Endoscopic Treatment for Weight Reduction in Patients With Obesity Using the TransPyloric Shuttle® System: A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design Study
Phase: NA
Conditions: Obesity
Sponsor: BaroNova, Inc.

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 1 of 83 
 
 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the 
TransPyloric Shuttle® System: A Multicenter, Prospective, Randomized, Double-
Blind, Sham-Controlled, Parallel-Design Study (ENDObesity® II Study) 
 
 
 
Protocol number DTC006 
 
 
 
Principal Investigator: 
 
Richard Rothstein, MD 
Dartmouth-Hitchcock Medical Center 
Department of Medicine 
1 Medical Center Drive, Lebanon, NH  03756 
Telephone: (603) 650-7936 
Richard.I.Rothstein@Hitchcock.org 
 
Sponsor: 
 
BAROnova, Inc. 
1551 Industrial Rd  
San Carlos, CA  94070  USA 
Telephone: (650) 638-9796 
Contact: Lian Cunningham 
 
 
 
 
 
 
Version 8.0 
November 15, 2016 
 
 
 
 
Confidential and Proprietary 
Do not distribute or reproduce without prior written permission of BAROnova® Inc.   
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 2 of 83 
 
 
Contents 
1. 
PROTOCOL SUMMARY .......................................................................................................................................... 6 
2. 
BACKGROUND ..................................................................................................................................................... 12 
2.1. 
Definition of Obesity ........................................................................................................................................... 12 
2.2. 
Obesity Related Comorbidities and the Benefit of Modest Weight Loss ............................................................ 12 
2.3. 
Treatment Options ............................................................................................................................................. 12 
2.3.1. 
Lifestyle Modification Interventions ......................................................................................................... 12 
2.3.2. 
Pharmacotherapy ...................................................................................................................................... 13 
2.3.3. 
Bariatric Surgery ........................................................................................................................................ 13 
2.3.4. 
Endoscopic Approaches to Obesity ........................................................................................................... 15 
2.3.5. 
Weight-Loss Maintenance ......................................................................................................................... 15 
3. 
DEVICE DESCRIPTION ........................................................................................................................................... 16 
3.1. 
System Description ............................................................................................................................................. 16 
3.1.1. 
TransPyloric Shuttle ................................................................................................................................... 16 
3.1.2. 
TPSS Delivery System................................................................................................................................. 17 
3.1.3. 
TPS Retrieval Kit......................................................................................................................................... 20 
3.2. 
Proposed Mechanism of Action .......................................................................................................................... 21 
3.3. 
Proposed Indication ............................................................................................................................................ 22 
3.4. 
Prior Investigations ............................................................................................................................................ 22 
3.4.1. 
Pre-Clinical Testing .................................................................................................................................... 22 
3.4.2. 
Biocompatibility Testing ............................................................................................................................ 22 
3.4.3. 
Prior Clinical Experience ............................................................................................................................ 23 
3.5. 
Risks and Benefits ............................................................................................................................................... 25 
3.5.1. 
Potential Benefits ...................................................................................................................................... 25 
3.5.2. 
Anticipated Adverse Events (AEs) Associated with the TPS Placement, Residence, and Removal ........... 25 
3.5.3. 
Residual Risks Associated with the Investigational Device, as Identified in the Risk Analysis Report ...... 26 
3.5.4. 
Risks Associated with Participation in the Clinical Investigation ............................................................... 26 
3.5.5. 
Possible Interactions with Concomitant Medication ................................................................................ 27 
3.5.6. 
Minimization of Risks ................................................................................................................................ 27 
4. 
STUDY OBJECTIVES .............................................................................................................................................. 27 
5. 
STUDY DESIGN ..................................................................................................................................................... 28 
5.1. 
Study Design ....................................................................................................................................................... 28 
5.2. 
Subject Recruitment and Enrollment .................................................................................................................. 30 
5.3. 
Randomization and Masking ............................................................................................................................. 30 
5.4. 
Staged Safety Monitoring .................................................................................................................................. 31 
5.5. 
Criteria for Discontinuation of Routine Endoscopic Surveillance ........................................................................ 31 
5.6. 
Early Study Termination ..................................................................................................................................... 32 
5.7. 
Measures Taken to Avoid/Minimize Bias ........................................................................................................... 32 
6. 
STUDY ENDPOINTS .............................................................................................................................................. 33 
6.1. 
Primary Effectiveness Endpoints ........................................................................................................................ 33 
6.2. 
Secondary Effectiveness Endpoints .................................................................................................................... 33 
6.3. 
Safety Evaluations .............................................................................................................................................. 33 
7. 
PATIENT SELECTION AND WITHDRAWAL ............................................................................................................. 33 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 3 of 83 
 
 
7.1. 
Study Population ................................................................................................................................................ 33 
7.2. 
Inclusion Criteria................................................................................................................................................. 34 
7.3. 
Exclusion Criteria ................................................................................................................................................ 34 
7.4. 
Point of Enrollment ............................................................................................................................................ 36 
7.5. 
Patient Discontinuation ...................................................................................................................................... 36 
7.6. 
Lost to Follow-up ................................................................................................................................................ 36 
8. 
LIFESTYLE INTERVENTIONS .................................................................................................................................. 37 
8.1. 
Diet Recommendations ...................................................................................................................................... 37 
8.2. 
Physical Activity Recommendations ................................................................................................................... 37 
8.3. 
Behavior Modification ........................................................................................................................................ 37 
8.4. 
Telephone Contacts ............................................................................................................................................ 37 
9. 
CONCOMITANT MEDICATIONS ............................................................................................................................ 38 
9.1. 
Prohibited Concomitant Medications ................................................................................................................. 38 
9.1.1. 
Weight-Loss Medications .......................................................................................................................... 38 
9.1.2. 
NSAIDs (Non-Steroidal Anti-inflammatory Drugs) ..................................................................................... 38 
9.1.3. 
Other Medications ..................................................................................................................................... 38 
9.2. 
Required Concomitant Medications ................................................................................................................... 38 
9.2.1. 
Proton Pump Inhibitors (PPIs) ................................................................................................................... 38 
10. POST PROCEDURE PATIENT MANAGEMENT ........................................................................................................ 38 
10.1. 
Managing GI Symptoms ..................................................................................................................................... 38 
10.2. 
Managing Endoscopic Observations .................................................................................................................. 39 
10.2.1. 
Ulcer Definition ......................................................................................................................................... 39 
10.2.2. 
Guidelines for Managing Endoscopic Observations .................................................................................. 39 
10.3. 
Managing Hypoglycemia Risks in Diabetic Subjects .......................................................................................... 41 
10.3.1. 
Subject Education ...................................................................................................................................... 41 
10.3.2. 
Subject Management (adapted from algorithms developed and used in the LookAhead Study 32 ) ........ 41 
10.4. 
Managing Hyperglycemia Risks in Diabetic Subjects ......................................................................................... 46 
10.5. 
Early Device Removal ......................................................................................................................................... 46 
11. STUDY EVALUATION AND TREATMENT PROCEDURES ......................................................................................... 46 
11.1. 
Demographics .................................................................................................................................................... 46 
11.2. 
Medical History and Concomitant Medication ................................................................................................... 46 
11.3. 
Measurement of Weight, Body Circumference and Calculation of Body Mass Index (BMI) .............................. 46 
11.4. 
Biochemical Measurements ............................................................................................................................... 47 
11.5. 
Satiety Assessment ............................................................................................................................................. 47 
11.6. 
Patient Health Questionnaire 9 (PHQ-9) ............................................................................................................ 47 
11.7. 
Impact of Weight on Quality of Life (IWQOL– Lite)34 ......................................................................................... 47 
11.8. 
Test for Helicobacter Pylori ................................................................................................................................ 47 
11.9. 
Visit Schedules .................................................................................................................................................... 47 
11.9.1. 
Screening Visit (Within 8 Weeks Prior to the Index Procedure) ................................................................ 48 
11.9.2. 
Baseline Visit (Within One Week Prior to the Index Procedure) ............................................................... 48 
11.9.3. 
Index Procedure (Day 0) ............................................................................................................................ 49 
11.9.4. 
One Week Post-Index Procedure (7 ± 2 Days) ........................................................................................... 50 
11.9.5. 
One Month Post-Index Procedure (30 ± 7 Days) ....................................................................................... 50 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 4 of 83 
 
 
11.9.6. 
Two-Month Post-Index Procedure (60 ± 14 Days) .................................................................................... 50 
11.9.7. 
Four-Month Post-Index Procedure (120 ± 14 Days) .................................................................................. 51 
11.9.8. 
Six-Month Post-Index Procedure (180 ± 14 Days) ..................................................................................... 51 
11.9.9. 
Nine-Month Post-Index Procedure (270 ± 21 Days) .................................................................................. 51 
11.9.10. 
Twelve-Month Post-Index Procedure (365 ± 30 Days) .............................................................................. 51 
11.9.11. 
Unscheduled Visit ...................................................................................................................................... 53 
11.9.12. 
Telephone Contact at Months 7 (210±7 days), 8 (240±7 days), 10 (300±7 days), and 11 (330-14 days) .. 53 
12. ASSESSMENT OF SAFETY ...................................................................................................................................... 53 
12.1. 
Adverse Events ................................................................................................................................................... 53 
12.1.1. 
Serious Adverse Event ............................................................................................................................... 54 
12.1.2. 
Serious Adverse Device Effect ................................................................................................................... 54 
12.1.3. 
Unanticipated Adverse Device Effects....................................................................................................... 54 
12.2. 
Device Relationship (Causality) .......................................................................................................................... 54 
12.3. 
Adverse Event Reporting .................................................................................................................................... 55 
12.3.1. 
Sponsor Reporting Requirements ............................................................................................................. 55 
12.3.2. 
Clinical Site Reporting Requirements ........................................................................................................ 55 
13. CLINICAL EVENT COMMITTEE .............................................................................................................................. 55 
14. DATA SAFETY MONITORING BOARD .................................................................................................................... 55 
15. STATISTICAL DESIGN AND ANALYSIS .................................................................................................................... 56 
15.1. 
Statistical Overview ............................................................................................................................................ 56 
15.2. 
Analysis Populations........................................................................................................................................... 56 
15.3. 
Study Objectives and Hypotheses....................................................................................................................... 57 
15.3.1. 
Primary Effectiveness Objective ................................................................................................................ 57 
15.3.2. 
Safety Objective......................................................................................................................................... 58 
15.4. 
Sample Size Considerations ................................................................................................................................ 58 
15.5. 
Statistical Analysis .............................................................................................................................................. 58 
15.5.1. 
Accountability and Demographics ............................................................................................................. 58 
15.5.2. 
Comparability of the Treatment Groups ................................................................................................... 58 
15.5.3. 
Primary Analysis ........................................................................................................................................ 58 
15.5.4. 
Secondary Analysis .................................................................................................................................... 59 
15.5.5. 
Safety Analysis ........................................................................................................................................... 60 
15.5.6. 
Staged Safety Monitoring Analysis ............................................................................................................ 60 
15.5.7. 
Analysis for Discontinuation of Routine Endoscopic Surveillance ............................................................. 61 
15.5.8. 
Assessment of Poolability .......................................................................................................................... 61 
16. QUALITY CONTROL AND QUALITY ASSURANCE ................................................................................................... 62 
16.1. 
Selection of Study Sites and Investigators .......................................................................................................... 62 
16.2. 
Training .............................................................................................................................................................. 62 
16.2.1. 
Site Training ............................................................................................................................................... 62 
16.2.2. 
Monitor Training ....................................................................................................................................... 62 
16.3. 
Study Monitoring................................................................................................................................................ 62 
16.4. 
Source Data Verification..................................................................................................................................... 63 
16.4.1. 
Definition of Source Data .......................................................................................................................... 63 
16.5. 
Direct Access to Source Data/Documents .......................................................................................................... 63 
16.6. 
Maintain Blinding during the Study ................................................................................................................... 63 
16.7. 
Protocol Deviations ............................................................................................................................................ 63 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 5 of 83 
 
 
16.8. 
Termination of Study Site Participation ............................................................................................................. 64 
16.9. 
Study Steering Committee (SSC) ......................................................................................................................... 64 
17. DATA HANDLING AND RECORD KEEPING ............................................................................................................. 64 
17.1. 
Source Documentation ....................................................................................................................................... 64 
17.2. 
Case Report Form Completion ............................................................................................................................ 65 
17.3. 
Record Retention ................................................................................................................................................ 65 
18. ETHICAL CONSIDERATIONS .................................................................................................................................. 65 
18.1. 
Institutional Review Board Review ..................................................................................................................... 65 
18.2. 
Informed Consent ............................................................................................................................................... 65 
18.3. 
Confidentiality .................................................................................................................................................... 66 
19. INVESTIGATIONAL DEVICE MANAGEMENT .......................................................................................................... 66 
19.1. 
Device Accountability ......................................................................................................................................... 66 
19.2. 
Device Return ..................................................................................................................................................... 66 
20. REFERENCES ........................................................................................................................................................ 67 
APPENDIX A:  DEFINITIONS and ACRONYMS ................................................................................................................ 70 
APPENDIX B: SCHEDULE OF EVENTS ............................................................................................................................. 74 
APPENDIX C: LIFESTYLE MODIFICATIONS PROGRAM...REDACTED ................................................................................ 75 
APPENDIX D: BMI CALCULATOR ................................................................................................................................... 76 
APPENDIX E:  SAMPLE OF PATIENT HEALTH QUESTIONAIRE (PHQ-9)… REDACTED ....................................................... 77 
APPENDIX F: IWQOL – LITE…REDACTED ......................................................................................................................... 78 
APPENDIX G: SAMPLE OF SUBJECT INFORMATION CARD ............................................................................................. 79 
APPENDIX H: SAMPLE OF CONTROL OF EATING QUESTIONAIRE…REDACTED ............................................................... 80 
APPENDIX I: EATING INVENTORY…REDACTED ............................................................................................................. 81 
 
 
Figure 1. Long-term Weight Loss after Bariatric Surgery in SOS Study ........................................... 14 
Figure 2. TransPyloric Shuttle ......................................................................................................... 16 
Figure 3. TPS Dimensions (mm) ..................................................................................................... 17 
Figure 4. TPSS Delivery Device ...................................................................................................... 18 
Figure 5. TPSS Access Sheath ....................................................................................................... 18 
Figure 6. TPSS Stand with TPS Delivery Device in Place ............................................................... 19 
Figure 7. Reusable TPSS Insufflation System ................................................................................. 19 
Figure 8. TPS Retrieval Kit (w/OTS Overtube) ................................................................................ 20 
Figure 9. Overtube Insertion Assembly ........................................................................................... 21 
Figure 10. TPS in Gastric (A) and Transpyloric (B) Position ............................................................ 22 
Figure 11. %EWL in Proposed Target Population of 30-40 BMI Subjects ........................................ 24 
Figure 12. Study Diagram ............................................................................................................... 29 
Figure 13.  Management of Endoscopic Observations .................................................................... 40 
Figure 14. Guideline for Managing Hypoglycemic Medication(s) (Pre-Procedure) .................. 43 
Figure 15. Guideline for Managing Hypoglycemic Medication(s) (Post-Procedure) ................ 45 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 6 of 83 
 
 
1. PROTOCOL SUMMARY 
Protocol Title 
ENDObesity II Study: Endoscopic Treatment for Weight Reduction in Patients with 
Obesity Using the TransPyloric Shuttle® System: A Multicenter, Prospective, 
Randomized, Double-blind, Sham-controlled, Parallel-design Study 
Protocol Number 
DTC006 
Investigational 
Device 
TransPyloric Shuttle® System (TPSS) 
Proposed 
Indication 
The TransPyloric Shuttle System is indicated for weight reduction in patients with 
obesity with a Body Mass Index (BMI) of 35.0-40.0 kg/m2 or a BMI of 30.0 to 34.9 
kg/m2 with one or more obesity-related comorbid conditions. 
Regulatory Status 
The device is under clinical investigation in the US for the proposed indication stated 
above. 
Objectives 
The objective of this study is to assess the safety and effectiveness of the TransPyloric 
Shuttle (TPS®) for weight reduction in obese subjects with BMIs of 30-40 kg/m2. 
Study Design 
This is a multicenter, prospective, randomized, double-blind, sham-controlled, 
parallel-design study conducted in the United States. 
The pivotal study cohort will consist of 270 pre-planned study subjects which will be 
randomized in 2:1 ratio to the Treatment or the Control group from up to 12 sites. 
Subjects who sign the informed consent and are deemed eligible following a general 
and endoscopic screening will be enrolled in the study and randomized.  
Subjects assigned to the Treatment group will receive the TPS placement and the 
subjects in the Control group will undergo a sham procedure without TPS placement. 
The subjects will be blinded to their treatment. The Investigators and/or study 
coordinators who collect the primary outcome data will be masked to subjects’ 
treatments.  
Subjects will be followed for 12 months or less than 12 months if the subject achieves 
the midpoint of the normal BMI range (22 kg/m2), at which time the subject is 
considered to have completed the study and the device removed if the subject had 
received the TPS device.  
Subjects will receive brief (15 minute) lifestyle-modification counseling sessions at 
each follow up visit. They also will receive brief (15min) telephone calls in the months 
that do not include in person visits between 6 and 12 months (in months 7, 8, 10, and 
11). These counseling sessions are centrally designed to improve adherence to 
recommendations to consume a healthy diet and increase physical activity to promote 
weight loss and overall health. The counseling sessions and telephone calls will be 
provided by a member of the research team (dietitian, nurse, etc.) trained in the 
delivery of the prescribed lifestyle counseling. 
 
Patient Population 
Male and female subjects, 22-60 years of age, with a BMI of 35.0 to 40.0 kg/m2, 
inclusive, or a BMI of 30.0 to 34.9 kg/m2 with at least one obesity-related comorbidity. 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 7 of 83 
 
 
Co-Primary 
Endpoints 
• 
Mean percent total body weight loss (% TBL) between the Treatment and the 
Control group at 12 months after the index procedure.  
• 
The proportion of subjects in the Treatment group who achieve ≥ 5% TBL at 12 
months after the index procedure.  
Secondary 
Endpoints 
• 
Proportion of subjects who achieve at least 7% and 10% TBL at 12 months in the 
Treatment versus Control group 
• 
Percent total body weight loss over 12 months in the Treatment versus Control 
group 
• 
Percent excess weight loss over 12 months in the Treatment versus Control 
group 
• 
Proportion of subjects who achieve at least one obesity class reduction at 12 
months in the Treatment versus Control  group 
• 
Change of BMI over 12 months from baseline in the Treatment group 
• 
Change in weight-related quality of life over 12 months as assessed by IWQOL-
Lite Questionnaire  
• 
Change in eating behavior over 12 months as assessed by the Eating Inventory  
• 
Change in appetite, hunger and fullness over 12 months as assessed by Visual 
Analog Scales  
• 
Change in comorbid conditions over 12 months in the Treatment group: 
o Prevalence of the metabolic syndrome and its individual components  
o Glucose, insulin, and insulin resistance (as estimated by HOMA)  
o High sensitivity C-reactive protein (hsCRP)  
o Lipid levels (LDL-C, HDL-C, and triglycerides)  
o Blood pressure  
o Waist circumference 
 
Safety Evaluation  
Safety will be characterized through a summary of the incidence of adverse events.  
A Clinical Event Committee (CEC) will review and adjudicate all serious device-
related adverse events and any other events deemed necessary.  
Key Inclusion 
Criteria 
1. Male and female subjects between the ages of 22 to 60 
2. A BMI between 30.0 to 40.0 kg/m2, inclusive.  Subjects with a BMI of 30.0 
kg/m2 to 34.9 kg/m2 are required to have one or more of the following 
obesity-related mild-moderate comorbidities: 
a. Type 2 Diabetes: meet one of the following criteria and currently not 
using insulin 
i. HbA1c 6.5%-7.5% 
ii. Controlled, on stable dose of oral medications for at least 3 
months 
b. Hypertension, meet one of the following criteria: 
i. Arterial blood pressure >140 mmHg systolic or >90 mmHg 
diastolic on or off hypertensive medication 
ii. Arterial blood pressure ≤140 mmHg systolic and ≤90 mmHg 
diastolic on hypertensive medication 
c. Hyperlipidemia, meeting at least one of the following criteria: 
i. Fasting blood total cholesterol level of ≥240 mg/dl  
ii. Fasting total triglyceride level of ≥200 mg/dl  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 8 of 83 
 
 
iii. Low density Lipoprotein cholesterol ≥160mg/dl 
iv. Currently taking lipid-lowering medication based on an 
elevation of total cholesterol, triglycerides, or LDL 
3. History of obesity for at least 2 years, with history of failure of medically or 
commercially supervised weight loss program  
4. History of weight stability (defined as a < 5% change in body weight) for at 
least 3 months prior to the screening visit 
5. Female subjects of childbearing potential must have a negative urine 
pregnancy test and must commit to practice their physician-agreed form of 
birth control for the duration of participation  
6. Willing and able to provide written informed consent  
7. Willing and able to comply with study procedures and return for all study 
visits 
Key Exclusion 
Criteria 
1. Pregnancy or planned pregnancy in next 12 months after enrollment 
2. Nursing or pregnancy within the 6 months prior to enrollment 
3. Known hormonal or genetic cause for obesity 
4. Prior history of any surgery or endoscopic intervention that has altered 
esophageal, gastric or duodenal anatomy, including any bariatric surgery, 
such as gastric bypass, and restrictive procedures such as laparoscopic 
adjustable gastric banding 
5. Prior treatment with an intragastric balloon for the purpose of weight loss, 
where the balloon was removed less than 12 month prior to the screening  
visit for this study  
6. Chronic use (at least past 6 months) of medications likely to contribute to 
weight gain or prevent weight loss (e.g., corticosteroids, lithium, olanzapine, 
risperidone, clozapine, anticonvulsants, glitazones (e.g., pioglitazone), 
monoamine oxidase inhibitors) 
7. A history of gastric or duodenal ulcers 
8. After treatment for Heliobacter pylori, subject still tests positive for H. pylori  
9. A history of severe dyspepsia  
10. GI tract motility disorders such as esophageal motility disorders, 
gastroparesis diabeticorum, or intractable constipation 
11. History of inflammatory disease of GI tract, such as Crohn’s disease 
12. History of coeliac disease 
13. History of pancreatitis 
14. History of portal hypertension, cirrhosis, and/or varices 
15. Diabetes treated with insulin or significant likelihood of requiring insulin in 
next 12 months 
16. HbA1c >7.5% 
17. Uncontrolled thyroid and adrenal gland disease 
18. Uncontrolled hypertension defined as systolic blood pressure > 160 mmHg 
or diastolic blood pressure > 100 mmHg 
19. A history of cardiac arrhythmia, ischemic heart disease, myocardial 
infarction or chronic heart failure  
20. History of cerebrovascular disease, transient ischemic attack, or stroke 
21. Presence of localized or systemic infection 
22. Anemia (hemoglobin <11.0 g/dl for female and <12.0 g/dl for male) 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 9 of 83 
 
 
23. History of asthma likely to require systemic steroid therapy during the 
duration of the study participation or frequent use of rescue inhalers 
24. Autoimmune connective tissue disorders or known  to be 
immunocompromised or at risk of becoming immunocompromised (e.g., 
HIV positive) 
25. A history of malignancy except non-melanoma skin cancer 
26. Continuous therapy with known ulcerogenic medication (e.g., aspirin greater 
than 81mg/day, NSAIDs) 
27. On anticoagulation or antiplatelet therapy (e.g., Coumadin, Warfarin, 
Heparin, Pradaxa, Xarelto, Plavix) 
28. Unwilling to avoid use of any weight-loss medication, including over-the-
counter treatments and/or herbal supplements, during the course of study, or 
on prescription medications that can be used for weight loss, even if they are 
not prescribed for weight loss (e.g., Topiramate, Wellbutrin) and stimulant 
medications (e.g., for ADHD) 
29. Currently participating, or unwilling to avoid participation in any non-study-
related organized weight-loss program (medical or commercial) during the 
course of the study 
30. Unable to take proton pump inhibitor (a daily 40+mg of Omeprazole or 
equivalent), or addition of PPI may cause adverse drug interaction with 
subject’s medication or interruption of treatment 
31. Clinically significant abnormal laboratory values or an EKG that make the 
subject a poor study candidate in the opinion of the Investigator 
32. Inability to walk at least 0.8 kilometers per day (10 minutes of continuous 
walking) 
33. Planned surgical procedure that can impact the conduct of the study 
34. Started on a prescribed medication regimen within the last three weeks, or 
whose concomitant medication regimen is expected to change during the 
course of the study, and where the Investigator determines the medication 
may affect the study outcome 
35. Known allergy to any component materials in the TPSS such as silicone, 
barium sulfate, parylene 
36. Current smoker or user of nicotine product or smoking cessation within 1 
year of the screening date 
37. Current abuse of drug or alcohol or past treatment for substance abuse 
38. Presence of any severe, uncontrolled psychiatric illness 
39. Inpatient psychiatric treatment within the past year 
40. A score of ≥10 on the Patient Health Questionnaire 9 (PHQ-9), indicating 
moderate depression 
41. Diagnosis of bulimia nervosa or binge eating disorder 
42. Any medical condition (including psychiatric disease) that would interfere 
with the interpretation of the study results, the conduct of the study, or would 
not be in the best interest of the subject in the opinion of the site Primary 
Investigator. 
43. Participation in another clinical study within 60 days of screening date, in 
previous or ongoing clinical study, or plan to participate in another clinical 
study at any time during this study 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 10 of 83 
 
 
44. Employee or family member of BAROnova, the Investigator, or site study 
staff  
45. The Investigator judges the candidate unsuitable for the study 
46. Have any of the following endoscopic exclusion criteria 
a. Esophageal stricture 
b. Barrett’s esophagus 
c. Erosive esophagitis  
d. Varices 
e. Angiectasias 
f. Gastric mass 
g. Antral or peri-pyloric polyps 
h. Peptic ulceration 
i. 
Hiatal hernia ≥ 4 cm 
j. 
Pyloric stricture 
k. Any other abnormalities/characteristics that would preclude safe use 
of the TPS 
Post Procedure 
Follow-up and 
Assessment 
Schedule 
• 
Office visits: 1 week, and 1, 2, 4, 6, 9, and 12 month(s)   
• 
Endoscopic follow up: 2, 6, and 12 months 
• 
Blood tests: 6 and 12 months 
• 
Eating Inventory and Visual Analog Scales: 1 week, and 1, 6, 12 months 
• 
IWQOL-Lite:  6 and 12 months 
• 
Device removal: 12 months 
Analysis 
Population 
Intent-to-Treat: includes all randomized and enrolled subjects regardless of whether or 
not the subject receives the randomized treatment. 
Per -Protocol: includes all subjects who receive the assigned treatment and do not have 
any major eligibility violations. 
Modified Intent-to-Treat: consists of the Intent-to-Treat population that have received 
the assigned treatment and have at least one post-treatment follow up, including the 
index procedure visit. 
Completed Cases: includes all enrolled subjects who have the 12-month follow-up 
visit, or have completed the study based on reaching the BMI objective of ≤ 22 kg / m2 
in two consecutive follow-up visits as described in Section 5.1. 
Proton Pump 
Inhibitor (PPI) 
Use 
Subject will be placed on PPI (Omeprazole 40 mg daily or equivalent) starting at least 
one week before the index procedure and continue until the TPS removal (or the last 
visit in the Control subjects).   
Post Procedure 
Patient 
Management 
• Subject will be on a liquid diet for 3 days, followed by soft food for 7 days, and 
then a normal diet. 
• Subject will have antiemetic and antispasmodic on standby. 
Safety Monitoring 
Safety will be monitored throughout the study. The Investigators will assess the 
occurrence of adverse events at each follow up visit. The Data Safety Monitoring 
Board (DSMB) will monitor and evaluate the safety data throughout the study. A 
pre-specified staged safety monitoring will be performed after the first 30, 60 and 90 
subjects in the Treatment group have reached 80 days post index procedure. 
Timeline 
• 
First Subject Enrolled: Q4 2015 
• 
Estimated Enrollment Duration: 12 months (Q4 2016) 
• 
Last Subject to Primary Endpoint Follow-up: (Q4 2017) 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 11 of 83 
 
 
• 
Study Duration: 24 months 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 12 of 83 
 
 
2. BACKGROUND 
Obesity is a major public health issue in the United States with 78 million adults now obese. In 2009-2010, the 
prevalence of obesity in the US was 35.5% among men and 35.8% among women.1  The annual healthcare 
costs associated with obesity have been estimated at up to 8% of overall healthcare budgets. Recognizing the 
health consequence and the morbidity and mortality associated with obesity, the American Medical 
Association officially classified obesity as a disease in 2013.2 
2.1. Definition of Obesity  
Obesity is defined as a body mass index (BMI) that exceeds 30 kg/m2.  A BMI of 18.5-25 kg/m2 is defined as 
normal and 25-30 kg/m2 as overweight. Obesity is further classified into three groups:  moderate (Class I, BMI 
30.0 – 34.9), severe (Class II, BMI 35.0 – 39.9), and very severe (Class III, BMI > 40).3  
2.2. Obesity Related Comorbidities and the Benefit of Modest Weight Loss  
Substantial evidence suggests that obesity is associated with significant morbidity and mortality. A 
comprehensive systematic review and meta-analysis including 87 high quality prospective cohort studies 
concluded that excess body weight was associated with the incidence of multiple comorbidities, including 
Type 2 diabetes mellitus, cardiovascular diseases, cancers, asthma, osteoarthritis and gallbladder disease.4  A 
BMI ≥30 kg/m2 is also associated with reduced life expectancy.5,6 
Weight loss has been shown to improve many of the comorbidities associated with obesity and results in 
significant improvements in components of the metabolic syndrome.7,8,9 A weight loss as small as 3% can 
result in improvements in some cardiovascular disease risk factors and a weight loss of 5% or more is 
generally considered to be clinically meaningful.10,11 A loss of 5% to 10% of body weight is associated with 
decreased cardiovascular disease risk factors, prevention or delay of the development of Type 2 diabetes, and 
improvement of other health consequences of obesity.12,13 Greater weight loss produces greater reductions in 
cardio metabolic risk.14 The recently published 2013 AHA/AAC/TOS Guideline recommends a chronic 
disease management model for obesity, in which patients are encouraged to lose 5% to 10% of their body 
weight as an initial goal to decrease the risk of the development, or amelioration of, obesity-related medical 
conditions and cardiovascular risk factors.15  
2.3. Treatment Options  
2.3.1. Lifestyle Modification Interventions 
Lifestyle modification focuses on caloric reduction, increased physical activity, and behavioral modification 
strategies. Lifestyle intervention by itself results in moderate weight loss. Although studies performed in 
academic centers have shown that intensive lifestyle modification delivered in weekly counseling sessions can 
produce a 7-10% weight loss and improvements in weight-related health problems within 6 months, the “real 
world” outcomes are often more modest and  are largely influenced by the delivery methods, intensity, and 
duration of the interventions. A recent example of this is the POWER-UP study which randomized 390 
subjects into three types of intervention: usual care, consisting of quarterly primary care provider (PCP) visits 
that included education about weight management; brief lifestyle counseling, consisting of quarterly PCP visits 
combined with brief monthly sessions with lifestyle coaches who instructed participants about behavioral 
weight control; or enhanced brief lifestyle counseling, which also provided quarterly physician visits and 
monthly lifestyle counseling sessions but included the use of meal replacement products or weight-loss 
medication.  The change in body weight (% TBL) with usual care, brief lifestyle counseling, and enhanced 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 13 of 83 
 
 
brief lifestyle counseling was 2.1% ± 0.6%, 3.5% ± 0.6%, and 7.0% ± 0.6% at 1 year (P<0.001), and 1.6% ± 
0.6%, 2.9% ± 0.7%, and 4.7% ± 0.6% (P<0.001) at 2 years, respectively.16  
Outcomes of lifestyle modification interventions are greatly influenced by patient motivation as well as 
adherence and compliance over time. It is, however, important to recognize that lifestyle modification is an 
essential component of any weight loss intervention, including pharmacotherapy and bariatric surgery.  
2.3.2. Pharmacotherapy 
Pharmacotherapy for weight loss is often used as a more intensive treatment for obesity after lifestyle 
modification fails. Pharmacotherapy is typically recommended for patients with a BMI > 30 kg/m2 or > 27 
kg/m2 in the presence of weight related comorbidities and when weight-loss goals and related health 
improvements were not achieved with lifestyle modification.  
When combined with lifestyle interventions, obesity medications can produce a moderate weight loss ranging 
from approximately 3% of initial weight for orlistat and lorcaserin to 9% for top-dose (15/92 mg) phentermine 
plus topiramate–extended release at 1 year. Mean total weight loss ranges from 1% to 5% of placebo-
subtracted values, and varies based on factors including patient population and intensity of concomitant 
lifestyle intervention.17 Thirty percent to more than 60% of patients may not achieve a clinically meaningful 
weight reduction (5%) at 12 weeks. 17 
Adverse effects of weight loss medications range from headache, nausea, fatigue, and dizziness to more severe 
concerns such as cardiovascular events and birth defects. During the history of antiobesity drugs, many have 
been withdrawn in the United States secondary to concerns with their side effects. Various guidelines 
recommend prescribing drug therapy for obesity after thorough consideration of potential risks against 
potential benefit for each individual patient. The cost effectiveness of long-term pharmacotherapy of obesity is 
still an unresolved question.  
2.3.3. Bariatric Surgery 
Patients with BMIs ≥ 40 kg/m2 or ≥ 35 – 39.9 kg/m2 with significant weight-related co-morbidities, and who 
have failed more conservative weight-loss treatments (such as lifestyle modification and pharmacotherapy), 
are potential candidates for bariatric surgery15. The most common surgical procedures include gastric bypass 
surgery, sleeve gastrectomy, and adjustable gastric banding procedures. Patients lose 50%-60% excess body 
weight (EWL) with the gastric bypass procedure and 40%-50% with restrictive procedures at 2 years.  The 
Swedish Obesity Subjects (SOS) study13,18 is a landmark investigation that provided high quality evidence on 
the long-term effect of bariatric surgery. It included 4,047 obese subjects, prospectively matched between 
three surgical interventions (1471) and the control group (1444). The surgically treated subjects underwent 
nonadjustable or adjustable banding (n = 376), vertical banded gastroplasty (VBG; n = 1369), or gastric bypass 
(GBP; n = 265). All three types of surgeries produced larger weight losses than seen in the control group. In 
addition, the study demonstrated patterns of initial maximum weight loss at 1-2 years and subsequent weight 
regain over time (Figure 1). A more recent longitudinal study from the US (LABS-2) showed similar results to 
those observed in the Swedish study over 3 years of follow up, with 31.5% total weight loss for Roux-en-Y 
gastric bypass (RYGB) and 15.9% for laparoscopic adjustable gastric band (LAGB)19.  
 
  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 14 of 83 
 
 
Figure 1. Long-term Weight Loss after Bariatric Surgery in SOS Study 
 
While surgery is most effective in weight loss, a significant proportion of patients experience surgical 
complications. Early post-operative complications include leak, bleeding, stricture, perioperative blood loss 
and reoperation occurring in 5-10% of patients. Colquitt et al.20 conducted a detailed analysis of complications 
in a systematic review of surgical studies. Operative re-intervention occurred in 13% of surgical patients, 
laparoscopic revision (10%), port infection (2.6%) and acute cholecystitis (2.6%). The SOS study13 reported 
complications of operative death (0.25%), perioperative complications (13%), infection (2.1%), pulmonary 
symptoms (6.2%), thromboembolism (0.8%) and bleeding (0.9%). Late complications including anemia and 
B12 deficiency, have been reported in at least 25% of patients.21 Vomiting and gastric dumping have been 
reported in one- to two-thirds of patients. The mortality rate is generally thought to be approximately 1%.   
Despite the success often seen with bariatric surgery, only 1% of the clinically eligible population receives 
surgical treatment for obesity.22,23 This is likely due to many factors, including lack of insurance coverage for 
the procedures, as well as perceived risks of the procedures among potential patients and their providers. 
Regardless of the specific reasons, there is a need for additional, effective treatments to promote weight loss in 
patients with obesity.  
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 15 of 83 
 
 
2.3.4. Endoscopic Approaches to Obesity 
Endoluminal interventions performed entirely through the GI tract by using flexible endoscopy offer the 
potential for an ambulatory weight-loss procedure that may be safer and more cost-effective when compared to 
current surgical approaches. A number of innovative devices are currently in development and are at various 
stages. The only device that was previously approved in the US was the Garren-Edwards Gastric Bubble®, 
which was sold in the U.S. market from 1985 to 1987.  The device was subsequently removed from the US 
market by the manufacturer because of a high rate of device deflation and subsequent GI obstructions. The 
BioEnterics Intragastric Balloon (BIB or Orbera®) and similar intragastric balloon devices are currently 
available outside the US. 
Intragastric balloons are designed to be an adjunctive therapy to lifestyle modification. The device typically 
remains within the stomach for up to 6 months. Patients undergo intensive lifestyle modification during the 
treatment period and afterwards, with the hope that the device will provide the patient with a window of 
opportunity to develop eating and activity habits that can be used to maintain weight loss once the device is 
removed.  
A meta-analysis24 pooled 15 articles (3,608 patients) and showed that the intragastric balloon intervention 
achieved 12.2% of total weight loss and 32.1% of excess weight loss at balloon removal. A recently published 
randomized study25, which compared intragastric balloon plus lifestyle intervention to lifestyle intervention 
alone, rendered similar results with 14.2% TBL in the intragastric balloon group versus 4.8% in the lifestyle 
modification alone at 6 months. Genco et al26 reported a multicenter experience of 261 patients treated with the 
intragastric balloon that were followed up to 3 years. The mean BMI fell from 28.6 kg/m2 ± 0.4 kg/m2 at 
baseline to 25.4 kg/m2 ± 2.6 kg/m2 at 6 months and to 27.0 kg/m2 ± 3.1 kg/m2 at 3 years from BIB removal. 
The mean %EWL was 55.6% at 6 months and 29.1% at 3 years. Despite a weight regain after balloon removal, 
improvements in comorbidities were observed at 3 years, with hypertension decreasing from 29% at baseline 
to 16% at 3 years, diabetes from 15% to 10%, dyslipidaemia from 20% to 18%, hypercholesterolaemia from 
32% to 21% and osteoarthropathy from 25% to 13%.  
Common adverse effects include intractable nausea and vomiting affecting over 70% of patients, resulting in 
patient intolerance and early device removal in 4.2% of patients26. Other complications include balloon 
leaking/deflation, obstruction, gastritis, and gastric or duodenal ulcerations.  
2.3.5. Weight-Loss Maintenance 
Weight regain following a successful weight-loss intervention historically has been a challenge for all types of 
weight loss treatments. A typical pattern of weight loss in patients undergoing a lifestyle intervention is that 
maximum weight loss is achieved at 6 months, followed by a plateau and gradual regain over time. A similar 
pattern is observed in medication-assisted weight loss when medication is stopped. For bariatric surgery 
patients, maximum weight loss occurs within 1 year followed by gradual weight regain overtime, as shown in 
Figure 1. For example, gastric bypass patients had a maximum weight loss of 38% TBL at one year, followed 
by a weight regain of about 13% with maintenance of a 25% body weight loss at 10 years. 
Recently published AHA/ACC/TOS Guideline15 advises individuals who have lost weight to participate in a 
long-term (≥1 year) comprehensive weight-loss maintenance program to enforce lifestyle modification in order 
to maintain weight loss.  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 16 of 83 
 
 
It is increasingly recognized that treating obesity requires a range of effective therapies, and combinations of 
these therapies are often required to provide long-term control. While bariatric surgery is the most effective 
weight-loss therapy, it carries significant short-term and long-term morbidities and costs. Pharmacotherapy in 
combination with lifestyle intervention can only achieve modest weight reduction while carrying the potential 
of systemic side effects of pharmacologic agents. In order to effectively manage the epidemic of obesity and 
reduce the societal burden of the associated co-morbidities, there is an urgent need for therapies that are safer, 
less invasive, and reversible while providing clinically meaningful weight loss to patients. In this study, we 
aim to evaluate an endoscopic, non-surgical interventions using the BAROnova TransPyloric Shuttle System.   
3. DEVICE DESCRIPTION 
The investigational device is the TransPyloric Shuttle System (TPSS). The TPSS has undergone three 
generations of device iterations. The current study device represents the third generation device (GEN III 
TPSS). 
3.1. System Description 
The TransPyloric Shuttle System consists of a TransPyloric Shuttle (TPS), its delivery system, and the TPS 
Retrieval Kit. The TPS is designed to be delivered into and removed from the gastric cavity using a trans-
esophageal endoscopic procedure.  
3.1.1. TransPyloric Shuttle 
The TPS is constructed of three main components: the external skin, the inner coil and the lock-release button. 
These components are preloaded into the TPS Delivery Device. During the TPS delivery, the three 
components are mechanically joined to construct the functional configuration of the TPS device. The 
components are secured by an internal locking mechanism.  
After being constructed, the TPS forms a smooth large proximal bulb with a compliant distal tapered region 
connected to a smaller distal bulb by a flexible silicone tether (Figure 2). The dimensions of the device are 
shown in Figure 3. 
The TPS is principally made of a medical-grade silicone elastomer and the internal coil is loaded with barium 
sulfate for radiopacity. The external surface is coated with parylene.  
 
 
 
Figure 2. TransPyloric Shuttle 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 17 of 83 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 3. TPS Dimensions (mm)  
 
3.1.2. TPSS Delivery System 
The TPS Delivery System consists of the TPS Delivery Device (Figure 4) and the TPSS Access Sheath (Figure 
5). Both are designed for single-use and are disposed after the procedure. 
BAROnova also provides a reusable TPSS Accessory Kit for use with the Delivery System that includes: an 
insufflation system, a TPSS stand, an Allen key, and a hook tool. The insufflation system is designed to 
provide pressure-controlled air to the stomach to insufflate the gastric space during deployment. The TPSS 
stand and tools facilitate use and troubleshooting of the system.  
3.1.2.1. 
TPSS Delivery Device 
The TPS Delivery Device is designed for trans-esophageal delivery of TPS through the TPSS Access Sheath. 
The Delivery Device consists of a distal PTFE catheter preloaded with TPS components, a proximal handle 
that controls the delivery mechanism, an outer slidable introducer sleeve that protects the TPS components 
during catheter introduction, and an access-sheath connector that enables secure engagement with the proximal 
end of the Access Sheath for device positioning (Figure 4). An insufflation port allows for inflation of the TPS 
skin and insufflation of the gastric cavity during TPS delivery.  
The handle on the Delivery Device provides the user interface for actuation of the delivery-system 
mechanisms that control deployment and release of the TPS. The advance/torque knob limits the force that can 
be put into the system to ensure safe delivery, and the progress indicator provides visual feedback on the 
progress of the TPS coil deployment. The Delivery Tube Disconnect enables removal of the internal shaft 
component without losing the access. This allows for endoscopic inspection of the constructed TPS before 
final removal of the delivery system.  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 18 of 83 
 
 
 
Figure 4. TPSS Delivery Device 
 
3.1.2.2. 
TPSS Access Sheath 
The TPSS Access Sheath consists of a non-reinforced PTFE catheter with a polyurethane distal positioning 
balloon and an obturator. It is designed to protect the esophagus during the TPS delivery procedure. After 
inflation, the distal balloon is positioned against the gastroesophageal junction under endoscopic visualization. 
This sets the position for TPS deployment. Once the Delivery Device is fully inserted, its Connector engages 
the Access Sheath handle, and the system is ready for deployment.  
Figure 5. TPSS Access Sheath 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 19 of 83 
 
 
3.1.2.3. 
TPSS Accessory Kit 
The TPSS is provided with a reusable TPSS Accessory Kit to facilitate deployment of the device. The primary 
components of the Accessory Kit are described below.  
 
 
Figure 6. TPSS Stand with TPS Delivery Device in Place 
For the convenience of the operator, the handle of the TPS Delivery Device may be placed in the reusable, 
stand (Figure 6) for deployment. Once the Access Sheath has been placed and the TPS Delivery Device is 
fully-inserted into it with the connectors engaged, the system is ready for deployment.  
Prior to initiating TPS coil advancement with the handle controls, the TPS Delivery Device is connected to the 
reusable insufflation system using the disposable tubing set provided with the system. The insufflation system 
is designed to provide pressure-controlled air to the stomach to insufflate the gastric space during deployment. 
A schematic of the insufflation system is shown in Figure 7.  
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 7. Reusable TPSS Insufflation System 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 20 of 83 
 
 
3.1.3. TPS Retrieval Kit  
A commercially available 19.5mm OD gastric over-tube (Guardus® Overtube - Gastric, Model Nos. 
00711148, US Endoscopy, Mentor, OH) will be used to protect the esophagus and enable device retrieval.  
BAROnova will provide a TPS Retrieval Kit designed for use with the Guardus overtube and intended to 
facilitate endoscopic removal of the TPS device. The TPS Retrieval Kit includes the TPS Collector Tip 
(overtube tip insert), an Obturator Adapter, an Installer Tool, a Handle Spacer, a Seal Cap, a Push Tube and 
two Endoscope Caps ( 
 
 
 
 
 
 
 
 
 
 
Figure 8). The TPS Collector Tip is made of medical grade PTFE and is designed to provide an optimized 
interface for TPS unlocking, deconstruction and retrieval through the overtube. The Endoscope Cap fits onto 
the end of a standard gastroscope and is used to enable tissue exclusion and orient the TPS as it is drawn 
towards and into the TPS Collector Tip for unlocking and retrieval. Two sizes of the Endoscope Cap are 
included in the TPS Retrieval Kit to accommodate different gastroscope diameters. The TPS Collector Tip is 
applied to the overtube prior to insertion.  The overtube, with the TPS Collector Tip installed, is inserted 
through the esophagus and into the stomach over a gastroscope using standard techniques. The Obturator 
Adapter and Handle Spacer are used to adjust the length and tip profile of the overtube obturator to 
accommodate the TPS Collector Tip and create an atraumatic profile for insertion. The Installer Tool, 
consisting of the Installer Tool Handle and Installer Tool Collar are used to place the Obturator Adapter onto 
the obturator.  The Seal Cap is designed to create a robust seal around the gastroscope shaft at the proximal 
end of the overtube during the retrieval procedure.  The Push Tube is a tool optionally used to aid retrieval of 
the TPS coil through the overtube. The TPS Retrieval Kit is composed of single-use items that are disposed 
after the retrieval procedure.  
 
 
 
 
 
 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 21 of 83 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 8. TPS Retrieval Kit (w/OTS Overtube) 
Figure 9 illustrates the overtube when assembled for insertion with the retrieval accessories as well as close up 
views of the tip configured for insertion (gastroscope is not shown) and the tip insert component. 
 
 
Figure 9. Overtube Insertion Assembly 
3.2. Proposed Mechanism of Action 
The TPS is delivered directly into the gastric cavity in a non-surgical, endoscopic, outpatient procedure.  Once 
delivered, the device is designed to self-position across the pylorus and create an intermittent obstruction to 
outflow that may result in delayed gastric emptying (Figure 10). Slowing gastric emptying may enable an 
overall reduction in caloric intake and weight loss by helping the subject feel full sooner (early satiation) 
and/or feel full longer (prolonged satiety/reduced hunger).  While in residence in the stomach, the TPS may 
also affect mechanisms near the gastric outlet and in the proximal duodenum to augment feelings of fullness.  
The device is mainly constructed in medical-grade silicone with a small volume and light weight, thus 
minimizing intolerance symptoms as seen in intragastric balloon devices.  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 22 of 83 
 
 
The TPS is designed to be a removable device. The device residence time is 12 months in the current study. 
After which time, the TPS is removed in a non-surgical, endoscopic, outpatient procedure. The strategies for 
weight maintenance after device removal should follow clinical practice guidelines for weight loss 
maintenance.15 
Figure 10. TPS in Gastric (A) and Transpyloric (B) Position 
3.3. Proposed Indication 
The TransPyloric Shuttle System is indicated for weight reduction for patients with obesity, with a Body Mass 
Index (BMI) of 35.0-40.0 kg/m2, or a BMI of 30.0 to 34.9 kg/m2 with one or more obesity-related comorbid 
conditions. 
3.4. Prior Investigations 
3.4.1. Pre-Clinical Testing 
Development of the TPSS includes a preclinical testing program intended to ensure safe use of the system in 
human studies for weight loss. TPS device testing is based on the anticipated biomechanical environment 
associated with one-year residence. Delivery system and device-retrieval testing is based on the anatomical 
and operational requirements in an outpatient setting employing endoscopically-based, non-surgical, 
transesophageal procedures.  
The BAROnova quality system requires that the TPSS final product configuration meets all specifications in 
the TPSS Product Specification prior to human use.  The testing also demonstrates that all risks identified in in 
the TPSS Risk Analysis, which is developed in accordance with ISO 14971:2007, have been adequately 
mitigated. Preclinical bench testing verifies system performance relative to a broad spectrum of system 
characteristics, including but not limited to: 
• 
Biocompatibility 
• 
Durability, including acute strength, cyclic fatigue, and material composition 
• 
Simulated use 
• 
Shelf life/package integrity 
Acute animal studies in porcine and canine models are performed to validate comprehensive simulated use 
bench testing for system functionality in delivery and retrieval. Chronic studies performed in live pigs 
demonstrated successful endoscopic deployment and retrieval of the TPS and robustness of the device in the 
gastric environment.  
A 
B 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 23 of 83 
 
 
A similar pre-clinical testing program was utilized to characterize the previous iteration of the TPSS that was 
used in the ENDObesity I clinical study. In the ENDObesity I study, devices were safely delivered and 
successfully retrieved from 10 subjects after three months of residence time, and from 10 subjects after six 
months.  Retrieved devices were returned to BAROnova and evaluations of device integrity were performed. 
These evaluations showed:  
• 
No gross damage or component failures after device residence 
• 
No changes in mass or gross dimensions  
• 
No significant changes to the mechanical properties of the materials of construction of the device 
The performance of the TPSS in the ENDObesity I study provides validation of BAROnova’s pre-clinical 
testing program to produce a safe and robust system for use in human clinical trials.  
3.4.2. Biocompatibility Testing 
The TransPyloric Shuttle System is comprised of the TransPyloric Shuttle device, the TPS delivery system and 
a TPS Retrieval Kit.  
The TPS device is evaluated in accordance with the requirements of ISO 10993-1: 2009, Biological Evaluation 
of Medical Devices to ensure that the devices are suitable for the anticipated exposure to human mucosal 
tissues.   
The required biocompatibility evaluation for the system is performed on device samples that are manufactured 
with the materials and processes representative of the device that will be used in the proposed IDE pivotal 
clinical trial.  All tests performed are managed in accordance with the FDA Good Laboratory Practices (GLP) 
regulation (21 CFR Part 58). 
The TPS device is evaluated as a “surface device” with “mucosal membrane contact” of greater than 30 days 
duration.    As the TPS may also come into contact with irritated mucosa in the stomach, testing for a “surface 
device” for “breached or compromised surface” of contact duration of greater than 30 days is also considered.  
The TPSS Delivery System is composed of the TPS delivery device and Access Sheath and is evaluated as a 
“surface device” with “mucosal membrane contact” with contact duration of less than 24 hours.  
The TPS Retrieval Kit is designed to be used with the commercially available gastric overtube for TPS 
retrieval. Components in the TPS Removal Accessory Kit are also evaluated as a “surface device” with 
“mucosal membrane contact” with contact duration of less than 24 hours. 
An evaluation of the TPSS has been performed which included a review of existing data on the same materials 
previously tested and used in the GEN II TPSS in addition to confirmatory testing on any new materials in the 
current device. All of the materials in the GEN III TransPyloric Shuttle System have been tested and assessed 
per the requirements of ISO 10993-1:2009.  The acceptable data confirmed that the GEN III TransPyloric 
Shuttle System meets the biocompatibility requirements per ISO 10993:2009 and is safe and suitable for 
human use as intended.  
 
3.4.3. Prior Clinical Experience 
A feasibility study (ENDObesity I Study) was conducted in 20 subjects in a single-center study that evaluated 
the safety and effectiveness of the second generation TPSS. The study included male and female obese 
subjects, 18 to 55 years of age, with a BMI 35-50 kg/m2 or 30-34.9 kg/m2 with one or more obesity-related 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 24 of 83 
 
 
comorbid conditions. The key exclusion criteria included pregnancy, previous gastrointestinal bariatric 
surgery, GI motility disorder, severe psychiatric conditions, and clinically important comorbid diseases such as 
insulin-dependent diabetes and uncontrolled hypertension. Subjects with significant endoscopic abnormalities 
(such as gastroduodenal ulcer, hiatal hernia ≥ 2cm, and erosive esophagitis) were also excluded.  Subjects were 
assigned to two groups of ten subjects. The device residence time was 3 months in first group of 10 subjects 
and 6 months in the second group of 10 subjects. The primary effectiveness endpoint was percent excess 
weight loss (EWL). The Impact of Weight on Quality of Life-Lite Questionnaire (IWQOL-Lite) was used to 
assess patient weight-related quality of life status before and after the treatment.  
Subjects were provided nutritional guidelines and encouraged to increase their physical activity at the 
beginning of the study. No specific dietary or exercise counseling was provided during the study duration after 
the initial baseline consultation.  
The average age of the subjects was 40.7 years ± 10.7 years and 18/20 (90%) were female. The baseline 
weight was 100.9 kg ± 20.5 kg, with a mean BMI of 36 kg/m2 ± 5.5 kg/m2 (34.0 kg/m2 ± 4.9 kg/m2 and 37.9 
kg/m2 ± 7.3 kg/m2 for 3- and 6-month subjects, respectively).  Baseline comorbidities included 
gastroesophageal reflux (50%), osteoarthritis (45%), hypertension (20%), Type 2 diabetes (5%), and sleep 
apnea (5%). 
TPS devices were successfully deployed and removed endoscopically in all subjects with no device or 
procedure related SAEs peri-procedurally.  Mean procedure times were 10.9 minutes ± 3.9 minutes for device 
deployment (from TPSS insertion to system removal) and 12.9 minutes ± 6.4 minutes for device removal 
(from overtube insertion to TPS and overtube removal).  
The excess weight loss was 33.1% ± 18.7% for the 3-month subjects and 50.0% ± 26.4% for the 6-months 
subjects. Those who had the device for 3 months lost, on average, 8.9 kg of weight (8.9% of TBL). Those who 
had the device for 6 months lost, on average, 14.6 kg (14.5% of TBL). All 10 subjects (100%) who had the 
device for 6 months achieved at least 5% TBL and 80% of them achieved more than 10% TBL. The weight-
loss curve in the target patient population (BMI 30-40 kg/m2) is shown in Figure 7.  
 
(N=17 for week 1 through month 3; N=7 for months 4-6) 
58.4%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
Week 1
Month 1
Month 2
Month 3
Month 4
Month 5
Month 6
%Change EW  from Day 0
Time
ENDObesity I - 30-40 BMI Subjects
%EWL +/- SD (BMI Method)

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 25 of 83 
 
 
Figure 11. %EWL in Proposed Target Population of 30-40 BMI Subjects 
Statistically significant improvements in the IWQOL-Lite overall scores were observed for both the three-
month and six-month cohorts. Mean increases of 23.5 and 23.6 points in the 3-month and 6-month study 
groups greatly exceeded the 7.7 to 12 point threshold considered to define a clinically significant change27. 
The device was well tolerated by patients. There were no deaths, no major gastrointestinal events such as 
bleeding or perforation, and no surgical interventions for any complications. Device-related adverse events 
were mostly mild to moderate in nature, including transient abdominal pain (8/20), nausea (6/20), vomiting 
(4/20), GERD (4/20), feeling heaviness (2/20), sore throat (1/20), constipation (1/20), candidiasis (1/20), 
pyloric spasm (1/20) and bloating (1/20). Endoscopic observations of ulcers (defined as ≥ 5mm in diameter 
with unequivocal depth) were noted in 10/20 patients, with 8/20 of them managed medically without 
complications.  In two patients, the ulcers were associated with SAEs (hospitalizations for acute gastric pain 
and pyloric spasm/inflammation).  In these 2 subjects, the devices were removed prior to their planned 
residence time, and ulcers resolved with medication without sequelae.   
Endoscopic observations suggested that the tissue effects observed were likely related to specific surface 
features of the GEN II TPS.  Device modifications have been implemented to improve the device-tissue 
interface in the current iteration (GEN III for the IDE pivotal study).  
 
3.5. Risks and Benefits  
3.5.1. Potential Benefits 
There are clear potential benefits for subjects who participate in this clinical study.  Subjects to be included in 
the present study have an existing indication for weight loss. The majority of these subjects may have 
attempted weight loss by diet or other means at some point in their life. The potential benefit of participating in 
this study is the ability to achieve clinically-significant weight loss without the need for bariatric surgery.  
There are potential societal benefits to a successful study. Obesity and its associated comorbidities is a widely 
recognized global problem that consumes a large amount of health care resources. If the device is shown to be 
safe and effective, it will provide a therapy that fills the gap between lifestyle intervention and bariatric 
surgery in terms of their risk and effectiveness profile, and thus contribute to overall management of obesity.  
3.5.2. Anticipated Adverse Events (AEs) Associated with the TPS Placement, Residence, and 
Removal  
Anticipated AEs associated with the TPS placement and removal procedures and TPS residence may include, 
but are not limited to, the following: 
• Abdominal cramps and discomfort from the air used to distend the stomach 
• Aspiration of gastric contents, aspiration pneumonia  
• Complications related to sedation and anesthesia 
• Complications related to upper GI endoscopy and the use of routine endoscopic instruments 
• Infection in the throat, esophagus, stomach, or duodenum 
• Gastric, esophageal, or pharyngeal trauma, including sore or irritated throat, ulceration, bleeding, or 
perforation in upper GI tract, and their associated complications 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 26 of 83 
 
 
• Injury to the digestive tract by the TPS delivery system or during device removal 
• TPS placement in an improper location such as in the esophagus or duodenum, which results in 
obstruction, bleeding, or perforation 
• Esophageal sphincter and/or pyloric sphincter incompetency associated with sphincter dilation 
during placement, residence or removal of the TPS 
• Inability to endoscopically remove part or all of the TPS device, which may result in the need for 
surgery 
• Cardiac or respiratory arrest during endoscopy 
• Halitosis 
• A feeling of heaviness in the abdomen 
• Abdominal or back pain, either steady or cyclic 
• Gastric discomfort, feelings of nausea, and vomiting 
• Constipation or diarrhea 
• Dyspepsia 
• Allergic reaction to the device’s materials (e.g., silicone, barium sulfate and parylene)  
• Excess reduction in oral intake, resulting in dehydration or malnutrition  
• Alteration of the absorption rate of medications, particularly to enteric-coated medications 
• Influence on medication dosing, leading to the need to adjust dosing and potential associated 
complications if dosing is not adjusted, such as hypoglycemia, hypotension, etc.  
• Influence on digestion of food 
• Pharyngeal, esophageal, or gastrointestinal obstruction by the TPS  
• Formation of intragastric bezoars  
• Gastroesophageal reflux 
• Distension of stomach 
• Injury or irritation to upper GI tract, resulting in acute or chronic tissue inflammatory response, pain, 
bleeding, erosion, ulceration, strictures, stenosis, or perforation  
• Bacterial or fungal growth on the surfaces of the TPS, resulting in infection  
• Biliopancreatic infection or obstruction, cholecystitis, pancreatitis  
• Need for medication, endoscopic intervention, early TPS removal, or surgery to treat/correct 
complications 
• Death 
3.5.3. Residual Risks Associated with the Investigational Device, as Identified in the Risk 
Analysis Report 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 27 of 83 
 
 
BAROnova has conducted extensive assessment of the risk associated with the device. The conclusion of the 
current risk assessment is that, with respect to perceivable conditions in which the product would be subjected 
to a worst-case environment or human error scenario, the outcome of the residual risk is considered acceptable 
as none of the recognized hazards leads to a risk within the intolerable range.   
The risk assessment does not contain foreseeable risks of intolerable levels. The device is designed and 
manufactured such that, when used as intended, it will not compromise the conditions of safety of the patients 
or operator, and any remaining risk is managed with a high level of protection of subject safety. 
3.5.4. Risks Associated with Participation in the Clinical Investigation 
There are risks associated with participation in a clinical investigation. There is only limited clinical 
experience with the device to date and there may be unanticipated adverse events. There are protocol-defined 
tests and follow-up studies such as endoscopy that may carry additional risk to the subjects. In addition, this is 
a sham-controlled, double-blinded study. The sham procedure and the blinding may carry additional risk to the 
subjects. 
 
   
3.5.5. Possible Interactions with Concomitant Medication 
The effect of the TPS device to the absorption of orally administered medication is unknown. The physician 
should evaluate the risk and benefit of this procedure for patients who take concomitant medications and 
carefully monitor the patients.  
Patients who receive hypoglycemic or anti-hypertension agents should be monitored closely as their 
medication dosages may need to be adjusted with the decrease in food intake and weight loss.  
3.5.6. Minimization of Risks 
The following steps have been taken to further minimize the risks of the study: 
• The study protocol has built in measures to control potential adverse effects, including study 
inclusion/exclusion criteria, prophylactic medications, clinical and endoscopic surveillance, 
guidelines for post-procedure management, and provisions for early removal of the device if 
necessary. 
• Patient informed consent contains sufficient information on the potential risks. 
• Subjects will be provided with subject information cards that contain brief device and physician 
contact information if  needed 
• Unblinding is permitted when the Investigational Device information is necessary for the 
management of adverse events and ensuring subject’s safety 
• Training and technical support will be provided for device placement/removal procedures in the 
study 
• A DSMB is set up to monitor the safety of the study 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 28 of 83 
 
 
In summary, subjects included in the present study have a clinical indication for weight loss. Prior clinical 
experience shows that the device can be deployed successfully, that subjects achieve significant weight loss 
over a 3-6 month residence time, and that the complications can be managed clinically. The risks associated 
with the device have been mitigated to the extent possible. The current study design includes additional 
measures to further minimize risks. These data and study design features indicate a favorable risk-benefit 
profile for the subjects to be included in the present study.   
4. STUDY OBJECTIVES 
The objective of this study is to demonstrate the safety and effectiveness of the BAROnova TransPyloric 
Shuttle for weight reduction in patients with BMIs of 30-40 kg/m2 compared with the sham-control over the 12 
months treatment period.   
The study will also assess, as secondary endpoints, changes in weight-related comorbidities, weight-related 
quality of life, and eating behavior. 
The study will be considered a success for efficacy purposes if it meets both of the primary efficacy analyses. 
The safety will be characterized, with all adverse events reported. The Clinical Event Committee (CEC) will 
adjudicate all serious device-related adverse events and any other events deemed necessary. 
 
5. STUDY DESIGN 
5.1. Study Design 
This is a multicenter, prospective, randomized, parallel design, double-blinded, sham-controlled study. A total 
of 270 subjects are planned for the pivotal study cohort. Subjects meeting the general inclusion/exclusion 
criteria will undergo baseline endoscopic assessment. Those who meet endoscopic eligibility will be 
randomized in a 2:1 allocation to the Treatment or Control group stratified according to center. The Treatment 
group will receive the TPS placement and the Control group will receive a sham endoscopic procedure that 
does not include TPS placement.  
Subjects will be followed up for 12 months after the index procedure or until the device is removed.   
At 12 months, subjects in the Treatment group will undergo an endoscopic assessment followed by the TPS 
removal. Subjects in the Control group will complete all the same assessments as the Treatment group except 
the endoscopy.  
Subjects who achieve a BMI of ≤ 22 kg/m2 for two consecutive visits before the 12-months follow up will be 
considered a treatment success, have the device removed if in the Treatment group, and exit the study. A BMI 
of 22 kg/m2 is selected as a reference value since it is a midpoint value of the normal BMI range, and a BMI ≥ 
23 kg/m2 has been shown to be associated with an increased risk of developing diabetes in the Nurses’ Health 
Study that followed 43,581 women over 8 years.28 The handling of these subjects in the analysis is described 
in Section 15.5. 
Subjects in both groups will receive the same lifestyle modification education and counseling during the 12-
month follow up duration. In brief, subjects will receive written instruction in lifestyle modification strategies 
for weight loss (e.g., caloric restriction, increasing physical activity, behavioral modification, etc.) at the 
beginning of the study. At each follow up visit, subjects will receive a brief (15 minute) lifestyle modification 
counseling performed by a medical provider (i.e., registered dietitian, nurse, behavioral health specialist) 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 29 of 83 
 
 
trained in the delivery of the intervention. In months 7, 8, 10, and 11 where an in-person follow-up visit is not 
scheduled, site provider will have a brief (15 minute) telephone call with the subject. During these calls, the 
provider and patient will discuss changes in weight, diet, eating behavior and physical activity over the past 
month. These calls are designed to promote adherence to the lifestyle modification strategies previously taught 
to the subject. 
A schematic diagram of the study design is shown in Figure 12. 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 30 of 83 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 12. Study Diagram 
Study Exit 
 (TPS Removal 
in Treatment 
arm) 
 1wk,   1M,    2M,   4M,    6M,       9M,      12M 
No 
Yes 
Screen Failure 
General 
Inclusion/Exclusion 
Criteria 
Yes 
Informed 
consent 
No 
Yes 
Endoscopic 
Eligibility 
No 
Yes 
Baseline Visit: 
Continued eligibility 
Endoscopic 
Screen 
Randomization 
Treatment 
TPS Placement 
Control 
Sham Procedure 
Physical exam 
Body mass assessment 
Medication assessment 
AE assessment 
Brief lifestyle modification counseling 
Satiety assessment 
IWQOL-Lite 
Blood tests 
Endoscopy 
* * 
* * 
*telephone contacts at 7, 8, 10, 11M 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 31 of 83 
 
 
5.2. Subject Recruitment and Enrollment  
Subjects will be recruited by Investigators at each study site. Candidates may be recruited during routine office 
visits; by IRB-approved advertisements such as brochures, flyers, letters, and other methods in the individual 
sites; or by referral from IRB-approved sponsor’s advertisements in newspapers, radio, the internet, or other 
methods. Candidates who are potentially eligible for the study will be scheduled for a screening visit. 
After giving written informed consent, subjects will undergo screening assessments. As part of the recruitment 
and enrollment process, potential participants will undergo a behavioral/psychosocial evaluation similar to that 
performed prior to bariatric surgery, as recommended by the American Society for Metabolic and Bariatric 
Surgery, and required by most third party payers for reimbursement for bariatric surgery. 29 This clinical 
assessment will include direct questioning about the potential participants psychosocial status (with specific 
focus on symptoms of disordered eating and depression), mental health treatment history, and a review of the 
potential participant’s current diet and regular eating behaviors. This evaluation is designed to assess for the 
presence of significant psychopathology that would contraindicate weight loss treatment and/or successful 
participation in the study. The evaluation will be performed by a member of the study team (registered 
dietitian, behavioral specialist, mental health professional, etc.) who will be trained by a consultant to the study 
with extensive expertise in the psychosocial and behavioral aspects of obesity and bariatric surgery. This 
consultant also will provide periodic supervision to the individuals performing these evaluations and to ensure 
that the sites are using similar criteria to evaluate and include/exclude study participants.   
Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and 
none of the general exclusion criteria will be scheduled for a baseline visit within one week of the planned 
procedure. Subjects who remain eligible after the baseline visit will be scheduled for the procedure.  
On the day of the procedure, subjects will undergo endoscopic assessment to confirm endoscopic eligibility. 
Subjects who meet the endoscopic exclusion criteria will be excluded from the study and will be considered a 
screening failure. Subjects who meet the endoscopic eligibility will be randomized using a web-based 
randomization tool provided by the study data management organization.  A TPSS Access Sheath is placed 
allowing delivery of the TPS during the same procedure.  TPS is delivered in the treatment group but not in the 
control group. 
A subject is considered enrolled in the study when the subject has given written informed consent and the 
TPSS Access Sheath has been placed in the subject.  
5.3. Randomization and Masking 
Eligible subjects will be randomized to either the Treatment or the Control group in a 2:1 ratio stratified 
according to center. Randomization will be according to a random permuted block design within strata. Block 
size of 3 and 6 will be used.  
Randomization occurs on the day of the procedure after endoscopic screening. The Investigator who performs 
the index procedure and endoscopic follow-ups will not collect the primary outcome data. The Investigator 
and/or the study coordinator who collect the primary outcome data will be masked to the subject’s 
intervention.   
The subject will be blinded to the intervention for the duration of participation in the study.  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 32 of 83 
 
 
The Clinical Event Committee (CEC) will be masked to the subject’s intervention. The Data Safety 
Monitoring Board (DSMB) will have access to unmasked subject data, as required, to monitor and evaluate the 
safety data throughout the study.  
5.4. Staged Safety Monitoring   
In the ENDObesity I study that used a previous generation device, the endoscopic observation of gastric ulcer 
was reported in 10/20 subjects. Device modification has since been implemented to address the device-tissue 
interface. A number of protocol measures has also been implemented to further mitigate the risks, including 
subject selection, prophylactic PPI, avoidance of ulcerogenic medications and endoscopic surveillance. 
Additionally, multiple-staged evaluations of endoscopic ulcer occurrence rate will be performed at regular 
intervals based on explicit statistical criteria to ensure subject safety.  
The occurrence of endoscopic ulcer events will be evaluated by estimating cumulative incidence in the 
investigational and the sham groups using the Kaplan-Meier (K-M) product-limit survival estimator as 
described in Section 15.5.6.  
The analysis will be performed after the first 30, 60 and 90 subjects in the Treatment group have reached 80 
days post index procedure. Based on the data from the ENDObesity I study, 80% of the endoscopic ulcer 
events occurred by 74 days after device placement.  Eighty days has been selected to coincide with the current 
study-mandated endoscopic follow-up at 2-month (60 ±14 days).  
For clarification, the cumulative incidence will include observations from study pre-scheduled 2 and 6 months 
endoscopic evaluations and all unscheduled evaluations accumulated at the time of analysis. The estimated 
endoscopic ulcer occurrence rate will be evaluated against a pre-specified threshold rate of 25%. If the 
threshold rate is exceeded during the analysis, the Sponsor will suspend enrollment. The Data Safety 
Monitoring Board (DSMB) review will be triggered as described in Section 14. The analysis data will be 
submitted to DSMB within 15 days after the last respective subject in each analysis point (i.e. 30th, 60th, and 
90th subject) has reached 80 days post-procedure. The DSMB will review the data and provide 
recommendation to the Sponsor within 15 days.  Based on DSMB recommendation, Sponsor will implement 
necessary actions which may range from continuing enrollment without modification, protocol modification 
(including modification of ulcer management algorithm), stopping of enrollment to device removal. Sponsor 
will submit an adverse event report to the FDA and inform FDA about the course of action following the 
DSMB review.   
 
The threshold of 25% is selected based on literature data on the performance of approved devices for the 
treatment of obesity and the ulcer rate associated with approved medications.  The band erosion rate associated 
with use of lap-band devices is 28%.30 Furthermore, 15-30% of the patients on chronic NSAID use experience 
endoscopic ulcers.31 This safety threshold represents a 50% reduction in point estimate ulcer rate in the 
ENDObesity I study. 
5.5.  Criteria for Discontinuation of Routine Endoscopic Surveillance 
Routine endoscopic surveillance carries certain risks for subjects and may be discontinued if a low incidence 
of ulcer is detected by the endoscopic surveillance and none of the detected ulcers have a smallest dimension 
(the smaller measurement between the length and width) greater than 1cm and that there are no stigmata of 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 33 of 83 
 
 
bleeding. The incidence rate of endoscopic ulcers will be assess when about 60 (or about 90 if needed) 
subjects in the treatment group have completed the 2- and/or 6-month surveillance endoscopies. The pre-
planned surveillance endoscopy at 2-month may be discontinued if the upper boundary of the 95% confidence 
interval for the ulcer incidence rate is less than 15%. In practice, in order to satisfy this criterion, the observed 
ulcer rate detected by the 2-month routine surveillance endoscopy should not exceed 3 ulcer events per 60 
subjects, or 6 ulcer events per 90 subjects.  Similarly, the observed ulcer rate at 6-month routine endoscopy 
should not exceed 3 ulcer events per 60 subjects, or 6 ulcer events per 90 subjects. The 15% upper boundary of 
the 95% confidence interval provides 10% safety margin to 25% safety stopping threshold described in 
Section 5.4. The statistical approach to evaluate if the 15% upper boundary of the 95% confidence interval 
discontinuation threshold is reached is described in Section 15.5.7.  
If detected ulcers are larger than 1cm in a smallest length or with dimension or have stigmata of bleeding, the 
endoscopic surveillance should not be discontinued. Clinically driven endoscopy based upon investigator 
clinical judgement remains part of the protocol. Any study subject with symptoms suggestive of a gastric ulcer 
should be evaluated. 
Based on ulcer characteristics and their clinical course, the DSMB may recommend to Sponsor to continue 
routine surveillance endoscopy even if these criteria were met.  
5.6.  Early Study Termination 
Sponsor may discontinue the study at any stage for any reason or no reason. Possible reasons for early 
termination may include unanticipated adverse device effects that may present unreasonable patient risk.  
The Study Steering Committee assists Sponsor in making a final decision for early study termination based on 
Data Safety Monitoring Board (DSMB) recommendations (refer to Section 14). 
If the study is terminated early, the sponsor will provide a written statement describing why premature 
termination has occurred, and notify the Investigator, Institutional Review Board (IRB) and the regulatory 
authority (if applicable). All applicable clinical study documents will be subject to the same retention policy as 
detailed in Section 17. 
5.7. Measures Taken to Avoid/Minimize Bias  
This is a randomized, double-blinded, and sham-controlled study. The study design minimizes the bias of 
placebo effect, patient selection, and the effect of lifestyle intervention. The outcome data will be collected by 
the Investigator or study coordinator who are masked to the intervention, thus minimizing Investigator bias.  
Subjects in both groups and at all study sites will be provided with the same lifestyle educational materials. 
Site personnel will be trained in the delivery of the centrally prescribed lifestyle modification intervention 
prior to the onset of the study and will receive ongoing supervision during the study to ensure treatment 
fidelity across study sites. 
An independent Clinical Events Committee (CEC) will be established to adjudicate safety events as described 
in Section 13. The CEC will be masked to the subject’s intervention, thus minimizing bias in safety 
assessment. A Data Safety Monitoring Board (DSMB) (Section 14) will be established to monitor and evaluate 
the safety data throughout the study. 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 34 of 83 
 
 
6. STUDY ENDPOINTS 
6.1. Primary Effectiveness Endpoints   
The effectiveness of the TPS will be assessed by the following co-primary endpoints: 
• 
Mean percent total body weight loss (% TBL) between the Treatment and the Control group at 12 
months after the index procedure.  
• 
The proportion of subjects in the Treatment group who achieve ≥ 5% TBL at 12 months after the 
index procedure.  
6.2. Secondary Effectiveness Endpoints 
The following secondary endpoints will be assessed in this study:  
• 
Proportion of subjects who achieve at least 7% and 10% TBL at 12 months in the Treatment versus 
Control group 
• 
Percent total body weight loss over 12 months in the Treatment versus Control group 
• 
Percent excess weight loss over 12 months in the Treatment versus Control group 
• 
Proportion of subjects who achieve at least one obesity class reduction at 12 months in the 
Treatment versus Control group 
• 
Change of BMI over 12 months from baseline in the Treatment group 
• 
Change in weight-related quality of life over 12 months as assessed by IWQOL-Lite Questionnaire  
• 
Change in eating behavior over 12 months as assessed by the Eating Inventory  
• 
Change in appetite, hunger and fullness over 12 months as assessed by Visual Analog Scales.  
• 
Change in comorbid conditions over 12 months in the Treatment group: 
a) Prevalence of the metabolic syndrome and its individual components  
b) Glucose, insulin, and insulin resistance (as estimated by HOMA)  
c) High sensitivity C-reactive protein (hsCRP)  
d) Lipid levels (LDL-C, HDL-C, and triglycerides)  
e) Blood pressure  
f) Waist circumference 
6.3. Safety Evaluations 
The overall device safety profile is characterized by assessing the incidence of adverse events (AEs), serious 
adverse events (SAEs), serious adverse device effects (SADEs), and unanticipated serious adverse device 
effects (UADEs) as detailed in Section 12. No formal hypothesis testing will be performed.  
7. PATIENT SELECTION AND WITHDRAWAL   
7.1. Study Population 
Subjects with a BMI of 30.0-40.0 kg/m2 who meet the inclusion and exclusion criteria will be evaluated for 
participation in the study. To ensure the safety of the subjects during weight loss, we aim to enroll individuals 
with controlled weight-related co-morbidities, such as Type 2 diabetes, hypertension, and hyperlipidemia. 
Conversely, individuals with a recent cardiovascular event and those with serious internal organ disease will 
be excluded.  
The pivotal study cohort will consist of 270 subjects that will be enrolled from up to twelve study sites in the 
US, with no one site enrolling more than 25% of the total number of subjects in the pivotal cohort.  
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 35 of 83 
 
 
7.2. Inclusion Criteria 
1. Male and female subjects between the ages of 22 to 60 
2. A BMI between 30.0 to 40.0 kg/m2, inclusive.  Subjects with a BMI of 30.0 kg/m2 to 34.9 kg/m2 are 
required to have one or more of the following obesity-related mild-moderate comorbidities: 
a. Type 2 Diabetes: meet one of the following criteria and currently not using insulin 
i. HbA1c 6.5%-7.5% 
ii. Controlled, on stable dose of oral medications for at least 3 months 
b. Hypertension: meet one of the following criteria: 
1. Arterial blood pressure >140 mmHg systolic or >90 mmHg diastolic on or off 
hypertensive medication 
2. Arterial blood pressure ≤140 mmHg systolic and ≤90 mmHg diastolic on 
hypertensive medication 
c. Hyperlipidemia, meeting at least one of the following criteria: 
i. Fasting blood total cholesterol level of ≥240 mg/dl  
ii. Fasting total triglyceride level of ≥200 mg/dl  
iii. Low density Lipoprotein cholesterol ≥160mg/dl 
iv. Currently taking lipid-lowering medication based on an elevation of total cholesterol, 
triglycerides, or LDL 
3. History of obesity for at least 2 years, with history of failure of medically or commercially supervised 
weight loss program  
4. History of weight stability (defined as a < 5% change in body weight) for at least 3 months prior to the 
screening visit 
5. Female subjects of childbearing potential must have a negative urine pregnancy test and must commit 
to practice their physician-agreed form of birth control for the duration of participation  
6. Willing and able to provide written informed consent  
7. Willing and able to comply with study procedures and return for all study visits 
7.3. Exclusion Criteria 
1. Pregnancy or planned pregnancy in next 12 months after enrollment 
2. Nursing or pregnancy within the 6 months prior to enrollment 
3. Known hormonal or genetic cause for obesity 
4. Prior history of any surgery or endoscopic intervention that has altered the esophageal, gastric, or 
duodenal anatomy, including any bariatric surgery, such as gastric bypass, and restrictive procedures 
such as laparoscopic adjustable gastric banding   
5. Prior treatment with an intragastric balloon for the purpose of weight loss, where the balloon was 
removed less than 12 month prior to the screening visit for this study 
6. Chronic use (in the past 6 months) of medications likely to contribute to weight gain or prevent weight 
loss (e.g., corticosteroids, lithium, olanzapine, risperidone, clozapine, anticonvulsants, glitazones (e.g., 
pioglitazone), monoamine oxidase inhibitors) 
7. A history of gastric or duodenal ulcers 
8. After treatment for Heliobacter pylori, subject still tests positive for H. pylori  
9. A history of severe dyspepsia  
10. GI tract motility disorders such as esophageal motility disorders, gastroparesis diabeticorum, or 
intractable constipation 
11. History of inflammatory disease in the GI tract, such as Crohn’s disease  
12. History of coeliac disease 
13. History of pancreatitis 
14. History of portal hypertension, cirrhosis, and/or varices 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 36 of 83 
 
 
15. Diabetes treated with insulin or significant likelihood of requiring insulin treatment in the next 12 
months 
16. HbA1c >7.5% 
17. Uncontrolled thyroid and adrenal gland disease 
18. Uncontrolled hypertension defined as systolic blood pressure > 160 mmHg or diastolic blood pressure 
> 100 mmHg 
19. A history of cardiac arrhythmia, ischemic heart disease, myocardial infarction or chronic heart failure  
20. History of cerebrovascular disease, transient ischemic attack or stroke 
21. Presence of localized or systemic infection 
22. Anemia (hemoglobin < 11.0 g/dl for female and < 12.0 g/dl for male) 
23. History of asthma likely to require systemic steroid therapy during the duration of the study 
participation or frequent use of rescue inhalers 
24. Autoimmune connective tissue disorders or known to be immunocompromised or at risk of becoming 
immunocompromised (e.g., HIV positive) 
25. A history of malignancy except non-melanoma skin cancer 
26. Continuous therapy with known ulcerogenic medication (e.g., aspirin greater than 81mg/day, 
NSAIDs) 
27. On anticoagulant therapy (e.g., Coumadin, Warfarin, Heparin Pradaxa, Xarelto, Plavix) 
28. Unwilling to avoid use of any weight-loss medication, including over-the-counter treatments and/or 
herbal supplements during the course of study,  or on prescription medications that can be used for 
weight loss, even if they are not prescribed for weight loss (e.g., Topiramate, Wellbutrin) and 
stimulant medications (e.g., for ADHD) 
29. Currently participating or unwilling to avoid participation in any non-study-related organized weight-
loss program (medical or commercial) during the course of the study 
30. Unable to take proton pump inhibitors (a daily 40+ mg of Omeprazole or equivalent), or addition of 
PPI may cause adverse drug interaction with subject’s medication or interruption of treatment 
31. Clinically significant abnormal laboratory values or an EKG that make the subject a poor study 
candidate in the opinion of the Investigator 
32. Inability to walk at least 0.8 kilometers per day (10 minutes of continuous walking) 
33. Planned surgical procedure that can impact the conduct of the study 
34. Started on a prescribed concomitant medication regimen within the last three weeks, or whose 
concomitant medication regimen is expected to change during the course of the study, and where the 
Investigator determines the medication may affect the study outcome 
35. Known allergy to any component materials in the TPSS including silicone, barium sulfate, and 
parylene 
36. Current smoker or user of nicotine product or smoking cessation within 1 year of the screening date 
37. Current abuse of drug or alcohol or past treatment for substance abuse 
38. Presence of any severe uncontrolled psychiatric illness  
39. Inpatient psychiatric treatment within the past year 
40. A score of ≥10 on the Patient Health Questionnaire 9 (PHQ-9), indicating moderate depression 
41. Diagnosis of bulimia nervosa or binge eating disorder 
42. Any medical condition (including psychiatric disease) that would interfere with the interpretation of 
the study results, the conduct of the study, or would not be in the best interest of the subject in the 
opinion of the site Primary Investigator  
43. Participation in another clinical study within 60 days of screening date, in a previous or ongoing 
clinical study, or plan to participate in another clinical study at any time during this study 
44. Employee or family member of BAROnova, the Investigator, or site study staff  
45. The Investigator judges the candidate unsuitable for the study 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 37 of 83 
 
 
46. Have any of the following endoscopic exclusion criteria: 
a. Esophageal stricture 
b. Barrett’s esophagus 
c. Erosive esophagitis  
d. Varices 
e. Angiectasias 
f. Gastric mass 
g. Antral or peri-pyloric polyps 
h. Peptic ulceration 
i. 
Hiatal hernia ≥ 4 cm 
j. 
Pyloric stricture 
k. Any other abnormalities or characteristics that preclude safe use of the TPS 
7.4. Point of Enrollment 
The point of enrollment occurs when a subject or subject’s legally authorized representative has provided 
written informed consent and the TPSS Access Sheath has been introduced in the subject during the index 
procedure.  
7.5. Patient Discontinuation  
Once enrolled, each subject will remain in the study until the required follow-up period is complete. However, 
the subject has the right to withdraw from the study at any time without penalty or loss of benefit. The 
following events will result in terminating the subject’s follow-up:  
• 
Subject voluntary withdrawal  
• 
Subject withdrawn by the Investigator as clinically indicated  
• 
Subject becomes pregnant 
• 
Subject lost to follow-up 
• 
Subject death  
• 
Study is terminated according to Section 5.6 (Early Study Termination) 
In the case of subject withdrawal from the study, the TPS must be removed before the subject exits the study. 
In case the TPS is removed early as described in Section 10.5, the subject’s participation in the study is 
considered terminated. Any Adverse Events will be followed until resolution or stabilization according to 
Section 12.1. 
In case a subject achieves normal BMI (≤ 22 kg/m2) for two consecutive visits before the 12-month follow up, 
the subject is considered to have completed the study. Subject will exit the study and the device should be 
removed in the treatment subjects.  
A final endoscopy should be performed whenever possible before the Treatment subject exits the study.  
The Sponsor must be notified of the reason for subject discontinuation. The site will document this 
information on the electronic case report form (eCRF) and make every effort to give a full description of the 
reason for withdrawal. Investigators must also report this information to the local IRB as defined by their 
institution’s procedure. 
Subjects who are terminated early will not be replaced by enrolling additional subjects.   
7.6. Lost to Follow-up  
Subjects that do not complete the scheduled follow-up visits and have not officially withdrawn from the study 
are considered lost to follow-up; this term does not apply to missed visits. Site personnel should make 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 38 of 83 
 
 
considerable effort to locate and communicate with the subject using all available methods (e.g., telephone, 
emails, and postal mail). The following contact procedure is recommended at each time point:  
• 
A minimum of two telephone calls on different days over the specified follow-up windows should be 
recorded in the source documentation including date, time, and site personnel initials for the staff 
attempting to contact the subject.  
• 
If these attempts are unsuccessful, a certified letter should be sent to the subject.  
• 
If the subject misses two consecutive scheduled contact time points and the above mentioned attempts 
at communicating with the subject are unsuccessful, the subject will be considered lost to follow-up.  
While a subject becoming lost-to-follow-up must be considered a possibility, it is imperative that all subjects 
have the device removed, as the long-term response of the device materials to the stomach environment is not 
yet known. 
8. LIFESTYLE INTERVENTIONS 
The goal of the lifestyle modification counseling is to promote use and adherence to a reduced calorie diet 
(approximately 1500 kcal/d), increase physical activity (primarily through daily walking), and to recommend 
behavioral modification strategies.  
This intervention is adapted from the Brief Lifestyle Counseling condition in the POWER-UP study16 
described previously. A detailed protocol for the lifestyle intervention is attached in Appendix C. Prior to the 
start of the study, study personnel from the study sites will participate in a training session which will focus on 
the delivery of the intervention. These study personnel also will participate in ongoing conference calls where 
they will receive supervision on the delivery of the lifestyle modification intervention to study participants. 
8.1. Diet Recommendations  
The diet recommendation will follow the recommendations of the Diabetes Prevention Program and as used in 
the POWER-UP study. Subjects who weigh ≤ 114 kg (≤ 250 lb) will be prescribed 1200-1500 kcal/d and those 
> 114 kg (> 250 lb) 1500-1800 kcal/d. All subjects will receive the same written information regarding food 
intake at lifestyle counseling sessions.   
8.2. Physical Activity Recommendations 
Subjects will be encouraged to increase their physical activity, performing such tasks as taking 10,000 steps a 
day, avoiding elevators and escalators, etc. No specific methods will be provided to enforce or facilitate 
subject compliance.  
8.3.  Behavior Modification 
At the same time as the diet prescription and activity advice, subjects will be instructed in behavioral 
modification strategies to promote weight control and that can be used in their daily lives. Examples of these 
strategies include reducing food intake by using smaller plates, reducing consumption of high calorie 
beverages, putting the fork down between bites, etc.  These are detailed in the Appendix C.  
8.4. Telephone Contacts 
In months 7, 8, 10, and 11, when subjects are not scheduled for an in-person follow up visit, subjects will 
participate in a brief (15-minute) telephone call with study site personnel providing the lifestyle modification 
counseling. During these calls, subjects will report on changes in weight, dietary intake, eating behavior, and 
physical activity level. These telephone calls are designed to promote adherence to the lifestyle modification 
protocol in the absence of in-person visits. The provider will reinforce positive behaviors consistent with the 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 39 of 83 
 
 
lifestyle modification program and problem solve issues related to weight gain, increased caloric intake or 
decreases in physical activity.  
9. CONCOMITANT MEDICATIONS 
Concomitant medications deemed medically necessary for the subject will be allowed during the course of the 
study; however, any changes in medications will be documented on the Concomitant Medication Log.  
Medications used during the placement/removal of the TPS, such as anesthesia, will not be tracked via the 
Concomitant Medication Log. 
9.1. Prohibited Concomitant Medications 
9.1.1. Weight-Loss Medications 
Study subjects will not be allowed to take any weight-loss products during the course of the study, including 
prescription, over-the-counter (OTC), and herbal products.   
9.1.2. NSAIDs (Non-Steroidal Anti-inflammatory Drugs) 
Subjects must be off NSAIDs and aspirin for at least two weeks prior to TPS placement and remain off for 
the duration of the study. Treatment with Acetaminophen may be continued. Low dose aspirin (81 mg/day) 
may be used if needed in combination with prophylactic PPI.  
9.1.3. Other Medications 
Medications affecting subject motility, such as Reglan and Erythromycin should be discouraged, but allowed if 
necessary.  
9.2. Required Concomitant Medications 
9.2.1. Proton Pump Inhibitors (PPIs) 
Subject will be placed on Omeprazole at 40 mg once daily, or its equivalent starting at least one week before 
the index procedure and continue for 12 months until the TPS removal (or the last visit in the Control 
subjects). The dose may be adjusted based on the judgment of the Investigator. Use of the PPIs will be 
recorded on the Concomitant Medication Log. 
10. POST PROCEDURE PATIENT MANAGEMENT 
10.1. Managing GI Symptoms 
Following the index procedure, the subject should be on liquid diet for three days, followed by soft food for a 
week, and then slowly return to a normal diet in ten days. 
Clinical experience suggest the TPS therapy is well-tolerated by subjects. However, some subjects may 
experience nausea, vomiting, and bloating after the procedure. Antiemetic (such as Ondansetron) and 
antispasmodics (such as Butylscopolamine) should be provided on standby, and the subjects should be 
educated on their use.  
In case of prolonged vomiting (more than 4-6 times in 24 hours), subjects should be evaluated and, if 
necessary, be managed with PO, IV fluid, and intravenous antiemetic.  
In case of recurrent vomiting (every day over 3-5 days), abdominal pain, and non-response to medical 
management, the patient should be evaluated (including endoscopy if necessary) to rule out obstruction or an 
ulcer.  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 40 of 83 
 
 
10.2. Managing Endoscopic Observations  
Tissue effects such as erythema, erosions, or ulcers may be observed during endoscopic surveillance. Limited 
clinical experience to date suggests that some patients may be asymptomatic while others may develop 
symptoms.  
10.2.1. Ulcer Definition 
For the purpose of this study, an ulcer is defined as ≥ 5mm in diameter with unequivocal depth by endoscopy. 
Ulcer is defined as endoscopically significant if it is ≥ 3cm in length and ≥ 1cm in width. Ulcers will be 
classified as symptomatic or asymptomatic, complicated or uncomplicated. An ulcer is complicated if the 
patient develops clinical complications including bleeding, perforation or obstruction.  
Efforts should be made to capture clear images with an accessory of known dimensions next to the lesion to 
estimate size.  
10.2.2. Guidelines for Managing Endoscopic Observations  
The following algorithm ( 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 41 of 83 
 
 
Figure 13) is suggested for managing endoscopic observations in subjects after the index procedure.  
 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 42 of 83 
 
 
Figure 13.  Management of Endoscopic Observations   
 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 43 of 83 
 
 
     
If an ulcer is ≥2cm in diameter or width (the smaller measurement between the length and width), device 
removal is recommended. If an ulcer is smaller than 2cm in the smaller diameter but endoscopically 
significant, signs of healing defined by a 25% reduction in either length or width should be observed after the 
first 8 weeks of medical therapy and a 50% reduction from baseline in either length or width after an 
additional 8 weeks of medication. If an endoscopically significant ulcer does not show signs of healing after 8 
weeks of medication, shows less than 50% reduction in length or width after 16 weeks of medication, device 
removal is recommended.   
Blood hemoglobin should be monitored during scheduled or unscheduled endoscopies in patients who have 
ulcers or report signs of upper GI bleeding (hematemesis or melena).  
Subjects in whom an ulcer is diagnosed and treated will have endoscopic confirmation of complete resolution.  
The above algorithm is provided as a general guideline. Investigators should always use their best clinical 
judgment in patient management.  
Worsening of clinical symptoms and/or signs may indicate early device removal as discussed in Section10.5.  
10.3. Managing Hypoglycemia Risks in Diabetic Subjects 
Subjects with diabetes are potentially at risk of developing hypoglycemia during a weight loss study. The risk 
may be greatest upon initiation of dietary and device intervention. Among patients with diabetes who qualify 
for inclusion in this study, the risk of hypoglycemia is very low to absent in those managed with diet alone, 
and the risk is greater in patients treated with sulfonylureas, repaglinide or nateglinide, than in patients treated 
with other oral anti-diabetes agents. The following guideline is provided for minimizing severe hypoglycemia 
in diabetic subjects during the study. The treating physicians should exercise their clinical judgment for the 
treatment of individual subjects. 
10.3.1. Subject Education 
At the onset of the study, subjects with T2DM, regardless of diabetic medication regimen, should be educated 
on the potential for development of hypoglycemia, the symptoms and signs of hypoglycemia, instruction in the 
use of home blood glucose monitoring to detect hypoglycemia, and instruction on treating hypoglycemia. 
Symptoms suggestive of hypoglycemia include lightheadedness, tremor, shaking, sweating, tingling, blurred 
vision, difficulty concentrating, and confusion. With marked hypoglycemia, patients may develop altered 
consciousness, coma, or seizures. Subjects treated with anti-diabetic medication should self-monitor blood 
glucose (BG) in the first week post intervention and are encouraged to self-monitor BG throughout the study. 
Additionally, for subjects treated with sulfonylureas, repaglinide or nateglinide, self-monitoring of BG should 
be performed twice daily starting one week before the index procedure and continuing for a minimum of 4 
weeks post-procedure or until stabilization of glycemic control. Subjects should be instructed to promptly 
contact site staff for any documented or suspected hypoglycemia.  
10.3.2. Subject Management (adapted from algorithms developed and used in the LookAhead 
Study 32 ) 
During periods of weight loss, subjects who are taking sulfonylureas, repaglinide or nateglinide may need 
reductions in diabetes medication(s) to reduce their risk of hypoglycemia.   

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 44 of 83 
 
 
Each diabetic subject should have a treating physician identified for managing subject’s diabetic medication 
during the study. The treating physician maybe the site PI, site clinical staff, or a treating physician not on the 
study team, in which case the study site will work collaboratively with the subject’s non-study treating 
physician in managing their risks. The treating physician will be responsible for diabetes medication 
adjustment while the need for medication reduction may be identified by the study subject, research staff, or 
individual delivering the lifestyle modification intervention.  
At the screening visit, subjects who are taking sulfonylureas, repaglinide or nateglinide will be identified by 
the site. If non-study treating physicians will be responsible for medication adjustment, they will be contacted 
by the site regarding the plan for glycemic control during the study. Evidence of the treating physician’s 
acknowledgement on a subject’s participation in the study will be obtained before a subject’s enrollment in the 
study.  
The definition of hypoglycemic episodes can be found in Appendix A. Study subjects or study staff may 
identify these episodes.  
Hypoglycemic Decision Point is defined as one episode of severe hypoglycemia or non-severe hypoglycemia 
occurring greater than twice weekly. If a Hypoglycemic Decision Point should occur in a study subject, this, 
should prompt reassessment of the anti-diabetic regimen and reduction or discontinuation of anti-diabetic 
medications. Before medication changes are made, judgment should be used in determining whether 
exceptional and/or alterable circumstances are responsible for the low glucose levels (e.g., hypoglycemia 
attributable to missing a meal or an unusual degree of physical exercise). 
10.3.2.1. 
Prior to Index Procedure 
Prior to the start of the study, subjects treated with sulfonylureas, repaglinide or nateglinide medications will 
be asked to start monitoring blood glucose (BG) at least twice daily (pre-breakfast and pre-supper). After at 
least one week of BG measurements have been collected, the BG data will be reviewed and used to make 
decisions on pre-emptively reducing anti-diabetic medication according to the scheme below (Figure 14). 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 45 of 83 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The above algorithm provides general guidelines for adjustments in doses of sulfonylureas, repaglinide and 
nateglinide, because of the risk of hypoglycemia associated with their use. The exact adjustments in doses of 
these medications and also a decision on whether the doses of other anti-diabetic medications should be 
reduced for individual subjects should be determined by the subject’s managing physician based on the overall 
profile of blood glucose levels, with the goal of reducing the risk of hypoglycemia.  
10.3.2.2. 
During Study Follow up 
Self-monitoring of blood glucose should be performed twice daily for subjects on sulfonylureas, repaglinide 
and nateglinide medications during the first 4 weeks after the index procedure, and one week before each 
scheduled visit. For subjects on other anti-diabetic medications, self-monitoring of BG should be performed 
during the first week after the procedure. Subjects also will be encouraged to measure BG levels at any time 
that symptoms suggestive of hypoglycemia occur. Additionally, subjects will be asked to promptly report 
Figure 14. Guideline for Managing Hypoglycemic Medication(s) (Pre-Procedure)  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 46 of 83 
 
 
documented or suspected episodes of hypoglycemia to the site staff. Subjects will be referred to the treating 
physician for medication dose adjustment if they experience one episode of severe hypoglycemia or episodes 
of non-severe hypoglycemia 2 times per week.  Guidelines for medication dose adjustment are provided 
below (Figure 15).  
The process of reviewing BG records by study staff or treating physician should continue until the blood 
glucose records satisfy the following criteria: 
(1) no ongoing episode of severe hypoglycemia,  
(2) episodes of non-severe hypoglycemia occurring no more often than two times per week, and  
(3) No blood glucose values less than 100 mg/dL.  
If the risk of hypoglycemia has not been adequately reduced, doses of sulfonulureas, repaglinide, nateglinide, 
or possibly other anti-diabetic medication(s) should be further reduced or discontinued if appropriate and in 
the clinical judgment of the subject’s treating physician.  
In the event of severe hypoglycemia, study staff will document these episodes on the Adverse Event form. 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 47 of 83 
 
 
Figure 15. Guideline for Managing Hypoglycemic Medication(s) (Post-Procedure) 
 
 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 48 of 83 
 
 
10.4. Managing Hyperglycemia Risks in Diabetic Subjects 
Although hyperglycemia is not anticipated as a consequence of the device, some subjects may develop 
uncontrolled hyperglycemia in the course of the study (e.g., as a result of progression of their diabetes or an 
intercurrent illness). Signs or symptoms of acute metabolic deterioration, or presence of serious intercurrent 
illness or trauma should lead to prompt subject evaluation. Responses may include close follow up, adjustment 
of anti-diabetic medication or diet, or hospitalization. Subjects who require insulin treatment for greater than 
14 consecutive days should terminate study participation and have the study device removed.  
10.5. Early Device Removal 
Early device removal should be considered in the following situations: 
• 
Subject experiences abdominal pain and the pain does not resolve in 5-7 days, in combination with 
ulcer observation 
• 
Subject has signs of ulcer progression: 
• 
Enlargement of peptic ulcer by greater than or equal to 25% in length or width over 8 weeks 
and with a minimum width (short axis) of 1 cm 
• 
Bleeding, Hgb drops ≥2 g/dL 
• 
Developing upper abdominal pain, which does not resolve on medical therapy 
• 
Subject has an ulcer size of ≥2cm in diameter or width (the smaller measurement between the 
length and width), OR ≥ 3cm x 1cm not responding to medication 
• 
Subject requires insulin treatment for greater than 14 consecutive days  
• 
Subject loses ≥ 20% of his/her total body weight in any four-week post-placement period 
• 
Subject achieves a BMI of ≤ 22 kg/m2 for two consecutive visits before the 12-months follow up 
• 
Subject becomes pregnant 
 
Device removal should be performed according to the device removal procedure described in Section 
11.9.10.1 and in the IFU.  
To ensure that both study groups are treated the same in a sham-controlled study, the control subjects will be 
treated as if he/she has received the device. For example, if a control subject has lost ≥ 20% of his/her total 
body weight in any four-week period during follow up, the subject will exit the study as if he/she will have 
the device removed.  
11. STUDY EVALUATION AND TREATMENT PROCEDURES 
11.1. Demographics 
A self-reported demographic questionnaire will be administered at baseline to assess subject characteristics 
that include age, race/ethnicity, psychological health status, and health insurance status. 
11.2. Medical History and Concomitant Medication 
Subject medical conditions and medication usage will be reviewed, assessed, and documented at each study 
visit.  
11.3. Measurement of Weight, Body Circumference and Calculation of Body Mass Index (BMI) 
When the subject is weighed, s/he should be wearing only undergarments and an exam gown.   
The weight will be measured in duplicate at each visit. If the two readings are discrepant, it should be repeated 
until two consecutive identical readings are obtained.   

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 49 of 83 
 
 
Height will be measured and recorded at the screening visit. 
The BMI is calculated to one decimal place, using the subject’s weight at each visit and the height value 
obtained at baseline. A BMI calculator is provided in Appendix D.  
Body circumference measures will be performed with the subject standing feet together. The following 
circumference measurements will be made: 
• 
Hip: measured at the widest part of the hips  
• 
Waist: measured midway between the lowest rib and the iliac crest 
• 
Chest: measured at the 4th intercostal space in the mid-clavicular line  
• 
Neck: measured at the widest part of the neck  
11.4. Biochemical Measurements 
Fasting blood samples will be obtained at the screening and baseline visits, and at the 6- and 12-month follow-
up visits. The following analyses will be performed:  
• 
CBC (Complete blood count), including differential (screen and baseline visits only) 
• 
Chemistry Panel 20 (screen and baseline visits only) 
• 
Lipid levels and lipoproteins (triglycerides, LDL-C, HDL-C, and total cholesterol) 
• 
Glucose, insulin, HbA1c 
• 
High sensitivity C-reactive protein 
11.5. Satiety Assessment  
Visual analogue scales by Control of Eating Questionnaire (Appendix H) will be used to assess the subject’s 
hunger, fullness, cravings and related dimensions of appetite. 33 The Eating Inventory (Appendix I) will be 
used to assess cognitive restraint, disinhibition, and hunger. These instruments will be administered at the 
baseline, 1 week, and 1, 6, 12 month(s) visits. 
11.6. Patient Health Questionnaire 9 (PHQ-9) 
The Patient Health Questionnaire 9 (PHQ-9) is to be used to assess the subject’s level of depression prior to 
participation in the study.  If the subject’s score is ≥10, s/he will not be enrolled into the study.   
A sample of the PHQ-9 is provided in Appendix E. 
 
11.7. Impact of Weight on Quality of Life (IWQOL– Lite)34 
The IWQOL-Lite is a subject-completed 31-item instrument that reliably measures how a subject’s weight 
affects his/her quality of life in the five domains of physical function, self-esteem, sexual life, public distress, 
and work. The IWQOL–Lite will be collected at baseline and at the 6- and 12-month follow-up visits.  
A sample of the IWQOL-Lite is provided in Appendix F. 
11.8. Test for Helicobacter Pylori 
A negative stool antigen test for H. pylori is required for study inclusion. The subject should be off antibiotics, 
antacids, and bismuth for 2 weeks, and not be bleeding before the testing.  If the test reveals the subject is 
positive for H. pylori, the subject will be treated accordingly. If a stool retest is negative following completion 
of the treatment, the subject may be entered into the study. If, after treatment, the subject tests positive for H. 
pylori at the retest, s/he is to be excluded from the study. 
11.9. Visit Schedules 
The table in Appendix B provides an overview of the schedule of exams and procedures for the study. 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 50 of 83 
 
 
11.9.1. Screening Visit (Within 8 Weeks Prior to the Index Procedure) 
At the screening visit, the following procedures/assessments will be performed to determine subject eligibility:  
• 
Informed consent prior to the conduct of any study-related procedures 
• 
Demographics (ethnicity, age, gender, education, marital status) 
• 
Medical history, especially the assessment of risk factors and morbidities related to obesity and 
age when subject first noticed obesity 
• 
Concomitant medications 
• 
Physical examination  
• 
Body mass assessment (body weight, height, calculation of BMI, and measurement of 
circumferences) 
• 
Patient Health Questionnaire (PHQ-9) 
• 
Behavioral evaluation by registered dietitian, behavioral specialist, or mental health professional 
• 
Urine pregnancy test for females capable of becoming pregnant 
• 
Stool test for H. pylori 
• 
Blood tests 
▪ 
CBC with differential  
▪ 
Chemistry panel 20 
▪ 
Fasting lipid panel 
▪ 
Fasting blood glucose, insulin, HbA1c, C-reactive protein  
• 
EKG 
• 
Assessment of enrollment eligibility (inclusion/general exclusion criteria) 
Each subject will be assessed for suitability to participate in the study by the site Investigator.    
Subjects who meet all the inclusion criteria but none of the exclusion criteria will be scheduled for a baseline 
visit.  
11.9.2. Baseline Visit (Within One Week Prior to the Index Procedure) 
The following evaluations/procedures are to be performed within 7 days prior to the index procedure:  
• 
Abbreviated physical examination including vital signs (temperature, systolic/diastolic blood 
pressure, respiration rate, heart rate) 
• 
Body mass assessment (body weight, calculation of BMI, and measurement of circumferences) 
• 
Concomitant medications 
• 
IWQOL-Lite assessment 
• 
Eating Inventory  assessment 
• 
Visual Analog Scale assessment 
• 
Urine pregnancy test for females capable of becoming pregnant 
• 
Blood tests  
▪ 
CBC with differential  
▪ 
Chemistry panel 20 
▪ 
Lipid levels and lipoproteins,  
▪ 
Glucose, insulin, HbA1c, high sensitivity C-reactive protein 
• 
Assessment for eligibility 
• 
Brief lifestyle counseling according to Appendix C, including recommendation and instruction 
to follow the caloric target of 1200-1500 kcal/day for subjects ≤ 114 kg (≤ 250 lb) and 1500-
1800 kcal/day for subjects > 114 kg (> 250 lb)  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 51 of 83 
 
 
If the subject is no longer eligible for the study due to a change in the subject’s condition, such as pregnancy, 
abnormal blood test values, or weight change resulting in a BMI outside of the protocol range, the subject will 
be excluded from the study and documented as a screen failure.  
This visit is not required in subjects whose screening visits and tests are performed within 7 days of the index 
procedure. In this case, data collected from the screening visit will serve as baseline data.  
11.9.3. Index Procedure (Day 0) 
The TPS placement procedure will be performed under general or monitored anesthesia care (MAC). Eligible 
subjects will undergo standard preparation for an endoscopic procedure, followed by an endoscopic 
assessment of the esophagus, stomach, antrum, pylorus and duodenum. Subjects who meet the endoscopic 
exclusion criteria will be considered an endoscopic screening failure and excluded from the study. 
Subjects who do not possess any endoscopic exclusion criteria will be randomized into Treatment or Control 
group using a web-based randomization system provided by the study data management organization. 
Procedure details can be found in the instruction for use (IFU). In brief, a TPSS Access Sheath is inserted over 
the gastroscope using standard techniques to position the distal tip approximately 6 cm below the 
gastroesophageal junction. Endoscopic visualization is used to monitor inflation of the distal positioning 
balloon on the Access Sheath and confirm final insertion position. After removal of the gastroscope and 
obturator, the TPS Delivery Device is lubricated and inserted into the Access Sheath until fully-seated with the 
connectors engaged. The TPS Delivery Device is placed on the TPSS Stand and connected to the insufflation 
system. Deployment of the TPS is accomplished by forward rotation of TPS Advance Torque Knob on the 
delivery device handle. Following actuation of the TPS locking mechanisms on the TPS Delivery Device, the 
formed TPS is released into the stomach and the Access Sheath and TPS Delivery Device are withdrawn from 
the patient. A final endoscopic evaluation is performed to inspect the final device configuration and assess the 
gastroesophageal tissues prior to completion of the procedure.  
In the Control subject, the sham procedure consists of anesthesia and the TPSS Access Sheath placement but 
no TPS delivery. Effort will be made so that the overall sham procedure time is similar to the TPS placement 
procedure time.  
Subject will be discharged when the site and physician’s discharge criteria are met (if designated by the 
hospital policy and procedures). 
Before the subject is discharged, s/he is to be provided with a subject information card.  This card provides the 
phone number and name of the person to contact in case s/he needs medical attention related to the therapy. 
Additionally, the subject can provide this card to an emergency room doctor, allowing them to contact the 
Primary Investigator and obtain information about the study. A sample of the card is provided in Appendix G.  
The subject should be placed on a liquid diet for 3 days, followed by soft food for a week, slowly returning to 
normal food in 10 days. 
The following procedures/assessments will be performed during this visit: 
• 
Abbreviated physical examination including vital signs  (temperature, systolic/diastolic blood 
pressure, respiration rate, heart rate) 
• 
Body mass assessment (body weight,  calculation of BMI, and measurement of 
circumferences) 
• 
Assessment of medications 
• 
Endoscopic assessment 
• 
Confirmation of eligibility 
• 
TPS placement procedure 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 52 of 83 
 
 
• 
Assessment of AEs that occurred during the procedure 
Post-Procedure Follow-Up Visits 
Post-procedure follow-up visits are summarized in Appendix B. They include: 
• 
Office visits at 1 week, and 1, 2, 4, 6, 9, 12 months 
• 
Endoscopic assessments at 2, 6, and 12 months  
• 
Visual Analog Scale assessment at 1 week and 1, 6, and 12 month(s) 
• 
Eating Inventory assessment at 1 week and 1, 6 and 12 month(s) 
• 
Blood tests at 6 and 12 months 
• 
IWQOL-Lite at  6 and 12 months 
• 
Device removal at 12 months 
• 
AE assessments at each follow-up visit 
• 
Brief lifestyle counseling at each follow-up visit and brief telephone calls at 7, 8, 10, and 11 
months. 
11.9.4. One Week Post-Index Procedure (7 ± 2 Days) 
The following data are to be collected: 
• 
Abbreviated physical examination (temperature, systolic/diastolic blood pressure, respiration 
rate, heart rate)  
• 
Body mass assessment (body weight, calculation of BMI, and measurement of 
circumferences) 
• 
Visual Analog Scale assessment 
• 
Eating Inventory assessment 
• 
Concomitant medications 
• 
Assessment of AEs that occurred since the last visit  
• 
Assessment of blinding  
• 
Brief lifestyle counseling, with specific instruction for participants to transition from a diet of 
soft foods to a balanced diet of regular foods and calorie target specific to their weight range 
as described in Section 11.9.2 
11.9.5. One Month Post-Index Procedure (30 ± 7 Days) 
The following data are to be collected: 
• 
Abbreviated physical examination (temperature, systolic/diastolic blood pressure, respiration 
rate, heart rate) 
• 
Body mass assessment (body weight, calculation of BMI, and measurement of 
circumferences) 
• 
Visual Analog Scale assessment 
• 
Eating Inventory assessment 
• 
Concomitant medications 
• 
Assessment of AEs that occurred since the last visit 
• 
Brief lifestyle counseling   
11.9.6. Two-Month Post-Index Procedure (60 ± 14 Days) 
The following data are to be collected: 
• 
Abbreviated physical examination (temperature, systolic/diastolic blood pressure, respiration 
rate, heart rate) 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 53 of 83 
 
 
• 
Body mass assessment (body weight, calculation of BMI, and measurement of 
circumferences) 
• 
Concomitant medications 
• 
Endoscopic assessment until the 2M surveillance endoscopy is discontinued per Section 5.5.  
• 
Assessment of AEs that occurred since the last visit 
• 
Brief lifestyle counseling   
11.9.7. Four-Month Post-Index Procedure (120 ± 14 Days) 
The following data are to be collected: 
• 
Abbreviated physical examination (temperature, systolic/diastolic blood pressure, respiration 
rate, heart rate) 
• 
Body mass assessment (body weight, calculation of BMI, and measurement of 
circumferences) 
• 
Concomitant medications 
• 
Assessment of AEs that occurred since the last visit 
• 
Brief lifestyle counseling   
11.9.8. Six-Month Post-Index Procedure (180 ± 14 Days) 
The following data are to be collected: 
• 
Abbreviated physical examination (temperature, systolic/diastolic blood pressure, respiration 
rate, heart rate) 
• 
Body mass assessment (body weight, calculation of BMI, and measurement of 
circumferences) 
• 
Concomitant medications 
• 
IWQOL-Lite 
• 
Visual Analog Scale assessment 
• 
Eating Inventory assessment 
• 
Blood tests (lipid levels and lipoproteins, glucose, insulin, HbA1c, high sensitivity C-reactive 
protein) 
• 
Endoscopic assessment until the 6 M surveillance endoscopy is discontinued per Section 5.5. 
• 
Assessment of AEs that occurred since the last visit 
• 
Brief lifestyle counseling    
11.9.9. Nine-Month Post-Index Procedure (270 ± 21 Days) 
The following data are to be collected: 
• 
Abbreviated physical examination (temperature, systolic/diastolic blood pressure, respiration 
rate, heart rate) 
• 
Body mass assessment (body weight, calculation of BMI, and measurement of 
circumferences) 
• 
Concomitant medications 
• 
Assessment of AEs that occurred since the last visit  
• 
Brief lifestyle counseling   
11.9.10. Twelve-Month Post-Index Procedure (365 ± 30 Days) 
The following data are to be collected: 
• 
Physical examination  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 54 of 83 
 
 
• 
Body mass assessment (body weight, calculation of BMI, and measurement of 
circumferences) 
• 
Concomitant medications 
• 
IWQOL-Lite 
• 
Visual Analog Scale assessment 
• 
Eating Inventory assessment 
• 
Blood tests (lipid levels and lipoproteins, glucose, insulin, HbA1c, high sensitivity C-reactive 
protein) 
• 
Endoscopic assessment 
• 
Assessment of AEs that occurred since the last visit  
• 
Assessment of blinding  
• 
Brief lifestyle counseling   
• 
Unblinding and Pivotal study exit 
 
The above data are to be collected prior to unblinding with the exception of the endoscopic assessment, which 
is to be collected at the time of removal.  
Subjects who were assigned to the Control group will not require an endoscopy at this visit since device 
removal is unnecessary but they should remain blinded until the all other data are collected.  
11.9.10.1. TPS Device Removal 
The TPS is to be removed 365 ± 30 days after the index procedure under general or MAC anesthesia. An 
endoscopic assessment will be performed in all subjects followed by TPS removal in the Treatment group. The 
device removal procedure is described in detail in the IFU. In brief, a 19.5mm OD gastric overtube (Guardus 
Overtube - Gastric, Model Nos. 00711148, US Endoscopy, Mentor, OH) is used to enable device retrieval and 
protect the subject’s esophagus during the removal procedure. Prior to inserting the overtube in the subject, the 
overtube is assembled with accessories from the TPS Retrieval Kit, including the TPS Collector Tip (overtube 
tip insert). The overtube assembly is then lubricated and inserted over the gastroscope using standard 
procedures. An Endoscope Cap is applied to the tip of the gastroscope, which is then used to locate the TPS 
device in the stomach. Reusable endoscopic rat-tooth forceps will be used to manipulate the TPS and engage 
the lock-release button at the proximal aspect of the device. Once engaged, the TPS is pulled back to the 
overtube assembly where the TPS is unlocked using the forceps to apply traction to the lock-release button 
with the overtube assembly providing the counterforce. The lock-release button is withdrawn through the 
overtube and externalized. The gastroscope is reinserted though overtube assembly and a standard endoscopic 
snare is used engage the snare bead on the proximal aspect of the TPS inner coil. Traction against the overtube 
assembly is used to draw the coil out of the TPS external skin and through the overtube assembly for removal. 
After removal of the coil, the gastroscope and snare are reinserted and the external skin is captured on the 
tether proximal to the TPS distal bulb. The skin is withdrawn into the overtube assembly and the system is 
removed to complete TPS retrieval. A final endoscopic evaluation is performed to assess the gastroesophageal 
tissues prior to completion of the procedure. 
Subjects will be discharged according to the hospital and physician’s discharge criteria.  
All procedure- and device-related AEs must be followed until resolution or stabilization (the Investigator does 
not expect any further improvement or worsening of the event).   Following study exit, follow-up will be 
according to clinical practice.   
Subjects will be informed that his/her participation in this study is complete. The subject’s study exit will be 
documented.   

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 55 of 83 
 
 
11.9.11. Unscheduled Visit  
If a subject is hospitalized, seen in the emergency room, or has an unscheduled clinic visit, efforts should be 
made to collect the following data:  
• 
Relevant medical history, physical examination, and laboratory testing findings 
• 
Concomitant medications 
• 
Assessment of AEs  
These assessments should be documented on the eCRFs as appropriate. 
11.9.12. Telephone Contact at Months 7 (210±7 days), 8 (240±7 days), 10 (300±7 days), and 11 
(330-14 days) 
In Months 7, 8, 10, and 11, subjects will be contacted by telephone by study personnel(s) who deliver(s) the 
lifestyle interventions. The subject and study personnel will have a brief (15-minute) telephone calls. During 
these calls, subjects will report on changes in weight, dietary intake, eating behavior, and physical activity 
level. These telephone calls are designed to promote adherence to the lifestyle modification protocol. The 
provider will reinforce positive behaviors consistent with the lifestyle modification program and problem 
solve issues related to weight gain, increased caloric intake or decreases in physical activity.  
12. ASSESSMENT OF SAFETY 
Safety will be evaluated through a risk-benefit assessment of the adverse events profile compared to the 
efficacy demonstrated by the TPS treatment. The incidence of Adverse Events (AEs), Serious AEs (SAEs), 
Serious Adverse Device Effects (SADEs), and Unanticipated Serious Adverse Device Effects (UADEs) will 
be captured.   
12.1. Adverse Events 
An AE is any untoward medical occurrence in a subject or clinical investigation subject that occurs during any 
part of the clinical study, whether related to the investigational device or not. Pre-existing conditions are not 
reported as AEs unless there has been a worsening in severity or frequency which cannot be attributed to the 
disease’s natural history or progression. Protocol-defined follow-up visits and pre-scheduled endoscopies 
(including device placement/removal, patient surveillance, and planned diagnostic endoscopies) are not 
considered adverse events.  
For AEs, the event description, severity, date of onset, treatment, outcome, and relationship to device will be 
collected on the AE eCRF.  
All procedure- and device-related AEs must be followed until resolution or stabilization (the Investigator does 
not expect any further improvement or worsening of the event). 
An Adverse Device Effect (ADE) is any adverse event that is considered possibly-related or related to the 
device. An ADE may occur at any time after exposure to the investigational device.  
Determination of whether there is a reasonable possibility that the investigational device caused or contributed 
to an AE will be reported by the Investigator and reviewed by the CEC as described in Section 12.2. 
Determination will be based on assessment of temporal relationships, biologic plausibility, association (or lack 
of association) with underlying disease, and presence (or absence) of more-likely cause.  
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 56 of 83 
 
 
12.1.1. Serious Adverse Event   
A SAE is an event that:  
• 
Led to a death 
• 
Led to a serious deterioration in health resulting in  
• 
a life threatening illness or injury 
• 
a permanent impairment of a body structure or body function 
• 
in-patient hospitalization (>24 hours) or prolongation of an existing hospitalization  
• 
requires medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment of a body structure or body function 
• 
Led to fetal distress, fetal death or a congenital abnormality or birth defect 
Here, “life-threatening” refers to an event when the patient is at substantial risk of dying at the time of the 
adverse event, it does not refer to an event that hypothetically might have caused death if it were more severe; 
“permanent” is defined as irreversible impairment or damage to a body structure or function, excluding 
trivial impairment or damage.  
For the purpose of this study, endoscopic observations managed by medication and endoscopic surveillance as 
described in Guidelines for Managing Endoscopic Observations (Section 10.2.2) are not considered as SAEs. 
Diagnostic endoscopy is not considered as “intervention” in the context of SAE. Planned hospitalization for a 
pre-existing condition is not considered as a SAE.  
12.1.2. Serious Adverse Device Effect 
An SADE is a SAE that is possibly related or related to the device.  
12.1.3. Unanticipated Adverse Device Effects  
Unanticipated adverse device effects (UADE) are any serious adverse device effects on health or safety or any 
life-threatening problem or death caused by, or associated with, the investigational study 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 IFU) or any other unanticipated serious problem associated with a device that 
relates to the rights, safety, or welfare of subjects.   
When an AE meets the definition of a UADE or that relationship is unknown, the Investigator will report the 
event to BAROnova within 24 hours but no later than 10 working days after the Investigator first learns of the 
effect and reports to the reviewing IRB as required. 
12.2. 
Device Relationship (Causality)  
Causality assessment is required for AEs (and SAEs) that occur during clinical investigations. There is 
currently no standard international nomenclature to describe the degree of causality or relatedness of an AE 
with the Investigational Device (ICH, Clinical Safety Data Management: Definitions and Standards for 
Expedited Reporting, 1994). The following terms will be used during this study:  
• 
Related - An AE that is directly and clearly related to the Investigational Device; 
• 
Possibly Related - There is a reasonable likelihood that the event is due to the Investigational 
Device, as evidenced by the following:  
• There may be temporal association with the Investigational Device (e.g., within 24 
hours of device placement) 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 57 of 83 
 
 
• The event, or level of severity of the event, is unlikely to be explained by other 
etiologies (known to be related to the study disease, subject’s baseline medical 
condition, or concomitant medication) 
• 
Unlikely Related - The AE is not temporally related to the Investigational Device, or is known 
to be related to one of the following:  
• Morbidity associated with underlying medical condition 
• Anesthesia 
• Upper GI endoscopy 
• Concomitant medication 
• A relationship to the Investigational Device is not biologically plausible  
• 
Not related - The AE is definitely not related to the Investigational Device 
12.3. 
Adverse Event Reporting 
12.3.1. Sponsor Reporting Requirements  
The Sponsor will conduct an evaluation of any reported UADEs and will report the results of this evaluation to 
the FDA, IRBs, and participating Investigators within 10 working days after first receiving notice of the event 
12.3.2. Clinical Site Reporting Requirements  
• 
All AEs and ADEs will be recorded by the Investigator or designee on the eCRFs provided 
• 
Any SAEs are to be reported to the Sponsor within 36 hours except UADE or suspected UADE 
which is to be reported within 24 hours of knowledge of the event, followed by a written 
confirmation by the Investigator within 5 working days 
• 
The Investigator at each site is ultimately responsible for reporting AEs , SAEs and UADEs to 
the IRB according to local IRB requirements   
13. CLINICAL EVENT COMMITTEE   
An independent Clinical Events Committee will be formed to review and adjudicate clinical adverse events. 
The committee will be comprised of physicians who will not participate in the enrollment or treatment of 
subjects in this study.  
Events to be reviewed by this committee will be defined in the CEC charter. Any event listed in the CEC 
charter that is reported in an eCRF may result in the acquisition of relevant explanatory or supportive 
documents, which may include source documents from the hospital, as needed. Copies of these documents will 
be distributed to members of the CEC. The CEC will be blinded to subject’s treatment whenever possible. 
When evaluating the device relationship of an event, the CEC will treat the subject as if he/she is in the 
treatment group.   
The interpretation of the event as classified and adjudicated by the CEC will be used in the final safety 
analyses.   
14. DATA SAFETY MONITORING BOARD   
The DSMB is composed of independent physicians and a biostatistician who are not participating in the study 
and will not be affiliated with BAROnova, the Investigators, or the investigational sites. The DSMB has access 
to unmasked data, will review the study on a periodic basis, is responsible for making recommendations 
regarding any safety or compliance issues throughout the course of the study and may recommend to the 
Steering Committee to modify or stop the study. However, all final decisions regarding study modifications or 
study termination rest with the Steering Committee.  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 58 of 83 
 
 
All cumulative safety data will be reported to the DSMB and reviewed on an ongoing basis throughout 
enrollment and follow-up periods to ensure subject safety. Every effort will be made to allow the DSMB to 
conduct an unbiased review of subject safety information. All DSMB reports will be made available to the 
FDA upon request but will otherwise remain strictly confidential.  
DSMB will meet according to the following schedule: 
a. Initial meeting will commence before the study start or shortly after the study start 
b. DSMB will convene as often as necessary but at a minimum twice a year during enrollment phase, 
with the first review meeting occur within the first six months of enrollment or no later than the first 45 
subjects have completed the 1-month follow up visit. If the enrollment dynamic changes, the Sponsor 
may increase or decrease the frequency of the meeting 
c. DSMB meeting will be convened if the staged safety monitoring threshold has been exceeded as 
described in Section 5.4 and Section 15.5.6.  
d. Additionally, a DSMB meeting may be requested by DSMB member, the Sponsor, IRB, or the Study 
Steering Committee at any time to discuss safety concerns if it arises.  
In the case that a DSMB meeting is triggered by the staged safety monitoring threshold, the DSMB will review 
the data and provide recommendation to the Sponsor within 15 days.  Based upon DSMB recommendation, 
Sponsor will implement necessary actions which may range from continuous monitoring, protocol 
modification, stopping of enrollment to device removal. Sponsor will inform FDA about the course of action 
following the DSMB review as described in Section 5.4. 
15. STATISTICAL DESIGN AND ANALYSIS  
15.1. Statistical Overview 
Data will be summarized by the number, mean, median, standard deviation and range for continuous variables 
and by number and relative frequency for categorical variables. Summaries will be presented by treatment 
group and visit as appropriate.  A summary of the subjects combined will be provided for the baseline 
information only.  Missing data imputation approaches are outlined below.     
The alpha level will be set to 0.05 based on the two-sided testing and 0.025 for the one-sided approach, if not 
explicitly stated otherwise. Study success criteria are defined in Section 15.3.1. Statistical testing and 
confidence intervals for sensitivity analyses and secondary endpoints will be presented as an aid in interpreting 
study results, but statistical significance is not required for study success.  Unless otherwise indicated, all 
statistical inferences will be based on two-sided 95% confidence intervals and p-values less than or equal to 
0.05 will be considered significant.  
15.2. Analysis Populations  
The following analysis populations are defined for the study: Intent-to-Treat (ITT), modified Intent-to-Treat 
(mITT), Per-Protocol (PP) and Completed Cases (CC). The primary effectiveness hypotheses will be tested on 
the PP population.  The primary safety analysis will be performed on mITT population. The ITT and CC 
populations will be used in a sensitivity analysis of the primary effectiveness endpoint. 
• 
Intent-to-Treat: The Intent-to-Treat population includes all randomized and enrolled subjects as 
defined in Section 7.4 regardless of whether or not the subject received the randomized 
treatment.  
• 
Per-Protocol: The Per-Protocol population is a subset of the ITT population and includes all 
subjects who receive the assigned treatment and do not have any major eligibility violations. 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 59 of 83 
 
 
• 
Modified Intent-to-Treat: The mITT population consists of the ITT population subjects who 
received the assigned treatment and that have at least one post-treatment follow-up, including 
the index procedure visit. 
• 
Completed Cases: The CC population includes all enrolled subjects who have the 12-month 
follow-up visit, or have completed the study based on reaching the BMI objective of ≤ 22 kg / 
m2 in two consecutive follow-up visits as described in Section 5.1. 
15.3. Study Objectives and Hypotheses 
15.3.1. 
Primary Effectiveness Objective 
The primary objective of this study is to assess the clinical effectiveness of the BAROnova TransPyloric 
Shuttle for weight reduction in patients with obesity, with a BMI of 35.0 to 40.0 kg/m2, or a BMI of 30.0 
through 34.9 kg/m2 with one or more obesity-related comorbid conditions over the 12 months treatment 
period.  
The hypothesis associated with the first co-primary endpoint is that the subjects in the Treatment group will 
have superior weight loss in %TBL compared to subjects in the Control group at 12-month follow up.  The 
statistical null and alternative hypothesizes are: 
Hi0: µT - µC ≤ δ vs. 
HiA: µT - µC > δ, 
Where, 
T is the mean % TBL at 12 months in the treated group  
µC is the mean % TBL in the control group at 12 months.  
δ is the superiority margin. 
The hypotheses will be tested using a one-sided two-sample t-test for independent samples at the alpha level of 
0.025. If the test value exceeds the nominal critical point, the H0 will be rejected.  The testing may be 
performed using mixed model repeated measurements approach.  If the mixed model is used, the decision 
about the rejection of null hypothesis will be based upon the test for the 12-month follow-up outcomes. The 
primary statistical test will use δ = 0. If the H0 is rejected, the 95% confidence interval for the difference in 
%TBL between the groups will be created.  The lower limit of the interval is the statistically achieved 
superiority margin.  
The second co-primary effectiveness endpoint is the percentage of Treatment subjects with a  5% TBL at 12 
months. Proportion of subjects who lose at least 5% of their baseline weight will be compared against the 
target proportion of 50% using a one-sided test for hypothesized population proportion.   
The statistical null and alternative hypotheses are: 
Hii0: pT < 0 vs. 
HiiA: pT ≥ 0, 
 Where, 
pT is the proportion in the study subjects from the Treatment group 
0 is the reference proportion (i.e 0.5 (50%))  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 60 of 83 
 
 
Study statistical success is achieved if study null hypotheses for both co-primary endpoints are rejected. FDA 
recommends that the Hi0 is rejected with superiority margin δ = 5% and the Hii0 is rejected.   
15.3.2. 
Safety Objective 
The objective of the safety analysis is to provide safety information sufficient to characterize and summarize 
adverse events observed during the study.   
15.4. Sample Size Considerations 
A total sample size of 270 subjects is planned for the pivotal study cohort.  The ENDObesity I study provided 
estimates for the mean %TBL of 14.5 (SD=5.8) at 6 months of follow-up.  For the purposes of the sample size 
calculation, the assumed means were 13% in Treatment and 5% in Control subjects.  This provides a 
difference (Treatment – Sham Control) in mean %TBL of 8% and the assumed standard deviation was 
increased to 9% (approximately 1.5 times that observed in the ENDObesity I study) to account for a more 
conservative estimate of the standard deviation.  Under these assumptions, a sample size of 243 subjects (162 
Treatment, 81 Control) has 90% power to reject H0 under the 4% superiority margin scenario and 68.4% power 
under the superiority margin of 5%.  Under less conservative scenario of standard deviation of 7, the study has 
88% power to reject H0 under the 5% superiority margin scenario and 99% power under the 4% superiority 
margin. The study will enroll 270 subjects (approximately 180 in the Treatment groups and 90 in the Control 
group) to compensate for losses to follow-up.   
The second co-primary endpoint is to demonstrate the proportion of subjects with a  5% TBL at 12 months is 
greater than 50%. Under the assumption of 65% responder rate in the Treatment group, the study requires 113 
treatment subjects in order to have 90% power to reject null hypothesis for the second co-primary endpoint. 
A third consideration for the sample size is the ability to provide reasonable safety data from the study.  With 
the proposed sample size of 180 subjects in the Treatment group, there is an 80% likelihood to observe at least 
one event of any specific complication if it occurs in at a rate of 0.9% or greater in subjects treated with the 
TPSS.  The upper limit of 95% exact binomial confidence interval for an event rate if none of 180 subjects has 
specific complication is 2.0%.   
15.5. Statistical Analysis 
15.5.1. 
Accountability and Demographics 
The number of subjects in each population will be summarized overall and by site for each treatment group.  In 
addition, the number of subjects completing the study and withdrawing from the study will be presented along 
with reasons for withdrawal. 
Descriptive summaries for baseline and demographic characteristics including age, gender, height, weight, 
baseline BMI, medical history, and co-morbidities will be presented by treatment group.   
15.5.2. 
Comparability of the Treatment Groups 
The demographic and prognostic variables measured at study entry will be compared between the Treatment 
and the Control groups.  Continuous variables will be compared with Student t-test for two independent 
samples or Wilcoxon rank sum test, and categorical variables will be compared with Fisher’s exact test or Chi-
square test. 
15.5.3. 
Primary Analysis 
The %TBL will be calculated as (Weight(kg)BL – Weight(kg)FUP)/Weight(kg)BL. Where Weight(kg)BL is the 
subject’s weight at baseline in kilograms and Weight(kg)FUP is the subject’s weight at follow-up in kilograms. 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 61 of 83 
 
 
The %TBL will be summarized at each follow-up visit through 12 months along with the observed total body 
weight at baseline and each follow-up visit by treatment group.   
The testing of null hypotheses for the co-primary efficacy endpoints is described in Section 15.3.1.  
In order to accommodate missing data in the primary effectiveness analyses, a multiple imputation approach 
will be used to impute missing follow-up weight observations.  A total of 5 imputed samples will be created.  
Covariates (e.g., gender) will be used in the imputation procedure in addition to the subject’s weight from 
previous visits. The multiple imputation approach was first described by Rubin.35  The SAS procedures MI and 
MIANALYZE will be used to create the imputations and perform the analysis. The statistical null hypotheses 
for both co-primary endpoints will be tested on multiply imputed data sets.  Sensitivity analyses will be done 
by evaluating the primary analysis on the ITT and CC cohorts. Further, a last observation carry forward 
(LOCF) imputation will be performed for the sensitivity purposes.  
Additionally, the %TBL median, mean and standard deviation and percent of subjects with greater than 
5%TBL will be summarized by treatment group and levels of covariates.  Covariates include gender (male 
versus female), race (Caucasian versus non-Caucasian), age ( median, > median), and baseline BMI (30-34.9 
kg/m2 and 35-40.0 kg/m2).  
15.5.4. 
Secondary Analysis 
Secondary endpoints will be summarized by treatment group for the ITT and per-protocol cohorts based on the 
observed data and include the following summaries: 
• 
Proportion of subjects achieving at least 7% and 10% TBL at 12 months; 
• 
Percent TBL at 1 week, 1, 2, 4, 6, 9 and  12 months in the Treatment versus Control group; 
• 
Percent EWL at 1 week, 1, 2, 4, 6, 9 and 12 months in the Treatment versus Control group; 
• 
Proportion of subjects who achieve at least one obesity class reduction at 1 week, 1, 2, 4, 6, 9 
and 12 months in the Treatment versus Control group; 
• 
Change of BMI at 1 week, 1, 2, 4, 6, 9 and 12 months from baseline in the Treatment versus 
Control group; 
• 
Change in weight-related quality of life at 1 week, 1, 2, 4, 6, 9 and 12 months as assessed by 
IWQOL-Lite Questionnaire in the Treatment versus Control group; 
• 
Change in eating behavior at 1 week, 1 month and 12 months as assessed by the Eating 
Inventory;  
• 
Change in appetite, hunger and fullness at 1 week, 1 month, 6 and 12 months as assessed by 
Visual Analog Scales in the Treatment versus Control group; 
• 
Change in comorbid conditions and selected clinical parameters at 6 and 12 months in the 
Treatment group: 
o Prevalence of the metabolic syndrome and its individual components  
o Glucose, insulin, and insulin resistance (as estimated by HOMA)  
o High sensitivity C-reactive protein (hsCRP)  
o Lipid levels (LDL-C, HDL-C, and triglycerides)  
o Blood pressure  
o Waist circumference 
The analysis of total body weight loss is described above.  The other continuous and binary variables will be 
summarized descriptively by visit with 95% CIs presented for the mean values and proportions, respectively.  
For continuous endpoints, the change from baseline will be calculated if appropriate, and a t-test or a sign-rank 
test used to evaluate the null hypothesis that the change from baseline is centered around 0 (no change) within 
each treatment group. Treatment group comparisons for continuous endpoints will be made using mixed 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 62 of 83 
 
 
models with post-hoc tests for each follow-up, and comparisons for qualitative variables will be made using 
Fisher’s exact test, McNemar test or chi-square test, as appropriate.  
The percent excess weight loss (%EWL) will be calculated as (Weight(kg)BL – Weight(kg)FUP)/ 
ExcessWeight(kg)BL where ExcessWeight(kg)BL is calculated as difference between the subject’s baseline 
weight in kilograms and the kilograms at which the subject’s BMI would be 25.  
15.5.5. 
Safety Analysis 
The safety analyses will be performed using the mITT Population.  
An overall summary of AEs will be provided including the number of events and percent of subjects with any 
AEs, SAEs, and UADEs. For each type of event, the number of events and number and percent of subjects 
with the event will be provided in a table. Separate summaries of all adverse events will be summarized by 
relationship to device and procedure. Adverse events will be coded using MedDRA medical dictionary. 
15.5.6. 
 Staged Safety Monitoring Analysis  
The staged analysis of the endoscopic ulcer occurrence rate is planned per Section 5.4.  The threshold 
endoscopic ulcer rate is set at 25 per 100 (25%).  The occurrence of endoscopic ulcer events against this 
threshold will be evaluated by estimating cumulative incidence in the Treatment and the Control groups using 
the Kaplan-Meier (K-M) product-limit survival estimator.  The first calculation of K-M based cumulative 
incidence will occur at the time when the last of the first 30 investigational subjects (subjects in the device 
treatment group) reaches 80 days after the index procedure. Only subjects that have reached 80 days post-
procedure will be included.  For clarification, the cumulative incidence will include observations from study 
pre-scheduled 2 and 6 months endoscopic evaluations and all unscheduled evaluations accumulated at the time 
of analysis. A life table with the point estimate of the endoscopic ulcer rate will be calculated as: 
(1 – K-M Survival estimate) x 100 
The log-log transformation will be used to obtain the point-wise equal-precision confidence bands for the 
survivor function.  These confidence intervals will be translated into confidence intervals for the event rate as 
follows: 
Lower limit event rate C.I. = (1-Upper limit survival C.I.) * 100 
Upper limit event rate C.I. = (1-Lower limit survival C.I.) * 100 
The confidence intervals will be created using alpha = 0.1 (i.e., 90% C.I.), which is a conservative approach 
concerning safety. Safety analysis by the DSMB will be triggered if the lower limit event rate C.I. is larger 
than 25 per 100.  
If due to study operational reasons there are more than 30, 60 or 90 investigational subjects respectively at the 
time when the last respective subject is at 80 days post index procedure (i.e., multiple subjects were enrolled 
on the same day), all available subjects will be included in the analysis. By the way of example, if the last of 
the first 28 investigational subjects reach 80 days post-procedure on Datet and last of the first 35 subjects reach 
80 days post-implantation on Datet+1, the analysis will be performed using 35 subjects. Analyses will continue 
to be performed in increments of 30 investigational subjects.  That is, the next analysis will be performed when 
the last of the first 60 investigational subjects reaches 80 days after the implantation.  The study enrollment 
will not discontinue due to staged analysis unless the threshold has been exceeded. No efficacy data will be 
analyzed for the purpose of the staged analysis. The final staged safety analysis will be performed when the 
last of the first 90 investigational subjects reaches 80 days follow-up.  At that time, sufficient safety 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 63 of 83 
 
 
information concerning the rate of endoscopic ulcers will be collected and further staged safety monitoring 
will not be warranted.   
 
15.5.7.  Analysis for Discontinuation of Routine Endoscopic Surveillance 
The statistical margin for discontinuation of routine endoscopic surveillance is less than 15% (Section 5.5).  
The statistical approach is to test a H0 that ulcer rate detected at specific endoscopic surveillance follow-up is 
≥ 15%.  Rejection of such null hypothesis is consistent with meeting the criteria for the discontinuation of 
routine endoscopic surveillance. This hypothesis will be evaluated by constructing the 95% binomial 
confidence interval using the Wilson approach. The will be performed when about 60 consecutive (or about 90 
if criterion is not met with the 60 subjects) subjects in the treatment group have completed the endoscopies at 
the respective time point.  The following describes application details and acceptance simulation results of this 
criterion. 
A. Two-month routine (surveillance) endoscopy will discontinue if: 
i. 
When about 60 Treatment subjects complete the 2-month follow up endoscopy, the observed 
number of ulcers detected by the two-month endoscopy is not more than 3 out of 60 cases and 
none of the detected ulcers have a smallest width or length dimension greater than 1cm and that 
there are no stigmata of bleeding.  In this case the maximum observed rate is 5.0% and the upper 
limit of the 95% C.I. is 13.7%); OR, if A.(i) is not met, 
ii. 
When about 90 Treatment subjects completes the 2-month follow up endoscopy, the observed 
number of ulcers detected by the two-month endoscopy is not more than 6 out of 90 cases and 
none of the detected ulcers have a smallest width or length dimension greater than 1cm and that 
there are no stigmata of bleeding. In this case, the maximum observed rate is 6.7% and the upper 
limit of the 95% C.I. is 13.8%). 
B. Six-month routine (surveillance) endoscopy will discontinue if: 
i. 
When about 60 Treatment subjects complete the 6-month follow up endoscopy, the observed 
number of ulcers detected by the six-month endoscopy is not more than 3 out of 60 cases and none 
of the detected ulcers have a smallest width or length dimension greater than 1cm and that there 
are no stigmata of bleeding.  In this case the maximum observed rate is 5.0% and upper limit of 
the 95% C.I. is 13.7%); OR, if B.(i) is not met 
ii. 
When about 90 Treatment subjects completes the 6-month follow up endoscopy, the observed 
number of ulcers detected by the six-month endoscopy is not more than 6 out of 90 cases and none 
of the detected ulcers have a smallest width or length dimension greater than 1cm and that there 
are no stigmata of bleeding. In this case, the maximum observed rate is 6.7% and upper limit of 
the 95% C.I. is 13.8%). 
15.5.8. Assessment of Poolability 
The poolability of the study results across study sites will be assessed. A regression model with covariates for 
study site, treatment group, and site*treatment interaction will be fit. Study sites with fewer than 10 subjects 
will be combined into a single pseudo-site for this analysis. If the p-value for the site*treatment interaction 
term is < 0.10, this will be considered statistical evidence of a potential differential treatment effect by site.  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 64 of 83 
 
 
16. QUALITY CONTROL AND QUALITY ASSURANCE 
16.1. Selection of Study Sites and Investigators 
The Sponsor will select Investigators who are qualified by training and experience to perform clinical research 
in this field and to participate in the clinical investigation. Sites will be selected based upon an assessment of 
the qualifications of the Primary Investigator and the facilities at each site. All Investigators will be trained on 
the device, the protocol and all study procedures prior to enrolling subjects.     
A pre-investigation visit will be conducted at each study site to assure that the Investigator and the study staff 
understand the obligations for using and managing the investigational device, following the study protocol, 
obtaining informed consent, adhering to FDA and IRB regulations, and conducting clinical research.   
16.2. Training 
16.2.1. 
Site Training 
All Investigators/study personnel are required to attend Sponsor training sessions, which may be conducted at 
an Investigator's meeting, a site initiation visit or other appropriate training sessions. Remote over-the-phone 
or web-based training will take place as necessary. Training of Investigators/study personnel will include, but 
is not limited to, the investigational plan, participant recruitment, enrollment (including review of inclusion 
and exclusion criteria), subject retention, investigational device usage, protocol requirements, case report form 
completion, and study personnel responsibilities.  At least one individual at each site also will be trained in the 
delivery of the lifestyle modification counseling and the behavioral/psychosocial assessment by a consultant 
with relevant expertise. All Investigators/study personnel that are trained must sign a training log (or an 
equivalent) upon completion of the training.  Investigator/study personnel must not perform any study-related 
procedures prior to being trained.  
Investigators who perform the device placement/removal procedures will be trained on device use. BAROnova 
personnel will provide in-person technical support for a minimum of the first five procedures at each site.  
16.2.2. 
Monitor Training 
The Sponsor or designee will engage monitors that are qualified by appropriate training and experience to 
review the conduct and quality of the study. Prior to working on the study, monitors will be trained to the 
investigational plan, case report forms, and the device/procedure knowledge.  Such training will be 
documented.     
16.3. Study Monitoring 
BAROnova and/or a designee (e.g., a Contract Research Organization), will monitor the clinical study in a 
manner consistent with FDA regulations and the Good Clinical Practice (GCP) standards adopted by 
BAROnova.  
The Investigator is required to ensure compliance with all procedures required by the Investigational plan and 
by study procedures provided by the Sponsor. The Investigator agrees to provide reliable data and all 
information requested by the Investigational Plan including eCRFs, Discrepancy Clarification Forms or other 
appropriate instrument according to the instructions provided, and to ensure direct access to source documents 
to Sponsor representatives. 
Clinical Monitors will periodically monitor all eCRFs and corresponding source medical records for each 
subject. The monitoring visits provide the Sponsor with the opportunity to evaluate the progress of the study, 
to verify the accuracy and completeness of eCRFs, to resolve any inconsistencies in the study records, and to 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 65 of 83 
 
 
ensure that all protocol requirements, applicable regulatory regulations, and Investigator’s obligations are 
being fulfilled. Monitoring and data verification may be performed remotely or onsite.  
The Investigator and his/her staff will be expected to cooperate with Sponsor’s personnel or designee and to be 
available during the monitoring visits to answer questions sufficiently and to provide any missing information.  
16.4. Source Data Verification 
Source data verification ensures accuracy and credibility of the data obtained. During monitoring, reported 
data are reviewed with regard to being accurate, complete, and verifiable from source documents (e.g., subject 
files, physician notes, discharge summaries, operative records, study worksheets, etc.). All data reported on the 
eCRF should be supported by source documents, unless the eCRF also serves as a source document. 
16.4.1. 
Definition of Source Data 
Source data includes all information in source documents (original records, certified copies of original records, 
appointment books, original laboratory records, and original data recorded on customized worksheets) and 
includes all original recordings or copies of clinical findings, observations, or other activities in a clinical study 
necessary for the reconstruction and evaluation of the study. Certain data may be directly entered into eCRF. 
In this case, the eCRF serves as source document. 
16.5. Direct Access to Source Data/Documents 
The Investigator(s)/institution(s) will permit direct access to source data/documents for study-related 
monitoring, audits, IRB/IEC and regulatory inspection(s). 
Consenting subjects are agreeing to allow the Sponsor or designee access and copying rights to pertinent 
information in their medical records relevant to study participation. As part of the informed consent, the 
Investigator or designee will obtain permission for regulatory authorities to review any records identifying 
subjects in this study. Sponsor will not otherwise release any personal information (refer to Section 18.3 
Confidentiality). 
16.6. Maintain Blinding during the Study 
Only the data management organization and the unblinded statistician have access to the randomization code. 
The Sponsor’s study management team, the Study Steering Committee, the CEC, and the statistician who is 
responsible for study design and data analysis will be blinded to subject’s treatment during the study. The 
monitors from the monitoring organization will have access to subjects’ treatment information in order to 
perform study monitoring and source data verification.  
At each site, the Investigator who performs the index procedure and endoscopic follow up will not collect the 
outcome data. The Investigator or study coordinator who collects outcome data will be masked. Source 
documents containing subject treatment information will be either masked or access-controlled according to 
each site’s practice. Each site’s blinding procedure will be assessed by the study monitors at the monitoring 
visits.  
In exceptional circumstances when knowledge of the Investigational Device is essential for patient safety in 
case of serious adverse event, the blinding for this subject may be broken.  
The Investigator should promptly (within 24 hours) document and explain to the Sponsor any premature 
unblinding (e.g., accidental unblinding, unblinding due to a serious adverse event) of the study subject. 
16.7. Protocol Deviations 
It is the Investigator's responsibility to ensure that there are no deviations from the protocol except in cases of 
medical emergencies, when the deviation is necessary to protect the life or physical well-being of the subject. 
In the event of any deviation from the protocol, a Protocol Deviation Case Report Form will be completed. 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 66 of 83 
 
 
The occurrence of protocol deviations will be monitored by the Sponsor for evaluation of Investigator 
compliance to the protocol, Good Clinical Practice (GCP), and regulatory requirements. The Investigator will 
inform the IRB of protocol deviations according to requirements of each reviewing IRB.  
A protocol deviation for this protocol consists of, but is not limited to, the following:  
• 
Failure to obtain subject’s informed consent prior to any study-related activities and the index 
procedure 
• 
Enrollment of subjects who do not meet all eligibility requirements 
• 
Failure to conduct protocol required clinical follow-ups and within time windows  
• 
Failure to report SAEs/UADEs according to protocol requirements  
In the event of any deviation from the protocol, the Investigator will be notified of the site’s non-compliance. 
Corrective actions will be advised if necessary and the methods, plan or other activities put in place to ensure 
non-recurrence will be documented by the Investigator and forwarded to the sponsor or their designee. 
Continued protocol deviations despite re-education of study site personnel and/or persistent protocol 
deviations may result in termination of the site’s study participation. Subjects already enrolled at these sites 
will continue to be followed per protocol guidelines. 
16.8. Termination of Study Site Participation 
The Sponsor reserves the right to stop the enrollment of subjects at a study center at any time during the study. 
Specific instances that may precipitate terminating a study center may include the following:  
• 
Unsatisfactory subject enrollment  
• 
Failure to comply with protocol  
• 
Failure to obtain informed consent  
• 
Inaccurate and/or incomplete data recording on a recurrent basis 
• 
Failure to report SAEs in timely manner  
• 
Loss of (or unaccounted for) investigational product inventory 
• 
Severe protocol deviations without justification or failure to implement corrective actions 
16.9. Study Steering Committee (SSC) 
The Steering Committee is composed of Principal Investigators, subject experts, and BAROnova’s 
representatives. The Steering Committee has the overall responsibility for producing and conducting a 
scientifically sound study. In that capacity, the Steering Committee will participate in protocol development 
and review; address and resolve scientific issues encountered during the study; oversee ongoing study conduct 
and address operational issues that may warrant a protocol amendment or other corrective action; and 
recommend corrective actions, including premature termination of the study. The Steering Committee will also 
oversee the presentation and /or publication aspect of the study.  
17. DATA HANDLING AND RECORD KEEPING  
For the study duration, the Investigator will maintain complete and accurate documentation including but not 
limited to the following: medical records, study progress records, laboratory reports, case report forms, signed 
informed consent forms, device records, and correspondence with the IRB and study monitor/Sponsor, AE 
reports, and information regarding subject discontinuation or study completion.  
17.1. Source Documentation 
For the duration of the study, the Investigator shall take responsibility for maintaining complete and accurate 
source documentation.   

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 67 of 83 
 
 
The following materials should be included in the patient record:  
• 
Subject medical history/physical condition prior to study involvement  
• 
Dated and signed notes on the day of entry into the study referencing BAROnova, the study, 
subject study ID number, and a statement confirming informed consent  
• 
Dated and signed notes from each subject’s visit (for specific results of procedures and exams)  
• 
AEs reported and their outcome including supporting documents  
• 
Subject’s condition upon study completion or withdrawal  
17.2. Case Report Form Completion 
Accurate primary data collection will be performed by site staff trained on the protocol and eCRF completion. 
All data fields will be completed where appropriate. However, if data are not available (i.e., missed visit, etc.), 
the site will receive instruction regarding electronic documentation. As data are entered, automated cross-
check programs will search for any data discrepancies in the eCRFs. Appropriate error messages will be 
generated, allowing for the modification and/or verification of the entered data. Queries will generally be sent 
to the investigational site using an electronic data query system that includes an automated audit trail of the 
corrections. The Investigator, or designee, will certify that the data are complete and accurate by applying an 
electronic signature to the eCRF. Any subsequent alterations, corrections, or additions will be reviewed and 
electronically signed by the Investigator prior to the database lock. 
The Sponsor or designee will provide clinical monitoring to include eCRF review and parity checks with the 
source documentation, including operator worksheets retained with eCRF documentation and health care 
facility charts. 
17.3. Record Retention 
The Investigator/Site will maintain all records pertaining to this study for the later of (a) five years following 
study completion, or (b) five years after FDA notified that the study under the IDE has been terminated by the 
Sponsor, or (c) as otherwise instructed by the Sponsor. Investigator will be notified by Sponsor of the date of 
completion or discontinuation of the study.   
To comply with these requirements, the Investigator will not dispose of or transfer any records relevant to this 
study without either (1) written permission from the Sponsor, or (2) providing an opportunity for the Sponsor 
to archive the records with an external vendor.   
18. ETHICAL CONSIDERATIONS  
18.1. Institutional Review Board Review 
IRB approval for the protocol and informed consent form will be obtained by the Investigator prior to study 
participation by subjects. The approval letter must be obtained prior to beginning this study and a copy must 
be provided to the Sponsor. No changes will be made to the protocol or informed consent form without 
appropriate approval from the IRB, the Sponsor and/or the regulatory agencies. Additionally, the Primary 
Investigator or representative will provide an IRB membership list or assurance number to the Sponsor or its 
designee.   
As per local IRB requirements, the Investigator will report study progress until it is completed. Further, any 
protocol amendments as well as associated informed consent changes will be submitted to the IRB and written 
approval must be obtained prior to implementation.  
18.2. Informed Consent 
Written informed consent must be obtained prior to any study-related activities and the index procedure.  

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 68 of 83 
 
 
The Investigator should clearly explain that this is an elective procedure and should discuss the potential risks 
and benefits associated with participation in this study.  Subjects should be advised that the BAROnova TPS 
should not be considered a lifetime device and must be removed at 12 months post-placement since it has not 
been tested for such use.  
Subjects providing informed consent agree to permit the Sponsor or designee access to pertinent information 
in their medical records concerning their participation in this study.   This confidential patient information may 
be shared with regulatory agencies as required; however, the Sponsor undertakes not to otherwise release the 
subject's personal and private health information. 
18.3. Confidentiality 
The identity of subjects enrolled in the study and the information contained in their study records will be kept 
confidential by BAROnova.  As part of the Investigator training session, Investigators will be instructed in the 
importance of confidentiality and the techniques for protecting subjects’ privacy and rights.  Subject’s personal 
information will be handled at all times in accordance with appropriate confidentiality standards and 
applicable data protection and local privacy laws. 
Each subject will be assigned a study identification number to be used on eCRFs and other study records sent 
to the Sponsor or its designee.  Initials will also be used to track study subjects. 
Confidentiality will be protected as much as possible throughout the study.  Medical records will be reviewed 
by representatives of BAROnova and/or its designee and will be made available for review as required by the 
IRB and regulatory authorities.  Results of data collected will be reported as statistical information only.  The 
subject’s name will not be used or otherwise disclosed unless required by US law or regulation.   
19. INVESTIGATIONAL DEVICE MANAGEMENT  
19.1. Device Accountability 
The Sponsor will only distribute investigational devices to sites that are part of the clinical investigation.  The 
Sponsor will maintain complete, current and accurate records pertaining to the distribution of the 
investigational devices and follow record keeping requirements in accordance with Good Clinical Practices 
and FDA Regulations. 
The Investigator is responsible for maintenance of adequate records of the receipt, disposition, and/or return of 
all investigational devices distributed to their site.  At study termination, or termination of the site from 
participation in the study the Sponsor will provide specific instructions to the study sites on unused 
investigational devices.   
Use of the investigational device outside of the protocol (e.g., compassionate use) without prior written 
approval is strictly forbidden and may constitute grounds for removal of the Investigator/site from the study. 
19.2. Device Return 
All unused investigational devices, including those unused due to malfunction, device failure, device 
complaint or device dropped on the floor, must be returned to the Sponsor immediately according to the 
returned goods process.  All devices and/or remaining components that are associated with a device 
malfunction or clinical procedural failure should be returned to the Sponsor.   
 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 69 of 83 
 
 
20. REFERENCES 
1. 
Flegal, K. M., Carroll, M. D., Kit, B. K. & Ogden, C. L. Prevalence of obesity and trends in the 
distribution of body mass index among US adults, 1999-2010. JAMA 307, 491–497 (2012). 
2. 
American Medical Association. AMA Resolution: Recognition of Obesity as a Disease. 420, (2013). 
3. 
Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in 
Adults--The Evidence Report. National Institutes of Health. Obes Res 6 Suppl 2, 51S–209S (1998). 
4. 
Guh, D. P. et al. The incidence of co-morbidities related to obesity and overweight: a systematic review 
and meta-analysis. BMC Public Health 9, 88 (2009). 
5. 
Bray, G. A. Medical consequences of obesity. J Clin Endocrinol Metab 89, 2583–2589 (2004). 
6. 
Peeters, A. et al. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. 
Ann Intern Med 138, 24–32 (2003). 
7. 
Orchard, T. J. et al. The effect of metformin and intensive lifestyle intervention on the metabolic 
syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med 142, 611–619 (2005). 
8. 
Hong, K., Li, Z., Wang, H. J., Elashoff, R. & Heber, D. Analysis of weight loss outcomes using VLCD 
in black and white overweight and obese women with and without metabolic syndrome. Int J Obes 29, 
436–442 (2005). 
9. 
Case, C. C., Jones, P. H., Nelson, K., O’Brian Smith, E. & Ballantyne, C. M. Impact of weight loss on 
the metabolic syndrome. Diabetes Obes Metab 4, 407–414 (2002). 
10. 
Carvajal, R., Wadden, T. A., Tsai, A. G., Peck, K. & Moran, C. H. Managing obesity in primary care 
practice: a narrative review. Ann N Y Acad Sci 1281, 191–206 (2013). 
11. 
Moyer, V. A. & Force, U. S. P. S. T. Screening for and management of obesity in adults: U.S. 
Preventive Services Task Force recommendation statement. Ann Intern Med 157, 373–378 (2012). 
12. 
Knowler, W. C. et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or 
metformin. N Engl J Med 346, 393–403 (2002). 
13. 
Sjostrom, L. et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N 
Engl J Med 351, 2683–2693 (2004). 
14. 
Wing, R. R. et al. Benefits of modest weight loss in improving cardiovascular risk factors in 
overweight and obese individuals with type 2 diabetes. Diabetes Care 34, 1481–1486 (2011). 
15. 
Jensen, M. D. et al. 2013 AHA / ACC / TOS Guideline for the Management of Overweight and 
Obesity in Adults : A Report of the American College of Cardiology / American Heart Association 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 70 of 83 
 
 
Task Force on Practice Guidelines and The Obesity Society World Wide Web at : 2013 AHA / AC. 
(2013). 
16. 
Wadden, T. A. et al. A two-year randomized trial of obesity treatment in primary care practice. N Engl 
J Med 365, 1969–1979 (2011). 
17. 
Yanovski, S. Z. & Yanovski, J. A. Long-term Drug Treatment for Obesity: A Systematic and Clinical 
Review. JAMA (2013). doi:10.1001/jama.2013.281361 
18. 
Sjostrom, L., Narbro, K., Sjostrom, C. D. & et, al. Effects of bariatric surgery mortality in Swedish 
Obese Subjects. N. Engl. J. Med. 357, 741–752 (2007). 
19. 
Courcoulas, A. P. et al. Weight change and health outcomes at 3 years after bariatric surgery among 
individuals with severe obesity. JAMA 310, 2416–25 (2013). 
20. 
Colquitt, J. L., Picot, J., Loveman, E. & Clegg, A. J. Surgery for obesity. Cochrane Database Syst Rev 
CD003641 (2009). doi:10.1002/14651858.CD003641.pub3 
21. 
Thaisetthawatkul, P., Collazo-Clavell, M. L., Sarr, M. G., Norell, J. E. & Dyck, P. J. A controlled study 
of peripheral neuropathy after bariatric surgery. Neurology 63, 1462–1470 (2004). 
22. 
Mechanick, J. I. et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and 
nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American 
Association of Clinical Endocrinologists, The Obesity Society, and American Society f. Obes. (Silver 
Spring) 21 Suppl 1, S1–27 (2013). 
23. 
Sarwer, D. B. et al. Attitudes about the safety and efficacy of bariatric surgery among patients with 
type 2 diabetes and a body mass index of 30-40 kg/m2. Surg Obes Relat Dis 9, 630–635 (2013). 
24. 
Imaz, I., Martinez-Cervell, C., Garcia-Alvarez, E. E., Sendra-Gutierrez, J. M. & Gonzalez-Enriquez, J. 
Safety and effectiveness of the intragastric balloon for obesity. A meta-analysis. Obes Surg 18, 841–
846 (2008). 
25. 
Fuller, N. R. et al. An intragastric balloon in the treatment of obese individuals with metabolic 
syndrome: a randomized controlled study. Obes. (Silver Spring) 21, 1561–1570 (2013). 
26. 
Genco, A. et al. Multi-centre European experience with intragastric balloon in overweight populations: 
13 years of experience. Obes Surg 23, 515–521 (2013). 
27. 
Crosby, R. D., Kolotkin, R. L. & Williams, G. R. An integrated method to determine meaningful 
changes in health-related quality of life. J. Clin. Epidemiol. 57, 1153–60 (2004). 
28. 
Carey, V. J. et al. Body Fat Distribution and Risk of Non-lnsulin-dependent Diabetes Mellitus in 
Women. Am J Epidemiol. 145, 614–619 (1997). 
29. 
Sarwer DB. in Bariatr. Surg. (Block AR & Sarwer DB) (AMERICAN PSYCHOLOGICAL 
ASSOCIATION, 2013). 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 71 of 83 
 
 
30. 
Himpens, J. et al. Long-term outcomes of laparoscopic adjustable gastric banding. Arch. Surg. 146, 
802–7 (2011). 
31. 
Lanza, F. L., Chan, F. K. L. & Quigley, E. M. M. Guidelines for prevention of NSAID-related ulcer 
complications. Am. J. Gastroenterol. 104, 728–38 (2009). 
32. 
The Look Ahead Research Group. Eight-year weight losses with an intensive lifestyle intervention: The 
Look AHEAD Study. Obes. (Silver Spring) 22, 5–13 (2014). 
33. 
Greenway, F. L. et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese 
adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 376, 
595–605 (2010). 
34. 
Kolotkin, R. L., Head, S., Hamilton, M. & Tse, C. K. Assessing Impact of Weight on Quality of Life. 
Obes Res 3, 49–56 (1995). 
35. 
Rubin, D. B. Multiple Imputation for Nonresponse in Surveys. (Wiley&Sons, 1987). 
36. 
Alberti, K. G. M. M. et al. Harmonizing the metabolic syndrome: a joint interim statement of the 
International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, 
and Blood Institute; American Heart Association; World Heart Federation; International . Circulation 
120, 1640–5 (2009).  
 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 72 of 83 
 
 
APPENDIX A:  DEFINITIONS AND ACRONYMS 
1. ACC: American College of Cardiology 
2. ADHD: Attention Deficit Hyperactivity Disorder 
3. Adverse Events (AEs): Any untoward medical occurrence in a clinical investigation subject that may 
occur during any part of the clinical study. This definition includes events occurring during the 
procedure and through the follow-up period whether related to the investigational device or not.  
Pre-existing conditions are not reported as AEs unless there has been a worsening in severity or 
frequency which cannot be attributed to the disease’s natural history or progression. Protocol-defined 
follow up visits and pre-scheduled endoscopies (including device placement/removal, patient 
surveillance and planned diagnostic endoscopies) are not considered adverse events. 
4. Adverse Events Severity:  
a. Mild: Causes no limitation of usual activities, may or may not require treatment and resolves 
with no permanent consequence.  
b. Moderate: Interferes temporarily and causes some limitation of usual activities and most 
often requires treatment.  
c. Severe: Prevents or severely limits usual activities 
5. Adverse Device Effect (ADE):  An adverse event that is considered possibly-related or related to the 
device.  
6. AE stabilization: when the AE (in the investigator’s opinion) is not likely to improve or worsen 
7. AHA: America Heart Association 
8. Anemia: hemoglobin <11.0 g/dl for female and <12.0 g/dl for male 
9. BG: Blood Glucose 
10. BIB: BioEnterics Intragastric Balloon 
11. BMI:  Body Mass Index 
12. CBC:   Complete Blood Count 
13. CEC: Clinical Event Committee 
14. DSMB: Data Safety Monitoring Board 
15. eCRFs:  Electronic Case Report Forms 
16. EKG: Electrocardiogram 
17. Enrolled: when subject has given written informed consent and the TPSS Access Sheath has been 
placed in the subject 
18. EWL: Excess Weight Loss 
19. GBP: Gastric Bypass 
20. GERD: Gastroesophageal Reflux Disease 
21. GI: Gastrointestinal 
22. HbA1c: Glycated haemoglobin (A1c) 
23. HDL: High-density lipoprotein 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 73 of 83 
 
 
24. Hgb: Hemoglobin 
25. HOMA: Homeostasis Model Assessment.  
26. hsCRP: High sensitivity C-reactive protein 
27. Hypertension: arterial blood pressure > 140 mmHg systolic or > 90 mmHg diastolic 
28. (Uncontrolled) hypertension: systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 
mmHg  
29. Hypoglycemia Classification (from the American Diabetes Association).  
a. Severe hypoglycemia: 
An event requiring assistance of another person to actively administer carbohydrate, glucagon, or other 
resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce 
seizure or coma. Plasma glucose measurements may not be available during such an event, but 
neurological recovery attributable to the restoration of plasma glucose to normal is considered 
sufficient evidence that the event was induced by a low plasma glucose concentration. 
b. Non-Severe hypoglycemia: 
• 
Documented symptomatic hypoglycemia: An event during which typical symptoms of 
hypoglycemia are accompanied by a measured plasma glucose concentration less than or 
equal to 70 mg/dL. 
• 
Asymptomatic hypoglycemia: An event not accompanied by typical symptoms of 
hypoglycemia but with a measured plasma glucose concentration less than or equal to 70 
mg/dL. 
• 
Probable symptomatic hypoglycemia: An event during which symptoms of hypoglycemia are 
not accompanied by a plasma glucose determination, but the event was presumably caused by 
a measured plasma glucose concentration less than or equal to 70 mg/dL. 
• 
Relative hypoglycemia: An event during which the person with diabetes reports any of the 
typical symptoms of hypoglycemia, and interprets the symptoms as indicative of 
hypoglycemia, but with a measured plasma glucose concentration greater than 70 mg/dL. This 
classification subcategory reflects the fact that subjects with chronically poor glycemic control 
can experience symptoms of hypoglycemia at plasma glucose levels greater than 70 mg/dL as 
plasma glucose concentrations decline toward that level. 
 
30. IFU:  Instructions for Use 
31. Index Procedure: The TPS placement or sham TPS placement procedure  
32. IRB: Institutional Review Board 
33. ITT: Intent to Treat  
34. IWQOL-Lite: The Impact of Weight on Quality of Life-Lite Questionnaire 
35. K-M: Kaplan-Meier 
36. LOCF: Last Observation Carried Forward 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 74 of 83 
 
 
37. MAC: Monitored Anesthesia Care, refers to the anesthesia personnel presenting during a procedure. It 
includes all aspects of anesthesia care–a pre-procedure visit, intra-procedure care and post-procedure 
anesthesia management 
38. Metabolic syndrome: Defined by the presence of at least 3 of the following 5 risk factors according 
to AHA/NHLBI guideline36 
1) Fasting glucose ≥100 mg/dL, or receiving drug therapy for hyperglycemia 
2) Blood pressure ≥130 mm Hg systolic and/or ≥85 mm Hg diastolic, or receiving drug therapy 
for hypertension 
3) Triglycerides ≥150 mg/d (1.7 mmol/L), or receiving drug therapy for hypertriglyceridemia 
4) HDL-C < 40 mg/d (1.0 mmol/L) in men or < 50 mg/dL(1.3 mmol/L) in women, or receiving 
drug therapy for reduced HDL-C 
5) Waist circumference ≥102 cm (40 in) in men or ≥88 cm (35 in) in women 
39. NPO: nil per os, nothing by mouth 
40. LAGB: Laparoscopic Adjustable Gastric Band 
41. LDL: Low-density lipoprotein 
42. NSAIDs: Non-steroidal anti-inflammatory drugs 
43. Obesity Class: moderate (Class I, BMI 30.0 – 34.9), severe (Class II, BMI 35.0 – 39.9), and very 
severe (Class III, BMI > 40) 
44. OTC:  Over the Counter 
45. PCP: Primary care provider 
46. POWER-UP: Practice-based Opportunities for Weight Reduction trial at the University of 
Pennsylvania 
47. % TBL: Percent Total Body Weight Loss, calculated as:  
a. (Weight(kg)BL – Weight(kg)FUP)/Weight(kg)BL 
b. Where Weight(kg)BL is the subject’s weight at baseline in kilograms and Weight(kg)FUP is 
the subject’s weight at follow-up in kilograms. 
48. PHQ-9:  Patient Health Questionnaire 9 
49. PPIs:  Proton Pump Inhibitors 
50. PTFE: Polytetrafluroroethylene 
51. RYGB: Roux-en-Y Gastric Bypass 
52. SSC: Study Steering Committee 
53. SADE: Serious Adverse Device Effect  
54. SAE: Serious Adverse Event:  defined as an adverse event that  
a. led to a death 
b. led to a serious deterioration in health resulting in  
i. a life threatening illness or injury 
ii. a permanent impairment of a body structure or body function 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
 
Protocol No. DTC006 
 
 
 
Sheet 75 of 83 
 
 
iii. in-patient hospitalization (>24 hours) or prolongation of an existing hospitalization  
iv. requires medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment of a body structure or body function 
c. led to fetal distress, fetal death or a congenital abnormality or birth defect 
55. SOS: Swedish Obesity Study 
56. TOS: The Obesity Society 
57. TPS: TransPyloric Shuttle 
58. TPSS: TransPyloric Shuttle System 
59. VBG: Vertical Banded Gastroplasty 
60. UADE: unanticipated adverse device effect are any serious adverse device effects on health, safety 
or any life-threatening problem or death caused by, or associated with the investigational study 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 IFU) or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects.   
61. Ulcer:  defined as a defect in the gastric or duodenal wall ≥ 5mm in diameter with unequivocal depth. 
62. (Prolonged) vomiting: more than 4-6 times in 24 hours 
63. (Recurrent) vomiting: every day over 3-5 days 
64. Weight Stability: a < 5% change in body weight for at least 3 months prior to the screening visit 
  

 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® System:  A Multicenter, Prospective, Randomized, 
Double-Blind, Sham-Controlled, Parallel-Design Study (ENDObesity® II Study) 
 
Protocol No. DTC006 Rev. E (DCN-0826) 
 
 
 
Sheet 76 of 83 
 
 
 
 
APPENDIX B: SCHEDULE OF EVENTS 
1 – Abbreviated physical:  temperature, systolic/diastolic blood pressure, respiration rate, heart rate 
2 -- Blood tests include lipid panel, fasting blood glucose, insulin, HbA1c, C - reactive protein 
3 – For Treatment group only  
4 – Until discontinued 
 
Visit 
Screen 
Baseline 
Index 
Procedure 
1wk 
1M 
2M 
4M 
6M 
7M 
8M 
9M 
10M 
11M 
12M 
Evaluation 
Days 
Within 
56 days 
Within 7 
days 
Day 0 
D7 
±2 
D30 
±7 
D60 
±14 
D120 
±14 
D180 
±14 
D210 
±7 
D240 
±7 
D270 
±21 
D300 
±7 
D330 
-14 
D365
±30 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Current medication 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
Psychological evaluation 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Exclusion criteria (general) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Exclusion criteria (endoscopic) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Lifestyle counseling  
 
X 
 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
Follow up telephone call 
 
 
 
 
 
 
 
 
X 
X 
 
X 
X 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
BMI 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
Body circumference 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
Physical exam 
X 
X1 
X1 
X1 
X1 
X1 
X1 
X1 
 
 
X1 
 
 
X 
EKG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC w/differential 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistry panel 20 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Blood tests2   
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
Urine pregnancy test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Stool H pylori test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient Health Questionnaire 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
IWQOL-Lite 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
Satiety Assessments (VAS & 
Eating Inventory) 
 
X 
 
X 
X 
 
 
X 
 
 
 
 
 
X 
Endoscopic assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event assessment 
 
 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
Blinding assessment 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
Device removal 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Study exit 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
Protocol No. DTC006 Rev. E (DCN-0826) 
 
 
 
Sheet 77 of 83 
 
 
 
 
APPENDIX C: LIFESTYLE MODIFICATIONS PROGRAM...REDACTED 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
Protocol No. DTC006 Rev. E (DCN-0826) 
 
 
 
Sheet 78 of 83 
 
 
 
 
APPENDIX D: BMI CALCULATOR 
 
To calculate the subject’s Body Mass Index, using the website below:  
http://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htmEnter the subjects Weight and 
Height and then calculate BMI (print screen for source documentation)  
Formulas used to calculate Body Mass Index:  
 
English BMI Formula  
BMI = Weight in pounds/ (height in inches x height in inches) x 703  
 
Metric BMI Formula  
BMI = Weight in kilograms/ (height in meters x height in meters)  
Note that BMI may also be calculated within the eCRF. 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
Protocol No. DTC006 Rev. E (DCN-0826) 
 
 
 
Sheet 79 of 83 
 
 
 
 
APPENDIX E:  SAMPLE OF PATIENT HEALTH QUESTIONAIRE (PHQ-9)… REDACTED 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
Protocol No. DTC006 Rev. E (DCN-0826) 
 
 
 
Sheet 80 of 83 
 
 
 
 
 
APPENDIX F: IWQOL – LITE…REDACTED 
 
 
 
 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
Protocol No. DTC006 Rev. E (DCN-0826) 
 
 
 
Sheet 81 of 83 
 
 
 
 
APPENDIX G: SAMPLE OF SUBJECT INFORMATION CARD 
 
<< Front of the Card>> 
 
 
If you are required to see your doctor for other medical conditions, please show this card to your doctor.  
PLEASE CARRY THIS CARD AT ALL TIMES 
 
Patient Card for the ENDObesity® II Study 
 
Model #:  ______________________________ 
 
 
Device Lot #:  ___________________________ 
 
 
Date of Implant:  _________________________ 
 
 
Investigator Physician’s contact information:  _______________________ at (XXX) XXX-XXXX 
 
*This person is participating in a double-blind weight loss study and may or may not have a TransPyloric Shuttle® in 
his/her stomach. The TransPyloric Shuttle may slow down the food and medication from passing through stomach. For 
questions regarding the TransPyloric Shuttle and the ENDObesity II Study, please contact the Investigator. Please do not 
disclose to the subject any findings that may indicate randomization assignment without discussion with the Investigator.  
------------------------------------------------------------------------------------------------------------------------------------ 
 BAROnova, Inc., 1509 Industrial Road, San Carlos, CA 94070, USA, Telephone: (844) 870-6682 
 
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
<< Back of the Card>> 
 
 
MRI SAFETY INFORMATION 
 
Non-clinical testing has demonstrated the BAROnova TransPyloric Shuttle® (TPS) is MR Conditional. 
A patient with this device can be safely scanned in an MR system meeting the following conditions: 
• 
Static magnetic field of 3-Tesla or less 
• 
Maximum spatial field gradient of 4,000 gauss/cm (40 T/m) 
• 
Maximum MR system reported, whole body averaged specific absorption rate (SAR) of 4 W/kg (First 
Level Controlled Operating Mode) 
 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
Protocol No. DTC006 Rev. E (DCN-0826) 
 
 
 
Sheet 82 of 83 
 
 
 
 
APPENDIX H: SAMPLE OF CONTROL OF EATING QUESTIONAIRE…REDACTED 
 
 

 
 
Endoscopic Treatment for Weight Reduction in Patients with Obesity Using the TransPyloric Shuttle® 
System:  A Multicenter, Prospective, Randomized, Double-Blind, Sham-Controlled, Parallel-Design  
Study (ENDObesity® II Study) 
 
 
Protocol No. DTC006 Rev. E (DCN-0826) 
 
 
 
Sheet 83 of 83 
 
 
 
 
APPENDIX I: EATING INVENTORY…REDACTED