A Prospective, Multicenter, Double Blind, Randomized, Clinical Study to Evaluate the Safety and Efficacy of the Optilume™ BPH Catheter System in Men With Symptomatic BPH
Phase: NA
Conditions: Benign Prostatic Hyperplasia
Sponsor: Urotronic Inc.

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PINNACLE 
A prospective, multicenter, double blind, randomized, clinical study 
to evaluate the safety and efficacy of the Optilume™ BPH Catheter 
System in men with symptomatic BPH 
 
PROTOCOL No. PR1087 
VERSION J 
 
March 14, 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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PINNACLE 
A prospective, multicenter, double blind, randomized, clinical study 
to evaluate the safety and efficacy of the Optilume™ BPH Catheter 
System in men with symptomatic BPH 
 
PROTOCOL No. PR1087 
VERSION J 
 
March 14, 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’s Institutional Review Board (IRB)/Research Ethics Board (REB). I will discuss this 
material with them and ensure they are fully informed regarding the conduct of the study 
according to this protocol, ICH Good Clinical Practice (GCP), ISO 14155, Declaration of 
Helsinki, 21 CFR 50, 56 and 812 and hospital IRB/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:   
PINNACLE: A prospective, multicenter, double blind, randomized, 
clinical study to evaluate the safety and efficacy of the Optilume™ 
BPH Catheter System in men with symptomatic BPH 
Investigational Device: 
Optilume™ BPH Catheter System 
Control Device: 
21 Fr sheathed Optilume™ BPH Prostatic Pre-dilation Catheter 
(modified to prevent inflation) 
Objective: 
To evaluate the safety and efficacy of Optilume™ BPH Catheter 
System in the treatment of benign prostatic hyperplasia (BPH) 
Study Design:  
Prospective, multicenter, double blind, randomized, sham-controlled 
study with a non-randomized, Pharmacokinetics (PK) study arm 
Enrollment: 
162 subjects will be randomized and/or treated in the study at up to 
30 clinical sites in the United States and Canada (up to 28 sites in 
the US and up to 2 sites in Canada).  147 subjects will be 
randomized in the randomized portion of the study, and 15 subjects 
will be treated in the Pharmacokinetics arm of the study. 
Individual site treatments in the randomized portion of the study 
may not exceed 25% of the total randomized study treatments. 
Up to 625 subjects will be enrolled (i.e. consented) in the study in 
order to identify 162 eligible subjects to be randomized and/or 
treated. 
Clinical Follow-up: 
The following follow-up visits are required post-procedure:  
• Foley Removal, 14-Day, 30-Day, 3-Month, 6-Month and 
12-Month 
In addition, all subjects treated with the Optilume BPH Catheter 
System will be followed annually through 5 years 
Study Duration 
Approximately 8 years 
Endpoints 
 
Primary Efficacy Endpoint: Change in IPSS 
In order to meet this endpoint, the observed improvement in IPSS 
at 12 months post-treatment in the Test arm must be at least 25% 
greater than that of the Control arm at 3 months. 
 
Primary Safety Endpoint : Major Device-Related Serious 
Complications 
A major device-related serious complication is defined as any of the 
following events through 12 months:     
• Device-related rectal fistula or gastrointestinal (GI) fistula 

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• Device-related formation of fistula between the rectum and 
urethra 
• Device-related new onset severe urinary retention lasting > 
14 consecutive days post-healing 
• Device-related unresolved new onset stress urinary 
incontinence by 90 days  
• Device-related bleeding requiring transfusion 
• Device-related urethra or prostatic capsule rupture requiring 
surgical intervention 
 
Secondary Endpoint 1: Average IPSS improvement in the Test 
arm at 12 months 
The average IPSS improvement in the Test arm from baseline to 
12 months must be ≥ 30% 
 
Secondary Endpoint 2: Percentage of responders at 3 months 
The responder rate at 3 months of subjects randomized to the 
Test arm will be compared to the responder rate of subjects in 
the Control arm. 
A responder for this endpoint is defined as a subject who has an 
IPSS improvement ≥ 30% post-treatment as compared to 
baseline. 
 
Secondary Endpoint 3: Durability – Percentage of responders  
The responder rate at 12 months of subjects randomized to the 
Test arm will be compared to the responder rate at 3 months of 
subjects in the Control arm. 
A responder for this endpoint is defined as a subject who has an 
IPSS improvement ≥ 30% post-treatment as compared to 
baseline. 
 
Secondary Endpoint 4: Qmax  
The change or increase in Qmax at 12 months for all treated 
subjects randomized to the Test arm will be compared to the 
change or increase in Qmax at 3 months for subjects 
randomized to the Control arm. 

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Ancillary Endpoints: 
A1: Additional responder analyses with a responder defined as 
IPSS improvement of 35%, 40% and 50% 
A2: Change in PVR  
A3: Change in sexual function 
A4. Change in BPH-II 
A5: Change in quality of life 
A6: Change in pain score 
A7: Procedure parameters 
A8: Change in Qmax 
A9: Proportion of subjects experiencing a return to ‘normal’ 
symptom severity 
Study Success Criteria 
For the study to be declared a success, the Primary Efficacy Endpoint 
and Secondary Endpoint 1 must be met without any safety concerns.  
Randomization Arm 
Inclusion Criteria: 
1. Male subject 50-80 years of age who has symptomatic BPH 
2. International Prostate Symptom Score (IPSS) ≥ 13 
3. Peak urinary flow rate (Qmax) ≥ 5 ml/sec and ≤ 12 ml/sec (with 
minimum voided volume of ≥ 150 ml) 
4. Prostate volume 20 to 80 gm as determined by TRUS 
5. Prostatic urethral length ≥ 32 mm and ≤ 55 mm as determined 
by TRUS 
6. History of inadequate response, contraindication, or refusal of 
BPH medical therapy 
7. Able to complete the study protocol in the opinion of the 
investigator 
 
Randomization Arm 
Exclusion Criteria: 
 
 
 
 
 
 
 
 
 
1. Unable or unwilling to sign the Informed Consent Form (ICF) 
and/or comply with all the follow-up requirements 
2. Unwilling to abstain or use protected sex for the first 30 days 
post treatment 
3. Unwilling to abstain from sexual intercourse or use a highly 
effective contraceptive for at least 6 months post-procedure 
4. Presence of an artificial urinary sphincter or stent(s) in the 
urethra or prostate 
5. Any prior minimally invasive intervention (e.g. TUNA, 
Balloon, Microwave, Rezūm, UroLift) or surgical intervention 
of the prostate  
6. PSA ≥ 10 ng/ml unless prostate cancer is ruled out by biopsy   
7. Confirmed or suspected malignancy of prostate or bladder 
8. Active or history of epididymitis within the past 3 months 

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9. Previous pelvic irradiation or pelvic trauma surgery 
10. Active urinary tract infection (UTI) confirmed by culture  
11. Bacterial prostatitis within the last 12 months 
12. Non-bacterial prostatitis within the last 5 years 
13. Visible or invisible hematuria (> 4 RBCs per high power field) 
on 2 separate urine specimens within the last 3 months without a 
known contributing factor 
14. Neurogenic bladder or sphincter abnormalities or neurological 
disorders that might affect bladder or sphincter function 
15. History of urinary incontinence 
16. Previous or current diagnosis of urethral strictures, bladder neck 
contracture or detrusor muscle spasms 
17. Previous rectal surgery, other than hemorrhoidectomy 
18. Use of antihistamines, anticonvulsants or antispasmodics within 
1 week prior to baseline assessment unless there is documented 
evidence of stable dosing for at least 6 months  
19. Use of antidepressants with adrenergic effects (i.e. duloxetine, 
imipramine and amitriptyline), long-acting anticholinergics 
(LAAC) for chronic obstructive pulmonary disease (COPD), or 
androgens within 2 weeks prior to baseline assessment unless 
there is documented evidence of stable dosing for at least 3 
months prior to baseline assessment 
20. Use of Luteinizing Hormone-Releasing Hormone (LHRH) 
analogs within 12 months prior to baseline assessment 
21. Use of Type II 5-alpha reductase inhibitor [e.g. finasteride 
(Proscar, Propecia)] within 3 months of baseline assessment 
22. Use of 5-alpha reductase inhibitor [e.g. dutasteride (Avodart)] 
within 6 months of baseline assessment 
23. Use of estrogen or drugs producing androgen suppression unless 
there is documented evidence of stable dosing for 3 months 
prior to baseline assessment  
24. Use of alpha blockers or daily dose PDE5 inhibitor (e.g. Cialis) 
within 2 weeks of baseline assessment 
25. Use of warfarin or novel oral anti-coagulants [e.g., apixaban 
(Eliquis), fondaparinux (Arixtra), rivaroxaban (Xarelto) or 
edoxaban (Savaysa)], unless the medication is safely 
discontinued prior to the procedure and is not planned to be 
restarted for at least 5 days post-procedure 
26. Use of anti-platelet medications (e.g., clopidogrel, aspirin) 
within 10 days prior to the procedure or planned use within 5 
days post-procedure 

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27. History of hypersensitivity reactions to paclitaxel, on 
medication that may have negative interaction with paclitaxel, 
presence of solid tumor with a baseline neutrophil count of 
<1500 cells/mm3 or AIDS-related Kaposi’s sarcoma with 
baseline neutrophil count of <1000 cells/mm3 
28. Incidence of spontaneous urinary retention within 6 months 
prior to baseline assessment 
29. Current post-void residual volume > 300 ml or catheter 
dependent bladder drainage 
30. Known poor detrusor muscle function (e.g. Qmax < 5 ml/sec) 
31. Current bladder or prostatic urethral stones  
32. Biopsy of prostate within 40 days prior to procedure  
33. History of cancer in non-genitourinary system which is not 
considered in complete remission (except basal cell or 
squamous cell carcinoma of the skin).  A potential participant is 
considered in complete remission if there has been no evidence 
of cancer within five years 
34. Current uncontrolled diabetes (i.e. hemoglobin A1c ≥ 8%) 
35. 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 
36. 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 
37. Life expectancy < 10 years 
38. Anatomy (e.g. presence of false passage or size of meatus) is 
not suitable for treatment in this study 
39. Significant median lobe component [e.g. intravesical prostatic 
protrusion (IPP) > 1 cm] 
40. Device that corresponds with the subject’s prostate size is not 
available 
41. Currently enrolled in or plan to enroll in another investigational 
clinical study for any disease except for observational only 
study 
42. In the opinion of the investigator, it is not in the subject's best 
interest to participate in the study 
 
Pharmacokinetics Arm 
Inclusion Criteria: 
Subjects must meet all the inclusion criteria for the Randomization 
arm of the study with the exception of Inclusion 3; the subject’s 

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Qmax  must be ≥ 5 ml/sec and ≤ 15 ml/sec (with minimum voided 
volume of ≥ 150 ml) in order to be eligible to participate in the PK 
arm of the study 
Pharmacokinetics Arm 
Exclusion Criteria: 
In addition to not meeting any of the exclusion criteria for the 
Randomization arm of the study, subjects must also not meet the 
following criteria in order to be eligible to participate in the PK arm 
of the study: 
• Previous treatment with any device or medical therapy that 
contains paclitaxel  
• Unable or unwilling to provide viable semen samples 
 
 

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Table of Contents 
1 
INTRODUCTION ............................................................................................................................. 15 
1.1 
DISEASE STATE OVERVIEW AND EPIDEMIOLOGY ............................................................................................ 15 
1.2 
HISTORY OF USE OF PACLITAXEL ................................................................................................................. 15 
1.3 
PREVIOUS CLINICAL EXPERIENCES OF DCB USE FOR BPH ................................................................................ 16 
1.3.1 
EVEREST-I Efficacy Results ......................................................................................................... 16 
1.3.2 
EVEREST-I Safety Results ........................................................................................................... 17 
1.3.3 
EVEREST-I Pharmacokinetics Results ......................................................................................... 18 
1.4 
RATIONALE FOR STUDY ............................................................................................................................. 19 
2 
DEVICE DESCRIPTION ..................................................................................................................... 20 
3 
RISK-BENEFIT ANALYSIS ................................................................................................................. 21 
3.1 
RISK ANALYSIS ........................................................................................................................................ 21 
3.1.1 
Risk Assessment ........................................................................................................................ 21 
3.1.2 
Risk Mitigation .......................................................................................................................... 21 
3.2 
POTENTIAL BENEFIT ................................................................................................................................. 22 
3.3 
STUDY PARTICIPATION ASSOCIATED RISKS .................................................................................................... 22 
4 
STUDY OBJECTIVES AND DESIGN .................................................................................................... 22 
4.1 
OBJECTIVE ............................................................................................................................................. 22 
4.2 
STUDY DESIGN ........................................................................................................................................ 23 
4.2.1 
Test Arm Description ................................................................................................................. 25 
4.2.2 
Control Arm Description ............................................................................................................ 25 
4.2.3 
Cross-over/Alternative Therapy ................................................................................................ 25 
4.3 
PHARMACOKINETICS ARM DESCRIPTION ...................................................................................................... 25 
4.3.1 
Blood PK Collection .................................................................................................................... 26 
4.3.2 
Urine PK Collection .................................................................................................................... 26 
4.3.3 
Semen PK Collection .................................................................................................................. 27 
4.4 
STUDY ENDPOINTS .................................................................................................................................. 27 
4.4.1 
Primary Efficacy Endpoint : Change in IPSS ............................................................................... 27 
4.4.2 
Primary Safety Endpoint : Major Device-Related Serious Complications .................................. 28 
4.4.3 
Secondary Endpoint 1: Average IPSS improvement in the Test arm at 12 months ................... 28 
4.4.4 
Secondary Endpoint 2: Percentage of responders at 3 months ................................................. 28 
4.4.5 
Secondary Endpoint 3: Durability - Percentage of responders .................................................. 28 
4.4.6 
Secondary Endpoint 4: Qmax .................................................................................................... 28 
4.4.7 
Ancillary Endpoints .................................................................................................................... 29 
5 
SUBJECT SELECTION ....................................................................................................................... 29 
5.1 
ENTRANCE CRITERIA FOR RANDOMIZATION ARM ........................................................................................... 29 
5.1.1 
Inclusion Criteria for Randomization Arm ................................................................................. 29 
5.1.2 
Exclusion Criteria for Randomization Arm ................................................................................. 29 
5.2 
ENTRANCE CRITERIA FOR PHARMACOKINETICS ARM ....................................................................................... 31 
5.2.1 
Inclusion Criteria for PK Arm ..................................................................................................... 31 
5.2.2 
Exclusion Criteria for PK Arm ..................................................................................................... 31 
6 
SITE SELECTION ............................................................................................................................. 31 
7 
PHYSICIAN SELECTION ................................................................................................................... 32 

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7.1 
TRAINING .............................................................................................................................................. 32 
8 
STUDY PROCEDURES ..................................................................................................................... 32 
8.1 
PRE-SCREENING, SCREENING, AND BASELINE ................................................................................................ 32 
8.2 
SUBJECT ENROLLMENT ............................................................................................................................. 36 
8.3 
CONCOMITANT THERAPY .......................................................................................................................... 37 
8.4 
RANDOMIZATION .................................................................................................................................... 37 
8.5 
BLINDING .............................................................................................................................................. 37 
8.6 
STUDY PROCEDURE – RANDOMIZATION ARM ............................................................................................... 41 
8.6.1 
Peri-procedural Medication ....................................................................................................... 41 
8.6.2 
Test Arm Procedure Description ................................................................................................ 42 
8.6.3 
Control Arm Procedure Description ........................................................................................... 42 
8.7 
STUDY PROCEDURE - PK ARM ................................................................................................................... 42 
8.7.1 
Peri-procedural Medication ....................................................................................................... 43 
8.7.2 
PK Arm Procedure Description .................................................................................................. 43 
8.8 
CATHETERIZATION ................................................................................................................................... 43 
8.9 
IN-HOSPITAL TO DISCHARGE ..................................................................................................................... 44 
8.10 PHYSICAL ACTIVITIES ................................................................................................................................ 44 
8.11 SEXUAL ACTIVITIES .................................................................................................................................. 44 
8.12 SCHEDULED FOLLOW-UP EVALUATIONS ....................................................................................................... 44 
8.13 UNSCHEDULED FOLLOW-UP VISITS ............................................................................................................. 48 
8.14 LOST TO FOLLOW-UP ............................................................................................................................... 48 
8.15 SUBJECT WITHDRAWAL FROM STUDY .......................................................................................................... 48 
8.15.1 Voluntary Withdrawal ............................................................................................................... 48 
8.15.2 Involuntary Withdrawal ............................................................................................................ 48 
8.15.3 Alternative Treatments ............................................................................................................. 48 
8.16 FOLLOW-UP FOR GENERAL HEALTH ............................................................................................................ 49 
8.17 END OF STUDY ........................................................................................................................................ 49 
9 
SUBJECT EVALUATION DESCRIPTION .............................................................................................. 49 
9.1 
PLACE OF SERVICE ................................................................................................................................... 49 
9.2 
PHYSICAL EXAMINATION ........................................................................................................................... 49 
9.3 
SUBJECT QUESTIONNAIRES ........................................................................................................................ 50 
9.3.1 
IPSS (Standard) .......................................................................................................................... 50 
9.3.2 
IPSS (Acute) ............................................................................................................................... 51 
9.3.3 
BPH Impact Index ...................................................................................................................... 51 
9.3.4 
International Index of Erectile Function .................................................................................... 51 
9.3.5 
EQ-5D ........................................................................................................................................ 51 
9.3.6 
MSHQ-EjD .................................................................................................................................. 51 
9.3.7 
Subject Pain Questionnaire ....................................................................................................... 52 
9.3.8 
Subject Satisfaction Questionnaire ............................................................................................ 52 
9.4 
BLOOD ANALYSIS .................................................................................................................................... 52 
9.5 
DIPSTICK URINE ANALYSIS ......................................................................................................................... 52 
9.5.1 
Urine culture .............................................................................................................................. 53 
9.6 
UROFLOWMETRY .................................................................................................................................... 53 
9.6.1 
Peak Flow Rate (Qmax) Measurement ...................................................................................... 53 
9.6.2 
Post Void Residual Urine Volume .............................................................................................. 53 
9.7 
CYSTOSCOPY .......................................................................................................................................... 53 
9.8 
TRUS ................................................................................................................................................... 54 
9.9 
SEMEN ANALYSIS .................................................................................................................................... 54 
9.10 REMOTE ASSESSMENTS ............................................................................................................................ 54 

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10 
STATISTICAL CONSIDERATIONS ...................................................................................................... 54 
10.1 PRIMARY EFFICACY ENDPOINT ANALYSIS ...................................................................................................... 55 
10.2 PRIMARY SAFETY ENDPOINT ANALYSIS ........................................................................................................ 55 
10.3 SECONDARY ENDPOINT ANALYSES .............................................................................................................. 55 
10.4 ANCILLARY ENDPOINT ANALYSES ................................................................................................................ 56 
10.5 SAMPLE SIZE JUSTIFICATION ...................................................................................................................... 56 
10.6 STUDY SUCCESS CRITERIA ......................................................................................................................... 56 
10.7 ANALYSIS POPULATIONS ........................................................................................................................... 56 
10.8 HANDLING OF MISSING DATA .................................................................................................................... 57 
10.8.1 For the Primary Efficacy Endpoint and Secondary Endpoints S1 ............................................... 57 
10.8.2 For the Primary Efficacy Endpoint ............................................................................................. 57 
11 
DEFINITION OF ADVERSE EVENT(S) ................................................................................................ 57 
11.1 TREATMENT RELATED SYMPTOMS .............................................................................................................. 57 
11.2 URINARY RETENTION AND CATHETERIZATION ............................................................................................... 58 
11.3 ACUTE URINARY RETENTION DEFINITION ..................................................................................................... 58 
11.4 OBSTRUCTIVE LUTS ................................................................................................................................ 58 
11.5 REPORTING AND CLASSIFICATION OF AES ..................................................................................................... 59 
11.6 POTENTIAL ANTICIPATED ADVERSE EVENTS .................................................................................................. 60 
11.7 DEFINITION OF SERIOUS ADVERSE EVENT(S) ................................................................................................. 64 
11.8 UNANTICIPATED ADVERSE DEVICE EFFECT(S) (UADE) ................................................................................... 64 
11.9 REPORTING OF ALL ADVERSE EVENTS .......................................................................................................... 65 
11.10 RELATIONSHIP OF AES TO THE DEVICE AND PROCEDURE ................................................................................. 65 
11.11 ADVERSE EVENT SEVERITY ......................................................................................................................... 66 
11.12 DEVICE FAILURES, MALFUNCTIONS AND NEAR INCIDENTS ............................................................................... 66 
12 
TRAINING ...................................................................................................................................... 66 
13 
DATA MANAGEMENT .................................................................................................................... 67 
13.1 STUDY DATABASE AND ELECTRONIC CASE REPORT FORMS .............................................................................. 67 
13.2 SUBJECT IDENTIFICATION .......................................................................................................................... 67 
13.3 CENTRAL DATABASE ................................................................................................................................ 67 
14 
STUDY RESPONSIBILITIES AND MANAGEMENT ............................................................................... 67 
14.1 CLINICAL EVENTS COMMITTEE ................................................................................................................... 67 
14.2 DATA MONITORING COMMITTEE ............................................................................................................... 67 
14.3 INVESTIGATOR RESPONSIBILITIES ................................................................................................................ 68 
14.3.1 Confidentiality ........................................................................................................................... 68 
14.3.2 Amending the Investigational Study Protocol ........................................................................... 69 
14.3.3 Protocol Deviations ................................................................................................................... 69 
14.3.4 Protocol Deviation Notification/Approval to IRB/REB/Sponsor before Implementation .......... 69 
14.3.5 Site Noncompliance and Nonperformance ................................................................................ 69 
14.3.6 Device Accountability ................................................................................................................ 70 
14.4 SUBJECT ENROLLMENT PROCESS ................................................................................................................ 70 
14.5 INSTITUTIONAL REVIEW BOARD (IRB)/RESEARCH ETHICS BOARD (REB) ............................................................ 70 
14.6 INFORMED CONSENT FORM (ICF) .............................................................................................................. 71 
14.7 CASE REPORT FORMS (CRFS) .................................................................................................................... 71 
14.8 RECORDS ............................................................................................................................................... 71 
14.9 REPORTS ............................................................................................................................................... 72 
14.10 SPONSOR RESPONSIBILITIES ....................................................................................................................... 73 
14.10.1 Sponsor Reporting Responsibilities............................................................................................ 73 

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15 
STUDY ADMINISTRATION .............................................................................................................. 74 
15.1 MONITORING PROCEDURES ...................................................................................................................... 74 
15.1.1 Monitoring Visit ......................................................................................................................... 75 
15.1.2 Study Closure ............................................................................................................................. 76 
16 
STUDY CONTACT ........................................................................................................................... 76 
16.1 STUDY PRINCIPAL INVESTIGATOR ................................................................................................................ 76 
16.2 SPONSOR ............................................................................................................................................... 77 
16.3 DATA MANAGEMENT ............................................................................................................................... 77 
17 
POTENTIAL DEVICE CHANGE .......................................................................................................... 77 
18 
PUBLICATION POLICY ..................................................................................................................... 77 
19 
REFERENCES .................................................................................................................................. 79 
 
 
 
 
 
 
 

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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 
CBC 
Complete Blood Count 
CMI 
Clinically Meaningful Improvement 
CMP 
Complete Metabolic Panel 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCB 
Drug Coated Balloon 
eCRF 
Electronic Case Report Form 
EQ-5D  
Standardized instrument for use as a measure of health outcome 
GCP 
 
Good Clinical Practice 
GI 
 
Gastrointestinal 
ICF 
 
Informed Consent Form 
IFU 
 
Instructions for Use 
IIEF 
 
International Index of Erectile Function 
IPP 
 
Intravesical Prostatic Protrusion 
IPSS  
International Prostate Symptom Score 
IRB 
 
Institutional Review Board 
LHRH  
Luteinizing Hormone-Releasing Hormone 
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 
PTX 
 
Paclitaxel (coating drug on the balloon) 
PV 
 
Prostate Volume 
PVR 
 
Post Void Residual Urine Volume 
Qmax  
Peak Flow Rate 

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QoL 
 
Quality of Life 
REB 
 
Research Ethics Board 
SAE 
 
Serious Adverse Event 
TRUS  
Transrectal Ultrasonography 
TUAP  
Transurethral Anterior Commissurotomy of the Prostate 
TUMT  
Transurethral Microwave Thermotherapy 
TUNA  
Transurethral Needle Ablation 
TURP  
Transurethral Resection of the Prostate 
UADE  
Unanticipated Adverse Device Effect 
USA  
United States of America 
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) or its 
related International Prostate Symptom Score (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-eluting stents (DES) and drug-coated 
balloons (DCB) 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 obstructive BPH. 
 

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Table 1-1: US Approved Paclitaxel-Coated Devices 
Paclitaxel-Coated Device 
US Approval Date 
Boston Scientific TASUX DES 
2004 
Cook Medical Zilver PTX DES 
2012 
BD Lutonix DCB 
2014 
Medtronic In.Pact Admiral DCB 
2015 
Covidien/Spectranetics/Philips Stellarex DCB 
2017 
 
1.3 
Previous Clinical Experiences of DCB use for BPH 
The Optilume™ BPH Catheter System is currently under investigation.  The EVEREST-I pilot study 
has completed enrollment and the treatment of 80 subjects with BPH at six Latin American 
investigational sites, two in Panama and four in the Dominican Republic.  Subject follow-up is 
currently ongoing.  As of July 3, 2019, 79 subjects had completed the 3-Month follow-up visit, 53 
subjects had completed the 6-Month follow-up visit and 45 subjects had completed the 1-Year 
follow-up visit.   
1.3.1 EVEREST-I Efficacy Results 
The EVEREST-I clinical efficacy data show that the percentage of study therapeutic responders, 
defined as ≥ 40% improvement in IPSS at the 3-Month follow-up from baseline, was 81.3% (65/80).  
It means that the study Primary Efficacy Endpoint was met.  
The average IPSS improved from severely symptomatic at baseline (IPSS=22.3) to mildly moderate 
symptomatic at 3-Month follow-up (IPSS = 8.1), which is durable at 6-Month (IPSS = 8.0) and at 1-
Year (IPSS = 8.2) follow-ups. The average improvements in IPSS at 3-Month, 6-Month and 1-Year 
were 14.2, 14.7 and 14.0 points.  The minimal clinically important difference (MCID) of IPSS for 
patients with mild-to-moderate LUTS is 2 points, whereas for patients with severe LUTS  is 6 points.  
It means that the IPSS improvement after Optilume BPH Catheter /procedure is considered clinically 
meaningful improvement (CMI). 
 

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Figure 1-1: Effect of Optilume BPH Prostatic DCB on IPSS  
The improvement observed in IPSS is also seen in the improvement in Qmax.  Mean Qmax increased 
from 10.9 ml/sec at baseline to 20.5 ml/sec at 3-Month, 21.7 ml/sec at 6-Month and 19.3 ml/sec at 
1-Year follow-ups.  The average improvements in Qmax were 9.6, 11.0 and 8.2 ml/sec from baseline 
to 3-Month, 6-Month and 1-Year follow ups.   The minimal clinically important difference (MCID) 
for Qmax is 2 ml/sec.   It means that Qmax improvement after Optilume BPH Catheter /procedure is 
considered clinically meaningful improvement (CMI). 
Furthermore, the averages of PVR were reduced from 63.1 ml at baseline, to 34.3 ml at 3-Month, 
27.5 ml at 6-Month and 32.4 ml at 1-Year follow-ups. The average improvements in PVR from 
baseline were 30.0 ml, 42.5 ml and 41.1 ml at 3-Month, 6-Month and 1-Year respectively.   These 
improvements indicate that the subjects were able to void more completely, thus alleviating the 
lower urinary tract symptoms (LUTS) secondary to BPH. 
1.3.2 EVEREST-I Safety Results 
The Primary Safety Endpoint was defined as any of the following device- or procedure-related 
serious adverse events at 3 months: 
• 
Device- or procedural-related new onset severe urinary retention lasting > 14 consecutive 
days post-healing 
• Device- or procedural-related unresolved new onset stress urinary incontinence by 90 days  
• Device- or procedure-related bleeding requiring transfusion 
One major device- or procedure-related complication (1.3%, 1/80) was identified, which was stress 
urinary incontinence. 

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As of July 3, 2019, a total of 103 AEs was reported, regardless of relationship to the study device  
or procedure.  58 of the AEs were reported from the 58 subjects treated with either a 30 mm or 35 
mm diameter DCB, and 45 of the AEs were reported from the 22 subjects treated with a 40 mm 
diameter DCB. 
 
The most frequently reported adverse events in the EVEREST-I study are listed in Table 1-2. 
Table 1-2: EVEREST-I Most Frequent Adverse Events 
AE Name 
Events in All Subjects 
(N=80) 
Events in Subjects 
Treated with   
30 or 35 mm DCB 
(N=58) 
Events in Subjects 
Treated with   
40 mm DCB 
 (N=22) 
Urinary symptoms: 
Urethrorrhagia or 
Hematuria 
12/80 (15.0%) 
5/58 (8.6%) 
7/22 (31.8%) 
Urinary Tract 
Infection 
9/80 (11.3%) 
5/58 (8.6%) 
4/22 (18.2%) 
Urinary clot retention 
9/80 (11.3%) 
6/58 (10.3%) 
3/22 (13.6%) 
Ejaculatory 
dysfunction 
7/80 (8.8%) 
6/58 (10.3%) 
1/22 (4.5%) 
Urinary symptoms: 
Dysuria 
7/80 (8.8%) 
3/58 (5.2%) 
4/22 (18.2%) 
Urinary symptoms: 
Incontinence - Stress 
6/80 (7.5%) 
1/58 (1.7%) 
5/22 (22.7%) 
Stricture 
5/80 (6.3%) 
4/58 (6.9%) 
1/22 (4.5%) 
Urinary symptoms: 
Incontinence - Urge 
4/80 (5.0%) 
1/58 (1.7%) 
3/22 (13.6%) 
No unanticipated adverse device effects (UADE) have been reported. 
1.3.3 EVEREST-I Pharmacokinetics Results 
Pharmacokinetic (PK) testing was studied for paclitaxel in a subset of EVEREST-I subjects on the 
plasma, urine and semen samples collected. Test results confirmed that the amount of drug found in 
the plasma and semen following treatment is very small and does not present a health hazard.  The 
pharmacokinetics of the drug in the plasma, semen and urine is shown in Figure 1-2.  The majority 
of the drug delivered was limited to the surface of the urethra/prostate.  Very low amounts of drug 
were found in plasma.  The amount of drug in the semen correlate with the amount of drug in the 
urine since semen is expelled through the urethra. 
Drug concentration in the urine dropped significantly between the procedure and the 4-Day follow-
up.   

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Figure 1-2: Summary of EVEREST-I PK Data 
1.4 
Rationale for Study 
Balloon dilation is one of the least invasive interventional therapies to treat BPH. Extensive clinical 
research on balloon dilation of the prostate was completed in the 1990s using balloon sizes ranging 
from 20-35mm. These studies showed that balloon dilation was safe and well tolerated by patients. 
However, mixed efficacy at 3-6 months in certain patient populations and 12-month LUTS 
reoccurrence for many patients caused the technology to be abandoned.  
The Optilume™ BPH Catheter System is used to perform a TransUrethral Anterior commissurotomy 
of the Prostate (TUAP).  The system combines the procedural advantage of simplicity with improved 
efficacy over other balloon dilation through its unique balloon geometry with a localized application 
of paclitaxel to prevent future cellular proliferation and excessive scar tissue generation during the 
healing process. The goal of this technology is to provide immediate relief via balloon dilation and 
create lasting durable results to alleviate LUTS associated with BPH. 
This study is designed to assess the safety and efficacy of the Optilume BPH Catheter System to 
alleviate moderate-to-severe LUTS/BPH. 
 

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2 DEVICE DESCRIPTION 
The Optilume™ BPH Catheter System consists of two investigational catheters: 
• Optilume™ BPH Prostatic Pre-dilation Catheter 
• Optilume™ BPH Prostatic Dilation DCB Catheter 
The pre-dilation catheter is constructed identically to the drug coated balloon catheter, but without 
the paclitaxel drug coating. The pre-dilation and drug coated balloon catheters are packaged 
separately.    
The Optilume™ BPH, Prostatic Pre-dilation Catheter is a dilation catheter used to exert radial force 
to dilate the prostatic urethra resulting in a commissurotomy.  The distal end of the catheter has a 
semi-compliant inflatable double lobe balloon with a neck separating the two sections.  The balloon 
neck is reinforced which makes the neck section non-compliant thereby minimizing diameter growth 
in the neck during the inflation process. 
The Optilume™ BPH, Prostatic Dilation DCB has a double lobe balloon that is coated with a 
proprietary coating containing the active pharmaceutical paclitaxel.  (See Figure 2-1).  
 
Figure 2-1: Inflated Drug Coated Balloon  
 
The double lobe design allows the balloon neck to naturally seek and seat in the bladder neck during 
inflation and inhibits migration of the balloon into the bladder.  The distal lobe of the balloon inflates 
in the bladder and aids in anchoring the device, while the proximal lobe of the balloon is positioned 
in the prostatic urethra and dilates the prostate separating the anterior prostatic commissure. The 
balloon body and a portion of the proximal cone are coated with the active pharmaceutical ingredient 
(API), paclitaxel, as shown in Figure 2-1.  The pre-dilation balloon has the same design but provided 
uncoated. 
All materials used in the construction of the Optilume™ BPH Catheter System are known 
biocompatible materials and are commonly used in the medical device industry.   
The device is supplied STERILE for single use only (ethylene oxide sterilization).  
The full device description and balloon sizes available for the study are described in the Instructions 
for Use. 

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3 RISK-BENEFIT ANALYSIS  
3.1 
Risk Analysis 
Balloon dilation to treat BPH is an established treatment and the risk associated with the procedure 
is well understood.  The investigational device contains a drug coated balloon that is intended to 
suppress cellular proliferation and hence potentially mitigate the risk of recurrence of LUTS/BPH at 
the treatment site.  
Refer to Instructions for Use as well as the Section 11 Definition of Adverse Event(s) of this protocol 
for the associated risks. 
3.1.1 Risk Assessment 
In conducting the risk analysis, the concepts of risk estimation, risk acceptability, risk control and 
overall risk evaluation were applied in accordance with ISO 14971. The intended use and treatment 
procedure was taken into consideration along with the materials and mechanical features of the 
Optilume BPH Catheter System. Based on an evaluation of residual risk acceptability, it was 
determined that no individual residual risks values are considered unacceptable and that all 
individual risks are balanced against the benefit of the device.  
3.1.2 Risk Mitigation  
The potential AEs and device issues associated with the Test device are not fully understood in the 
treatment of BPH, so there is the potential for device issues and adverse events not previously 
identified to occur.  To minimize potential risks, the device shall only be used by physicians who 
are specialized in urology and have been trained on the use of the device. The patients will be 
carefully screened against the inclusion and exclusion criteria before randomization/treatment in the 
study. All device deficiencies and adverse events from the study will be closely monitored.  
A potential health risk of study participation is due to the paclitaxel drug coating. Paclitaxel is a 
lipophilic, anti-mitotic agent that has been reported to prevent proliferation of smooth muscle cells, 
inflammatory cells and fibroblast. The purpose of using paclitaxel in the coating of the device is to 
prevent or reduce recurrence of LUTS by inhibiting smooth muscle cell proliferation and urothelial 
hyperplasia. The potential risks of paclitaxel in the coating include:  
• Chromosomal abnormalities and the risk of cancer 
• Fetal harm when a pregnant woman is exposed 
• Anaphylaxis and hypersensitivity with paclitaxel intravenous infusion have been reported 
• It may inhibit the healing of the urethra post procedure 
• 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 essentially localized to the urethra.  

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Therefore, the risk of drug toxicity is anticipated to be very low as the concentration of the drug in 
the body fluid is very low.  The complete list of potential anticipated adverse events is provided in 
Section 11.6 of this protocol. 
3.2 
Potential Benefit 
The subjects participating in this study potentially could benefit from the reduction in LUTS or BPH 
symptoms.  Data from EVEREST-I showed that majority of the subjects treated received a benefit 
from the treatment.  The data obtained from this study will be used to establish the safety and efficacy 
of the device and this data may benefit others in the future.   
3.3 
Study Participation Associated Risks  
In addition to the risk to health, there is a risk of violation of subject’s privacy during the data 
collection and monitoring of the subject’s health data.  All precaution will be taken to prevent the 
accidental disclosure of subject’s medical records.  All subjects will be listed by the study ID and no 
personal data will be collected. 
The risks associated with study participation (Table 3-1) are those associated with standard clinical 
diagnostic and evaluative practice procedures.  All subjects will provide informed consent prior to 
participating in the study. 
The procedures required per study protocol are consistent with standard of care procedures given the 
indication for the associated treatment.  
Table 3-1: Study Participation Associated Risks 
Study Procedure 
Risk(s) 
Medical History, Physical Exam,  
Quality of Life Questionnaires 
None, minimal 
Urinalysis  
None, minimal 
Uroflowmetry and Post-Void Residual  Written informed consent consistent with clinic policy 
Cystoscopy  
Written informed consent consistent with clinic policy 
TRUS 
Written informed consent consistent with clinic policy 
Laboratory Testing  
Usual risks associated with phlebotomy  
4 STUDY OBJECTIVES AND DESIGN 
4.1 
Objective 
The objectives of the study are:    
• To assess the efficacy of Optilume BPH Catheter System to alleviate LUTS believed to be 
secondary to BPH (LUTS/BPH)  
• To evaluate the safety of Optilume BPH Catheter System in the treatment of LUTS/BPH 

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4.2 
Study Design  
This is a prospective, multi-center, double blind, randomized controlled clinical trial in a 2:1 
allocation of Test versus sham Control.  In addition, a single arm of 15 non-randomized subjects 
will be added to study the Pharmacokinetics of the drug.   
A total of 162 subjects will be randomized and/or treated in the study at up to 30 clinical sites in the 
United States and Canada  (up to 28 sites in the US and up to 2 sites in Canada).  One hundred and 
forty seven (147) subjects will be randomized (2:1) and treated with either the Optilume BPH 
Catheter System or a sham procedure at up to 30 clinical sites.  Some of the 30 clinical sites will 
also be participating in the PK arm of the study.  Fifteen (15) non-randomized subjects will be treated 
in the PK arm.  Up to 625 subjects will be enrolled (i.e. consented) in the study in order to screen 
and identify 162 eligible subjects to be treated.   
All subjects will be followed up post-treatment at Foley removal, 14 days, 30 days, 3 months, 6 
months and 12 months.  In addition, all subjects treated with the Optilume BPH Catheter System 
will be followed annually through 5 years.    
The number of subjects randomized at an individual site may not exceed 25% (n=37) of the total 
randomized study sample size.  There is no site enrollment/treatment limitation for the PK arm.  
The study duration is anticipated to be approximately 8 years. 
The schematics of the study treatment arms and cross-over are shown in Figure 4-1 and Figure 4-2.  
 

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Figure 4-1: Schematic of Study Randomization and Cross-over 
 
 
Figure 4-2: Schematic of PK Arm 

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4.2.1 Test Arm Description  
Subjects randomized to the Test arm will be treated with the Urotronic Optilume BPH Catheter 
System. For the Primary Endpoint, the analysis population will be intent to treat (ITT).  Data from 
subjects randomized to this arm will be used in the analyses.  
4.2.2 Control Arm Description  
Subjects randomized to the Control arm will receive a sham procedure. A cystoscopy will be 
performed followed by insertion of the 21 Fr Optilume BPH, Prostatic Pre-dilation Catheter within 
the sheath. The catheter hub of the sham device will be modified to prevent inflation of the balloon.   
4.2.3 Cross-over/Alternative Therapy  
If a subject’s condition did not improve after the assigned index treatment (either Test or Control) 
the blinded site personnel will counsel the subject on available treatment options, including 
‘watchful waiting’ while continuing to perform study required follow up visits. During this ongoing 
subject counseling, the blinded personnel will describe the ability for the patient to cross over to the 
Treatment arm after the 3-Month follow-up visit has been completed. Although every effort should 
be made to maintain blinding for 12 months in each study arm, subjects may opt to be unblinded and 
seek alternative BPH therapy at any time.  
This counseling will be consistent regardless of which study arm the subject was randomized to in 
order to maintain study blinding. The subject may choose at any time to receive an alternative BPH 
therapy (e.g. TURP, medication) and forego the opportunity to cross over. If the subject chooses to 
receive an alternative BPH therapy, they will be discontinued from the standard study follow up 
once the alternative therapy is received and be followed for general health only. See Figure 4-1.  
After the 3-Month follow-up visit, if a subject continues to be symptomatic and determines that they 
wish to receive an alternative BPH therapy, the Investigator will unblind the subject and counsel the 
subject on available treatment options, including cross-over treatment with the Optilume BPH 
Catheter System for subjects that were randomized to the Control arm.  A cross-over treatment must 
be complete before the end of the subject’s 12-Month follow-up visit window.  
Subjects must meet all the study inclusion criteria and no exclusion criteria in order to qualify to 
cross-over.  The safety and efficacy data collected post-cross-over will be summarized separately.  
Cross-over subjects will be followed out to 5 years, starting from the cross-over procedure, under 
the same subject ID. 
4.3 
Pharmacokinetics Arm Description 
In the subset of 15 non-randomized subjects at selected sites, small amounts of blood, urine and 
semen will be collected for pharmacokinetic testing and sperm quality testing.   
Efforts should be made to include only those subjects who will be available to provide all required 
samples.  A PK Manual with detailed instructions and materials will be provided to select sites. 

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In order to qualify for participation in the PK arm of the study, subjects must meet all the study 
eligibility criteria with the exception of Inclusion 3; the Qmax, which must be ≥ 5 ml/sec and ≤ 15 
ml/sec (with minimum voided volume of ≥ 150 ml) for subjects to qualify for the PK sub-study.  
Any subjects who have been treated with any device or medical therapy that contains paclitaxel or 
are unable or unwilling to provide viable semen samples are excluded from participation in the PK 
testing. 
All qualified subjects who are enrolled in the Pharmacokinetics arm of the study will be treated with 
the Optilume BPH Catheter System.  A minimum of five PK subjects must be treated with the 30 x 
45 mm Optilume BPH DCB. 
A central core laboratory in the United States, Inotiv, will be utilized for analysis of the PK samples. 
Supplies for collection, storage and shipment of samples will be provided by the Sponsor.  
4.3.1 Blood PK Collection  
A total of 9 blood samples for PK analysis will be collected per subject. (See Table 4-1) The first 
blood sample is collected at baseline, and the following 4 (#2-5) blood samples will be drawn post-
procedure and prior to discharge. The 6th blood sample will be drawn post-discharge at the Foley 
Removal Visit.  The remaining 3 blood samples will be drawn at the 30-Day, 3-Month and 6-Month 
Visits.  If paclitaxel is still present in a subject’s 6-Month blood sample, that subject will be asked 
to provide additional blood samples at least every six months until paclitaxel is no longer detected.  
Table 4-1: Blood PK Sample Collection Times 
Sample 
No. 
Time Point 
Compliance Window 
1 
Baseline 
Within 30 days prior to procedure 
2 
0 Hour* 
0 - 30 min post-procedure 
3 
1 Hour 
60 - 90 min post-procedure 
4 
3 Hours 
2 - 4 hrs post-procedure 
5 
5 Hours  
4 - 6 hrs post-procedure 
6 
Foley Removal 
≥ 48 hrs post-procedure 
7 
30-Day Visit 
23 - 37 days post-procedure 
8 
3-Month Visit 
76 - 104 days post-procedure 
9 
6-Month Visit 
150 - 210 days post-procedure 
*0 hours post-procedure is defined as after collecting the 2nd void urine sample 
 
4.3.2 Urine PK Collection  
A total of 6 urine samples for PK analysis will be collected per subject. Table 4-2 lists the samples 
and their associated timepoints. If paclitaxel is still present in a subject’s 6-Month urine sample, that 
subject will be asked to provide additional urine samples at least every six months until paclitaxel is 
no longer detected. 

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Table 4-2: Urine PK Sample Collection Times 
Sample 
No. 
Time Point 
Compliance Window 
1 
Pre-Procedure 
Within 30 days prior to procedure 
2 
Post-Procedure 2nd Void  
Before subject exits procedure room 
3 
Foley Removal 
≥ 48 hrs post-procedure 
4 
30-Day Visit 
23 - 37 days post-procedure 
5 
3-Month Visit 
76 - 104 days post-procedure 
6 
6-Month Visit 
150 - 210 days post-procedure 
4.3.3 Semen PK Collection 
A total of 4 semen samples will be collected per subject. (See Table 4-3)   
A baseline semen sample will be collected within 30 days prior to the procedure.  Semen samples 
will also be collected at the 30-Day, 3-Month and 6-Month Visits. If paclitaxel is still present in a 
subject’s 6-Month semen sample, that subject will be asked to provide additional semen samples at 
least every six months until paclitaxel is no longer detected. The semen samples will be split when 
the sample size is sufficient; half for sperm quality assessment by the site’s lab and the other half 
divided into 2 aliquots to be sent to Inotiv for PK analysis. A minimum sample volume of 0.3 mL is 
required for PK analysis. If a semen sample does not contain enough volume to split while 
maintaining this minimum volume, the PK analysis aliquot 1 sample will be prioritized followed by 
the sample for sperm quality.  The PK analysis aliquot 2 sample will only be prepared when the total 
semen sample is at least 1 mL. 
Table 4-3: Semen Sample Collection Times 
Sample No. Time Point 
Compliance Window 
1 
Pre-Procedure 
Within 30 days prior to procedure 
2 
30-Day Visit 
23 - 37 days post-procedure 
3 
3-Month Visit 
76 - 104 days post-procedure 
4 
6-Month Visit 
150 - 210 days post-procedure 
 
4.4 
Study Endpoints 
4.4.1 Primary Efficacy Endpoint : Change in IPSS 
In order to meet this endpoint, the observed improvement in IPSS at 12 months post-treatment in the 
Test arm must be at least 25% greater than that of the Control arm at 3 months. 
IPSS is a non-invasive measure of subjects’ symptoms and is universally accepted to assess severity 
of LUTS/BPH. 

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4.4.2 Primary Safety Endpoint : Major Device-Related Serious Complications  
A major device-related serious complication is defined as any of the following events through 12 
months:     
• Device-related rectal fistula or GI fistula 
• Device-related formation of fistula between the rectum and urethra 
• Device-related new onset severe urinary retention lasting > 14 consecutive days post-healing 
• Device-related unresolved new onset stress urinary incontinence by 90 days  
• Device-related bleeding requiring transfusion 
• Device-related urethra or prostatic capsule rupture requiring surgical intervention  
 
A composite endpoint is being used due to the low incidence rate of each of the device-related serious 
complications. 
The Primary Safety Endpoint will be analyzed with descriptive statistics and nominal 95% 
confidence interval.  There will be no formal statistical hypothesis test. 
4.4.3 Secondary Endpoint 1: Average IPSS improvement in the Test arm at 12 
months 
The average IPSS improvement in the Test arm from baseline to 12 months must be ≥ 30% 
4.4.4 Secondary Endpoint 2: Percentage of responders at 3 months 
The responder analysis will provide the actual rate of subjects who benefited from the study 
treatment.  The  responder rate at 3 months of subjects randomized to the Test arm will be compared 
to the responder rate of subjects in the Control arm. 
A responder is defined as a subject who has an IPSS improvement of ≥ 30% post-treatment as 
compared to baseline.  
4.4.5 Secondary Endpoint 3: Durability - Percentage of responders  
The responder rate at 12 months of subjects randomized to the Test arm will be compared to the 
responder rate at 3 months of subjects in the Control arm. 
A responder is defined as a subject who has an IPSS improvement ≥ 30% post-treatment as compared 
to baseline.  
4.4.6 Secondary Endpoint 4: Qmax  
The maximum urinary flow rate (Qmax) provides an objective, non-invasive measurement of the 
subject’s BPH symptoms. 
The change or increase in Qmax at 12 months for all treated subjects randomized to the Test arm 
will be compared to the change or increase in Qmax at 3 months for subjects randomized to the 
Control arm. 

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4.4.7 Ancillary Endpoints 
The following Ancillary Endpoints are to provide additional characterization of the safety and 
efficacy of the Optilume BPH Catheter System in the treatment of LUTS/BPH. 
• A1: Additional responder analyses with a responder defined as IPSS improvement of 35%, 
40% and 50%  
• A2: Change in PVR  
• A3: Change in sexual function  
• A4: Change in BPH-II 
• A5: Change in quality of life  
• A6: Change in pain score 
• A7: Procedure parameters  
• A8: Change in Qmax 
• A9: Proportion of subjects experiencing a return to ‘normal’ symptom severity 
5 SUBJECT SELECTION 
Only subjects who meet all inclusion criteria and no exclusion criteria, agree to comply with the 
follow-up visit schedule and provide informed consent will be eligible to be randomized/treated and 
participate in the study. If a subject moves away during the study, every effort should be made to 
maintain the follow-up schedule including having an appropriate physician follow the subject.  
5.1 
Entrance Criteria for Randomization Arm 
5.1.1 Inclusion Criteria for Randomization Arm 
1. Male subject 50-80 years of age who has symptomatic BPH 
2. International Prostate Symptom Score (IPSS) ≥ 13 
3. Peak urinary flow rate (Qmax) ≥ 5 ml/sec and ≤ 12 ml/sec (with minimum voided volume of ≥ 
150 ml) 
4. Prostate volume 20 to 80 gm as determined by TRUS 
5. Prostatic urethral length ≥ 32 mm and ≤ 55 mm as determined by TRUS 
6. History of inadequate response, contraindication, or refusal of BPH medical therapy 
7. Able to complete the study protocol in the opinion of the investigator 
5.1.2 Exclusion Criteria for Randomization Arm 
1. Unable or unwilling to sign the Informed Consent Form (ICF) and/or comply with all the follow-
up requirements 
2. Unwilling to abstain or use protected sex for the first 30 days post treatment 
3. Unwilling to abstain from sexual intercourse or use a highly effective contraceptive for at least 
6 months post-procedure 
4. Presence of an artificial urinary sphincter or stent(s) in the urethra or prostate 
5. Any prior minimally invasive intervention (e.g. TUNA, Balloon, Microwave, Rezūm, UroLift) 
or surgical intervention of the prostate  

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6. PSA ≥ 10 ng/ml unless prostate cancer is ruled out by biopsy  
7. Confirmed or suspected malignancy of prostate or bladder 
8. Active or history of epididymitis within the past 3 months 
9. Previous pelvic irradiation or pelvic trauma surgery 
10. Active urinary tract infection (UTI) confirmed by culture  
11. Bacterial prostatitis within the last 12 months 
12. Non-bacterial prostatitis within the last 5 years 
13. Visible or invisible hematuria (> 4 RBCs per high power field) on 2 separate urine specimens 
within the last 3 months without a known contributing factor 
14. Neurogenic bladder or sphincter abnormalities or neurological disorders that might affect bladder 
or sphincter function 
15. History of urinary incontinence 
16. Previous or current diagnosis of urethral strictures, bladder neck contracture or detrusor muscle 
spasms 
17. Previous rectal surgery, other than hemorrhoidectomy 
18. Use of antihistamines, anticonvulsants or antispasmodics within 1 week prior to baseline 
assessment unless there is documented evidence of stable dosing for at least 6 months  
19. Use of antidepressants with adrenergic effects (i.e. duloxetine, imipramine and amitriptyline), 
long-acting anticholinergics (LAAC) for chronic obstructive pulmonary disease (COPD), or 
androgens within 2 weeks prior to baseline assessment unless there is documented evidence of 
stable dosing for at least 3 months prior to baseline assessment 
20. Use of Luteinizing Hormone-Releasing Hormone (LHRH) analogs within 12 months prior to 
baseline assessment 
21. Use of Type II 5-alpha reductase inhibitor [e.g. finasteride (Proscar, Propecia)] within 3 months 
of baseline assessment 
22. Use of 5-alpha reductase inhibitor [e.g. dutasteride (Avodart)] within 6 months of baseline 
assessment 
23. Use of estrogen or drugs producing androgen suppression unless there is documented evidence 
of stable dosing for at least 3 months prior to baseline assessment  
24. Use of alpha blockers or daily dose PDE5 inhibitor (e.g. Cialis) within 2 weeks of baseline 
assessment 
25. Use of warfarin or novel oral anti-coagulants [e.g., apixaban (Eliquis), fondaparinux (Arixtra), 
rivaroxaban (Xarelto) or edoxaban (Savaysa)], unless the medication is safely discontinued prior 
to the procedure and is not planned to be restarted for at least 5 days post-procedure  
26. Use of anti-platelet medications (e.g., clopidogrel, aspirin) within 10 days prior to the procedure 
or planned use within 5 days post-procedure 
27. History of hypersensitivity reactions to paclitaxel, on medication that may have negative 
interaction with paclitaxel, presence of solid tumor with a baseline neutrophil count of <1500 
cells/mm3 or AIDS-related Kaposi’s sarcoma with baseline neutrophil count of <1000 cells/mm3 
28. Incidence of spontaneous urinary retention within 6 months prior to baseline assessment 
29. Current post-void residual volume > 300 ml or catheter dependent bladder drainage 
30. Known poor detrusor muscle function (e.g. Qmax < 5 ml/sec) 

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31. Current bladder or prostatic urethral stones  
32. Biopsy of prostate within 40 days prior to procedure  
33. History of cancer in non-genitourinary system which is not considered in complete remission 
(except basal cell or squamous cell carcinoma of the skin).  A potential participant is considered 
in complete remission if there has been no evidence of cancer within five years 
34. Current uncontrolled diabetes (i.e. hemoglobin A1c ≥ 8%) 
35. 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 
36. 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 
37. Life expectancy < 10 years 
38. Anatomy (e.g. presence of false passage or size of meatus) is not suitable for treatment in this 
study 
39. Significant median lobe component [e.g. intravesical prostatic protrusion (IPP) > 1 cm] 
40. Device that corresponds with the subject’s prostate size is not available 
41. Currently enrolled in or plan to enroll in another investigational clinical study for any disease 
except for observational only study 
42. In the opinion of the investigator, it is not in the subject's best interest to participate in the study 
5.2 
Entrance Criteria for Pharmacokinetics Arm 
5.2.1 Inclusion Criteria for PK Arm 
Subjects must meet all the eligibility criteria for the Randomization arm of the study with the 
exception of Inclusion 3; the subject’s Qmax, which must be ≥ 5 ml/sec and ≤ 15 ml/sec (with 
minimum voided volume of ≥ 150 ml) in order to be eligible to participate in the PK arm of the 
study. 
5.2.2 Exclusion Criteria for PK Arm 
• In addition to not meeting any of the exclusion criteria for the Randomization arm 
of the study, subjects must also not meet either of the following exclusion criteria in 
order to be eligible to participate in the PK arm of the study: 
• Treated with any device or medical therapy that contains paclitaxel  
• Unable or unwilling to provide viable semen samples 
6 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 and other 
applicable guidelines and regulations. 

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In addition, the sites must be able to comply with any country-specific requirements as well as other 
requirements specified by their respective Institutional Review Board (IRB)/Research Ethics Board 
(REB).   
7 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 Optilume BPH Catheter System 
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.   
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. 
7.1 
Training  
The Sponsor, or designee, will be responsible for training of appropriate clinical site personnel.  Prior 
to the start of study enrollment at a study site, the Sponsor or designee will perform formal device 
and study training for study site personnel to ensure proper procedural technique, uniform data 
collection and protocol compliance.  At this training session material will include, but may not be 
limited to: 
• Investigational Plan 
• Techniques for the identification of eligible subjects 
• Device Training 
• Instructions on data collection including adverse events 
• Schedules for subject follow-up 
• Regulatory requirements 
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.  
8 STUDY PROCEDURES 
8.1 
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 to discuss the study, asked to participate 
and sign the IRB/REB approved informed consent form.  The site may not initiate any study-specific 
(non-standard of care) procedures without first obtaining informed consent. 

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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. 
The evaluations listed in Table 8-1 are to be conducted and recorded for all subjects prior to 
randomization/treatment in the study.  Subjects who require a washout period should have these 
evaluations, with the exception of informed consent, conducted following completion of the washout 
period.  Cystoscopy and TRUS that were performed as standard of care within 90 days of the 
procedure, even if they were performed prior to a required drug washout, are acceptable.  Subjects 
who cannot tolerate a drug washout or are considered high risk from the drug washout should be 
excluded from the study.  See Table 8-2 for the list of drug washout periods. 
Table 8-1: Baseline Evaluations 
Evaluations 
Accepted interval 
prior to procedure 
(unless specified 
otherwise) 
Condition 
Informed consent 
Prior to any study-
specific procedures or 
drug wash-out 
 
Medical and Genitourinary history  
Within 30 days 
Evaluation is complete and adequately 
documented in source documents 
Physical exam evaluation (with 
genital exam, digital rectal exam, 
demographics, height, weight and 
vital signs of body temperature, 
sitting blood pressure, sitting heart 
rate and respiratory rate) 
Within 30 days 
Evaluation is complete and adequately 
documented in source documents 
Current or prior (up to 6 months) 
medication use 
Prior to procedure  
A list of current and prior medication from the 
past 6 months is required to be documented to 
determine if the dose is stable. Vitamins and 
supplements do not need to be documented 
unless the indication is related to urinary 
symptoms.  The medical record must be 
reviewed for up to 12 months prior to confirm 
no LHRH analogues have been administered.   
Blood analysis 
• Complete blood cell count (CBC)  
• Comprehensive Metabolic Panel 
(CMP) 
 
Within 30 days  
 
 
CBC includes: hemoglobin, hematocrit, 
platelets, RBC and WBC.  
 
CMP includes: glucose, hemoglobin A1c (as 
appropriate), calcium, protein (albumin, total 
protein), electrolytes (bicarbonate, chloride, 
sodium, potassium), kidney (creatinine, blood 
urea nitrogen [BUN]), liver (alkaline 
phosphatase [ALP], alanine amino transferase 
[ALT], aspartate amino transferase [AST], 
bilirubin) 
 

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Evaluations 
Accepted interval 
prior to procedure 
(unless specified 
otherwise) 
Condition 
Serum prostate-specific antigen level 
(PSA) 
 
Within 30 days  
 
Must be <10 ng/ml or prostate cancer must be 
ruled out by biopsy 
Semen analysis 
• Lab assessment for sperm quality 
o Density or concentration 
o Total number (Sperm count) 
o Motility 
o Progressive motility 
o Morphology 
 
Within 30 days  
 
Analysis is complete and includes sperm 
concentration. These tests are only applicable 
for the 15 subjects treated in the PK arm of the 
study 
Dipstick urine analysis 
• Glucose 
• Protein 
• Leukocytes 
• Blood 
• Nitrite 
 
Within 14 days 
Must be negative for indications of infection 
before index procedure. More comprehensive 
urinalysis (e.g. microscopy) may be utilized in 
lieu of a dipstick test. 
 
Urine samples for this test must be taken 7 days 
or more after discontinuation of all antibiotics 
Urine culture for infection  
Within 14 days 
Must be negative for infection before index 
procedure 
 
Urine samples for this test must be taken 7 days 
or more after discontinuation of all antibiotics 
Uroflowmetry 
• Voided volume (must be ≥ 150 
mL or test must be repeated for 
all the uroflow tests) 
• Voiding time 
• Peak flow rate (Qmax)  
• 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  
Must be performed before cystoscopy or ≥14 
days after cystoscopy 
 
There must be no evidence of UTI prior to 
conducting test.  If the baseline urine culture is 
performed after the baseline uroflowmetry and 
comes back positive for UTI, the uroflowmetry 
must be repeated after confirmation that the UTI 
has resolved. 
 
The PVR method used during screening must be 
the same as that used in the follow-up tests 
Cystoscopy 
Within 90 days prior to 
treatment up to the day 
of the procedure 
Prior cystoscopy before index procedure is 
acceptable only if images were collected in the 
last 3 months and images are available for 
source documentation 
Transrectal ultrasound (TRUS)  
Within 90 days  
Determine prostate volume (PV), length, width 
and height, and to measure any intravesical 
prostatic protrusion (IPP) 
Subject questionnaires  
• International Prostate Symptoms 
Score (IPSS) - Standard 
Within 30 days 
There must be no evidence of UTI prior to 
administering the IPSS at baseline.  If the 
baseline urine culture is performed after the 
baseline IPSS and comes back positive for UTI, 

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Evaluations 
Accepted interval 
prior to procedure 
(unless specified 
otherwise) 
Condition 
• International Index of Erectile 
Function (IIEF) 
• BPH Impact Index (BPHII) 
• EQ-5D 
• MSHQ-EjD 
• VAS Pain Scale 
the IPSS must be repeated after confirmation 
that the UTI has resolved. 
 
If multiple same questionnaires were filled out, 
the last questionnaire will be used to qualify for 
the study 
PK samples: 
• Plasma 
• Urine 
• Semen  
Within 30 days 
These tests are only applicable for the 15 
subjects treated in the PK arm of the study 
Table 8-2: Drug Washout Periods Prior to Baseline Assessment 
Drug 
Washout Period 
Luteinizing Hormone-Releasing Hormone (LHRH) 
analogs  
12 months 
5-alpha reductase inhibitor [e.g. dutasteride (Avodart)] 
6 months 
Type II 5-alpha reductase inhibitor [e.g. finasteride 
(Proscar or Propecia)] 
3 months 
Estrogen 
Drug is excluded  
(unless there is documented evidence 
of stable dosing for the last 3 months) 
Drug-producing androgen suppression 
Drug is excluded  
(unless there is documented evidence 
of stable dosing for the last 3 months) 
Daily dose of PDE5 inhibitor (e.g. Cialis) 
2 weeks 
Alpha blockers 
2 weeks 
Antidepressants with adrenergic effects (i.e. duloxetine, 
imipramine and amitriptyline) 
2 weeks 
(unless there is documented evidence 
of stable dosing for the last 3 months) 
Long-acting anticholinergics (LAAC) for chronic 
obstructive pulmonary disease (COPD) 
2 weeks 

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(unless there is documented evidence 
of stable dosing for the last 3 months) 
Androgens 
2 weeks 
(unless there is documented evidence 
of stable dosing for the last 3 months) 
Anti-platelets (e.g. clopidogrel, aspirin)  
10 days prior to procedure 
Antihistamines 
1 week  
(unless there is documented evidence 
of stable dosing for the last 6 months) 
Anticonvulsants 
1 week  
(unless there is documented evidence 
of stable dosing for the last 6 months) 
Antispasmodics 
1 week  
(unless there is documented evidence 
of stable dosing for the last 6 months) 
Warfarin and novel oral anti-coagulants [e.g., apixaban 
(Eliquis), fondaparinux (Arixtra), rivaroxaban (Xarelto) 
or edoxaban (Savaysa)] 
Prior to procedure 
 
8.2 
Subject Enrollment 
Only subjects who meet the entrance criteria, agree to comply with the follow-up visit schedule and 
provide informed consent will be eligible to participate in the study.   
If the subject is on BPH medication or any excluded 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.  Subjects must provide informed consent before 
beginning a washout that is specifically for the study.  If the subject successfully goes through the 
washout period and still meets the entrance criteria, the subject will be eligible to participate in the 
study After the subject provides informed consent, the subject will be considered enrolled and will 
be entered into the study database and assigned a unique subject identification code (ID). Consented 
subjects meeting all inclusion criteria and no exclusion criteria may be randomized to a study 
treatment or treated in the non-randomized PK arm.  
A subject is considered enrolled in the study when informed consent is provided. 

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A subject is eligible for randomization when:  
• It is confirmed that ALL the inclusion criteria are met 
• It is confirmed that NO exclusion criteria are met 
A subject is considered evaluable in the PK arm of the study upon treatment with the Optilume BPH 
System (i.e. insertion of the pre-dilation catheter into the urethra).  
8.3 
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 results, per physician’s discretion. Pyridium may be given prophylactically for 3 days post-
procedure if it is given to all subjects in both the Test and Control arms at the study site. 
Antispasmodics (e.g. hyoscyamine) may also be given prophylactically the day prior to and the day 
of the procedure and for up to 3 days post-procedure if standard-of-care at the site. 
8.4 
Randomization  
Subjects in the Randomization arm of the study will be randomized in a 2:1 allocation of Test 
(Optilume BPH Catheter System) to Control (sham). Randomization will be stratified by IPSS 
severity using permuted blocks within each site using an Electronic Data Capture (EDC) system.  
Each subject will be randomized after it is confirmed that he meets all the inclusion criteria and none 
of the exclusion criteria and prior to initiation of the Test / Control procedure. Only randomized 
subjects will be considered evaluable in the Randomization arm. Those subjects who do not meet all 
entrance criteria after baseline evaluation will be counted as screening failures and will not be 
randomized.  
8.5 
Blinding  
In order to execute this study design, since the treating physicians in the Randomization arm of the 
study will be unblinded, they will not be allowed to conduct the study follow-up visits on any subject 
they treated themselves until the subject is unblinded. A blinded person at the study site will be 
conducting all study follow-up visits through the 12-Month follow-up visit (or until the subject is 
unblinded) to maintain blinding.  
Subjects in the Randomization arm of the study will be blinded to the treatment received through 
their 12-Month follow-up visit, at which point the subjects will be unblinded.  All Test and Control 
procedures will take place in the same setting at each investigational site (in-office, hospital or 
ambulatory surgical center). The treatment procedure location must be identified upfront and used 
for all study treatments, Test or Control. Switching between study treatment locations at a site will 
not be allowed unless the switch is made for all study treatments.  
In order to maintain subject blinding during the treatment procedure, a sheet should be placed to 
block the subject’s view of the treatment area for all randomized subjects.  For all subjects, the 

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Optilume and sham devices will be visible in the treatment room when subject is being prepped for 
the procedure irrespective of treatment assignment.  Noise cancelling headphones with music 
playing will be used by all subjects who are conscious during a randomized procedure.  If noise 
cancelling headphones are not available, a script will be used during the Control procedures to 
replicate the discussion associated with the Test arm.   
Subjects will be unblinded after the 12-Month follow-up examination, or to protect the subject’s 
health prior to the 12-Month follow-up. If any subject returns to the urologist with no improvement 
or worsening LUTS and receives further treatment for BPH, they will be considered a failure for the 
purposes of endpoint analyses.  
Every effort should be made to maintain the study blind in all subjects for  12 months after the Test 
or Control arm treatment. To allow for proper care of the subject who receives further treatment for 
BPH however, the subject’s assignment to Test versus Control arms may be made known prior to 
12 months at the time the subject has opted to receive additional BPH treatment and wishes to further 
discuss treatment options. To aid in maintaining the blind, a blinded member of the site will counsel 
the subject on available treatment options as described in Section 4.2.3. If a non-urgent clinical need 
requires the subject to be unblinded prior to the 12-Month follow-up and if time allows, the physician 
will notify the Sponsor prior to unblinding the subject.   
The study blind may be broken at any time during the study due to medical necessity.  All subjects 
will complete the Subject Satisfaction questionnaire at the 3-Month and 12-Month follow-up visits; 
the subjects will be asked which treatment they think they received and their degree of certainty. 
Blinding procedures will be reviewed at the time of each Site Initiation Visit (SIV) by a Sponsor 
representative. Blinding procedures and instructions are summarized in Table 8-3.  
Table 8-3: Blinding Procedures 
Time Point 
Blinding Procedure 
Informed Consent 
During the informed consent process, the study procedures, 
treatments and blinding procedure should be discussed with the 
subject and family/caretakers as appropriate.  
Randomization 
The randomization assignment should be communicated to the 
Investigator in a way to prevent the subject from overhearing which 
group they have been assigned to if applicable.  Each site should 
develop a process that works best with their treatment location and 
processes.  

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Time Point 
Blinding Procedure 
Treatment 
All treatment procedures will take place in the same setting at each 
investigational site (in-office, hospital or ambulatory surgical 
center). The treatment procedure location must be the same for all 
study treatment arms. Switching treatment locations based on 
treatment arms will not be allowed.  
During the treatment procedure, a sheet should be placed to block 
the subject’s view of the treatment area for all subjects.  For all 
subjects, the Optilume and sham devices will be visible in the 
treatment room when subject is being prepped for the procedure 
irrespective of treatment assignment.  Noise cancelling headphones 
with music will be used by all subjects who are conscious during a 
randomized procedure.  If noise cancelling headphones are not 
available, a script will be used during the Control procedures to 
replicate the discussion associated with the Test arm. 
The number of medical personnel exposed to the randomization 
assignment should be limited as far as possible on a need to know 
basis. 

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Time Point 
Blinding Procedure 
Post-Procedure  
All subjects will be provided the same instructions on post-
procedure recovery precautions including: 
1. ABSTAIN from ALL sexual activities including 
masturbation for a minimum of fourteen (14) days post- 
procedure 
2. Abstain from sexual activities or use a condom for a 
minimum of thirty (30) days post-procedure.  The time of 
protected sex may be extended by the physician  
3. Abstain from sexual intercourse or use a highly effective 
contraceptive for at least 6 months post-procedure to prevent 
harm to an embryo or fetus  
4. No strenuous activity (e.g. heavy lifting, running) for 30 
days post-treatment 
Blinded personnel at the study site will be conducting all study 
follow-up visits through the 12-Month follow-up visit or subject 
unblinding (whichever comes first). 
Any recovery and hospital/clinic staff should be educated to the 
protocol blinding procedures and instructed to not inadvertently 
unblind the subject and/or family/caretakers during the recovery 
period.  
In addition, the subject’s medical record should clearly identify the 
subject as a study participant and not list the treatment assignment.    
Follow-up 
The site study staff should maintain blinding procedures through 
the 12-Month follow-up. Clinic staff will be educated to the 
protocol blinding procedures and instructed not to inadvertently 
unblind the subject and/or family/caretakers during the follow-up 
period.  
Unblinding  
A subject should not be unblinded to the treatment assignment prior 
to the 12-Month follow-up unless it is determined to be medically 
necessary by the Investigator. This includes seeking alternative 
BPH therapy due to continued or recurrent LUTS/BPH symptoms.  

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Time Point 
Blinding Procedure 
Cross-over 
In the event a subject in the Control arm requires BPH treatment 
due to recurrent LUTS/BPH prior to the 12-Month follow-up, the 
subject may be unblinded to discuss treatment options, including a 
cross-over into the Test (Optilume DCB) arm and to consent for 
treatment with the Optilume DCB if appropriate. The subject may 
only cross-over into the Test arm after the 3-Month visit has been 
completed.  Subject may choose to opt for non-study treatments, at 
which point the subject will exit the study upon initiation of the 
therapy. 
 
8.6 
Study Procedure – Randomization Arm 
The treatments for the study may be performed in a hospital, ambulatory surgical center or in-office 
setting. Data collected from each Test or Control procedure will include, but may not be limited to: 
operating physician, procedure times, device use and disposition, medications used, adverse events 
and any device malfunctions. A summary of a typical procedure is described in the sections below.  
See the Instructions for Use (IFU) for additional details.  If the summary is different from the IFU, 
follow the instruction in the IFU.    
Use baseline TRUS to determine the prostate volume and dimensions. Select the corresponding pre-
dilation balloon catheter and drug coated balloon catheter based on the sizing guides in the IFU and 
confirm device availability.  
The inflation pressure must be recorded for each inflated balloon. 
In order to maintain subject blinding during the treatment procedure, a sheet should be placed to 
block the subject’s view of the treatment area for all randomized subjects.  For all subjects, the 
Optilume and sham devices will be visible in the treatment room when subject is being prepped for 
the procedure irrespective of treatment assignment.  Noise cancelling headphones or a script will be 
used during the Control procedures to replicate the discussion associated with the Test arm.   
8.6.1 Peri-procedural Medication  
Local block or systemic anesthetics are required; in addition it is recommended that a bolus of 
lidocaine gel is injected into the urethra 10 minutes prior to the study procedure.  In general, the 
study procedure approach for all arms of the study is similar to cystoscopy, including the 
administration of a pre-procedure antibiotic as appropriate.  The use of any medication (e.g. 
antibiotic, anesthetic and/or sedative) will be recorded in the Procedure case report form.  Any 
antibiotics should be recorded on the Concomitant Medication Log.  The peri-procedural anesthetic 
and sedative medications do not have to be listed in the Medications CRF. 

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Peri-procedural short acting anti-spasmodic medication (e.g. hyoscyamine sulfate [Levsin], 
oxybutynin) is recommended and post-procedural prophylactic medications such as 
phenazopyridine (Pyridium) may be used at physician’s discretion for both the Test and Control 
arms.  These medications should be listed on the Concomitant Medication Log. 
8.6.2 Test Arm Procedure Description 
8.6.2.1 Pre-dilation  
Pre-dilation with the Optilume BPH Pre-dilation Catheter is required for all subjects.  Select the 
correct size pre-dilation catheter (30 x 30 mm or 30 x 35 mm) based on the sizing guide in the IFU.  
Prepare and use the pre-dilation catheter per the IFU.  Document the location of the 
commissurotomy. 
8.6.2.2 DCB Treatment 
Select the correct size drug coated balloon catheter based on the sizing guide in the IFU.  Prepare 
the drug coated balloon catheter and complete the procedure per the IFU. 
8.6.3 Control Arm Procedure Description   
1. Insert cystoscope and survey urethra, prostate and bladder. 
2. Remove cystoscope. 
3. Prepare the Optilume BPH Prostatic Pre-dilation Catheter modified to prevent inflation, insert it 
transurethrally and advance to the prostatic urethra. 
4. Do NOT pull back the insertion sheath to expose the balloon and do NOT inflate the balloon. 
5. Place noise cancelling headphones on the subject or read the prepared script out loud to replicate 
the discussion associated with the Test arm. 
6. Leave the Optilume BPH Prostatic Pre-dilation Catheter modified to prevent inflation in place 
for a minimum of 5 minutes. 
7. Withdraw catheter and sheath from the subject’s body and dispose of properly. 
8.7 
Study Procedure - PK Arm  
Some of the study sites will participate in the PK arm of the study.  The treatments for the study may 
be performed in a hospital, ambulatory surgical center or in-office setting. Data collected from each 
procedure will include, but may not be limited to: operating physician, procedure times, device use 
and disposition, medications used, adverse events and any device malfunctions.  A summary of a 
typical procedure is described in the sections below.  See the Instructions for Use (IFU) for additional 
details.  If the summary is different from the IFU, follow the instruction in the IFU.    
Use baseline TRUS to determine the prostate volume and dimensions.  Select the corresponding pre-
dilation balloon catheter and DCB catheter based on the sizing guide in the IFU and confirm device 
availability.   
The inflation pressure must be recorded for each inflated balloon. 

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8.7.1 Peri-procedural Medication  
Local block or systemic anesthetics are required; in addition it is recommended that a bolus of 
lidocaine gel is injected into the urethra 10 minutes prior to the study procedure.  In general, the 
study procedure approach for all arms of the study is similar to cystoscopy, including the 
administration of a pre-procedure antibiotic as appropriate.  The use of any antibiotic, anesthetic 
and/or sedative will be recorded in the case report form. 
8.7.2 PK Arm Procedure Description 
It is recommended to fill the bladder prior to dilation in order to facilitate urine collection at the end 
of the procedure.   
8.7.2.1 Pre-dilation  
Pre-dilation with the Optilume BPH Pre-dilation Catheter is required for all subjects.  Prepare and 
use the pre-dilation catheter per the IFU.  Document the location of the commissurotomy. 
8.7.2.2 DCB Treatment 
Prepare the selected drug coated balloon catheter and complete the procedure per the IFU. 
8.7.2.3 Post-Procedure Urine Collection for PK Arm 
Collect a post-procedure urine sample from the subject for drug content measurement from the 2nd 
void sample (prior to catheterization).  
1. Palpate the subject’s bladder to allow about 1 cup (100 – 150 ml) of fluid to flow out of the 
urethra to flush any residual coating particles. This is recognized as the 1st void. (If palpation 
does not produce urine, collection may be done through the Foley catheter.)  
2. Then 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.   
Refer to Table 4-2 for all urine PK collection times. 
8.7.2.4 Post-Procedure Blood Collection for PK Arm 
Collect a post-procedure blood sample from the subject for drug content measurement after 
collecting the 2nd void urine sample.   
Refer to Table 4-1 for all blood PK collection times. 
8.8 
Catheterization 
Insert a Foley catheter for a minimum of 48 hours.  Record the Foley catheter size.  The Foley 
catheter may be removed or replaced prior to 48 hours if it becomes blocked. 
Record the date and time of Foley catheter removal.  If the subject requires re-catheterization within 
24 hours of the initial removal, document the date and time of the final removal.  If re-catheterization 

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occurs within 24 hours, it is counted as the same catheterization event as the previous catheterization.  
In this case, this will be considered a continuation of the procedure “healing” phase. 
8.9 
In-Hospital to Discharge 
Prophylactic antibiotics are recommended post procedure according to treatment guidelines.   
All subjects should be counseled to not take any anti-platelet medications (e.g. aspirin [Bayer, 
Ecotrin], Brilinta, Effient, Plavix) or oral anti-coagulants (e.g. Arixtra, Coumadin, Eliquis, Pradaxa, 
Savaysa, Xarelto) for at least 5 days after the procedure. 
 
8.10 Physical Activities 
All subjects must be counseled about physical activities post-treatment: 
• No strenuous activity (e.g. heavy lifting, running) for 30 days post-treatment  
8.11 Sexual Activities 
Paclitaxel can cause serious harm to an embryo or fetus and has been detected in the semen for at 
least 30 days following the Optilume BPH procedure. The time required for complete clearance of 
paclitaxel from semen following the Optilume BPH procedure is currently unknown.   
All subjects must be counseled about sexual activities post-treatment as follows:  
• ABSTAIN from all sexual activities including masturbation for 14 days post-treatment 
• Abstain from sexual activities or use a condom for a minimum of 30 days post-procedure 
• Abstain from sexual intercourse or use a highly effective contraceptive for at least 6 months 
post-procedure to prevent harm to an embryo or fetus   
8.12 Scheduled Follow-up Evaluations 
During the post-procedure period, investigators are encouraged to follow the current American 
Urological Association (AUA) guidelines in managing their subjects for the detection of prostate 
cancer in addition to the required evaluations in this protocol.   
The following evaluations will be completed at each visit as indicated in Table 8-4.  All subjects 
will be evaluated at baseline, immediately post-procedure, at Foley removal, 14 days, 30 days, 3 
months, 6 months and 12 months.  In addition, all subjects treated with the Optilume BPH Catheter 
System will be followed annually through 5 years post-procedure or until study close, whichever 
comes first.  

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Table 8-4: Scheduled Evaluations and Follow Up 
Study Visit 
Baseline 
 
Intra-Op 
 
Pre-
Discharge 
Foley 
Removal 
14-Day  
 
30-Day 
 
3-Month 
 
6- Month 
 
12-Month 
 
Annual9 
(through 
5 years) 
 
Unscheduled 
Visit Windows 
w/in 30 
days3 
N/A 
N/A 
≥ 48 hrs 
post-
procedure 
±3 days 
±7 days 
±14 days 
±30 days 
±30 days 
±30 days 
 
Informed 
Consent 
√ 
 
 
 
 
 
 
 
 
 
 
Medical and 
genitourinary 
history  
√ 
 
 
 
 
 
 
 
 
 
 
Physical exam 
 
√4  
 
 
 
√ 
√ 
√ 
√ 
√4 
√4 
if indicated 
Review 
Protected 
Sexual 
Activities 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
 
Blood Analysis5 
 
√ 
 
 
 
√ 
√ 
√ 
√ 
√ 
if indicated 
Prostate 
specific antigen 
(PSA) 
√ 
 
 
 
 
 
 
 
√ 
√ 
 
TRUS 
 
√ 
 
 
 
 
 
 
 
 
 
 
Cystoscopy 
√ 
√ 
 
 
 
 
 
√ 
 
 
if indicated 
Randomization 
 
√11 
 
 
 
 
 
 
 
 
 
Balloon 
Dilation 
 
√ 
 
 
 
 
 
 
 
 
 
Uroflow (Qmax 
+ PVR) 
√ 
 
 
 
√ 
√ 
√ 
√ 
√ 
if indicated 
Urine Analysis 
 
 
√ 
 
 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
optional 

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Study Visit 
Baseline 
 
Intra-Op 
 
Pre-
Discharge 
Foley 
Removal 
14-Day  
 
30-Day 
 
3-Month 
 
6- Month 
 
12-Month 
 
Annual9 
(through 
5 years) 
 
Unscheduled 
Visit Windows 
w/in 30 
days3 
N/A 
N/A 
≥ 48 hrs 
post-
procedure 
±3 days 
±7 days 
±14 days 
±30 days 
±30 days 
±30 days 
 
Urine Culture 
 
 
√ 
 
 
if 
indicated 
if 
indicated 
if 
indicated 
if 
indicated 
if 
indicated 
if 
indicated 
if 
indicated 
if indicated 
IPSS1 
 
√ 
 
 
 
√6 
√ 
√ 
√ 
√ 
√ 
if indicated 
BPH Impact 
Index1 
√ 
 
 
 
√ 
√ 
√ 
√ 
√ 
if indicated 
EQ5D1 
 
√ 
 
 
 
 
√ 
√ 
√ 
√ 
√ 
if indicated 
MSHQ-EjD1 
√ 
 
 
 
 
 
√ 
√ 
√ 
√ 
if indicated 
Sexual function 
(IIEF) 1 
√ 
 
 
 
 
 
√ 
√ 
√ 
√ 
if indicated 
Pain scale1 
 
√ 
√ 2 
√ 
√ 
√ 
√ 
 
 
 
 
Subject 
Satisfaction 
Questionnaire 
 
 
 
 
  
 
√ 
 
√ 
 
 
Adverse 
event(s)  
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
All 
Medication(s) 
used 
  
 
√ 
(prior BPH 
medications 
and all 
current) 
√ 
(since the 
previous 
visit) 
√ 
(since the 
previous 
visit) 
√ 
(since the 
previous 
visit) 
√ 
(since the 
previous 
visit) 
√ 
(since the 
previous 
visit) 
√ 
(since the 
previous 
visit) 
√ 
(since the 
previous 
visit) 
√ 
(since the 
previous 
visit) 
√ 
(since 
the 
previous 
visit) 
√ 
(since the 
previous visit) 
Blood PK 
Samples7 
√ 
 
 
√8 
 
√ 
 
 
√ 
√ 
√ 
 
 
 

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Study Visit 
Baseline 
 
Intra-Op 
 
Pre-
Discharge 
Foley 
Removal 
14-Day  
 
30-Day 
 
3-Month 
 
6- Month 
 
12-Month 
 
Annual9 
(through 
5 years) 
 
Unscheduled 
Visit Windows 
w/in 30 
days3 
N/A 
N/A 
≥ 48 hrs 
post-
procedure 
±3 days 
±7 days 
±14 days 
±30 days 
±30 days 
±30 days 
 
Urine PK 
Sample7 
√ 
 
 
√ 
 
√ 
 
 
√ 
 
√ 
 
√ 
 
 
 
 
Semen PK 
Sample7 
√10 
 
 
 
 
 
√10 
 
√10 
 
√10 
 
 
 
 
1 If multiple responses to the same questionnaires are available for each visit window, the last questionnaire will be used to qualify for the study 
2 Intra-operative pain scale must be done post-procedure while the subject is in recovery 
3 Cystoscopy and TRUS that were done within 90 days prior to the procedure may be used for the study baseline.  Urine analysis and urine culture must be conducted 
within 14 days prior to the procedure 
4 Baseline physical exam also includes digital rectal exam (DRE), demographics, height, weight and vital signs. Annual physical exams to include DRE. 
5 Blood analysis includes Complete Blood Count (hemoglobin, hematocrit, platelets, red blood cell count and white blood cell count), Blood Chemistry [glucose, 
calcium, protein (albumin, total protein), Electrolytes (bicarbonate, chloride, sodium, potassium), Kidney (blood urea nitrogen, creatinine), Liver (alkaline 
phosphatase, alanine amino transferase, aspartate amino transferase, bilirubin)] and Hb A1c as appropriate 
6 IPSS (acute) at the 14-Day Visit 
7 PK samples are only collected for the 15 subjects in the PK arm of the study  
8 Pre-discharge blood PK samples are required at 0 hours (after collecting 2nd void urine sample), 1 hour, 3 hours and 5 hours 
9 All subjects who exit the study for any reason prior to 5 years post-procedure (including Control subjects who complete the 12-Month follow-up) will be requested to 
allow continued follow up for general health information through 5 years post-procedure 
10 Semen quality analysis will be captured for all Semen PK samples  
11 Randomization must take place after all eligibility criteria has been confirmed but prior to initiating the Test/Control procedure. If the baseline cystoscopy is 
performed in the same setting as the index procedure, the subject may be randomized after verification of eligibility but prior to initiation of the Test/Control treatment 
 

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8.13 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). 
8.14 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.     
8.15 Subject Withdrawal from Study 
8.15.1 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. 
All subjects who withdraw from the study will be asked to provide general health information for 5 
years post-procedure if possible. 
8.15.2 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.   
All subjects who are withdrawn from the study will be followed for 5 years post-procedure for 
general health information if possible. 
8.15.3 Alternative Treatments 
If the subject opts to receive an alternative BPH therapy and does not wish to cross-over to the Test 
arm or was already randomized to receive treatment with the Optilume BPH catheter system, the 
subject will be withdrawn from the study at the time the alternative therapy is received unless there 
is an unresolved device or procedure related adverse event, in which case, they may be followed for 
another 30 days or until the AE is resolved, whichever comes first. The subject will be asked to 
provide general health information for 5 years post-procedure if possible. Subjects who receive the 

 
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Optilume BPH Catheter System but later decide they require alternative treatment will be considered 
treatment failures. 
8.16 Follow-up for General Health 
All subjects who exit the study for any reason prior to 5 years post-procedure (including Control 
subjects who complete the 12-Month follow up) will be requested to allow continued follow up for 
general health information through 5 years.  The information collected includes mortality status and 
significant safety events that have occurred since the last subject contact.  Every effort should be 
made to collect this information at the annual follow-up visit timepoints.  General health information 
may be collected via telephone and does not require an in-office visit.  The inability to collect the 
information will not constitute a protocol deviation.  Any significant safety events occurring after 
the subject has exited the study will be reported on a General Health Information CRF.  
8.17 End of Study 
All subjects treated with the sham device will be followed as described in Table 8-4 until they 
complete the 12-Month follow-up, and all subjects treated with the Optilume BPH Catheter System 
will be followed as described in Table 8-4 until they complete the 5-Year follow-up visit or the study 
is discontinued by the Sponsor, whichever comes first.  
An End of Study CRF will be completed for each subject. 
9 SUBJECT EVALUATION DESCRIPTION 
9.1 
Place of Service 
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 that 
require an in-office visit as described in Table 8-4 must still be documented as a protocol deviation 
as described in Section 14.3.3.  If the subject is unable to visit the study site, blood analysis, PSA, 
urinalysis, urine culture and uroflow measurements collected at non-study locations as standard of 
care may be utilized without the need to document a protocol deviation unless the testing does not 
meet the requirements of the protocol (e.g. voided volume < 150 mL). 
If the 3-Month visit or the 12-Month visit (primary endpoint) is unable to be performed in-person, 
it is encouraged that site 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 possible to complete remaining assessments.  Questionnaires should be re-
administered at this Unscheduled visit.  
9.2 
Physical Examination 
A physical examination will be conducted at each scheduled follow-up visit beginning with the 14-
Day visit and will include a genital examination by an active study investigator.  A digital rectal 

 
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examination will be performed by an active study investigator at the 12-Month visit and all annual 
visits.  Vital signs (body temperature, blood pressure and heart rate) will also be collected as part of 
the physical exam. 
9.3 
Subject Questionnaires 
All questionnaires are preferentially 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 or emailed 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 compliance is uncertain, the IPSS, VAS and Subject Satisfaction questionnaires may be 
interview administered at the time of the phone/telemedicine follow up. If a questionnaire is 
interview administered, this should be noted 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. If multiple responses to the same questionnaires are available for each visit window, the last 
set of scores will be used unless there are valid scientific reasons to exclude one of the readings.  
9.3.1 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. 
 
 
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 standard IPSS is self-administered and will be completed at baseline and at each in-office 
follow-up visit beginning with the 30-Day Visit.   
9.3.2 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 questionnaire will be completed by the 
subject at the 14-Day follow-up visit. 
9.3.3 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. 
The BPH Impact Index will be completed at baseline and at each follow-up visit beginning with the 
30-Day Visit. 
9.3.4 International Index of Erectile Function 
The International Index of Erectile Function (IIEF) is a standardized, validated, self-administered 
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-Day Visit. 
9.3.5 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 30-Day 
Visit. 
9.3.6 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 3-
Month Visit. 

 
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9.3.7 Subject Pain Questionnaire 
The Visual Analog Scale (VAS) pain score (1 to 10 scale) will be used to assess the subject’s pain.  
The person administering the questionnaire should explain to the subject that the pain being assessed 
is limited to urological and pelvic pain including pain associated with urinating and/or bowel 
movements. 
The pain scale will be administered at baseline, post-procedure while the subject is in recovery, 
following Foley removal and at the 14-Day, 30-Day and 3-Month Visits. 
9.3.8 Subject Satisfaction Questionnaire 
This questionnaire is specific to the Urotronic DCB procedure on the treatment of moderate-to-
severe LUTS/BPH and will assess subject blinding and 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 self-administered at the 3-Month and 12-Month 
Visits. 
9.4 
Blood Analysis  
Complete Blood Count (CBC):  
• CBC includes hemoglobin, hematocrit, platelets, RBC and WBC  
Comprehensive Metabolic Panel (CMP):  
• Glucose, HbA1c (as appropriate), calcium, protein (albumin, total protein), electrolytes 
(bicarbonate, chloride, sodium, potassium), kidney (creatinine, blood urea nitrogen [BUN]), 
liver (alkaline phosphatase [ALP], alanine amino transferase [ALT], aspartate amino 
transferase [AST], bilirubin) 
Prostate Specific Antigen (PSA) 
9.5 
Dipstick Urine Analysis  
A urine dipstick analysis must be performed at the baseline visit and at each follow up visit starting 
at the 14 Day Follow-up. A more sensitive test (e.g. microscopy) may be performed in lieu of a 
dipstick test. The Baseline measurement must be performed within 14 days prior to treatment. 
Samples taken for this test must be taken at least seven (7) days following discontinuation of all 
antibiotics. Subjects need to have a negative urine analysis prior to the study index procedure. Data 
collected should include, at minimum:  
• Glucose  
• Protein 
• Leukocytes 
• Blood 
• Nitrite 
 

 
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9.5.1 Urine culture  
A urine culture needs to be performed within 14 days prior to treatment. Samples taken for this test 
must be taken at least seven (7) days following discontinuation of all antibiotics. Subjects need to 
have a negative urine culture prior to the study index procedure. Urine cultures will be performed 
during follow up only if indicated. 
9.6 
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 (≥150 ml required for a valid test) 
• Peak flow rate (Qmax), averaged over an approximately 2-second interval if an artifact is 
noted 
• Voiding time 
If the voided volume is less than 150 ml, the test must be repeated at least once.  If the voided volume 
is still less than 150 ml, the test with the highest voided volume will be used.   
Uroflow must be performed before cystoscopy or at least 14 days after cystoscopy, when applicable. 
9.6.1 Peak Flow Rate (Qmax) Measurement 
Most uroflow equipment will automatically identify the peak flow rate of a voiding pattern, however 
this may result in spurious, non-physiologically relevant readings if a sudden spike is captured (e.g. 
due to bumping equipment, etc.). The recommendation for determining the Qmax reading is to have 
an Investigator review the readout and apply the 2-second rule to improve consistency if an artifact 
is noted. The Investigator’s reading of the peak flow rate should be documented on the uroflow 
readout.    
9.6.2 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.  
9.7 
Cystoscopy 
A screening cystoscopy will be performed to confirm the presence of obstructive BPH, to estimate 
the BPH severity, and identify any significant contribution of the median lobe to obstruction.    
Flexible or rigid cystoscope will be used to facilitate the DCB procedure. 

 
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A cystoscopy will also be performed at the 6-Month follow-up visit concentrating on the prostatic 
urethra.   
9.8 
TRUS 
Transrectal Ultrasonography (TRUS) at baseline is required to determine the prostate size and to 
measure any intravesical prostatic protrusion (IPP). 
9.9 
Semen Analysis 
Semen analyses will be evaluated in subjects enrolled in the PK cohort at baseline, 30 days, 3 months 
and 6 months post-procedure.  
The semen will be analyzed by the site’s local laboratory for sperm quality: 
• Sperm density or concentration 
• Total number (Sperm count) 
• Motility 
• Progressive motility 
• Morphology  
9.10 Remote Assessments 
If a subject is not able to return for an in-person follow-up visit, the site should collect as much 
information as possible remotely by calling the subject.  The site should attempt to conduct the 
following: 
• Follow-up on any ongoing adverse events 
• Determine if the subject has experienced any new adverse events since the previous visit 
• Determine if there have been any changes to the medications since the previous visit 
• Review protected sexual activities, if applicable 
• Ask the subject to complete the applicable study questionnaires 
o Mail or email the study questionnaires to the subject to complete and return.  If that 
is not possible, the site may fill out the questionnaires by asking the subject the 
questions over the phone and noting on the questionnaires that they were completed 
over the phone   
 
A Protocol Deviation must be completed to document any protocol-required assessments that were 
not completed at the visit. 
10 STATISTICAL CONSIDERATIONS 
This section summarizes the main statistical considerations for the data analysis.  Statistical details 
including plans for subgroup analyses, poolability, handling of missing data and control of the type 
I error for secondary endpoints are provided in a standalone Statistical Analysis Plan (SAP).  

 
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10.1 Primary Efficacy Endpoint Analysis 
Subjects will be randomized in a 2:1 ratio to Test:Control.  Randomization will be stratified by IPSS 
severity at baseline.  The number of subjects randomized at an individual site in the randomization 
arm may not exceed 25% of the total randomized study sample size (n=37). 
To meet the primary efficacy endpoint, the observed improvement in IPSS (π) at 12 months post-
treatment in the Test arm must be at least 25% greater than that of the Control arm at 3 months: 
Ho:  πTest,12 – 1.25 πControl,3 ≤ 0 
HA:    πTest,12 – 1.25 πControl,3 > 0 
Where: 
πTest,12 = Mean reduction in IPSS from baseline for the Test arm at 12 months 
πControl,3= Mean reduction in IPSS from baseline for the Control arm at 3 months 
 
The statistical hypothesis test for the primary efficacy endpoint will be based on a two-sample t-
test at a one-sided 0.025 alpha level (equivalent to a two-sided 0.05 alpha level).  
 
10.2 Primary Safety Endpoint Analysis 
The Primary Safety Endpoint will be analyzed with descriptive statistics and nominal 95% 
confidence interval.  There will be no formal statistical hypothesis test. 
A major device-related serious complication is defined as any of the following events through 12 
months:     
• Device-related rectal fistula or GI fistula 
• Device-related formation of fistula between the rectum and urethra 
• Device-related new onset severe urinary retention lasting > 14 consecutive days post-healing 
• Device-related unresolved new onset stress urinary incontinence by 90 days  
• Device-related bleeding requiring transfusion  
• Device-related urethra or prostatic capsule rupture requiring surgical intervention 
 
10.3 Secondary Endpoint Analyses 
Secondary endpoints will be tested against the corresponding null hypotheses using a sequential 
gatekeeping strategy to control the type I error rate. Significance of the secondary endpoints will be 
based on sequential testing of the endpoints, proceeding in the order listed, until a non-significant 
result is reached at which time no further claims of significance will be made. Significance will only 
be claimed if success for the hypothesis test for the primary endpoint is achieved. Each test will be 
performed at a one-sided 0.025 alpha level. 

 
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10.4 Ancillary Endpoint Analyses 
For those endpoints without a specified hypothesis test, descriptive statistics will be used in reporting 
outcomes. Continuous variables will be summarized with means or medians and standard deviations. 
Adverse Events, protocol deviations, and device malfunctions will be summarized with descriptive 
statistics. 
10.5 Sample Size Justification 
Sample size for the Randomization arm of the study is based on the Primary Efficacy Endpoint using 
the following assumptions: 
• 
Statistical power of 90%  
• One-sided 0.025 alpha  
• 2:1 randomization allocation (treatment : control) 
• A common standard deviation of 7 
• Mean improvement in the Control arm of 6 points and mean improvement in the Test arm of 
12.5 points 
• 10% loss of follow-up rate 
Based on these assumptions, a sample size of 132 evaluable subjects (88 Test and 44 Control) 
provides approximately 90% power.  Assuming a 10% loss of follow-up rate, the randomization 
sample size is 147 (approximately 98 Test and 49 Control). With the 15 subjects in the PK arm, the 
total number of subjects required is 162 randomized/treated subjects (147+15). It should be noted 
that more than 162 subjects will be need to be consented (i.e. enrolled) to reach this total of 147 
randomized and 15 PK subjects. 
10.6 Study Success Criteria 
For the study to be declared a success, the Primary Efficacy Endpoint and Secondary Endpoint 1 
must be met without any safety concerns.  
10.7 Analysis Populations 
All subjects enrolled in the study, including those withdrawn from the study or lost to follow up, 
will be accounted for and documented. The primary endpoint analysis and secondary endpoints will 
be analyzed using the Intent To Treat (ITT) population, under which all randomized subjects will be 
included for the analysis, regardless of whether or not the subject received the randomized treatment. 
In addition, the analyses will be completed on an As Treated (AT) basis (i.e. based on treatment 
actually received) and a Per Protocol (PP) basis. The PP analysis population will exclude subjects 
with the following significant protocol violations: 
• Subject’s rights are violated or did not give consent and subject data was requested to be 
excluded by IRB/REB 
• Subject has a confirmed diagnosis of urethral stricture,  bladder neck contracture at the time 
of treatment that would confound study results  

 
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• Subject had UTI at the time of treatment 
• Subject had radiation of the pelvic region 
• Subject had a previous surgery for BPH 
• Subject did not complete wash out of drugs 
• 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 
• Subjects who are unblinded before the Primary Endpoint evaluation as required by the cohort  
10.8 Handling of Missing Data 
10.8.1 For the Primary Efficacy Endpoint and Secondary Endpoints S1 
Subjects who withdraw due to adverse events, lack of effectiveness, or who initiate alternative BPH 
therapies will be considered as having no improvement in IPSS score. For subjects that have missing 
data for the primary efficacy endpoint, data will be imputed via multiple imputation as described in 
the SAP. 
10.8.2 For the Primary Efficacy Endpoint 
Unless there is evidence of occurrence of a primary safety endpoint event, subjects with missing 
data for the primary safety endpoint are presumed to not have experienced a primary safety endpoint 
event. 
11 DEFINITION OF ADVERSE EVENT(S) 
For purposes of this study, an adverse event (AE) is defined as any adverse change 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 the day of the study index procedure.  
All AE’s will be recorded on an Adverse Event CRF whether considered procedure-related or not, 
and will be classified as described in Section 11.5.   
Any adverse changes occurring between the time the subject is enrolled (i.e. consented) and the day 
of the study index procedure will be captured on the Medical History CRF.    
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.  
11.1 Treatment Related Symptoms 
The Urotronic DCB procedure is designed to alleviate the moderate-to-severe LUTS/BPH.  Subjects 
to be treated have moderate-to-severe LUTS/BPH prior to treatment.  These symptoms are expected 
to continue and may even worsen slightly prior to improvement as part of the healing process.  Other 

 
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expected acute but transient symptoms from the treatment are dysuria, hematuria, and acute urinary 
retention as the tissue heals.  
Worsening or new onset LUTS, dysuria or non-obstructive hematuria that occur and resolve within 
14 days of treatment that do not require intervention (other than initial catheterization, 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 aggressively treated 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 new onset LUTS requiring intervention or persisting beyond 14 days post 
treatment 
b. Worsening or new onset 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 (post-discharge) 
d. Urinary tract infection defined as >105 CFU/mL of a single organism plus symptoms 
localized to bladder 
e. Urinary retention after index procedure healing 
f. If new onset LUTS recurs after the same symptom is resolved and is considered clinically 
significant or requiring re-catheterization. 
11.2 Urinary Retention and Catheterization 
A catheterization that occurs within 24 hours of a prior catheterization will be considered to be the 
same catheterization event. 
All catheterizations and cystoscopies will be recorded in the CRF.   
While catheterization in and of itself is not an AE, the reason for catheterization must be evaluated 
for purposes of determining an AE.   
11.3 Acute Urinary Retention Definition 
Acute urinary retention is the lack of ability to urinate.  It typically has to be treated with a catheter 
to avoid serious complications of the bladder and/or kidney. 
11.4 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: 
• 
Poor stream 
• 
Hesitancy 
• 
Terminal dribbling 

 
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• 
Incomplete voiding 
• 
Overflow incontinence (occurs in chronic retention) 
11.5 Reporting and 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 11-1 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 11-1: 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 name of the AE and 
the other symptoms should be included in the event description.   
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 name of the AE should be 
UTI and the other symptoms should be included in the event description.   
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, the name of the 
AE should be hematuria with clot retention and the other symptoms should be included in the event 
description. 
The AEs in the study may be further coded by Medical Dictionary for Regulatory Activities 
(MedDRA) and graded according to Common Terminology Criteria for Adverse Events (CTCAE) 
for the purpose of regulatory reporting or publication. 
11.6 Potential Anticipated Adverse Events 
Potential anticipated adverse events are those that may occur in association with a BPH treatment or 
procedure, including those AEs listed below or reported in the literature associated with surgical or 
minimally invasive obstructive BPH procedures: 
Procedural Risks 
• Adverse reaction to the drug coating 
• Sepsis and infection 

 
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• Fever 
• Perforation of urethra 
• Perforation of bladder 
• Splitting of the prostate capsule 
• Urinary symptoms and adverse events including: 
o Dysuria 
o Frequency 
o Urgency 
o Nocturia 
o Acute urinary retention (not due to clot) 
o Acute urinary retention (due to clot) 
o Acute urinary retention (due to clogged Foley catheter)  
o Chronic urinary retention 
o Incontinence 
o Sensation of not emptying bladder completely 
o Urethritis 
o Urethral injury causing false passage or adhesion 
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 
o Urethral Stricture 
• Abscess (prostatic, bladder, scrotal) 
• Bladder problems or damage (reduced bladder sensation, spasms, bladder neck contracture, 
bladder neck stenosis, bladder fistula) 
• Bladder perforation or rupture 
• Damage to the urethral system 
• Worsening of LUTS/BPH 
• Seroma 
• Kidney compromise or failure  
• Reproductive system disturbances such as infertility and/or miscarriages 
• Prostate abnormalities and damage 
• Device embolization or separation (defined as a separation of the device or parts of the device 
such that it cannot be removed from the body by withdrawing the device but requires another 
method to retrieve the device)  
 

 
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Other Pelvic Health Risks 
• Unmasking of incontinence – underlying stress or urge incontinence may be unmasked and 
symptoms of incontinence controlled previously by the BPH may be evident 
• Rectal incontinence 
• Rectal damage 
• Rectal fistula 
• Rectal stenosis 
• Rectal, perineal findings 
• Anal irritation 
• Elevated PSA 
• Nerve damage 
• Weakness or numbness  
• Abdominal or low back pain 
• Flu-like symptoms 
• Hematospermia 
• Epididymitis 
• Erectile dysfunction 
• Retrograde ejaculation or ejaculatory dysfunction 
• Pressure sensation 
• Prostatitis 
• Cancer - the risk of cancer due to chromosomal damage is unknown 
Other potential non-pelvic anticipated adverse events that may occur in this subject population are: 
• Blood pressure change during therapy 
• Arrhythmia 
• Flank pain 
• Blood loss (> 500 ml)  
• Adverse reaction to medication and anesthesia as listed in the labeling 
• Low blood pressure (hypotension) 
• High blood pressure (hypertension) 
• Fainting, dizziness, or blurred vision (vasovagal reaction, syncope) 
• Allergic reaction 
• Fatigue 
• Dyspnea 
• Confusion 
• Memory loss 
• Swelling or bruising (edema, hematoma) 
• Aneurysm – thoracic and cranial 

 
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• Low back pain 
• Pneumonia 
• Collapsed lung  
• Pulmonary embolism 
• Pneumothorax 
• Upper respiratory disease 
• Cough 
• Sore throat 
• Apnea 
• Coughing up blood (hemoptysis) 
• Choking (aspiration) 
• Venous thrombosis 
• Myocardial infarction, angina, ischemia 
• Cardiac arrhythmia 
• Stroke or transient ischemic attack 
• Brain damage 
• Headache 
• Depression 
• Perforation of or damage to the gastrointestinal tract 
• Abdominal pain 
• Constipation 
• Nausea or vomiting 
• Fetal risk 
• Adverse reaction to medication 
 
Drug Risks  
Adverse reaction to the paclitaxel and symptoms observed derived primarily from IV infusion 
studies of the drug in treating cancer subjects include:  
• Chromosomal abnormalities and the risk of cancer  
• Fetal harm when a pregnant woman is exposed  
• Anaphylaxis and hypersensitivity with paclitaxel  
• Inhibition of the healing of the urethra post procedure 
• Myelosuppression including: neutropenia, leukopenia, thrombocytopenia, anemia 
• Arrhythmia 
• Peripheral neuropathy  
• Myalgia or Arthralgia 
• Alopecia 
• Hypotension  

 
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• Nausea, vomiting or diarrhea 
• Elevated bilirubin, ALP and AST 
• Potential effect on the liver and kidneys is unknown and have not been studied 
The amount of the paclitaxel delivered locally during the Optilume DCB procedure is much lower 
than a single dose of  systemic chemotherapy provided to cancer patients and the drug appears to be 
essentially remain localized in the prostate and urethra. 
11.7 Definition of Serious Adverse Event(s) 
An adverse event is considered to be a serious adverse event (SAE) when the subject outcome is any 
of the following: 
• Death  
• Life-threatening 
• In-patient hospitalization or prolongation of an existing hospitalization 
• Persistent or significant disability/incapacity 
• Substantial disruption of a person’s ability to conduct normal life functions, i.e. the 
adverse event resulted in a significant, persistent or permanent change, impairment, 
damage or disruption in the subject’s body function/structure including chronic 
diseases, physical activities and/or quality of life 
• Congenital anomaly or birth defect 
• Required medical or surgical intervention to prevent permanent impairment of a body 
function or damage to a body structure 
• Important medical event 
• If the AE does not fit the other outcomes, but the event may jeopardize the health of 
the subject or require medical or surgical intervention (treatment) to prevent one of 
the outcomes listed above   
An SAE may or may not be related to the study procedure. 
Note: A planned hospitalization for a pre-existing condition, or a procedure required by the protocol 
without serious deterioration in health, is not considered a serious adverse event.  
11.8 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 degree of incidence in 
the investigational plan (e.g., ICF, Study Protocol, Instructions for Use (IFU), publications, etc.), or 

 
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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/REB as soon as possible.   
The Sponsor will investigate the event and notify the authorities and IRB/REB and all other 
participating IRBs/REBs and investigators.  Should the Sponsor determine that an unanticipated 
adverse device effect presents an unreasonable risk to all participating subjects, the Sponsor will 
suspend the clinical investigation and notify all participating investigators, IRBs/REBs and country 
regulatory bodies.  
11.9 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) severity; (c) relationship to the study device and study procedure; (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 and (g) whether the event meets the definition of a UADE.  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 AEs must be reported to the Sponsor within the period outlined in Table 14-1.  
All deaths 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. 
11.10 Relationship of AEs to the Device and Procedure 
A description of how an AE relates to the study device and to the study procedure will be reported 
on the Adverse Event CRF and be determined by the Investigator using the following definitions: 
• 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. 
• 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. 
• 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.  However, 
other factors such as underlying disease, concomitant medications, or concurrent treatment 
are presumable. 

 
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• 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. 
• 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. 
Adverse events will be reviewed and adjudicated by the Clinical Events Committee (CEC) as 
described in Section 14.1.   
11.11 Adverse Event Severity 
A description of the severity of the adverse event will be reported on the Adverse Event CRF and 
be determined by the Investigator using the following definitions: 
• Mild: An event that is easily tolerated by the subject, causing minimal discomfort and 
not interfering with everyday activities  
• Moderate: An event that causes discomfort sufficient to interfere with normal everyday 
activities, non-invasive intervention may be indicated 
• Severe: An event that prevents normal everyday activities or is incapacitating; invasive 
intervention may be indicated 
NOTE: The term ‘Severe’ does not necessarily equate to ‘Serious’ when determining if an event is 
a Serious Adverse Event. Please refer to Section 11.7 for the definition of a Serious Adverse 
Event. 
11.12 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/REB (if required) within the IRB/REB required timeframe.  The malfunctioning 
investigational device involved in the incident should be returned to the Sponsor for evaluation.   
12 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, study 
blinding procedures, schedules for follow-up, and regulatory requirements will be reviewed. 

 
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13 DATA MANAGEMENT 
13.1 Study Database and Electronic Case Report Forms 
All required clinical data will be collected and compiled on web-based, standardized, electronic Case 
Report Forms (eCRFs).  
The eCRFs are designed to accommodate the specific features of the study design. Modification of 
the eCRF will only be made if deemed necessary by the Sponsor and/or appropriate regulatory body.  
Appropriate quality control measures will be established to ensure accurate and complete transfer of 
information from the study documentation to the study database. 
13.2 Subject Identification 
Subjects that provide informed consent will be assigned a unique identification code (ID) using the 
format “6XX-YYY” where: 
 
6XX = 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 
 The subject ID will be used to track subject information throughout the study. 
13.3 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. 
14 STUDY RESPONSIBILITIES AND MANAGEMENT 
14.1 Clinical Events Committee 
An independent Clinical Events Committee (CEC) will be utilized for this study. The CEC will be 
responsible for adjudicating the CTCAE severity, seriousness and relatedness of all adverse events 
occurring during the study period. The CEC will also adjudicate whether the event qualifies as a 
primary safety endpoint event.  A charter will be completed for the CEC outlining membership, 
duties and functions.  
The CEC will be made up of a minimum of two clinicians with expertise in urology and one clinician 
with expertise in cardiology.  All members of the CEC will be blinded to the subjects’ treatment and 
the primary results of the study. The CEC will meet regularly to review and adjudicate all adverse 
events. The committee will also review and rule on all deaths that occur throughout the study.  
14.2 Data Monitoring Committee 
An independent Data Monitoring Committee (DMC) will be utilized for this study. The DMC will 
be responsible for the oversight and safety monitoring of the study. A charter will be completed for 
the DMC outlining membership, duties, functions and meeting frequencies.  

 
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The DMC will be comprised of leading experts in urology, cardiology and biostatistics who are not 
participating in the study and have no affiliation with the Sponsor. All members of the DMC will be 
unblinded to the subjects’ treatment and the primary results of the study.  The DMC will review 
accumulating safety data during the enrollment phase of the study to monitor for incidence of serious 
adverse events that would warrant modification or termination of the study.  
14.3  Investigator Responsibilities 
Each investigator is responsible for ensuring the investigation is conducted according to all signed 
agreements, the study protocol, IRB/REB 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 
• IRB/REB roster 
• IRB/REB 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. 
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 IRB/REB and the Sponsor. 
14.3.1 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).   

 
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14.3.2  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 FDA and IRB/REB 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 IRB/REB prior to 
implementation.  Following approval, any Investigational Protocol amendment must be distributed 
to all protocol recipients at the site. 
14.3.3  Protocol Deviations 
A protocol deviation/violation is generally an unplanned digression 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 IRB/REB policy. 
A Protocol Deviation CRF must be completed by the site for each study protocol deviation (e.g., 
failure to obtain informed consent, randomizing or treating 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 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 IRB/REB 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. 
14.3.4  Protocol Deviation Notification/Approval to IRB/REB/Sponsor before 
Implementation 
A protocol deviation may be a limited prospective exception to the protocol (e.g. agreement between 
Sponsor and Investigator to randomize 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 IRB/REB and the Sponsor prior to 
implementation.  These types of deviations are only approved if they do not impact data integrity or 
put subjects at unreasonable risk. 
14.3.5  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.   

 
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14.3.6  Device Accountability 
Urotronic’s sham catheters, pre-dilation balloon catheters and Optilume BPH Prostatic Drug Coated 
Balloon Dilation Catheters allocated for investigational site use will be stored in a secured area at 
room temperature until use.  Each site will be responsible for tracking the receipt and disposition of 
all investigational devices.  All unused sham, pre-dilation and DCB catheters must be returned to 
the Sponsor at the end of the study.   
The Investigator must ensure the device is used only in accordance with the protocol and current 
IFU. The Investigator must maintain records that document device delivery to the study site, 
inventory at the site and administration to subjects. This record should include dates, quantities, 
model and lot numbers (if applicable) and the unique subject ID assigned to study subjects. The 
Investigator should maintain records that document which device(s) the subject received according 
to the protocol and assigned randomization. In the case where a device has failed, the Investigator 
must make every possible effort to return the device to the Sponsor. 
14.4 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 IRB/REB 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 subject’s medical record.  Administering the questionnaires can be done 
prior to signing the ICF if those questionnaires are collected as standard of care at the site, the 
questionnaires are consistent with the IRB/REB approved versions of the questionnaire, and are 
collected within the time specified. 
Timely communication by each site is critical to avoid over enrolling when the enrollment is close 
to the end. When enrollment is close to the end, the following procedures will be implemented: 
• Before the subject signs the study ICF, the study site must confirm the availability of an 
enrollment slot.  A phone call to the Sponsor is the preferred method. 
• Immediately after the procedure, the study site must inform the Sponsor of the subject’s 
eligibility and the completion of the procedure.  A phone call to the Sponsor is the preferred 
method. 
14.5 Institutional Review Board (IRB)/Research Ethics Board (REB)  
Investigators must submit the study protocol to their respective Institutional Review Board (IRB)/ 
Research Ethics Board (REB) and obtain the IRB’s/REB’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 IRB/REB, such as regular reporting, study timing, etc.  
Investigators will provide the Sponsor or its designee with copies of such approvals and reports. 

 
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14.6 Informed Consent Form (ICF) 
The Sponsor will provide a template informed consent form (ICF) to each study site for IRB/REB 
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 IRB/REB.   
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 any study-specific assessments.  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. 
14.7 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. 
14.8 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; 
• IRB/REB 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 and lot numbers of devices received, 
o Name of person(s) who received, used or disposed of each device, 

 
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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; 
• Signature authorization and delegation log; and, 
• Any other records that applicable regulation requires to be maintained. 
14.9 Reports 
Table 14-1 lists those reports that are the investigator's responsibility to deliver to the Sponsor.  Each 
study investigator must follow the IRB/REB reporting requirements for their respective site.  If 
applicable regulations or IRB/REB requirements mandate stricter reporting requirements than those 
listed, the stricter requirements must be followed. 
Table 14-1: Reports Required from Investigators to Sponsor 
Type of Report 
Prepared by PI for 
Notification Time Frame 
UADE 
 
Sponsor, IRB/REB 
 
Within 24 hours of knowledge 
Death 
Sponsor  
IRB/REB, if 
required 
Written reports (e.g., via e-mail) 
within 24 hours of knowledge 
SAE  
Sponsor 
 
IRB/REB, if 
required 
Within 24 hours of knowledge  
Per IRB/REB requirement 
Device malfunction with clinical 
sequelae 
Sponsor 
 
IRB/REB, if 
required 
Within 48 hours via written 
communication.  Return the device to 
Sponsor within 48 hours or as 
requested. 
Serious protocol deviations (e.g., 
ICF not obtained, to protect the 
Sponsor 
 
Within 5 working days of knowledge 
Per IRB/REB requirement 

 
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Type of Report 
Prepared by PI for 
Notification Time Frame 
life or physical well-being of a 
subject in an emergency) 
IRB/REB, if 
required 
Withdrawal of IRB/REB approval 
Sponsor 
 
Within 5 working days of knowledge 
Progress report 
Sponsor, IRB/REB 
As required by IRB/REB 
Final report 
Sponsor, IRB/REB 
Within 3 months of study completion 
or termination 
Note: Each IRB/REB may require more stringent reporting requirements that those listed in this 
table. 
 
14.10 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. 
14.10.1 Sponsor Reporting Responsibilities  
Table 14-2 lists those reports that are the Sponsor's responsibility and timelines to report to the 
IRB/REB and FDA.  If applicable regulations or IRB/REB and FDA requirements mandate 
stricter reporting requirements than those listed, the stricter requirements must be followed. 
 

 
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Table 14-2: Sponsor Reporting Responsibilities 
Type of Report 
Sponsor Reporting Responsibilities 
Report 
Prepared For 
Reporting Time Frame 
Unanticipated  
Adverse Device 
Effect (UADE) 
Investigators, 
IRBs/REBs and 
FDA 
Written - Within 10 working days from 
the time the Sponsor first learns of the 
effect. 
Withdrawal of IRB/REB 
Approval or other action on part 
of the IRB/REB that affects the 
study 
Investigators, 
IRBs/REBs and 
FDA 
Written – Within 5 working days. 
Withdrawal of FDA 
approval 
Investigators and 
IRBs/REBs 
Written – Within 5 working days. 
Current investigator list 
FDA 
Written – At 6-month intervals. Submit 
the first list 6 months after FDA approval. 
Device Recall 
Investigators, 
IRBs/REBs and 
FDA 
Written – Within 30 working days. 
Progress Reports 
Investigators, 
IRBs/REBs and 
FDA 
At regular intervals, but in no event less 
than yearly. 
Inappropriate 
Informed Consent 
IRB/REB and 
FDA 
Investigator’s report submitted within 5 
working days of notification 
Study Closure 
Investigators, 
IRBs/REBs and 
FDA 
Within 10 days 
Final Report 
Investigators, 
IRBs/REBs and 
FDA 
Significant risk device – Notify FDA 
within 30 working days of the completion 
the investigation 
Final report - within 6 months of study 
closure. 
15 STUDY ADMINISTRATION 
15.1 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 

 
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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 IRB/REB 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).  
The study monitoring will be done by the following Sponsor representative: 
Clinlogix, LLC  
8 Springhouse Innovation Park, Suite 100  
Lower Gwynedd, PA  19002  
USA 
15.1.1 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.  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: 
• 
Verification that the current IRB/REB-approved informed consent was signed and dated 
by each subject prior to participating in the study required procedures. 

 
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• 
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 entrance 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 
IRB/REB-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. 
15.1.2 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 IRB/REB.  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.)   
16 STUDY CONTACT 
16.1 Study Principal Investigator 
Steven A. Kaplan, MD 
Professor of Urology 
Icahn School of Medicine at Mount Sinai 
Director, Benign Urologic Diseases and The Men’s Health Program 
Mount Sinai Health System 

 
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625 Madison Avenue 
New York, NY 10022 
USA 
16.2 Sponsor  
Urotronic Inc 
2495 Xenium Lane N 
Minneapolis, MN 55441 
USA 
info@urotronic.com 
16.3 Data Management  
Libra Medical Inc 
8401 73rd Ave N, Suite 63 
Brooklyn Park, MN 55428 
USA 
612-801-6782 
17 POTENTIAL DEVICE CHANGE 
Future product line extensions 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.  All device changes will be submitted to the FDA 
for review and approval prior to use in the clinical study.  Significant changes that may affect the 
device safety or performance will be provided to the IRB/REB 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 

 
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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 will register the study on the ClinicalTrials.gov website upon approval by an 
IRB/REB in order to meet the criteria of the International Committee of Medical Journal Editors.  
Institution(s) and/or Principal Investigator(s) shall not take any action to register the trial. 

 
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19 REFERENCES 
 
 
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2 Barry MJ, Fowler FJ Jr, O'Leary MP, et al. Measurement committee of the American 
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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)