Clinical trial NCT03423979
Conditions: Benign Prostatic Hyperplasia Benign Prostatic Hypertrophy
Keywords: BPH
Sponsor: Urotronic Inc.
Start date: 2017-12-19; Completion date: 2024-05-25
Enrollment: 80 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
A prospective, non-randomized study. The subjects will be enrolled and treated with the Optilume BPH Prostatic DCB Dilation Catheter System at up to 8 clinical sites. The post-treatment follow-up visit can be up to 5 years.

The objective of the study is to evaluate the safety and efficacy of the Optilume™ BPH Prostatic Drug Coated Balloon Dilation Catheter System in the treatment of BPH.

Detailed description:
A prospective, non-randomized, multi-center study. The study will enroll up to 85 subjects to be enrolled and treated with the Optilume BPH Prostatic DCB Dilation Catheter System at up to 8 clinical sites. Subjects will be followed up post-treatment at Foley removal, and up to 1 year. The subjects may choose to be followed-up annually for 5 years or until study close, whichever comes first.

Study device is Optilume™ BPH Prostatic Drug Coated Balloon Dilation Catheter System.

Study primarily outcomes are measured by 1). Change in IPSS score at 3-month post-procedure follow-up; 2). Major device or procedure related complications at 3-month post-procedure follow-up.

Arms: arm 1: Optilume™ BPH Prostatic DCB treatment procedure
Interventions: intervention 1: Optilume™ BPH Prostatic DCB Dilation Catheter intervention 2: Paclitaxel
Intervention descriptions: intervention 1: BPH Prostatic DCB treatment - The Optilume BPH Prostatic DCB Dilation Catheter System should be prepared per the Instructions for Use (IFU). intervention 2: paclitaxel will release to adjacent tissue after the balloon inflated in the urethra

Protocol documents:
SAP_002.pdf: 
SAP_PR1051-002_Rev A 
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EVEREST-I 
Evaluation of Optilume™ BPH Prostatic Drug Coated Balloon Dilation Catheter in 
the Treatment of Moderate-to-Severe Lower Urinary Tract Symptoms Secondary 
to Benign Prostatic Hyperplasia 
 
Statistical Analysis Plan (SAP) 
 
PR1051-002, Rev. A 
 
 
19 July 2018 
 
 
 
 
 
 
 
 


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Table of Contents 
 
1 
Introduction ............................................................................................................. 3 
2 
Study Objective(s) ................................................................................................... 3 
3 
Study Design ........................................................................................................... 3 
3.1 
Study Endpoints ............................................................................................................... 3 
4 
Sample Size ............................................................................................................. 4 
5 
Analysis sets ........................................................................................................... 4 
6 
Statistical Methods of Analyses ............................................................................. 5 
6.1 
General Considerations .................................................................................................... 5 
6.2 
Baseline Characteristics ................................................................................................... 5 
6.3 
Analysis of the Primary Endpoint(s) ................................................................................ 5 
6.4 
Analysis of Primary Safety Endpoint ............................................................................... 6 
6.5 
Analysis of the Secondary Endpoint 1 ............................ Error! Bookmark not defined. 
6.6 
Analysis of the Secondary Endpoint 2 ............................ Error! Bookmark not defined. 
6.7 
Analysis of the Secondary Endpoint 3 ............................ Error! Bookmark not defined. 
6.8 
Analysis of the Exploratory Endpoints ............................................................................ 6 
6.9 
Analysis of Safety Data .................................................................................................... 6 
6.10 
Handling of Missing Data ................................................................................................ 7 
6.11 
Visit Windows .................................................................................................................. 7 
6.12 
Unscheduled Assessments................................................................................................ 7 
7 
Other Analyses ........................................................................................................ 7 
7.1 
Subject Disposition .......................................................................................................... 7 
7.2 
Medical Histroy ................................................................................................................ 7 
7.3 
Poolability Across Investigational Sites ........................................................................... 7 
7.4 
Changes in Planned Analysis ........................................................................................... 7 
  
 


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1  INTRODUCTION 
This document outlines the detailed statistical methods for the data collected within the scope of 
Protocol # PR1051 EVEREST-I Study Revision 3.0.  The purpose of this plan is to provide a 
framework within which answers if the study objectives can be achieved via statistically 
appropriate analytical methods.  Specifically, the SAP serves to prospectively (a priori) outline 
the types of analyses and presentations of data that will form the basis for conclusions to be 
reached that will answer the study objectives outlined in the protocol, and to explain in detail 
how the data will be handled and analyzed, adhering to commonly accepted standards and 
practices of biostatistical analyses in the medical industry. Results obtained from the analyses 
outlined in this document will be the basis of the Clinical Study Report for this study. 
 
If a future protocol revision necessitates a substantial change to the statistical analysis of the trial 
data, this SAP will be amended accordingly.  Amendments to this document will be finalized 
prior to database lock (DBL). 
 
2 STUDY OBJECTIVE(S) 
The objectives of the study are to evaluate the safety and efficacy of the Optilume™ BPH  
Prostatic Drug Coated Balloon Dilation Catheter System in the treatment of BPH: 
• To assess the efficacy of the Optilume BPH Prostatic DCB Dilation Catheter System to 
alleviate LUTS believed to be secondary to BPH (LUTS/BPH)  
• To evaluate the safety of the Optilume BPH Prostatic DCB Dilation Catheter System in 
the treatment of LUTS/BPH. 
3 STUDY DESIGN 
This is a prospective, single arm, multi-center, open label, non-randomized study focusing on 
male subjects with BPH.   
 
Subjects will be followed up post-treatment at foley removal, 2 weeks, 30 days, 90 days, 180 
days and 365 days, and then annually for up to 5 years or until study close, whichever comes 
first.  The annual follow-up after the first year is optional.  A subset of the subjects will be 
included in the PK study cohort which includes extra follow-up visits at 1 day and 4 days post-
treatment. Scheduled visits are listed in Table 5 in the protocol. 
 
All subjects will be treated with a pre-dilation balloon and a drug-coated balloon (DCB) 
according to the EVEREST-I Protocol #PR1051.   
 
3.1 STUDY ENDPOINTS 
3.1.1 Primary Efficacy Endpoint: Change in IPSS score at 3 months 
Improvement in International Prostate Symptom Score (IPSS) at 3 months is measured by baseline score 
minus 3 months score.  The percent of improvement is calculated as the improvement in IPSS divided 
by the baseline score. A therapeutic responder is defined as a subject who has an IPSS improvement of ≥ 
40%.  The primary efficacy endpoint is the proportion of therapeutic responders at 3 months.   


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3.1.2  Primary Safety Endpoint: Major device or procedure related complications at 3 months 
A major device related complication is defined as any of the following device or procedure related 
serious adverse events at 3 months.   
• Device or procedure related new onset severe urinary retention lasting > 14 consecutive 
days post-healing 
• Device or procedure related unresolved new onset stress urinary incontinence by 90 days  
• Device or procedure related bleeding requiring transfusion  
 
3.1.6 Exploratory Endpoints 
• Change in IPSS  
• Change in Qmax (Peak Urinary Flow Rate) 
• Change in BPH-II (BPH Impact Index) 
• Change in pain score  
• Change in IIEF (International Index of Erectile Function)  
• Change in EQ-5D quality of life  
• Subject satisfaction  
• Procedure parameters 
• Change in MSHQ-EjD (Men’s Sexual Health Questionnaire – Ejaculatory Dysfunction) 
 
4 SAMPLE SIZE 
Sample size calculation is based on the following assumptions: 
• One-sided alpha = 5%     
• Power = 80% 
• Target performance goal = 50% 
• Anticipated responder rate at 3 months = 70% 
Under an exact, one-sided test for a single binomial proportion, at the 0.05 significance level, a 
sample size of 42 subjects will be required to provide at least 80% power to meet this target 
primary efficacy goal of 50% given the anticipated rate of 70%.  With 5-10% lost to follow up, a 
minimum of 45 subjects will be required in this study. 
 
5 ANALYSIS SETS 
Intent-to-Treat (ITT): the ITT set will be comprised of all subjects who have provided informed 
consent and meet all the inclusion and none of the exclusion criteria. 
 
Modified Intent-to-Treat (mITT): all ITT subjects who have the investigational device attempted. 
 


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Per-Protocol (PP): the PP set will be comprised of all subjects in the ITT set who have no major 
protocol deviations. All major protocol deviations will be reviewed and finalized before the data 
lock for final analysis. 
 
The primary analysis for efficacy and safety will be based on a modified intent-to-treat principle. 
The per-protocol analysis set is designated as supportive. 
 
6 STATISTICAL METHODS OF ANALYSES 
6.1 GENERAL CONSIDERATIONS 
The data from the study will be tabulated using descriptive analyses.  In general, categorical 
variables will be summarized with the number and percent of subjects with the characteristic.  
Quantitative variables will be summarized with the mean, median, standard deviation, minimum 
value and maximum value.   
 
Descriptive analyses of all adverse events (AEs) and urinary symptoms will be provided in the 
report.  In addition, the report will include tabulated results of study deviations and device 
malfunctions.   
 
6.2 BASELINE CHARACTERISTICS  
Baseline characteristics will be summarized using the mean, standard deviation, median and 
range for continuous characteristics and using counts and percentages for categorical 
characteristics.   
6.3 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
The primary efficacy endpoint is the proportion of therapeutic responders defined as a subject 
who has an IPSS improvement of ≥ 40% at 3 months. The performance goal is defined as > 50% 
responders at 3 months.   
 
The statistical hypothesis for the primary efficacy endpoint is:   
 
H0:  p ≤ 0.50 
Ha:  p > 0.50  
 
The analysis of the primary efficacy endpoint will be performed in the mITT analysis set. The 
primary efficacy endpoint will be assessed by calculating the proportion of subjects who have 
improved IPSS by 40% or more at 3 months aggregated over the mITT subjects.  A 95% one-
sided confidence interval (i.e., 90% two-sided confidence interval) will be estimated using the 
Clopper-Pearson interval (F-distribution method). In this analysis, the denominator includes all 
subjects in the mITT set.  Subjects who have exited the study prematurely before 3 months will 
be assumed as a non-responder.  Subjects with a missing IPSS value at 3 months will have 
success carried backward if the IPSS at 6 months is shown as a responder.  If the lower bound of 
this 95% confidence interval is greater than to the performance goal of 50%, we can conclude the 
primary efficacy objective is met. 


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As a supportive analysis, the primary efficacy endpoint will also be analyzed as a continuous 
score for the improvement in IPSS at 3 months. 
 
The improvement in IPSS at 3 months is calculated as baseline score minus 3 months score.  
Summary statistics including n, mean, SD, median, Q1 and Q3 for the improvement score will be 
calculated. The 95% confidence interval for the mean improvement will be calculated using an 
asymptotic approach.   
The analyses will also be conducted in the PP set as a supportive analysis. 
6.4 ANALYSIS OF PRIMARY SAFETY ENDPOINT  
The primary safety endpoint, major device or procedure-related complications as defined in the 
section 3.1.2, will be analyzed in the mITT set.  The number and percentage of subjects 
experiencing at least one major device or procedure-related complication will be calculated, 
along with the 95% confidence interval.  
Each component of the primary safety endpoint will be also analyzed in the similar fashion as the 
aggregated primary safety endpoint in the mITT set.  
6.5 ANALYSIS OF THE EXPLORATORY ENDPOINTS 
For continuous endpoint variables, change from baseline will be summarized at each post-
treatment visit using descriptive statistics such as mean, median, standard deviation, minimum 
value and maximum value. For categorical variables, the number and percentage of subjects with 
the characteristic will be presented at each post-treatment visit.  In addition, 95% confidence 
intervals will be presented where applicable.    
6.6 ANALYSIS OF SAFETY DATA  
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.  See the Protocol for further details on AE and Serious Adverse 
Event (SAE) classification.    
 
Adverse experiences will be coded using a customized AE coding list based on the Medical 
Dictionary for Regulatory Activities (MedDRA v21.1).  All AEs will be captured from the 
initiation of treatment through the final visit. Adverse events will be summarized by presenting: 
• 
The number and percentage of subjects experiencing any AE 
• 
The number and percentage of subjects experiencing any AE by System Organ Class 
(SOC) and Preferred Term (PT) 
• 
The number and percentage of subjects experiencing any SAE 
• 
The number and percentage of subjects experiencing any AE associated with study 
discontinuation  
• 
The number and percentage of subjects experiencing any AE related to the study device 


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• 
The number and percentage of subjects experiencing any AE according to degree of 
severity 
6.7 HANDLING OF MISSING DATA   
Unless otherwise specified, no imputation or other substitution for missing data will be made for 
analysis purposes. 
6.8 VISIT WINDOWS 
Visit windows are assigned to visit time points as follows: 
 
Baseline 24 Hours Foley 
Removal 
4 
days 
2 
weeks 
30 
days 
3 
Months 
6 and 12 
Months 
Annually 
for up to 
5 years 
within 
30 days 
± 3 hours 
> 48 hours ± 1 
day 
+ 3 
days 
± 7 
days 
± 14 
days 
± 30 days ± 30 days 
 
6.9 UNSCHEDULED ASSESSMENTS   
Information acquired during unscheduled assessments will be included in the study listings. 
 
7 OTHER ANALYSES 
7.1 SUBJECT DISPOSITION 
Subject accountability and study discontinuation will be summarized for the ITT set. Subject 
accountability at each protocol required visit will be summarized as the number of subjects with 
complete visits, missed visits, or study discontinuations prior to the visit. 
 
All subjects who do not complete the study will be tabulated by reason for discontinuation. 
Additional variables summarized may include total study duration, study completion status, and 
the primary reason for study discontinuation.  
7.2 MEDICAL HISTROY 
Medical history will be summarized for the ITT Set. 
7.3 POOLABILITY ACROSS INVESTIGATIONAL SITES 
This study is designed and conducted as a multi-center clinical trial. Data from all the sites will 
be pooled. All subjects will be treated and evaluated following the same protocol to ensure 
generalizability of the study results.   
 
A list of variables such as baseline demographics and characteristics will be compared across 
sites to assess the appropriateness of pooling data from across all sites. 
 
7.4 CHANGES IN PLANNED ANALYSIS 
Deviations or changes from this SAP deemed necessary due to violation of critical underlying 
statistical assumptions, data characteristics, or missing data will be clearly described with 
justification and rationale. 

Prot_001.pdf: 
Page 1 of 51 
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EVEREST-I 
Evaluation of Optilume™ BPH Prostatic Drug Coated Balloon 
Dilation Catheter in the Treatment of Moderate-to-Severe Lower 
Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia  
 
PROTOCOL No. PR1051 
REVISION No. 4.0 
 
March 25, 2022 
 
 
SPONSOR 
Urotronic Inc 
2495 Xenium Lane N 
Minneapolis, MN 55441 
USA 
 
 
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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EVEREST-I 
Evaluation of Optilume™ BPH Prostatic Drug Coated Balloon 
Dilation Catheter in the Treatment of Moderate-to-Severe Lower 
Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia  
 
PROTOCOL No. PR1051 
REVISION No. 4.0 
 
March 25, 2022 
 
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 Investigator Signature 
 
 
 
 
Date 
 
__________________________________ 
Site Investigator, Printed Name 


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Protocol Summary 
Title:   
EVEREST-I: Evaluation of Optilume™ BPH Prostatic Drug Coated 
Balloon Dilation Catheter in the Treatment of Moderate-to-Severe 
Lower Urinary Tract Symptoms Secondary to Benign Prostatic 
Hyperplasia  
Investigational Device: 
Optilume™ BPH Prostatic Drug Coated Balloon Dilation Catheter 
System 
Objective: 
To evaluate the safety and efficacy of Optilume™ BPH Prostatic 
Drug Coated Balloon (DCB) Dilation Catheter System in the 
treatment of benign prostatic hyperplasia (BPH). 
1. To assess the efficacy of the Optilume BPH Prostatic DCB 
Dilation Catheter System to alleviate lower urinary tract 
symptoms (LUTS) believed to be secondary to BPH 
(LUTS/BPH). 
2. To evaluate the safety of the Optilume BPH Prostatic DCB 
Dilation Catheter System in the treatment of LUTS/BPH. 
Study Design:  
Prospective, multi-center, open-label, non-randomized global study 
 
 
  
 
  
 
 
 
 
 
 
 
 
Endpoints 
 
Primary Efficacy Endpoint: Change in IPSS score at 3 months 
 
A therapeutic responder is defined as a subject who has an IPSS 
improvement of > 40%.  The study is considered a success if at 
least 50% of the subjects are considered responders. 
 
Primary Safety Endpoint: Major Device or Procedure Related 
Complications at 3 Months 
 
Any of the following major device or procedure related 
complications at 3 months:   
• Device or procedure related new onset severe urinary 
retention lasting > 14 consecutive days post-healing  


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• Device or procedure related unresolved new onset stress 
urinary incontinence by 90 days  
• Device or procedure related bleeding requiring transfusion  
 
Secondary Endpoint 1: Average Improvement of IPSS Compared to 
Baseline at each of the major follow up timepoints at or after 3 
months 
 
Secondary Endpoint 2: Change in Peak urinary flow rate (Qmax)   
 
Secondary Endpoint 3: Proportion of subjects whose IPSS 
improvement is > 30%, 40%, 50% and 75% post-treatment at each of 
the major follow up timepoints at or after 3 months 
Exploratory Endpoints: 
E1: Change in pain score  
E2: Change in IIEF (International Index of Erectile Function)  
E3: Change in EQ-5D quality of life  
E4: Subject satisfaction 
E5: Procedure parameters 
E6: Change in MSHQ-EjD 
Inclusion Criteria: 
1. Male subject > 50 years of age who has moderate-to-severe 
LUTS (IPSS score of ≥ 13) and is a candidate for interventional 
therapy 
2. LUTS felt to be secondary to an enlarged prostate (henceforth 
termed LUTS/BPH) 
3. Peak urinary flow rate (Qmax) ≥ 5 mL/sec and ≤ 15 ml/sec with 
minimum voided volume of ≥ 125 ml 
4. Post-void residual (PVR) ≤ 250 ml 
5. Prostate volume 20 - 80 gm as determined by TRUS 
6. Prostatic urethra length is 35 – 55 mm as determined by TRUS 
7. Able to complete the study protocol in the opinion of the 
investigator 
Exclusion Criteria: 
1. Interested in maintaining fertility and unwilling to use protected 
sex for the first 30 days post treatment 
2. Unwilling to abstain or use protected sex for ninety (90) days 
post treatment if sexual partner is of child bearing potential 
3. Presence of a penile implant or stent(s) in the urethra or prostate 
4. Any prior minimally invasive intervention (e.g. TUNA, 
Balloon, Microwave, Rezūm, UroLift) or surgical intervention 
of the prostate  
 
 


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5. PSA > 10 ng/ml unless prostate cancer is ruled out by biopsy.  
If PSA is > 4 ng/ml and ≤ 10 ng/ml, prostate cancer must be 
ruled out to the satisfaction of the investigator via additional 
tests including digital rectal exam (DRE) and/or biopsy 
6. Confirmed or suspected malignancy of prostate or bladder 
7. Active or history of epididymitis within the past 3 months 
8. Previous pelvic irradiation or radical pelvic surgery 
9. Documented active urinary tract infection (UTI) by culture or 
bacterial prostatitis within last year documented by culture (UTI 
is defined as >100,000 colonies per ml urine from midstream 
clean catch or catheterization specimen) 
10. Visible hematuria with subject urine sample without known 
contributing factor 
11. Neurogenic bladder or sphincter abnormalities or neurological 
disorders that might affect bladder or sphincter function 
12. Previous or current diagnosis of urethral strictures, bladder neck 
contracture or detrusor muscle spasms 
13. Use of beta blockers, antihistamines, anticonvulsants, or 
antispasmodics within 1 week prior to treatment unless there is 
documented evidence of stable dosing for last 6 months (no 
dose changes) 
14. Use of alpha blockers, antidepressants, anticholinergics, 
androgens, daily tadalafil or gonadotropin-releasing hormonal 
analogs (prescribed for BPH) within 3 weeks prior to treatment  
15. Use of 5-alpha reductase inhibitor within 6 months prior to 
treatment 
16. Incidence of spontaneous urinary retention within 6 months 
prior to baseline assessment 
17. Post-void residual volume > 250 ml or catheter dependent 
bladder drainage 
18. Overactive bladder (OAB) or urge incontinence  
19. Known poor detrusor muscle function (e.g. Qmax < 5 ml/sec) 
20. Current bladder stones or prostatic calculi 
21. Biopsy of prostate within 30 days prior to procedure or planned 
within 30 days following the procedure 
22. 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 
23. History of clinically significant comorbidities or presence of 
unstable conditions (e.g. cardiovascular, lung, renal [serum 
creatinine > 2.0 mg/dl], hepatic, bleeding disorders, or 
metabolic impairment) that may confound the results of the 
study or have a risk to subject per investigator’s opinion 


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24. Any cognitive disorder that interferes with or precludes direct 
and accurate communication with the study investigator 
regarding the study or affects the ability to complete the study 
quality of life questionnaires 
25. Expected life expectancy < one year 
26. Unable or unwilling to sign the Informed Consent Form (ICF) 
and/or comply with all the follow-up requirements 
27. Currently enrolled in or plan to enroll in another investigational 
clinical trial for any disease except for observational only study 
28. In the opinion of the investigator, it is not in the subject's best 
interest to participate in the study 
29. Current treatment with anti-coagulants (e.g., warfarin or 
enoxaparin) or anti-platelet medications other than aspirin (e.g., 
clopidogrel) 
30. Anatomy, e.g. presence of false passage or size of meatus, is not 
suitable for treatment in this study 
31. Device that corresponds with the subject’s prostate size per the 
IFU is not available 
32. Intravesical prostatic protrusion (IPP) > 1 cm 
33. Current uncontrolled diabetes (hemoglobin A1c > 7%) 
34. Unable or unwilling to provide all the protocol-required semen 
samples 
35. Sensitivity to paclitaxel, on medication that may have negative 
interaction with paclitaxel, or contraindicated for systemic 
paclitaxel 
 
 
 


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Table of Contents 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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List of Abbreviations 
AE 
 
Adverse Event 
ALP 
 
Alkaline Phosphatase  
ALT 
 
Alanine Amino Transferase  
AST 
 
Aspartate Amino Transferase 
AUASI 
American Urological Association Symptom Index 
BPH 
Benign Prostatic Hyperplasia; also known as Benign Prostatic Hypertrophy 
BPHII 
BPH Impact Index (bother Score) 
BUN 
Blood Urea Nitrogen 
CRF 
Case Report Form 
CTCAE  
Common Terminology Criteria for Adverse Events  
DCB 
Drug Coated Balloon 
EC/REB 
Ethics Committee/Research Ethics Board 
EQ-5D  
Standardized instrument for use as a measure of health outcome 
GCP 
 
Good Clinical Practices 
ICF 
 
Informed Consent Form 
IFU 
 
Instructions for Use 
IIEF 
 
International Index of Erectile Function 
IPSS  
International Prostate Symptom Score 
LUTS  
Lower Urinary Tract Symptoms 
LUTS/BPH 
LUTS Secondary to BPH 
MedDRA  
Medical Dictionary for Regulatory Activities  
MSHQ-EjD 
Male Sexual Health Questionnaire to assess ejaculatory dysfunction  
PI 
 
Principal Investigator 
PK 
 
Pharmacokinetics 
PSA 
 
Prostate Specific Antigen 
PV 
 
Prostate Volume 
PVR 
 
Post Void Residual Urine Volume 
Qmax  
Peak Flow Rate 
QoL 
 
Quality of Life 
SAE 
 
Serious Adverse Event 
TRUS  
Transrectal Ultrasonography 
TUMT  
Transurethral Microwave Thermotherapy 
TUNA  
Transurethral Needle Ablation 
TURP  
Transurethral Resection of the Prostate 
UADE  
Unanticipated Adverse Device Effect 
UTI 
 
Urinary Tract Infection 
 


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1 INTRODUCTION 
1.1 Disease State Overview and Epidemiology 
Benign prostatic hyperplasia (BPH) is a histologic diagnosis that refers to the proliferation of smooth 
muscle and epithelial cells within the prostatic transition zone.1,2 BPH with associated lower urinary 
tract symptoms (LUTS) is a common medical condition in the aging male.  The prevalence and the 
severity of LUTS in the aging male can be progressive, and is an important diagnosis in the 
healthcare of our patients and the welfare of society. BPH is the second highest reason for patients 
to seek a urologist.3  The incidence has been estimated to increase from 40% among males between 
the ages of 50 and 60 years to 90% among males older than 80 years of age.4 In 2015, there were 
38.1 million men with BPH pathology and 21.3 million with International Prostate Symptom Score 
(IPSS) >7; 12.2 million of them were managed for LUTS secondary to BPH (LUTS/BPH), primarily 
with watchful waiting (35%) and drug management (54.8%).3  
Initially, watchful waiting (observing without treatment) is normally employed.  Treatment initiation 
usually occurs once symptoms of bladder outlet obstruction and bladder irritability interfere with the 
patient’s quality of life.  The American Urological Association Symptom Index (AUASI) and the 
IPSS are now considered the gold standard measurement tools for the assessment of LUTS and 
response to treatment.  
Medications are the most common way to control mild to moderate symptoms of BPH and 
significantly reduce major symptoms for many men who try them.  However, medications have 
systemic side effects, are costly in the long run, and some patients may have difficulty with 
complying with the medication, particularly in the older population. Further, many patients have 
moderate to severe symptoms that are not fully alleviated by medical therapy.  
Transurethral surgical resection of the enlarged prostate (TURP) is still considered a bench mark for 
the treatment of moderate-to-severe LUTS/BPH or other BPH-related complications.5 However, 
surgical intervention, by definition, is the most invasive option for BPH management. 
For this reason, minimally invasive therapies have been gaining favor over medication and over the 
traditional TURP even though the effectiveness of minimally invasive procedures has been reported 
to be less than TURP.  Development of an effective treatment method but one with shorter treatment 
time, fewer complications, and faster recovery time, would be an advantage. 
1.2 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.  The improvement in restenosis rates led Urotronic to design a 
similar system to treat urinary strictures and obstructive BPH. 
 






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The device is intended for single use and provided sterile packaged within a Tyvek pouch.  The 
pouch is sealed within a foil pouch with a desiccant within the foil pouch.   
The full device description and balloon sizes available for the study are described in the 
Instructions for Use. 
3 STUDY OBJECTIVES AND DESIGN 
3.1 Objective 
The objective of the study is to evaluate the safety and efficacy of the Optilume™ BPH Prostatic 
Drug Coated Balloon Dilation Catheter System in the treatment of BPH. 
• To assess the efficacy of the Optilume BPH Prostatic DCB Dilation Catheter 
System to alleviate LUTS believed to be secondary to BPH (LUTS/BPH)  
• To evaluate the safety of the Optilume BPH Prostatic DCB Dilation Catheter 
System in the treatment of LUTS/BPH 
3.2 Study Design  
This is a prospective, non-randomized, open label, multi-center study.  
 
 
 
 
 
 
3.3 Study Endpoints 
3.3.1 Primary Efficacy Endpoint 1: Change in IPSS score at 3 Months 
This endpoint will be measured by the change of IPSS between the baseline and 3 months post-
procedure. A therapeutic responder is defined as a subject who has an IPSS improvement of ≥ 40%.    
The study is considered a success if at least 50% of the subjects are considered responders. 


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3.3.2 Primary Safety Endpoint 1: Major Device or Procedure Related Complications 
at 3 Months  
A major device related complication is defined as any of the following device or procedural related 
serious adverse events at 3 months:     
• Device or procedure related new onset severe urinary retention lasting > 14 
consecutive days post-healing 
• Device or procedure related unresolved new onset stress urinary incontinence by 90 
days  
• Device or procedure related bleeding requiring transfusion  
3.3.1 Secondary Endpoint 1: Average Improvement of IPSS Compared to Baseline 
at each of the major follow up timepoints at or after 3 months 
3.3.2 Secondary Endpoint 2: Change in Peak urinary flow rate (Qmax)   
3.3.3 Secondary Endpoint 3: Proportion of subjects whose IPSS improvement is > 
30%, 40%, 50% and 75% post-treatment at each of the major follow up 
timepoints at or after 3 months 
3.3.4 Exploratory Endpoints 
• E1: Change in pain score  
• E2: Change in IIEF (International Index of Erectile Function)  
• E3: Change in EQ-5D quality of life  
• E4: Subject satisfaction  
• E5: Procedure parameters 
• E6: Change in MSHQ-EjD 
4 SUBJECT SELECTION 
 
 
 
 
 
 
 
 
4.1 Inclusion Criteria 
1. Male subject > 50 years of age who has moderate-to-severe LUTS (IPSS score of ≥ 
13) and is a candidate for interventional therapy 
2. LUTS felt to be secondary to an enlarged prostate (henceforth termed LUTS/BPH) 
 


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3. Peak urinary flow rate (Qmax) ≥ 5 mL/sec and ≤ 15 ml/sec with minimum voided 
volume of ≥ 125 ml 
4. Post-void residual (PVR) ≤ 250 ml 
5. Prostate volume 20 - 80 gm as determined by TRUS 
6. Prostatic urethra length is 35 – 55 mm as determined by TRUS 
7. Able to complete the study protocol in the opinion of the investigator 
4.2 Exclusion Criteria 
1. Interested in maintaining fertility and unwilling to use protected sex for the first 30 
days post treatment 
2. Unwilling to abstain or use protected sex for ninety (90) days post treatment if 
sexual partner is of child bearing potential 
3. Presence of a penile implant or stent(s) in the urethra or prostate 
4. Any prior minimally invasive intervention (e.g. TUNA, Balloon, Microwave, 
Rezūm, UroLift) or surgical intervention of the prostate  
5. PSA > 10 ng/ml unless prostate cancer is ruled out by biopsy.  If PSA is > 4 ng/ml 
and ≤ 10 ng/ml, prostate cancer must be ruled out to the satisfaction of the 
investigator via additional tests including digital rectal exam (DRE) and/or biopsy 
6. Confirmed or suspected malignancy of prostate or bladder 
7. Active or history of epididymitis within the past 3 months 
8. Previous pelvic irradiation or radical pelvic surgery 
9. Documented active urinary tract infection (UTI) by culture or bacterial prostatitis 
within last year documented by culture (UTI is defined as >100,000 colonies per ml 
urine from midstream clean catch or catheterization specimen) 
10. Visible hematuria with subject urine sample without known contributing factor 
11. Neurogenic bladder or sphincter abnormalities or neurological disorders that might 
affect bladder or sphincter function 
12. Previous or current diagnosis of urethral strictures, bladder neck contracture or 
detrusor muscle spasms 
13. Use of beta blockers, antihistamines, anticonvulsants, or antispasmodics within 1 
week prior to treatment unless there is documented evidence of stable dosing for 
last 6 months (no dose changes) 
14. Use of alpha blockers, antidepressants, anticholinergics, androgens, daily tadalafil 
or gonadotropin-releasing hormonal analogs (prescribed for BPH) within 3 weeks 
prior to treatment  
15. Use of 5-alpha reductase inhibitor within 6 months prior to treatment 
16. Incidence of spontaneous urinary retention within 6 months prior to baseline 
assessment 
17. Post-void residual volume > 250 ml or catheter dependent bladder drainage 
18. Overactive bladder (OAB) or urge incontinence  
19. Known poor detrusor muscle function (e.g. Qmax < 5 ml/sec) 
20. Current bladder stones or prostatic calculi 
21. Biopsy of prostate within 30 days prior to procedure or planned within 30 days 
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22. 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 
23. History of clinically significant comorbidities or presence of unstable conditions 
(e.g. cardiovascular, lung, renal [serum creatinine > 2.0 mg/dl], hepatic, bleeding 
disorders, or metabolic impairment) that may confound the results of the study or 
have a risk to subject per investigator’s opinion 
24. Any cognitive disorder that interferes with or precludes direct and accurate 
communication with the study investigator regarding the study or affects the ability 
to complete the study quality of life questionnaires 
25. Expected life expectancy < one year 
26. Unable or unwilling to sign the Informed Consent Form (ICF) and/or comply with 
all the follow-up requirements 
27. Currently enrolled in or plan to enroll in another investigational clinical trial for any 
disease except for observational only study 
28. In the opinion of the investigator, it is not in the subject's best interest to participate 
in the study 
29. Current treatment with anti-coagulants (e.g., warfarin or enoxaparin) or anti-platelet 
medications other than aspirin (e.g., clopidogrel) 
30. Anatomy, e.g. presence of false passage or size of meatus, is not suitable for 
treatment in this study 
31. Device that corresponds with the subject’s prostate size per the IFU is not available 
32. Intravesical prostatic protrusion (IPP) > 1 cm 
33. Current uncontrolled diabetes (hemoglobin A1c > 7%) 
34. Unable or unwilling to provide all the protocol-required semen samples 
35. Sensitivity to paclitaxel, on medication that may have negative interaction with 
paclitaxel, or contraindicated for systemic paclitaxel 
5 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 with sufficient resources and 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 ethics committee (EC).   
6 PHYSICIAN SELECTION 
Physicians selected must have experience in performing cystoscopy and endoscopic treatment of 
BPH.  Selected physicians will be trained in the use of Urotronic’s pre-dilation balloon catheter and 
Optilume BPH Prostatic Drug Coated Balloon Dilation Catheter prior to enrolling subjects.  The 
primary investigator at each site will ensure that only trained sub-investigators who satisfy the 
physician selection criteria can perform the study interventional procedure.   


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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. 
7 STUDY PROCEDURES 
7.1 Pre-screening, Screening, and Baseline 
The site may pre-screen potential subjects by reviewing medical records to identify potential study 
subjects.  Once identified, these subjects are approached for the study and 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 scheduled treatment as 
possible and repeated if needed.  Any required procedures performed before obtaining informed 
consent as part of the standard of care may be used in lieu of the study tests. 
 
  
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


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8. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7.2 Subject Enrollment 
Only subjects who meet the entrance criteria will be eligible to be enrolled and participate in the 
study.   
Once it is determined that a subject meets the enrollment criteria (except for the use of the 
concomitant medication), the subject will be given an informed consent to read.  If the subject is on 
BPH medication, they will then go through a washout period.  Subjects who cannot tolerate a drug 
washout or are considered high risk from the drug washout should be excluded from the study. If 
the subject successfully goes through the washout period and still meets the entrance criteria, the 


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subject will be eligible to be enrolled.  Screening information will be sent to the Study Principal 
Investigator (PI) for review and approval.  After the subject provides informed consent, is approved 
by the Study PI, and is confirmed to meet all the entrance criteria, the subject will be considered 
enrolled and assigned a unique identification code (ID). 
7.3 Concomitant Therapy 
Therapy (medication and non-medication therapies) not restricted by protocol 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, per physician’s discretion.   
7.4 
 
 
 
 
 
 
    
 
  
 
 
  
 
 
 
 
 
 
  
 
  
 
   
 
 
  
 
 
 
 
  
 
   


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3. 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
   
 
 
  
 
 
 
  
 












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7.6 Unscheduled Follow-up Visits 
If subjects are seen for unscheduled/interim visits because of an AE, appropriate Case Report 
Form(s) (CRF), including the AE CRF, will be completed.  At the investigator’s discretion, some of 
the evaluations and tests may be repeated if indicated.  The Sponsor requests that if any additional 
tests or procedures listed within this protocol are performed during an unscheduled visit, the 
investigator should provide the results on the Unscheduled Visit CRF(s). 
7.7 Lost to Follow-up 
If a subject fails to comply with follow-up visits, 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 visits, but is present at the subsequent follow-up, the subject 
should be queried retrospectively for basic information (e.g., AEs); however, the IPSS and other 
questionnaires will be collected prospectively only. The missed visit must be documented on a 
Protocol Deviation CRF.     
7.8 Subject Withdrawal from Study 
7.8.1 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. 
7.8.2 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 entrance criteria.  However, these subjects will continue to be followed unless instructed 
otherwise by the EC.  The major entrance criteria that would cause the withdrawal of the subjects’ 
data are: 
• Failure to obtain an informed consent prior to treatment; 
• Subject had bladder or sphincter dysfunctions or anything else that would confound the 
results; 
• Subject had a psychiatric or cognitive disorder that prevents him from adequately answering 
the study questionnaires. 
The decision to exclude the subject’s data from analysis will be documented on the End of Study 
CRF. 


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7.8.3 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.   
7.9 End of Study 
Subjects receiving the Urotronic DCB procedure may exit the study at the end of the study, either 
when the subject has completed the 1-year or 5-year follow-up visit or the study is discontinued by 
the Sponsor, whichever comes first, unless the subject opted to find an alternative treatment.  
If a subject receives additional BPH therapy, ongoing follow-up will be limited to general health 
information at the planned follow-up visits after receiving this therapy. General health information 
may include vital status, adverse events that have occurred, or additional BPH therapies that have 
been received since the last subject contact. General health follow-up information may be collected 
remotely.   
An End of Study CRF will be completed at the time the study is completed, discontinued, or lost to 
follow-up for each subject. 
8 SUBJECT EVALUATION DESCRIPTION 
Follow-up evaluations are expected to be conducted via an in-office visit to allow for collection of 
all the required follow-up assessments. Remote follow-up visits may be conducted in the event an 
in-person visit is not feasible (e.g., due to COVID-19), but the inability to conduct assessments as 
described in Table 5 that require an in-office visit must still be reported as a protocol deviation as 
described in Section 13.8.3. Urinalysis, urine culture and uroflow measurements collected at non-
study sites as standard of care may be utilized if the subject is unable to visit the study site without 
the need to document a protocol deviation unless the testing does not meet the requirements of the 
protocol (e.g., voided volume < 125 ml). 
If a visit is unable to be performed in-person due to COVID-19 restrictions, it is encouraged that 
sites complete a remote visit within the visit-window to assess subject safety and administer 
questionnaires at a minimum. The subject should be brought in for an Unscheduled visit as soon as 
individual and public health concerns allow. Questionnaires should be re-administered at this 
Unscheduled visit.  
8.1 Subject Questionnaires 
All questionnaires are preferably self-administered and will be completed at baseline (with the 
exception of the Subject Satisfaction Questionnaire) and at required follow-up visits. If the 
assessment is required to be conducted remotely (e.g., due to COVID-19 limitations), the 
questionnaires may be mailed to the subject for completion prior to phone/telemedicine follow up, 
and the subject may be queried for understanding of the questions during the visit. If subject 


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compliance is uncertain, the IPSS, VAS, and Subject Satisfaction questionnaires may be interview 
administered at the time of the phone follow up. If a questionnaire is interview administered, this 
should be recorded in the source documentation. Evidence exists that interview administration 
produces equivalent results for these questionnaires.1.2    
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. 
8.1.1 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.   
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).  The IPSS 
can be interpreted 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 beginning with the 
30 Days Visit.   
8.1.2 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 Two 
Week follow-up visit and if indicated, at unscheduled visits. 
8.1.3 BPH Impact Index 
The BPH Impact Index is a self-administered questionnaire that measures the impact of BPH 
symptoms on the subjects’ quality of life.  The questionnaire assesses physical discomfort, 
anxiety/worry, bothersome, and effect on activities of daily living. 
 
1 Plante M, Corcos J, Gregoire M, et al. The International Prostate Symptom Score: Physician vs Self-
Administration in the Quantification of Symptomology. Urology. 1996;47:326-8. 
2 Von Korff M, Jensen MP, Karoly P. Assessing Global Pain Severity by Self-Report in Clinical and Health 
Services Research. Spine. 200;25(24):3140-51. 


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The BPH Impact Index will be administered at baseline and at each follow-up visit beginning with 
the Two Week Visit. 
8.1.4 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. 
The standard IIEF will be administered at baseline and at each follow-up visit beginning with the 30 
Days Visit. 
8.1.5 EQ-5D 
EQ-5D™ is a standardized instrument for use as a measure of health outcome.  EQ-5D-5L is a self-
reported generic preference-based measure of health, developed by the EuroQol Group. The 
instrument can be applied to, and has been shown to be valid for, a wide range of health conditions. 
The EQ-5D has been used in many studies as a way of capturing the health-related quality of life of 
patients, trial participants and the general public. 
The EQ-5D will be administered at baseline and at each follow-up visit beginning with the Two 
Week Visit. 
8.1.6 MSHQ-EjD 
MSHQ-EjD is the four-item version of Male Sexual Health Questionnaire (MSHQ) to assess 
ejaculatory dysfunction (EjD).  It is a self-reported questionnaire that contains three ejaculatory 
function items and one ejaculation bother item.  
The MSHQ-EjD will be administered at baseline and at each follow-up visit beginning with the 30 
Days Visit. 
8.1.7 Subject Pain Questionnaire 
The Visual Analog Scale (VAS) pain score (1 to 10 scale) will be used to access the subject’s pain.  
The pain scale will be administered at baseline, post-procedure while the subject is in recovery, 
following Foley removal and at the 2 Weeks and 30 Days Visits. 
8.1.8 Subject Satisfaction Questionnaire 
This questionnaire is specific to the Urotronic DCB procedure on the treatment of moderate-to-
severe LUTS/BPH and will measure overall satisfaction with the procedure, recommendation of 
treatment to friends/family and if the subject would undergo the treatment again if symptoms were 
to recur within 1 year. 
The Subject Satisfaction Questionnaire will be administered at the 3 Months Visit. 


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8.2 Uroflowmetry 
Subjects will be asked to hydrate and refrain from voiding for two hours prior to each uroflowmetry.  
Hydration may be achieved by asking the subject to drink 2 or more cups of non-caffeinated fluids.   
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 CRFs 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: 
• Voided volume (≥125 ml required for a valid test) 
• Peak flow rate (Qmax), averaged over a 2-second interval 
• Average flow rate 
• Voiding time 
8.2.1 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.  
8.2.2 Post Void Residual Urine Volume 
Following uroflowmetry, residual urine volume in the bladder shall be assessed by either 
bladder scanner ultrasound or catheterization.  The same method must be used pre- and post-
treatment.  
8.3 Cystoscopy 
A screening cystoscopy with video will be performed to confirm the presence of obstructive BPH 
and to estimate the BPH severity.    
Flexible or rigid cystoscope will be used to facilitate the DCB procedure. 
A cystoscopy with video will also be performed at the 3-month follow-up visit concentrating on 
the prostatic urethra. 
8.4 TRUS 
Transrectal Ultrasonography (TRUS) at baseline is required to determine the prostate size and to 
measure any intravesical prostatic protrusion (IPP). 
A TRUS will also be performed at the 3-month follow-up visit. 
9 STATISTICAL CONSIDERATIONS 
The details of the analysis is provided in the statistical analysis plan.  The treatment will be 
considered a success if the primary efficacy endpoint is met and there are no safety concerns.   


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o 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 


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• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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• 
  
 
 
 
   
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
   
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 


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11 TRAINING 
The Sponsor will be responsible for training of appropriate clinical site study personnel.  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. 


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12 DATA MANAGEMENT 
 
 
 
 
 
   
 
 
 
12.2 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. 
13 STUDY RESPONSIBILITIES AND MANAGEMENT 
13.1 Investigator Responsibilities  
Each investigator is responsible for ensuring the investigation is conducted according to all signed 
agreements, the study protocol, EC 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: 
• Signed Investigator Agreement 
• Financial disclosure forms for all participating investigators 
• EC roster 
• EC protocol and ICF approvals 
• Investigators’ current curricula vitae (CV) 
• Signed Site Delegation Log 
 
It is acceptable for Investigators to delegate one or more of the study functions to an associate or 
Co- or Sub-Investigator, or a trained Study Coordinator; however, the Principal 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. 


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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 and the Sponsor. 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
13.3 Ethics Committee (EC)  
Investigators must submit the study protocol to their respective Ethics Committee (EC) and obtain 
the EC’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, 
such as regular reporting, study timing, etc.  Investigators will provide the Sponsor or its designee 
with copies of such approvals and reports. 
13.4 Informed Consent Form (ICF) 
The Sponsor will provide a template informed consent form (ICF) to each study site for EC 
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.   
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 


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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 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. 
13.5 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), 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 
using his/her electronic signature. 
13.6 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: 
• All signed agreements; 
• EC approval letter(s); 
• Signed ICFs; 
• Records of AEs, including supporting documents; 
• Records of protocol deviations, including supporting documents; 
• Records showing receipt, use and disposition of all investigational devices, 
including: 
o Date, quantity, model, lot and serial numbers (if applicable) 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; 
• All correspondence related to the study; 
• Records of each subject’s case history, including study-required CRFs, signed ICF, 
all relevant observations of AEs, the condition of each subject upon entering and 
during the course of the investigation, relevant medical history, the results of all 
diagnostic testing, etc.; 
• Study personnel visit log; 




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13.8 Sponsor Responsibilities  
Urotronic, Inc. is the Sponsor of this study.  The Sponsor’s responsibilities in the study include: 
• Selecting the Principal Investigator(s), all clinical investigators and study sites, and 
other consultants (e.g., monitors) who participate in the study. 
• 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. 
• Select all qualified clinical Investigators and study sites and other consultants (e.g., 
the study monitors) who participate in the study. 
• Provide financial support to each study site. 
• Follow/promote all regulatory standards per appropriate regulations for study sites, 
core laboratories, and other participants, and ensure compliance by periodically 
monitoring sites. 
• Ensure completion of site monitoring of clinical data at each clinical study site.  
• Retain ownership of all clinical data generated in this study, and control the use of 
the data for appropriate purposes only.   
• Review and approve publication of study results in the literature. 
13.8.1 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., cystograms).   
13.8.2 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 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 prior to implementation.  Following approval, 
any Investigational Protocol amendment must be distributed to all protocol recipients at the site. 
13.8.3 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 


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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 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.).  Those deviations from the 
protocol that occur due to limitations related to the COVID-19 pandemic should be reported in the 
study database for each applicable visit (i.e., not in bulk), with the type of deviation describing how 
the specific activity failed to follow protocol-specified requirements and the reason for deviation 
describing how COVID-19 impacted the ability to perform the specific activity. 
An Investigator must notify the Sponsor and the reviewing EC 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. 
13.8.4 Protocol Deviation Notification/Approval to EC/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). This type of deviation initiated by the clinical investigator 
must be reviewed and approved by the EC and the Sponsor prior to implementation.  This type of 
deviation can be used for historical data that is out of window (i.e., 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. 
13.8.5 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 3 months after “Ready 
to Enroll” status, the Sponsor may elect to terminate the investigational site and allocate the slot to 
another candidate site.   
 
 
 
 
 
 
   


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14 STUDY ADMINISTRATION 
14.1 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:  
• 
The signed Investigator’s Agreement 
• 
The Investigational Plan  
• 
Appropriate laws and regulations  
• 
Any conditions of approval imposed by the reviewing EC 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.  Not all 
sites will require a qualification visit.  The reason for waiving the visit (e.g. participation in a 
previous Urotronic clinical study) will be documented in a Note to File.  All study monitors will be 
required to follow the monitoring plan and monitoring standard operating procedures (SOPs).  
 
  
  
  
 
14.1.1 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.  
 
 
 


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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: 
• 
Verification that the current EC-approved informed consent was signed and 
dated by each subject prior to participating in the study required procedures. 
• 
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. 
• 
Source documentation verification by reviewing the CRFs against source 
documentation for accuracy and completeness of information. 
• 
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. 
• 
Verification that subjects met study enrollment criteria. 
• 
Confirmation that the study is being conducted according to the Clinical 
Investigation Plan and applicable regulations. 
• 
Verification that study deviations are documented and reported. 
• 
Verification that the procedures for recording and reporting adverse events to the 
Sponsor are followed. 
• 
Ensuring proper error correction. 
• 
Verification of training documentation of all study personnel participating in 
study related activities. 
• 
Reviewing all correspondence and regulatory documents, including confirmation 
of EC-approved Clinical Investigation Plan or amendments. 
• 
Resolution of outstanding issues and completion of assigned tasks will be 
documented by the monitors. 
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. 
14.1.2 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.  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.)   


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17 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 performance will be provided to the EC as 
a supplemental application.    
The device design or process changes will be evaluated to ensure that they continue to meet the 
product specifications. 
18 PUBLICATION POLICY 
The data and results from the trial are the sole property of the Sponsor. The Sponsor shall have the 
right to access and use all data and results generated during the clinical trial. The Investigators will 
not use the clinical trial/investigation-related data without the written consent of the Sponsor for any 
other purpose than for clinical trial/investigation completion or for generation of publication 
material, as referenced in the Clinical Trial Agreement/Investigator Agreement.  
The Sponsor acknowledges that the trial’s Principal Investigators intend to publish a multi-center 
publication regarding the clinical trial/investigation results, and numerous secondary publications. 
The Sponsor must receive any proposed publication and/or presentation materials at least 30 days 
prior to the proposed date of the presentation or the initial submission of the proposed publication in 
order for the materials to be reviewed by the Sponsor in compliance with the Sponsor’s publication 
policy set forth in the Clinical Trial Agreement/Investigator Agreement. 
The Sponsor is responsible for determining whether to register the Clinical Investigation on 
www.clinicaltrials.gov. Institution(s) and/or Principal Investigator(s) shall not take any 
action to register the trial. 
 


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19 REFERENCES 
 
1 Hansen B, Flyger H, Brasso K, et al. Validation of the self-administered Danish prostatic 
symptom score (DAN-PSS-1) system for use in benign prostatic hyperplasia. Br J Urol. 
1995;76:451-458. 
2 Barry MJ, Fowler FJ Jr, O'Leary MP, et al. Measurement committee of the American 
Urology Association. Med Care. 1995;22:AS145 
3 Vuichoud C and Loughlin KR. Benign prostatic hyperplasia: epidemiology, economics and 
evaluation. Can J Urol. 2015 (Internal Suppl):1-6 
4 Barry MJ, Fowler FJ Jr, O'Leary MP, et al. Measuring disease-specific health status in men 
with benign prostatic hyperplasia. Measurement Committee of The American Urological 
Association. Med Care. 1995 Apr;33(4 Suppl):AS145-55. 
5 McVary KT, Roehrborn CG, Avins AL, et al. Management of benign prostatic hyperplasia 
(BPH) http://www.auanet.org/guidelines/benign-prostatic-hyperplasia-(2010-reviewed-and-
validity-confirmed-2014)