. 

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14.2
Study Records Retention
Study documents will be retained for the longer of 3 years after close-out, 5 years after final 
reporting/publication, or 2 years after the last approval of a marketing application is approved for the drug 
for the indication for which it is being investigated or 2 years after the investigation is discontinued and 
FDA is notified if no application is to be filed or if the application has not been approved for such indication. 
No records will be destroyed without the written consent of the sponsor, if applicable. It is the responsibility 
of the sponsor to inform the investigator when these documents no longer need to be retained. 
14.3 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or Manual of Procedures 
(MOP) requirements. The noncompliance may be either on the part of the participant, the investigator, or 
the study site staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly. 
 
These practices are consistent with ICH E6: 
 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
 5.1 Quality Assurance and Quality Control, section 5.1.1 
 5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
 
It is the responsibility of the site PI/study staff to use continuous vigilance to identify and report deviations 
within 5 working days of identification of the protocol deviation, or within 5 working days of the scheduled 
protocol-required activity. 
 
Protocol deviations must be reported to the local IRB per their guidelines. The site PI/study staff is 
responsible for knowing and adhering to their IRB requirements. Further details about the handling of 
protocol deviations will be included in the MOP. 
14.4 Publication and Data Sharing Policy 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted a clinical 
trials registration policy as a condition for publication. The ICMJE defines a clinical trial as any research 
project that prospectively assigns human subjects to intervention or concurrent comparison or control 
groups to study the cause-and-effect relationship between a medical intervention and a health outcome. 
Medical interventions include drugs, surgical procedures, devices, behavioral treatments, process-of-care 
changes, and the like. Health outcomes include any biomedical or health-related measures obtained in 
patients or participants, including pharmacokinetic measures and adverse events. The ICMJE policy, and 
the Section 801 of the Food and Drug Administration Amendments Act of 2007, requires that all clinical 
trials be registered in a public trials registry such as ClinicalTrials.gov, which is sponsored by the National 
Library of Medicine. Other biomedical journals are considering adopting similar policies. For interventional 
clinical trials performed under NIH IC grants and cooperative agreements, it is the grantee’s responsibility 
to register the trial in an acceptable registry, so the research results may be considered for publication in 
ICMJE member journals. The ICMJE does not review specific studies to determine whether registration is 
necessary; instead, the committee recommends that researchers who have questions about the need to 
register err on the side of registration or consult the editorial office of the journal in which they wish to 
publish. 
 
FDAAA mandates that a "responsible party" (i.e., the sponsor or designated principal investigator) register 
and report results of certain "applicable clinical trials": 
 

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Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase I investigations 
of a product subject to FDA regulation; 
Trials of Devices: Controlled trials with health outcomes of a product subject to FDA regulation 
(other than small feasibility studies) and pediatric postmarket surveillance studies. 
NIH grantees must take specific steps to ensure compliance with NIH implementation of FDAAA.
 
The proposed clinical trial will be registered at ClinicalTrials.gov. 
15 Study Finances 
15.1 Funding Source 
The study is funded by OVESCO USA and NYU Langone Health Division of Gastroenterology. OVESCO 
USA provides HemoPill acute capsules as well as HemoPill Receivers. OVESCO supports this IIT 
investigating the performance of the HemoPill acute. The data aids users in interpreting a HemoPill acute 
measurement. Data shared with OVESCO will be HemoPill acute measurements, endoscopic findings and 
images, available baseline data. Data will be provided pseudonymized. No identifiable information will be 
shared. Data will be shared to OVESCO via TrialMaster. 
15.2 Participant Reimbursements or Payments 
Participants receive a $100 gift card.  
16 Conflict of Interest Policy 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain 
greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the NYU 
Langone Conflict of Interest Management Unit (CIMU) with a Committee-sanctioned conflict management 
plan that has been reviewed and approved by the study sponsor prior to participation in this study. All 
NYULMC investigators will follow the applicable conflict of interest policies. 
 
 

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