XprESS Eustachian Tube Dilation Study
Phase: NA
Conditions: Eustachian Tube Dysfunction
Sponsor: Entellus Medical, Inc.

 
 
 
 
 
XprESS Eustachian Tube Dilation Study 
 
 
Investigational Plan Number 2909-001 
 
REVISION C 
September 2015 
 
 
Entellus Medical Inc. 
3600 Holly Lane North, Suite 40 
Plymouth, MN 55447 
 
 
This study will be conducted in accordance with the protocol and applicable regulatory 
requirements. 
 
 
CONFIDENTIAL INFORMATION 
No use or disclosure of information contained within this document is permitted without prior 
written authorization from Entellus Medical Inc. 
 

Clinical Investigational Plan 
 
Page ii 
2909-001 Rev C. 
Entellus Medical Confidential 
Study Contact Information 
 
Study Sponsor: 
Entellus Medical Inc. 
3600 Holly Lane North, Suite 40 
Plymouth, MN 55447 
 
Study Contact: 
Robyn Schacherer 
Entellus Medical Inc. 
3600 Holly Lane North, Suite 40 
Plymouth, MN 55447 
Phone: (763) 463-7054 
Fax: 
(763) 463-1599 
E-mail: rschacherer@entellusmedical.com  
 
 

Clinical Investigational Plan 
 
Page iii 
2909-001 Rev C. 
Entellus Medical Confidential 
Investigational Plan Summary 
Title: 
XprESS Eustachian Tube Dilation Study 
Study device: 
XprESS™ Multi-Sinus Dilation System (XprESS device) 
Study design: 
A prospective, multicenter, 2-phase, controlled study. Phase 1 consists of a 
nonrandomized design. Phase 2 consists of a randomized design.  
Enrollment: 
A total of 50 subjects: 
Phase 1 – 10 nonrandomized balloon dilation subjects 
Phase 2 – 40 subjects randomized 1:1 to balloon dilation (treatment) or 
continued current medical therapy (control) 
Treatment: 
Phase 1: All subjects will receive balloon dilation 
Phase 2: Subjects will be randomized 1:1 to the following study arms: 
1. Control arm: Continued current medical management with ability to 
crossover to dilation after 6 weeks, if not improved 
2. Treatment arm: Eustachian tube dilation – bilateral or unilateral, as 
indicated 
Clinical centers: 
Up to 7 US investigational centers  
Inclusion 
criteria: 
Subjects MUST: 
1. Be ≥18 years old 
2. Have been diagnosed with Eustachian tube dysfunction (ETD) for no less 
than 12 months before enrollment with 3 or more of the following 
symptoms: ear pain, ear pressure, ringing in the ears, cracking or popping 
sounds in the ears, muffled hearing, or feeling that ears are clogged or 
“under water” 
3. Have an overall ETDQ-7 score ≥3.0 
4. Have a record of failed medical management for ETD consisting of a 
minimum of either 4 weeks of daily intranasal steroid spray or 1 completed 
course of an oral steroid within the 12-month period before enrollment 
5. Be a candidate for unilateral or bilateral transnasal balloon Eustachian tube 
dilation using the XprESS device 
6. Have a temporal bone CT scan (showing the Eustachian tube) without 
contrast within 6 months of the enrollment date 
7. Be able to read and understand English 
8. Be able and willing to provide consent 
9. Be willing to comply with the protocol requirements 
Exclusion 
criteria: 
Subjects MUST NOT: 
1. Have had any head or neck surgery (eg, adenoidectomy, tonsillectomy) 
including sinonasal surgery or ear tube placement performed within 3 
months before enrollment 
2. Require concomitant procedures at the time of study enrollment or 
procedure 
3. Have ear tubes in place (tympanostomy tubes, myringotomy tubes, 
ventilation tubes, or pressure equalization tubes) or perforation of the 
tympanic membrane at the time of the study enrollment or procedure 
(patients with healed tympanic membranes after extrusion of tubes are not 
excluded) 

Clinical Investigational Plan 
 
Page iv 
2909-001 Rev C. 
Entellus Medical Confidential 
4. Have patulous Eustachian tubes 
5. Have had any previous laser tuboplasty surgery or microdebridement 
6. Have temporomandibular joint (TMJ) disorders 
7. Have early hydrops (Meniere’s disease) 
8. Have had head or neck radiation therapy or sinonasal malignancy 
9. Have a diagnosis of chronic rhinosinusitis (CRS/RARS) that is 
uncontrolled 
10. Have an immunodeficiency 
11. Have craniofacial abnormalities or other anatomical conditions (eg, 
severely deviated septum, tumor, enlarged adenoids or tonsils, severe 
turbinate hypertrophy) that would prevent transnasal access of the 
Eustachian tubes 
12. Have evidence of internal carotid artery dehiscence or anatomic 
abnormalities 
13. Have uncontrolled allergies 
14. Have unmanaged gastroeosophageal reflux disease (GERD) or 
laryngopharyngeal reflux (LPR) 
15. Be pregnant at the time of study enrollment or procedure 
16. Be currently participating in any other drug or device clinical studies 
excluding postapproval or marketing registry studies 
Objective:  
To demonstrate the safety and efficacy of the XprESS device in treating 
patients with ETD. 
Primary  
endpoints: 
• Comparison of mean change in overall ETDQ-7 scores from baseline to 6 
weeks between randomization arms  
• Complication rate 
Secondary 
endpoints: 
• Mean change in overall ETDQ-7 score from baseline to follow-up (balloon 
dilation subjects) 
• Technical success rate 
• Revision dilation rate 
Study 
assessments 
• 
Baseline 
• 
6-Week crossover evaluation (control subjects only) 
• 
Procedure 
• 
6-Week postprocedure follow-up 
• 
3-Month postprocedure follow-up  
• 
6-Month postprocedure follow-up (for 510(k) submission and publication 
purposes) 
• 
12-Month postprocedure follow-up (for publication purposes) 
Sponsor: 
Entellus Medical Inc. 
United States 
Data 
management and 
monitoring: 
Entellus Medical Inc. 
United States 

Clinical Investigational Plan 
 
Page v 
2909-001 Rev C. 
Entellus Medical Confidential 
Abbreviations and Acronyms 
AE 
Adverse event 
ANSI 
American National Standards Institute 
CFR 
Code of Federal Regulations (US) 
CI 
Confidence interval 
CRF 
Case report form 
CRS/RARS 
Chronic rhinosinusitis/recurrent acute rhinosinusitis 
CT 
Computed tomography 
DICOM 
Digital Imaging and Communications in Medicine 
ENT 
Ear, nose, and throat 
EQ-5D 
EuroQol-5 dimension survey 
ET 
Eustachian tube 
ETD 
Eustachian tube dysfunction 
ETDQ-7 
Eustachian tube dysfunction 7-item questionnaire 
FDA 
Food and Drug Administration (US) 
GCP 
Good clinical practices 
GERD 
Gastroesophageal reflux disease 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 (US) 
ICF 
Informed consent form 
IFU 
Instructions for use 
IRB 
Institutional Review Board 
LPR 
Laryngopharyngeal reflux 
PTA 
Pure tone audiometry 
SAE 
Serious adverse event 
UADE 
Unanticipated adverse device effect 
VAS 
Visual analog scale 
 

ETD Clinical Investigational Plan 
 
Page 6 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
 
Table of Contents 
Study Contact Information .............................................................................................................. ii 
Investigational Plan Summary ....................................................................................................... iii 
Abbreviations and Acronyms ......................................................................................................... v 
1 
Background and Purpose ........................................................................................................ 8 
1.1 
Background ...................................................................................................................... 8 
1.2 
Purpose ............................................................................................................................. 8 
2 
Protocol ................................................................................................................................... 9 
2.1 
Study design ..................................................................................................................... 9 
2.2 
Study objective ............................................................................................................... 10 
2.3 
Study endpoints .............................................................................................................. 10 
2.3.1 
Primary endpoints ................................................................................................... 10 
2.3.2 
Secondary endpoints ............................................................................................... 10 
2.4 
Study size and duration .................................................................................................. 10 
2.5 
Study hypothesis ............................................................................................................ 10 
2.6 
Sample size estimation ................................................................................................... 11 
2.7 
Data analyses .................................................................................................................. 11 
2.7.1 
Poolability analysis ................................................................................................. 11 
2.7.2 
Missing data ............................................................................................................ 12 
2.8 
Study population ............................................................................................................ 12 
2.8.1 
Inclusion criteria ..................................................................................................... 12 
2.8.2 
Exclusion criteria .................................................................................................... 12 
2.9 
Methods and procedures................................................................................................. 13 
2.9.1 
Eligibility assessment.............................................................................................. 14 
2.9.2 
Baseline visit ........................................................................................................... 14 
2.9.3 
Enrollment............................................................................................................... 15 
2.9.4 
Randomization ........................................................................................................ 15 
2.9.5 
Control arm assignment .......................................................................................... 15 
2.9.6 
Balloon dilation arm assignment and procedure ..................................................... 16 
2.9.7 
Follow-up visits ...................................................................................................... 17 
2.9.8 
Revision dilations or additional surgery ................................................................. 18 
2.9.9 
Early withdrawal and lost to follow-up .................................................................. 18 
2.9.10 End of study ............................................................................................................ 19 
2.10 Study assessments and data collection ........................................................................... 19 
2.10.1 Primary and secondary endpoint assessments ........................................................ 19 
2.10.2 Other measure assessments ..................................................................................... 20 
3 
Risk/Benefit Analysis ........................................................................................................... 23 
3.1 
Benefits........................................................................................................................... 23 
3.2 
Potential risks ................................................................................................................. 23 
3.3 
Risk mitigation ............................................................................................................... 23 
4 
Device Information ............................................................................................................... 24 
4.1 
Investigational device description .................................................................................. 24 
4.2 
Anticipated changes in device design ............................................................................ 24 
4.3 
Investigational device management ............................................................................... 24 
4.4 
Device malfunctions ....................................................................................................... 24 

Clinical Investigational Plan 
 
Page 7 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
5 
Monitoring Procedures.......................................................................................................... 25 
5.1 
Name and address of the Lead Monitor ......................................................................... 25 
5.2 
Investigators ................................................................................................................... 25 
5.3 
Investigational center monitoring................................................................................... 25 
6 
Adverse Event Definitions and Reporting ............................................................................ 26 
6.1 
Adverse events ............................................................................................................... 26 
6.2 
Serious adverse events ................................................................................................... 26 
6.3 
Unanticipated adverse device effects ............................................................................. 26 
6.4 
Assessing, recording, and reporting AEs, SAEs, and UADEs ....................................... 26 
7 
Protocol Deviations ............................................................................................................... 28 
8 
Labeling ................................................................................................................................ 29 
9 
Administrative Information .................................................................................................. 30 
9.1 
Investigational center selection ...................................................................................... 30 
9.2 
Training .......................................................................................................................... 30 
9.3 
Informed consent process ............................................................................................... 30 
9.4 
Confidentiality ................................................................................................................ 31 
9.5 
Institutional Review Board (IRB) .................................................................................. 31 
9.6 
Investigator responsibilities............................................................................................ 31 
9.7 
Sponsor responsibilities.................................................................................................. 32 
9.8 
Criteria for terminating study ......................................................................................... 32 
9.9 
Criteria for terminating an investigational center .......................................................... 32 
10 Reports and Records ............................................................................................................. 33 
10.1 Records ........................................................................................................................... 33 
10.2 Reporting requirements .................................................................................................. 33 
11 References ............................................................................................................................. 35 
 
Table of Tables 
Table 1. Phase 2 Study Assessment Schedule .............................................................................. 13 
Table 2. Preferred Frequency (Hz) Testing Sequence for Air-bone Conduction Tests ................ 22 
Table 3. Summary of Investigator Reporting Requirements ........................................................ 33 
Table 4. Summary of Sponsor Reporting Requirements .............................................................. 34 
 
 
 

Clinical Investigational Plan 
 
Page 8 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
1 Background and Purpose 
1.1 Background 
The Eustachian tube (ET) connects the middle ear to the nasopharynx. It serves 3 functions: 
pressure regulation, deflection of pathogens/foreign objects, and middle ear fluid clearance.1 The 
ET is comprised of a bony isthmus and a cartilaginous region. The cartilaginous part of the ET is 
normally closed but opens when needed to equalize pressure within the middle ear. Transient 
opening of the ET occurs with yawning, swallowing, or popping of the ears. 
Dysfunction of the Eustachian tube can result from the tube being too open (patulous ET), too 
closed (mechanical obstruction), or unable to efficiently open during swallowing (functional 
obstruction).2 Mechanical obstruction of the ET can be from either extrinsic (eg, tumors, 
adenoids, nasal septal deviations) or intrinsic (eg, inflammation, stenosis) mechanisms. 
Functional obstruction, a common cause of Eustachian tube dysfunction (ETD), occurs when the 
tube fails to open in the absence of a mechanical obstruction and can be caused by increased 
tubal compliance, inefficient opening mechanism, and/or abnormal pressures at either ET end.2  
When the ET does not function properly there is abnormal pressure equalization in the middle 
ear. Symptoms of ETD include fullness in the ear, dizziness, tinnitus, and pain or discomfort 
with barometric changes (eg, flying, diving). ETD can lead to tympanic membrane retraction, 
cholesteatoma, and hearing loss and is frequently associated with chronic otitis media. Chronic 
rhinosinusitis, allergic rhinitis, gastroesophageal reflux disease, and smoking exposure may all 
have roles in development of ETD. 
Historically, treatments have been geared toward management or prevention of otitis media, not 
correcting the dysfunction of the ET. Recently, research has been initiated to study the possibility 
that balloon dilation could offer a minimally invasive treatment for ETD. It is thought that ET 
balloon dilation increases the luminal diameter, reduces local inflammation, and facilitates the 
muscular action necessary for ET opening.3 Theoretically, balloon dilation results in minimal 
mucosal injury, sparing the clearance and protective functions of the ET, while improving 
pressure equalization within the middle ear. 
1.2 Purpose 
The purpose of the current study is to collect 6-month safety and efficacy data on the use of the 
XprESS device to support a 510(k) application to FDA to add a new indication for use. Six- and 
12-month data will also be collected for publication purposes. 
 
 

Clinical Investigational Plan 
 
Page 9 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
2 Protocol 
2.1 Study design 
The study is a prospective, multicenter, 2-phase, controlled study. Phase 1 will include 10 
subjects treated with balloon dilation.  
Phase 2 will include 40 subjects randomized 1:1 to balloon dilation or control (6 weeks of 
continued current medical therapy). Phase 2 is designed to test the primary efficacy endpoint 
hypothesis that ETD symptom improvement (overall ETDQ-7 score) after balloon dilation is 
superior to the control group. For subjects randomized to the control arm, if ETD symptoms 
persist at 6 weeks after randomization (overall ETDQ-7 score ≥3.0 or change <0.4), the subjects 
will be allowed to crossover to the balloon dilation arm. Control subjects who do not have 
persistent ETD symptoms at 6 weeks after randomization will be exited from the study. Figure 1 
presents the study design and subject flow for Phase 2. 
 
Baseline assessment 
Balloon Dilation 
Inclusion/exclusion criteria 
Control: 
6 weeks continued current medical therapy 
Randomization 
1:1 
6-Week crossover evaluation 
Exit study 
6-Week postprocedure visit 
3-Month postprocedure visit 
6-Month postprocedure visit 
12-Month postprocedure visit 
Exit study 
Figure 1. Phase 2 Study Design and Subject Flow 
Overall ETDQ-7 ≥3.0 
or change <0.4 
No 
Yes 
Crossover 

&OLQLFDO,QYHVWLJDWLRQDO3ODQ
3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
2.2 Study objective 
7KHSULPDU\REMHFWLYHRIWKHVWXG\LVWRGHPRQVWUDWHWKHVDIHW\DQGHIILFDF\RIWKH;SU(66
GHYLFHIRUWUHDWLQJ SDWLHQWVZLWK(XVWDFKLDQWXEHG\VIXQFWLRQ(7'
2.3 Study endpoints 
 Primary endpoints 
7KHIROORZLQJPHDVXUHVZLOOEHFROOHFWHGDVWKHSULPDU\HQGSRLQWV
x &RPSDULVRQRIPHDQFKDQJHLQRYHUDOO(7'4VFRUHIURPEDVHOLQHWRZHHNVEHWZHHQ
EDOORRQGLODWLRQDUPDQGFRQWURODUP
x &RPSOLFDWLRQUDWH
 Secondary endpoints 
7KHIROORZLQJPHDVXUHVZLOOEHFROOHFWHGDVVHFRQGDU\HQGSRLQWV
x 0HDQFKDQJHLQRYHUDOO(7'4VFRUHIURPEDVHOLQHWRIROORZXSEDOORRQGLODWLRQ
VXEMHFWV
x 7HFKQLFDOVXFFHVVUDWH
x 5HYLVLRQGLODWLRQUDWH
2.4 Study size and duration 
,QLWLDOO\XSWRVXEMHFWVZLOOEHHQUROOHGDWXSWR86LQYHVWLJDWLRQDOFHQWHUVDQGWUHDWHGZLWK
EDOORRQGLODWLRQSKDVH7KHVHFRQGSKDVHZLOOLQFOXGHHQUROOPHQWRIDQDGGLWLRQDOVXEMHFWV
UDQGRPL]HGWREDOORRQGLODWLRQRUFRQWLQXHGFXUUHQWPHGLFDOWKHUDS\FRQWURODWXSWR
LQYHVWLJDWLRQDOFHQWHUV$GGLWLRQDOVXEMHFWVPD\EHDGGHGDVQHHGHGXSRQDSSURYDOIURP)'$
,WLVDQWLFLSDWHGWKDWWKHILUVWVXEMHFWVIURPSKDVHZLOOEHSRROHGZLWKWKHUHPDLQLQJEDOORRQ
GLODWLRQVXEMHFWVIRUWKHILQDODQDO\VLVFRKRUWEDVHGRQVLPLODULQFOXVLRQH[FOXVLRQFULWHULDDQG
GDWDFROOHFWLRQ
7KHH[SHFWHGGXUDWLRQRIWKHVWXG\LVWRPRQWKV,WLVHVWLPDWHGWKDWHQUROOPHQWZLOOWDNH
IURPWRPRQWKV:KHQDPLQLPXPRISKDVHVXEMHFWVKDYHFRPSOHWHGZHHNVRI
IROORZXSDQGDPLQLPXPRISKDVHDQGSKDVHVXEMHFWVWUHDWHGZLWKEDOORRQGLODWLRQKDYH
FRPSOHWHGDWOHDVWPRQWKVRIIROORZXSDNDSSOLFDWLRQZLOOEHVXEPLWWHGWRWKH)'$WR
REWDLQFOHDUDQFHIRUWKHQHZLQGLFDWLRQ$OOWUHDWHGVXEMHFWVZLOOFRQWLQXHIROORZXSWKURXJK
PRQWKVIRUSXEOLFDWLRQSXUSRVHV&RQWUROVXEMHFWVZKRGRQRWFURVVRYHUWRWKHEDOORRQGLODWLRQ
WUHDWPHQWZLOOEHH[LWHGIURPWKHVWXG\DWZHHNVDIWHUUDQGRPL]DWLRQ
2.5 Study hypothesis 
7KHVWXG\LVGHVLJQHGWRWHVWWKHSULPDU\HIILFDF\HQGSRLQWK\SRWKHVLVWKDW(7'V\PSWRP
LPSURYHPHQWDIWHUEDOORRQGLODWLRQLVVXSHULRUWRWKHFRQWUROJURXS
7KHIROORZLQJK\SRWKHVLVZLOOEHWHVWHGLQWKHFRPSDULVRQRIPHDQFKDQJHIURPEDVHOLQHLQ
RYHUDOO(7'4VFRUHVDWZHHNVXVLQJDVLGHG6WXGHQW¶VWWHVWZKHUHDSYDOXHOHVVWKDQ
ZLOOEHFRQVLGHUHGVWDWLVWLFDOO\VLJQLILFDQW

&OLQLFDO,QYHVWLJDWLRQDO3ODQ
3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
+RG
+DG
:KHUHGLVWKHGLIIHUHQFHEHWZHHQEDOORRQGLODWLRQDQGFRQWUROJURXSEDOORRQGLODWLRQ±
FRQWUROIRUWKHPHDQFKDQJHIURPEDVHOLQHWRZHHNVLQWKHRYHUDOO(7'4VFRUH
2.6 Sample size estimation 
7KHVDPSOHVL]HZDVFDOFXODWHGXVLQJ3$66,QHTXDOLW\7HVWVIRU7ZR0HDQVVDPSOHWWHVWWR
WHVWIRUVXSHULRULW\RILPSURYHPHQWRI(7'4VFRUHVDWZHHNVDQGZDVEDVHGRQWKHIROORZLQJ
DVVXPSWLRQV
x 6LJQLILFDQFHOHYHOVLGHGDOSKD 
x 3RZHU 
x 0HDQFKDQJHLQRYHUDOO(7'4VFRUHLQWKHEDOORRQGLODWLRQJURXS 
x 0HDQFKDQJHLQRYHUDOO(7'4VFRUHLQFRQWUROJURXS 
x &RPPRQVWDQGDUGGHYLDWLRQIRUERWKJURXSV 
8QGHUWKHDVVXPSWLRQVRXWOLQHGDERYHDWRWDOVDPSOHVL]HRIUDQGRPL]HGVXEMHFWVSHU
DUPLVDGHTXDWHWRWHVWWKLVK\SRWKHVLV7RDFFRXQWIRUXSWRDWWULWLRQDPLQLPXPRI
VXEMHFWVZLOOEHHQUROOHGLQ3KDVHRIWKHVWXG\
2.7 Data analyses 
6XPPDU\VWDWLVWLFVZLOOEHFDOFXODWHGIRUDOOVWXG\HQGSRLQWV&DWHJRULFDOYDULDEOHVZLOOEH
VXPPDUL]HGXVLQJIUHTXHQF\GLVWULEXWLRQVDQGFRQWLQXRXVYDULDEOHVZLOOEHVXPPDUL]HGZLWK
PHDQVVWDQGDUGGHYLDWLRQVDQGUDQJHV&RQILGHQFHLQWHUYDOV&,PD\EHFRPSXWHGIRU
VHOHFWVWXG\HQGSRLQWPHDVXUHV7KHSULPDU\HIILFDF\HQGSRLQWZLOOEHWHVWHGDWDVLGHGDOSKD
OHYHORI7KHVHFRQGDU\HQGSRLQWRIWKHPHDQFKDQJHLQWKHRYHUDOO(7'4VFRUHIURP
EDVHOLQHWRIROORZXSLQVXEMHFWVWUHDWHGZLWKEDOORRQGLODWLRQZLOOEHWHVWHGDWDVLGHGDOSKD
OHYHORI
6XEMHFWVZKRDUHUDQGRPL]HGEXWGURSRXWEHIRUHUHFHLYLQJWKHLUUDQGRPL]HGWUHDWPHQWEDOORRQ
GLODWLRQRUFRPSOHWLRQRIWKHZHHNFRQWLQXHGPHGLFDOWKHUDS\ZLOOQRWEHLQFOXGHGLQWKHGDWD
DQDO\VLV
 Poolability analysis 
3RRODELOLW\RIWKHSULPDU\HIILFDF\HQGSRLQWEHWZHHQLQYHVWLJDWLRQDOFHQWHUVZLOOEHHYDOXDWHG
7KLVDVVHVVPHQWZLOOHYDOXDWHWKHVLJQLILFDQFHRIDQ\GLIIHUHQFHVRULPEDODQFHVWKDWH[LVWDFURVV
LQYHVWLJDWLRQDOFHQWHUVLQWKHSULPDU\HQGSRLQW&HQWHUVZLWKOHVVWKDQSDWLHQWVHQUROOHGZLOOEH
FRPELQHGLQWRDSVHXGRFHQWHUIRUSXUSRVHVRIDQDO\VLV7RSURWHFWDJDLQVWKDYLQJDQRYHUO\ODUJH
SVHXGRFHQWHUZKHQRQHSVHXGRFHQWHUH[FHHGVVXEMHFWVDVHFRQGSVHXGRFHQWHUZLOOEHIRUPHG
7KLVSURFHVVZLOOFRQWLQXHDVQHHGHGHDFKWLPHDSVHXGRFHQWHUH[FHHGVVXEMHFWV
7KHW\SH,,,SYDOXHIURPDQ$129$PRGHOZLOOEHXVHGWRDVVHVVFHQWHUSRRODELOLW\IRUWKH
SULPDU\HIILFDF\HQGSRLQW$QDOSKDOHYHORIZLOOEHXVHGWRDVVHVVVWDWLVWLFDOVLJQLILFDQFHRI
WKHFHQWHUHIIHFW

&OLQLFDO,QYHVWLJDWLRQDO3ODQ
3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
 Missing data 
0LVVLQJGDWDFDQLPSDFWWKHLQWHJULW\DQGFUHGLELOLW\RIDQ\FOLQLFDOVWXG\7KHUHIRUHDOODWWHPSWV
ZLOOEHPDGHWRPLQLPL]HPLVVLQJGDWD7KHVHDWWHPSWVLQFOXGHWUDLQLQJRIWKHLQYHVWLJDWRUVDQG
VLWHSHUVRQQHODQGGLVFXVVLRQVZLWKWKHVXEMHFWVGXULQJWKHLQIRUPHGFRQVHQWSURFHVVRQWKH
LPSRUWDQFHRIDFFXUDWHDQGFRPSOHWHGDWDFROOHFWLRQ7KHVWXG\VSRQVRUZLOOWUDFNLVVXHVZLWK
VLWHVUHJDUGLQJPLVVLQJGDWDWKURXJKWKHXVXDOPRQLWRULQJSURFHVV$QDO\VHVWKDWDFFRXQWIRU
PLVVLQJGDWDZLOOEHFRQGXFWHGRQWKHSULPDU\HIILFDF\HQGSRLQWIRUDFKDQJHIURPEDVHOLQH
2.8 Study population 
7KHVWXG\SRSXODWLRQLVSDWLHQWV\HDUVDQGROGHUZLWKPHGLFDOO\UHIUDFWRU\(7'7REH
HOLJLEOHIRUHQUROOPHQWLQWKHVWXG\WKHSDWLHQWVPXVWPHHWDOOWKHLQFOXVLRQFULWHULDDQGQRQHRI
WKHH[FOXVLRQFULWHULD
 Inclusion criteria 
6XEMHFWV0867

%H\HDUVROG

+DYHEHHQGLDJQRVHGZLWK(7'IRUQROHVVWKDQPRQWKVEHIRUHHQUROOPHQWZLWKRU
PRUHRIWKHIROORZLQJV\PSWRPVHDUSDLQHDUSUHVVXUHULQJLQJLQWKHHDUVFUDFNLQJRU
SRSSLQJVRXQGVLQWKHHDUVPXIIOHGKHDULQJRUIHHOLQJWKDWHDUVDUHFORJJHGRU³XQGHU
ZDWHU´

+DYHDQRYHUDOO(7'4VFRUH

+DYHDUHFRUGRIIDLOHGPHGLFDOPDQDJHPHQWIRU(7'FRQVLVWLQJRIDPLQLPXPRI
HLWKHUZHHNVRIGDLO\LQWUDQDVDOVWHURLGVSUD\RUFRPSOHWHGFRXUVHRIDQRUDOVWHURLG
ZLWKLQWKHPRQWKSHULRGEHIRUHHQUROOPHQW

%HDFDQGLGDWHIRUXQLODWHUDORUELODWHUDOWUDQVQDVDOEDOORRQ(XVWDFKLDQWXEHGLODWLRQ
XVLQJWKH;SU(66GHYLFH

+DYHDWHPSRUDOERQH&7VFDQVKRZLQJWKH(XVWDFKLDQWXEHZLWKRXWFRQWUDVWZLWKLQ
PRQWKVRIWKHHQUROOPHQWGDWH

%HDEOHWRUHDGDQGXQGHUVWDQG(QJOLVK

%HDEOHDQGZLOOLQJWRSURYLGHFRQVHQW

%HZLOOLQJWRFRPSO\ZLWKWKHSURWRFROUHTXLUHPHQWV
 Exclusion criteria 
6XEMHFWV0867127

+DYHKDGDQ\KHDGRUQHFNVXUJHU\HJDGHQRLGHFWRP\WRQVLOOHFWRP\LQFOXGLQJ
VLQRQDVDOVXUJHU\RUHDUWXEHSODFHPHQWSHUIRUPHGZLWKLQPRQWKVEHIRUHHQUROOPHQW

5HTXLUHFRQFRPLWDQWSURFHGXUHVDWWKHWLPHRIVWXG\HQUROOPHQWRUSURFHGXUH

+DYHHDUWXEHVLQSODFHW\PSDQRVWRP\WXEHVP\ULQJRWRP\WXEHVYHQWLODWLRQWXEHVRU
SUHVVXUHHTXDOL]DWLRQWXEHVRUSHUIRUDWLRQRIWKHW\PSDQLFPHPEUDQHDWWKHWLPHRIWKH
VWXG\HQUROOPHQWRUSURFHGXUHSDWLHQWVZLWKKHDOHGW\PSDQLFPHPEUDQHVDIWHU
H[WUXVLRQRIWXEHVDUHQRWH[FOXGHG

+DYHSDWXORXV(XVWDFKLDQWXEHV

&OLQLFDO,QYHVWLJDWLRQDO3ODQ

3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO

+DYHKDGDQ\SUHYLRXVODVHUWXERSODVW\VXUJHU\RUPLFURGHEULGHPHQW

+DYHWHPSRURPDQGLEXODUMRLQW70-GLVRUGHUV

+DYHHDUO\K\GURSV0HQLHUH¶VGLVHDVH

+DYHKDGKHDGRUQHFNUDGLDWLRQWKHUDS\RUVLQRQDVDOPDOLJQDQF\

+DYHDGLDJQRVLVRIFKURQLFUKLQRVLQXVLWLV&565$56WKDWLVXQFRQWUROOHG

+DYHDQLPPXQRGHILFLHQF\

+DYHFUDQLRIDFLDODEQRUPDOLWLHVRURWKHUDQDWRPLFDOFRQGLWLRQVHJVHYHUHO\GHYLDWHG
VHSWXPWXPRUVHQODUJHGDGHQRLGVRUWRQVLOVVHYHUHWXUELQDWHK\SHUWURSK\WKDWZRXOG
SUHYHQWWUDQVQDVDODFFHVVRI(XVWDFKLDQWXEHV

+DYHHYLGHQFHRILQWHUQDOFDURWLGDUWHU\GHKLVFHQFHRUDQDWRPLFDEQRUPDOLWLHV

+DYHXQFRQWUROOHGDOOHUJLHV

+DYHXQPDQDJHGJDVWURHRVRSKDJHDOUHIOX[GLVHDVH*(5'RUODU\QJRSKDU\QJHDO
UHIOX[/35

%HSUHJQDQWDWWKHWLPHRIVWXG\HQUROOPHQWRUSURFHGXUH

%HFXUUHQWO\SDUWLFLSDWLQJLQDQ\RWKHUGUXJRUGHYLFHFOLQLFDOVWXGLHVH[FOXGLQJ
SRVWDSSURYDORUPDUNHWLQJUHJLVWU\VWXGLHV
2.9 Methods and procedures 
6WXG\PHWKRGVDQGSURFHGXUHVDUHGHVFULEHGEHORZ$QRYHUYLHZRIWKHUHTXLUHG3KDVHVWXG\
DVVHVVPHQWVDWHDFKIROORZXSYLVLWLVSURYLGHGLQ7DEOH(DFKVXEMHFW¶VIROORZXSVFKHGXOHLV
EDVHGRQWKHGDWHRIUDQGRPL]DWLRQFRQWURODUPRUWKHVWXG\SURFHGXUHEDOORRQGLODWLRQDUP
DQGFURVVRYHUVXEMHFWV
7DEOH3KDVH6WXG\$VVHVVPHQW6FKHGXOH
Study evaluation
Baseline
Within 60 
days of 
procedure
for balloon 
dilation arm
6-Week
crossover 
evaluation 
(control arm 
only) 
± 7 days
Procedure
Within 60 days 
of baseline or 
6-week 
crossover 
evaluation
6-Week 
post 
procedure
± 7 days
3-Month
post 
procedure
± 15 days
6-Month post 
procedure
± 30 days
(for 510(k) and 
publication)
12-Month
post 
procedure
± 45 days
(for publication)
,QIRUPHGFRQVHQW
9






(OLJLELOLW\DVVHVVPHQW
9
9





'HPRJUDSKLFVKLVWRU\
9






&7VFDQZLWKRXWFRQWUDVW
9D






6\PSWRPVH[DP
9
9

9
9
9
9
0HGLFDWLRQVE
9
9
9
9
9
9
9
1DVDOHQGRVFRS\
9
9

9
9
9
9
2WRVFRS\H[DPLQDWLRQ
9
9

9
9
9
9
7\PSDQRPHWU\
9
9

9
9
9
9
9DOVDOYDHYDOXDWLRQ
9
9

9
9
9
9
(4'TXHVWLRQQDLUH
9
9

9
9
9
9
(7'4TXHVWLRQQDLUH
9
9

9
9
9
9
(DULQIHFWLRQDVVHVVPHQW
9F


9
9
9
9

&OLQLFDO,QYHVWLJDWLRQDO3ODQ
3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
Study evaluation
Baseline
Within 60 
days of 
procedure
for balloon 
dilation arm
6-Week
crossover 
evaluation 
(control arm 
only) 
± 7 days
Procedure
Within 60 days 
of baseline or 
6-week 
crossover 
evaluation
6-Week 
post 
procedure
± 7 days
3-Month
post 
procedure
± 15 days
6-Month post 
procedure
± 30 days
(for 510(k) and 
publication)
12-Month
post 
procedure
± 45 days
(for publication)
$XGLRORJLFH[DPLQDWLRQ
9




9

3UHJQDQF\WHVWZKHQ
DSSOLFDEOH
9

9
3URFHGXUHSDLQ

9G
7HFKQLFDOVXFFHVV


9




'HYLFHPDOIXQFWLRQ


9




$GYHUVHHYHQWV

9
9
9
9
9
9
5HYLVLRQGLODWLRQRU
DGGLWLRQDOVXUJHU\



9
9
9
9
6XEMHFWVDWLVIDFWLRQ


9
9
9
9
D
7KHHOLJLELOLW\&7VFDQFDQEHSHUIRUPHGZLWKLQPRQWKVRIHQUROOPHQW
E 2QO\(17UHODWHGPHGLFDWLRQVZLOOEHUHFRUGHGHJDQWLELRWLFVVWHURLGVDOOHUJ\WUHDWPHQWGHFRQJHVWDQWV
F $WEDVHOLQHGHWHUPLQHWKHQXPEHURIHDULQIHFWLRQVLQWKHPRQWKSHULRGEHIRUHHQUROOPHQW
G
7KHSDLQVFDOHVKRXOGEHFRPSOHWHGEHIRUHGLVFKDUJHIURPWKHLQGH[SURFHGXUH6XEMHFWVWUHDWHGXQGHUJHQHUDODQHVWKHVLDDUHQRWUHTXLUHGWRDVVHVV
SURFHGXUHSDLQ
 Eligibility assessment 
3DWLHQWVDUHFRQVLGHUHGHOLJLEOHIRUWKLVVWXG\LIWKH\PHHWDOOWKHLQFOXVLRQFULWHULDDQGQRQHRI
WKHH[FOXVLRQFULWHULDDVGHILQHGLQ6HFWLRQ7KHSULQFLSDOLQYHVWLJDWRURUVXELQYHVWLJDWRUDW
HDFKLQYHVWLJDWLRQDOFHQWHUZLOOGHWHUPLQHSDWLHQWHOLJLELOLW\EDVHGRQWKHLQFOXVLRQH[FOXVLRQ
FULWHULD
$OOSRWHQWLDOVXEMHFWVPXVWKDYHD&7VFDQZLWKRXWFRQWUDVWRIWKHWHPSRUDOERQHGRQHZLWKLQ
PRQWKVEHIRUHVWXG\HQUROOPHQW7KH&7VFDQPXVWLQFOXGHFRURQDODQGD[LDOLPDJHVRIWKH
WHPSRUDOERQHLQFOXGLQJWKH(XVWDFKLDQWXEH7ZRHOHFWURQLFFRSLHVLQ',&20IRUPDWRIWKH&7
VFDQPXVWEHDYDLODEOHFRS\WREHUHWDLQHGE\WKHLQYHVWLJDWLRQDOFHQWHUDQGFRS\WREH
UHWULHYHGE\WKHVSRQVRU
 Baseline visit 
$OOFDQGLGDWHVIRUWKHVWXG\ZLOOKDYHWKHIROORZLQJEDVHOLQHFOLQLFDOHYDOXDWLRQVGRQHEHIRUH
HQUROOPHQWDQGUDQGRPL]DWLRQ
x ,QIRUPHGFRQVHQWVLJQHG
x %DVHOLQHPHGLFDOKLVWRU\GHPRJUDSKLFVV\PSWRPVDQGPHGLFDWLRQKLVWRU\LQWKH
PRQWKSHULRGEHIRUHHQUROOPHQW
x (OLJLELOLW\DVVHVVPHQWVXEMHFWVPHHWDOOLQFOXVLRQDQGQRH[FOXVLRQFULWHULD
x 1DVDOHQGRVFRS\
x 2WRVFRS\H[DPLQDWLRQ
x 7\PSDQRPHWU\
x 9DOVDOYDHYDOXDWLRQ

&OLQLFDO,QYHVWLJDWLRQDO3ODQ
3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
x $VVHVVPHQWRIHDULQIHFWLRQVRYHUWKHPRQWKSHULRGEHIRUHHQUROOPHQW
x $XGLRORJLFH[DPLQDWLRQLQFOXGLQJDSXUHWRQHDXGLWRU\37$WHVW
x (4'DQG(7'442/TXHVWLRQQDLUHVFRPSOHWHGE\WKHVWXG\VXEMHFW
x 3UHJQDQF\WHVWIRUIHPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDO
7KHUHVXOWVRIDOOEDVHOLQHHYDOXDWLRQVZLOOEHGRFXPHQWHGRQWKHDSSURSULDWH&DVH5HSRUW)RUPV
&5)V
)RUVXEMHFWVXQGHUJRLQJEDOORRQGLODWLRQSUHSURFHGXUHDQWLELRWLFVDQGVWHURLGVPD\EH
SUHVFULEHGDWWKHGLVFUHWLRQRIWKHVWXG\SK\VLFLDQ0HGLFDWLRQVPD\EHSUHVFULEHGWRWUHDWDFWLYH
LQIHFWLRQVDQGSURFHGXUHVPD\EHUHVFKHGXOHGXQWLODFWLYHLQIHFWLRQVUHVROYH
 Enrollment 
$SDWLHQWZLOOEHFRQVLGHUHGHQUROOHGLQWKHVWXG\DIWHUWKHEDVHOLQHDVVHVVPHQWRQFH DOOWKH
LQFOXVLRQH[FOXVLRQFULWHULDKDYHEHHQPHWDQGDWWKHWLPHRIUDQGRPL]DWLRQ
 Randomization 
5DQGRPL]DWLRQDVVLJQPHQWVZLOOEHJHQHUDWHGE\DQLQGHSHQGHQWVWDWLVWLFLDQXVLQJDGLVWULEXWLRQ
LQYDULDEOHEORFNVVL]HVIRUHDFKFHQWHUZLWKDDOORFDWLRQWRFRQWURORUEDOORRQGLODWLRQ7KH
PDVWHUUDQGRPL]DWLRQOLVWZLOOEHVWRUHGE\WKH6SRQVRU5DQGRPL]DWLRQDVVLJQPHQWVZLOOEH
SODFHGLQWRVHTXHQWLDOO\QXPEHUHGDQGVHDOHGHQYHORSHV7KHWUDLQHGVWXG\FHQWHUSHUVRQQHOZLOO
FRQWDFW6SRQVRUWRUHFHLYHWKHUDQGRPL]DWLRQDVVLJQPHQWDIWHUWKHIROORZLQJVWHSVKDYHEHHQ
FRPSOHWHG
 $OOEDVHOLQHHYDOXDWLRQVKDYHEHHQSHUIRUPHG
 6XEMHFWKDVEHHQGHWHUPLQHGHOLJLEOHIRUWKHVWXG\LHLQFOXVLRQH[FOXVLRQFULWHULD
UHYLHZHG
 6XEMHFWKDVVLJQHGDQ,QIRUPHG&RQVHQW
7KH6SRQVRUZLOOUHWULHYHWKHILUVWRUQH[WVHTXHQWLDOO\QXPEHUHGHQYHORSHIRUWKDWFHQWHUDQG
RSHQLW7KHUDQGRPL]DWLRQDVVLJQPHQWLQFOXGLQJWKHUDQGRPL]DWLRQ,'QXPEHUDQGWUHDWPHQW
DVVLJQPHQWZLOOEHUHFRUGHGRQWKH5DQGRPL]DWLRQ(QUROOPHQW&DVH5HSRUW)RUP7KH6SRQVRU
SHUVRQQHOZLOOUHFRUGWKHVXEMHFW,'LQWKHUDQGRPL]DWLRQORJ
 Control arm assignment 
6XEMHFWVUDQGRPL]HGWRWKHFRQWURODUPZLOOFRQWLQXHWKHLUFXUUHQW(7'PHGLFDOWUHDWPHQW
UHJLPHQIRUZHHNVDIWHUUDQGRPL]DWLRQ$WUHDWPHQWUHJLPHQFRQVLVWLQJRIQRPHGLFDWLRQLV
SHUPLWWHGLIFRQVLVWHQWZLWKWKHVXEMHFW¶VFXUUHQWWUHDWPHQWSODQ0HGLFDWLRQVZLOOEHGRFXPHQWHG
RQWKH0HGLFDWLRQV&5)&RQWUROVXEMHFWVDUHQRWDOORZHGWRXQGHUJRDQ\VXUJLFDOWUHDWPHQWV
GXULQJWKLVVWXG\SHULRG
$IWHUWKHZHHNSHULRGRIFRQWLQXHGPHGLFDOWKHUDS\FRQWUROVXEMHFWVZKRFRQWLQXHWRKDYH
(7'V\PSWRPVGHILQHGDVDQRYHUDOO(7'4VFRUHRUDFKDQJHRIZLOOEHDOORZHG
WRFURVVRYHUWREDOORRQGLODWLRQWUHDWPHQWDQGZLOOXQGHUJRWKHGLODWLRQSURFHGXUHDQG
SRVWSURFHGXUHIROORZXSYLVLWVFKHGXOHIRUWKHEDOORRQGLODWLRQDUP&RQWUROVXEMHFWVZKRGRQRW

&OLQLFDO,QYHVWLJDWLRQDO3ODQ
3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
FURVVRYHUZLOOEHH[LWHGIURPWKHVWXG\DWWKLVWLPH7KHZHHNFURVVRYHUHYDOXDWLRQZLOOVHUYH
DVWKHSUHSURFHGXUHDVVHVVPHQWIRUFURVVRYHUVXEMHFWV
 Balloon dilation arm assignment and procedure 
6XEMHFWVVKRXOGXQGHUJRWKHEDOORRQGLODWLRQSURFHGXUHZLWKLQGD\VRIWKHEDVHOLQH
DVVHVVPHQWUDQGRPL]HGWREDOORRQGLODWLRQRUWKHZHHNFURVVRYHUHYDOXDWLRQFURVVRYHU
VXEMHFWV$OOIHPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDODUHUHTXLUHGWRKDYHDQHJDWLYHEORRGRU
XULQHSUHJQDQF\WHVWZLWKLQGD\VEHIRUHDEDOORRQGLODWLRQSURFHGXUH
5HIHUWRWKH;SU(66,QVWUXFWLRQVIRU8VH,)8IRUVSHFLILFLQVWUXFWLRQVRQV\VWHPSUHSDUDWLRQ
VXEMHFWSUHSDUDWLRQGHYLFHVHWXSVKDSLQJWKHGHYLFHDQGGHWDLOHGWUHDWPHQWSURFHGXUHIRUXVLQJ
;SU(66WRSHUIRUP(XVWDFKLDQWXEHGLODWLRQ
3URFHGXUHVLWHRIVHUYLFH
,QYHVWLJDWRUVPD\FKRRVHWRFRPSOHWHVWXG\SURFHGXUHVXQGHUJHQHUDOSOXVORFDODQHVWKHVLDLQD
VXUJLFDOVHWWLQJRUXQGHUORFDODQHVWKHVLDDORQHLQWKHRIILFHVHWWLQJEDVHGRQWKHLUPHGLFDO
GLVFUHWLRQDQGVXEMHFWWROHUDQFH,IWKHVWXG\SURFHGXUHLVILUVWDWWHPSWHGLQWKHRIILFHVHWWLQJEXW
FDQQRWEHFRPSOHWHGXQGHUORFDODQHVWKHVLDDORQHGXHWRVXEMHFWWROHUDQFHWKHVXEMHFWPD\EH
WUHDWHGXQGHUJHQHUDODQHVWKHVLDLQDVXUJLFDOVHWWLQJZLWKRXWEHLQJZLWKGUDZQIURPWKHVWXG\
6XFKFDVHVZLOOQRWEHFRQVLGHUHGWUHDWPHQWIDLOXUHV3URFHGXUHVFRQYHUWHGIURPORFDODQHVWKHVLD
DORQHWRJHQHUDODQHVWKHVLDZLOOEHGRFXPHQWHGRQWKH3URFHGXUH&5)
3URFHGXUHDQHVWKHVLD
$QHVWKHVLDVKRXOGEHDGPLQLVWHUHGDSSURSULDWHO\WRDOORZVXEMHFWWROHUDQFHDQGEDVHGRQWKH
WUHDWLQJSK\VLFLDQ¶VPHGLFDOWUDLQLQJ3K\VLFLDQVPD\FKRRVHWRXVHJHQHUDODQGRUORFDO
DQHVWKHVLDUHJLPHQVWKDWZLOODOORZVDIHDQGWROHUDEOHXVHRIWKHGHYLFHLQWKHVXEMHFW7\SHRI
DQHVWKHVLDDQGORFDWLRQRIORFDOLQMHFWLRQVZLOOEHGRFXPHQWHG
(XVWDFKLDQWXEHDVVHVVPHQW
$WHPSRUDO&7VFDQZLWKD[LDODQGFRURQDOYLHZVSHUIRUPHGZLWKLQWKHODVWPRQWKVEHIRUH
VWXG\HQUROOPHQWZLOOEHUHYLHZHGWRHQVXUHWKHUHDUHQRDQDWRPLFDQRPDOLHVWKDWZRXOGSUHYHQW
WUDQVQDVDODFFHVVWRWKH(XVWDFKLDQWXEHRUSXWWKHVXEMHFWDWLQFUHDVHGULVNHJGHKLVFHQFHRIWKH
FDURWLGDUWHU\,IVXFKFRQGLWLRQVH[LVWWKHVXEMHFWLVQRWHOLJLEOHIRUWKHVWXG\
'HYLFHVL]HVHOHFWLRQ
,QYHVWLJDWRUVPD\FKRRVHWKH;SU(66GHYLFHVL]HEDVHGRQWKHLUPHGLFDONQRZOHGJHDQGWKH
VXEMHFW¶V(XVWDFKLDQWXEHDQDWRP\$OOEDOORRQVL]HVDUHDSSURSULDWHIRUWUHDWLQJ(XVWDFKLDQ
WXEHVVHOHFWLRQLVEDVHGRQSK\VLFLDQSUHIHUHQFH7KH;SU(66GHYLFHVL]HVDUHOLVWHGLQ6HFWLRQ

(XVWDFKLDQWXEHEDOORRQGLODWLRQ
7KH;SU(66EDOORRQLVGHVLJQHGIRUDWUDQVQDVDODSSURDFKRQO\3URFHGXUDOLQIRUPDWLRQRQ
GHYLFHXVHLVSURYLGHGLQWKH;SU(66,)8
7KHIROORZLQJGDWDZLOOEHFROOHFWHGGXULQJWKHVWXG\SURFHGXUHDQGGRFXPHQWHGRQWKH
DSSURSULDWH&5)V

&OLQLFDO,QYHVWLJDWLRQDO3ODQ
3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
x 6LWHRIVHUYLFH
x $GPLVVLRQDQGGLVFKDUJHGDWHWLPHV
x 3URFHGXUHVWDUWVWRSWLPHV
x 7\SHRIDQHVWKHVLDDQGORFDWLRQDQGGRVDJHRIDQ\ORFDOLQMHFWLRQV
x ,GHQWLILFDWLRQRIDOO;SU(66GHYLFHVXVHG
x 7HFKQLFDOVXFFHVVIRU;SU(66GHYLFH
x 7RWDOQXPEHURIEDOORRQLQIODWLRQVIRUHDFKWUHDWPHQWVLGH
x 7RWDOGXUDWLRQRIEDOORRQLQIODWLRQVLQVHFRQGVIRUHDFKWUHDWPHQWVLWH
x 3URFHGXUHVWKDWFRQYHUWIURPORFDODQHVWKHVLDDORQHWRJHQHUDODQHVWKHVLD
x 3URFHGXUHSDLQVFRUHIRUVXEMHFWVWUHDWHGXQGHUORFDODQHVWKHVLDDORQHQRWUHTXLUHGIRU
VXEMHFWVZKRDUHWUHDWHGXQGHUJHQHUDODQHVWKHVLD
x $GYHUVHHYHQWV
x 'HYLFHPDOIXQFWLRQV
3RVWSURFHGXUHFDUH
3RVWSURFHGXUHFDUHLQFOXGLQJPHGLFDOPDQDJHPHQWLVDWWKHGLVFUHWLRQRIWKHSK\VLFLDQ
3RVWSURFHGXUHPHGLFDODQGFOLQLFDOPDQDJHPHQWZLOOEHFROOHFWHGRQWKH0HGLFDWLRQ&5)DWWKH
ZHHNSRVWSURFHGXUHYLVLW
&RQFRPLWDQWSURFHGXUHV
&RQFRPLWDQWSURFHGXUHVDUHQRWDOORZHGLQWKLVVWXG\6SHFLILFDOO\VXEMHFWVUDQGRPL]HGWRWKH
FRQWURODUPDUHQRWDOORZHGWRXQGHUJRDQ\VXUJLFDOSURFHGXUHVRIWKHHDUVRUVLQXVHVGXULQJWKH
ZHHNSHULRGRIFRQWLQXHGPHGLFDOWKHUDS\
 Follow-up visits 
6XEMHFWVUDQGRPL]HGWRWKHFRQWURODUPDUHVFKHGXOHGIRUDIROORZXSYLVLWDWZHHNVGD\V
DIWHUWKHLUUDQGRPL]DWLRQ$WWKLVYLVLWFRQWUROVXEMHFWVZLOOEHHYDOXDWHGDQGLIWKHLU(7'
V\PSWRPVSHUVLVWGHILQHGDVRYHUDOO(7'4VFRUHRUFKDQJHWKHVXEMHFWVDUHHOLJLEOH
IRUFURVVRYHUWREDOORRQGLODWLRQWUHDWPHQW6XEMHFWVZKRGRQRWKDYHSHUVLVWHQW(7'V\PSWRPV
DUHH[LWHGIURPWKHVWXG\DIWHUFRPSOHWLRQRIWKLVYLVLW
6XEMHFWVUDQGRPL]HGWREDOORRQGLODWLRQDQGFURVVRYHUVXEMHFWVDUHVFKHGXOHGIRUWKHIROORZLQJ
SRVWSURFHGXUHIROORZXSYLVLWVZLQGRZ
x :HHNGD\V
x 0RQWKGD\V
x 0RQWKGD\V
x 0RQWKGD\V
7KHIROORZLQJDVVHVVPHQWVDUHUHTXLUHGDWDOOIROORZXSYLVLWV
x 6\PSWRPDVVHVVPHQW
x 1DVDOHQGRVFRS\H[DPLQDWLRQ
x 2WRVFRS\H[DPLQDWLRQ

&OLQLFDO,QYHVWLJDWLRQDO3ODQ
3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
x 7\PSDQRJUDP
x 9DOVDOYDHYDOXDWLRQ
x 0HGLFDWLRQXVHVLQFHODVWVWXG\YLVLW
x (DULQIHFWLRQVVLQFHODVWVWXG\YLVLW
x 5HYLVLRQGLODWLRQRUDGGLWLRQDOVXUJHU\
x 6XEMHFWVDWLVIDFWLRQ
x (4'
x (7'4
x $GYHUVHHYHQWV
,QDGGLWLRQWRWKHDVVHVVPHQWVQRWHGDERYHDQDXGLRORJLFH[DPLQDWLRQLVUHTXLUHGDWWKH
PRQWKYLVLW
 Revision dilations or additional surgery 
5HYLVLRQGLODWLRQVRURWKHUVXUJLFDOSURFHGXUHVDUHSHUPLWWHGIRUVXEMHFWVZKRGRQRWH[SHULHQFH
UHOLHIRI(7'V\PSWRPVDIWHUEDOORRQGLODWLRQWUHDWPHQW+RZHYHULWLVUHFRPPHQGHGWKDW
UHYLVLRQSURFHGXUHVDUHQRWSHUIRUPHGEHIRUHWKHPDMRULW\RIWLVVXHKHDOLQJUHPRGHOLQJKDVEHHQ
DOORZHGWRRFFXU7KLVSURFHVVFDQWDNHXSWRPRQWKVDIWHUWKHLQLWLDOSURFHGXUH6WDQGDUGRI
FDUHPHGLFDOWUHDWPHQWLVSHUPLWWHGDWDQ\WLPHGXULQJWKHVWXG\WRDGGUHVVVXEMHFWV\PSWRPV
,IDVXEMHFWKDVDUHYLVLRQGLODWLRQRUDGGLWLRQDO(17VXUJHU\GXULQJWKHSRVWSURFHGXUHIROORZXS
SHULRGWKHLQYHVWLJDWLRQDOFHQWHUVKRXOGPDNHHYHU\HIIRUWWRFROOHFWWKHSURFHGXUHRSHUDWLYH
QRWHVIRUWKHSURFHGXUHV7KHGDWHDQGW\SHRISURFHGXUHSHUIRUPHGZLOOEHGRFXPHQWHGRQWKH
5HYLVLRQ'LODWLRQ$GGLWLRQDO6XUJHU\&5)$FRS\RIWKHGHLGHQWLILHGUHYLVLRQSURFHGXUHQRWHV
ZLOOEHUHWULHYHGIRUWKHVSRQVRUVWXG\ILOHV
 Early withdrawal and lost to follow-up 
6WXG\VXEMHFWVDUHIUHHWRZLWKGUDZIURPWKHLQYHVWLJDWLRQDWDQ\WLPHZLWKRXWKDYLQJWRMXVWLI\
WKHLUUHDVRQVDQGZLWKRXWDIIHFWLQJWKHLUUHODWLRQVKLSZLWKWKHLQYHVWLJDWRU$QLQYHVWLJDWRUPD\
DOVRZLWKGUDZDVXEMHFWIURPWKHVWXG\DWDQ\WLPHLILWLVGHWHUPLQHGWREHLQWKHVXEMHFW¶VEHVW
LQWHUHVWV
$VXEMHFW¶VIXWXUHPDQDJHPHQWZLOOQRWEHFKDQJHGE\DGHFLVLRQYROXQWDU\RURWKHUZLVHWR
ZLWKGUDZIURPWKHVWXG\$OOUHDVRQDEOHHIIRUWVVKRXOGEHPDGHWRUHWDLQVXEMHFWV XQWLO
FRPSOHWLRQRIWKHFOLQLFDOVWXG\5HDVRQVIRUWHUPLQDWLRQRUZLWKGUDZDOLQFOXGHEXWDUHQRW
OLPLWHGWRWKHIROORZLQJ
x 6XEMHFWGHDWK
x 6XEMHFWUHTXHVW
x 6XEMHFWORVWWRIROORZXS$VXEMHFWLVFRQVLGHUHG³ORVWWRIROORZXS´DIWHUDPLQLPXPRI
GRFXPHQWHGDWWHPSWVWRUHDFKWKHVXEMHFWE\SKRQHFDOOE\DPHPEHURIWKHVWXG\VWDII
DQGDQXQDQVZHUHGFHUWLILHGOHWWHUVHQWWRWKHVXEMHFW¶VODVWNQRZQDGGUHVVE\DWUDFHDEOH
PHWKRGHJFHUWLILHGPDLOFRXULHUFRPPHUFLDOVKLSSLQJWUDQVSRUWFRPSDQ\
x 6XEMHFW¶VSDUWLFLSDWLRQWHUPLQDWHGE\WKHLQYHVWLJDWRU

&OLQLFDO,QYHVWLJDWLRQDO3ODQ
3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
x 6WXG\WHUPLQDWHGE\WKHVSRQVRU
)RUDQ\VXEMHFWVZLWKHDUO\ZLWKGUDZDORUWHUPLQDWLRQWHUPLQDWLRQLQIRUPDWLRQZLOOEHUHFRUGHG
LQWKHVXEMHFW¶VUHFRUGVDQGWKHGDWHRIODVWFRQWDFWZLWKWKHVXEMHFWQRWHGRQWKH(QGRI6WXG\
&5)
 End of study
6XEMHFWVUDQGRPL]HGWRWKHFRQWURODUPZKRGRQRWFURVVRYHUWREDOORRQGLODWLRQWUHDWPHQWDUH
H[LWHGXSRQFRPSOHWLRQRIWKHZHHNFURVVRYHUHYDOXDWLRQ
3DUWLFLSDWLRQLQWKHVWXG\LVFRQVLGHUHGFRPSOHWHIRUDOOEDOORRQGLODWLRQDQGFURVVRYHUVXEMHFWV
XSRQFRPSOHWLRQRIWKHPRQWKSRVWSURFHGXUHYLVLW
,IDVXEMHFWKDVDQ;SU(66GHYLFHLQVHUWHGWUDQVQDVDOO\EXWGRHVQRWXQGHUJRDEDOORRQGLODWLRQ
SURFHGXUHWKHVXEMHFWZLOOEHIROORZHGWRWKHZHHNSRVWSURFHGXUHYLVLWDQGWKHQGLVFRQWLQXHG
IURPWKHVWXG\XQOHVVWKHVXEMHFWKDVDQRQJRLQJDGYHUVHHYHQW$(,IWKHVXEMHFWKDVDQ
RQJRLQJ$(DWWKHZHHNSRVWSURFHGXUHYLVLWWKHVXEMHFWZLOOEHIROORZHGXQWLO$(UHVROXWLRQRU
PRQWKVSRVWSURFHGXUHZKLFKHYHUFRPHVILUVW
$Q(QGRI6WXG\&5)ZLOOEHFRPSOHWHGZKHQWKHVXEMHFWKDVFRPSOHWHGWKHLUODVWUHTXLUHG
IROORZXSYLVLWRUDWWKHWLPHRIZLWKGUDZDORUORVWWRIROORZXSLIWKHVXEMHFWGLVFRQWLQXHVWKH
VWXG\SUHPDWXUHO\
2.10 Study assessments and data collection 
6WXG\GDWDZLOOEHFROOHFWHGDFFRUGLQJWR*RRG&OLQLFDO3UDFWLFHVXVLQJSDSHU&5)VFRPSOHWHGDW
WKHLQYHVWLJDWLRQDOFHQWHU&5)VZLOOEHFROOHFWHGIURPWKHFHQWHUVDQGZLOOEHHQWHUHGLQWRD
&OLQ'H[GDWDEDVHE\(QWHOOXVVWDIIXVLQJSDVVHQWU\SURFHGXUHV7KHGDWDZLOOEHUHYLHZHGE\
(QWHOOXVVWDIIDQGDQ\TXHULHVZLOOEHGRFXPHQWHGDQGVXEPLWWHGWRWKHLQYHVWLJDWLRQDOFHQWHUIRU
FODULILFDWLRQ
7KHUHTXLUHGVWXG\DVVHVVPHQWVIRUHDFKVSHFLILHGLQWHUYDODUHRXWOLQHGLQWKH6HFWLRQ6HH
7DEOHIRUDQRYHUYLHZRIWKHUHTXLUHGVWXG\DVVHVVPHQWVDWHDFKIROORZXSYLVLW(DFKVXEMHFW¶V
IROORZXSVFKHGXOHLVEDVHGRQWKHGDWHRIUDQGRPL]DWLRQFRQWURODUPRUWKHVWXG\SURFHGXUH
EDOORRQGLODWLRQDQGFURVVRYHUDUPV
 Primary and secondary endpoint assessments 
0HDQFKDQJHLQRYHUDOO(7'4VFRUH
7KH(XVWDFKLDQ7XEH'\VIXQFWLRQ4XHVWLRQQDLUH(7'4LVDVWDQGDUGL]HGLWHP
TXHVWLRQQDLUHGHVLJQHGWRDVVHVVTXDOLW\RIOLIHDVVRFLDWHGZLWK(XVWDFKLDQWXEHG\VIXQFWLRQ7KH
GLPHQVLRQVRIWKHTXHVWLRQQDLUHDUHSUHVVXUHSDLQIHHOLQJFORJJHGFROGVLQXVLWLVSUREOHPV
FUDFNOLQJSRSSLQJULQJLQJDQGIHHOLQJPXIIOHG(DFKLWHPLVDVVHVVHGRQDQRSUREOHPWR
VHYHUHSUREOHPVFDOHDQGDQRYHUDOOVFRUHZKLFKLVWKHPHDQRIWKHGLPHQVLRQVFRUHVLV
FDOFXODWHG7KHTXHVWLRQQDLUHLVGHVLJQHGWREHVHOIFRPSOHWHGE\WKHVXEMHFW(7'4
TXHVWLRQQDLUHVZLOOEHFRPSOHWHGDWEDVHOLQHDQGDWDOOVWXG\YLVLWV&KDQJHVLQRYHUDOO(7'4
VFRUHVZLOOEHEDVHGRQWKHPHDQFKDQJHEHWZHHQWKHEDVHOLQHDVVHVVPHQWRUZHHNFURVVRYHU

&OLQLFDO,QYHVWLJDWLRQDO3ODQ
3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
HYDOXDWLRQIRUFURVVRYHUVXEMHFWVDQGHDFKIROORZXSDVVHVVPHQW6WDQGDUGWUHDWPHQWHIIHFWVL]H
PD\DOVREHFDOFXODWHGIRUWKHPHDQRYHUDOO(7'4VFRUH7KH(7'4&5)PD\EH
FRQVLGHUHGDVRXUFHGRFXPHQWLIFRPSOHWHGGLUHFWO\E\WKHVXEMHFWRQWKH&5)
&RPSOLFDWLRQUDWH
$FRPSOLFDWLRQLVGHILQHGDVDVHULRXVDGYHUVHHYHQWWKDWLVGHYLFHUHODWHGRUSURFHGXUHUHODWHGDV
QRWHGLQ6HFWLRQ7KHSDUDPHWHURILQWHUHVWLVWKHSHUFHQWRIVXEMHFWVZKRH[SHULHQFHRUPRUH
FRPSOLFDWLRQVIURPWKHWLPHRIWKHLQGH[SURFHGXUHWKURXJKWKHPRQWKIROORZXS
7HFKQLFDOVXFFHVV
7HFKQLFDOVXFFHVVZLOOEHFROOHFWHGIRUHDFK(XVWDFKLDQWXEHLQZKLFKGLODWLRQLVDWWHPSWHG
6XFFHVVRIWKH;SU(66GHYLFHZLOOEHFDOFXODWHGDVWKHQXPEHURIVXFFHVVIXOGLODWLRQVGLYLGHGE\
WKHQXPEHURI(7VZLWKGLODWLRQDWWHPSWV6XFFHVVLVGHILQHGDVDQDWWHPSWZKHUHWKH;SU(66
GHYLFHLVVXFFHVVIXOO\GHOLYHUHGWRWKHWDUJHWORFDWLRQLQIODWHGGHIODWHGDQGZLWKGUDZQIURPWKH
WUHDWHG(XVWDFKLDQWXEH
5HYLVLRQGLODWLRQUDWH
5HYLVLRQGLODWLRQLVGHILQHGDVDQ\UHSHDWEDOORRQGLODWLRQSURFHGXUHSHUIRUPHGRQDQ(7WKDW
ZDVLQLWLDOO\WUHDWHGZLWKDQ;SU(66GHYLFH7KHSDUDPHWHURILQWHUHVWLVWKHSHUFHQWRIVXEMHFWV
ZKRH[SHULHQFHRUPRUHUHYLVLRQGLODWLRQVGXULQJWKHVWXG\
 Other measure assessments 
*HQHUDOTXDOLW\RIOLIHDVVHVVPHQW
4XDOLW\RIOLIHUHJDUGLQJJHQHUDOKHDOWKZLOOEHDVVHVVHGXVLQJWKH(XUR4RO(4'
7KH(4'LVDVWDQGDUGL]HGTXHVWLRQQDLUHXVHGWRHYDOXDWHJHQHUDOKHDOWKUHODWHGTXDOLW\RIOLIH
7KHTXHVWLRQQDLUHLVPDGHXSRITXHVWLRQVIRUHDFKKHDOWKGLPHQVLRQPHDVXUHGPRELOLW\
VHOIFDUHXVXDODFWLYLWLHVSDLQGLVFRPIRUWDQGDQ[LHW\GHSUHVVLRQDQGDYLVXDODQDORJVFDOH
9$6WRLQGLFDWHRYHUDOOKHDOWKRQDVFDOHRIWR(DFKKHDOWKGLPHQVLRQKDVSRVVLEOH
UHVSRQVHVQRSUREOHPVVOLJKWSUREOHPVPRGHUDWHSUREOHPVVHYHUHSUREOHPVRUH[WUHPH
SUREOHPV7KHTXHVWLRQQDLUHLVGHVLJQHGWREHVHOIFRPSOHWHGE\WKHVXEMHFW7KH(4'
TXHVWLRQQDLUHZLOOEHFRPSOHWHGDWDOOVWXG\YLVLWV7KH(4'&5)PD\EHFRQVLGHUHGDVRXUFH
GRFXPHQWLIFRPSOHWHGGLUHFWO\E\WKHVXEMHFWRQWKH&5)
3URFHGXUHSDLQ
7KHSURFHGXUHSDLQDVVHVVPHQWZLOOEHFROOHFWHGEHIRUHGLVFKDUJHIURPHDFKVXEMHFWZKR
XQGHUJRHVWKHGLODWLRQSURFHGXUHZLWKORFDODQHVWKHVLDDORQH3DLQZLOOEHDVVHVVHGXVLQJDQ
SRLQW9$67KH3URFHGXUH&5)PD\EHFRQVLGHUHGWKHVRXUFHGRFXPHQWIRUWKHSURFHGXUHSDLQ
DVVHVVPHQW
2WRVFRS\ILQGLQJV
2WRVFRS\H[DPLQDWLRQVZLOOEHSHUIRUPHGDWEDVHOLQHDQGDWHDFKIROORZXSYLVLW7KH
H[DPLQDWLRQZLOOLQFOXGHDVVHVVPHQWRIWKHW\PSDQLFPHPEUDQHHDUGUXPIRUFRORU
WUDQVOXFHQF\PRELOLW\VKDSHEXOJLQJUHWUDFWLRQDQGWKHDSSHDUDQFHRIEXEEOHV7KHHDUFDQDO

Clinical Investigational Plan 
 
Page 21 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
will be observed for edema, fluid/pus, or cerumen (wax). For evaluation, otoscopy findings will 
be categorized as normal (within normal limits) or abnormal (1 or more characteristic not within 
normal limits). Results of the otoscopic examination will be documented on the Baseline or 
Follow-up CRF, as appropriate. 
Tympanometry 
Tympanometry will be performed at baseline and at each follow-up visit. The test will be 
performed with a 226 Hz signal and a copy the tympanogram will be filed with the subject study 
files. The following parameters from the tympanogram will be documented on the Baseline or 
Follow-up CRF, as appropriate: 
• Peak pressure (daPa) 
• Compliance (cm3) 
• Ear canal volume (mL) 
• Type (A, B, or C) 
Valsalva maneuver 
Each subject will attempt to perform a Valsalva maneuver at baseline and at each follow-up visit 
after tympanometry is completed. The maneuver is performed by forcing expiration with closed 
mouth and nostrils which increases the pressure in the middle ear. This typically results in 
opening of the Eustachian tube with relief of ear congestion. Popping and/or clicking are often 
heard during the maneuver. If the subject does not experience clearing, popping, or clicking in 
the ears after attempting the maneuver, the result is considered negative. Results of the Valsalva 
maneuver will be documented as appropriate. 
Ear infection frequency and healthcare visits 
The number of ear infections experienced in the 12-month period before enrollment will be 
recorded at the baseline visit. At each follow-up visit, the number of ear infections since the last 
visit will be recorded.  
Similarly, the number of physician/nurse visits for ETD-related issues will be recorded and 
compared between the 12 months before and 12 months after balloon dilation.  
Subject satisfaction 
At each follow-up visit, balloon dilation and crossover subjects will be asked to indicate their 
satisfaction with the procedure outcome and whether they would recommend the procedure to 
their friends/family. The subject satisfaction questions will be documented on the ETDQ-7 CRF, 
which may be considered the source document for the satisfaction ratings. 
Audiologic examination 
An audiologic examination will be performed on all subjects at baseline and on all balloon 
dilation and crossover subjects at the 6-month follow-up.  
Audiometry procedures should be conducted in compliance with the ANSI Method for Manual 
Pure-Tone Threshold Audiometry, ANSI S3.21-1978 (R1997). Computerized or self-recording 
audiometers should be used according to their manufacturer’s instructions. 

&OLQLFDO,QYHVWLJDWLRQDO3ODQ

3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
3XUHWRQHDLUERQHJDSDXGLRPHWU\WHVWLQJZLOOEHSHUIRUPHGXVLQJSXOVHGWRQHVZLWKWKHEHWWHU
HDULINQRZQWHVWHGILUVW7KHSUHIHUUHGIUHTXHQF\VHTXHQFHVIRUDLUDQGERQHFRQGXFWLRQ
PHDVXUHVDUHVKRZQLQ7DEOH,IPDVNLQJLVXVHGWKHW\SHDQGOHYHOVKRXOGEHQRWHGRQWKH
&5)7KHDLUERQHJDSZLOOEHFDOFXODWHGDQGUHSRUWHGRQWKH&5)
7DEOH3UHIHUUHG)UHTXHQF\+]7HVWLQJ6HTXHQFHIRU$LUERQH&RQGXFWLRQ7HVWV
Test Order
1 
2 
3 
4 
5 
6 
7 
$LU




D


%RQH



D



D :KHQWHVWLQJWKHVHFRQGHDUWKHUHSHDW+]WHVWLVQRWQHFHVVDU\EHIRUHWHVWLQJWKHORZHUIUHTXHQFLHV



Clinical Investigational Plan 
 
Page 23 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
3 Risk/Benefit Analysis 
3.1 Benefits 
Participation in this study is voluntary; however, information gathered from this study will be 
used to apply for FDA clearance of a new indication for the XprESS device for Eustachian tube 
dilation. Subjects with ETD may experience an improvement in their symptoms. 
3.2 Potential risks 
Study subjects will be informed of all known potential side effects and complications associated 
with study treatment and study assessments before consenting for the study. The risks associated 
with participating in the study are the same as those that the subject would have if treated with 
transnasal Eustachian tube balloon dilation outside of the study. These potential risks include: 
• 
Complications from anesthesia 
• 
Preauricular emphysema 
• 
Pain 
• 
Damage to the ET 
• 
Bruising and swelling 
• 
Patulous ET 
• 
Bleeding 
• 
Permanent hearing loss 
• 
Infection 
• 
Tympanic membrane damage 
• 
Continued or worsening symptoms 
• 
Carotid artery damage 
• 
Revision surgery 
• 
Cerebrospinal fluid leak 
• 
Tinnitus 
 
3.3 Risk mitigation 
The protocol has been developed to minimize the risks for the subject in a number of ways. 
Sample size was calculated to expose the smallest number of subjects while still being able to 
adequately test the study objectives. The subject selection criteria were designed to minimize risk 
by excluding patients who have comorbidities or conditions that may put the patient at higher 
risk for the balloon dilation procedure. Concomitant procedures that could increase risk and 
confound study results are not permitted during the study. The subjects are closely monitored by 
frequent follow-up visits during the study. Finally, the selected investigators are experienced in 
endoscopic surgery, specifically trained on use of the XprESS device, and expected to comply 
with the manufacturer’s IFU for the XprESS device for Eustachian tube dilation. 
 
 

Clinical Investigational Plan 
 
Page 24 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
4 Device Information 
4.1 Investigational device description 
The device under investigation in this study is the XprESS Multi-Sinus Dilation System 
(XprESS device). The device is currently a Class I, 510(k)-cleared, commercially available 
device for balloon sinus dilation.  
The XprESS device combines features of a curved suction tip and an ostium seeker with the 
tissue expansion effect of balloon dilation. The features of this device enable a physician to track 
the device to the Eustachian tubes using endoscopic visualization. The distal end of the device is 
re-shapeable, allowing easy access to the Eustachian tubes. The XprESS curved suction tip has 
an atraumatic ball tip. A suction tube may be connected to the proximal barbed fitting to provide 
active suction by covering the suction vent. The XprESS balloon is available in diameters of 3-5 
mm and in lengths of 8, 18, and 20 mm. All sizes are appropriate for treating Eustachian tubes; 
selection is based on physician preference. The XprESS device is provided sterile and for single 
use only. 
4.2 Anticipated changes in device design 
Changes to the device during the course of the IDE study are not anticipated. If such changes 
occur, Entellus Medical will inform investigators and will submit the appropriate supplemental 
applications to FDA, as necessary.  
4.3 Investigational device management 
Entellus Medical will control the use of the investigational devices by the following activities: 
• Shipping or hand-carrying devices only to approved investigators who are participating in 
the study 
• Maintaining records of shipment and distribution of the devices 
• Maintaining records of devices used on subjects and returned devices 
4.4 Device malfunctions 
A device malfunction is defined as a failure of a device to meet its performance specifications or 
otherwise to perform as intended. A malfunction may be a result of any of the following: failure, 
malfunction, improper or inadequate design, manufacturing, labeling, or user error. 
All device malfunctions must be reported on the Device Malfunction CRF. All attempts should 
be made to return malfunctioning devices to Entellus Medical for evaluation. Contact the clinical 
monitor for instructions on used device preparation and return procedures. 
 
 

Clinical Investigational Plan 
 
Page 25 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
5 Monitoring Procedures 
Entellus Medical personnel or qualified designees will monitor the clinical study in a manner 
consistent with 21 CFR 812, Subpart C, Responsibilities of Sponsor.  
5.1 Name and address of the Lead Monitor 
Clinical Monitor: 
Robyn Schacherer 
 
Entellus Medical Inc. 
 
3600 Holly Lane North, Suite 40 
 
Plymouth, MN 55447 
 
Phone: (763) 463-7054 
 
Fax: 
(763) 463-1599 
 
E-mail: rschacherer@entellusmedical.com  
Additional designated program monitors may be assigned and contact information provided 
separately. 
5.2 Investigators 
The clinical monitors will ensure investigators are selected based on their qualifications and 
ability to fulfill the investigator responsibilities. Investigator qualifications and responsibilities 
are outlined in the Investigator Agreement that each investigator must sign before enrolling 
subjects in the study. An updated list of investigators and Institutional Review Boards (IRBs) 
will be provided to the FDA every 6 months during the study, or as otherwise requested. 
5.3 Investigational center monitoring 
Monitoring visits to the investigational centers will be conducted frequently during the study to 
ensure that all aspects of the current approved protocol and any amendment(s) are followed. 
Source documents will be reviewed for verification with data on the CRFs and all regulatory 
documents will be checked for accuracy including but not limited to IRB approvals, study-
related correspondence, and subject informed consent. The investigator and/or investigational 
center staff must be available to meet with the sponsor during monitoring visits. 
Upon reasonable notice, the investigator and institution agree to provide the sponsor 
representatives or designees and applicable regulatory authorities with direct access to source 
documents relevant to the study for sponsor quality assurance audits or inspections by the 
regulatory authorities. 
 
 

Clinical Investigational Plan 
 
Page 26 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
6 Adverse Event Definitions and Reporting 
6.1 Adverse events 
An adverse event (AE) is any undesirable clinical occurrence experienced by the subject during 
the follow-up period regardless of the event’s relationship to either the study device or the 
procedure. An underlying disease that was present at the time of enrollment is not an AE; 
however, any increase in the severity of an underlying disease is an AE. All adverse events will 
be reported to FDA in annual progress reports. 
Microtears (<5 mm) of the ET mucosa after balloon dilation in the absence of other undesirable 
effects are not considered adverse events. It is hypothesized that the microtears are related to the 
mechanism of action and are critical to the tissue healing and remodeling of the ET after balloon 
dilation. 
6.2 Serious adverse events 
A serious adverse event (SAE) is an event that results in any of the following: 
• Death 
• Life-threatening 
• Hospitalization or prolongation of an existing hospitalization 
• Invasive surgical intervention to correct or prevent further injury 
• Persistent or significant disability or incapacity 
• An important medical event 
An important medical event that may not meet one of the above definitions might be considered 
as an SAE if it jeopardizes the health of the subject or requires surgical intervention to prevent 
one of the outcomes listed in the above definition. An example of an important medical event is 
postoperative bleeding that requires an intervention such as cautery or additional packing but 
does not require hospitalization. 
An elective hospitalization/intervention that was planned before the subject enrolled in the study 
is not considered an SAE as defined above. 
6.3 Unanticipated adverse device effects 
As defined in the IDE regulation 21 CFR 812.3, an unanticipated adverse device effect (UADE) 
is any serious adverse effect on health or safety, or any life-threatening problem or death caused 
by, or associated with, a device, if that effect was not previously identified in nature, severity, or 
degree of incidence in the protocol, subject informed consent form, or application, or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or 
welfare of subjects. 
6.4 Assessing, recording, and reporting AEs, SAEs, and UADEs 
An AE may be volunteered spontaneously by the subject or discovered as a result of questioning 
or physical examination by the investigator or study staff. The following information should be 

Clinical Investigational Plan 
 
Page 27 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
reported for all AEs as soon as the investigator becomes aware of the event and updated as 
needed until the event resolves: 
• Date the AE occurred 
• Date the investigator (or staff) became aware of the AE 
• Description of the AE (main complaints or symptoms) 
• Relationship to the study device 
• Relationship to the study procedure 
• Seriousness 
• Interventions undertaken 
• Status of the AE 
Source documents (eg, procedural notes, treatment notes, clinical summary) may be required as 
supporting documentation for an AE, SAE, or UADE.  
During the study, all subject deaths must be reported to the sponsor within 24 hours of the 
investigator’s (or designated staff’s) knowledge of the death. Deaths should be reported on the 
End of Study CRF and the event leading to the death reported on an AE CRF. A copy of death 
records, medical records for the event(s) that led to the subject’s death, death certificate (if 
available), and an autopsy report (if performed) should be deidentified and sent to the sponsor as 
soon as they become available. 
 
 

Clinical Investigational Plan 
 
Page 28 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
7 Protocol Deviations 
Investigators are required to adhere to the study protocol, signed Investigator Agreement, 
applicable national or local laws and regulations, and any conditions required by the applicable 
IRB or regulatory authority.  
A protocol deviation is used to describe situations in which the protocol was not followed 
(including all required activities at each scheduled visit or activities occurring outside of the 
study windows). All attempts should be made to obtain sponsor approval for deviations before 
their occurrence. 
An investigator must notify the sponsor and the applicable IRB of any deviation from the study 
protocol done to protect the life or physical well-being of a subject (medical emergencies). Such 
notice should be given within 24 hours. The sponsor will determine if the subject affected is 
eligible to continue in the study. 
Documentation of deviations identified by the investigational center, the monitor, or other 
sponsor representative(s) will be entered onto the Protocol Deviation CRF for the purpose of 
tracking compliance with the protocol. The investigational centers will be required to document 
actions taken to prevent recurrence of deviations. The sponsor representative will initiate 
corrective actions based on individual deviations or trending reports, as appropriate. 
 
 

Clinical Investigational Plan 
 
Page 29 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
8 Labeling 
Entellus Medical will modify the existing FDA-cleared labeling (package labels and IFU 
documents) for the XprESS device to include the required investigational device statement 
(below), the indication statement, risks, and treatment procedure specific to Eustachian tube 
dilation. 
The following statement will be included on the outer packaging unit and the IFU as required by 
21 CFR 812.5: 
• CAUTION-Investigational Device. Limited by Federal (or United States) law to 
investigational use. 
 
 

Clinical Investigational Plan 
 
Page 30 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
9 Administrative Information 
9.1 Investigational center selection 
The study will be conducted at up to 7 investigational centers in the US. Centers will be 
evaluated to ensure each center has the capacity and capability to obtain informed consent and 
comply with all protocol requirements. The investigators and investigational center personnel are 
required to comply with the principles of Good Clinical Practices (GCP) as described in the FDA 
regulations. 
9.2 Training 
The training of investigational center personnel will be the responsibility of the sponsor or 
sponsor-authorized representatives. All treating physicians must be proficient in the use of 
endoscopic techniques. All physicians will be trained on the preparation and use of the XprESS 
device before subject enrollment in this study. 
To insure uniform data collection and protocol compliance, the sponsor or sponsor-authorized 
representatives will review all components of the study with the study coordinator(s)/study staff 
at each investigational center. The review will include the study protocol, techniques for the 
identification of eligible patients, instructions for data collection during the procedure, and 
schedules for follow-up. 
9.3 Informed consent process 
Informed consent must be obtained in accordance with US regulation 21 CFR 50. The subjects 
must be informed about their right to withdraw from the study at any time and for any reason 
without sanction, penalty, or loss of benefits to which the subject is otherwise entitled and also 
informed that withdrawal from the study will not jeopardize their future medical care. The 
standard institutional patient consent form does not replace the study informed consent form 
(ICF). 
The sponsor will provide a study-specific ICF template to each investigational center for IRB 
submission. This template may be modified to suit the requirements of the individual 
investigational center. The sponsor must preapprove all changes to the ICF before initial 
submission to the IRB. The IRB-approved consent form must be sent to and approved by the 
sponsor before the first device shipment. One approved copy must be retained in the 
investigational center’s study files along with the other investigational forms.  
Each enrolled subject must be given a copy of their signed consent form and another copy must 
be retained in the investigational center study file for that subject. Informed consent documents 
must be available for review by the sponsor during monitoring visits. 
Modifications to the study-specific ICF and/or any other written information distributed to 
subjects must be preapproved by the sponsor and the IRB, as necessary. 

Clinical Investigational Plan 
 
Page 31 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
9.4 Confidentiality 
All information and data sent to the sponsor concerning subjects or their participation in this 
study will be considered confidential. Subjects will be identified by a study-specific 
identification code. All data used in the analysis and reporting of this investigation will use the 
study-specific codes and will not include identifiable references to individual subjects. Any 
source documentation must be deidentified by the investigational center before being sent to the 
sponsor.  
The investigator will allow visits by the sponsor representatives and the US FDA inspectors or 
any other local governmental body to review the study subjects’ medical records, including test 
or laboratory data that might have been recorded on diagnostic test media (eg, CT scan). 
9.5 Institutional Review Board (IRB) 
It is the investigator’s responsibility to obtain and maintain written approval of the final 
investigational plan and ICF from the applicable IRB. The investigator is responsible for 
submitting and obtaining initial and continuing review of the study by the IRB. It is also the 
investigator’s responsibility to notify the IRB of any amendments to these documents. Written 
IRB approval must identify the study by title and version, document the date of review, and be 
forwarded to the sponsor before the first device shipment.  
The investigator must keep all study-related correspondence with the IRB on file and forward 
copies of such correspondence to the sponsor. 
9.6 Investigator responsibilities 
The investigator for each investigational center is responsible for ensuring the study is conducted 
according to: 
• All signed agreements 
• The study protocol 
• IRB guidelines 
• Applicable local and federal regulations 
The investigator for each center may not begin enrollment until the sponsor receives and 
approves (when necessary) required documents, including the signed Investigator Agreement 
and the IRB approvals of the investigational plan and ICF. 
It is acceptable for the investigator to delegate 1 or more of the above functions to a 
subinvestigator or trained study coordinator; however, the investigator remains responsible for 
the proper conduct of the clinical investigation, including obtaining informed consent, collecting 
all required data, and submitting accurate and complete CRFs. 
At each investigational center, appropriate procedures must be followed to maintain subject 
confidentiality according to HIPAA (Health Insurance Portability and Accountability Act) 
regulations. Each center may have its own internal procedures or requirements for use and 
release of subject medical information in research studies. Each investigator is responsible for 

Clinical Investigational Plan 
 
Page 32 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
obtaining appropriate approvals, consents, or releases of medical information as dictated by their 
relevant patient privacy laws. 
The study is not transferable to other centers/facilities attended by the investigator unless 
preapproval is obtained from the applicable IRB and the sponsor. 
9.7 Sponsor responsibilities 
The sponsor’s responsibilities for this study are to: 
• Provide sufficient training to participating investigational centers to support study 
activities according to the agreements executed with the centers 
• Select all clinical investigators and investigational centers and other consultants (eg, the 
study monitors) who participate in the study 
• Provide financial support to each center according to the agreements executed with each 
center 
• Follow/promote all regulatory standards according to local/federal regulations for the 
investigational centers, core laboratories, and other participants, and ensure regular 
investigational center monitoring to assure compliance with the regulations 
• Retain ownership of all clinical data generated in this study and control the use of the 
data for appropriate purposes only 
• Review and approve publication of study results in the literature 
• Ensure timely and appropriate study registration in a public clinical trial database (eg, 
Clinicaltrials.gov), if applicable 
9.8 Criteria for terminating study 
The sponsor reserves the right to terminate the study early but intends only to exercise this right 
for valid scientific or administrative reasons or reasons related to the protection of study subjects. 
Investigators, applicable IRBs, and FDA will be notified in writing in the event of study 
termination. Reasons for study termination include but are not limited to: 
• The discovery of an unexpected, significant, or unacceptable risk to the study subjects 
• A decision on the part of the sponsor to suspend or discontinue commercial distribution 
of the device 
9.9 Criteria for terminating an investigational center 
The sponsor reserves the right to stop enrollment of subjects at a particular investigational center 
at any time after the study initiation visit for any of the following reasons: 
• Repeated failure to complete CRFs in a timely manner 
• Failure to obtain appropriate informed consent 
• Failure to report any study subject deaths, SAEs, or UADEs within the timeframes 
specified in Table 3 
• Loss of or unaccounted product inventory 
• Repeated protocol deviations 
• Lack of study enrollment or study activity 

&OLQLFDO,QYHVWLJDWLRQDO3ODQ

3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
10Reports and Records 
10.1 Records 
,QDFFRUGDQFHZLWK&)5GDOOUHFRUGVSHUWDLQLQJWRWKHFOLQLFDOVWXG\ZLOOEHNHSW
IRUDPLQLPXPRI\HDUVIROORZLQJWKHGDWHRQZKLFKWKHVWXG\LVWHUPLQDWHGRUFRPSOHWHG,IDQ
LQYHVWLJDWRUZLVKHVWRZLWKGUDZIURPWKHUHVSRQVLELOLW\RIPDLQWDLQLQJWKHVHVWXG\UHFRUGVD
WUDQVIHURIWKDWUHVSRQVLELOLW\WRDSHUVRQZLOOLQJWRDFFHSWWKHUHVSRQVLELOLW\DVRXWOLQHGLQ
&)5PXVWRFFXUDQGEHUHSRUWHGWRWKHVSRQVRUQRWPRUHWKDQGD\VDIWHUWKHWUDQVIHU
RFFXUV
10.2 Reporting requirements 
7DEOHVKRZVDVXPPDU\RIDOOLQYHVWLJDWRUUHSRUWLQJUHTXLUHPHQWV,QDGGLWLRQWRWKLVOLVW
LQGLYLGXDO,5%VPD\DGGDGGLWLRQDOUHSRUWLQJUHTXLUHPHQWVDQGRUUHTXLUHDGLIIHUHQWQRWLILFDWLRQ
WLPHIUDPH7KHSULQFLSDOLQYHVWLJDWRUDWHDFKLQYHVWLJDWLRQDOFHQWHULVUHVSRQVLEOHIRUHQVXULQJ
DQ\DGGLWLRQDOORFDO,5%UHSRUWLQJUHTXLUHPHQWVDUHPHW
7DEOH6XPPDU\RI,QYHVWLJDWRU5HSRUWLQJ5HTXLUHPHQWV
Type of report
Prepared by
Investigator for:
Notification time frame
8QDQWLFLSDWHG$GYHUVH'HYLFH(IIHFW8$'(
6SRQVRU	,5%
:LWKLQZRUNLQJGD\VRINQRZOHGJH
)DLOXUHWRREWDLQLQIRUPHGFRQVHQWSULRUWRGHYLFH
XVH
6SRQVRU	,5%
:LWKLQZRUNLQJGD\V
:LWKGUDZDORI,5%DSSURYDO
6SRQVRU
:LWKLQZRUNLQJGD\VRINQRZOHGJH
6XEMHFWZLWKGUDZDO
6SRQVRU
:LWKLQZRUNLQJGD\VRINQRZOHGJH
)LQDOUHSRUW
6SRQVRU	,5%
:LWKLQPRQWKVDIWHUFRPSOHWLRQRU
WHUPLQDWLRQ
3URJUHVVUHSRUW
6SRQVRU	,5%
$WPLQLPXPDQQXDOO\
'HYLDWLRQVGXHWRHPHUJHQF\
6SRQVRU	,5%
:LWKLQZRUNLQJGD\VRIHPHUJHQF\

7DEOHOLVWVWKHVSRQVRUUHSRUWLQJUHTXLUHPHQWVDQGQRWLILFDWLRQWLPHIUDPHV

&OLQLFDO,QYHVWLJDWLRQDO3ODQ

3DJHRI
5HY&
(QWHOOXV0HGLFDO&RQILGHQWLDO
7DEOH6XPPDU\RI6SRQVRU5HSRUWLQJ5HTXLUHPHQWV
Type of report
Prepared by Sponsor for:
Notification time frame
8QDQWLFLSDWHG$GYHUVH'HYLFH(IIHFW8$'(
)'$
:LWKLQZRUNLQJGD\VRIUHFHLSW
)DLOXUHWRREWDLQLQIRUPHGFRQVHQWSULRUWR
GHYLFHXVH
)'$
:LWKLQZRUNLQJGD\VRIUHFHLSW
:LWKGUDZDORI,5%DSSURYDO
)'$
:LWKLQZRUNLQJGD\VRIUHFHLSW
:LWKGUDZDORI)'$DSSURYDO
,QYHVWLJDWRUV	,5%
:LWKLQZRUNLQJGD\VRIUHFHLSW
5HFDOOVDQGGHYLFHGLVSRVLWLRQ
)'$	,5%
:LWKLQZRUNLQJGD\VDIWHUUHTXHVW
)LQDOUHSRUW
)'$,5%	,QYHVWLJDWRUV
PRQWKVDIWHUFRPSOHWLRQRUWHUPLQDWLRQ
RIVWXG\
3URJUHVVUHSRUWV
)'$	,5%
$QQXDOO\
&XUUHQWLQYHVWLJDWRUOLVW
)'$
PRQWKLQWHUYDOVDIWHU)'$DSSURYDO
6WXG\FRPSOHWLRQRUWHUPLQDWLRQ
)'$
:LWKLQGD\VRIFRPSOHWLRQRU
WHUPLQDWLRQ
 
 

Clinical Investigational Plan 
 
Page 35 of 35 
2909-001 Rev C. 
Entellus Medical Confidential 
11 References 
1  Seibert JW, Danner CJ. Eustachian tube function and the middle ear. Otolaryngol Clin N Am. 
2006;39:1221-1235. 
2  Bluestone CD. Eustachian Tube: Structure, Function, Role in Otitis Media. Hamilton, 
Ontario, Canada: BC Decker, Inc.; 2005. 
3  Poe DS, Hanna BMN. Balloon dilation of the cartilaginous portion of the eustachian tube: 
initial safety and feasibility analysis in a cadaver model. Am J Otolaryngol. 2011;32:115-
123.