ROBUST I Pilot Study, ROBUST I Study, Re-Establishing Flow Via Drug Coated Balloon For The Treatment Of Urethral Stricture Disease
Phase: EARLY_PHASE1
Conditions: Stricture Urethra
Sponsor: Urotronic Inc.

Urotronic 
 ROBUST I Clinical Study 
 DSC016 Rev F 
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Rev 
Date 
Change Description 
Author 
Initials 
A 
6-16-2016
Initial Release sent to DR for translation 
SWT 
B 
7-14-2016
Minor changes to the required evaluations in Table 6-2 
uncovered during the review of the CRF with Urotronic 
team. 
x
Remove the term “screen” from title
x
Remove cystoscopy requirement intraprocedure
x
Remove VAS score after 30 days follow up
x
Add exclusion criteria to exclude participation in
other pre-approved studies
x
Remove drug testing in blood from 30 days and 3
months
x
Add drug testing in blood at pre-discharge
x
Correct the compliance window at baseline to be -
30
SWT 
C 
9/12/2016 
Changes made based on input from FDA 
1. Increase frequency of serum drug content for a
limited number of patients
2. Semen collection – add baseline collection.
Change 7 day semen collection to 14 day.  Add
sperm quality to analysis of semen.
3. Abstain from all sexual activities for 2 weeks post
treatment
4. Patients abstain from ejaculation for 48 hrs before
collection
5. Add semen collection and analysis at day 180
6. Modify Endpoint 1 to add urethral rupture or burst
7. Define Endpoint 2: Urethral measurement as
3DVVDJHRIDIOH[LEOHF\VWRVFRSHWRGHWHUPLQH
Fr urethral caliber
If the 16F flexible scope would not pass, then a 14
Fr flexible rubber catheter will be inserted through
the treated section
8. Redefine 3 months success
9. Standardize catheterization – all patients will be
catheterized for a minimum of 5 days
10. Add monitoring of creatinine post procedure.
11. Change exclusion criteria #12 from 2.5 mg/dl to 2
mg/dl
12. Add exclusion #24 – BXO
13. Modify inclusion #5
SWT 

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14. Add PVR monitoring at 5, 14. 30 days
15. Add CBC and ALT monitoring at baseline, pre-
discharge and 5 days follow-up visit
16. Remove prophylactic antibiotic
17. Recommend general anesthesia for all patients
18. Added baseline TRUS
C2 
11-9-2016
Editorial changes based on requests of the EC in Panama 
SWT 
D 
2-17-2017
1. Correct error on the timepoints of blood samples for
drug test in “Table 6-2: Scheduled Evaluations and
Follow UP”
2. Clarify POBU and DCB dilation should not exceed the
rated burst pressure of the balloon.
3. Allow bladder neck contracture
4. Increase enrollment number
5. Add reference to SAP
SWT 
E 
6-8-2017
1. Remove requirement of using 20F POBU predil
balloon.
2. Add requirement that post dilation diameter must be
)SULRUWRWUHDWPHQWZLWK'&%
3. Update Table 6.2 to record urethrogram and/or
fluoroscopy during treatment procedure to be
consistent with narrative.  No change in requirements.
4. Update Table 6.2 to clarify bacterial analysis of urine
should include a UTI test
5. Detailed guidance on DVIU procedure per physician
input
6. Increased # of study site from “up to 3 clinical sites”
to “up to 5 clinical sites”
7. Add “Retreatment”-  Section 6.5
8. Excluded patients with a suprapubic catheter
9. Increased blood PK samples from 15 to 30 subjects
SWT 
F 
8-10-2017
Adminstrative update only.  No change in patient selection 
or treatment.   
1. Rearrange the order of endpoints to be consistent with
SAP.  Delete section 3.3.10 as it is redundant.
2. Clarify section 6.5 that all retreatment data will be
pooled but a separate summary will also be provided
3. Section 8: Remove redundant description of analysis
and refer to SAP only.
4. Add a condition for excluding patients with a
suprapubic catheter
5. Specify the risks of paclitaxel
SWT 

Urotronic 
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DSC016 Rev F 
ROBUST I Pilot Study
Re-Establishing Flow Via Drug Coated Balloon For The 
Treatment Of Urethral Stricture Disease  
August 11, 2017 
DSC016 Rev F 
NCT03014726 

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ROBUST I Pilot Study
Re-Establishing Flow Via Drug Coated Balloon For The 
Treatment Of Urethral Stricture Disease  
PROTOCOL No. DSC016 Rev F
August 11, 2017
SPONSOR
Urotronic Inc
13705 26th Ave N #102
Minneapolis, MN 55441
This study will be conducted in compliance with the protocol and applicable regulatory 
requirements.
CONFIDENTIAL INFORMATION
No use or disclosure of this document outside Urotronic is permitted without prior written authorization from 
Urotronic

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ROBUST I Pilot Study
Re-Establishing Flow Via Drug Coated Balloon For The 
Treatment Of Urethral Stricture Disease  
PROTOCOL No. DSC016
Revision F
August 11, 2017
I have read this protocol and agree to adhere to the requirements. I will provide copies of 
this protocol and all pertinent information to the study personnel under my supervision and 
my hospital Ethics Committee/Research Ethics Board (EC/REB). I will discuss this 
material with them and ensure they are fully informed regarding the conduct of the study 
according to this protocol, applicable regulatory requirements, and hospital EC/REB
requirements.
I agree to and understand the material presented in this protocol, and must not publicly 
disclose in any manner the design, results, or conclusions of this investigation without prior 
written consent from Urotronic. 
___________________________________ 
Clinical Site Name
___________________________________   
 
_____________________ 
Site Principal Investigator Signature  
 
 
Date
__________________________________ 
Site Principal Investigator
Printed Name

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Protocol Summary 
 
Title:   
ROBUST 1 
Re-Establishing Flow Via Drug Coated Balloon For The Treatment Of 
Urethral Stricture Disease 
Objective: 
The study described below is designed to determine the safety and 
effectiveness for drug-coated balloon (DCB).  
Study Design:  
Single arm, multicenter study 
Enrollment: 
Up to 50 Subjects 
Target Subject 
Population: 
1. Male subjects  18 years’ old  
2. Visual confirmation of stricture via cystoscopy or urethrogram 
3. Single lesion anterior urethral stricture or bladder neck contracture 
less than or equal to 2 cm  
4. One to three (1-3) prior diagnosis and treatment of stricture treatments 
(including self-catheterization) including DVIU, but no prior 
urethroplasty 
5. Significant symptoms of stricture such as frequency of urination, 
dysuria, urgency, hematuria, slow flow, feeling of incomplete 
emptying, recurrent UTI's.   
6. IPSS score of 13 or higher  
7. Lumen diameter <12F by urethrogram 
8. Able to complete validated questionnaire independently 
9. Qmax <10 ml/sec  
Follow-up: 
5 days, 14 days, 30 days, 3 months, 6 months, 12 months,  Annually up to 
5 years 
Endpoint 1 
Rate of Treatment Related Serious Complication  
Endpoint 2 
Improvement in IPSS  
Endpoint 3 
Improvement LUTS Voiding Construct (Mundy PROM) Score 
Endpoint 4 
Stricture Recurrence Rate 
Endpoint 5 
Change in IIEF  
Endpoint 6 
Repeat Treatment Rate 
Endpoint 7 
Change in Qmax at 3 and 6 months 

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Endpoint 8 
Paclitaxel content in blood, urine and semen 
Endpoint 9  
Stress Urinary Incontinence at <90 days and >90 days 
Study and Data 
Management: 
Libra Medical, Inc. 
8401 73rd Ave N, Suite 63 
Minneapolis, MN 55428 
Tel: 763-477-5606 
Fax: 763-477-6357 
Email: swtay@libramed.com 
Study Monitors: 
Libra Medical, Inc. 
8401 73rd Ave N, Suite 63 
Minneapolis, MN 55428 
Tel: 763-477-5606 
Fax: 763-477-6357 
Email: swtay@libramed.com 
Sponsor: 
Urotronic Inc 
13705 26th Ave N #102 
Minneapolis, MN 55441 
 
 
 
 

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Table of Content 
1 
INTRODUCTION ............................................................................................................................. 11 
1.1 
DISEASE STATE OVERVIEW AND EPIDEMIOLOGY ............................................................................................ 11 
1.2 
STRICTURE DIAGNOSIS ............................................................................................................................. 11 
1.3 
CURRENT STANDARD OF CARE ................................................................................................................... 12 
1.4 
HISTORY OF USE OF PACLITAXEL ................................................................................................................. 13 
1.5 
RATIONALE FOR STUDY ............................................................................................................................. 14 
2 
DEVICE DESCRIPTION ..................................................................................................................... 14 
3 
STUDY OBJECTIVES AND DESIGN .................................................................................................... 15 
3.1 
OBJECTIVE ............................................................................................................................................. 15 
3.2 
STUDY DESIGN ........................................................................................................................................ 15 
3.3 
STUDY ENDPOINTS .................................................................................................................................. 16 
3.3.1 
Endpoint 1: Rate of Treatment Related Serious Complication .................................................. 16 
3.3.2 
Endpoint 2: Improvement in IPSS (International Prostate Symptoms Score) ............................ 17 
3.3.3 
Endpoint 3: Stricture Recurrence Rate ...................................................................................... 17 
3.3.4 
Endpoint 4: Improvement LUTS (Lower urinary tract symptoms) Voiding Construct (Mundy 
PROM) Score (Patient-reported outcome measure) ............................................................................... 17 
3.3.5 
Endpoint 5: Change in IIEF (International Index of Erectile Function) ....................................... 17 
3.3.6 
Endpoint 6: Repeat Treatment Rate ......................................................................................... 17 
3.3.7 
Endpoint 7: Change in Qmax (Peak Flow Rate) at 3 and 6 months .......................................... 17 
3.3.8 
Endpoint 8: Paclitaxel content in blood, urine and semen ........................................................ 17 
3.3.9 
Endpoint 9: Stress Urinary Incontinence at <90 days and >90 days ......................................... 17 
3.3.10 
Endpoint 10: Treatment Failure at 90 days .............................. Error! Bookmark not defined. 
4 
SUBJECT SELECTION ....................................................................................................................... 17 
4.1 
INCLUSION CRITERIA ................................................................................................................................ 18 
4.2 
EXCLUSION CRITERIA ................................................................................................................................ 18 
4.3 
SITE SELECTION ....................................................................................................................................... 19 
5 
PHYSICIAN SELECTION ................................................................................................................... 19 
6 
STUDY PROCEDURES ..................................................................................................................... 19 
6.1 
PRE SCREENING, SCREENING, AND BASELINE ................................................................................................ 19 
6.2 
SUBJECT ENROLLMENT ............................................................................................................................. 22 
6.3 
CONCOMITANT THERAPY .......................................................................................................................... 22 
6.4 
DCB TREATMENT STUDY PROCEDURE ......................................................................................................... 22 
6.4.1 
Peri Procedural Medication ...................................................................................................... 24 
6.4.2 
DCB Treatment ......................................................................................................................... 24 
6.4.3 
Treatment Rules ........................................................................................................................ 25 
6.4.4 
In-Hospital to Discharge ........................................................................................................... 25 
6.5 
RETREATMENT ........................................................................................................................................ 26 
6.5.1 
Retreatment Rules .................................................................................................................... 26 
6.6 
SCHEDULED FOLLOW-UP EVALUATIONS ....................................................................................................... 27 
6.7 
UNSCHEDULED FOLLOW-UP VISITS ............................................................................................................. 31 
6.8 
PREMATURE EXIT OR ALTERNATE TREATMENTS ............................................................................................. 31 

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6.9 
MULTIPLE IPSS AND MUNDY PROM RESPONSES ......................................................................................... 31 
6.10 
LOST TO FOLLOW-UP .......................................................................................................................... 31 
6.11 
SUBJECT WITHDRAWAL FROM STUDY ..................................................................................................... 31 
6.11.1 
Voluntary Withdrawal.......................................................................................................... 31 
6.11.2 
Data Withdrawal Due to Exclusion Criteria ......................................................................... 31 
6.11.3 
Involuntary Withdrawal ....................................................................................................... 32 
6.12 
END OF STUDY ................................................................................................................................... 32 
7 
SUBJECT EVALUATION DESCRIPTION .............................................................................................. 32 
7.1 
SUBJECT QUESTIONNAIRES ........................................................................................................................ 32 
7.1.1 
USS Score .................................................................................................................................. 32 
7.1.2 
Mundy PROM ............................................................................................................................ 32 
7.1.3 
IPSS (Standard) ......................................................................................................................... 33 
7.1.4 
IPSS (Acute) ............................................................................................................................... 33 
7.1.5 
International Index of Erectile Function .................................................................................... 33 
7.1.6 
Subject Pain Questionnaire ....................................................................................................... 33 
7.2 
UROFLOWMETRY .................................................................................................................................... 33 
7.2.1 
Peak Flow Rate (Qmax) Measurement ..................................................................................... 34 
7.2.2 
Post Void Residual Urine Volume .............................................................................................. 34 
7.3 
FLEXIBLE CYSTOSCOPY .............................................................................................................................. 34 
7.4 
URETHROGRAM ...................................................................................................................................... 34 
7.5 
RUBBER CATHETER .................................................................................................................................. 35 
8 
STATISTICAL CONSIDERATIONS ...................................................................................................... 35 
8.1 
STATISTICAL ANALYSES ............................................................................................................................. 35 
9 
DEFINITION OF ADVERSE EVENT(S) ................................................................................................ 35 
9.1 
TREATMENT RELATED SYMPTOMS .............................................................................................................. 35 
9.2 
URINARY RETENTION AND CATHETERIZATION ............................................................................................... 36 
9.3 
URINARY RETENTION DEFINITION ............................................................................................................... 36 
9.4 
OBSTRUCTIVE LUTS ................................................................................................................................ 36 
9.5 
CODING OR CLASSIFICATION OF AES ........................................................................................................... 37 
9.6 
POTENTIAL ANTICIPATED ADVERSE EVENTS .................................................................................................. 38 
9.7 
DEFINITION OF SERIOUS ADVERSE EVENT(S) ................................................................................................. 41 
9.8 
UNANTICIPATED ADVERSE DEVICE EFFECT(S) (UADE) .................................................................................. 41 
9.9 
REPORTING OF ALL ADVERSE EVENTS .......................................................................................................... 42 
9.10 
RELATIONSHIP OF AES TO THE DEVICE .................................................................................................... 42 
9.11 
DEVICE FAILURES, MALFUNCTIONS AND NEAR INCIDENTS .......................................................................... 43 
10 
TRAINING ...................................................................................................................................... 43 
11 
DATA MANAGEMENT .................................................................................................................... 43 
11.1 
SUBJECT IDENTIFICATION ..................................................................................................................... 43 
1.1 
CENTRAL DATABASE ................................................................................................................................ 44 
12 
STUDY RESPONSIBILITIES AND MANAGEMENT ............................................................................... 44 
12.1 
INVESTIGATOR RESPONSIBILITIES ........................................................................................................... 44 
12.2 
SUBJECT ENROLLMENT PROCESS ............................................................................................................ 45 
12.3 
ETHICS COMMITTEE (EC) / INSTITUTIONAL REVIEW BOARD (IRB) ............................................................... 45 
12.4 
INFORMED CONSENT FORM (ICF) ......................................................................................................... 45 
12.5 
CASE REPORT FORMS (CRFS) ............................................................................................................... 46 
12.6 
RECORDS .......................................................................................................................................... 46 

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12.7 
REPORTS ........................................................................................................................................... 47 
12.8 
SPONSOR RESPONSIBILITIES .................................................................................................................. 48 
12.8.1 
Confidentiality ...................................................................................................................... 48 
12.8.2 
Amending the Investigational Study Protocol ...................................................................... 49 
12.8.3 
Protocol Deviations .............................................................................................................. 49 
12.8.4 
Protocol Deviation Notification/Approval to EC/IRB/Sponsor before Implementation ....... 49 
12.8.5 
Site Noncompliance and Nonperformance .......................................................................... 49 
12.8.6 
Device Accountability ........................................................................................................... 50 
13 
STUDY ADMINISTRATION .............................................................................................................. 50 
13.1 
MONITORING PROCEDURES .................................................................................................................. 50 
13.1.1 
Monitoring Visit ................................................................................................................... 51 
13.1.2 
Study Closure ....................................................................................................................... 52 
14 
STUDY CONTACT ........................................................................................................................... 52 
14.1 
STUDY PRINCIPAL INVESTIGATOR ........................................................................................................... 52 
14.2 
SPONSOR .......................................................................................................................................... 52 
14.3 
MONITOR AND DATA MANAGEMENT ..................................................................................................... 52 
15 
POTENTIAL DEVICE CHANGE .......................................................................................................... 52 
16 
GLOSSARY OF ABBREVIATION ........................................................................................................ 53 
17 
REFERENCES .................................................................................................................................. 54 
 
 
 

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1 INTRODUCTION 
 
1.1 Disease State Overview and Epidemiology 
A urethral stricture is scarring in the urethra or surrounding tissue that narrows or blocks 
the passageway through which urine flows from the bladder. The stricture can result from 
inflammation, infection or injury, and is much more common in men than in women. The 
scarring can occur anywhere between the bladder and the tip or opening of the urethra. In 
addition to uncomfortable urinary symptoms such as reduced flow rate and frequent 
urination, a urethral stricture can lead to complications that include urinary tract infections, 
prostatitis, urinary retention and kidney damage. There were 1.5 million office visits from 
1992 to 2000 in US for the treatment of urethral strictures, and resulted in $191 million in 
health care expenditures11. 
Initial therapy for strictures is frequently dilation, which involves either balloon or rigid 
dilation to open the urethral stricture and allow normal voiding to occur. The most common 
complication subsequently to dilation is stricture recurrence, possible with increased 
length, due to adjacent tissue damage2. Potential advantages of balloon dilation vs. 
sequential rigid dilation has been described1.2.  Balloon dilation allows less discomfort and 
reduced risks because of less shearing force and reduced trauma, compared to the 
traditional rigid dilators2. More severe strictures can require surgical intervention for 
recurrent or long complicated lesions. 
 
1.2 Stricture Diagnosis 
Patients with lower urinary tract symptoms will have their urinary flow rate measured as 
part of the initial investigation of lower urinary tract symptom.  In those who have a 
urethral stricture, the peak flow rate is typically low but with a flat flow pattern as shown in 
Figure 1-1. 
This flow pattern is pathognomomic of a urethral stricture.  The presence of the stricture 
must be diagnosed by urethrogram to determine the exact site and length of the stricture 
and its potential complications.  Ultrasound may show a thickening of the bladder wall 
associated with longstanding outflow obstruction, and a presence of residual urine. 
 

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  Figure 1-1: Characteristic Pattern for Urine Flow in the Presence of Stricture 
 
1.3 Current Standard of Care 
Urethral strictures are still a common and challenging problem in urology.  Although open 
urethroplasty remains the gold standard of care, it requires good expertise and is invasive.11   
The simplest form of treatment is urethral dilation using a balloon, or rigid dilators.  The 
normal urethral caliber is 24-26F at the external urinary meatus, a little wider in the penile 
urethra, and about 36F at the bulbar urethra.13  
The principle of urethral dilation is to stretch the urethral stricture up or to disrupt it to 
restore the urethral caliber to normal or thereabout.  Urethrotomy and dilation are equally 
effective with expected cure rate of about 50% for short bulbar urethral strictures when first 
used.  The success rate of repeated procedure is lower13.   
When strictures recur, they usually do so within weeks or months and almost always within 
two years.  The expected recurrence rate reported are schematically summarized in Figure 
1-2. 

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        Figure 1-2: Stricture Recurrence Rate
The average time to recurrence for previously treated stricture is 3 months.  Hazard 
function analysis showed that the risk of stricture recurrence was greatest at 6 months, 
whereas the risk of failure after 12 months was slight11.  
1.4
History of Use of Paclitaxel
Paclitaxel has been used extensively and successfully in drug-coated devices to reduce the 
rate of stenosis in vascular tissue.  Examples of the devices coated with this drug and the 
dates of approval in the US are shown in Table 1-1.  The improvement in restenosis rates 
led Urotronic to design a similar system to treat urinary strictures.
Table 1-1: US Approved Paclitaxel Coated Devices
Drug Coated Balloon 
US Approval Date 
Boston Taxus DES 
2004 
Cook Zilver PTX DES 
2012 
Lutonix DCB 
2014 
Medtronic DCB
2015 
Urotronic DCB
TBD

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1.5 Rationale for Study 
Balloon dilation is the least invasive treatment for strictures.  However, because of the 
nature of strictures, recurrence of the stricture (50% - 75%) following balloon dilation is  
common2.  When stricture recurs after balloon dilation, treatment often progresses to more 
invasive treatments: internal urethrotomy is a slightly more invasive approach that involves 
an endoscopic incision of the stricture, but is not more effective than dilation8,9,10; 
urethroplasty is an open surgery for stricture disease that is more effective but far more 
invasive than dilation or internal urethrotomy.  Urethroplasty is performed by a minority 
(~2%) of urologists and the vast majority of subjects are managed by less invasive 
therapies.  Any improvement in technique or means of changing the natural history and 
progression of the disease would make a significant clinical contribution.  The study 
described below is designed to determine the safety and effectiveness of the drug coated 
balloon (DCB).    
2 DEVICE DESCRIPTION 
 
Figure 2-1:  Urotronic 0.038” Paclitaxel-Coated Balloon Catheter  
 
The Urotronic Drug Coated Balloon (DCB) is a 0.038” guidewire compatible over-the-wire 
catheter with a tapered atraumatic tip. The distal end of the catheter has a semi-compliant 
inflatable balloon coated with a proprietary coating containing the drug paclitaxel and 
carriers that facilitates the drug’s transfer to the urethral wall upon inflation.    
Paclitaxel is an anti-inflammatory and anti-proliferative drug commonly used to prevent 
arterial restenosis. The drug coating covers only the balloon body.  Initially, the device will 
be available in one size only 24Fr diameter.   Urotronic believes this size will be sufficient 
to treat the majority of the stricture.  However, during the study, other sizes may be 
introduced if the need arises. 
The device has two radiopaque marker bands that indicate the drug coated working length 
of the balloon under fluoroscopy.  The device is provided sterile, and is intended for single 
use only. 

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3 STUDY OBJECTIVES AND DESIGN 
3.1 Objective 
The study described below is designed to determine the safety and effectiveness for drug 
coated balloon (DCB).  
3.2 Study Design  
This is a prospective, non-randomized, open label, multi-center pilot study.  Up to 50 
subjects will be enrolled and treated with the device at up to 5 clinical sites.  Due to the 
significantly higher prevalence of strictures in men vs. women and the etiology of those 
strictures being different, the study will focus on male subjects with single anterior urethral 
stricture.  Subjects will be followed up post-treatment at 5 days, 14 days, 30 days, 90 days, 
180 days and 365 days, and then annually for up to 5 years.  The annual follow up after the 
first year is optional.  The diagnostic and treatment algorithm for the trial is shown in 
Figure 3-1.   

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Figure 3-1: Study Treatment Flow Chart 
 
3.3 Study Endpoints 
3.3.1 Endpoint 1: Rate of Treatment Related Serious Complication  
This safety endpoint is defined as a composite device related serious complications at 90 
days.  Device related is defined to include both device and procedure related.   

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x Device related formation of fistula  
x Device related de novo severe urinary retention lasting > 14 consecutive days’ post-
treatment. 
x Device related Unresolved de novo stress urinary incontinence (requiring >1 
pad/day) at 90 days or earlier 
x Urethra rupture or burst 
3.3.2 Endpoint 2: Improvement in IPSS (International Prostate Symptoms Score) 
 
3.3.3 Endpoint 3: Stricture Recurrence Rate 
The definition of stricture recurrence is the urethra lumen being < 14 F with or without 
recurrence of symptoms at 6 months.  The urethra caliber will be measured as follows: 
• 
3DVVDJHRIDIOH[LEOHF\VWRVFRSHWRGHWHUPLQH)UXrethral caliber   
• 
If the 16F flexible scope would not pass, then a 14 Fr flexible rubber 
catheter will be inserted through the treated section  
Note: Obstruction symptoms due to BPH (Benign Prostatic Hyperplasia) will not be 
considered a stricture recurrence. 
3.3.4 Endpoint 4: Improvement LUTS (Lower urinary tract symptoms) Voiding 
Construct (Mundy PROM) Score (Patient-reported outcome measure) 
3.3.5 Endpoint 5: Change in IIEF (International Index of Erectile Function) 
3.3.6 Endpoint 6: Repeat Treatment Rate 
This is defined as repeat surgery or treatment for urethral stricture in the same location of 
the urethra. 
3.3.7 Endpoint 7: Change in Qmax (Peak Flow Rate) at 3 and 6 months 
Assessment of the maximum urinary flow rate during uroflowmetry.  The test is only valid 
if the voided volume is greater than 125ml. 
3.3.8 Endpoint 8: Paclitaxel content in blood, urine and semen 
Measurements will be measured by an independent laboratory following GLP regulations. 
3.3.9 Endpoint 9: Stress Urinary Incontinence at <90 days and >90 days 
x   
Cystoscope or catheter should not be passed through the treatment area unless medically 
indicated or physician suspect the patient’s health is in jeopardy or treatment failure is 
suspected based on one or both of the criteria above.  Obstructive symptoms due to other 
reasons (e.g. BPH, bladder neck constriction) other than stricture is not considered a 
treatment failure. 
4 SUBJECT SELECTION 
A subject is considered enrolled if: 

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x Meet all the inclusion criteria  
x Does not meet ANY exclusion criteria 
x Provided informed consent 
x Introduced the investigational device 
4.1 Inclusion Criteria 
1. Male sXEMHFWV\HDUV¶ROG 
2. Visual confirmation of stricture via cystoscopy or urethrogram 
3. Single lesion anterior urethral stricture or bladder neck contracture, less than or 
equal to 2.0 cm 
4. One to three (1-3) prior diagnosis and treatment of the same stricture (including 
self-catheterization) including DVIU (Direct Vision Internal Urethrotomy), but 
no prior urethroplasty 
5. Significant symptoms of stricture such as frequency of urination, dysuria, 
urgency, hematuria, slow flow, feeling of incomplete emptying, recurrent UTI's.   
6. IPSS score of 13 or higher  
7. Lumen diameter <12F by urethrogram 
8. Able to complete validated questionnaire independently 
9. Qmax <10 ml/sec  
4.2 Exclusion Criteria 
1. Strictures greater than 2.0 cm long. 
2. Subjects that have more than 1 stricture. 
3. Sensitivity to paclitaxel or on medication that may have negative interaction 
with paclitaxel 
4. Subjects who have a suprapubic catheter and are unable to complete study 
required testing, such as uroflowmetry 
5. Previous urethroplasty within the anterior urethra 
6. Stricture due to bacterial urethritis or untreated gonorrhea 
7. Stricture dilated or incised within the last 3 months 
8. Presence of local adverse factors, including abnormal prostate making 
catheterization difficult, urethral false passage or fistula.   
9. Presence of signs of obstructive voiding symptoms not directly attributable to 
the stricture such as BPH at the discretion of the clinical investigator 
10. Previous radical prostatectomy  
11. Previous pelvic radiation 
12. Diagnosed kidney, bladder, urethral or ureteral stones or active stone passage in 
the past 6 months.   
13. Diagnosed with chronic renal failure unless under hemodialysis or has a serum 
creatinine level greater than 2 mg/dL 
14. Use of alpha blockers, beta blockers, OAB (Overactive Bladder) medication, 
anticonvulsants (drugs that prevent or reduce the severity and frequency of 
seizures), and antispasmodics where the dose is not stable.  (Stable dose is 
defined as having the same medication and dose in the last six months.)  
15. Use of Botox (onabotulinumtoxinA) in urinary system within the last 12 months 

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16. Presence of a penile implant, artificial urinary sphincter, or stent(s) in the 
urethra or prostate 
17. Known neurogenic bladder, sphincter abnormalities, or poor detrusor muscle 
function 
18. Diagnosed with Lichen Sclerosus, or previous hypospadias repair  
19. History within the last 5 years of carcinoma of the bladder or prostate 
20. History of cancer in non-genitourinary system, which is not considered, cured 
(except basal cell or squamous cell carcinoma of the skin).  A potential 
participant is considered cured if there has been no evidence of cancer within 
five years of randomization 
21. Any cognitive or psychiatric condition that interferes with or precludes direct 
and accurate communication with the study investigator regarding the study or 
affect the ability to complete the study quality of life questionnaires 
22. 8QZLOOLQJWRXVHSURWHFWHGVH[IRUGD\VSRVWWUHDWPHQW 
23. Inability to provide legally effective Informed Consent Form (ICF) and/or 
comply with all of the required follow-up requirements 
24. Participation in other pre-market studies 
25. Stricture due to balanitis xerotica obliterans (BXO) 
 
4.3 Site Selection 
Sites will be selected based on the availability of the subject pool to be included in the 
study and the sites’ ability to perform the research in compliance with GCP guidelines. 
In addition, the sites must be able to comply with any country-specific requirements as 
well as other requirements specified by their respective institutional ethics committees 
(EC).   
5 PHYSICIAN SELECTION 
Physicians selected must have experience in performing cystoscopies, treating strictures 
endoscopically as well as urethral reconstruction and/or other male urological therapies.  
Selected physicians will be trained in the use of the Urotronic DCB prior to enrolling 
subjects.  The primary investigator will ensure that only trained sub-investigators who 
satisfy the physician selection criteria can perform any part of the study interventional 
procedure.   
Healthcare professionals or site staff that assist or perform the follow-up evaluations do not 
need to be trained on the use of the device but must be delegated and trained to perform the 
follow-up visit procedures. 
6 STUDY PROCEDURES 
6.1 Pre Screening, Screening, and Baseline 
The site may pre-screen potential subjects by reviewing medical records to identify the 
study population.  Once identified these subjects are approached for the study and 

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consented.  The site may not initiate any study specific (non-standard of care) procedures 
without first obtaining informed consent.    
All baseline testing and evaluations must be done as close to the time of treatment as 
possible and repeated if needed.  A baseline urethrogram must be performed prior to 
enrollment.  Any required procedures performed before obtaining informed consent as part 
of the standard of care may be used in lieu of the study tests as described in Table 6-1.  
The following evaluations will be completed for all study candidates.   Evaluations 
performed within the screening window may be acceptable.  The required baseline 
evaluations prior to enrollment are shown below: 
 
Table 6-1: Screening Evaluations Conditions 
Evaluations 
Accepted interval 
prior to procedure 
(unless specified 
otherwise) 
Condition 
Medical history  
Within 30 days 
Evaluation is complete and 
adequately documented in 
report for assessment 
Physical exam evaluation 
Within 30 days 
Evaluation is complete and 
adequately documented in 
report for assessment 
Uroflowmetry1 
x 9RLGHGYROXPHPXVWEHP/
or test must be repeated for all the 
uroflow tests) 
x Voiding time 
x Peak flow rate (Qmax)1  
x Average flow rate 
 
 
The uroflow reading 
must be within 30 
days of treatment 
Must be performed before 
F\VWRVFRS\RUGD\VDIWHU
cystoscopy and no evidence of 
UTI 
The uroflow method used in 
the second screening test must 
be the same as that used in the 
follow-up tests. 
Post-void residual urine volume (PVR; 
may be measured by either ultrasound or 
catheterization but the same method 
must be used pre- and post-treatment) 
 
Within 30 days of 
treatment 
Must be performed before 
F\VWRVFRS\RUGD\VDIWHU
cystoscopy and no evidence of 
UTI 
The PVR method used during 
screening must be the same as 
that used in the follow-up 
tests. 
Blood analysis 
x 
Complete blood cell count 
(CBC) 
x 
Blood urea nitrogen  (BUN) 
Within 30 days  
 
 
 
 

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Evaluations 
Accepted interval 
prior to procedure 
(unless specified 
otherwise) 
Condition 
x 
Serum creatinine 
x 
Alanine aminotransferase 
(ALT) 
x 
Drug Analysis 
 
Urine analysis 
x 
Sugar 
x 
Protein 
x 
WBC/RBC 
x 
Bacteria 
x 
Drug analysis 
x 
UTI 
Within 7 days 
Must be negative for infection 
before enrolling 
Urine culture for infection only if 
infection is suspected 
Within 7 days 
Must be negative for infection 
before enrolling 
Semen collection 
Within 30 days 
Patients must abstain from 
ejaculation 48 hours prior to 
semen collection 
Urethral Stricture Score (USS) 
Within 30 days 
None 
Subject questionnaires  
x 
Mundy PROM  
x 
International Prostate 
Symptoms Score (IPSS) - 
Standard 
x 
International Index of Erectile 
Function (IIEF) 
x 
VAS Pain Scale 
Within 30 days 
Must have documented 
negative infection before 
enrolling and before taking the 
IPSS Mundy PROM at 
baseline 
Screening flexible cystoscopy  
Within 2 months prior 
to enrollment 
Prior cystoscopy before 
enrollment is acceptable only 
if video is available for 
viewing 
Screening urethrogram (recorded)  
Within 30 days prior 
to enrollment 
Prior urethrogram before 
enrollment is acceptable only 
if video is available for view 
Current or prior (up to 6 months) 
medication consumption 
Prior to enrollment 
A list of current and prior 
medication is required to 
determine if the dose is stable.  

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6.2 Subject Enrollment 
Only subjects who meet the inclusion/exclusion criteria will be eligible to be enrolled and 
participate in the study.   
6.3 Concomitant Therapy 
Therapy (medication and non-medication therapies) not restricted by a protocol 
requirement may be used during the study for the treatment or prevention of disease or to 
maintain good health. However, the subjects should not take concomitant medications that 
affect the urinary symptoms which might confound the study result.   
Standard dose of antibiotic is required to be administered before and after treatment. 
6.4 DCB Treatment Study Procedure 
The treatments for the study may be performed in a hospital or ambulatory surgical center.  
A summary of a typical procedure is described in this section.  The treatment algorithm is 
schematically shown in Figure 6-1. 

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Figure 6-1: Treatment Algorithm 
 

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6.4.1 Peri Procedural Medication  
General anesthetics is recommended for all patients.  Recorded anesthesia used in the case 
report form.  
A 5-day course of oral antibiotic is required to be administered prior to the procedure.  If a 
urinary tract infection (UTI) is indicated, the patient must be treated until the infection is 
cured before the study procedure. Oral NSAID or low dose aspirin is also recommended to 
be given prior to the procedure. 
 
6.4.2 DCB Treatment 
The DCB should be prepared per the Instructions for Use (IFU).  A summary is provided 
below.  If the summary is different from the IFU, follow the instruction for the IFU. 
 
Predilation 
1. Perform a baseline urethrogram if one was not recorded within 7 days.  
RECORD the urethrogram. 
2. Place the guidewire through the urethra with the tip of the guidewire in the 
bladder.  Typically, this will be through the working channel of a 
cystoscope. 
3. Track the selected predilation catheter over the guidewire with the aid of the 
cystoscope alongside the catheter.   
4. Check the position of the balloon radiopaque markers are in the correct 
position using fluoroscopy. 
5. Predilate the stricture with a standard uncoated balloon (POBU), plain old 
balloon urethroplasty).  Do not exceed rated burst pressure of the balloon.  If 
the stricture is not dilatable (Dilatable is defined as stricture diameter post 
prHGLODWLRQLQFUHDVHE\20F by visual estimation or at physician 
discretion), the subject will be treated per DVIU prior to DCB treatment. 
6. If DVIU is indicated (see Figure 6-1); perform DVIU in 3 positions 
(approximately: 12 o’clock, 5 o’clock and 7 o’clock).   
7. Perform a urethrogram.  If the lumen is <20F, perform predilation with an 
uncoated balloon.  Record lumen size with urethrogram.   
DCB Treatment 
8. Ensure that the urethra is flushed with saline and fill the bladder with saline 
before introduction of the DCB. 
9. Position the DCB across the predilated or DVIU treated stricture with the 
cystoscope proximal to the balloon (away from the bladder) to visualize the 
proper placement of the balloon across the stricture.  Leave the balloon in 
position uninflated for a minimum of 1 minute prior to inflation. 
10. Check that the balloon radiopaque markers are in the correct position using 
fluoroscopy. 

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11. Inflate the balloon with a 50/50 contrast solution  using the Balloon 
Indeflator.  Do not exceed rated burst pressure of the balloon.  Maintain 
pressure for a minimum of 5 min. 
12. RECORD the fluoroscopic image with the balloon inflated.  Record the 
inflation pressure. 
13. Remove the device(s).   
14. Collect urine sample (2nd void): 
a. Ask subject to void or palpate the bladder to allow about 1 cup (100 
– 150ml) of fluid to flow out of the urethra to flush any residual 
coating particles. This is recognized as the 1st void  
b. Then ask subject to void or palpate the bladder again, collect the 
urine sample for about 100 ml or any remaining residual fluid for 
analysis. This is recognized as the 2nd void.   
15. Insert a 12-14 Fr Foley catheter (provided by the sponsor) for at least 5 days.  
Record the Foley catheter size and time of catheter removal. 
6.4.3 Treatment Rules 
x An increase of urethral caliber lumen to 20F or greater must be achieved by 
predilation to proceed to DCB treatment.  If dilation failed to increase the lumen by 
20F or greater, the subject will be treated with DVIU, followed with a DCB 
treatment.  At the physician discretion, the patients may be enrolled directly into the 
DVIU group.  
x The DCB balloon catheter must be inflated at the target stricture to the 
recommended pressure for a minimum of 5 minutes with saline/contrast.   
x After dilation with DCB, no instrumentation can be passed through the stricture 
acutely with the exception of the Foley catheteU)VL]HZKHQPHGLFDOO\
needed. 
x Use only the lubricious Foley catheter provided by the sponsor. 
 
6.4.4 In-Hospital to Discharge 
Oral non-steroidal anti-inflammatory drugs (NSAIDs) are recommended together with the 
use of antibiotic.   
 
Blood PK (Pharmacokinetics) Samples 
For subjects (up to 30), who agreed to be part of the PK cohort, a total of 8 blood samples 
will be collected per subject, at the following time points. The first blood sample at 
baseline, then the next 6 blood samples (#2 - #7) will be drawn prior to discharge.  The 8th 
blood sample will be drawn post discharge at the 5 days follow up visit.  After June 5th, 
2017, only the subjects who have DVIU, or have the 2nd study procedure (Retreatment), 
will be asked to participate in the PK test.          
          
 

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Time points of blood sample collection: 
   # of 
Samples 
Time points 
Approximate 
Compliance Window* 
1.  
Baseline  
- 30 days of procedure 
2.  
0 hr  
+ 25 min 
3.  
1 hr 
+ 30 min 
4.  
3 hrs 
± 1 hr 
5.  
5 hrs 
± 1 hr 
6.  
10 hrs 
± 2 hrs 
7.  
24 hrs 
± 4 hrs 
8.  
5 days 
± 1 day 
The definition for “0 hour” is post-procedure soon after collecting the urine sample.  
 Sexual Activities 
All subjects must be counseled about sexual activities post treatment as follows: 
x All patients will be asked to ABSTAIN from ALL sexual activities including 
masturbation for 14 days 
x 48 hours prior to semen collection, patients must abstain from ejaculation 
x Use of condom or abstain from sex for the first 30 days after treatment.  The time of 
protected sex may be extended by the physician depending on the drug test results 
in the semen. 
 
6.5 Retreatment  
6.5.1 Retreatment Rules 
A subject may undergo a retreatment procedure at any point after the 3-month follow-up or 
before the 6-month follow-up visit, if the retreatment is recommended by the treating 
physician and meet one of the following criteria: 
1. 
Treatment was not successful and subject still experienced retention and continue 
to meet the inclusion and exclusion criteria  
2. 
Initial DCB treatment was abandoned or truncated due to discomfort, poor 
visibility or incorrect placement of DCB.  In this instance, retreatment can be 
performed prior to the 3 months. 
3. 
Subjects must continue to meet the initial inclusion/exclusion criteria to be 
eligible for retreatment. 
All retreatment subjects will have the stricture predilated with DVIU prior to DCB 
treatment.  Only one retreatment is allowed for each subject.  The safety and effectiveness 
data collected post-retreatment will be pooled with the other subjects for analysis but the 
retreatment cohort data will also be summarized and provided separately.  Retreated 

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subjects will be followed out to 5 year follow-up time points, starting from the retreatment 
time , under the same subject ID.   
 
 
6.6 Scheduled Follow-up Evaluations 
The following evaluations will be completed at each visit as indicated in Table 6-2.  
Subjects will be evaluated at baseline, immediately post-procedure, 5 days, 14 days, 30 
days, 3 months, 6 months and 12 months’ post-procedure.   
Annual evaluation of the stricture treatment may be followed for up to 5 years post 
treatment. 

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Table 6-2: Scheduled Evaluations and Follow UP 
 
Baseline 
Intra-
Procedure  
Pre-
Discharge 
5 days 
14 days 
30 days 
3 
Months 
6 and 12 
Months 
Annually for 
up to 5 years 
Unschedul
ed Visit 
Compliance 
Window 
-30 days 
NA 
NA 
± 1 
day 
± 2 days 
± 5 days 
± 14 
days 
± 30 days 
± 60 days 
NA 
Physical 
Examination 
 
 
 
 
 
 
 
 
 
 
Medication 
Usage Review 
 
 
 
 
 
 
 
 
 
 
Antibiotic 
 (pre-
procedure) 
 
 
 
 
 
 
 
 
 
Blood analysis 
(Complete blood 
cell count (CBC), 
Blood urea 
nitrogen  (BUN), 
Serum 
creatinine) 
 
 
 
 
 
 
 
 
 
 
Alanine 
aminotransferase 
(ALT) 
 
 
 
 
 
 
 
 
 
 
Urine Analysis 
(sugar, protein, 
WBC/RBC, 
Bacteria (UTI))  
 
Within 7 days 
of procedure 
 
 
 
 
 
 
 
 
 
 Urine collection 
(drug analysis) 
 
 
 
(2nd Void) 
 
 
 
 
 
 
 

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Baseline 
Intra-
Procedure  
Pre-
Discharge 
5 days 
14 days 
30 days 
3 
Months 
6 and 12 
Months 
Annually for 
up to 5 years 
Unschedul
ed Visit 
Compliance 
Window 
-30 days 
NA 
NA 
± 1 
day 
± 2 days 
± 5 days 
± 14 
days 
± 30 days 
± 60 days 
NA 
Blood collection 
(drug analysis) 
 1 
 
 1 
(multiple 
samples in 
24 hrs) 
 1 
 
 
 
 
 
 
Review Protected 
Sexual Activities  
 
 
 
 
 
 
 3 
 3 
(6 months 
only) 
 
 
Semen 
Evaluation 
 
(sperm 
quality) 
 
 
 
 
(sperm 
and drug) 
 
(sperm 
and drug) 
 
  
(6 months 
for sperm 
only) 
 
 
USS 
 
 
 
 
 
 
 
 
 
 
Mundy PROM  
 
 
 
 
 
 
 
 
 
 
IPSS, IIEF 
 
 
 
 
 
 
 
 
 
 
VAS Pain score 
 
 
 
 
 
 
 
 
 
 
Qmax 
 
 
 
 
 
 
 
 
 
 
PVR 
 
 
 
 
 
 
 
 
 
 
 
Urethrogram 
 
Record 
 4 
Record 
 
 
 
 
 
Record  
 
Record  
 
 

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Baseline 
Intra-
Procedure  
Pre-
Discharge 
5 days 
14 days 
30 days 
3 
Months 
6 and 12 
Months 
Annually for 
up to 5 years 
Unschedul
ed Visit 
Compliance 
Window 
-30 days 
NA 
NA 
± 1 
day 
± 2 days 
± 5 days 
± 14 
days 
± 30 days 
± 60 days 
NA 
 
Cystoscopy 
 
Record 
 
 
 
 
 
 
 
Record 
(16F 
cystoscope) 
 
 
Record 
14F Rubber 
catheter urethral 
Lumen 
evaluation 
 
 
 
 
 
 
 
 
(If 16F 
scope failed 
to pass) 
 
 
Subject 
Satisfaction 
Questionnaire 
 
 
 
 
 
 
 
 
 
 
AE Review 
 
 
 
 2 
 
 
 
 
 
 
Note 
1 – For the PK test, a total of 8 blood samples will be collected /patient. It requires patients to stay in the hospital overnight for blood draws at 0 , 1, 3, 5, 
10, 24 hrs post-procedurely. The blood draws at baseline and 5 days follow-up will be done accordingly, but no hospital stay is required. 
2 – Pain /discomfort after the procedure is common and to be expected. Steps can be taken to minimize or eliminate pain /discomfort. It is at physician’s 
discretion, whether the pain /discomfort is an adverse event, or a normal healing process. 
3 –  Review may be eliminated depending on the results of drug analysis from first 5 subjects. If so, a notice will be given to the study sites by Sponsor. 
4 – Recorded Fluroscopy/urethrogram required before any intervention, during predil, post dil, during DCB, after DCB (fluoroscopy only) 
 

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6.7 Unscheduled Follow-up Visits 
If subjects are seen for unscheduled/interim visits because of an AE, appropriate Case 
Report Form(s), including the AE CRF, will be completed if applicable.  At the 
investigator’s discretion, some of the evaluations and tests may be repeated if indicated.  
Sponsor requests that if any additional tests or procedures listed within this protocol are 
performed during an unscheduled visit the investigator provide the results on the 
Unscheduled Visit CRF. 
6.8 Premature Exit or Alternate Treatments 
Subjects that opt for alternate treatments for stricture within 3 months of treatment will be 
considered to have failed the treatment.  Treatment for BPH symptoms are not considered a 
failure. 
6.9 Multiple IPSS and Mundy PROM Responses 
If multiple responses to the same questionnaires are available for each visit window, the 
average value of the scores will be used unless there are valid scientific reasons to exclude 
one of the readings. 
6.10 Lost to Follow-up 
If a subject fails to comply with follow-up evaluations, the investigational site must make 
at least three repeated attempts to contact the subject.  Each attempt to contact the subject 
and the method used (e.g., telephone contact, registered letter) must be documented in the 
subject’s records.   
If a subject misses one of the follow-up evaluations, but is present at the subsequent 
follow-up, the subject can be readmitted into the study and queried retrospectively for basic 
information (e.g., AEs); however, the missed evaluation must be documented on a Protocol 
Deviation CRF.  The IPSS and other questionnaires will be collected prospectively only.   
 
6.11 Subject Withdrawal from Study 
6.11.1 Voluntary Withdrawal 
A subject may voluntarily withdraw from the study at any time.  If a subject officially 
withdraws from the study, the investigator must ensure that the reason for the withdrawal is 
documented.  If the subject had an AE, the subject should be followed until the resolution 
of the AE, if possible.  Data from these subjects will be included in the analysis up to the 
point of each subject’s withdrawal. 
6.11.2 Data Withdrawal Due to Exclusion Criteria 
A subject’s data may be excluded from the analysis if the subject is later found not to meet 
one or more major exclusion criteria.  However, these subjects will continue to be followed 
per the requirements of their particular arm unless instructed otherwise by the IRB/EC.  
The major exclusion criteria that would cause the withdrawal of the subjects’ data are: 
 

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x Failure to obtain an informed consent prior to treatment; 
x Subject has severe BPH 
x Subject had bladder or sphincter dysfunctions or anything else that will confound the 
results; 
x Subject had a psychiatric condition that prevents him from adequately answering the study 
questionnaires; or 
x Subject had a neuromuscular disorder that will confound the results. 
The decision to exclude the subject’s data from analysis will be documented in the CRF. 
6.11.3 Involuntary Withdrawal 
A subject also may be withdrawn by the investigator if the subject’s participation in the 
study will have a negative effect on the safety of the subject.  Data obtained up to the date 
of the subject’s withdrawal will be included in the study, if applicable.   
 
6.12 End of Study 
Subjects receiving the DCB treatment may exit the study at the end of the study (i.e., the 
study is discontinued by the Sponsor) or when the subject has completed the 5-year follow-
up visit, whichever comes first, unless the subject opted to find an alternative treatment.   
An End of Study CRF will be completed at the time the study is completed, discontinued, or 
lost to follow-up for each subject. 
 
7 SUBJECT EVALUATION DESCRIPTION 
7.1 Subject Questionnaires 
All questionnaires are self-administered and will be completed at baseline and at required 
follow-up visit.  Questionnaires completed at baseline will be compared to those completed 
at follow-ups to assess the effect of treatment.  The major instruments and assessments 
administered are described in this section. 
7.1.1 USS Score 
The USS is a numerical score based on five components of anterior urethral stricture 
disease that help dictate operative decision-making: (1) urethral stricture etiology; (2) t otal 
number of strictures; (3) retention (luminal obliteration); (4) anatomic location; and (5) 
length. The USS describes the essential factors in determining surgical treatment selection 
for urethral stricture disease. The USS is a concise, easily applicable instrument that 
delineates the clinically significant features of urethral strictures. 
7.1.2 Mundy PROM 
This is a validated patient-reported outcome measure (PROM) for anterior urethral stricture 
surgery constructed from existing questionnaire.  This PROM defined a succinct, practical, 
and psychometrically robust PROM designed specifically to quantify changes in voiding 

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symptoms and HRQoL following urethral stricture surgery and for this study will be 
referred to as the Mundy PROM for convenience.  Q1 to Q6 are based on ICIQ-MLUTS 
voiding construct and will be referred to as Mundy Prom Voiding Construct.   
7.1.3 IPSS (Standard) 
The International Prostate Symptom Score (IPSS) contains the well-validated, highly 
reliable and responsive American Urological Association symptom score (AUASS) 
assessment to identify the severity of BPH symptoms.  However, the symptoms of BPH 
and urinary stricture are very similar and has been used with strictures. 
The first seven questions in the IPSS address frequency, nocturia, weak urinary stream, 
hesitancy, intermittence, incomplete emptying, and urgency, and scored on a 6-point scale 
(0 to 5).  Although there are no standard recommendations for grading patients with mild, 
moderate, or severe symptoms, patients can be tentatively classified as follows: 0-7 mildly 
symptomatic, 8-19 moderately symptomatic, and 20-35 severely symptomatic. 
The IPSS also includes the following eighth question that is designed to assess the degree 
of "bother" associated with the subject's urinary symptoms: "If you were to spend the rest 
of your life with your urinary condition just the way it is now, how would you feel about 
that?"  Answers range from "delighted" to "terrible" (0-6).  This question correlates well 
with the overall BPH symptom score and summarizes the impact of urologic symptoms on 
quality of life. 
The standard IPSS will be administered at baseline and at each follow-up visit, except the  
one week follow-up.   
7.1.4 IPSS (Acute) 
The acute IPSS is the same as the standard IPSS except that the questions refer to the 
subject’s condition in the past week instead of the past month.  This IPSS will be 
administered at the one week follow-up visits and if indicated, at unscheduled visits. 
7.1.5 International Index of Erectile Function 
The International Index of Erectile Function (IIEF) is a standardized, validated, self-
administrated questionnaire that is used to assess the subject's erectile function.  The Sexual 
Health Inventory for Men (SHIM) is part of the IIEF and consist of 5 questions.  This is 
sometimes called IIEF-5 and is used as a diagnostic test for erectile dysfunction and 
impotence. 
7.1.6 Subject Pain Questionnaire 
Pre and post-procedure pain will be evaluated using a standardized pain questionnaire. 
 
7.2 Uroflowmetry 
Subjects will be asked to hydrate and refrain from voiding for two hours.  Hydration may 
be achieved by asking the subject to drink 2 or more cups of non-caffeinated fluids.   

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A bladder scan is recommended to be performed prior to voiding to ensure the subject has a 
bladder volume of at least 250 ml.  
Outcomes will be recorded for each qualified void on the case report forms and the strip 
recordings collected.  Voiding data will be obtained with the subjects in the standing or 
sitting position, voiding into the uroflow instrumentation.  The uroflow meter will provide 
the following information: 
x 9RLGHGYROXPHPOUHTXLUHGfor a valid test) 
x Peak flow rate, Qmax (5ml/sec to < 15 ml/sec to qualify) averaged over a 2 
second interval 
x Average flow rate 
x Voiding time 
7.2.1 Peak Flow Rate (Qmax) Measurement 
The recommendation for determining the Qmax reading is to apply the 2 second-rule to 
improve consistency.  This would avoid artifacts in the reading.   
7.2.2 Post Void Residual Urine Volume 
Following uroflowmetry, residual urine volume in the bladder shall be assessed by bladder 
scanner ultrasound.   
7.3 Flexible Cystoscopy 
A screening flexible cystoscopy may be performed to confirm the presence of stricture and 
to estimate the stricture conditions (length and size) prior to enrollment in the study.  The 
size and length is to be estimated without crossing the stricture at screening.  A post 
treatment flexible cystoscopy will be performed at the 6-month follow-up and subsequent 
follow up when cystoscopy is warranted.  
7.4 Urethrogram  
A retrograde urethrogram (RUG) is taken to diagnose the stricture, ensure the stricture is 
dilatable post predilation, and to assess stricture recurrence at follow-ups.  The general 
procedure steps are outlined below. 
x 
Position the patient and fluoroscope equipment so a lateral view, with the urethra in a 
single plane relative to the image is obtained. 
x 
Retract the foreskin and clean the tip of penis with betadine or antiseptic solution. 
x 
Liberally administer lidocaine jelly over the outside tip and shaft of a short 8F 
introducer sheath. 
x 
Place the introducer sheath into the tip of the penis.  Then place a markerwire into the 
introducer sheath down into the urethra.  Ensure the markers are visible in the 
fluoroscopic image. This is used for urethogram image distance calibration. 
x 
Attach a 50/50 saline/contrast loaded syringe to the introducer sheath. 
x 
Simultaneously inject the contrast and start a cine to capture the urethrogram. 

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Ideal image frames used for analysis demonstrate the entire length of the urethra with 
contrast beginning to fill the bladder. 
7.5 Rubber Catheter 
Rubber catheters with known diameters may be used to estimate the status of the stricture.   
 
8 STATISTICAL CONSIDERATIONS 
8.1 Statistical Analyses 
The data from the study will be tabulated using descriptive analyses.   
Descriptive analyses of all AEs and urinary symptoms will be provided in the report.  In 
addition, the report will include tabulated results of study deviations and device 
malfunctions. 
Details of the statistical analysis will be provided in the statistical analysis plan (SAP). 
 
9 DEFINITION OF ADVERSE EVENT(S) 
For purposes of this study, an adverse event (AE) is defined as any adverse change (i.e., de 
novo or preexisting condition) from the subject’s baseline medical condition(s) occurring 
during the course of the study.  For the purpose of AE documentation, the start of the 
course of the study is defined as any time after the treatment has been initiated.  All AE’s 
will be recorded in the CRF whether considered procedure-related or not, and will be 
classified as described in Section 9.5.  
Pre-existing conditions will not be reported as an AE unless there is an adverse change in 
that condition.  Any AE which resolved and then recurred will be reported as a separate 
AE.   
An AE may be volunteered spontaneously by the subject or discovered as a result of 
questioning or physical examination by an investigator or study staff. 
  
9.1 Treatment Related Symptoms 
The Urotronic DCB procedure is designed to treat strictures.  Subjects to be treated have 
moderate to severe LUTS prior to treatment.  These symptoms are expected to continue and 
may even worsen slightly prior to improvement as part of the healing process.  All reported 
LUTS will be documented in the CRF.  Other expected acute but transient worsening of 
symptoms from the treatment are dysuria, frequency of urination, urgency of urination, urge 
incontinence, hematuria, slowing of the urinary stream and acute retention as the tissue 
heals.  
Worsening or de novo LUTS, dysuria or non-obstructive hematuria that occur and resolve 
within 14 days of treatment that do not require intervention (other than catheterization, 

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prophylactic antibiotic, anti-inflammatory medication, and pain medication) will not be 
considered an AE as these are expected and part of the healing process.  However, all 
treatment and related symptoms will be recorded in the CRF.  
Intervention as it relates to hematuria includes but is not limited to, hospitalization, the 
need to irrigate the bladder and urethra, or the need for transfusion therapy.   
 
Common urinary symptoms will be considered an AE if any of the following occur: 
a. 
Worsening or de novo LUTS requiring intervention or persisting 
beyond 14 days post treatment; 
b. 
Worsening or de novo LUTS requiring hospitalization or intervention 
other than the use of catheterization, one standard course of antibiotic, 
anti-inflammatory and/or pain medication; 
c. 
Hematuria that requires irrigation or is obstructive; 
d. 
Urinary tract infection defined as >105 CFU of a single organism plus 
symptoms localized to bladder. 
e. 
Urinary retention that did not resolve within 10 days of treatment; or 
f. 
If de novo LUTS recurs after the same symptom is resolved and is 
considered clinically significant. 
 
9.2 Urinary Retention and Catheterization 
Acute urinary retention that resolves within 10 days will not be considered an AE.  
However, any catheterizations or cystoscopies will be recorded in the CRF.  Resolution is 
defined as a removal of the catheter without the need to reinsert it or use of intermittent 
self-catheterization.   
While catheterization in and of itself is not an AE, the reason for catheterization must be 
evaluated for purposes of determining an AE.    
9.3 Urinary Retention Definition 
Urinary retention, also known as ischuria, is a total lack of ability to urinate.  It is 
sometimes referred to as acute urinary retention and typically has to be treated with a 
catheter or stent to avoid serious complications of the bladder and/or kidney. 
9.4 Obstructive LUTS 
Obstructive LUTS has some symptoms similar to Urinary Retention.  Obstructive LUTS is 
usually a chronic condition and is sometimes referred to as chronic urinary retention.  
Symptoms of obstructive LUTS are: 
x 
Poor stream 
x 
Hesitancy 
x 
Terminal dribbling 
x 
Incomplete voiding 

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x 
Overflow incontinence (occurs in chronic retention) 
9.5 Coding or Classification of AEs 
Adverse events should be classified according to their underlying cause, if known (e.g., fever 
resulting from infection should be reported as “infection”).  Symptoms related to a diagnosis 
should not be reported as separate AEs.  In the above example, fever is a symptom caused by 
infection and should be reported as infection only.   
Concomitant AEs that are unrelated (in the clinician’s judgment) should be reported as 
separate events. 
 
AE determination is based on three levels of evidence: 
 
Level 1 – final diagnosis 
Level 2 – signs 
Level 3 – symptoms 
 
Every effort should be made to collect Level 1 evidence of any AE.  If an AE has all three 
levels of evidence, the AE should be reported only once at the highest level of severity, 
which is the final diagnosis (Level 1).  A single AE should not be reported as multiple AEs 
based on separate symptoms and signs. 
In cases where a diagnosis is not possible, AE determination should be based on the next 
highest level of evidence (i.e., Level 2: signs), followed by symptoms (Level 3), if 
symptoms are all that are available to the investigator.  
A corrective action (e.g. catheterization) itself is not an AE but the reason of the 
catheterization may be an AE.  The AE determination always should be based on the 
reason that a corrective action was taken.  Note: there may be multiple signs or symptoms 
representing only one AE.  Figure 9-1 below is an AE determination and outcome 
flowchart. 

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Complaint
Or Symptoms of 
AE?
Was 
there a medical
 exam?
Was 
there a final 
diagnosis?
Record Sign 
as AE
(Level 2)
Record 
diagnosis as AE
(Level 1)
Record AE as 
symptom
(Level 3)
Yes
Yes
No
No
Did AE 
cause death, 
permanent injury, 
Hospitalization or
required invasive 
intervention?
Report as SAE
Report as 
AE
Yes
No
 
Figure 9-1: AE Determination and Outcome Flowchart 
Example 1 (Diagnosis): prostatitis often has dysuria, urinary frequency, nocturia, difficult 
urination, pain in the groin, pelvic area or genitals, painful ejaculation, and sometimes, flu-
like symptoms such as fever and chills.  If the diagnosis can be established, prostatitis 
should be the AE, not the other symptoms.  The other symptoms may be listed with the AE. 
 
Example 2 (Diagnosis): Urinary tract infection (UTI) often has dysuria, urinary frequency, 
urinary urgency, and hematuria.  If the diagnosis of UTI can be established, the AE should 
be classified as an infection with sub-classification of UTI.  The symptoms may be listed 
with the AE.   
 
Example 3 (Sign): Hematuria may lead to other symptoms, such as dysuria, pain in flank 
and back, in addition to blood in the urine.  A blood clot may obstruct the urethra and lead 
to urinary retention.  A disease diagnosis is preferred but a diagnosis may not be possible.  
In this case, hematuria (with clot retention) should be the AE classification/category, not 
the other symptoms. 
 
9.6 Potential Anticipated Adverse Events 
Potential anticipated adverse events are those that may occur in association with a stricture 
treatment or procedure, include those AEs listed below or reported in the literature 
associated with surgical or minimally invasive stricture procedures: 
Surgical and Procedural Risks 
x Adverse reaction to the drug (paclitaxel) coating 

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Paclitaxel has been reported to prevent proliferation (growth of certain cells in the 
body). In this study, the purpose of using paclitaxel on the device is to help prevent 
or reduce restenosis (stricture reoccurring). However, the risks of exposure to 
Paclitaxel include: 
o Chromosomal abnormalities and the risk of cancer  
o Fetal harm when a pregnant woman is exposed  
o Anaphylaxis (allergic reaction) and hypersensitivity reaction with paclitaxel 
intravenous infusion 
o Delayed healing of the wound in urethra due to the procedure 
o Potential effect on the liver and kidneys is unknown and have not been studied 
The amount of the paclitaxel delivered is much lower than a single dose of chemotherapy 
provided to cancer patients and the drug appears to remain relatively localized. 
 
x Sepsis and infection 
x Fever 
x Perforation of urethra 
x Perforation of adjacent organs including the rectum, bladder and GI tract 
x Urinary symptoms and adverse events including: 
o Dysuria 
o Frequency 
o Urgency 
o Nocturia 
o Acute urinary retention 
o Incontinence 
o Sensation of not emptying bladder completely 
o Urethritis 
o Irritative urinary symptom 
o Urethral injury causing false passage or adhesion 
o Urinary clot retention 
o Chronic pain in the pelvic area 
o Bladder spasm 
o Urethrorrhagia or Hematuria with or without clot in urethra 
o Discharge or cloudy urine 
o Discharge of tissue material during urination 
o Scarring of the urethral system 
o Urinary tract infection 
x Abscess (prostatic, bladder, scrotal) 
x Bladder problems or damage (reduced bladder sensation, spasms, bladder neck 
contracture, bladder neck stenosis) 
x Bladder perforation or rupture 
x Damage to the urethral system 
x Worsening of stricture or de novo stricture 

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x Seroma 
x Kidney compromise or failure  
x Reproductive system disturbances such as infertility and miscarriages 
x Prostate abnormalities and damage 
 
Other Pelvic Health Risks 
x Rectal incontinence 
x Rectal damage 
x Rectal stenosis 
x Rectal, perineal findings 
x Anal irritation 
x Elevated PSA 
x Nerve damage 
x Weakness or numbness  
x Abdominal or low back pain 
x Flu-like symptoms 
x Hematospermia 
x Epididymitis 
x Bowel irritation 
x Erectile dysfunction 
x Retrograde ejaculation or ejaculatory dysfunction 
x Pressure sensation 
x Prostatitis 
 
Other potential non-pelvic anticipated adverse events that may occur in this subject population are: 
x Blood pressure change during therapy 
x Arrhythmia 
x Flank pain 
x Blood loss (> 500 ml)  
x Adverse reaction to medication and anesthesia as listed in the labeling 
x Low blood pressure (hypotension) 
x High blood pressure (hypertension) 
x Fainting, dizziness, or blurred vision (vasovagal reaction, syncope) 
x Allergic reaction 
x Fatigue 
x Dyspnea 
x Confusion 
x Memory loss 
x Swelling or bruising (edema, hematoma) 
x Aneurysm – thoracic and cranial 
x Low back pain 

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x Pneumonia 
x Collapsed lung  
x Pulmonary embolism 
x Pneumothorax 
x Upper respiratory disease 
x Cough 
x Sore throat 
x Apnea 
x Coughing up blood (hemoptysis) 
x Choking (aspiration) 
x Venous thrombosis 
x Myocardial infarction, angina, ischemia 
x Cardiac arrhythmia 
x Stroke or transient ischemic attack 
x Brain damage 
x Headache 
x Depression 
x Perforation of or damage to the gastrointestinal tract 
x Abdominal pain 
x Constipation 
x Nausea or vomiting 
x Adverse reaction to medication 
 
9.7 Definition of Serious Adverse Event(s) 
An adverse event is considered to be a serious adverse event (SAE) if it resulted, or could 
result in, if not mitigated in: 
x Death  
x Is life-threatening 
x Requires the subject to be hospitalized or prolongs an existing hospitalization   
x Results in persistent or significant disability/incapacity 
x Is considered an important medical event 
 
Important medical events that may not meet one of the above definitions could be 
considered SAEs if they jeopardize the health of the subject or require surgical intervention 
to prevent one of the outcomes listed above.  An SAE may or may not be related to the 
study procedure. 
9.8 Unanticipated Adverse Device EFFECT(s) (UADE) 
An unanticipated adverse device effect (UADE) is any serious adverse effect on the health 
or safety of a subject, any life-threatening problem or death caused by, or associated with a 
device, if such effect, problem, or death was not previously identified in nature, severity, or 

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degree of incidence in the investigational plan (e.g., ICF, Study Protocol, Instructions for 
Use (IFU), publications, etc.), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects.  
If an unanticipated adverse effect associated with the investigational device occurs, the 
investigator shall notify the Sponsor and the IRB/EC as soon as possible.   
The Sponsor will investigate the event and notify the authorities and IRB/EC and all other 
participating IRBs/EC and investigators.  Should the Sponsor determine that an 
unanticipated adverse effect presents an unreasonable risk to all participating subjects, the 
Sponsor will suspend the clinical investigation and notify all participating investigators, 
IRBs/EC, country regulatory bodies.  
9.9 Reporting of all Adverse Events 
The signs, symptoms and sequelae of an underlying AE should not be reported as separate 
AEs. 
 
All AEs must be recorded on a CRF.  All AEs also must be described by (a) duration (start 
and resolution dates); (b) adjudicated for severity; (c) relationship to the study device; (d) 
action taken to resolve the event; (e) outcome of the event; and (f) whether or not such 
event is considered to have been serious.  Additional information, such as procedural notes, 
treatment notes, or a signed clinical summary, may be required as supporting 
documentation for the reported AE. 
During the study, all deaths must be reported to the Sponsor within the period outlined in 
Table 12-1.  All deaths also should also be reported on the End of Study CRF.  A copy of 
the subject’s death records, medical records for the events that led to the subject’s death, 
and a death certificate (if available) should be provided. 
 
9.10 Relationship of AEs to the Device 
A description of how an AE relates to the study procedure will be reported on the Adverse 
Event CRF and be determined by the Investigator using the following definitions: 
 
x Definite:  The AE follows a reasonable temporal sequence from the time of the 
index procedure, which includes AEs that occur during the index procedure or 
during the follow-up period. 
x Probable:  The AE follows a reasonable temporal sequence from the time of the 
index procedure, and the possibility can be excluded that factors other than the index 
procedure, such as underlying disease, concomitant drugs, or concurrent treatment 
caused the AE. 
x Possible:  The AE follows a reasonable temporal sequence from the time of the index 
procedure and the possibility of index procedure involvement cannot be excluded.  

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However, other factors such as underlying disease, concomitant medications, or concurrent 
treatment are presumable. 
x Unlikely:  The AE has an improbable temporal sequence from the time of the 
index procedure, or such AE can be reasonably explained by other factors, 
including underlying disease, concomitant medication, or concurrent treatment. 
x Not related: The AE has no temporal sequence from the time of the index procedure, 
or it can be explained by other factors, including underlying disease, concomitant 
medication, or concurrent treatment. 
Those SAEs that are possibly related to the device, the procedure, or the disease state being 
treated will be reviewed and adjudicated by the sponsor.   
9.11 Device Failures, Malfunctions and Near Incidents 
Device failures or malfunctions will be reported to the sponsor by the clinical sites.  If the 
failure or malfunction results in negative clinical sequelae, the event shall be reported to 
the Sponsor within two (2) working days after the Investigator becomes aware of the 
device-related adverse event and reported to the IRB/EC (if required) within the IRB/EC 
required timeframe.  The malfunctioning investigational device involved in the incident 
should be returned to the Sponsor for evaluation.   
 
10 TRAINING 
The Sponsor will be responsible for training of appropriate clinical site study personnel.  All 
physicians proctored by the Sponsor, as well as other trained physicians, must sign the site 
Proctoring Form in connection with this study.  To ensure proper procedural technique, 
uniform data collection and protocol compliance, the Sponsor will present a formal training 
session to personnel at each study site.  At this training session, the study protocol, 
techniques for the identification of eligible subjects, instructions on data collection, 
schedules for follow-up, and regulatory requirements will be reviewed. 
 
11 DATA MANAGEMENT 
11.1 Subject Identification 
Subjects that successfully pass the screening tests and wish to participate in the study will be 
assigned a unique identification code (ID) using the format “XX-YYY” where: 
 
 
XX = Institution Number, assigned by the Sponsor to each study site 
YYY = Enrollment Number, assigned by the institution as each subject is enrolled  
 
in the study 

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In addition to the ID, each subject’s initials will be used as an identifier included on documentation 
submitted to the Sponsor. 
 
1.1 Central Database 
All study documentation will be collected and compiled in a central database.  Appropriate quality 
control measures will be established to ensure accurate and complete transfer of information from 
the study documentation to the central database 
 
12 STUDY RESPONSIBILITIES AND MANAGEMENT 
12.1 Investigator Responsibilities  
Each investigator is responsible for ensuring the investigation is conducted according to 
all signed agreements, the study protocol, EC/IRB requirements, and applicable laws and 
regulations.  Also, Investigators may not begin enrollment until Sponsor or its designee 
receives and approves (when necessary) the following documents: 
x 
Signed Investigator Agreement 
x 
Financial disclosure forms for all participating investigators 
x 
EC/IRB roster (or IRB registration number from the Office of Human Research Protection) 
x 
EC/IRB protocol and ICF approvals 
x 
Investigators’ current curricula vitae (CV) 
x 
Signed Site Delegation Log 
 
It is acceptable for Investigators to delegate one or more of the above functions to an 
associate or Co or Sub-Investigator, or a trained Study Coordinator; however, the 
Investigator remains responsible for the proper conduct of the clinical investigation, 
including obtaining and documenting proper study informed consent, collecting all required 
data, submitting accurate and complete CRFs, etc. 
At each study site, appropriate procedures must be followed to maintain subject 
confidentiality according to appropriate local regulations.  Each site may have its own 
internal procedures or requirements for use and release of subject medical information in 
research studies.  Each Investigator is responsible for obtaining appropriate approvals, 
consents, or releases of medical information as dictated by their relevant subject privacy 
laws. 
The study is not transferable to other sites attended by the Investigator unless prior 
approval is obtained from the appropriate EC/IRB and the Sponsor. 
 

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12.2 Subject Enrollment Process 
All study candidates, after pre-procedure screening, must appropriately consent to 
participate in the study, as administrated by qualified study site personnel using an EC/IRB 
and Sponsor-approved informed consent form (ICF) prior to beginning any aspect of the 
study procedure or tests that are not standard of care for the site.  Investigational sites will 
be required to document the consent process within each enrolled subjects medical record.  
Administering the questionnaires can be done prior to signing the ICF. 
Only subjects who meet the inclusion/exclusion criteria, who signed the study enrollment 
informed consent will be considered enrolled in the study.  
Timely communication by each site is critical to avoid over enrolling when the enrollment 
is close to the end of each phase. When enrollment is close to the end of each phase, the 
following procedures will be implemented: 
 
x Before the subject signs the study ICF, the Study Coordinator must confirm the 
availability of an enrollment slot.  A phone call to the Sponsor or Data Coordinating 
Center is the preferred method. 
x Immediately after the procedure, the Study Coordinator must inform (phone call or 
fax or e-mail) the Sponsor or Data Coordinating Center to confirm the subject’s 
eligibility and the completion of the procedure.  A phone call to the Sponsor is the 
preferred method. 
 
12.3 Ethics Committee (EC) / Institutional Review Board (IRB)  
Investigators must submit the study protocol to their respective Ethics Committee (EC) and 
or Institutional Review Board (IRB) and obtain the EC’s/IRB’s written approval before 
being allowed to conduct and participate in the study.  Each Investigator is responsible for 
fulfilling any conditions of approval imposed by their respective EC/IRB, such as regular 
reporting, study timing, etc.  Investigators will provide the Sponsor or its designee with 
copies of such approvals and reports. 
 
12.4 Informed Consent Form (ICF) 
The Sponsor will provide a template informed consent form (ICF) to each study site for 
EC/IRB submission.  The template may be modified to suit the requirements of the 
individual study site but the Sponsor must pre-approve all changes to the ICF prior to initial 
submission to the EC/IRB.   
Each Investigator or assigned designee must administer this approved ICF to each 
prospective study subject, and obtain the subject's signature or a legally-approved 
designee’s signature along with the date of consent prior to enrollment in the study.  The 
ICF must be obtained in accordance with the applicable guidelines of the Declaration of 
Helsinki, or local regulations and laws, whichever represents the greater protection of the 

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individual.  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 be informed that withdrawal from the study will not jeopardize 
their future medical care.  A copy of their signed ICF must be given to each subject 
enrolled in the study.  The institutional standard subject consent form does not replace the 
study ICF. 
 
12.5 Case Report Forms (CRFs) 
The Sponsor will provide standardized case report forms (CRFs) for each individual 
subject.  The CRFs will be electronic (EDC, 21 CRF Part 11 compliant), and will be used 
to record study data, and are an integral part of the study and subsequent reports.   
The electronic CRFs for individual subjects will be provided by the Sponsor via a web 
portal.  After the data have been monitored and submitted, corrections will be initiated via a 
data query or Data Clarification Form (DCF) to be completed by study site personnel.  This 
DCF also will be done electronically via the web portal.  Electronic CRFs must be 
approved and signed by the Investigator in the appropriate spaces provided using his/her 
electronic signature. 
 
12.6 Records 
Each Investigator must maintain the following accurate, complete, and current records 
relating to the conduct of the study investigation.  The final responsibility for maintaining 
such records remains with the Investigator.  These records include, but not limited to: 
 
x All signed agreements; 
x IRB/EC approval letter(s); 
x Signed ICF; 
x Records of AEs, including supporting documents; 
x Records of protocol deviations, including supporting documents 
x Records showing receipt, use and disposition of all investigational devices, 
including: 
o Date, quantity, model and serial numbers of devices received, 
o Name of person(s) who received, used or disposed of each device, 
o The number of devices returned to the Sponsor and the reason(s) for 
return; 
x All correspondence related to the study; 
x Records of each subject’s case history, including study-required CRFs, 
signed ICF, all relevant observations of AEs, the condition of each subject 

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upon entering and during the course of the investigation, relevant medical 
history, the results of all diagnostic testing, etc.; 
x Study personnel visit log; 
x Signature authorization and delegation log; and, 
x Any other records that applicable regulation requires to be maintained. 
 
12.7 Reports 
Table 12-1 lists those reports that are the investigator's responsibility to deliver to the 
Sponsor.  Each study investigator must follow the EC/IRB reporting requirements for their 
respective site.  If applicable regulations or EC/IRB requirements mandate stricter 
reporting requirements than those listed, the stricter requirements must be followed. 
 
Table 12-1:  Reports Required from Investigators to Sponsor 
Type of Report 
Prepared by PI for 
Notification Time Frame 
UADE 
 
Sponsor, EC/IRB 
 
Within 10 working days of 
knowledge 
Death 
Sponsor, EC/IRB 
Written reports (e.g., via e-mail) 
within 48 hours 
SAE  
Sponsor 
 
EC/IRB, if required 
Within 10 working days of 
knowledge  
Per EC/IRB requirement 
Device malfunction with 
clinical sequelae 
Sponsor 
 
EC/IRB, if required 
Within 48 hours via written 
communication.  Return the device to 
sponsor within 48 hours. 
Serious protocol deviations 
(e.g., ICF not obtained, to 
protect the life or physical 
well-being of a subject in an 
emergency) 
Sponsor 
 
EC/IRB, if required 
Within 5 working days of knowledge 
Per EC/IRB requirement 
Withdrawal of EC/IRB 
approval 
Sponsor 
 
Within 5 working days of knowledge 

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Type of Report 
Prepared by PI for 
Notification Time Frame 
Progress report 
Sponsor, EC/IRB 
As required by EC/IRB 
Final report 
Sponsor, EC/IRB 
Within 3 months of study completion 
or termination 
Note: Each IRB/EC may require more stringent reporting requirements than those listed in  
          this table. 
 
12.8 Sponsor Responsibilities  
Urotronic, Inc. is the Sponsor of this study.  The Sponsors responsibilities in the study 
include: 
x Selecting the Principal Investigator(s), all clinical investigators and study sites, and 
other consultants (e.g., monitors) who participate in the study. 
x Provide study protocol, device, and GCP training to participating study sites, in 
quantities sufficient to support study activities, per agreements executed with the 
study sites. 
x Select all qualified clinical Investigators and study sites and other consultants (e.g., 
the study monitors) who participate in the study. 
x Provide financial support to each study site. 
x Follow/promote all regulatory standards per appropriate regulations for study sites, 
core laboratories, and other participants, and ensure compliance by periodically 
monitoring sites. 
x Ensure completion of site monitoring of clinical data at each clinical study site.  
x Retain ownership of all clinical data generated in this study, and control the use of 
the data for appropriate purposes only.   
x Review and approve publication of study results in the literature. 
 
12.8.1 Confidentiality 
All information and data sent to the Sponsor concerning subjects or their participation in 
this study will be considered confidential according to the country’s patient confidentiality 
regulations.  Data used in the analysis and reporting of this evaluation will be used in a 
manner without identifiable reference to the subject.  Investigators will consent to visits by 
Sponsor’s staff and its authorized representatives, as well as by the FDA or local 
governmental body, to review the study subjects’ medical records, including any test or 
laboratory data that might have been recorded on diagnostic test media (e.g., urethrogram).   

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12.8.2 Amending the Investigational Study Protocol 
Neither any Investigator nor the Sponsor will modify the Investigational Protocol without 
first obtaining concurrence of the other in writing.  All changes to the Investigational 
Protocol must be submitted to the EC/IRB for review and approval unless the changes do 
not affect the subject’s safety or the integrity of the data (e.g. administrative changes).  Any 
change that would require alteration to the ICF must receive approval from the applicable 
EC/IRB prior to implementation.  Following approval, any Investigational Protocol 
amendment must be distributed to all protocol recipients at the site. 
12.8.3 Protocol Deviations 
A protocol deviation/violation is generally an unplanned excursion from the protocol that is 
not implemented or intended as a systematic change. An investigator failed to perform tests 
or examinations as required by the protocol or failures on the part of study subjects to 
complete scheduled visits as required by the protocol, would be considered protocol 
deviations. These type of deviations are reported to the sponsor and in accordance with the 
EC/IRB policy. 
A Protocol Deviation CRF must be completed by the site for each study protocol deviation 
(e.g., failure to obtain informed consent, enrolling a subject who does not meet inclusion / 
exclusion criteria, not performing required testing, missed follow-up window, etc.).  An 
Investigator must notify the Sponsor and the reviewing EC/IRB of any deviation from the 
Study Protocol that was done to protect the life or physical well-being of a subject.  Such 
notice should be given as soon as possible, but no later than five (5) working days after the 
emergency occurred. 
12.8.4 Protocol Deviation Notification/Approval to EC/IRB/Sponsor before 
Implementation 
A protocol deviation may be a limited prospective exception to the protocol (e.g. agreement 
between sponsor and investigator to enroll a single subject who does not meet all 
inclusion/exclusion criteria due to out of window historical data).   
These types of deviations initiated by the clinical investigator must be reviewed and 
approved by the EC/IRB and the sponsor prior to implementation.  This type of deviation 
can be used for historical data that is out of window (ie) due to date of screening visit. The 
objective is to prevent subjects from being subject to repeat and possible invasive testing.  
These type of deviations are only approved if they do not impact data integrity or put 
subjects at unreasonable risk. 
12.8.5 Site Noncompliance and Nonperformance 
Repeat serious protocol deviations will be closely monitored.  If excessive deviations or a 
failure to reduce deviations are noted, the Sponsor reserves the right to suspend study 
enrollment at that site until a sufficient system is in place at the site to reduce further 
deviations.  
After a site completes all required approvals and training, a site initiation visit will be 
conducted as a final check of the site readiness.  If a site is not able to enroll its first subject 

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3 months after “Ready to Enroll” status, the Sponsor may elect to terminate the 
investigational site and allocate the slot to another candidate site.   
12.8.6 Device Accountability 
The DCB allocated for investigational site use will be stored in a secured area until use.  
Each site will be responsible for tracking the receipt and disposition of all investigational 
Devices.  All unused DCB Devices must be returned to the Sponsor at the end of the study.   
 
13 STUDY ADMINISTRATION 
13.1 Monitoring Procedures 
It is the responsibility of the study sponsor to ensure that proper monitoring of this 
investigation is conducted.  Appropriately trained personnel, appointed by the study sponsor, 
will complete any monitoring that is done.  The monitoring will be the responsibility of 
sponsor study personnel with an address as listed in the title page of this document.  Monitors 
will ensure that the investigation is conducted in accordance with:  
 
x 
The signed Investigator’s Agreement 
x 
The Investigational Plan  
x 
Appropriate laws and regulations  
x 
Any conditions of approval imposed by the reviewing EC/IRB and/or other regulatory 
agencies 
 
The clinical study will be monitored according to the guidelines summarized below.  The 
sponsor may choose to perform random inspections throughout the study as an element of 
quality assurance.  Investigators shall allow auditing of their clinical investigation 
procedures. 
 
A study specific Monitoring Plan is created and implemented to standardize monitoring 
activities across centers and ensure human subject protection and verify data integrity.  The 
monitors shall receive study specific and SOP training prior to conducting any monitoring 
visits.  Study monitors are selected based on their training, qualifications and experience to 
monitor the progress of an investigation.  Study monitors may be Sponsor’s employees or 
representatives.  This study monitoring will include a site qualification, study initiation, 
interim, and close out visits.  All study monitors will be required to follow the Sponsor’s 
monitoring plan and monitoring standard operating procedures (SOPs).  
The study monitoring will be done by the following Sponsor representative: 
Libra Medical Inc 
8401 73rd Ave North, Suite 63 
Brooklyn Park, MN 55428 
 

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13.1.1 Monitoring Visit 
The following factors will be taken into account when determining the frequency of the 
monitoring visits: subject accrual rate at each center, total number of subjects enrolled at 
each center, and Clinical Investigation Plan compliance at each center.  It is anticipated each 
site will be monitored at least once upon the completion of the 3-month follow-up visits for 
all enrolled subjects at the study site.  Monitors will require direct access to subjects’ medical 
records pertinent to the study (and study inclusion criteria), study management documents, 
regulatory documents and Subject Informed Consent documents, as well as other potential 
applicable records not listed here.   
 
Monitors may ensure the clinical investigators have and continue to have staff and facilities 
to conduct the clinical investigation safely and effectively.  Monitors may conduct the 
following monitoring activities throughout the study: 
 
x 
Verification that the current EC/IRB-approved informed consent was signed and 
dated by each subject prior to participating in the study required procedures. 
x 
Verification of documentation in the subject’s record that informed consent was 
signed prior to initiation of the study procedures and that a copy of the signed 
and dated consent was provided to the subject. 
x 
Source documentation verification by reviewing the CRFs against source 
documentation for accuracy and completeness of information. 
x 
Verification that the device is being used according to the Clinical Investigation 
Plan, Instructions for Use and, all malfunctions/ IFU deficiencies are reported. as 
required. 
x 
Verification that subjects met study enrollment criteria. 
x 
Confirmation that the study is being conducted according to the Clinical 
Investigation Plan and applicable regulations. 
x 
Verification that study deviations are documented and reported. 
x 
Verification that the procedures for recording and reporting adverse events to the 
sponsor are followed. 
x 
Ensuring proper error correction. 
x 
Verification of training documentation of all study personnel participating in 
study related activities. 
x 
Reviewing all correspondence and regulatory documents, including confirmation 
of IRB-approved Clinical Investigation Plan or amendments. 
x 
Resolution of outstanding issues and completion of assigned tasks will be 
documented by the monitors. 
 

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Each monitoring visit will be documented via a monitoring report and follow-up letter.  
The follow up visit letter shall be sent to the Investigator to document issues identified, 
corrective actions and if applicable preventative actions.  At subsequent visits the issues 
resolved shall be documented in this letter to demonstrate resolution. 
13.1.2 Study Closure 
Study closure is defined as a specific date that is determined by study completion and/or 
regulatory requirements have been satisfied per the Clinical Investigation Plan (CIP) and/or 
by decision of the Sponsor or EC/IRB.  Study closure visits will be conducted at all enrolling 
clinical sites in order to review record retention requirements with site personnel.  A 
telephone contact may take the place of a study closure visit if appropriate (e.g., low subject 
enrollment, recent monitoring visit, etc.)   
 
14 STUDY CONTACT 
14.1 Study Principal Investigator 
Sean Elliot, MD  
Mayo Building, Fourth Floor 
420 Delaware St. SE 
Minneapolis MN 55455 
 
14.2 Sponsor  
Urotronic Inc 
13705 26th Ave N #102 
Minneapolis, MN 55441 
 
14.3 Monitor and Data Management  
Libra Medical Inc 
8401 73rd Ave N, Suite 73 
Brooklyn Park, MN 55428 
763-477-5606 
 
15 POTENTIAL DEVICE CHANGE 
Future product line extensions (e.g. larger diameter or longer length balloon) or design 
changes may be introduced into the study based on feedback from investigators.  In 
addition, manufacturing changes may be introduced.  All design and manufacturing process 
changes will be performed under the Sponsor’s design control process and fully tested to 
ensure that it meets specifications.  Significant changes that may affect the device safety or 
efficacy will be provided to the EC/IRB as a supplemental application.    

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The device design or process changes will be evaluated to ensure that it continue to meet 
the product specifications. 
 
 
 
16 GLOSSARY OF ABBREVIATION 
Abbreviation 
Definition 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
BPH 
Benign Prostatic Hyperplasia 
BUN 
Blood urea nitrogen   
CBC 
Complete blood cell count 
CFU 
Colony Forming Unit 
CIP 
Clinical Investigation Plan 
CRF 
Case Report Form 
DCB 
Drug Coated Balloon  
DES 
Drug-eluting stent 
DVIU 
Direct Vision Internal Urethrotomy 
EC/IRB 
Ethics Committee / Institutional Review Board 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ID 
Identification code 
IFU 
Instructions for Use 
IIEF 
International Index of Erectile Function 
IPSS 
International Prostate Symptoms Score 
LUTS 
Lower urinary tract symptoms 
NSAID 
Nonsteroidal anti-inflammatory drug 
OAB 
Overactive Bladder 
PROM 
Patient-reported outcome measure 
PSA 
Prostate Specific Antigen 
PVR 
Post Void Residual Urine Volum 
Qmax 
Peak Flow Rate Measurement 
RUG 
Retrograde Urethrogram 

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SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
TRUS 
Prostate ultrasound or transrectal ultrasound 
UADE 
Unanticipated Adverse Device EFFECT(s) 
USS Score 
Urethral Stricture Score 
UTI 
Urinary Tract Infection 
17  REFERENCES 
1. MacDiarmid SA, Harrigan CT, Cottone JL, McIntyre WJ, Johnson DE Assessment 
of a New Transurethral Balloon Dilation Catheter in the Treatment of Urethral 
Stricture Disease Urology 2000; 55 (3) 
2. Heyns 1998 Heyns CF, Steenkamp JW, De Kock ML, Whitaker P. Treatment of 
male urethral strictures: Is repeated dilation or internal urethrotomy useful?  Journal 
of Urology 1998;160(2):356–8. 
3. Pansadoro 1996 Pansadoro V, Emiliozzi P Internal urethrotomy in the management 
of anterior urethral strictures; long-term follow-up Journal of Urology 1996; 156:73 
4. Jezior 2002 Jezior JR and Schlossberg SM. Excision and primary anastomosis for 
anterior urethral stricture Urol Clin North AM, 2002; 29: 373 
5. Santucci 2002 Santucci RA, Mario LA and McAninch JW Anastomotic 
urethroplasty for bulbar urethral stricture; analysis of 168 subjects Journal of 
Urology 2002; 167: 1715 
6. Webster 1985 Webster GD, Koefoot RB, and Sihelnik SA Urethroplasty 
management in 100 cases of urethral stricture: a rationale for procedure selection 
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7. Barbagli 1997 Barbagli G, Palminteri E, Bartoletti R, Selli C, and Rizzo M Long-
term results of anterior and posterior urethroplasty with actuarial evaluation of the 
success rates Journal of Urology 1997; 158: 1380 
8. Albers 1996 Albers P, Fichtner J, Brühl P and Müller SC Long-term results of 
internal urethrotomy Journal of Urology 1996; 156:1611 
9. Charbit 1990 Charbit L, Mersel A, Beurton D and Cukier J5-year treatment results 
of urethral stenosis using internal urethrotomy in adults Ann Urology 1990; 24: 66 
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minimized approach to the bulbous urethral stricture Journal of Urology 2005; 173: 
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11. Steenkamp JW, Heyns CF, and de Kock ML: Internal urethrotomy versus dilation 
as treatment for male urethral strictures: a prospective, randomized comparison. J 
Urol 157: 98 –101, 1997.͒ 

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12. Stormont TJ, Suman VJ, and Oesterling JE: Newly diagnosed bulbar urethral 
strictures: etiology and outcome of various treatments. J Urol 150: 1725–1728, 
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13. USS AR 2006: Management of Urethral Strictures                                     
Postgraduate Med J. 2006 Aug; 82(970): 489-493