Conditions: Overactive Bladder
Keywords: Overactive Bladder Benign Prostatic Hyperplasia Vibegron Beta-3 adrenergic receptor (ß3-AR) ß3-AR agonist
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1105
Healthy volunteers: no

Brief summary:
This study will assess the efficacy of vibegron compared with placebo in men with overactive bladder (OAB) symptoms on pharmacological therapy for benign prostatic hyperplasia (BPH) as defined by micturition and urgency episodes.

Detailed description:

Arms:
arm 1: Participants will receive vibegron 75 milligrams (mg) orally once daily for 24 weeks. arm 2: Participants will receive matching placebo orally once daily for 24 weeks.

Interventions: intervention 1: Vibegron intervention 2: Placebo
Intervention descriptions: intervention 1: oral administration intervention 2: oral administration

Protocol document:
Prot_000.pdf: 
Urovant Sciences, GmbH  
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Protocol URO-901-3005 
Version 4.0 (Amendment 3) 
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25 February 2022 
Protocol Title: A Phase 3 Double-Blind, Randomized, Placebo-Controlled, Multi-Center Study 
to Evaluate the Efficacy, Safety and Tolerability of Vibegron in Men with Overactive Bladder 
(OAB) Symptoms on Pharmacological Therapy for Benign Prostatic Hyperplasia (BPH) 
Protocol Number:  
URO-901-3005 
Version Number: 
4.0 (supersedes Version 3.0) 
Amendment Number: 
3 
Product: 
Vibegron (URO-901, RVT-901, MK-
4618, KRP-114V) 
Development Phase: 
3 
Sponsor:  
Urovant Sciences, GmbH 
Grosspeter Tower 
Grosspeteranlage 29 
Suites 2006-2010 
4052 Basel, Switzerland 
Sponsor Contact: 
, PhD, MS 
Senior Director, Clinical Development 
Telephone: 
Email: 
IND Number: 
106410 
EudraCT Number: 
2018-003135-30 
Emergency Contact Telephone Number: 
Refer to separate Study Contacts Page 
Contact for Serious Adverse Events (SAEs): 
Email: PHV_Urovant@iqvia.com 
Phone: +1- 866-599-1341 
Phone: +1-984-219-4638 (International) 
Fax: +1-866-599-1342 
Fax: +1-984-219-5032 (International) 
Approval Date: 
25 February 2022 
Sponsor Signatory: 
, MD, PhD 
Chief Medical Officer 
CONFIDENTIAL 
This document contains proprietary and confidential information of Urovant Sciences, GmbH. Acceptance of this 
document constitutes agreement by the recipient that no previously unpublished information contained herein will 
be published or disclosed without the prior written approval of Urovant Sciences, GmbH with the exception that this 
document may be disclosed to study personnel under your supervision who need to know the contents for 
conducting the study and appropriate Institutional Review Boards (IRBs)/Ethics Committees (EC) under the 
condition that the personnel have agreed to keep this information confidential. The foregoing shall not apply to 
disclosure required by governmental regulations or laws, however, Urovant Sciences, GmbH shall be promptly 
notified of any such disclosure. 
   
 
 
 
NCT Number: NCT03902080   
This NCT number has been applied to the document for purposes of posting on Clinicaltrials.gov


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SPONSOR SIGNATURE PAGE
Study Title:  A Phase 3 Double-Blind, Randomized, Placebo-Controlled, Multi-Center Study to 
Evaluate the Efficacy, Safety and Tolerability of Vibegron in Men with Overactive Bladder 
(OAB) Symptoms on Pharmacological Therapy for Benign Prostatic Hyperplasia (BPH)
Study Number: URO-901-3005 (Amendment 3)
This protocol, including Amendment 3, has been approved by a representative of Urovant 
Sciences GmbH. The following signature documents this approval.
, MD, PhD 
Chief Medical Officer
Date
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g
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INVESTIGATOR STATEMENT 
Study URO-901-3005: A Phase 3 Double-Blind, Randomized, Placebo-Controlled, Multi-
Center Study to Evaluate the Efficacy, Safety and Tolerability of Vibegron in Men with 
Overactive Bladder (OAB) Symptoms on Pharmacological Therapy for Benign Prostatic 
Hyperplasia (BPH)  
 
Revised Protocol (Amendment 3) 
 
x I confirm agreement to conduct the study in compliance with the protocol. 
x I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study. 
x I agree to ensure that all associates, colleagues, and employees assisting in the 
conduct of the study understand their obligations and will comply with the study 
protocol. Mechanisms are in place to ensure that site staff receives the appropriate 
training and information throughout the study. 
 
 
 
 
Principal Investigator Name (Printed) 
 
Signature 
 
 
 
Date (DD/MMM/YYYY) 
 
Site Number 
 


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Protocol Amendment Summary of Changes Table 
DOCUMENT HISTORY 
Document 
Version 
Date 
Original protocol 
1.0 
29 January 2019 
Amendment 1 
2.0 
30 July 2020 
Amendment 2 
3.0 
16 December 2020 
Amendment 3 
4.0 
24 February 2022 
The current protocol amendment is summarized below. The previous amendments are 
summarized in Appendix 9. 
Protocol Amendment 3, 24 February 2022 
This protocol was amended to include the following notable changes: 
x Cover Page was updated with new Sponsor Contact information 
x Section 1.1 Synopsis, Overall Study Design, and Section 4.1 Overall Design 
o Updated to include a potential decision point to transition to enrollment of only 
subjects willing to participate in the urodynamics sub-study 
x Section 1.4 Schedule of Assessments – Part 2 
o Updated footnote c to remove statement regarding other procedures to be consistent 
with remainder of protocol 
o Updated footnote f to indicate that a historical urodynamics assessment will be 
acceptable 
x Table 1 Bladder Diary Completion Schedule 
o Run-in Diary Completion Timepoint to ‘Begin 3-day diary’ and ‘Acceptable 
completion window’ have been updated to allow completion on any 3 consecutive 
days at any time within the Screening period prior to the Run-in Visit 
x Section 5.2 Exclusion Criteria 
o Renumbered to be consistent with Note to File issued subsequent to Protocol 
Amendment 2 
o Exclusion Criterion 7 was reworded to clarify that irregular use of long-acting ED 
medications is excluded while irregular use short-acting ED medications is allowed 


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o Exclusion Criterion 11 was corrected to reflect the change made in Protocol 
Amendment 2 removing Qmax measurement at Visit 3 (Baseline) 
o Exclusion Criterion 19 has been modified to exclude uncontrolled sleep apnea and 
self-reported sleep apnea that has been neither confirmed nor diagnosed by a 
physician 
o Exclusion Criterion 25 has been clarified to indicate that all subjects taking any anti-
hypertensives must be taking stable doses for at least 3 months prior to the Screening 
Visit 
o Exclusion Criterion 36 has been modified to exclude all subjects who have been 
exposed to vibegron (through a clinical trial or commercial use) 
x Section 8.2.1 Bladder Diaries 
o Updated to allow completion on any 3 consecutive days at any time within the 
Screening period prior to the Run-in Visit 
x Section 8.3.7 Urodynamics Assessments 
o Added that use of a historical urodynamics trace obtained at the site within 6 months 
prior to Screening may be used in lieu of an assessment obtained between screening 
and randomization (Baseline/Visit 3) as long as the same equipment and procedure 
are used at the Week 12 (Visit 8) assessment 
o Clarified that the urodynamics assessment may be performed on a different day than 
the Week 12 (Visit 8) visit as long as it is performed within the ±4-day visit window 
x Section 8.4.6 Adverse Events of Special Interest 
o Formatting was changed for ease of understanding 
o New language was added to differentiate between AESI terms for hypertension and 
worsening of hypertension 
x Section 10.3 Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting, Events Meeting the AE Definition 
o Words added to clarify that events that meet the definition include abnormal 
laboratory test results or safety assessments that worsen from baseline or are 
considered clinically significant 
x Section 10.7.1 Screening, Visit 1 (Day -49 to Day -14) 


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o Clarified that Screening Visit assessments may be performed in a single day or over 
multiple days within the screening period 
x Section 10.7.3 Baseline, Visit 3 (Day 1) 
o Updated window to obtain baseline urodynamics assessment 


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Table of Contents 
Sponsor Signature Page .................................................................................................................2 
Investigator Statement...................................................................................................................3 
Protocol Amendment Summary of Changes Table ....................................................................4 
Table of Contents ...........................................................................................................................7 
List of Tables ................................................................................................................................10 
1. 
Protocol Summary ........................................................................................................11 
1.1. 
Synopsis ..........................................................................................................................11 
1.2. 
Schema for Parts 1 and 2 ................................................................................................14 
1.3. 
Schedule of Assessments - Part 1 ...................................................................................15 
1.4. 
Schedule of Assessments - Part 2 ...................................................................................17 
2. 
Introduction ...................................................................................................................21 
2.1. 
Study Rationale ...............................................................................................................21 
2.2. 
Background .....................................................................................................................21 
2.3. 
Overactive Bladder in Men with Benign Prostatic Hyperplasia .....................................21 
2.3.1. 
Vibegron .........................................................................................................................22 
2.4. 
Benefit/Risk Assessment ................................................................................................23 
2.4.1. 
Potential Benefits ............................................................................................................23 
2.4.2. 
Potential Risks ................................................................................................................23 
3. 
Objectives and Endpoints ............................................................................................25 
4. 
Study Design ..................................................................................................................27 
4.1. 
Overall Design ................................................................................................................27 
4.2. 
Scientific Rationale for Study Design ............................................................................28 
4.2.1. 
Clinical Hypotheses ........................................................................................................28 
4.3. 
Justification for Dose ......................................................................................................28 
4.4. 
End of Study Definition ..................................................................................................28 
5. 
Study Population ...........................................................................................................29 
5.1. 
Inclusion Criteria ............................................................................................................29 
5.2. 
Exclusion Criteria ...........................................................................................................30 
5.3. 
Lifestyle Considerations .................................................................................................32 
5.4. 
Screen Failures ................................................................................................................33 
6. 
Study Drug.....................................................................................................................34 
6.1. 
Study Drugs Administered..............................................................................................34 
6.1.1. 
Run-in Medications and Administration .........................................................................34 
6.1.2. 
Treatment Period Medications and Administration ........................................................35 
6.2. 
Preparation/Handling/Storage/Accountability ................................................................35 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................35 
6.4. 
Study Drug Compliance..................................................................................................36 
6.5. 
Concomitant Therapy .....................................................................................................36 
6.5.1. 
Prohibited Drugs and Washout Before the Study ...........................................................36 
6.5.2. 
Permitted Drugs ..............................................................................................................36 
6.6. 
Dose Modification ..........................................................................................................37 


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6.7. 
Drug After the End of the Study .....................................................................................37 
7. 
Discontinuation of Study Drug and Subject Discontinuation 
or Withdrawal ...............................................................................................................38 
7.1. 
Discontinuation of Study Drug .......................................................................................38 
7.2. 
Subject Discontinuation/Withdrawal from the Study .....................................................38 
7.3. 
Lost to Follow-Up ...........................................................................................................39 
7.4. 
Early Study Termination .................................................................................................39 
8. 
Study Assessments and Procedures.............................................................................40 
8.1. 
Baseline Procedures ........................................................................................................40 
8.1.1. 
Informed Consent............................................................................................................40 
8.1.2. 
Assignment of Subject Number ......................................................................................40 
8.1.3. 
Screening.........................................................................................................................40 
8.1.4. 
Medical History ..............................................................................................................41 
8.1.5. 
Demographics .................................................................................................................41 
8.1.6. 
Prior and Concomitant Medications ...............................................................................41 
8.1.7. 
Inclusion and Exclusion Post Placebo Run-In ................................................................41 
8.2. 
Efficacy Assessments .....................................................................................................42 
8.2.1. 
Bladder Diaries ...............................................................................................................42 
8.2.2. 
Patient-Reported Outcomes ............................................................................................43 
8.3. 
Safety Assessments .........................................................................................................44 
8.3.1. 
Vital Signs .......................................................................................................................44 
8.3.2. 
Orthostatic Blood Pressure (Part 1 Only) .......................................................................45 
8.3.3. 
Physical Examinations ....................................................................................................45 
8.3.4. 
Electrocardiograms .........................................................................................................46 
8.3.5. 
Post-Void Residual Volume ...........................................................................................46 
8.3.6. 
Clinical Safety Laboratory Assessments ........................................................................46 
8.3.7. 
Urodynamics Assessments..............................................................................................47 
8.3.8. 
Prostate Volume Measurement .......................................................................................48 
8.4. 
Adverse Events and Serious Adverse Events .................................................................48 
8.4.1. 
Time Period and Frequency for Collecting Adverse Event and 
Serious Adverse Event Information ................................................................................48 
8.4.2. 
Method of Detecting Adverse Events and Serious Adverse 
Events ..............................................................................................................................49 
8.4.3. 
Follow-up of Adverse Events and Serious Adverse Events ...........................................49 
8.4.4. 
Regulatory Reporting Requirements for Serious Adverse Events ..................................49 
8.4.5. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as Adverse Events or Serious Adverse Events .............................................50 
8.4.6. 
Adverse Events of Special Interest .................................................................................50 
8.4.7. 
Pregnancy Management and Reporting to the Sponsor ..................................................53 
8.4.8. 
Medication Errors ...........................................................................................................54 
8.5. 
Treatment of Overdose ...................................................................................................54 
8.6. 
Safety Measures due to COVID-19 Pandemic ...............................................................55 
9. 
Statistical Considerations .............................................................................................56 
9.1. 
Statistical Hypotheses .....................................................................................................56 
9.2. 
Sample Size Determination ............................................................................................56 


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9.3. 
Populations for Analyses ................................................................................................58 
9.4. 
Statistical Analyses .........................................................................................................59 
9.4.1. 
Demographic and Other Baseline Characteristics ..........................................................59 
9.4.2. 
Efficacy Analyses ...........................................................................................................60 
9.4.3. 
Safety Analyses ...............................................................................................................61 
9.4.4. 
Other Analyses ................................................................................................................63 
9.5. 
Interim Analyses .............................................................................................................63 
9.6. 
Data Safety Monitoring Board ........................................................................................63 
10. 
Supporting Documentation and Operational Considerations ..................................64 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................64 
10.1.1. Regulatory and Ethical Considerations ...........................................................................64 
10.1.2. Financial Disclosure........................................................................................................64 
10.1.3. Informed Consent Process ..............................................................................................65 
10.1.4. Data Protection................................................................................................................65 
10.1.5. Committees Structure......................................................................................................65 
10.1.6. Posting Clinical Study Data ............................................................................................65 
10.1.7. Data Quality Assurance ..................................................................................................66 
10.1.8. Source Documents ..........................................................................................................67 
10.1.9. Study and Site Closure ....................................................................................................68 
10.1.10. Publication Policy ...........................................................................................................68 
10.1.11. Compliance with Protocol...............................................................................................68 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................69 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .........................................................70 
10.4. 
Appendix 4: Abbreviations .............................................................................................75 
10.5. 
Appendix 5: Study Tabular Summary ............................................................................78 
10.6. 
Appendix 6: Prohibited Medications and Non-Drug Therapies .....................................80 
10.7. 
Appendix 7: Study Schedule Supplement ......................................................................81 
10.7.1. Screening, Visit 1 (Day -49 to Day -14) .........................................................................81 
10.7.2. Run-in, Visit 2 (Day -14 r 4 days) .................................................................................82 
10.7.3. Baseline, Visit 3 (Day 1) .................................................................................................82 
10.7.4. REMOTE Double-blind Treatment Period, Visit 4 (Week 1  4 
days) ................................................................................................................................83 
10.7.5. Double-blind Treatment Period, Visit 5 (Week 2 r 4 days) ...........................................83 
10.7.6. Double-blind Treatment Period, Visit 6 (Week 4 r 4 days) ...........................................84 
10.7.7. Double-blind Treatment Period, Visit 7 (Week 8 r 4 days) and 
Visit 10 (Week 20 r 4 days) ...........................................................................................84 
10.7.8. Double-blind Treatment Period, Visit 8 (Week 12 r 4 days) .........................................85 
10.7.9. REMOTE Double-blind Treatment Period, Visit 9 (Week 16 r 4 
days) ................................................................................................................................85 
10.7.10. Double-blind Treatment Period, Visit 11 (Week 24 r 4 days) or 
Early Withdrawal) ...........................................................................................................85 


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10.7.11. Safety Follow-up (for subjects who do not enter the extension 
Study URO-901-3006; 5 days after last dose of study drug 
[± 2 days]) .......................................................................................................................86 
10.8. 
Appendix 8: Patient-Reported Outcomes Questionnaires, 
Descriptions, and Instructions.........................................................................................86 
10.8.1. International Prostate Symptom Score (IPSS) ................................................................86 
10.8.4. Patient Global Impression Scale .....................................................................................95 
10.8.5. International Index of Erectile Function .........................................................................98 
10.9. 
Appendix 9: Summary of Previous Protocol Amendments ..........................................104 
10.9.1. Protocol Amendment 1, 30 July 2020...........................................................................104 
10.9.2. Protocol Amendment 2, 16 December 2020 .................................................................107 
11. 
References ....................................................................................................................113 
 
List of Tables 
Table 1 
Bladder Diary Completion Schedule ................................................................. 20 
Table 2 
Summary of Study Drugs .................................................................................. 34 
Table 3.  
Data and Sources Supporting Study Sample Size Calculations ........................ 57 
Table 4 
Clinical Laboratory Tests .................................................................................. 69 
 


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1. 
Protocol Summary 
1.1. 
Synopsis 
Protocol Title: A Phase 3 Double-Blind, Randomized, Placebo-Controlled, Multi-Center Study 
to Evaluate the Efficacy, Safety and Tolerability of Vibegron in Men with Overactive Bladder 
(OAB) Symptoms on Pharmacological Therapy for Benign Prostatic Hyperplasia (BPH) 
Protocol Number: URO-901-3005 
Brief Title: Vibegron in Men with BPH with OAB 
Study Rationale: Beta-3 adrenergic receptor (β3-AR) agonists have shown efficacy (with 
improved safety relative to anticholinergics) in treating persistent OAB symptoms in men on 
BPH therapies. This subset of the broader OAB population setting has unique safety needs (eg, 
possibility of urinary retention) that have not been fully evaluated in previous clinical programs 
of OAB treatments. Study URO-901-3005 is designed to evaluate the safety, tolerability, and 
efficacy of vibegron (75 mg once daily [QD] administered for 24 weeks) or placebo in men with 
symptoms of OAB while receiving pharmacological therapy for BPH.  
Objectives and Endpoints: The primary study objective is to assess the efficacy, safety, and 
tolerability of vibegron versus placebo in men with OAB symptoms on pharmacological therapy 
for BPH. The primary clinical efficacy hypothesis is that vibegron + BPH pharmacological 
therapy is more effective than placebo + BPH pharmacological therapy in reducing both a) the 
mean daily micturition episodes and b) mean daily urgency episodes, based on a 3-day diary. 
The safety hypothesis is that the vibegron + BPH pharmacological therapy is safe and tolerable 
in men with OAB symptoms and BPH.  
Primary and secondary study endpoints are as follows: (Note “per day” refers to a continuous 
24-hour period.) 
Co-Primary Efficacy Endpoints 
x Change from baseline (CFB) at Week 12 in the average number of micturition episodes 
per day 
x CFB at Week 12 in the average number of urgency episodes (urgency: need to urinate 
immediately) per day 
Secondary Efficacy Endpoints 
x CFB at Week 12 in the average number of nocturia episodes per night  
x CFB at Week 12 in the average number of urge urinary incontinence episodes per day for 
subjects with urinary incontinence at baseline 


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x CFB at Week 12 in the International Prostate Symptom Score (IPSS) Storage score (1-
week recall) 
x CFB at Week 12 in the average volume voided per micturition 
Overall Study Design: This study is an international Phase 3, randomized, double-blind, 
placebo-controlled, 2-part, parallel-group, multicenter study to evaluate the safety, tolerability, 
and efficacy of vibegron 75 mg in men with symptoms of OAB on stable doses of 
pharmacological therapy for BPH. At Baseline, subjects who meet all eligibility criteria are 
randomized 1:1 to receive either vibegron 75 mg, or placebo in a double-blind fashion. 
Randomization will be stratified based on baseline average number of micturition episodes per 
day (≤ 12 or > 12), alpha blocker use with or without 5α-reductase inhibitors (5-ARIs) use (yes 
or no), and urinary incontinence (yes or no).  
The study consists of two parts: Part 1 (approximately 80 subjects) and Part 2 (approximately 
1008 subjects). Part 2 will proceed following review of 4-week safety data from Part 1 (including 
orthostatic blood pressure results) by an independent Data Safety Monitoring Board (DSMB). 
The 2 study parts are of the same overall design as outlined below but with the following 
exceptions: 
x Part 1 includes additional orthostatic blood pressure and heart rate measurements at 
Screening, Run-in, Baseline, Week 2, and Week 4 to assess for potential orthostatic 
changes (pre-dose through 6 hours post dose, except pre-dose for Screening and Run-In).  
x Part 2 will include a urodynamics sub-study (approximately 60 subjects), which is 
described in detail in Section 8.3.7. 
o The rate of enrollment into both the main study and the urodynamics sub-study 
will be closely monitored. In the case of a discrepancy between the estimated date 
of completion of enrollment in the urodynamics sub-study and the main study, a 
decision may be made to continue enrolling only those subjects who are willing to 
participate in the urodynamics sub-study. 
Both study parts will consist of a Screening Period (approximately 1 to 4 weeks), a single-blind 
Run-in Period (approximately 2 weeks) in which placebo is added to BPH pharmacological 
therapy, and a randomized double-blind Treatment Period (24 weeks). Subjects who complete 
the Week 24 Visit may be offered the opportunity to enroll in a 28-week extension study, URO-
901-3006, which will be conducted under a separate study protocol. Subjects who do not enroll 
into the extension study will have a Safety Follow-up assessment (via telephone call) 
approximately 5 days (± up to 2 days) after the subject’s last dose of study treatment (or 
approximately 5 days [± up to 2 days] after withdrawal for subjects who discontinue the study 
early). Additionally, Unscheduled Visit(s) may be arranged as needed.  


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The study visit schedule is as follows:  
Visit # 
Study Timepoint 
Visit 1 
Screening 
Visit 2 
Run-in 
Visit 3 
Baseline 
Visit 4 
Week 1 (telephone/video call for Part 2 post Amendment 2) 
Visit 5 
Week 2 
Visit 6 
Week 4 
Visit 7 
Week 8 
Visit 8 
Week 12 (Primary efficacy timepoint) 
Visit 9 
Week 16 (telephone/video call for Part 2 post Amendment 2) 
Visit 10 
Week 20  
Visit 11 
Week 24 (End of the Treatment) 
Safety Follow-up 
5 (± 2) days after End of the Treatment (for subjects who do 
not enter the extension study) or after withdrawal (for subjects 
who discontinue early) 
Number of Subjects: It is estimated that approximately 1088 subjects (80 Part 1, 1008 Part 2) 
will be randomized to achieve approximately 924 evaluable subjects (assuming a 15% drop-out 
rate). The sample size justification is provided in Section 9.2. 
Number of Sites: Approximately 135 sites in North America and Europe. 
Study Drug Groups and Study Duration:  
Single-blind Run-in: 1 matched placebo oral tablet daily for 2 weeks 
Double-blind Treatment: 1 vibegron (75 mg) or matched placebo oral tablet daily for 24 weeks. 
No dosage adjustments will be allowed. 
Prior to the study, subjects will have been on alpha-blockers (eg, alfuzosin, doxazosin, silodosin, 
tamsulosin, terazosin) with or without 5-ARI (eg, alfatradiol, dutasteride, finasteride); they will 
continue these agents after adding study drug (vibegron or placebo).  
Data Safety Monitoring Board: A DSMB will be retained to assess, on an ongoing basis, all 
safety aspects of this study, including review of initial (4-week) safety/orthostatic blood pressure 
results from Part 1 prior to proceeding into Part 2. This committee will be an external 
independent DSMB that monitors the safety for both Study URO-901-3005 and the extension 
Study URO-901-3006. The detailed activities including meeting plans will be described and 
documented in the DSMB Charter. A separate statistical analysis plan will be prepared for the 
DSMB. 


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1.2. 
Schema for Parts 1 and 2 
 
 


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1.3. 
Schedule of Assessments - Part 1 
 
Screening Run-in 
 
Double-blind Treatment 
 
Safety  
Follow-up 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visits 
9 & 10 
Visit 11 
or Early 
WD 
Telephone 
Callb 
Day/Week 
Day -49 
to -14a 
Day -14 
Baseline 
Day 1 
Week 1 
(Day 8) 
Week 2  
(Day 15) 
Week 4  
(Day 29) 
Week 8 
(Day 57) 
Week 12 
(Day 85) 
Week 16  
(Day 113)  
& Week 20 
(Day 141) 
Week 24 
(Day 169) 
or Early 
WD  
5 days 
after last 
dose or 
Early WD 
Visit Window 
  
r 4  
days 
 
+4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 2  
days 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Subject entry into IWRS and 
subject registry 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion and Exclusion 
Criteria Review 
X 
X 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical History (includes 
drugs, alcohol, and tobacco 
usage) 
X 
 
 
 
 
 
 
 
 
 
 
Prior OAB and BPH 
medication review  
X 
 
 
 
 
 
 
 
 
 
 
AE/SAE Review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medication 
Review  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IPSSc  
X 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
PGIc  
 
 
X 
 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signsd and Orthostatic 
Blood Pressure 
Xe 
Xe 
Xe 
X 
Xe 
Xe 
X 
X 
X 
X 
 
Brief Physical Examination 
X 
 
X 
 
 
 
 
X 
 
X 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 


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Screening Run-in 
 
Double-blind Treatment 
 
Safety  
Follow-up 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visits 
9 & 10 
Visit 11 
or Early 
WD 
Telephone 
Callb 
Day/Week 
Day -49 
to -14a 
Day -14 
Baseline 
Day 1 
Week 1 
(Day 8) 
Week 2  
(Day 15) 
Week 4  
(Day 29) 
Week 8 
(Day 57) 
Week 12 
(Day 85) 
Week 16  
(Day 113)  
& Week 20 
(Day 141) 
Week 24 
(Day 169) 
or Early 
WD  
5 days 
after last 
dose or 
Early WD 
PVR Volume 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Prostate Volumef 
Measurement (via ultrasound) 
X 
 
 
 
 
 
 
 
 
X 
 
Uroflowmetry 
X 
 
X 
 
 
 
 
 
 
X 
 
Laboratory Assessmentsg  
X 
 
X 
 
 
X 
 
X 
 
X 
 
Review and Data Enter 
Completed Bladder Diaryg 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Dispense Bladder Diaryh  
X 
X 
 
X 
X 
X 
X 
X 
X 
 
 
Dispense Run-in Study Drug 
 
X 
 
 
 
 
 
 
 
 
 
Dispense Double-blind 
Study Drug 
 
 
X 
 
 
X 
X 
X 
X 
 
 
Administer Witnessed Dose 
of Study Drug 
 
X 
X 
 
X 
X 
 
 
 
 
 
AE = adverse event; BPH = benign prostatic hypertrophy; ECG = electrocardiogram;
 IPSS = 
International Prostate Symptom Score; IWRS = interactive web response system;
PGI = Patient Global Impression; 
OAB = overactive bladder; PRO = patient-reported outcomes; PVR = Post-void residual; SAE = serious adverse event; WD = withdrawal  
a 
All Screening procedures and the 3-day Bladder Diary must be completed prior to the Run-In (Visit 2).  
b The Safety Follow-up is not applicable for subjects who enter the extension study (URO-901-3006). 
c 
PRO questionnaires should be completed prior to other procedures, including vital signs, blood draws, and study drug dosing. 
d Vital signs (including blood pressure [in triplicate], pulse, body temperature, respiration rate, and weight) should be taken prior to blood draws and study drug dosing; height is 
measured at Screening only. 
e 
For visits with orthostatic blood pressure, blood pressure (in triplicate) and heart rate (by pulse) taken in both sitting and standing positions, measurements will be taken pre-
dose, 1 hour post dose, 2 hours post dose, 4 hours post dose, and 6 hours post dose. Post dose assessments of blood pressure and pulse may be r 15 minutes of the scheduled 
timepoints. Refer to Section 8.3.2 for additional details and requirements. 
f 
A historical prostate volume by ultrasound, performed within 12 months prior to the first day of Screening, is acceptable, if the criteria detailed in Section 8.3.8 are satisfied.  
g Blood draws should be performed after all PRO and vital sign assessments, with the exception of visits for which orthostatic blood pressure assessments are performed. During 
those visits, the blood draws may be performed after the 4-hour post dose blood pressure assessment, provided they are completed at least 45 minutes prior to the 6-hour post 
dose blood pressure assessment. Refer to Section 10.2 for a list of laboratory assessments performed.  
h 
Subject completes the Bladder Diary PRIOR TO each visit. 


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1.4. 
Schedule of Assessments - Part 2 
 
Screening Run-
in 
 
Double-blind Treatment 
 
Safety  
Follow-up  
 
Visit 1 Visit 2 
Visit 3 
Visit 4 
Telephone/ 
Video Call 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Telephone/ 
Video Call 
Visit 10 
Visit 11 
or Early 
WD 
Telephone/ 
Video Callb 
Day/Week 
Day -49 
to -14a 
Day -
14 
Baseline 
Day 1 
Week 1  
(Day 8) 
Week 2 
(Day 15) 
Week 
4 (Day 
29) 
Week 8 
(Day 57) 
Week 
12 (Day 
85) 
Week 16  
(Day 113) 
Week 20 
(Day 141) 
Week 24 
(Day 169) or 
Early WD  
5 days after 
last dose or 
Early WD 
Visit Window 
 
r 4  
days 
 
+4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 2  
days 
COVID Mitigation 
Window* 
 
 
 
None 
+ 10 
days 
+ 3 
weeks 
+ 3 
weeks 
+6 
weeks 
None 
+ 3 
weeks 
+ 3 weeks 
None 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Subject entry into IWRS and 
subject registry 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and Exclusion 
Criteria Review 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History (includes 
drugs, alcohol, and tobacco 
usage) 
X 
 
 
 
 
 
 
 
 
 
 
 
Prior OAB and BPH 
medication review 
X 
 
 
 
 
 
 
 
 
 
 
 
AE/SAE Review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medication 
Review  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IPSSc  
X 
 
X 
 
 
X 
X 
X 
 
X 
X 
 
 
 
PGIc  
 
 
X 
 
 
X 
 
X 
 
 
X 
 
 
Vital Signsd 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
X 
 
Brief Physical Examination 
X 
 
X 
 
 
 
 
X 
 
 
X 
 


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Screening Run-
in 
 
Double-blind Treatment 
 
Safety  
Follow-up  
 
Visit 1 Visit 2 
Visit 3 
Visit 4 
Telephone/ 
Video Call 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Telephone/ 
Video Call 
Visit 10 
Visit 11 
or Early 
WD 
Telephone/ 
Video Callb 
Day/Week 
Day -49 
to -14a 
Day -
14 
Baseline 
Day 1 
Week 1  
(Day 8) 
Week 2 
(Day 15) 
Week 
4 (Day 
29) 
Week 8 
(Day 57) 
Week 
12 (Day 
85) 
Week 16  
(Day 113) 
Week 20 
(Day 141) 
Week 24 
(Day 169) or 
Early WD  
5 days after 
last dose or 
Early WD 
Visit Window 
 
r 4  
days 
 
+4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 4  
days 
r 2  
days 
COVID Mitigation 
Window* 
 
 
 
None 
+ 10 
days 
+ 3 
weeks 
+ 3 
weeks 
+6 
weeks 
None 
+ 3 
weeks 
+ 3 weeks 
None 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
PVR Volume 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
X 
 
Prostate Volumee 
Measurement (via 
ultrasound) 
Xe 
 
 
 
 
 
 
 
 
 
 
 
Uroflowmetry 
X 
 
 
 
 
 
 
 
 
 
X 
 
Urodynamicsf 
X 
 
 
 
 
X 
 
 
 
 
Laboratory Assessmentsg  
X 
 
X 
 
 
X 
 
X 
 
 
X 
 
Dispense Bladder Diaryh  
X 
X 
X 
 
X 
X 
X 
X 
 
X 
 
 
Dispense Run-in Study 
Drug 
 
X 
 
 
 
 
 
 
 
 
 
 
Dispense Double-blind 
Study Drugi 
 
 
X 
 
 
X 
X 
X 
 
X 
 
 
Administer Witnessed Dose 
of Study Drug 
 
X 
X 
 
 
 
 
 
 
 
 
 
AE = adverse event; BPH = benign prostatic hypertrophy; ECG = electrocardiogram;
 IPSS = 
International Prostate Symptom Score; IWRS = interactive web response system; OAB = overactive bladder; 
PGI = 
Patient Global Impression; PRO = patient-reported outcomes; PVR = Post-void residual; SAE = serious adverse event; WD = withdrawal  
NOTE:  Certain study assessments and procedures also may be performed remotely to minimize contact, as outlined in Section 8.6.  
* To account for additional time that may be necessary to ensure safety through COVID-19 preventive measures, a COVID Mitigation Window, with extended windows for visit 
timings, has been implemented. However, if safe and feasible, study visits should adhere to the schedule outlined Visit Window when. 
a 
With the exception of prostate volume measurement (which can be completed any time prior to randomization), all Screening procedures and the initial 3-day Bladder Diary 
must be completed prior to Run-In (Visit 2).  
b The Safety Follow-up is not applicable for subjects who enter the extension study (URO-901-3006). 


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d Vital signs (including blood pressure [triplicate], pulse, body temperature, respiration rate, and weight) should be taken prior to blood draws and study drug dosing; height is 
measured at Screening only. 
e 
A historical prostate volume measurement by ultrasound, performed within 12 months prior to the first day of Screening, is acceptable if the criteria detailed in Section 8.3.8 
are satisfied. For subjects with no acceptable historical measurement, a prostate volume measurement by ultrasound must be completed prior to randomization 
(Baseline/Visit 3). 
f 
Urodynamics procedure only applies to the Urodynamics sub-study of 60 subjects. Subjects will provide an additional urodynamics sub-study consent at Screening. A 
historical urodynamics assessment, performed at the site within 6 months prior to screening, will be acceptable. For subjects with no acceptable historical trace, a urodynamics 
assessment must be completed prior to randomization (Baseline/Visit 3). The Week 12 urodynamics assessment may be conducted on a different day than the Week 12 visit if 
it is done within the ±4 day visit window. All assessments (historical/ Baseline and Week 12) must be performed using the same urodynamics equipment and procedure (fill 
rate, catheter size, fluid, etc). 
g Blood draws should be performed after all PRO and vital sign assessments. Refer to Section 10.2 for a list of laboratory assessments performed. 
h Refer to Table 1 for details on when subjects should complete the Bladder Diary for each study timepoint. Note that the Bladder Diary may be dispensed or returned remotely 
(ie, delivered by mail, courier, or curbside pickup) and may be dispensed at an earlier timepoint. If dispensing in-person, ensure an adequate supply of diaries is provided 
(eg, diaries to be completed by the subject prior to Week 2 are dispensed at Baseline, and diaries to be completed by the subject prior to Week 16 and Week 20 are dispensed 
at Week 12). 
i 
For visits that occur after Baseline, double-blind study drug may be dispensed to the subject by means other than by in-person contact (eg, via curbside pickup, trackable 
courier, or another method approved by the Sponsor/CRO).  
 
 


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Table 1 
Bladder Diary Completion Schedule 
Diary Completion 
Timepoint 
Run-In 
Baseline 
Week 2 
Week 4 
Week 8 
Week 12 
Week 16 
Week 20 
Week 24  
(Day 169) 
Begin 3-day Diary 
At least 3 Days 
prior to Run-In 
Visit 
3 to 7 Days 
prior to 
Baseline Visit 
Day 8 to 12 
 
Day 22 to 26 
Day 50 to 54 
Day 78 to 82 
 
Day 106 to 110 
Day 134 to 138 
Day 162 to 166 
Acceptable 
completion window 
After Initial 
Screening Visit 
and prior to 
Run-In Visit 
7 Days prior to 
Baseline Visit 
 
Days 8 to 14 
 
Days 22 to 28 
Days 50 to 56 
Days 78 to 84 
 
Days 106 to 
112 
Days 134 to 
140 
Days 162 to 168 
NOTES:  
• 
Subjects will complete the diary for 3 days (72 hours) in a row in the 7 days prior to each Diary Completion timepoint, during which they will be asked to record 
information in their diary every time they urinate in the toilet or whenever they have urinary urgency or urinary incontinence (accidental loss of urine). 
• 
On one of the 3 Diary Completion days, subjects will measure how much urine they produce for 24 consecutive hours and enter the volume in the diary. Subjects may 
choose which of the 3 Diary Completion days they will measure urine. 
• 
The study staff will call subjects before each 3-day diary period to remind them to complete the diary.  
• 
Subjects will be given Bladder Diaries and a container to measure the urine for each applicable timepoint.  
• 
Diaries may be dispensed and/or returned remotely (eg, by mail, courier, or curbside pickup). If dispensing in-person ensure an adequate supply of diaries is provided 
(eg, diaries to be completed by the subject prior to Week 2 are dispensed at Baseline, and diaries to be completed by the subject prior to Week 16 and Week 20 are 
dispensed at Week 12). 


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2. 
Introduction 
2.1. 
Study Rationale 
Vibegron is currently in Phase 3 clinical development for the treatment of overactive bladder 
(OAB) in women and men. This study is intended to evaluate use of vibegron for the treatment 
of persistent OAB symptoms in the subpopulation of men with benign prostatic hypertrophy 
(BPH) on pharmacological therapy. 
Men with OAB symptoms associated with BPH represent an OAB subpopulation that has not 
been extensively studied. Oftentimes in these patients, OAB symptoms remain inadequately 
addressed despite treatment for their BPH (ie, alpha-blocker with or without 5α-reductase 
inhibitors [5-ARIs]). For reasons described below, this population warrants specific clinical 
studies to adequately evaluate and address their unique medical needs. Study URO-901-3005 is 
designed to be a large (planned N = 1088 subjects), Phase 3, randomized, double-blind, placebo-
controlled, parallel-group, multicenter study to evaluate the safety, tolerability, and efficacy of 
vibegron (75 mg once daily [QD] administered for 24 weeks) in men with symptoms of OAB 
(ie, ≥ 8 and ≤ 20 micturition episodes per day and urgency episodes of ≥ 3 per day) on 
pharmacological therapy for BPH.  
2.2. 
Background 
2.3. 
Overactive Bladder in Men with Benign Prostatic Hyperplasia 
OAB is highly prevalent and affects approximately 16% of the population in the United States 
and Europe. Prevalence increases with age, affecting approximately a third of people 75 years 
and older [Stewart, 2003; Milsom, 2001]. Despite similar prevalence between the sexes and 
growing clinical trial evidence that men benefit from pharmacotherapy, men are less likely to use 
treatment for OAB [Goldman, 2016].  
The International Continence Society (ICS) defines OAB as urgency, with or without urge 
incontinence, usually associated with frequency and nocturia [Abrams, 2002]. Urgency is 
defined as a sudden compelling desire to void which is difficult to defer and, from the medical 
definition perspective, it is a necessary symptom for OAB. Urgency incontinence is the 
involuntary loss of urine accompanied by urgency (referred to as OAB Wet) and is present in 
approximately one-third of patients with OAB [Stewart, 2003; Milsom, 2001]. In the absence of 
incontinence, OAB is referred to as OAB Dry. Urgency incontinence is distinguished from stress 
urinary incontinence, which is the involuntary loss of urine on effort or physical exertion 
(eg, sporting activities), or upon sneezing or coughing. When both components are present, the 
classification is mixed urinary incontinence, with either urgency or stress specified as the 
predominant component.  


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Although the overall prevalence of OAB in men and women is similar, there are major 
differences in predominating symptoms. Men are more likely to experience urgency, frequency, 
and nocturia accompanied by lower urinary tract symptoms (LUTS) associated with voiding 
dysfunction, whereas women are twice as likely to experience incontinence [Tubaro, 2017]. 
Since most men with OAB symptoms do not have urinary incontinence, the micturition 
frequency and the urgency become the predominant symptoms that characterize the disease for 
the men with OAB on pharmacological therapy for BPH [Helfand, 2012]. Among men, urinary 
incontinence significantly increases after the age of 65 years.  
Historically in men with BPH, LUTS have been presumed to result from bladder outlet 
obstruction secondary to prostate enlargement. However, men may have OAB symptoms in the 
absence of, or in conjunction with, voiding symptoms associated with BPH or urodynamic 
evidence of bladder outlet obstruction [Nakagawa, 2008; Hyman, 2001]. BPH can be associated 
with debilitating LUTS, categorized by storage symptoms (eg, urinary frequency, urgency, and 
nocturia) and voiding dysfunction (eg, decreased and intermittent force of stream and the 
sensation of incomplete bladder emptying).  
2.3.1. 
Vibegron 
Initial pharmacologic therapy for OAB symptoms in men with BPH traditionally has been 
directed at minimizing the obstruction, and has included α1-adrenergic receptor antagonists to 
relax the muscles of the prostate and bladder neck or 5-ARIs to reduce prostate growth 
[American Urological Association, 2010]. While patients may see some improvement in OAB 
symptoms with these BPH therapies (eg, improvement in urinary flow), symptom control for 
OAB symptoms is incomplete, for many, and urinary urgency, incontinence, frequency, or 
nocturia persists [Abrams, 2002]. To address persistent OAB symptoms in men with BPH, 
combinations of BPH therapies with OAB medications, such as anticholinergics, have shown 
promise [Chapple, 2009; Oelke, 2008]. However, the clinical use of anticholinergics is limited 
by mechanism-based side effects including dry mouth and constipation [MacDiarmid, 2008] and 
the potential for CNS adverse effects [Gray, 2015; Risacher, 2016]. Further, 
contraindications/precautions exist due to the possibility of urinary retention and bladder outflow 
obstruction [Detrol prescribing information, 2016].  
ß3-adrenoceptor (β3-AR) agonists for OAB (eg, mirabegron) have demonstrated efficacy in 
treating persistent OAB symptoms in men on BPH therapies [Ichihara, 2014] with a more 
favorable safety profile relative to the anticholinergics. In fact, experts have recommended that 
these agents be specifically studied in this patient population [Maman, 2014; Chapple, 2009; 
Van Kerrebroeck, 2001; Chapple, 2017].  
Vibegron is a potent and highly selective β3-AR agonist demonstrating > 9000-fold selectivity 
for activation of E3-AR over E2-AR and E1-AR in cell based in vitro assays. β-adrenergic 
receptors are prototypic G-protein coupled receptors expressed on the surface of cells, and 
mediate intracellular signaling via coupling to Gs and increasing levels of intracellular cyclic 


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adenosine monophosphate (cAMP). β3-ARs are widely distributed in humans and are the most 
prevalent β-AR subtype expressed on human detrusor smooth muscle [Takeda, 2000]. In isolated 
human bladder smooth muscle, activation of β3-AR using subtype-selective agonists results in 
smooth muscle relaxation suggesting a role for β3-AR agonists during the filling phase of the 
micturition cycle [Yamaguchi, 2002; Biers, 2006]. In rodent models of bladder over activity, β3-
AR agonists relax bladder smooth muscle and suppress detrusor smooth muscle instability and 
hyperreflexia [Takeda, 2000; Woods, 2001; Takeda, 2002; Kaidoh, 2002]. In rhesus monkeys, 
dose-dependent increases in bladder capacity and decreases in micturition pressure were 
observed with vibegron. Bladder capacity was further increased by vibegron in combination with 
tolterodine or darifenacin [Di Salvo, 2017]. These results have supported a large and 
comprehensive clinical development program for vibegron in the general OAB population, 
including both male and female subjects. 
More than 2300 subjects (including 1840 with OAB and 460 healthy volunteers) have received 
vibegron in Phase 1, 2, and 3 clinical studies. Assessment of safety laboratory parameters and 
mean vital sign values over time, including heart rate and blood pressure, showed no clinically 
meaningful differences for any active treatment group relative to placebo or anti-muscarinic 
comparators. A large, multicenter Phase 3 study of vibegron for the treatment of OAB in women 
and men is ongoing. Discontinuation rates due to adverse events (AEs) were low (< 5%) in all 
clinical studies conducted to date with vibegron. In a completed Phase 3 study in Japan in more 
than 1200 subjects with symptoms of OAB, there were no notable mean changes in post-voided 
residuals observed [Yoshida, 2018]. A more detailed description of vibegron, including 
pharmacology, efficacy, and safety data in overactive bladder, is provided in the Investigator’s 
Brochure.  
2.4. 
Benefit/Risk Assessment 
2.4.1. 
Potential Benefits 
Vibegron’s mechanism of action has the potential to demonstrate significant therapeutic benefit in 
the treatment of OAB symptoms in men with BPH on pharmacological therapy for their BPH 
symptoms. 
2.4.2. 
Potential Risks 
The initial clinical program for vibegron in the treatment of OAB included subjects of both 
sexes. The Phase 3 program in OAB (RVT-901-3003 and RVT-901-3004) included 
approximately 15% males, contributing safety data comprising 217 men in addition to those 
enrolled in Study URO-901-3005.  More detailed information about the known and expected 
benefits and risks from the study and reasonably expected AEs of vibegron may be found in the 
Investigator’s Brochure. 


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Based on aggregate preclinical, clinical pharmacology, and Phase 2 and 3 studies, AEs of special 
interest (AESIs) were predefined for specific evaluations in vibegron clinical studies as follows:  
x Potential major cardiovascular events 
x Hypertension 
x AEs suggestive of orthostatic hypotension 
x AEs suggestive of cystitis or urinary tract infection 
x Elevated aspartate transaminase (AST) or alanine transaminase (ALT) laboratory value 
requiring that the study drug be temporarily withheld or permanently discontinued 
x Neoplasm 
In addition, the risk for increases in post void residual urine volume and urinary volume will be 
closely monitored for post-void retention during the study. The study’s enrollment criteria will 
exclude men with PVR volume ≥ 100 mL at screening and at baseline and those with maximum 
urinary flow (Qmax) less than 5 mL/second. Post-void residual urine volume will be assessed 
throughout the study, and subjects with a single PVR volume of ≥ 300 mL or an AE of urinary 
retention will be withdrawn.  
Prespecified definitions of urinary retention and other AESIs are provided in the Adverse Event 
of Special Interest section (Section 8.4.6).  


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3. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary Efficacy 
x 
To assess the efficacy of vibegron 
compared with placebo in men with 
OAB symptoms on pharmacological 
therapy for BPH as defined by 
micturition and urgency episodes 
Secondary Efficacy 
x 
To assess the efficacy of vibegron 
compared with placebo in men with 
OAB symptoms on pharmacological 
therapy for BPH as defined by other key 
measures 
Safety 
x 
To assess the safety and tolerability of 
vibegron compared with placebo in men 
with OAB symptoms on 
pharmacological therapy for BPH 
 
Other Efficacy 
Primary Efficacy 
x 
CFB at Week 12 in the average number of micturition 
episodes per day 
x 
CFB at Week 12 in the average number of urgency 
episodes (urgency: need to urinate immediately) per 
day 
Secondary Efficacy 
x 
CFB at Week 12 in the average number of nocturia 
episodes per night  
x 
CFB at Week 12 in the average number of urge urinary 
incontinence episodes per day for subjects with urinary 
incontinence at baseline  
x 
CFB at Week 12 in the IPSS Storage score (1-week 
recall) 
x 
CFB at Week 12 in the average volume voided per 
micturition 
 
Safety 
x 
AEs, concurrent medications, clinical laboratory, vital 
sign assessments, PVR volume, uroflow measures, 
IPSS, urodynamics (sub-study only) 
 
Other/Exploratory - Efficacy 
x 
CFB at Week 2, Week 4, Week 8, Week 16, Week 20 
and Week 24 in the average number of micturition 
episodes per day 
x 
CFB at Week 2, Week 4, Week 8, Week 16, Week 20, 
and Week 24 in the average number of urgency 
episodes per day 
x 
CFB at Week 2, Week 4, Week 8, Week 16, Week 20 
and Week 24 in the average number of nocturia 
episodes per night  
x 
CFB at Week 4, Week 8, Week 20, and Week 24 in the 
IPSS Storage score (1-week recall) 
x 
CFB at Week 4, Week 8, Week 12, Week 20, and 
Week 24 in the IPSS Quality of Life score (1-week 
recall) 
x 
CFB at Week 4, Week 8, Week 12, Week 20, and 
Week 24 in the IPSS Voiding score (1-week recall) 
x 
CFB at Week 2, Week 4, Week 8, Week 16, Week 20, 
and Week 24 in the average number of urge urinary 
incontinence episodes per day for subjects with urinary 
incontinence at baseline 
x 
CFB at Week 2, Week 4, Week 8, Week 16, Week 20, 
and Week 24 in the average volume voided per 
micturition 
x 
CFB at Week 2, Week 4, Week 8, Week 12, Week 16, 
Week 20, and Week 24 in the average number of total 
incontinence episodes per day for subjects with urinary 
incontinence at baseline 


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x 
Percent of all subjects with a 50% reduction from 
baseline in average urgency episodes (urgency: need to 
urinate immediately) per day at Week 2, Week 4, 
Week 8, Week 12, Week 16, Week 20, and Week 24 
x 
Percent of subjects with urinary incontinence at 
baseline with a 75% reduction from baseline in average 
urge urinary incontinence episodes per day at Week 2, 
Week 4, Week 8, Week 12, Week 16, Week 20, and 
Week 24 
Other/Exploratory - Quality-of-Life 
x 
CFB at Week 12 in Symptom Bother Score as assessed 
by 
, 1-week recall) 
x 
CFB at Week 12 in HRQL total score as assessed by 
 (HRQL includes subscales: coping, 
concern, sleep and social interaction. The total score 
will be calculated by adding the 4 subscales scores.) 
x 
CFB at Week 12 and Week 24 in HRQL subscale 
Coping score as assessed by 
 
x 
CFB at Week 12 and Week 24 in HRQL subscale 
Concern score as assessed by 
  
x 
CFB at Week 12 and Week 24 in HRQL subscale 
Sleep score as assessed by 
 
x 
CFB at Week 12 and Week 24 in HRQL subscale 
Social Interaction score as assessed by 
 
x 
CFB at Week 12 and Week 24 in
as 
assessed by measure of health stat
nnaire 
developed by the EuroQolGroup 
x 
CFB at Week 4, Week 12, and Week 24 in overall 
bladder symptoms based on 
 
x 
CFB at Week 4, Week 12, and Week 24 in overall 
control over bladder symptoms based on
 
x 
CFB at Week 4, Week 12, and Week 24 in overall 
symptom frequency based on
 
x 
CFB at Week 4, Week 12, and Week 24 in overall 
urgency-related leakage over bladder symptoms based 
on
 in subjects with urinary 
incontinence at baseline 
x 
Overall change of bladder symptoms based on
at 
Week 4, Week 12, and Week 24 
x 
CFB at Week 12 and Week 24 in the
 
 
Note: “per day” refers to a continuous 24-hour period. 
Abbreviations: AE = adverse events; BPH = benign prostatic hypertrophy; CFB = change from baseline; HRQL = health-related 
quality of life;
 IPSS = International Prostate Symptom Score; OAB = overactive 
bladder;
PGI = Patient Global Impression; QoL = quality of life; PVR 
= post-void residual 


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4. 
Study Design 
4.1. 
Overall Design 
This is a Phase 3, randomized, double-blind, placebo-controlled, 2-part, parallel-group, 
multicenter study to evaluate the safety, tolerability, and efficacy of vibegron 75 mg in men with 
symptoms of OAB on stable doses of pharmacological therapy for BPH. At Baseline, subjects 
who meet all eligibility criteria are randomized 1:1 to receive either vibegron 75 mg, or placebo 
in a double-blind fashion. Randomization will be stratified based on baseline average number of 
micturition episodes per day (≤ 12 vs > 12), alpha blocker use with or without 5-ARI (yes or no), 
and urinary incontinence (yes or no).  
The study consists of two parts: Part 1 (approximately 80 subjects) and Part 2 (approximately 
1008 subjects). Part 2 will proceed following review of 4-week safety data (including orthostatic 
blood pressure results) of all 80 subjects from Part 1 by an independent DSMB. The independent 
DSMB will review the safety data throughout the entire study. The 2 study parts are of the same 
overall design as outlined below but with the following exceptions: 
x Part 1 includes additional orthostatic blood pressure and heart rate measurements at 
Screening, Run-in, Baseline, Week 2, and Week 4 to assess for potential orthostatic 
changes (pre-dose through 6 hours post dose, except pre-dose for Screening and Run-In).  
x Part 2 will include a urodynamics sub-study (approximately 60 subjects), which is 
described in detail in Section 8.3.7. 
o The rate of enrollment into both the main study and the urodynamics sub-study 
will be closely monitored. In the case of a discrepancy between the estimated date 
of completion of enrollment in the urodynamics sub-study and the main study, a 
decision may be made to continue enrolling only those subjects who are willing to 
participate in the urodynamics sub-study. 
Both study parts will consist of a Screening Period (approximately 1 to 4 weeks), a single-blind 
therapy plus placebo Run-in Period (approximately 2 weeks), and a randomized double-blind 
Treatment Period (24 weeks).  
Study visit schedules: Visit 1 (Screening), Visit 2 (Run-in), Visit 3 (Baseline), Visit 4 (Week 1), 
Visit 5 (Week 2), Visit 6 (Week 4), Visit 7 (Week 8), Visit 8 (Week 12), Visit 9 (Week 16), Visit 
10 (Week 20), and Visit 11 (Week 24) (End of the Treatment). For subjects enrolled in Part 2 
after implementation of Protocol Amendment #2, Visit 4 (Week 1) and Visit 9 (Week 16) will be 
conducted remotely (via telephone or video call). 
Subjects who complete the Week 24 Visit may be offered the opportunity to enroll in a 28-week 
extension study URO-901-3006, which will be conducted under a separate study protocol. 
Subjects who do not enroll into the extension study will have a Safety Follow-up telephone call 


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approximately 5 days (± up to 2 days) after the subject’s last dose of study treatment (ie, or 
approximately 5 days [± up to 2 days] after withdrawal for subjects who discontinue the study 
early). Additionally, Unscheduled Visit(s) may be arranged as needed.  
Approximately 1088 subjects (544 per treatment group: 80 total in Part 1 and 1008 total in 
Part 2) will be randomized at up to approximately 135 sites in North America (United States and 
Canada) and Europe to have 924 subjects complete the study (assuming a 15% dropout rate). The 
sample size justification is provided in Section 9.2.  
4.2. 
Scientific Rationale for Study Design 
A single-blind, placebo Run-in Period will be used to assess placebo response and to ensure that 
subjects have adequate experience with dosing compliance and completing the Bladder Diaries. 
The double-blind Treatment Period will include a placebo arm to accurately demonstrate and 
measure the efficacy of vibegron. The clinical use of anticholinergics is limited by adverse 
effects and, notably, contraindications and precautions unique to men with OAB symptoms 
receiving treatment for BPH due to the possibility of urinary retention and bladder outflow 
obstruction. ß3-adrenoceptor agonists have shown efficacy (with improved safety relative to 
anticholinergics) in treating persistent OAB symptoms in men on BPH therapies 
[Ichihara, 2014]; however, no therapeutic agents are labeled specifically for this population, and 
clinical study data have been limited. In addition, this population has a distinct symptom profile 
and relevant efficacy needs (eg, nocturia) that warrant further study.   
4.2.1. 
Clinical Hypotheses 
The primary efficacy hypothesis is that vibegron + BPH pharmacological therapy is more 
effective than placebo + BPH pharmacological therapy in reducing both the mean daily 
micturition episodes and the mean daily urgency episodes, based on results from a 3-day diary. 
The safety hypothesis is that the vibegron + BPH pharmacological therapy is safe and tolerable 
in men with BPH with OAB. 
4.3. 
Justification for Dose 
This study will use a vibegron dose of 75 mg administered orally QD, which is the same dose 
used throughout the Phase 3 vibegron clinical program for the general OAB indication in both 
men and women. A placebo control was considered appropriate and justified because no active 
agents have been fully evaluated or approved specifically in this patient population. 
4.4. 
End of Study Definition 
The end of the study is defined as the date that the last subject has completed the study (ie, 
completes Week 24 Visit for subjects who enroll into Study URO-901-3006 or Safety Follow-up 
for subjects who do not enroll into Study URO-901-3006), discontinued from the study, or are 
lost to follow-up.  


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5. 
Study Population 
The study is being conducted in men with OAB symptoms while receiving pharmacological 
therapy for BPH. Specific inclusion and exclusion criteria are specified below. Prospective 
approval of protocol deviations to recruitment and enrollment criteria, also known as protocol 
waivers or exemptions, is not permitted; however, subjects may be rescreened once to meet 
inclusion criteria.  
5.1. 
Inclusion Criteria 
At the Visit 1 (Screening) visit (and other timepoints as noted), a subject will be eligible for 
inclusion in this study only if all of the following criteria apply, unless otherwise noted: 
1. Capable of giving written informed consent, which includes compliance with the 
requirements and restrictions listed in the consent form. 
2. Male subjects of 45 years of age and above. 
3. Body weight t 50 kg (inclusive).  
4. 
Subject should have been on and agree to continue to stay on a stable dose of BPH treatment 
with either a) alpha blocker monotherapy or b) alpha blocker + 5 ARI. Subjects on alpha 
blockers should have started their therapy at least 3 months prior to screening and be on a 
stable dose at the start of screening. Subjects on a 5-ARI should have started therapy at least 
6 months prior to screening and be on a stable dose at screening. 
5. Has a history of overactive bladder symptoms (frequency of ≥ 8 micturition episodes per 
day and urgency episodes of ≥ 3 per day with or without incontinence) while taking 
pharmacological therapy for at least 2 months to treat LUTS due to BPH. 
6. Subject has an IPSS total score of ≥ 8 at Screening and Visit 3 (Baseline). 
7. Subject has a prostate-specific antigen (PSA) level < 4 ng/mL, or if ≥ 4 ng/mL but 
≤ 10 ng/mL, prostate cancer has been ruled out to the satisfaction of the investigator. 
8. Subjects agrees to not participate in another interventional drug or device clinical trial 
during the study. 
9. In the opinion of the investigator, is able and willing to comply with the requirements of the 
protocol, including completing study questionnaires and the Bladder Diary. 
10. At Visit 2 (Run-in) and Visit 3 (Baseline) visits, subject must have both additional 
qualifications based on the 3-day Bladder Diary period: a) having an average of ≥ 8 but 
≤ 20 micturition episodes per day over the 3-day diary period, and (b) having an average of 
≥ 3 urgency episodes per day over the 3-day diary period.  
11. Subject must have a post void residual (PVR) volume value of < 100 mL at Screening, 
Visit 2 (Run-In) and Visit 3 (Baseline). 


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12. At Visit 2 (Run-in) and Visit 3 (Baseline) visits, having at least 2 average nocturia episodes 
per night based on 3-day Bladder Diary at baseline. Nocturia is defined as waking to pass 
urine during the main sleep period. 
5.2. 
Exclusion Criteria 
At the Visit 1 (Screening) visit (and other timepoints as noted), a subject will not be eligible for 
inclusion in this study if any of the following criteria apply, unless otherwise noted: 
1. Subject has a history of 24-hour urine volume greater than 3,000 mL or over 3,000 mL 
based on 3-day Bladder Diary at Visit 2 (Run-In) or Visit 3 (Baseline) visits. 
2. Subject is a night-shift worker or plans to become a night-shift worker during the study. 
3. Has lower urinary tract pathology that could, in the opinion of the investigator, be 
responsible for urgency, frequency, or incontinence; including, but not limited to, bladder 
stones, interstitial cystitis, prostate cancer, persistent urethral stricture, urogenital 
tuberculosis, and urothelial tumor.  
4. Has a history of prostate surgery, including minimally invasive transurethral or transrectal 
procedures, procedural treatments for BPH within 6 months of Screening or has a planned 
prostate surgery, including minimally invasive prostate procedures, during the study period. 
Has a previous or planned pelvic radiation, low anterior resections (LAR), or any 
abdominoperineal resections (APR) during the study period.  
5. Subject had prostatitis in the past 6 months. 
6. Has a history of urinary retention requiring an intervention (eg, catheterization) for any 
reason. 
7. Irregular use of long-acting medications (eg, tadalafil) to treat erectile dysfunction (ED). 
Note: ED medications with a short half-life such as sildenafil and vardenafil may be used on 
an irregular basis. 
8. Subject has any planned procedures to treat ED (eg, implantation of a penile device) during 
the treatment period, or has any planned prostate procedure. 
9. Subject is using any herbal medications to treat overactive bladder, lower urinary tract 
symptoms/BPH symptoms, or erectile dysfunction in the past 28 days prior to Screening. 
10. Subject started using diuretics within 28 days prior to Screening. Subjects already taking any 
diuretics on stable doses for at least 28 days prior to Screening are allowed to enroll to the 
study.  
11. Has maximum urinary flow (Qmax) < 5.0 mL/second with a minimum voided volume of 
125 mL at Screening. 
12. Has a history of or current nocturnal polyuria at Visit 2 (Run-In) or Visit 3 (Baseline) visits, 
based on 3-day Bladder Diary. Nocturnal polyuria is defined as more than one third of the 
total urine output per 24 hours occurring at night time. 
13. Has undergone bladder training or electrostimulation within 28 days prior to Screening or 
plans to initiate either during the study. 


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14. Has an active or recurrent (> 3 episodes per year) urinary tract infection by clinical 
symptoms or laboratory criteria (≥ 5 white blood cells [WBC]/hpf with presence of red 
blood cell [RBC] and/or a positive urine culture, defined as ≥ 105 colony forming units 
[CFU]/mL [ie, 100 × 103 CFU/mL] in a single specimen). Subjects diagnosed with a urinary 
tract infection (UTI) at the Screening Visit may be treated until the infection has resolved. 
15. Has received an intravesical or intraprostatic treatment with any botulinum toxin, 
resiniferatoxin, or capsaicin within 6 months prior to Screening Visit. 
16. Has an implanted sacral neurostimulation (SNS) or use of any posterior tibial nerve 
stimulation (PTNS) device.  
17. Has uncontrolled hyperglycemia (defined as fasting blood glucose > 150 mg/dL or 
8.33 mmol/L or non-fasting blood glucose > 200 mg/dL or 11.1 mmol/L) or, if in the 
opinion of the investigator, is uncontrolled. 
18. Has a prior diagnosis of diabetes insipidus. 
19. Has uncontrolled sleep apnea or has self-reported sleep apnea that has been neither 
confirmed nor diagnosed by a physician. (Note: Subjects with a prior diagnosis of sleep 
apnea who have been stable on treatment for ≥3 months prior to Screening or whose 
condition has resolved at least 3 months prior to Screening are not excluded based on this 
criterion.) 
20. Has a concurrent malignancy or history of any malignancy within 5 years prior to screening, 
except for adequately treated basal cell or squamous cell skin cancer. 
21. This exclusion criterion was removed with implementation of Amendment #1.  
22. Has history of clinically relevant liver disease or severe hepatic impairment (Child-Pugh 
Class C). 
23. Has clinically significant electrocardiogram (ECG) abnormality that, in the opinion of the 
investigator, exposes the subject to risk by participating in the study. 
24. Has uncontrolled hypertension (systolic blood pressure of ≥ 180 mmHg and/or diastolic 
blood pressure of ≥ 100 mmHg) or has a resting heart rate (by pulse) > 100 beats per minute. 
25. Subjects who have systolic blood pressures ≥ 160 mmHg but < 180 mmHg are excluded, 
unless deemed by the investigator as safe to proceed in this study and able to complete 
the study per protocol; All subjects taking anti-hypertensives must be on stable doses for at 
least 3 months prior to the Screening Visit. 
26. All subjects with signs and symptoms of uncontrolled hypertension, regardless of blood 
pressure measurement, are excluded from the study. These include, but are not limited to 
neurological symptoms or findings, hematuria, proteinuria, retinopathy, unstable angina, and 
acute heart failure. 
27. Has a history of cerebral vascular accident, transient ischemic attack, unstable angina, 
myocardial infarction, coronary artery interventions (eg, coronary artery bypass grafting or 
percutaneous coronary interventions [eg, angioplasty, stent insertion]), or neurovascular 
interventions (eg, carotid artery stenting) within 6 months prior to the Screening Visit. 


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Subjects with these conditions should be on stable medical therapy for at least 3 months 
prior to the Screening Visit. 
28. Has a history of injury, surgery, or neurodegenerative diseases (eg, multiple sclerosis, 
Parkinson’s) that could affect the lower urinary tract or its nerve supply. 
29. Has hematuria that was not evaluated, including microscopic hematuria (> 5 RBCs/hpf). 
Subjects with known, fully evaluated, benign hematuria may participate. Documentation 
must be obtained indicating an unremarkable upper urinary tract (kidneys and ureters) 
imaging study (eg, computerized tomography [CT] scan with and without contrast, renal 
ultrasound, magnetic resonance imaging [MRI], intravenous pyelogram, etc.) and 
cystoscopy. Subjects whose hematuria has not been previously evaluated may not be 
enrolled. 
30. Has alanine aminotransferase or aspartate aminotransferase > 2.0 times the upper limit of 
normal (ULN), or bilirubin (total bilirubin) > 1.5 x ULN (or > 2.0 x ULN if secondary to 
Gilbert syndrome or pattern consistent with Gilbert syndrome). 
31. Has an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2.  
32. Use of any prohibited medications as detailed in Section 6.5.1 (suitable washout periods 
from these medications are also described therein). 
33. Had changed the dose of any medications listed in Section 6.5.2 within 28 days prior to the 
Screening Visit or plans to initiate or change the dosing of any of these medications during 
the study. 
34. History of sensitivity to any of the study treatments, or components thereof or a history of 
drug or other allergy that, in the opinion of the investigator, contraindicates their 
participation. 
35. Is currently participating or has participated in a study with an investigational compound or 
device or procedure within 28 days prior to Screening Visit. 
36. Prior exposure to vibegron (either through clinical trial or commercial use). 
37. Has a history of significant drug or alcohol abuse/dependence within a year prior to 
screening, as assessed by the Investigator. 
38. Has coronary or neurovascular interventions planned during the duration of the study. 
39. Has a history or current evidence of any condition, therapy, laboratory abnormality, or other 
circumstances that might, in the opinion of the investigator, confound the results of the 
study, interfere with the subject’s ability to comply with the study procedure, or make 
participation in the study not in the subject’s best interest. 
40. At Visit 3 (Baseline), subject was non-compliant during the 2-week placebo -controlled run-
in period (taking < 80% or > 120% of the study medication). 
5.3. 
Lifestyle Considerations 
Not applicable for this study.  


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5.4. 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently randomized. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure subjects to meet the Consolidated Standards of Reporting 
Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any serious adverse event (SAE) that occurred within the Screening period. Individuals who 
do not meet the criteria for participation in this study (screen failures prior to initiation of run-in 
study medication) may be rescreened once upon consultation with, and approval by, the Sponsor 
or its designee. Subjects who initiate Run-in study drug dosing may not be rescreened. 
Rescreened subjects will be assigned a new subject number, and both subject numbers will be 
linked to the subject. 


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6. 
Study Drug 
6.1. 
Study Drugs Administered 
Table 2 provides a summary of the finished study drug products (vibegron and placebo). 
Table 2 
Summary of Study Drugs 
Study Drug Name 
Vibegron 
Matched Placebo 
Dosage Formulation 
tablet 
tablet 
Identity of Formulation 
75 mg 
placebo 
Route of 
Administration  
oral 
oral 
Dosing Instructions 
once daily 
once daily 
Packaging and Labeling 
Study drug will be provided in HDPE 
bottles with child-resistant caps. Each 
bottle will contain 32 tablets and will 
be labeled as required per country 
requirement. 
Study drug will be provided in HDPE 
bottles with child-resistant caps. Each 
bottle will contain 32 tablets and will 
be labeled as required per country 
requirement. 
Manufacturer 
Patheon, Cincinnati, Ohio, US 
Patheon, Cincinnati, Ohio, US 
Number and Timing of 
Drugs 
Treatment Period: 1 tablet daily  
Run-in Period: 1 tablet daily 
Treatment Period: 1 tablet daily 
HDPE = high density polyethylene 
The study drug will be supplied in bottles each containing 32 tablets (4-week supply) and labeled 
with the protocol number, bottle number, lot number, expiration date, study drug name (vibegron 
75 mg or placebo tablets) and number of tablets, directions for use, storage information, warning 
language (Keep Out of Reach of Children. For Clinical Trial Use Only. To be used by qualified 
investigators only. Caution: New Drug—Limited by United States Law to Investigational Use.), 
and the Sponsor name and address. Immediately before dispensing the study drug, the 
investigator (or appropriately trained designee) will write the subject number, visit no. and the 
dispense date on the detachable panel of the label, which also includes the protocol number, 
bottle number and lot number.  
To minimize in-person contact during the COVID-19 pandemic, double-blind study drug may be 
dispensed and delivered directly to the subject by means other than by in-person contact (eg, via 
curbside pickup, trackable courier, or another method approved by the Sponsor/CRO).  
6.1.1. 
Run-in Medications and Administration 
During the single-blind Run-in Period, all subjects will take 1 tablet of study drug (ie, placebo) 
once daily for approximately 2 weeks. All subjects will take their first dose of study drug at the 
study site as a witnessed dose. The date and time of the study drug dosing will be recorded. The 
investigator will be aware that the study drug is placebo, but the subject will not know the 


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identity of the treatment or that entry into the double-blind Treatment Period is dependent on 
compliance with dosing in the Run-in Period. The matched placebo will be identical in 
appearance to the study drug administered during double-blind treatment.  
6.1.2. 
Treatment Period Medications and Administration 
During the double-blind Treatment Period, subjects will take 1 tablet of study drug (vibegron or 
matched placebo) once daily for up to 24 weeks. The appearance of the vibegron and placebo 
tablets will be identical. All subjects will be administered a witnessed dose of study drug at the 
study site at Visit 3 (Baseline). Subjects in Part 1 additionally will be administered a witnessed 
dose of study drug at Visit 5 (Week 2) and Visit 6 (Week 4). The date and time of the study drug 
dosing will be recorded. 
6.2. 
Preparation/Handling/Storage/Accountability 
Clinical supplies must be stored in a secure, limited-access location under the storage conditions 
specified on the label. 
Receipt and dispensing of Study Treatment must be recorded by an authorized person at the 
study site. 
Clinical supplies may not be used for any purpose other than that stated in the protocol. 
The investigator is responsible for keeping accurate records of the clinical supplies received from 
the Sponsor or designee, the amount dispensed to and returned by the subjects, and the amount 
remaining at the conclusion of the study. These records will be monitored throughout the study. 
For all sites, the local country Sponsor personnel or designee will provide appropriate 
documentation that must be completed for drug accountability and return. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Single-blind (Run-in only) and double-blind (Treatment Period) techniques will be used. 
Vibegron and its matching placebo will be packaged identically so that the treatment blind is 
maintained. The subject, investigator, and Sponsor personnel or delegate(s) who are involved in 
the treatment or clinical evaluation of the subjects will be unaware of the treatment group 
assignments during the double-blind Treatment Period. Subjects will be centrally assigned to 
randomized study drug using an interactive web response system (IWRS) and the randomization 
schedule generated by the sponsor or designee. Before screening is initiated at each site, login 
information and directions for the IWRS will be provided.  
The IWRS will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a subject’s study drug 
assignment is warranted. Subject safety must always be the first consideration in making such a 
determination. If the investigator decides that unblinding is warranted, the investigator should 
make every effort to contact the Sponsor or designee prior to unblinding a subject’s study drug 
assignment unless this could delay emergency treatment of the subject. If a subject’s study drug 


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assignment is unblinded, the Sponsor or designee must be notified within 24 hours after breaking 
the blind. The date and reason that the blind was broken must be recorded in the source 
documentation. 
At the end of the study, the official, final database will be frozen and unblinded after 
medical/scientific review has been performed, and data have been declared final and complete. 
The Sponsor will be granted access to the unblinded database in order to analyze the data. A 
clinical study report will be prepared after all subjects complete the study. 
6.4. 
Study Drug Compliance 
Study drug compliance will be closely monitored by counting the number of tablets dispensed 
and returned. Before dispensing new study drug at applicable visits, study site personnel should 
collect all unused study drug and empty bottles. 
The study site will keep an accurate drug disposition record that specifies the amount of study 
drug administered to each subject and the date of administration. 
6.5. 
Concomitant Therapy 
The use of any concomitant medication, prescription or over-the-counter, is to be recorded on the 
subject’s electronic case report form (eCRF) at each visit along with the reason the medication is 
taken, the dates of administration, and the dose. 
6.5.1. 
Prohibited Drugs and Washout Before the Study 
Section 10.6 provides a listing of specific restrictions for concomitant therapy use during the 
study, with any necessary washout periods described and examples of prohibited drug categories. 
If there is a clinical indication for any therapy that is specifically prohibited during the study, 
discontinuation from Study Treatment may be required. The investigator should discuss any 
questions regarding this with the Sponsor’s representing Medical Monitor. The final decision on 
any supportive therapy rests with the investigator and/or the subject's primary physician. 
However, the decision to continue the subject on Study Treatment requires the mutual agreement 
of the investigator and the Sponsor’s designated Medical Monitor.  
Consult the Sponsor’s designated Medical Monitor if there is any uncertainty regarding subject 
use of a particular drug or drug class.  
6.5.2. 
Permitted Drugs 
With the exception of the agents described in Section 10.6, any other concomitant medication 
deemed necessary for the welfare of the subject during the study may be given at the discretion 
of the investigator. If the permissibility of a specific medication/drug is in question, please 
contact the Sponsor’s designated Medical Monitor. Any medication or vaccine (including over-


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the-counter or prescription medicines, vitamins, and/or herbal supplements) that the subject is 
receiving at the time of enrollment or receives during the study must be recorded in the eCRF. 
6.6. 
Dose Modification 
No dose modification of study drug is permitted. Study drug should be withheld for liver test 
abnormalities as described in Section 8.4.6.2. 
6.7. 
Drug After the End of the Study 
Subjects who complete the study through the Week 24 Visit may be offered the opportunity to 
enroll in a 28-week extension study (URO-901-3006), in which open-label vibegron will be 
provided. 


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7. 
Discontinuation of Study Drug and Subject Discontinuation or 
Withdrawal 
A premature discontinuation will occur if a subject who signs the informed consent form (ICF) 
and is randomized ceases participation in the study, regardless of circumstances, before the 
completion of the protocol-defined study procedures.  
7.1. 
Discontinuation of Study Drug 
Subjects who discontinue study drug will complete the Week 24/Early Withdrawal assessments 
specified in the Schedule of Assessments (Section 1.3 and Section 1.4).  
Reasons for discontinuation from the study drug include the following: 
x Any AE of urinary retention  
x Any occurrence of PVR volume ≥ 300 mL 
Discontinuation of study drug for abnormal liver function should be considered by the 
investigator when a subject meets all of the conditions outlined in Section 8.4.6.2 for Hy’s law or 
if the investigator believes that it is in the best interest of the subject (reason for discontinuation 
will be AE).  
7.2. 
Subject Discontinuation/Withdrawal from the Study 
x Subjects who discontinue study drug will also withdraw from the study. 
x A subject may choose to withdraw from the study at any time at his own request, or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. 
x If a subject withdraws consent for disclosure of future information, the Sponsor or 
designee may retain and continue to use any data collected before such a withdrawal of 
consent. 
x If a subject withdraws from the study, he may request destruction of any blood or urine 
samples taken and not tested, and the investigator must document this in the site study 
records. 
x Subjects who withdraw from the study will not be replaced (enrollment accounts for a 
predetermined dropout rate).  
The Week 24/Early Withdrawal assessments will be completed when a subject withdraws or is 
withdrawn from the study, if possible (see Schedule of Assessments in Section 1.3 and 
Section 1.4).  


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Reasons for discontinuation from the study include the following: 
x AE 
x Lack of efficacy 
x Noncompliance 
x Withdrawal of consent 
x Lost to follow-up 
x Physician decision 
x Protocol deviation 
x Death 
x Screen failure 
x Run-in Failure 
x Other 
7.3. 
Lost to Follow-Up 
Should a subject fail to attend a required study visit, the site should attempt to contact the subject 
and re-schedule the missed visit as soon as possible. The site should also counsel the subject on 
the importance of maintaining the assigned visit schedule and ascertain whether or not the 
subject wishes to and/or should continue in the study based on previous non-compliance. In 
cases where the subject does not return for the rescheduled visit and cannot be reached to 
reschedule the missed visit, the site should make every effort to regain contact with the subject 
so that they can appropriately be withdrawn from the study and all dispensed study medication is 
returned. If the subject cannot be reached, the subject should be withdrawn from the study with a 
primary reason of “Lost to Follow-up”. Including at least three documented attempts to contact 
the subject (ie, phone, email, or certified letter). Efforts to establish the possible reason for 
discontinuation should be documented. 
7.4. 
Early Study Termination 
The Sponsor reserves the right to terminate the study for any reason. The study may be 
terminated early if the extent (incidence and/or severity) of emerging effects/clinical endpoints is 
such that the risk/benefit ratio to the study population as a whole is unacceptable. In addition, 
further recruitment in the study overall or at a particular study site may be stopped due to 
insufficient compliance with the protocol, Good Clinical Practice and/or other applicable 
regulatory requirements, procedure-related problems or the number of discontinuations for 
administrative reasons is too high.  


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8. 
Study Assessments and Procedures 
Study procedures and their scheduled timepoints are summarized in the Schedule of Assessments 
(Section 1.3 [Part 1] and Section 1.4 [Part 2]). A detailed listing of study assessments by visit is 
provided in Section 10.7. Site personnel should note the following: 
x Protocol waivers or exemptions are not allowed; however, subjects who fail to meet 
eligibility criteria may be rescreened once, as appropriate. Any notable protocol 
deviations should be noted and raised to the Sponsor’s or designee’s attention. 
x Immediate safety concerns should be discussed with the Sponsor’s designated Medical 
Monitor immediately upon occurrence or awareness to determine if the subject should 
continue or discontinue study drug. 
x Adherence to the study design requirements, including those specified in the Schedule of 
Assessments, is essential and required for study conduct. 
x Note that if done on-site (in person), PRO assessments will be completed prior to vital 
signs, and vital signs will be taken prior to blood draws. 
x Certain study assessments and procedures may be performed remotely (eg, by telephone 
or video call). Refer to Section 8.6 for additional details. 
8.1. 
Baseline Procedures 
8.1.1. 
Informed Consent 
Documented consent must be obtained from each potential subject prior to participating in any 
study procedures according to the process described in Section 10.1.3.  
8.1.2. 
Assignment of Subject Number 
All subjects who sign the ICF will be assigned a unique subject number by IWRS. This number 
will be used to identify the subject throughout the study. Subjects who are rescreened will be 
assigned a new subject number. If a new subject number is assigned, the subject will be linked to 
both subject numbers. 
8.1.3. 
Screening 
All screening evaluations must be completed and reviewed to confirm that potential subjects 
meet all eligibility criteria. The investigator will maintain a screening log to record details of all 
subjects screened and to confirm eligibility or record reasons for screening failure, as applicable. 
Inclusion and exclusion criteria (Section 5.1 and Section 5.2) will be reviewed by the 
investigator or qualified designee at Screening, the start of the Run-in Period, and the start of the 
double-blind Treatment Period.  


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Subjects who fail to meet entry criteria may be rescreened once. (See Section 8.1.2 regarding 
assignment of subject number.) 
The Screening period may also be used for washout of prohibited medications (see 
Section 6.5.1). 
8.1.4. 
Medical History 
A medical history will be obtained by the investigator or qualified designee. Medical history will 
include all chronic and ongoing conditions, regardless of year diagnosed, surgical history, and 
substance abuse history. All events occurring after the subject signs the ICF will be recorded as 
AEs.  
8.1.5. 
Demographics 
Demographic data collection will include sex, age, race, and ethnicity.  
8.1.6. 
Prior and Concomitant Medications 
Prior OAB and BPH medications, as well as ongoing (concomitant) medications will be recorded 
beginning at the signing of the ICF and continuing until the Safety Follow-up call (5 days after 
the last dose of study drug). 
8.1.7. 
Inclusion and Exclusion Post Placebo Run-In 
All Inclusion and Exclusion criteria are to be rechecked for eligibility at the end of Placebo 
Run-In (prior to randomization). Specific inclusion criteria to be checked upon completion of the 
Placebo Run-In will include: 
x Laboratory assessments (as defined in Section 5.1) 
x 3-day Bladder Diary review to confirm: 
o average of ≥ 8 but ≤ 20 micturition episodes per day  
o average of ≥ 3 urgency episodes per day over the 3-day diary period 
o average of ≥ 2 nocturia episodes per night 
x IPSS total score of ≥ 8  
x PVR volume value of < 100 mL 
Specific exclusion criteria to be checked upon completion of the Placebo Run-In will include: 
x Laboratory assessments (as defined in Section 5.2) 


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x 24-hour urine volume > 3,000 mL based on 3-day Bladder Diary 
x Qmax < 5.0 mL/second with a minimum voided volume of 125 mL 
x Subject has taken < 80% or > 120% of the study medication during the Run-In period 
8.2. 
Efficacy Assessments 
Efficacy assessments will be collected as outlined in the Schedule of Assessments (Section 1.3 
and Section 1.4) in the form of 3-day Bladder Diary (refer to Table 1). Information collected in 
the diaries will be used for assessment of the primary and secondary efficacy endpoints related to 
the number of micturition, urgency, nocturia, and incontinence episodes per day as well as one 
24-hr volume voided of urine. In addition, subjects will complete IPSS assessments, and 
 
 PGI, and 
 scores to assess quality of life endpoints. 
Subjects will complete questionnaires either at the start of each required study visit (before vital 
signs and blood draws) or just prior to the visit if completing the forms remotely to assess 
subject-perceived symptom relief and health-related quality of life. The PRO questionnaires are 
provided in Section 10.8. Additional information on the Bladder Diary and questionnaires is 
provided below.  
8.2.1. 
Bladder Diaries 
The Bladder Diary is used by subjects to record the frequency of daily OAB symptoms including 
all micturitions, urgency, incontinence, nocturia, one 24-hr volume voided of urine, and main 
reason for incontinence, and volume voided per micturition (over one 24-hour period) by 
selecting the respective box for each symptom occurring during the course of a given day and 
night. To minimize unnecessary on-site contact and ensure that the subject has a basic 
understanding and ability to comply with completion of the diary, an optional prescreening diary 
may be provided to potential study subjects prior to completion of screening procedures. 
A schedule of completion timelines for the Bladder Diaries for each associated visit is provided 
in Table 1. The Bladder Diary should be completed by the subject on 3 consecutive days within 
the 7 days prior to each Bladder Diary Completion timepoint as outlined in in Table 1. Urine 
volume may be collected during any one (1) of the Bladder Diary Days, and it should be 
recorded for ~24 hours starting from the time the patient gets up for the day and continues until 
the time the patient gets up for the day on the next day.  
A “Diary Day” is defined as the time between when the subject gets up for the day each morning 
(ie, the time the subject got up for the day yesterday to the time the subject got up for the day 
today; approximately a 24-hour period).   


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To be eligible for the study, subjects must have a minimum of: 
x 3 consecutive Diary Days during the Screening Period (prior to the Run-in Visit), and  
x 3 consecutive Diary Days during the Run-in Period (over the 7 days prior to the 
Baseline Visit), and  
x be capable in the investigator’s opinion of maintaining compliance with the diary 
requirements, including the measurement and recording of urine volume, as required, 
at Baseline and throughout the course of the study.  
At all study visits, the site staff should inquire whether the subject had any difficulties with the 
diary and address any questions subjects may have. Instructions for proper completion of the 
diary should be re-reviewed. Subjects will be trained to enter data immediately following each 
event (in real time) and to input data from any “missed” events as soon as they are able. They 
will review and confirm that data from all events occurring within the preceding Diary Day 
(approximately 24 hours) have been entered at a consistent time each morning (eg, upon getting 
up for the day). 
Responses to the Bladder Diary will be reviewed by the site staff to assess whether subjects are 
capable of completing the diary and if subjects meet eligibility criteria. The daily averages for 
micturitions, urgency episodes, nocturia episodes, and urinary urge incontinence episodes will be 
calculated as average of the total by the number of events on Diary Days. Subjects who do not 
meet the OAB entry criteria will be excluded from the study. 
8.2.2. 
Patient-Reported Outcomes 
Subjects will complete questionnaires at the site at the start of each required study visit (before 
vital signs and blood draws) to assess subject-perceived symptom relief, symptom bother, and 
health-related quality of life. These include the following questionnaires: 
x The International Prostate Symptom Score (IPSS) includes 8 questions (7 concerning 
urinary symptoms and 1 concerning quality of life), each with answers based on a 6-point 
scale indicating increasing severity. The urinary symptom responses are assigned points 
from 0 to 5.  The Total IPSS Score can therefore range from 0 to 35 (asymptomatic to 
very symptomatic). The quality of life responses are assigned points from 0 to 6. A 
sample of the IPSS is provided in Section 10.8.1. 
x 
 1-week recall) is a 
multi-item questionnaire that was developed to assess symptom bother and the impact of 
overactive bladder on health-related quality of life. The instrument was developed and 
validated in both continent and incontinent OAB patients, including both men and 
women. A sample of the 
 scale is provided in Section 10.8.2. 
x The 
 health questionnaire is a standardized instrument for use as a measure of 
health outcome [Rabin 2014]. It is applicable to a wide range of health conditions and 


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treatments; it provides a simple descriptive profile and a single index value for health 
status. A sample of the 
 health questionnaire is provided in Section 10.8.3. 
x Global Impression Items include Patient Global Impression of 
(PGI
Patient Global Impression of 
 (PGI-
, Patient Global Impression of 
(PGI-
, Patient Global Impression of
(PGI-
 and 
Patient Global Impression of 
 (PGI-
. A sample of the PGI scale is 
provided in Section 10.8.4. 
x 
The investigator should not provide any additional information to subjects prior to completing 
the questionnaires that might influence responses. 
8.3. 
Safety Assessments 
Planned timepoints for all safety assessments, including assessments for PVR volume and 
orthostatic blood pressure and heart rate, are provided in the Schedule of Assessments 
(Section 1.3 and Section 1.4). Immediate safety concerns should be discussed with the Sponsor’s 
designated Medical Monitor immediately upon occurrence or awareness to determine if the 
subject should continue or discontinue study drug. 
8.3.1. 
Vital Signs 
Vital signs, including blood pressure, heart rate (by pulse), body temperature, respiration rate, 
weight, and height, will be assessed at the timepoints specified in the Schedule of Assessments 
(Section 1.3 and Section 1.4) and in Section 10.7 as follows: 
x Blood pressure and pulse will be measured after the subject has been resting in a seated 
position for 5 minutes, after PRO assessments and before blood draws. Note additional 
requirements on timing for blood pressure assessments for visits with orthostatic 
assessments in Part 1 (Section 8.3.2). 
x Blood pressure measurements will be taken on the same arm and by the same site staff 
throughout the study, if possible.  
x Sitting systolic and diastolic blood pressures will be determined by averaging 3 replicate 
measurements obtained approximately 1 to 2 minutes apart. The average of the 3 
measurements will be used for eligibility and safety assessments.  
x The same method for assessing temperature should be used at all visits for a particular 
subject. 


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x Body weight will be measured with subjects in street clothing with jacket/coat and shoes 
removed, using the same scale throughout the study, if possible. 
x Standing height will be measured without shoes at Screening only.  
8.3.2. 
Orthostatic Blood Pressure (Part 1 Only) 
In addition to routine vital signs (including standard blood pressure assessments), subjects in 
Part 1 of the study (ie, the first 80 subjects enrolled) will undergo serial blood pressure and heart 
rate (by pulse) assessments at Screening, Run-In, Baseline, and Weeks 2 and 4. Blood pressure 
should be assessed as described in Section 8.3.1, with the following additional requirements: 
x Triplicate measurements should be obtained for both sitting and standing blood pressure 
assessments at Hour 0 (pre-dose) and Hours 1, 2, 4, and 6 post dose. (For Screening Visit 
and Run-In assessments, use Hour 0 as the time from which subsequent assessments are 
collected.) A singular pulse rate also should be obtained in sitting and standing positions 
at the same hourly timepoint. Post-dose assessments of blood pressure and pulse may be 
r 15 minutes of each scheduled timepoint.  
x Sitting blood pressure and pulse will be measured after the subject has been resting in a 
sitting position for 5 minutes; standing blood pressure will be measured within 3 minutes 
of standing (after rising from the sitting position).  
x Subjects will be permitted to eat or drink during the 6-hour testing window, however 
caffeinated beverages will not be allowed.  
x Subjects are encouraged to eat breakfast and have the test done at least 1 hour after the 
meal.  
x Subjects should remain relatively inactive and should remain within or close to the 
facility during the 6-hour test window. 
x As stated above in Section 8.3.1, blood draws should be obtained either after all blood 
pressure assessments are completed or between the 4-hour and 6-hour post-dose blood 
pressure assessments, provided that blood draws are complete at least 45 minutes before 
the 6-hour timepoint.  
8.3.3. 
Physical Examinations 
Brief physical examinations will include examination of the heart, lungs, abdomen, and visual 
pelvic examination. In addition, any organ system in which a previous abnormality was noted at 
Baseline or a subject has a complaint or AE will be examined.  


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8.3.4. 
Electrocardiograms 
A 12-lead ECG will be performed in the supine position at the Screening visit using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals. ECGs will be read by trained personnel at the study site or appropriate delegates who 
are medically qualified.  
8.3.5. 
Post-Void Residual Volume 
The volume of urine that remains in the bladder after voiding (PVR) is an objective measurement 
that may serve as a proxy for impaired ability to void. The physician should assess subjects with 
an increase in PVR volume to determine whether an AE should be reported. (Refer to 
Section 8.4.6 for additional information on reporting AEs of urinary retention associated with 
increased PVR.) 
The PVR assessment will be performed via ultrasound (eg, bladder scanner) at the visits 
indicated in the Schedule of Assessments (Section 1.3 and Section 1.4). All efforts should be 
made to ensure the same device and operator are used for all PVR volume measurements for 
individual subjects. 
8.3.6. 
Clinical Safety Laboratory Assessments 
All protocol-required laboratory assessments must be conducted in accordance with the 
laboratory manual and the Schedule of Assessments. See Section 10.2 for the list of clinical 
laboratory tests to be performed and the Schedule of Assessments for the timing and frequency. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.  
The clinical significance of test results will be evaluated as follows: 
x At Screening (and at other eligibility assessment timepoints as specified in Section 5.1 and 
Section 5.2), the investigator or physician subinvestigator will assess the clinical significance 
of any values outside the reference ranges provided by the laboratory, and subjects with 
abnormalities judged to be clinically significant will be excluded from the study. 
x The investigator or physician subinvestigator must review the laboratory report, document 
this review, and record any clinically relevant changes occurring during the study in the AE 
section of the eCRF. The laboratory reports must be filed with the source documents. 
Laboratory abnormalities associated with the underlying disease are not considered clinically 
significant unless judged by the investigator to have worsened or be more severe than 
expected for the subject’s condition. 
x All laboratory tests with values considered clinically significant during participation in the 
study or within 5 days after the last dose of study drug should be repeated until the values 
return to normal or baseline or are no longer considered clinically significant by the 
investigator or Sponsor’s designated Medical Monitor.  


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- If such values do not return to normal/baseline within a period of time judged reasonable 
by the investigator, the etiology should be identified and the Sponsor’s designated 
Medical Monitor notified. 
- If laboratory values from nonprotocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in subject management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the eCRF. 
8.3.7. 
Urodynamics Assessments 
For the approximately 60 subjects participating in the urodynamics sub-study in Part 2, 
urodynamics will be taken at Baseline and Week 12 to measure the following parameters:  
x Instilled volume at first involuntary detrusor contraction (IDC) (Vol@1st IDC) (mL), if an 
IDC occurs 
x Corrected maximum detrusor pressure during the first involuntary detrusor contraction 
(Pdet@1st IDC) (cmH2O), if an IDC occurs 
x Corrected maximum cystometric capacity (MCC) (mL) 
x Corrected maximum detrusor pressure during the storage phase (Pdet@Max Storage) (cmH2O) 
x Peak flow rate during voiding (QMax) (mL/s) 
x Corrected detrusor pressure at peak flow rate (Pdet@QMax) (cmH2O) 
x Voided volume (VV) (mL) 
The urodynamics sub-study will be conducted at selected sites which meet the qualifications set 
by the independent urodynamics central reader.   
Randomization for the urodynamic sub-study will be stratified based on baseline average number 
of micturition episodes per day (≤ 12 or > 12), alpha blocker use with or without 5-ARI (yes or 
no), and urinary incontinence (yes or no). 
A historical urodynamics trace obtained at the site within 6 months prior to screening, which has 
the above parameters clearly identified will be accepted in lieu of an assessment obtained after 
the start of screening but prior to randomization (Baseline/Visit 3). For subjects with no 
acceptable historical trace, a urodynamics assessment must be completed prior to randomization 
(Baseline/Visit 3).  
The Week 12 (Visit 8) urodynamics assessment may be conducted on a different day than the 
Week 12 visit if done within the ±4-day visit window. 
All assessments (historical/Baseline and Week 12) must be performed using the same 
urodynamics equipment and procedure (fill rate, catheter size, fluid, etc). 


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8.3.8. 
Prostate Volume Measurement 
Prostate volume measurement will be collected via ultrasound prior to randomization 
(Baseline/Visit 3). Prostate volume measurement (by ultrasound) assessed within 12 months 
prior to Screening may be accepted in lieu of a measurement collected at any time prior to 
randomization (Baseline/Visit 3). 
8.4. 
Adverse Events and Serious Adverse Events 
The definitions of an AE and SAE can be found in Section 10.3. 
AEs will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
subject’s legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study drug or study procedures, or that caused 
the subject to discontinue the study drug or the study (see Section 7). 
8.4.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information 
All AEs and SAEs will be collected from the signing of the informed consent form through 
5 days after the last dose of study drug. AEs will be collected at the timepoints specified in the 
Schedule of Assessments (Section 1.3 and Section 1.4), and as observed or reported 
spontaneously by study subjects. 
Medical occurrences that begin before the start of study drug, but after obtaining informed 
consent will be recorded in the AE section of the eCRF. 
All SAEs (including serious AESIs) will be recorded and reported on the eCRF within 24 hours 
of the study site personnel’s knowledge of the event, as indicated in Section 8.4.4. Marking the 
event as “serious” will automatically send required notifications for Sponsor or designee review. 
The investigator will also submit any updated SAE data within 24 hours of receipt of the 
information. Nonserious AESIs will be reported on the eCRF within 72 hours of the site’s 
knowledge of the information. 
Investigators are not obligated to actively seek AE or SAE information after conclusion of the 
study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a subject has been discharged from the study, and he/she considers the event to be 
reasonably related to the study drug or study participation, the investigator must promptly notify 
the Sponsor or designee. 


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The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
8.4.2. 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about AE 
occurrences. 
8.4.3. 
Follow-up of Adverse Events and Serious Adverse Events 
After the initial AE or SAE report, the investigator is required to proactively follow each subject 
at subsequent visits/contacts. All AEs will be followed until the Safety Follow-up telephone call 
(5 days [± up to 2 days] after the last dose of study drug). All SAEs will be followed until 
resolution, stabilization, the event is otherwise explained, or the subject is lost to follow-up (as 
defined in Section 7.3). If a subject dies during participation in the study or within 5 days of the 
last dose of study drug, the investigator will provide the Sponsor or designee with a copy of any 
postmortem findings including histopathology. 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the Sponsor or 
designee to elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
New or updated information will be recorded in the originally completed eCRF. As noted above, 
the investigator will submit any updated SAE data to the Sponsor or designee within 24 hours of 
receipt of the information. 
8.4.4. 
Regulatory Reporting Requirements for Serious Adverse Events 
x Prompt notification of an SAE by the investigator to the Sponsor or designee is essential so 
that legal obligations and ethical responsibilities towards the safety of subjects and the safety 
of a study drug under clinical investigation are met.  
x The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation. The Sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRBs/IECs, and investigators.  
x Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and Sponsor policy and 
forwarded to investigators as necessary. 
x An investigator who receives an investigator safety report describing an SAE or other 
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will review and then file it and will notify the IRB/IEC, if appropriate according to local 
requirements. 
8.4.5. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
Adverse Events or Serious Adverse Events 
No disease-related events or outcomes are excluded from AE reporting. Any worsening of OAB 
or BPH symptoms and any events of bladder obstruction should be collected as AEs.  
8.4.6. 
Adverse Events of Special Interest 
Selected nonserious and SAEs will be reported as AESIs. AESIs that also meet the definition of 
an SAE must be reported as described in Section 10.3.  
Adverse events of special interest for this study include:  
x Adverse events consistent with urinary retention 
- An AE of urinary retention should only be recorded when a subject has a raised 
PVR that requires intervention with clean intermittent catherization (CIC) or 
temporary placement of a urinary catheter in addition to one of the following 
criteria: 
a) subject has a PVR of ≥ 300 mL (regardless of symptoms),  
OR 
b) subject has a PVR ≥ 200 mL and < 300 mL and the subject reports associated 
symptoms, ie, sensation of bladder fullness or inability to void despite 
persistent effort, that in the investigator’s opinion require CIC. 
Note: An AE of increased residual urine volume should be recorded if, in the 
investigator’s opinion, the raised PVR is clinically significant but does not fulfill 
the above definition for urinary retention. As stated above in Section 7, subjects 
with a single PVR volume of ≥ 300 mL or an AE of urinary retention will be 
withdrawn from the study. 
x Adverse events suggestive of cystitis or urinary tract infection (UTI) 
- An AE of UTI will be recorded if both the following criteria are fulfilled, regardless 
of subject symptoms: 
a) a positive urine culture result with a bacteriuria count of ≥ 105 CFU/mL 
(ie, 100 × 103 CFU/mL) 
AND 
b) leukocyturia of ≥ 5/hpf 
 
If a subject meets the criteria for the definition of a UTI, the investigator will 
record whether the UTI was “symptomatic” or “asymptomatic” on the AE 
eCRF. 


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Note: If urinalysis/culture results are reported which, in the opinion of the 
investigator, are considered clinically significant but do not fulfill the above 
definition of a UTI, the findings should be recorded as AEs (eg, bacteriuria, 
leukocyturia). 
x Potential major cardiac and cerebrovascular events, including death (or any event with fatal 
outcome), myocardial infarction, cerebrovascular accident, hospitalization for unstable 
angina or chest pain, hospitalization for heart failure requiring hospitalization, and coronary 
revascularization/angioplasty/stent  
x Hypertension: An AESI of Hypertension (or Worsening Hypertension, if the subject has 
history of hypertension) should be recorded if any of the following three criteria are met 
(regardless of clinical significance): 
- For subjects with systolic blood pressure < 140 mmHg AND diastolic blood pressure 
< 90 mmHg at baseline (Visit 3):  
The average of 3 systolic blood pressures ≥ 140 mmHg or diastolic blood pressures 
≥ 90 mmHg (or both) at any 2 consecutive visits after baseline (Visit 3) 
- For subjects with systolic blood pressure ≥ 140 mmHg OR diastolic blood pressure 
≥ 90 mmHg at baseline (Visit 3): 
An increase, compared to baseline (Visit 3) at 2 consecutive visits, in the average of 
3 systolic blood pressures by ≥ 20 mmHg or 3 diastolic blood pressures by 
≥ 10 mmHg 
- Initiation or increase in dose of medication for treatment of hypertension in any 
subject 
Note 1: The onset date for an AESI hypertension is the first of the dates when the event 
meets any of the above criteria. 
Note 2: An AE of “increased blood pressure” should be recorded if, in the investigator’s 
opinion, an elevated blood pressure measurement is clinically significant but does not 
fulfill the above definition for hypertension. 
x Adverse events consistent with orthostatic hypotension as confirmed by orthostatic vital 
signs 
x Elevated serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 
lab value requiring that study drug be temporarily withheld or permanently discontinued (see 
Sections 8.4.6.1 and 8.4.6.2). To date, no concern regarding drug-induced liver toxicity has 
been identified; however, the Sponsor is monitoring laboratory data for a potential safety 
signal, consistent with Food and Drug Administration guidance [FDA Guidance, 2009]. 
x Neoplasms 


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Serious AESIs and elevated liver enzymes or bilirubin requiring withholding of study drug (see 
Section 8.4.6.1) must be reported within 24 hours of the study site personnel’s knowledge of the 
event by marking the appropriate box on the AE eCRF and assigning the most appropriate 
category. Additional information should be provided as directed in the eCRF Completion 
Guidelines. AESIs that also meet the definition of an SAE must be reported as an SAE, as 
described in Section 8.4.4. Nonserious AESIs should be reported within 72 hours of the site 
personnel’s knowledge, using the AE eCRF. 
8.4.6.1. 
Criteria for Temporary Withholding of Study Treatment in Association with 
Liver Test Abnormalities 
Elevated liver enzymes or bilirubin sufficient to require withholding study medication must be 
reported within 24 hours of the study site personnel’s knowledge of the event using AESI 
specific eCRFs/forms/worksheets provided for the study.  
Hepatic enzymes will be monitored in accordance with FDA drug-induced liver injury guidelines 
[FDA, 2009].  
If any of the following liver test abnormalities develop, study drug should be withheld 
immediately with appropriate clinical follow-up (including repeat laboratory tests, until a 
subject’s laboratory profile has returned to normal/baseline status), and the event reported as an 
SAE:  
x ALT or AST > 8 x upper limit of normal (ULN) 
x ALT or AST > 5 x ULN and persists for more than 2 weeks  
x ALT or AST > 3 x ULN and total bilirubin > 2 x ULN or international normalized ratio 
(INR) > 1.5 
x ALT or AST > 3 x ULN with appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia (> 5%)  
Rechallenge may be considered if an alternative cause for the abnormal liver tests (ALT, AST, 
total bilirubin) is discovered and the laboratory abnormalities resolve to normal or baseline 
values. The investigator and Sponsor’s designated Medical Monitor must discuss and agree with 
any decision to rechallenge.  
Rechallenge should not occur when the etiology of the liver test abnormalities is considered 
possibly drug-induced. 
8.4.6.2. 
Criteria for Permanent Discontinuation of Study Treatment in Association with 
Liver Test Abnormalities 
Study treatment should be discontinued permanently if all of the following 4 criteria are met (ie, 
potential severe drug-induced liver injury/Hy’s law case):  
x Total bilirubin increases to > 2 x ULN or INR > 1.5 and  
x AST or ALT increases to ≥ 3 x ULN and  
x Alkaline phosphatase value does not reach 2 x ULN and  


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x No alternative cause explains the combination of the above laboratory abnormalities; 
important alternative causes include, but are not limited to the following:  
- Hepatobiliary tract disease 
- Viral hepatitis (eg, hepatitis A/B/C/D/E, Epstein-Barr virus) 
- Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and dietary 
supplements, plants, and mushrooms  
- Alcoholic hepatitis  
- Non-alcoholic steatohepatitis 
- Autoimmune hepatitis  
If an alternative cause for hepatotoxicity is identified, then it should be determined (based on the 
severity of the hepatotoxicity or event) whether study drug should be withheld or permanently 
discontinued as appropriate for the safety of the subject, following consultation with the 
Sponsor’s designated Medical Monitor. 
8.4.7. 
Pregnancy Management and Reporting to the Sponsor 
In the case of a male subject with a pregnant partner, if the patient agrees, the patient’s pregnant 
partner should be notified and requested to sign a Release of Information form, permitting 
transfer of information regarding the pregnancy and outcome to the sponsor. 
The investigator must inform the subject of his right to receive treatment information.  If the 
subject chooses to receive unblinded treatment information, the individual blind should be 
broken and the treatment assignment provided to the subject. The study team will remain blinded 
to the subject’s treatment assignment. 
In the event that a partner of a male study subject becomes pregnant during the study, if the 
subject agrees, the subject’s pregnant partner should be notified of the subject’s study 
participation and be requested to sign a Release of Information form, permitting transfer of 
information regarding the pregnancy and outcome to the sponsor. If the subject and the subject’s 
partner agree, the investigator should notify the partner’s primary care physician and provide 
details of the subject’s participation in the study and treatment (blinded or unblinded, as 
applicable). 
Partner pregnancies are to be reported to the sponsor within 24 hours of awareness by the study 
site personnel, using the pregnancy reporting forms and information for safety event reporting in 
Section 10.3.  The expected date of delivery or expected date of the end of the pregnancy, last 
menstruation, estimated conception date, pregnancy result, neonatal data, etc. should be included 
in this information, as available. 
If the subject and partner agree, the investigator will follow the medical status of the mother, the 
pregnancy, as well as the outcome of the infant at birth, and will report the outcome to the 
sponsor. 


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8.4.8. 
Medication Errors 
Medication error refers to any unintended error in the dosing and/or administration of the study 
drug as per instructions in the protocol. Medication errors generally fall into 4 categories as 
follows: 
x Wrong study drug 
x Wrong dose (including dosing regimen, strength, form, concentration, amount) 
x Wrong route of administration 
x Wrong subject (ie, not administered to the intended subject) 
Medication errors include occurrences of overdose and underdose of the study drug. 
Overdose: Unintentional administration of a quantity of the study drug given per administration 
or per day that is above the maximum recommended dose according to the protocol. This also 
takes into account cumulative effects due to overdose (see Section 8.5 for treatment and 
reporting of overdose). For this study, any dose of vibegron or placebo of 3 or more tablets 
within a 24-hour window is an overdose. There is no known antidote for an overdose.  
Underdose: No underdose is defined for this study. 
8.5. 
Treatment of Overdose 
In the event of an overdose (3 more tablets of study drug within 24 hours), the investigator or 
treating physician should:  
x Contact Sponsor’s designated Medical Monitor immediately  
x Closely monitor the subject for any AEs, SAEs, and laboratory abnormalities  
x Report all overdose events on the eCRF, whether or not the overdose is associated with 
an AE. If the overdose resulted in an AE or SAE, please refer to Section 10.3 for 
reporting requirements.  
x Document the quantity of the excess dose as well as the duration of the overdosing in the 
eCRF  
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Sponsor’s designated Medical Monitor based on the clinical evaluation of 
the subject. 


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8.6. 
Safety Measures due to COVID-19 Pandemic 
To minimize direct, in-person contact between site personnel and subjects, certain study 
procedures may be performed remotely by telephone contact or video call. All other procedures 
should be done in-person while the subject is on-site. Specifically, the following procedures may 
be done remotely: 
x Informed consent (where applicable, per approved IRB/IEC process) 
x Medical history 
x Demography 
x Prior medications (including prior OAB and BPH medication review) 
x Collection and dispensation of paper PRO questionnaires  
x Collection and dispensation of Bladder Diaries 
x Review of AEs/SAEs  
x Concomitant medications 
x Dispensation of study drug during Double-blind Treatment Phase for visits after Baseline 
(Visit 3) 
If a subject cannot attend the Week 12 visit (Visit 8), the site should bring him/her in for an 
early withdrawal visit (Visit 11) when safe and feasible.  
If a subject misses any other single on-site study visit as a result of the COVID-19 pandemic, 
then the site should collect the completed Bladder Diary (eg, by curbside pickup, mail, or 
courier) for review and data entry when feasible, and remotely review AEs/SAEs and 
concomitant medications. Study drug should be dispensed (eg, curbside pickup or shipped 
via trackable courier or other methods approved by the Sponsor/CRO), and the next visit’s 
bladder diary should be provided. In such cases, the subject will not be considered lost to 
follow-up or early withdrawal, if he remains in contact with the site and is compliant with 
study drug administration, completing study procedures as appropriate, and attends 
subsequent visits. 
 


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9. 
Statistical Considerations 
This section contains a brief summary of the statistical analyses for this study; full details will be 
provided in the Statistical Analysis Plan (SAP). 
The randomized allocation schedule will be generated by the Sponsor or designee and 
implemented by the vendor of the study. Stratification will be performed across the study (not 
per site). The statistical analysis of the data obtained from this study will be the responsibility of 
the Sponsor or designee. At the end of the study, the official, final database will be frozen and 
unblinded after medical/scientific review has been performed, and data have been declared final 
and complete. The SAP will be approved prior to data being unblinded.  
A subject is considered enrolled in the study at randomization. 
9.1. 
Statistical Hypotheses 
The primary clinical efficacy hypothesis is that vibegron + pharmacological therapy is more 
effective than placebo + pharmacological therapy in reducing both a) the mean daily micturition 
episodes and b) mean daily urgency episodes, based on a 3-day diary. 
9.2. 
Sample Size Determination 
Approximately 1088 subjects will be randomized in a 1:1 ratio to receive one of the following 
study treatments:  
x Vibegron 75 mg tablet (N = 544) 
x Matching placebo tablet (N = 544)   
Approximately 544 subjects each will be assigned to the vibegron and placebo treatment groups. 
Assuming a total of 15% of subjects will discontinue prior to Week 12 (for any reason), there 
will be approximately 462 evaluable subjects in the vibegron and placebo treatment groups 
(924 subjects total) at the end of Week 12. The study has approximately 94.3% power to detect a 
between-group treatment difference of 0.46 in change from baseline in micturitions at a 2-sided 
0.05 level assuming a variability estimate of 1.972 based on vibegron Study MRK-008 data and 
the FDA’s statistical reviewer of mirabegron NDA data showing that the micturition treatment 
effect in men taking 50 mg of mirabegron is 70% of the overall 50 mg of mirabegron population. 
Additional details are provided at the end of this section.  
For the second co-primary endpoint, 462 evaluable subjects per treatment group has 
approximately 90% power to detect a between-group treatment difference of 0.60 in change from 
baseline in urgency episodes at a 2-sided 0.05 level assuming a variability estimate of 2.811 
based on vibegron Study MRK-008 data and the FDA’s statistical reviewer of mirabegron NDA 
data. Additional details are provided at the end of this section. 


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The overall study power will be more than 84% with the co-primary endpoints based on the 
Bonferroni inequality (ie, for any events A and B, P(A∩B) ≥ P(A) + P (B) – 1).  
Derivation of Estimated Treatment Effect in Men 
Based on the published results of the Phase 2 trial of mirabegron and the FDA statistical 
reviewer of the OAB NDA, we estimated the following: 
x The Phase 3 results will have at least 85% of the treatment difference of the Phase 2 
results 
x The treatment difference for men is at least 70% of the effect of the general OAB 
population 
Table 3 summarizes this information and sources. 
Table 3.  
Data and Sources Supporting Study Sample Size Calculations 
Mirabegon Results 
  
N 
PBO Adj CFB 
Study 
Overall 
Men 
Overall 
178-CL-046 
473 
133 
-0.6 
178-CL-047 
425 
116 
-0.61 
 
Simple Average 
-0.61 
 
 
Phase 2 Micturition  
PBO Adj CFB 
Phase 3 Micturition  
PBO Adj CFB 
Phase 3 as a %  
of Phase 2 
Comparing Phase 3  
to Phase 2 
-0.64 
-0.605 
94.5% 
Merck 008 Results and Ph 3 Projections 
Measure 
Vib 50mg 
Vib 100mg 
SD 
Micturition 
-0.64 
-0.91 
1.972 
Urgency Episodes 
-0.76 
-1.24 
2.811 
Midpoint between 50mg and 100mg 
Micturition 
Urgency Episodes 
Ph 2 Projected Effect of 75mg 
-0.78 
-1.00 
Ph 3 Projected Effect of 75mg 
-0.66 
-0.85 
Ph 3 Projected Effect of 75mg in Men 
-0.46 
-0.60 


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Power in Baseline BPH Treatment Subgroups: 
Although this study will not formally test the treatment effect in subgroups by baseline BPH 
treatments, it is sufficiently sized to estimate treatment differences within these subgroups.  
Assuming that approximately half of the subjects are on alpha blockers alone and half on alpha 
blockers plus 5-ARI, then approximately 544 subjects will be randomized to each subgroup with 
462 evaluable (231 per arm). Using the above assumptions with a two-sided test with a type-I 
error of 0.10, each subgroup will have 97.1% power for micturitions and 94.5% power for 
urgency episodes. Assuming that the endpoints and subgroups are independent, then the power 
for each subgroup to be significant on both endpoints is 91.7%, and the power for both 
subgroups to be significant on both endpoints is 84.0%.  
The impact of imbalances in 5-ARI plus alpha blockers versus alpha blockers alone will be 
monitored and controlled if needed.  
9.3. 
Populations for Analyses 
Analysis Populations 
Screened Set 
The Screened Set consists of all subjects who are screened for the study. This population 
is used primarily for subject accounting purposes and will generally not be used for 
summary or analysis. 
Run-in Set 
The Run-in set consists of all subjects who entered the run-in period of the study. Subjects 
will be considered run-in failures if they enter the run-in period but are not randomized to 
receive double-blind medication. 
Randomized Set 
The Randomized Set consists of all subjects who are randomized to receive study 
medication regardless of whether they take a dose.  
Safety Analysis Set (SAF) 
The Safety Analysis Set consists of all subjects who receive at least one dose of double-
blind study medication. Subjects will be classified according to the treatment they 
actually received.  
Full Analysis Set (FAS) 
The Full Analysis Set (FAS) population will serve as the primary population for the 
analysis of efficacy data in this trial. Since the endpoints related to incontinence only 
apply to subjects who meet the definition of incontinence at trial entry, it is necessary to 
have a separate FAS definition with an additional criterion to define the primary analysis 
population for incontinence endpoints.  


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FAS consists of all randomized subjects who took at least one dose of double-blind study 
medication and have at least one evaluable change from baseline micturition 
measurement. Subjects will be analyzed according to their randomized treatment, 
irrespective of premature discontinuation, according to the Intent-to-Treat (ITT) 
principle.  
Full Analysis Set for Incontinence(FAS-I) 
FAS-I consists of all randomized subjects with incontinence at baseline who took at least 
one dose of double-blind study medication, have an evaluable baseline urgency urinary 
incontinence measurement, and have at least one evaluable change from baseline urgency 
urinary incontinence measurement. 
Note that “subjects with incontinence at baseline” are defined as meeting the following 
criteria: 
x An average of ≥ 8.0 micturitions per Diary Day 
x An average of ≥ 1.0 urinary incontinence episodes per Diary Day 
Per-Protocol Set (PPS) and Per-Protocol Set for Incontinence (PPS-I) 
The PPS and PPS-I exclude patients from the FAS and FAS-I due to important protocol 
deviations that may substantially affect the results of the efficacy endpoints (ie, major 
protocol deviations associated with efficacy). The final determination on protocol 
deviations, and thereby the composition of the PPS and PPS-I, will be made prior to the 
unblinding of the database  
A supportive analysis using the PPS and PPS-I will be performed for the co-primary efficacy and 
secondary endpoints. Subjects will be included in the treatment group to which they are 
randomized, regardless of which treatment actually received, for the analyses of efficacy data 
using the PPS and PPS-I. 
9.4. 
Statistical Analyses 
The statistical analysis plan (SAP) will be developed and finalized before database lock and will 
describe the subject populations to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data. This section is a summary of the planned statistical analyses 
of the primary and secondary endpoints. 
9.4.1. 
Demographic and Other Baseline Characteristics 
All demographic data such as age, race, and ethnicity and baseline characteristic data will be 
summarized by treatment group for the FAS. Subject disposition will be summarized using 
Screened Set.  


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Descriptions of medical history findings will be coded using the latest Medical Dictionary for 
Regulatory Activities (MedDRA) version. Medical history may be summarized in the descending 
order of overall frequency, by system organ class and preferred term.  
Prior and concomitant medications will be coded using the latest version of World Health 
Organization (WHO) Drug Dictionary. The number and percentage of subjects receiving prior or 
concomitant medications will be summarized by treatment group.  
Baseline prostate volume, Qmax, IPSS, and PVR will be summarized. Baseline disease 
characteristics related to primary and secondary variables will be summarized under primary 
and/or secondary efficacy analyses. 
9.4.2. 
Efficacy Analyses 
All statistical tests will be 2-sided hypothesis tests performed at the 5% level of significance for 
main effects. All confidence intervals will be 2-sided 95% confidence intervals, unless stated 
otherwise. 
9.4.2.1. 
Analysis Endpoints 
The primary and secondary efficacy endpoints are listed below and analyses will be defined in 
the following sections. All analyses for other efficacy/effectiveness and safety endpoints listed 
below will be defined in the SAP. 
Co-Primary Efficacy Endpoints 
x CFB at Week 12 in the average number of micturition episodes per day 
x CFB at Week 12 in the average number of urgency episodes (urgency: need to urinate 
immediately) per day 
Secondary Efficacy Endpoints 
x CFB at Week 12 in the average number of nocturia episodes per night  
x CFB at Week 12 in the average number of urge urinary incontinence episodes per day for 
subjects with urinary incontinence at baseline 
x CFB at Week 12 in the IPSS Storage score (1-week recall) 
x CFB at Week 12 in the average volume voided per micturition 


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9.4.2.2. 
Primary Analyses 
For the analysis of the first co-primary endpoint (change from baseline in the average daily 
number of micturition episodes at Week 12), a mixed model for repeated measure (MMRM) 
with restricted maximum likelihood estimation will be used. The analysis model for the efficacy 
endpoint will include terms for treatment, visit, baseline micturition score, alpha blocker use (yes 
or no), baseline urinary incontinence (yes or no), region (US vs non-US), and interaction of visit 
by treatment. An unstructured covariance matrix will be used to model the correlation among 
repeated measurements. The Kenward-Roger adjustment for denominator degrees of freedom 
will be used with restricted (or residual) maximum likelihood (REML) to make statistical 
inference. 
For the analysis of the second co-primary endpoint (change from baseline in the average daily 
number of urgency episodes at Week 12), a similar MMRM model will be used. The analysis 
model for the efficacy endpoint will include terms for treatment, visit, baseline score, baseline 
average micturition episodes per day (≤ 12 vs > 12), alpha blocker use with or without 5-ARI 
(yes or no), baseline urinary incontinence (yes or no), region (US vs non-US), and interaction of 
visit by treatment. 
Other change from baseline endpoints will be analyzed using the same MMRM model as 
urgency episodes. 
9.4.2.3. 
Secondary Analyses 
If the null hypothesis is rejected for both co-primary endpoints, then the secondary efficacy 
endpoints will be tested using a fixed-sequence testing procedure until a two-sided p-value 
≥ 0.05 is observed. The fixed-sequence testing procedure controls the family-wise error rate at a 
2-sided alpha level of 0.05. The order of the secondary efficacy endpoints is as specified in 
Section 9.4.2.1. 
9.4.3. 
Safety Analyses 
The safety analysis will be performed using the Safety Analysis Set and will be fully defined in 
the SAP. The safety parameters will include AEs and clinical laboratory and vital sign, 
parameters. For each safety parameter of the clinical laboratory and vital sign parameters, the last 
nonmissing safety assessment before the first dose of study drug will be used as the baseline for 
all analyses of that safety parameter. 
9.4.3.1. 
Adverse Events 
An AE will be considered a treatment-emergent AE (TEAE) if: 
x The AE began on or after the date of the first dose of study drug; or 


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x The AE was present before the date of the first dose of study drug, but increased in 
severity or became serious on or after the date of the first dose of study drug 
An AE that occurs more than 5 days after the last dose of study drug will not be counted as a 
TEAE. 
An AE will be considered a treatment-emergent SAE (TESAE) if it is a TEAE that additionally 
meets any SAE criteria. 
AEs will be coded using the latest version of MedDRA. An overall summary table of AEs by 
treatment group will be presented with number and percentage of subjects. The incidence of all 
TEAEs by primary SOC and PT will be prepared for all TEAEs, TESAEs, treatment-related 
TEAEs/TESAEs, TEAEs leading to discontinuation from study treatment and all TEAEs by 
maximum intensity. All AEs will be listed. The number and percentage of subjects with AEs of 
special interest, as defined in Section 8.4.6, will be summarized by treatment group. 
9.4.3.2. 
Clinical Laboratory Assessments 
All continuous safety laboratory parameters will be summarized descriptively by absolute value 
at each visit by treatment group, together with the corresponding changes from baseline. 
Laboratory reference ranges will be used to identify abnormalities with low, normal, or high 
values.  
9.4.3.3. 
Vital Signs 
Descriptive statistics of observed values and change from baseline for vital signs will be 
presented for each treatment group by visit. 
9.4.3.4. 
Urodynamics 
Descriptive statistics of observed values at Baseline and Week 12, and the change from baseline 
at Week 12 for the following urodynamic parameters will be presented for each treatment group 
by visit:  
x Instilled volume at first involuntary detrusor contraction (Vol@1st IDC) (mL) 
x Corrected maximum detrusor pressure during the first involuntary detrusor contraction 
(Pdet@1st IDC) (cmH2O) 
x Corrected maximum cystometric capacity (MCC) (mL) 
x Corrected maximum detrusor pressure during the storage phase (Pdet@Max Storage) (cmH2O) 
x Peak flow rate during voiding (QMax) (mL/s) 


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x Corrected detrusor pressure at peak flow rate (Pdet@QMax) (cmH2O) 
x Voided volume (VV) (mL) 
This analysis will only apply to the sub-study in Part 2. 
9.4.4. 
Other Analyses 
Response efficacy endpoints will be analyzed using the Cochran-Mantel-Haenszel risk difference 
estimate. Missing Week 12 data will be analyzed using multiple imputation. For each imputed 
dataset, the estimated difference in the proportion of responders and 95% confidence interval for 
the difference will be calculated using the Cochran-Mantel-Haenszel risk difference estimate 
stratified by baseline average micturition episodes per day (≤ 12 vs > 12) and alpha blocker use 
with or without 5-ARI (yes or no) with weights proposed by Greenland and Robins.  
9.4.4.1. 
Subgroup Analyses 
Subgroup analyses of primary and secondary endpoints may be conducted. These may include 
analysis by alpha blocker use with or without 5-ARI (yes or no), baseline urinary incontinence 
(yes or no), and region (US vs non-US).  
Sub-study may need to have a separate demographic and baseline characteristics analyses 
together with the urodynamic analysis to assess the effects of vibegron treatment on urodynamic 
parameters. 
9.5. 
Interim Analyses 
There are no interim analyses planned for this study. 
9.6. 
Data Safety Monitoring Board 
One external independent DSMB will be formed for the study URO-901-3005 and the extension 
study URO-901-3006. The detailed activities including meeting and analysis plan will be 
described and documented in the DSMB Charter and the DSMB SAP, respectively. 


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10. 
Supporting Documentation and Operational Considerations 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
x This study will be conducted in accordance with the protocol and with the following: 
- Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 
- Applicable ICH/ISO Good Clinical Practice (GCP) guidelines 
- Applicable laws and regulations 
x The protocol, protocol amendments, ICF, Investigator’s Brochure, and other relevant 
documents (eg, advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated. 
x Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study subjects.  
x The investigator will be responsible for the following: 
- Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
- Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
- Providing oversight of the overall conduct of the study at the site and adherence to 
requirements of applicable local regulations, for example 21 Code of Federal Regulations 
(CFR), ICH guidelines, the IRB/IEC, and European regulation 536/2014 for clinical 
studies (if applicable) 
10.1.2. 
Financial Disclosure 
Investigators and subinvestigators will provide the Sponsor or designee with sufficient, accurate 
financial information as requested to allow the Sponsor or designee to submit complete and 
accurate financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study. 


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10.1.3. 
Informed Consent Process 
x The investigator or his/her representative will explain the nature of the study to the subject or 
his legally authorized representative and answer all questions regarding the study.  
x Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representatives will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, HIPAA requirements, 
where applicable, and the IRB/IEC or study center.  
x The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 
x Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study.  
x A copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative.  
x Subjects who are rescreened are required to sign a new ICF. 
10.1.4. 
Data Protection 
x Subjects will be assigned a unique identifier. Any subject records or datasets that are 
transferred to the Sponsor or designee will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred. If a subject is 
rescreened and assigned a new subject number, both subject numbers for that individual will 
be linked. 
x The subject must be informed that his personal study-related data will be used by the Sponsor 
or designee in accordance with local data protection law. The level of disclosure must also be 
explained to the subject.  
x The subject must be informed that his medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the Sponsor or designee, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.5. 
Committees Structure 
Not applicable. 
10.1.6. 
Posting Clinical Study Data 
Clinical study information will be posted on external registries and websites (eg, US National 
Institutes of Health’s website www.ClinicalTrials.gov and European Clinical Trial Register) as 
per applicable regulatory requirements. 


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10.1.7. 
Data Quality Assurance 
x All subject data relating to the study will be recorded on case report forms (CRFs) unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.  
x The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.  
x The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.  
x The Sponsor is responsible for the data management of this study including quality checking 
of the data. Management of clinical data will be performed in accordance with applicable 
Sponsor-approved standards and data cleaning procedures to ensure the integrity of the data. 
x Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of subjects are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.  
Study Site 
All clinical study documentation must be retained by the investigator until at least 2 years after 
the last approval of a marketing application in an ICH region (ie, United States, Europe, or 
Japan) and until there are no pending or contemplated marketing applications in an ICH region; 
or, if no application is filed or if the application is not approved for such indication, until 2 years 
after the investigation is discontinued and regulatory authorities have been notified. investigators 
may be required to retain documents longer if required by applicable regulatory requirements, by 
local regulations, or by an agreement with the Sponsor. The investigator must notify the Sponsor 
before destroying any clinical study records. 
The study site and the record retainer should take measures in such a way that these records are 
not lost or abandoned during the designated period of preservation and that they are presented 
upon request. 
Institutional Review Board, Independent Ethics Committee, and Research Ethics Board 
(IRB/IEC/REB) 
The protocol, protocol amendments, informed consent form, Investigator’s Brochure, and any 
other relevant materials, including accompanying material to be provided to the subject (eg, 
advertisements, patient information sheets, or descriptions of the study used to obtain informed 
consent) will be submitted by the investigator to an IRB/REB/IEC. Approval from the 
IRB/REB/IEC must be obtained before starting the study and should be documented in a letter to 
the investigator specifying the following: 


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x Protocol number 
x Protocol version 
x Protocol date 
x Documents reviewed  
x Date on which the committee met and granted the approval 
Any amendments to the protocol will require IRB/REB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study subjects. 
The investigator will be responsible for the following: 
x Providing written summaries of the status of the study to the IRB/REB/IEC’s annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/REB/IEC 
x Notifying the IRB/REB/IEC of SAEs or other significant safety findings as required by 
procedures established by the IRB/REB/IEC. 
10.1.8. 
Source Documents 
x Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
x Data entered in the eCRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The investigator may need to 
request previous medical records or transfer records, depending on the study. Current 
medical records must be available during the site monitor’s visit. 
x The required source documents are: 
− Subject identification (name, date of birth, sex) 
− Documentation that the subject meets eligibility criteria, (eg, history, physical 
examination, and confirmation of diagnosis to support inclusion and exclusion 
criteria) 
− Participation in the study (including study number) 
− Study discussed and date of informed consent 
− Dates of all visits 
− Documentation that protocol-specific procedures were performed 
− Results of efficacy parameters, as required by the protocol 
− Start and end date (including dose regimen) of study drug (drug dispensing and 
return should be documented as well) 


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− Record of all AEs and other safety parameters (start and end date, and causality 
and intensity as assigned by the investigator) 
− Concomitant medication (including start and end date) 
− Date of study completion and reason for early discontinuation, if applicable 
10.1.9. 
Study and Site Closure 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected, and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include but are 
not limited to: 
x Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC/REB 
or local health authorities, the Sponsor’s procedures, or GCP guidelines 
x Inadequate recruitment of subjects by the investigator 
x Discontinuation of further study drug development 
10.1.10. 
Publication Policy 
x The Sponsor has proprietary interest in this study. Authorship and manuscript composition 
will reflect joint cooperation between multiple investigators and sites and Sponsor or 
designee personnel. Authorship will be established prior to the writing of the manuscript. As 
this study involves multiple centers, no individual publications will be allowed prior to 
completion of the final report of the multicenter study except as agreed with the Sponsor. 
x The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. 
10.1.11. 
Compliance with Protocol 
The investigator is responsible for compliance with the protocol at the investigational site. A 
representative of the Sponsor will make frequent contact with the investigator and his/her 
research staff and will conduct regular monitoring visits at the site to review subject and study 
drug accountability records for compliance with the protocol. Protocol deviations will be 
discussed with the investigator upon identification. The use of the data collected for the subject 
will be discussed to determine if the data are to be included in the analysis. The investigator will 
enter data that may be excluded from analysis as defined by the protocol deviation specifications. 


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Significant protocol deviations will be reported to the IRB/IEC/REB according to the 
IRB/IEC/REB’s reporting requirements. 
10.2. 
Appendix 2: Clinical Laboratory Tests 
The tests detailed in Table 4 will be performed by the central laboratory chosen by the Sponsor. 
Subjects do not need to fast prior to laboratory testing. A sample for urinalysis (including 
microscopy for RBCs, WBCs, epithelial cells, and bacteria) and urine culture will be sent to the 
central laboratory only if the urine dipstick tests positive for the presence of leukocytes, nitrites, 
or blood cells. If a subject reports symptoms suggestive of a urinary tract infection at any visit, a 
urine dipstick should be performed as needed, and a sample will be sent out for urinalysis and 
culture, and sensitivity testing.  
Table 4 
Clinical Laboratory Tests 
Hematology 
Chemistry 
Urinalysisa 
Other 
Hematocrit 
Albumin 
Blood 
PSAd 
Hemoglobin 
Alkaline phosphatase 
Glucose 
Coagulation 
INR/PT/APTTe 
Platelet count 
ALT 
Protein 
 
WBC (total and 
differential) 
AST 
Specific gravity 
 
RBC 
Bicarbonate 
Microscopic exam 
(RBCs, WBCs, 
epithelial cells, and 
bacteria) 
 
 
Calcium 
pH 
 
 
Chloride 
Color 
 
 
Creatinineb 
 
 
 
Glucose (fasting or non-
fasting) 
 
 
 
Potassium 
 
 
 
Sodium 
 
 
 
Total bilirubin 
 
 
 
Direct bilirubinc 
 
 
 
Blood urea nitrogen 
 
 
 
Total cholesterol 
 
 
ALT = alanine aminotransferase; APTT = activated partial thromboplastin time; AST = aspartate aminotransferase; 
eGRF = estimated glomerular filtration rate; INR = international normalized ratio; PSA = prostate-specific antigen; PT = 
prothrombin time; RBC = red blood cell count; WBC = white blood cell count  
a 
A sample for urinalysis and urine culture/sensitivity will be sent to the central laboratory only if the urine dipstick performed 
at the site is positive for the presence of leukocytes, nitrites, or blood cells.  
b 
eGFR will be calculated and reported by the central lab.  
c 
If total bilirubin is elevated above the upper limit of normal. 
d 
PSA performed by central laboratory at Screening. 
e 
Only upon request from Principal Investigator (if ALT, AST and bilirubin are increased). 


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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
Definition of an AE 
AE Definition 
An AE is any untoward medical occurrence in a clinical study subject, temporally associated 
with the use of study drug, whether or not considered related to the study drug. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of study drug. 
AE of Special Interest  
An AESI (serious or nonserious) is one of scientific and medical concern specific to the 
Sponsor’s study drug/device or program, which warrants ongoing monitoring and rapid 
communication by the investigator to the Sponsor or designee. Such an event might warrant 
further investigation in order to characterize and understand it. See Section 8.4.6 for AESIs 
defined for this study.  
Events Meeting the AE Definition  
x 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECGs, radiological scans, vital signs measurements), 
including those that worsen from baseline, or are considered clinically significant in the 
medical and scientific judgment of the investigator (ie, not related to progression of 
underlying disease) 
x 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition 
x 
New condition detected or diagnosed after study drug administration even though it may 
have been present before the start of the study 
x 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction 
x 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug or 
a concomitant medication.  
x 
Lack of efficacy or failure of expected pharmacological action per se will not be reported 
as an AE or SAE. Such instances will be captured in the efficacy assessments. However, 
the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AEs or SAEs if they fulfil the definition of an AE or SAE. Any worsening of 
OAB symptoms or BPH/bladder obstruction should be collected as an AE. 


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Events NOT Meeting the AE Definition  
x 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the subject’s condition. Merely 
repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE. Any abnormal test result that is determined to be an error does not 
require recording as an AE. 
x 
The disease/disorder being studied or expected signs, or symptoms (clearly defined) of 
the disease/disorder being studied, unless more severe than expected for the subject’s 
condition. 
x 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads 
to the procedure is the AE.  
x 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
x 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
x 
Abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) identified 
during Screening. 
Definition of an SAE 
SAEs must meet both the AE criteria described above and the seriousness criteria listed below. 
An SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life threatening 
The term life threatening in the definition of serious refers to an event in which the subject 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the subject has been admitted to the hospital or kept in 
the Emergency Room for ≥ 24 hours for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur 
during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other 
serious criteria, the event is serious. When in doubt as to whether hospitalization occurred or 
was necessary, the AE should be considered serious. 
Hospitalization for elective intervention of a preexisting condition that did not worsen from 
baseline is not considered an AE. 


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d. Results in persistent disability/incapacity 
x 
The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions. 
x 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent activities of 
daily living but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
x 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be 
immediately life threatening or result in death or hospitalization but may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered 
serious. 
Examples of such medically significant events include invasive or malignant cancers, 
intensive treatment with a drug in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, or 
development of drug dependency or drug abuse. 
Recording and Follow-Up of AEs and SAEs  
AE and SAE Recording 
x 
When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
x 
The investigator will then record all relevant AE or SAE information in the eCRF. 
x All SAEs (including serious AESIs) must be reported in the eCRF within 24 hours of 
the study site personnel’s knowledge of the event, regardless of the investigator 
assessment of the relationship of the event to study drug. 
x The event term, start date, severity, and initial causality assessment must be entered in 
the AE eCRF page and the event must be marked as “Serious”. This will activate 
additional assessment fields including “action taken with study drug”, “seriousness 
criteria”, and “brief description” which should be completed as soon as information is 
available. Marking the event as “serious” will automatically send required 
notifications for Sponsor or designee review. 


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x The initial SAE report should include: 
o The date of the report 
o A description of the SAE (event term, seriousness of the event, date of onset, 
intensity) 
o Causal relationship to the study drug 
 A discharge summary should be provided for all hospitalizations. If the subject died, 
the report should include the cause of death as the event term (with death as the 
outcome) and whether the event leading to death was related to study drug, as well as 
the autopsy findings, if available 
x Nonserious AESIs should be reported on the eCRF within 72 hours of knowledge of the 
information.  
x 
It is not acceptable for the investigator to send photocopies of the subject’s medical 
records to the Sponsor or designee in lieu of completion of the AE or SAE eCRF page. 
x 
There may be instances when copies of medical records for certain cases are requested by 
the Sponsor or designee. In this case, all subject identifiers, with the exception of the 
subject number, will be redacted on the copies of the medical records before submission 
to the Sponsor. 
x 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
1/MILD 
Asymptomatic or mild symptoms, clinical or diagnostic observations only; intervention 
not indicated. 
2/MODERATE 
Minimal, local, or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living 
3/SEVERE OR 
MEDICALLY 
SIGNIFICANT 
Not immediately life-threatening; hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self-care activities of daily living  
4/LIFE-
THREATENING 
Life threatening consequences; urgent intervention indicated 
5/DEATH 
Death related to adverse event 
An event is defined as serious when it meets at least one of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 


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Assessment of Causality 
x 
The investigator is obligated to assess the relationship between study drug and each 
occurrence of each AE or SAE. 
x 
A reasonable possibility of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
x 
The investigator will use clinical judgment to determine the relationship. 
x 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study drug administration will 
be considered and investigated. 
x 
The investigator will also consult the Investigator’s Brochure and/or product information, 
for marketed products, in his/her assessment. 
x 
For each AE or SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE or SAE and has provided an assessment of causality. 
x 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor or designee. However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE to the Sponsor or designee. 
x 
The investigator may change his/her opinion of causality in light of follow-up information 
and send an SAE follow-up report with the updated causality assessment. 
x 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
Reporting of SAEs 
SAE Reporting 
All SAEs must be reported in the eCRF within 24 hours of the study site personnel’s 
knowledge of the event, regardless of the investigator assessment of the relationship of the 
event to study drug. Marking the event as “Serious” will activate additional assessment fields. 
 


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10.4. 
Appendix 4: Abbreviations 
Term 
Description 
5-ARI 
5α-reductase inhibitors 
AE 
adverse event 
AESI 
Adverse Events of Special Interest 
ALT 
alanine aminotransferase 
APR 
abdominoperineal resection 
AR 
adrenergic receptor 
AST 
aspartate aminotransferase 
β3-AR 
beta-3 adrenergic receptor 
BPH 
benign prostatic hypertrophy 
cAMP 
cyclic adenosine monophosphate 
CFB 
change from baseline 
CFR 
Code of Federal Regulations 
CFU 
colony-forming unit 
CIC 
clean intermittent catheterization 
CIOMS 
Council for International Organizations of Medical Sciences 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
case report form 
CT 
computerized tomography 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
ED 
erectile dysfunction 
eGFR 
estimated glomerular filtration rate 
 
 
FAS 
full analysis set 
FAS-I 
full analysis set for incontinence 
FDA 
(United States) Food and Drug Administration 
GCP 
good clinical practice 
HRQL 
health-related quality of life 
ICF 
informed consent form 
ICH 
International Council on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 


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Term 
Description 
ICS 
International Continence Society 
IDC 
involuntary detrusor contraction 
IEC 
independent ethics committee 
 
 
INR 
international normalized ratio 
IPSS 
International Prostate Symptom Score 
IRB 
institutional review board 
IWRS 
interactive web response system 
LAR 
low anterior resection 
LF 
long form 
LUTS 
lower urinary tract symptoms 
MCC 
maximum cystometric capacity 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed model for repeated measure 
MRI 
magnetic resonance imaging 
OAB 
overactive bladder 
 
 
Pdet@1st IDC 
maximum detrusor pressure during the first involuntary detrusor contraction 
Pdet@Max Storage 
maximum detrusor pressure during the storage phase  
Pdet@QMax 
Detrusor pressure at peak flow rate  
PGI 
Patient Global Impression 
PRO 
patient-reported outcome 
PSA 
prostate-specific antigen 
PT 
preferred term 
PTNS 
percutaneous tibial nerve stimulation 
PVR 
post-void residual 
QD 
once daily 
Qmax 
maximum urinary flow; peak flow rate during voiding 
QTc 
corrected QT 
RBC 
red blood cell 
REB 
research ethics board  
REML 
restricted (or residual) maximum likelihood 
SAE 
serious adverse event 


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Term 
Description 
SAF 
Safety Analysis Set 
SAP 
statistical analysis plan 
SNS 
sacral neurostimulation 
SOC 
System Organ Class  
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
ULN 
upper limit of normal 
Urovant 
Urovant Sciences GmbH 
US 
United States 
UTI 
urinary tract infection 
Vol@1st IDC 
volume at first involuntary detrusor contraction  
VV 
voided volume  
WBC 
white blood cell 
WHO-DDE 
World Health Organization Drug Dictionary Enhanced 


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10.5. 
Appendix 5: Study Tabular Summary 
Parameter 
Group 
Parameter 
Value 
Trial 
information 
Trial Title 
A Phase 3 Double-Blind, Randomized, 
Placebo-Controlled, Multi-Center 
Study to Evaluate the Efficacy, Safety 
and Tolerability of Vibegron in Men 
with Overactive Bladder (OAB) 
Symptoms on Pharmacological 
Therapy for Benign Prostatic 
Hyperplasia (BPH) 
 
Clinical Study Sponsor 
Urovant Sciences, GmbH 
 
Trial Phase Classification 
Phase 3 
 
Trial Indication 
OAB Symptoms in Men with BPH 
 
Trial Indication Type 
Treatment 
 
Trial Type 
Randomized, controlled, double-blind 
 
Trial Length 
Up to 25 weeks 
 
Planned Country of Investigational Sites 
North America and Europe 
 
Planned Number of Subjects 
1088 enrolled; 924 evaluable 
 
FDA-Regulated Device Study 
No 
 
FDA-Regulated Drug Study 
Yes 
 
Pediatric Study 
No 
Subject 
information 
Diagnosis Group 
OAB Symptoms with BPH 
Healthy Subject Indicator 
No 
 
Planned Minimum Age of Subjects 
45 
 
Planned Maximum Age of Subjects 
None 
 
Sex of Subjects 
Male 
 
Stable Disease Minimum Duration 
3 months 


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Parameter 
Group 
Parameter 
Value 
Treatments 
Investigational Therapy or Treatment 
vibegron 
 
Drug Type 
drug 
 
Pharmacological Class of Invest. Therapy 
beta-3 adrenergic receptor agonist 
 
Dose per Administration 
75 
 
Dose Units 
mg 
 
Dosing Frequency 
Once daily 
 
Route of Administration 
Oral 
 
Current Therapy or Treatment 
Pharmacotherapy for BPH: alpha 
blocker monotherapy or alpha blocker 
+ 5 ARI 
 
Added on to Existing Treatments 
Subjects not receiving current 
treatments for OAB symptoms 
 
Control Type 
Placebo 
 
Comparative Treatment Name 
-- 
Trial design 
Study Type 
Randomized, controlled, double-blind 
 
Drug Model 
Parallel 
 
Planned Number of Arms 
2 
 
Trial is Randomized 
Yes 
 
Randomization Quotient 
1:1 
 
Trial Blinding Schema 
Double blind 
 
Stratification Factor 
Baseline average micturition episodes 
per day (≤ 12 vs > 12), alpha blocker 
use with or without 5-ARI (yes or no), 
and urinary incontinence (yes or no) 
 
Adaptive Design 
No 
BPH = benign prostatic hypertrophy; FDA = Food and Drug Administration; OAB = overactive 
bladder 
 


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10.6. 
Appendix 6: Prohibited Medications and Non-Drug Therapies 
The following medications are prohibited, as outlined in Section 6.5.1. 
Prohibited Medications Class 
Examples  
Washout Period/Comments  
Anticholinergics  
darifenacin, fesoterodine, 
hyoscyamine, oxybutynin, 
propantheline, solifenacin, 
tolterodine, and trospium  
Subject must discontinue use at least 28 days 
prior to beginning completion of the 
Screening Bladder Diary and remain off this 
therapy during the study. If an 
anticholinergic/ antimuscarinic is used in an 
inhaler on a PRN/ as needed basis for the 
treatment of chronic obstructive pulmonary 
disease, it will be permitted.  
Smooth muscle relaxants  
flavoxate, dicyclomine, 
propiverine  
Subject must discontinue use at least 28 days 
prior to beginning completion of the 
Screening Bladder Diary and remain off this 
therapy during the study  
Beta-2 adrenergic agonists used for the 
treatment of stress urinary incontinence  
clenbuterol  
Subject must discontinue use at least 28 days 
prior to beginning completion of the 
Screening Bladder Diary and remain off this 
therapy during the study  
Systemic beta-2 adrenergic agonist  
terbutaline  
No washout period; subject must remain off 
this therapy during the study  
Antidiuretic hormones  
desmopressin  
Subject must discontinue use at least 28 days 
prior to beginning completion of the 
Screening Bladder Diary and remain off this 
therapy during the study  
Beta-3 adrenergic agonists  
mirabegron  
Subject must discontinue use at least 28 days 
prior to beginning completion of the 
Screening Bladder Diary and remain off this 
therapy during the study  
New start of BPH medications  
Alpha-Blockers, eg, alfuzosin, 
doxazosin, silodosin, 
tamsulosin, and terazosin  
5-ARI, eg, alfatradiol, 
dutasteride, and finasteride  
PDE5 inhibitors, eg, tadalafil  
Subject must not start new use of these 
therapies during the study.  
Intradetrusor or intraprostatic 
botulinum toxins  
 
  
intradetrusor injection of 
botulinum toxin or 
intraprostatic injections   
Subject must not have received an injection 
within 6 months prior to the Screening Visit 
and must not receive this therapy during the 
study  
Any herbal medications to treat OAB 
symptoms, lower urinary tract 
symptoms of BPH or erectile 
dysfunction 
 
Subject must not have received the herbal 
medications within 28 days prior to the 
Screening Visit and must not receive them 
during the study. 
Diuretics 
 
Subject must not start new diuretics during 
the study. 
Percutaneous tibial nerve stimulation 
(PTNS) 
 
Subject must not start new PTNS or related 
therapies during the study. 
 
 


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10.7. 
Appendix 7: Study Schedule Supplement 
Note that subject assessments and procedures that can be done either on-site or remotely (without 
in-person subject contact) are marked with an asterisk (*).  
In addition, to account for additional time that may be necessary to ensure site and subject safety 
through COVID-19 preventive measures, extended windows for visit timings have been 
implemented for Part 2. Refer to the Schedule of Assessments – Part 2 (Section 1.4) for 
additional details. As feasible, study visits should adhere to the schedule outlined in the original 
protocol and shown in the sections below. 
Note that Bladder Diaries may be dispensed or returned remotely (ie, delivered by mail or 
courier) and may be dispensed at an earlier timepoint. If dispensing in-person, ensure an 
adequate supply of diaries is provided (eg, diaries to be completed by the subject prior to Week 
16 and Week 20 are dispensed at Week 12). 
10.7.1. 
Screening, Visit 1 (Day -49 to Day -14) 
Screening visit assessments must be performed prior to Run-in to determine subject eligibility 
with time for analysis and reporting of all results. Assessments may be performed in a single day 
or may be done over multiple days within the screening period. 
x Obtain Informed Consent (*may be conducted remotely per approved IRB/IEC process, 
where applicable) 
x Begin recording AEs/SAEs after signing ICF* 
x Enter subject into IWRS and subject registry 
x Assess inclusion/exclusion criteria* 
x Collect demographic data* 
x Collect medical and surgical history data including use of illicit drugs, alcohol, and 
tobacco* 
x Collect prior and current OAB and BPH pharmacotherapies*  
x Collect concomitant medications* 
x Administer IPSS scale* 
x Record blood pressure (3 results taken 1-2 minutes apart after sitting for 5 minutes), 
pulse, respiration, temperature, weight, and height (Part 2 subjects only) 
x Record respiration, temperature, weight, and height, and record triplicate orthostatic 
blood pressure (sitting blood pressure taken 1-2 minutes apart after sitting for 5 minutes, 
standing blood pressure taken 1-2 minutes apart within 3 minutes of standing) and 
orthostatic heart rate (by pulse) measurements (Part 1 subjects only) 


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x Perform brief physical examination 
x Perform 12-lead ECG 
x Collect uroflowmetry (eg, Qmax) 
x Collect prostate volume (in mL) via ultrasound (if no measurement is available in 
preceding 12 months); note that the prostate volume may be completed at any time prior 
to randomization 
x Measure post-void residual volume 
x Perform laboratory assessments 
x Dispense Bladder Diary and instruct subject on its completion* 
10.7.2. 
Run-in, Visit 2 (Day -14 r 4 days) 
x Assess inclusion/exclusion criteria 
x Review concomitant medications*  
x Review AEs/SAEs*  
x Review and data enter completed Bladder Diary* 
x Record blood pressure (3 results taken 1-2 minutes apart after sitting for 5 minutes), 
pulse, respiration, temperature, and weight (Part 2 subjects only) 
x Record respiration, temperature, and weight at Hour 0, and record triplicate orthostatic 
blood pressure (sitting blood pressure taken 1-2 minutes apart after sitting for 5 minutes, 
standing blood pressure taken 1-2 minutes apart within 3 minutes of standing) and 
orthostatic heart rate (by pulse) measurements at Hour 0 (pre-dose) (Part 1 subjects only) 
x Measure post-void residual volume 
x Dispense study drug for single-blind Run-in Period 
x Administer witnessed dose of study drug (Part 1 subjects only)  
x Dispense Bladder Diary* 
x If not collected previously (and not available within 12 months of Screening), collect 
prostate volume (in mL) via ultrasound any time prior to randomization 
10.7.3. 
Baseline, Visit 3 (Day 1) 
x Assess inclusion/exclusion criteria 
x Review concomitant medications*  
x Review AEs/SAEs* 
x Review and data enter completed Bladder Diary* 


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x Administer IPSS,
 PGI,
scales* 
x Record blood pressure (3 results taken 1-2 minutes apart after sitting for 5 minutes), 
pulse, respiration, temperature, and weight (Part 2 subjects only) 
x Record respiration, temperature, and weight at Hour 0, and record triplicate orthostatic 
blood pressure (sitting blood pressure taken 1-2 minutes apart after sitting for 5 minutes, 
standing blood pressure taken 1-2 minutes apart within 3 minutes of standing) and 
orthostatic heart rate (by pulse) measurements at Hour 0 (pre-dose) and 1, 2, 4, and 
6 hours (r 15 minutes) post-dose (Part 1 subjects only)  
x Perform brief physical examination 
x If not performed previously (and not available within 6 months prior to Screening), 
perform urodynamics assessment any time prior to randomization (for sub-study in Part 2 
only) 
x Measure post-void residual volume 
x Perform laboratory assessments 
x Dispense double-blind study drug 
x Administer witnessed dose of study drug 
x Option to dispense paper PRO questionnaires and diaries 
x Dispense Bladder Diaries* (for completion at Week 2) 
10.7.4. 
REMOTE Double-blind Treatment Period, Visit 4 (Week 1  4 days) 
x Review concomitant medications*  
x Review AEs/SAEs* 
10.7.5. 
Double-blind Treatment Period, Visit 5 (Week 2 r 4 days) 
x Review concomitant medications*  
x Review AEs/SAEs* 
x Review and data enter completed Bladder Diary* 
x Record blood pressure (3 results taken 1-2 minutes apart after sitting for 5 minutes), 
pulse, respiration, temperature, and weight (Part 2 subjects only) 
x Record respiration, temperature, and weight at Hour 0, and record triplicate orthostatic 
blood pressure (sitting blood pressure taken 1-2 minutes apart after sitting for 5 minutes, 
standing blood pressure taken 1-2 minutes apart within 3 minutes of standing) and 
orthostatic heart rate (by pulse) measurements at Hour 0 (pre-dose) and 1, 2, 4, and 6 
hours (r 15 minutes) post-dose (Part 1 subjects only) 
x Measure post-void residual volume 


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x Administer witnessed dose of study drug (Part 1 subjects only)  
x Dispense Bladder Diary* 
10.7.6. 
Double-blind Treatment Period, Visit 6 (Week 4 r 4 days)  
x Review concomitant medications*  
x Review AEs/SAEs* 
x Review and data enter completed Bladder Diary*  
x Administer IPSS and PGI scales* 
x Record blood pressure (3 results taken 1-2 minutes apart after sitting for 5 minutes), 
pulse, respiration, temperature, and weight (Part 2 subjects only) 
x Record respiration, temperature, and weight at Hour 0, and record triplicate orthostatic 
blood pressure (sitting blood pressure taken 1-2 minutes apart after sitting for 5 minutes, 
standing blood pressure taken 1-2 minutes apart within 3 minutes of standing) and 
orthostatic heart rate (by pulse) measurements at Hour 0 (pre-dose) and 1, 2, 4, and 6 
hours (r 15 minutes) post-dose (Part 1 subjects only) 
x Measure post-void residual volume 
x Perform laboratory assessments 
x Dispense double-blind study drug* 
x Administer witnessed dose of study drug (Part 1 subjects only) 
x Dispense Bladder Diary* 
10.7.7. 
Double-blind Treatment Period, Visit 7 (Week 8 r 4 days) and Visit 10 (Week 20 
r 4 days) 
x Review concomitant medications*  
x Review AEs/SAEs* 
x Review and data enter completed Bladder Diary*  
x Administer IPSS scale* 
x Record blood pressure (3 results taken 1-2 minutes apart after sitting for 5 minutes), 
pulse, respiration, temperature, and weight 
x Measure post-void residual volume 
x Dispense double-blind study drug* 
x Dispense Bladder Diary*  


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10.7.8. 
Double-blind Treatment Period, Visit 8 (Week 12 r 4 days) 
x Review concomitant medications*  
x Review AEs/SAEs* 
x Review and data enter completed Bladder Diary* 
x Administer IPSS, 
 PGI, 
 scales* 
x Record blood pressure (3 results taken 1-2 minutes apart after sitting for 5 minutes), 
pulse, respiration, temperature, and weight 
x Perform brief physical examination 
x Measure post-void residual volume 
x Urodynamics (for sub-study in Part 2 only) 
x Perform laboratory assessments 
x Dispense double-blind study drug* 
x Dispense Bladder Diaries* (for Week 16 and Week 20) 
10.7.9. 
REMOTE Double-blind Treatment Period, Visit 9 (Week 16 r 4 days) 
x Review concomitant medications*  
x Review AEs/SAEs* 
x Review and data enter completed Bladder Diary*  
x Remind subject to mail/drop-off Week 16 diary or bring it to the Week 20 visit 
x Dispense Bladder Diary (if not previously dispensed)* 
10.7.10. 
Double-blind Treatment Period, Visit 11 (Week 24 r 4 days) or Early 
Withdrawal) 
x Review concomitant medications*  
x Review AEs/SAEs* 
x Review and data enter completed Bladder Diary* 
x Administer IPSS,
, PGI,
 scales* 
x Record blood pressure (3 results taken 1-2 minutes apart after sitting for 5 minutes), 
pulse, respiration, temperature, and weight 
x Perform brief physical examination 
x Collect prostate volume (in mL) via ultrasound 
x Measure post-void residual volume 
x Collect uroflowmetry (eg, Qmax) 


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x Perform laboratory assessments 
10.7.11. 
Safety Follow-up (for subjects who do not enter the extension Study URO-901-
3006; 5 days after last dose of study drug [± 2 days]) 
Telephone contact with the subject for the following follow-up: 
x Review concomitant medications  
x Review AEs/SAEs 
10.8. 
Appendix 8: Patient-Reported Outcomes Questionnaires, 
Descriptions, and Instructions 
Information on each of the scales and questionnaires for patient-reported outcomes are provided 
below. A sample for each assessment is also provided. 
10.8.1. 
International Prostate Symptom Score (IPSS) 
The International Prostate Symptom Score (IPSS) is based on the responses to 7 questions 
concerning urinary symptoms and 1 question concerning quality of life. Each question 
concerning urinary symptoms allows the subject to choose 1 out of 6 answers indicating 
increasing severity of the particular symptom. The responses are assigned points from 0 to 5. The 
total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). 
The questions refer to the following urinary symptoms: 
Questions 
Symptom 
1 
Incomplete emptying 
2 
Frequency 
3 
Intermittency 
4 
Urgency 
5 
Weak Stream 
6 
Straining 
7 
Nocturia 
Question 8 refers to the subject’s perceived quality of life. 
The first 7 questions of the I-PSS are identical to the questions appearing on the American 
Urological Association (AUA) Symptom Index which currently categorizes symptoms as 
follows: 
Mild (symptom score ≤ 7) Moderate (symptom score range 8 to 19) Severe (symptom score 
range 20 to 35) 
The answers to the single question to assess the quality of life this question range from 
“delighted” to “terrible” or 0 to 6. Although this single question may or may not capture the 


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global impact of BPH Symptoms or quality of life, it may serve as a valuable starting point for a 
doctor-patient conversation.
A sample of the IPSS is provided below:


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10.8.4.
Patient Global Impression Scale
The Patient Global Impression (PGI) scale in this study is an OAB-specific quality of life 
questionnaire focused on 3 key aspects of the symptoms of the condition 
[PGI-
 


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Bother [PGI- B] and Improvement [PGI- I]). The tool was designed to assess the impact (and 
improvement) of urinary incontinence on activities of daily living, wellbeing, and function. The 
PGI scales are brief, general (ie, do not collect speciﬁc symptoms in contrast to other outcome 
measures for OAB), and easily completed.  


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10.9. 
Appendix 9: Summary of Previous Protocol Amendments 
10.9.1. 
Protocol Amendment 1, 30 July 2020 
The study protocol was previously amended on 30 July 2020 with the following notable changes: 
x Cover Page 
o Corrected street address for Urovant GmbH Swiss offices 
o Updated street address for Urovant US offices 
x Section 1.1 Synopsis, Overall Study Design 
o Changed the timing for Safety Follow Up telephone call from “21 days (+ up to 
4 days) after the subject’s last dose of study treatment (ie, at Week 27 for subjects 
who complete the Week 24 Visit, or approximately 3 weeks after withdrawal for 
subjects who discontinue the study early)” to “5 days (± up to 2 days) after the 
subject’s last dose of study treatment (or approximately 5 days [± up to 2 days] after 
withdrawal for subjects who discontinue the study early)” 
o Updated table with study visit schedule accordingly 
x Section 1.2, Schema for Parts 1 and 2 
o Changed timing for Safety Follow-Up telephone call from Day 190 (or 21 days 
following withdrawal) to Day 174 (or 5 days following withdrawal) for subjects who 
do not participate in the optional 28-week extension study 
x Sections 1.3 and 1.4, Schedule of Assessments (Part 1 and Part 2, respectively) 
o Changed window for Screening (Visit 1) from “-49 to -21 days” to “-49 to -14 days”; 
added new footnote “a” and updated numbering for other footnotes to clarify that all 
Screening procedures and the 3-day Bladder Diary must be completed prior to the 
Run-In (Visit 2). 
o Updated timing for Safety Follow-Up telephone call (ie, to 5 days ± 2) 
o Clarified that a prostate volume measurement taken within 12 months prior to the first 
day of Screening may be accepted in lieu of a Screening (Visit 1) measurement 


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x Section 4.1 Overall Design 
o Changed the timing for Safety Follow Up telephone call from “21 days (+ up to 
4 days) after the subject’s last dose of study treatment (ie, at Week 27 for subjects 
who complete the Week 24 Visit, or approximately 3 weeks after withdrawal for 
subjects who discontinue the study early)” to “5 days (± up to 2 days) after the 
subject’s last dose of study treatment (or approximately 5 days [± up to 2 days] after 
withdrawal for subjects who discontinue the study early)” 
x Section 4.4 End of Study Definition 
o Removed “Week 27” descriptor used to define the Safety Follow-up timepoint 
x Section 5.2 Exclusion Criteria 
o Changed Exclusion Criterion #7 from “Subject is taking or using any medications to 
treat erectile dysfunction (ED) and is not using them on a regular schedule. (ED 
medications with a short half-life such as sildenafil and vardenafil are allowed if used 
2 times or less per week in the past 3 months and during the study.)” to “Irregular use 
of any medications to treat erectile dysfunction (ED). If ED medication is used on an 
irregular basis, ED medications with a short half-life such as sildenafil and vardenafil 
are allowed.” 
o Changed timeframe in Exclusion Criterion #9 for exclusion of herbal supplements 
from “in the past 3 months” to “in the past 28 days prior to Screening” 
o Changed timeframe for Exclusion Criterion #10 for subject who started using 
diuretics from “within 3 months prior to Screening” to “within 28 days prior to 
Screening”. Also, changed timeframe in Exclusion Criterion #10 for subjects who 
were already taking a diuretic to allow for continuation of stable doses of diuretics 
from “at least 3 months prior to Screening” to “at least 28 days prior to Screening”.   
o Clarified that “prior” diagnosis of diabetes insipidus (Exclusion Criterion #18) or 
sleep apnea (Exclusion Criterion #19) were exclusionary (ie, not just diagnoses 
identified at the Screening visit). 
o Removed Exclusion Criterion #21: “Has known or suspected HIV or AIDS or 
unexplained alarm symptoms (eg, anemia, gastrointestinal bleeding, unintentional 
weight loss, suspected malignancy).” The item Exclusion Criterion #21 has been left 


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as blank intentionally to preserve the exclusion criteria numbering from the original 
protocol. 
o Removed Exclusion Criterion #33: Clarified duration for stable doses of prior 
medication from “4 weeks” to “28 days” for consistency in terminology with other 
criteria. 
o Additional minor clarifications were made to ensure consistency for duration of 1 
month (4 weeks) for consistency (Exclusion Criterion #33)  
x Section 5.4 Screen Failures 
o Removed redundant restriction that, if applicable, rescreening must occur “during the 
screening period”  
x Section 6.1.1 Run-in Medication and Administration 
o Clarified that the duration of medication administration during Run-in Period is 
“approximately” 2 weeks to account for the allowable ± 4-day window 
x Section 8.1.6, Prior and Concomitant Medications 
o Changed duration of monitoring of concomitant medications from 21 days to 5 days 
after the last dose of study drug  
x Section 8.3.6, Clinical Safety Laboratory Assessments 
o Changed duration of monitoring for clinically significant laboratory abnormalities 
from 21 days to 5 days after the last dose of study drug  
x Section 8.3.8, Prostate Volume Measurement 
o Added the following statement “Prostate volume measurement (by ultrasound) 
assessed within 12 months prior to the first day of Screening may be accepted in lieu 
of a Screening (Visit 1) measurement.” 
x Section 8.4.1, Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information 
o Changed timeframe for collection of AEs and SAEs from through 21 days after the 
last dose of study drug to through 5 days after the last dose of study drug. 
x Section 9.4.3.1, Adverse Events 
o Changed window for definition of treatment-emergent adverse events from “An AE 
that occurs more than 21 days after the last dose of study drug will not be counted as 


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a TEAE.” to An AE that occurs more than 5 days after the last dose of study drug will 
not be counted as a TEAE.” 
x Appendix 3, Definition of an AE 
o Added that abnormal laboratory results (hematology, clinical chemistry, or urinalysis) 
identified during Screening will not be considered as adverse events  
x Appendix 5, Study Tabular Summary 
o Changed trial length from “Up to 27 weeks” to “Up to 25 weeks" 
x Appendix 6, Prohibited Medications and Non-Drug Therapies 
o Reduced window of restriction for “any herbal medications to treat OAB symptoms, 
lower urinary tract symptoms of BPH or erectile dysfunction” from “in the past 3 
months” to “within 28 days prior to the Screening Visit”.  
x Appendix 7, Section 10.7.1, Screening Visit  
o Changed window for Screening (Visit 1) from “(Day -49 to Day -21)” to “(Day -49 to 
Day -14)” 
o Added “(if no measurement is available in preceding 12 months)” to bullet: Collect 
prostate volume (in mL) via ultrasound 
x Appendix 7, Section 10.7.10, Safety Follow-Up Visit 
o Changed timing from 3 weeks (±4 days) to 5 days (±2 days) 
10.9.2. 
Protocol Amendment 2, 16 December 2020 
The study protocol was previously amended on 16 December 2020 with the following notable 
changes: 
x Cover Page was updated with new Sponsor Contact information 
x Section 1.1 Synopsis, Secondary Efficacy Endpoints 
o Clarified that the International Prostate Symptom Score (IPSS) Storage (1-week 
recall) endpoint was not based on an average score 
x Section 1.1 Synopsis, Overall Study Design and Section 1.2, Schema for Parts 1 and 2 
o Updated to reflect that visits at Week 1 (Visit 4) and Week 16 (Visit 9) in Part 2 will 
be conducted by telephone/video call to minimize in-person contact during the 
COVID-19 pandemic; this change will remain in effect after resolution of the 
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x Section 1.1 Synopsis, Study Drug Groups and Study Duration 
o Added additional examples of alpha blockers (terazosin and silodosin) 
x Section 1.2 Schema for Parts 1 and 2 
o Updated to reflect the changes to study visits as described above (ie, Visit 4 and Visit 
9 to be conducted by telephone or video call) 
x Section 1.4, Schedule of Assessments - Part 2 
o Added an extended COVID-19 mitigation window in Part 2 to provide for additional 
timing for visits impacted by restrictions due to the COVID-19 pandemic 
o Updated to reflect that visits at Week 1 (Visit 4) and Week 16 (Visit 9) in Part 2 will 
be conducted via telephone or video call to minimize in-person contact during the 
COVID-19 pandemic; this change will remain in effect after resolution of the 
COVID-19 pandemic  
o Removed prostate volume measurement from Week 24 or Early Withdrawal 
(Visit 11) because the prostate volume is not expected to have a clinically relevant 
change between Baseline and Visit 11 
o Removed uroflowmetry from Baseline (Visit 3) because this assessment will have 
been done at Screening and does not need to be repeated 
o Clarified that if no historical prostate volume measurement is available within 
12 months of Screening, a prostate volume measurement by ultrasound must be 
performed prior to randomization (ie, done at any time between Screening and 
Baseline) 
o Updated footnotes to reflect the above changes 
o Clarified the timing for collection of 3-day Bladder Diaries  
x Section 2.4.2, Potential Risks 
o Updated background information to reflect study population in Phase 3 program in 
OAB (RVT-901-3003 and RVT-901-3004) 
x Section 3, Objectives and Endpoints 
o Clarified that the IPSS Storage (1-week recall) endpoint is not based on an average 
score, because it is based on a single value reported at each relevant timepoint  


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o Added CFB at Week 4, Week 8, Week 12, Week 20, and Week 24 in the IPSS 
Voiding score (1-week recall) as an “Other/exploratory endpoint” 
o Removed Week 16 timepoint from IPSS-associated endpoints  
o Clarified that endpoints for 50% and 75% reduction from baseline in urgency and 
urge urinary incontinence are based on average number of daily episodes 
x Section 4.1, Objectives and Endpoints 
o Updated to reflect that visits at Week 1 (Visit 4) and Week 16 (Visit 9) in Part 2 will 
be conducted via telephone or video call to minimize in-person contact during the 
COVID-19 pandemic; this change will remain in effect after resolution of the 
COVID-19 pandemic 
x Section 5.2, Exclusion Criteria 
o Clarified definition of positive urine culture results (ie, 105 CFU/mL, equivalent to 
100 × 103 CFU/mL) 
x Section 6.1, Study Drugs Administered 
o Clarified that for post-Baseline timepoints, double-blind study drug may be dispensed 
to the subject by means to minimize in-person contact (eg, trackable courier or 
curbside pickup) 
x Section 7.3, Lost to Follow-Up 
o Clarified that if a subject misses a visit and does not return for a rescheduled visit and 
cannot be reached to reschedule, the site should make every effort to ensure that all 
dispensed study medication is returned in addition to attempting to regain contact 
with the subject so that they can appropriately be withdrawn from the study  
x Section 8, Study Assessments and Procedures 
o Added a bulleted note that certain study assessments and procedures may be 
performed telephone/video call due to the COVID-19 pandemic.  
x Section 8.2, Efficacy Assessments 
o Clarified that when subjects complete PRO assessment forms remotely, they should 
be completed just prior to the applicable visit  
x Section 8, Study Assessments and Procedures 


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o Added a bulleted note that certain study assessments and procedures may be 
performed telephone/video call due to the COVID-19 pandemic.  
x Section 8.2.1, Bladder Diaries 
o Added that a prescreening Bladder Diary may be provided to potential study subjects 
in order to minimize on-site contact and assess subject’s ability to comply with diary 
completion. 
x Section 8.3.4, Electrocardiograms 
o Added that electrocardiograms (ECGs) may be read by appropriate site delegates who 
are medically qualified 
x Section 8.3.5, Post-Void Residual Volume 
o Clarified that “ultrasound” also refers to a bladder scanner 
x Section 8.3.7, Urodynamics Assessment 
o Clarified that the number of subjects expected to participate in the Urodynamics 
Substudy is approximately 60. 
x Section 8.3.8, Prostate Volume Measurement 
o Clarified that if no historical prostate volume measurement is available within 12 
months of Screening, a prostate volume measurement by ultrasound must be 
performed prior to randomization (ie, done at any time between Screening and 
Baseline) 
x Section 8.4.6, Adverse Events of Special Interest 
o Clarified that adverse events (AEs) of urinary retention are those events in which the 
subject has a raised PVR that requires catherization in addition to one of the criteria 
specified in the bulleted list 
o Clarified definition of positive urine culture results (ie, 105 CFU/mL, equivalent to 
100 × 103 CFU/mL) 
o Clarified that an AE of “increased blood pressure” should be recorded if, in the 
investigator’s opinion, an elevated blood pressure measurement is clinically 
significant but does not fulfill the definition for hypertension  
x Section 8.6, Safety Measures due to COVID-19 Pandemic 


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o Added this section to clarify the types of subject assessments that may be done 
remotely (via telephone or video call) to minimize in-person contact 
o Clarified that if a subject misses the Week 12 visit (Visit 8) due to restrictions 
resulting from the COVID-19 pandemic an early withdrawal visit (Visit 11) should be 
conducted when safe and feasible. However, if a subject missed any other single on-
site visit, then the site should collect the completed Bladder Diary (eg, by curbside 
pickup, mail, or courier) and remotely review AEs/SAEs and concomitant 
medications and dispense study drug (ie, subject will not be considered lost to follow-
up).  
x Section 9.2, Populations for Analyses 
o Made minor clarifications to the defined populations to align with the statistical 
analysis plan, including the addition of the Per-Protocol Set (PPS) and Per-Protocol 
Set for Incontinence (PPS-I) 
o Added the following statement to clarify sample size and statistical power estimates 
for Baseline BPH treatment subgroups: “The impact of imbalances in 5-ARI plus 
alpha blockers versus alpha blockers alone will be monitored and controlled if 
needed.” 
x Section 9.4.2.1, Analysis Endpoints 
o Clarified that the IPSS Storage (1-week recall) endpoint is not based on an average 
score, because it is based on a single value reported at each relevant timepoint 
x Section 10.6 Appendix 6, Prohibited Medications and Non-Drug Therapies 
o Added additional examples of alpha blockers (terazosin and silodosin) 
x Section 10.7, Appendix 7: Study Schedule Supplement 
o Added option to dispense paper PRO questionnaires and diaries 
o Clarified subject assessments and study procedures that may be done remotely for 
COVID-19 safety precautions; this change will remain in effect after resolution of the 
COVID-19 pandemic 
o Removed requirement for blood pressure measurement and post-void residual volume 
from list of study assessments for Visit 4 and Visit 9, as these visits will be conducted 


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by telephone or video call, and there are on-site assessments of these parameters 
before and after both visits. 
o Clarified procedures to align with the Schedule of Assessments – Part 2 
o Separated Visit 9 (Week 16) schedule into a new (standalone) subsection to reflect 
that this visit will be conducted remotely via telephone or video call 
x Section 10.9, Appendix 9: Summary of Previous Protocol Amendments 
o Created a new appendix to provide a list of changes previously implemented by 
Protocol Amendment 1 
In addition to the above-listed changes, minor edits were made for clarity throughout document 
(eg, added “approximately” to duration of study periods, added/updated cross-references, fixed 
punctuation or minor typographical errors). 
 


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11. 
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Donnell R, Foster H, Gonzalez C, Kaplan S, Penson D, Ulchaker J, Wei, J. Management 
of Benign Prostatic Hyperplasia; Published 2010; Reviewed and Validity Confirmed 
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Biers, SM, Reynard, JM and Brading, AF. The effects of a new selective β3- adrenoceptor 
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Chapple CR, et al. Persistence and Adherence with Mirabegron versus Antimuscarinic Agents in 
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Donnelly AJ, Jochnowitz N, Hurley AL, Pereira A, Sanfiz A, Veronin G, Villa K, Woods 
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Goldman HB, Anger JT, Esinduy CB, Zou KH, Russell D, Luo X, Ntanios F, Carlsson MO, 
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United States. Urol 2016;87:64-9. 
Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson 
EB. Cumulative use of strong anticholinergics and incident dementia: a prospective 
cohort study. JAMA Intern Med 2015 Mar;175(3):401-7. 
Helfand BT, Evans RM, McVary KT. A Comparison of the Frequencies of Medical Therapies 
for Overactive Bladder in Men and Women: Analysis of More than 7.2 Million Aging 
Patients. Eur Assoc Urol 2012;57:586-591. 
Hyman MJ, Groutz A, Blaivas JG. Detrusor instability in men: correlation of lower urinary tract 
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Ichihara K, Masumori N, Fukuta F, TsukamotoT, Iwasawa A, Tanaka Y. A Randomized 
Controlled Study of the Efficacy of Tamsulosin Monotherapy and its Combination with 
Mirabegron for Overactive Bladder Induced by Benign Prostatic Obstruction. J Urol. 
2014;193(3). 
Kaidoh K, Igawa Y, Takeda H, Yamazaki Y, Akahane S, Miyata H, Ajisawa Y, Nishizawa O, 
Andersson KE. Effects of selective [beta]2 and [beta]3- Adrenoceptor agonists on 
detrusor hyperreflexia in conscious cerebral infarcted rats. J Urol 2002;168:1247-52. 
MacDiarmid SA, Peters KM, Chen A, Armstrong RB, Orman C, Aquilina JW, et al. Efficacy and 
safety of extended- release oxybutynin in combination with tamsulosin for treatment of 
lower urinary tract symptoms in men: randomized, double- blind, placebo- controlled 
study. Mayo Clinic Proceedings. 2008;83(9):1002- 10. 
Maman K, Aballea S, Nazir J, Desroziers K, Neine ME, Siddiqui E, Odeyemi I, Hakimi 
Z.  Comparative efficacy and safety of medical treatments for the management of 
overactive bladder: a systematic literature review and mixed treatment comparison.  Eur 
Urol. 2014 Apr;65(4):755-65. 
Milsom I, Abrams P, Cardozo L, Roberts RG, Thüroff J, Wein AJ. How widespread are the 
symptoms of an overactive bladder and how are they managed? A population-based 
prevalence study. BJU International 2001;87:760-6. 
Mybertiq Prescribing Information. Astellas. Revised: [08/2016]. Available at: 
https://www.myrbetriq.com/. Accessed: 02 April 2017. 
Nakagawa H, Ikeda Y, Niu K, Kaiho Y, Ohmori-Matsuda K, Nakaya N, et al. Does nocturia 
increase fall-related fractures and mortality in a community-dwelling elderly population 
aged 70 years and over? Results of a 3-year prospective cohort study in Japan. Neurourol 
Urodyn. 2008;27:674–5.  
Oelke M, Baard J, Wijkstra H, et al. Age and bladder outlet obstruction are independently 
associated with detrusor overactivity in patients with benign prostatic hyperplasia. Eur 
Urol. 2008;54: 419-426. 
Rabin R, Gudex C, Selai C, Herdman M.  From translation to version management:  a history 
and review of methods for the cultural adaptation of the EuroQol five-dimensional 
questionnaire.  Value Health 2014 Jan;17(1):70-76, 01-01-2014. 
Risacher SL, McDonald BC, Tallman EF, West JD, Farlow MR, Unverzagt FW, Gao S, 
Boustani M, Crane PK, Petersen RC, Jack CR Jr, Jagust WJ, Aisen PS, Weiner MW, 
Saykin AJ; Alzheimer’s Disease Neuroimaging Initiative. Association Between 
Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in 
Cognitively Normal Older Adults. JAMA Neurol. 2016 Jun 1;73(6):721-32. 
Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, et al. Prevalence 
and burden of overactive bladder in the United States. World J Urol 2003;20: 327-36. 
Takeda H, Yamazaki Y, Akahane M, Igawa Y, Ajisawa Y, Nishizawa O. Role of the β 3-
adrenoceptor in urine storage in the rat: comparison between the selective β 3-
adrenoceptor agonist, CL316, 243, and various smooth muscle relaxants. J Pharm Exp 
Ther 2000;293: 939-45. 


Urovant Sciences, GmbH  
 
Confidential 
Protocol URO-901-3005 
 
Version 4.0 (Amendment 3) 
115 
25 February 2022 
 
Takeda H, Yamazaki Y, Igawa Y, Kaidoh K, Akahane S, Miyata H, Nishizawa O, Akahane M, 
Andersson KE. Effects of β3-adrenoceptor stimulation on prostaglandin E2-induced 
bladder hyperactivity and on the cardiovascular system in conscious rats. Neurology and 
Urodynamics 2002;21: 558-65. 
Tubaro, A, Batista JE, Nitti, VW, et al. Efficacy and safety of daily mirabegron 50 mg in male 
patients with overactive bladder: a critical analysis of five phase III studies. The Adv 
Urol, 2017, Vol, 9(6): 137-154. 
Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, and Wein A. Tolterodine once daily: superior 
efficacy and tolerability in the treatment of the overactive bladder. Urol 2001;57: 414–21. 
Woods M, Carson N, Norton N, Wesley S, Jeffery H, Argentieri TM. Efficacy of the [Beta]3-
adrenergic receptor agonist CL-316243 on experimental bladder hyperreflexia and 
detrusor instability in the rat. J Urol 2001;166: 1142-7. 
Yamaguchi O. β3-adrenoceptors in human detrusor muscle. Urology 2002;59 (Supplement 5A): 
25-29. 
Yoshida M, Takeda M, Gotoh M, Nagai S, Kurose T. Vibegron, a novel potent and selective B3-
Adrenoreceptor Agonist, for the treatment of patients with overactive bladder: a 
randomized, double-blind, placebo-controlled Phase 3 study. Euro Urol. 2018;73:783-90. 
 
 
 

SAP_001.pdf: 
Urovant Sciences 
Statistical Analysis Plan – URO-901-3005 V2.0 
07-Aug-2023
1 
STATISTICAL ANALYSIS PLAN 
Protocol Number: 
URO-901-3005 
Protocol Title: 
A Phase 3 Double-Blind, Randomized, Placebo-Controlled, Multi-
Center Study to Evaluate the Efficacy, Safety and Tolerability of 
Vibegron in Men with Overactive Bladder (OAB) Symptoms on 
Pharmacological Therapy for Benign Prostatic Hyperplasia (BPH) 
Protocol Version and 
Date: 
Version 4.0; 25 FEB 2022 
Investigational 
Product: 
Vibegron (URO-901, RVT-901, MK-4618, KRP-114V) 
Indication 
OAB symptoms for men with BPH 
Development Phase: 
Phase 3 
US IND Number: 
106410 
EudraCT Number: 
2018-003135-30 
Sponsor: 
Urovant Sciences, GmbH 
Gotthardstrasse 3 
6300 Zug Switzerland  
SAP Version 
Effective Date 
v2.0 
07-Aug-2023
SAP Author 
, MS 
Sr. Principal Biostatistician/Director, Urovant Sciences, Inc. 
   
 
 
 
NCT Number: NCT03902080
This NCT number has been applied to the document for purposes of posting on Clinicaltrials.gov






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TABLE OF CONTENTS 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES ...........................................................................................................................7 
SAP VERSION HISTORY............................................................................................................10 
1. 
INTRODUCTION ......................................................................................................11 
1.1. 
Study Objectives and Endpoints .................................................................................11 
1.1.1. 
Primary Efficacy Objectives .......................................................................................11 
1.1.2. 
Secondary Efficacy Objectives ...................................................................................11 
1.1.3. 
Safety Objectives ........................................................................................................11 
1.1.4. 
Other Efficacy Objectives ...........................................................................................12 
1.2. 
Study Design ...............................................................................................................14 
1.2.1. 
Overall Study Design ..................................................................................................14 
1.2.2. 
Randomization and Blinding ......................................................................................15 
1.2.3. 
Statistical Hypotheses .................................................................................................16 
1.2.3.1. 
Statistical Hypotheses for Co-Primary Efficacy Endpoints ........................................16 
1.2.3.2. 
Statistical Hypotheses for Secondary Efficacy Endpoints ..........................................16 
1.2.4. 
Sample Size Justification ............................................................................................16 
1.2.4.1. 
Power in Baseline BPH Treatment Subgroups ...........................................................18 
1.2.4.2. 
Urodynamics Substudy ...............................................................................................18 
2. 
PLANNED ANALYSES ............................................................................................19 
2.1. 
Interim Analysis ..........................................................................................................19 
2.2. 
Final Analysis .............................................................................................................19 
3. 
ANALYSIS POPULATION ......................................................................................20 
3.1. 
Analysis Sets ...............................................................................................................20 
3.1.1. 
Screened Set ................................................................................................................20 
3.1.2. 
Placebo Run-in Set .....................................................................................................20 
3.1.3. 
Randomized Set ..........................................................................................................20 
3.1.4. 
Safety Analysis Set .....................................................................................................20 
3.1.5. 
Urodyamics Evaluable Set ..........................................................................................21 
3.1.6. 
Full Analysis Set .........................................................................................................21 
3.1.7. 
Per-Protocol Set ..........................................................................................................21 
3.2. 
Violations and Deviation ............................................................................................22 


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Statistical Analysis Plan – URO-901-3005 V2.0 
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4. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................23 
4.1. 
General Principles for Data Analysis .........................................................................23 
4.1.1. 
Multicenter Study .......................................................................................................23 
4.1.2. 
Testing Strategy and Multiplicity Adjustments ..........................................................23 
4.1.3. 
Examination of Subgroups .........................................................................................23 
4.2. 
General Data Handling Conventions ..........................................................................24 
4.2.1. 
Study Treatment Description ......................................................................................24 
4.2.2. 
Reporting Conventions ...............................................................................................24 
4.2.3. 
Premature Withdrawal and Missing Data ...................................................................25 
4.2.4. 
Assessment Windows .................................................................................................27 
4.2.4.1. 
Study Reporting Periods .............................................................................................27 
4.2.4.2. 
Analysis Visit Windows .............................................................................................28 
4.3. 
Data Definitions and Derivations of Endpoints ..........................................................29 
4.3.1. 
Bladder Diary Endpoints ............................................................................................29 
4.3.1.1. 
Co-primary Efficacy Endpoint ...................................................................................30 
4.3.1.2. 
Secondary Efficacy Endpoint (Bladder Diary) ...........................................................30 
4.3.1.3. 
Other Exploratory Efficacy Endpoints .......................................................................31 
4.3.2. 
Patient Reporting Questionnaire Scoring ...................................................................31 
4.3.2.1. 
International Prostate Symptom Score .......................................................................31 
4.3.2.2. 
Overactive Bladder Questionnaire ..............................................................................32 
4.3.2.3. 
EQ-5D-5L ...................................................................................................................33 
4.3.2.4. 
International Index of Erectile Function .....................................................................34 
4.3.3. 
Study Day and Duration .............................................................................................34 
4.3.4. 
Baseline and Change from Baseline ...........................................................................35 
4.3.5. 
Pre-existing and Baseline Hypertension .....................................................................35 
5. 
STUDY SUBJECTS ...................................................................................................36 
5.1. 
Subject Disposition and Withdrawals .........................................................................36 
5.2. 
Demographic and Baseline Characteristics ................................................................36 
5.3. 
Other Baseline Characteristics ....................................................................................37 
5.4. 
Medical History and Concomitant Disease ................................................................37 
5.5. 
Procedures ...................................................................................................................37 
5.6. 
Prior and Concomitant Medication .............................................................................38 
5.6.1. 
Prior Medication .........................................................................................................38 


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Statistical Analysis Plan – URO-901-3005 V2.0 
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5.6.2. 
Concomitant Medication ............................................................................................38 
5.7. 
ECG ............................................................................................................................39 
5.8. 
Prostate Volume Measurements .................................................................................39 
5.9. 
Treatment Exposure ....................................................................................................39 
5.10. 
Treatment Compliance ................................................................................................39 
6. 
EFFICACY ANALYSIS ............................................................................................40 
6.1. 
Co-Primary Endpoint Analysis ...................................................................................40 
6.1.1. 
Primary Analysis ........................................................................................................40 
6.1.2. 
Sensitivity Analysis ....................................................................................................42 
6.1.2.1. 
Per-Protocol Analysis .................................................................................................42 
6.1.2.2. 
Analysis of Covariance with Multiple Imputed data ..................................................42 
6.1.2.3. 
MMRM with Stratification Factors as Observed ........................................................44 
6.1.3. 
Subgroup Analysis ......................................................................................................44 
6.2. 
Secondary Efficacy Analyses .....................................................................................44 
6.3. 
Other/Exploratory Endpoints ......................................................................................45 
6.3.1. 
Efficacy .......................................................................................................................45 
6.3.2. 
Quality of Life ............................................................................................................47 
6.3.2.1. 
CFB in 
Scores...........................................................................................47 
6.3.2.2. 
 ...................................................................................................................47 
6.3.2.3. 
Patient Global Impression Scores ...............................................................................47 
6.3.2.4. 
 .....................................................................48 
7. 
SAFETY ANALYSIS ................................................................................................48 
7.1. 
Adverse Events ...........................................................................................................48 
7.2. 
Laboratory Evaluations ...............................................................................................51 
7.3. 
Vital Sign Assessments...............................................................................................51 
7.3.1. 
Height, Weight, and Sitting Vital Signs .....................................................................51 
7.3.1.1. 
Vital Sign Subgroups ..................................................................................................52 
7.3.1.2. 
Categorical/Threshold Analysis ..................................................................................52 
7.3.2. 
Orthostatic Blood Pressure and Pulse Rate (Part 1 only) ...........................................52 
7.4. 
Physical Examination .................................................................................................54 
7.5. 
Post-Void Residual (PVR) Urine Volume ..................................................................54 
7.6. 
Urodynamics Assessments (Urodynamics Sub-study Only) ......................................54 
7.7. 
Uroflow Measures ......................................................................................................55 


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Statistical Analysis Plan – URO-901-3005 V2.0 
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7.8. 
IPSS Total Score .........................................................................................................55 
8. 
COVID-19 CONSIDERATIONS ...............................................................................56 
9. 
CHANGE FROM ANALYSIS PLANNED IN PROTOCOL....................................57 
9.1. 
Exploratory endpoints .................................................................................................57 
9.2. 
Responder Analysis ....................................................................................................57 
9.3. 
COVID-19 Considerations .........................................................................................57 
10. 
REFERENCES ...........................................................................................................58 
11. 
APPENDIX.................................................................................................................59 
11.1. 
Appendix 1. Multiple Imputation for the Response Efficacy Endpoints ....................59 
11.2. 
Table of Contents for Data Display Specifications ....................................................61 
11.2.1. 
Output Tables ..............................................................................................................61 
11.2.2. 
Output Figures ............................................................................................................74 
11.2.3. 
Output Listings ...........................................................................................................76 
 
LIST OF TABLES 
Table 1: 
Data and Sources Supporting Study Sample Size Calculations .................................17 
Table 2:  
Definition of Study Reporting Periods .......................................................................27 
Table 3:  
Analysis Window Slotting ..........................................................................................28 
Table 4: 
 Domain Questions ....................................................................................32 
Table 5:  
 Domain Questions ..............................................................................................34 
Table 6:  
OAB Medication Selection .........................................................................................38 
Table 7:  
PGI Scoring ................................................................................................................47 
Table 8: 
At Risk Subgroup for Vital Sign Summaries .............................................................52 
Table 9:  
List of Output Tables ..................................................................................................61 
Table 10: List of Output Figures .................................................................................................74 
Table 11: List of Output Listings ................................................................................................76 
 
 
 


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 LIST OF ABBREVIATIONS  
Abbreviation 
Term 
5-ARI 
5α-reductase inhibitor 
ADaM 
analysis data model 
AE 
adverse event 
AESI 
adverse events of special interest 
BMI 
body mass index 
BP 
blood pressure 
BPH 
benign prostatic hyperplasia 
CFB 
change from baseline 
CI 
confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CRF 
case report form 
DBP 
diastolic blood pressure 
DSMB 
data safety monitoring board 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
FAS 
full analysis set 
FAS-I 
full analysis set for incontinence 
HRQL 
health-related quality of life 
 
 
IPSS 
International Prostate Symptom Score 
IWRS 
interactive web response system 
LS 
least squares 
MAR 
missing at random 
MCC 
maximum cystometric capacity 
MCMC 
Markov chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed model for repeated measure 
OAB 
overactive bladder 
 
 
PdetQmax 
detrusor pressure at maximum urinary flow 
PGI 
patient global impression 
PPS 
per-protocol set 
PT 
preferred term 
PRO 
patient reported outcome 
PVR 
post-void residual 
Qmax 
peak flow rate during voiding 
REML 
restricted (or residual) maximum likelihood 
SAE 
serious adverse event 
SAF 
safety set 


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Abbreviation 
Term 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 
SD 
standard deviation 
SDTM 
study data tabulation model 
SE 
standard error 
SOC 
system organ class 
TEAE 
treatment emergent adverse event 
TLF 
table, listing, figure 
UUI 
urge urinary incontinence 
VAS 
visual analog scale 
VV 
volume voided 
WHO 
World Health Organization  
β3-AR 
beta-3 adrenergic receptor 


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Statistical Analysis Plan – URO-901-3005 V2.0 
07-Aug-2023 
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SAP VERSION HISTORY 
Version 
Date 
Description of Changes 
1.0 
02FEB2023 
Original Document 
2.0 
04AUG2023 
Updated Per Protocol exclusionary Protocol Deviations 
Updated Urodynamics, Uroflow, Post-Void Residual, 
and Vital Signs analyses 
Added Tipping Point Sensitivity analysis of primary 
efficacy endpoints 


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Statistical Analysis Plan – URO-901-3005 V2.0 
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1. INTRODUCTION 
This Statistical Analysis Plan (SAP) provides a description of the statistical methodology to be 
implemented for the analyses of data from Study URO-901-3005 per Protocol Version 4.0. This 
SAP is to be finalized, approved by the sponsor, and placed on file before the study database is 
locked. Changes to the final SAP will be documented in the final clinical study report.  
1.1. 
Study Objectives and Endpoints 
1.1.1. 
Primary Efficacy Objectives  
Co-Primary Efficacy Objectives 
 Endpoints 
To assess the efficacy of vibegron 
compared with placebo in men 
with OAB symptoms on 
pharmacological therapy for BPH 
as defined by micturition and 
urgency episodes  
x Change from baseline (CFB) to Week 12 in the 
average number of micturition episodes per day  
x CFB to Week 12 in the average number of urgency 
episodes (urgency: need to urinate immediately) 
per day  
1.1.2. 
Secondary Efficacy Objectives  
Secondary Efficacy Objectives 
 Endpoints 
To assess the efficacy of vibegron 
compared with placebo in men 
with OAB symptoms on 
pharmacological therapy for BPH 
as defined by other key measures  
x CFB to Week 12 in the average number of nocturia 
episodes per night 
x CFB to Week 12 in the average number of urge 
urinary incontinence episodes per day for subjects 
with urinary incontinence at baseline  
x CFB to Week 12 in the International Prostate 
Symptom Score (IPSS) Storage score (1-week 
recall)  
x CFB to Week 12 in the average volume voided per 
micturition  
1.1.3. 
Safety Objectives  
Safety Objectives 
 Endpoints 
To assess the safety and 
tolerability of vibegron compared 
with placebo in men with OAB 
symptoms on pharmacological 
therapy for BPH  
x Adverse Event (AE) 
x Clinical laboratory  
x Vital sign assessments 
x Orthostatic blood pressure (Part 1 only) 
x Physical exam (PE) 


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Statistical Analysis Plan – URO-901-3005 V2.0 
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x Post-Void residual (PVR) urine volume 
x Urodynamics (Part 2 sub-study only)  
x Uroflow measures 
x Prostate volume measurements 
x IPSS total score 
1.1.4. 
Other Efficacy Objectives  
Other Efficacy Objectives 
 Endpoints 
To assess the efficacy of vibegron 
compared with placebo in men 
with OAB symptoms on 
pharmacological therapy for BPH 
as defined by other measures  
CFB to Week 2, Week 4, Week 8, Week 16, Week 20 
and Week 24 in the following 5 parameters 
x Average number of micturition episodes per day  
x Average number of urgency episodes per day  
x Average number of nocturia episodes per night 
x Average number of urge urinary incontinence 
episodes per day for subjects with urinary 
incontinence at baseline  
x Average volume voided per micturition  
x CFB to Week 4, Week 8, Week 20, and Week 24 
in IPSS Storage score (1-week recall) 
CFB to Week 4, Week 8, Week 12, Week 20 and 
Week 24 in the following 3 parameters 
x IPSS Quality of Life score (1-week recall)  
x IPSS Voiding score (1-week recall) 
x IPSS total score 
x CFB to Week 2, Week 4, Week 8, Week 12, Week 
16, Week 20, and Week 24 in average number of 
total incontinence episodes per day for subjects 
with urinary incontinence at baseline  
Responder analysis at Week 2, Week 4, Week 8, Week 
12, Week 16, Week 20 and Week 24 measured by: 
x Percent of all subjects with a 50% reduction from 
baseline in average urgency episodes (urgency: 
need to urinate immediately) per day  
x Percent of subjects with urinary incontinence at 
baseline with a 75% reduction from baseline in 
average urge urinary incontinence episodes per day  


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Statistical Analysis Plan – URO-901-3005 V2.0 
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To assess the effects of vibegron 
compared with placebo on quality-
of-life assessments and patient-
reported outcomes (PROs) in men 
with OAB symptoms on 
pharmacological therapy for BPH  
CFB to Week 12 and Week 24  
x Symptom Bother Score as assessed by 
, 1-week recall)  
x HRQL scores as assessed by 
.  
x HRQL subscale Coping score  
x HRQL subscale Concern score  
x HRQL subscale Sleep score  
x HRQL subscale Social Interaction score  
x HRQL total score 
x 
 as assessed by measure of health 
status questionnaire  
x 
 
overall satisfaction and function domains 
 
CFB to Week 4, Week 12, and Week 24 
x Overall bladder symptoms based on Patient Global 
Impression of 
(PGI-
)  
x Overall control over bladder symptoms based on 
Patient Global Impression of 
)  
x Overall symptom frequency based on Patient 
Global Impression of Symptom 
  
x Overall urgency-related leakage over bladder 
symptoms based on Patient Global Impression of 
Urgency-Related 
 (PGI-
) in 
subjects with urinary incontinence at baseline  
x Overall change of bladder symptoms based on 
Patient Global Impression of 
 (
 
 


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1.2. 
Study Design 
1.2.1. 
Overall Study Design 
This is a Phase 3, randomized, double-blind, placebo-controlled, 2-part, parallel-group, 
multicenter study to evaluate the safety, tolerability, and efficacy of vibegron 75 mg in men with 
symptoms of OAB on stable doses of pharmacological therapy for BPH. At Baseline, subjects 
who meet all eligibility criteria are randomized 1:1 to receive either vibegron 75 mg or placebo 
in a double-blind fashion.  
The study consists of two parts: Part 1 (approximately 80 subjects) and Part 2 (approximately 
1008 subjects). Part 1 includes additional orthostatic blood pressure and heart rate measurements 
at Screening, Run-in, Baseline, Week 2, and Week 4 to assess for potential orthostatic changes 
(pre-dose through 6 hours post dose, except pre-dose for Screening and Run-In), but is otherwise 
consistent with the schedule for Part 2. Part 2 will proceed following review of 4-week safety 
data (including orthostatic blood pressure results) of all 80 subjects from Part 1 by an 
independent Data Safety Monitoring Board (DSMB). Details on tasks and responsibilities, 
assessments of safety parameters, including orthostatic blood pressure and criteria for defining 
clinically significant orthostatic events, will be provided in the DSMB Charter. Part 2 will also 
include a urodynamics sub-study (approximately 60 subjects). The independent DSMB will 
review the safety data throughout the entire study. 
Both study parts will consist of a Screening Period (1 to 4 weeks), a single-blind therapy plus 
placebo Run-in Period (2 weeks), and a randomized double-blind Treatment Period (24 weeks). 
Study visit schedules: Visit 1 (Screening), Visit 2 (Run-in), Visit 3 (Baseline), Visit 4 (Week 1), 
Visit 5 (Week 2), Visit 6 (Week 4), Visit 7 (Week 8), Visit 8 (Week 12), Visit 9 (Week 16), Visit 
10 (Week 20), and Visit 11 (Week 24) (End of the Treatment). 
Subjects who complete the Week 24 Visit may be offered the opportunity to enroll in a 28-week 
extension study URO-901-3006, which will be conducted under a separate study protocol. 
Subjects who do not enroll into the extension study will have a Safety Follow-up contact 
approximately 5 days (± up to 2 days) after the subject’s last dose of study treatment (i.e., or 
approximately 5 days (± up to 2 days) after withdrawal for subjects who discontinue the study 
early). Additionally, Unscheduled Visit(s) may be arranged as needed. 
Approximately 1088 subjects (544 per treatment group: 80 total in Part 1 and 1008 total in Part 
2) will be randomized at up to approximately 135 sites in North America (United States and 
Canada) and Europe to have 924 subjects complete the study (assuming a 15% dropout rate). The 
study schema is shown in Figure 1.  


Urovant Sciences 
Statistical Analysis Plan – URO-901-3005 V2.0 
07-Aug-2023 
15 
 
Figure 1: 
Study Schema 
 
1.2.2. 
Randomization and Blinding 
Randomization will occur centrally using an interactive web response system (IWRS) using 
central, stratified block randomization. Randomization will be stratified based on the following 
stratification factors: 
x Baseline average micturition episodes per day (≤ 12 vs > 12), and 
x Alpha blocker use with or without 5-ARI (with vs without), and 
x Urinary Incontinence (yes vs no)  
Part 1 and Part 2 excluding the urodynamics sub-study will use the same stratified block 
randomization list. In order to ensure balanced treatment assignment within the urodynamics 
sub-study a separate randomization list with the same stratification factors and the block size will 
be used for subjects enrolled in the sub-study. 
For this study in the double-blind treatment phase a double-blind/masking technique will be 
used: vibegron and its matching placebo will be packaged identically so that treatment 
blind/masking is maintained.  The patient, the Investigator, and Sponsor personnel or delegate(s) 
who are involved in the treatment or clinical evaluation of the patients will not be aware of the 
treatment group assignments. 


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1.2.3. 
Statistical Hypotheses 
1.2.3.1. 
Statistical Hypotheses for Co-Primary Efficacy Endpoints 
The co-primary efficacy objectives of the study are to demonstrate that vibegron 75 mg is 
superior to placebo with respect to mean CFB in the following co-primary endpoints after 12 
weeks treatment.   
x Daily Micturition 
o 
Co-Primary H0: In men with OAB-BPH, vibegron 75 mg will have the same mean 
CFB to Week 12 in the average number of daily micturition episodes as in men 
treated with placebo. 
o 
Co-Primary H1: In men with OAB-BPH, vibegron 75 mg will have different CFB to 
Week 12 in the average number of daily micturition episodes from placebo. 
x Daily Urgency Episode 
o 
Co-Primary H0: In men with OAB-BPH, vibegron 75 mg will have the same mean 
CFB to Week 12 in the average number of daily urgency episodes as in men treated 
with placebo. 
o 
Co-Primary H1: In men with OAB-BPH, vibegron 75 mg will have different mean 
CFB to Week 12 in the average number of daily urgency episodes from placebo. 
1.2.3.2. 
Statistical Hypotheses for Secondary Efficacy Endpoints 
The secondary efficacy objectives of the study are to demonstrate that vibegron 75 mg is 
superior to placebo with respect to mean CFB to Week 12 in the following 4 endpoints.  The null 
hypothesis is that there is no difference in mean CFB to Week 12 between vibegron 75 mg and 
placebo.  The alternative hypothesis is that vibegron 75 mg is different (i.e., two-sided 
hypothesis) from placebo with respect to CFB to Week 12 in the following parameters, 
respectively. These tests will be performed sequentially each at an alpha level of 0.05 after the 
co-primary endpoints are tested and both demonstrate statistical superiority of vibegron 75 mg 
over placebo at a significance level of 0.05, see details described in section 4.1.2. 
x Average number of nocturia episodes per night 
x Average number of daily urge urinary incontinence episodes for subjects with   
      urinary incontinence at baseline 
x IPSS Storage score (1-week recall) 
x Average volume voided per micturition 
1.2.4. 
Sample Size Justification 
Approximately 1088 subjects will be randomized in a 1:1 ratio to receive one of the following 
study treatments: 


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x Vibegron 75 mg tablet (N = 544) 
x Matching placebo tablet (N = 544) 
Approximately 544 subjects each will be assigned to the vibegron and placebo treatment groups. 
Assuming a total of 15% of subjects will discontinue study treatment prior to Week 12 (for any 
reason), there will be approximately 462 evaluable subjects in the vibegron and placebo 
treatment groups (924 subjects total) at the end of Week 12. The study has approximately 94.3% 
power to detect a between-group treatment difference of 0.46 in change from baseline in the 
average number of daily micturition episodes at a 2-sided 0.05 level. This calculation assumes a 
standard deviation (SD) of 1.972 based on vibegron Study MRK-008 data and mirabegron NDA 
data showing that the micturition treatment effect in men taking 50 mg of mirabegron is 70% of 
the overall 50 mg of mirabegron population. Additional details are provided at the end of this 
section in Table 1. 
For the second co-primary endpoint, 462 evaluable subjects per treatment group provides 
approximately 90% power to detect a between-group treatment difference of 0.60 in change from 
baseline in urgency episodes at a 2-sided 0.05 level. This calculation assumes a SD of 2.811 
based on vibegron Study MRK-008 data and mirabegron NDA data. Additional details are 
provided at the end of this section in Table 1. 
The overall study power will be greater than 84% with the co-primary endpoints based on the 
Bonferroni inequality (i.e., for any events A and B, P(A∩B) ≥ P(A) + P (B) – 1). 
Derivation of Estimated Treatment Effect in Men 
Based on the published results of the Phase 2 trial of mirabegron and the FDA statistical review 
of the OAB NDA, we estimated the following: 
x The Phase 3 results will have at least 85% of the treatment difference of the Phase 2 
results 
x The treatment difference for men is at least 70% of the effect of the general OAB 
population 
Table 1 summarizes this information and sources. 
Table 1: 
Data and Sources Supporting Study Sample Size Calculations 
Mirabegon Results for Mean Change in Average Number of Daily Micturitions 
 
N 
PBO Adj CFB 
Study 
Overall 
Men 
Overall 
Phase 2 178-CL-046 
473 
133 
-0.6 
Phase 3 178-CL-047 
425 
116 
-0.61 
 
 
Simple Average 
-0.605 


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Mirabegon Results for Mean Change in Average Number of Daily Micturitions 
 
 
Phase 2 (178-CL-046) 
Micturition PBO Adj 
CFB 
Phase 3 (178-CL-047) 
Micturition PBO Adj 
CFB 
Phase 3 as a % of 
Phase 2 
Comparing Phase 3 to 
Phase 2 
-0.64 
-0.605 
94.5% 
 
 
 
 
Vibegron Study MRK-008 Results 
Measure 
Vibegron 50 mg 
Vibegron 100 mg 
SD 
Micturition 
-0.64 
-0.91 
1.972 
Urgency Episodes 
-0.75 
-1.24 
2.811 
 
Ph3 Projections 
 
Midpoint between 50 mg and 100 mg 
Micturition 
Urgency Episodes 
Ph 2 Projected Effect of 75 mg 
-0.78 
-1.00 
Ph3 Projected Effect of 75 mg 
-0.66 
-0.85 
Ph 3 Projected Effect of 75 mg in Men* 
-0.46 
-0.60 
*Used for URO-901-3005 Sample Size Calculations 
1.2.4.1. 
Power in Baseline BPH Treatment Subgroups 
Although this study will not formally test the treatment effect in subgroups by baseline BPH 
treatments, it is sufficiently sized to estimate treatment differences within these subgroups. 
Assuming that approximately half of the subjects are on alpha blockers alone and half on alpha 
blockers plus 5-ARI per stratified randomization, then approximately 544 subjects will be 
randomized to each subgroup with 462 evaluable (231 per arm). Using the above assumptions 
with a two-sided test with a type-I error of 0.10, each subgroup will have 97.1% power for 
micturition episodes and 94.5% power for urgency episodes. Assuming that the endpoints and 
subgroups are independent, then the power for each subgroup to be significant on both endpoints 
is 91.7%, and the power for both subgroups to show significant treatment difference on both 
endpoints is 84.0%.  
1.2.4.2. 
Urodynamics Substudy 
Approximately 75 subjects will be enrolled in the Urodynamics substudy, randomized 1:1 to 
placebo or vibegron 75mg. Assuming a 20% drop-out rate, 60 subjects will be evaluable, 30 in 
each treatment arm. Noninferiority margins of -3 mL/second for maximum urinary flow (Qmax) 
and 15 cm H2O for detrusor pressure at maximum urinary flow (PdetQmax) from Abrams et al 
[1] were used to characterize power. Standard Deviation of each parameter was estimated from 
Nitti et al [2], which used the same noninferiority margins. 


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Using the noninferiority margins described above and a one-sided test of noninferiority with 
type-I error of 0.05: 
30 evaluable subjects per treatment group provides approximately 97% power against the 
alternative hypothesis of equality for Qmax assuming standard deviation of 3.2 mL/second. 
For PdetQmax, 30 evaluable subjects per treatment group provides approximately 79% power 
against the alternative hypothesis of equality assuming standard deviation of 23.5 cm H2O. 
Assuming independence of these tests and requiring both to be within the non-inferiority margin, 
the power of the composite outcome is approximately 77%. 
2. PLANNED ANALYSES  
2.1. 
Interim Analysis  
No interim analysis is planned for this study. 
 
An external independent DSMB will be utilized in the study to ensure external objective medical 
and/or statistical review of safety issues in order to protect the ethical and safety interests of 
subjects and to protect the scientific validity of the study.   
An external statistician will provide the summaries required to the DSMB. No adjustment to the 
type I error will be made because there is no efficacy data to be reviewed. The schedule of any 
planned analysis and analysis plan for DSMB review is described in the charter and separate 
DSMB SAP.  
2.2. 
Final Analysis  
The study consists of two parts: Part 1 (approximately 80 subjects) and Part 2 (approximately 
1008 subjects).  The two study parts are consistent with respect to the study schedule; the only 
exception is that Part 1 includes additional orthostatic blood pressure and heart rate 
measurements up to Week 4 to assess for potential orthostatic changes. Part 2 also contains a 
urodynamics sub-study (approximately 60 subjects). Thus, all data except for orthostatic blood 
pressure for Part 1 and urodynamic data from the subgroup of Part 2 will be pooled for analyses.  
The production and quality control of all tables, figures and listings will be provided by a clinical 
research organization (eClinical Solutions, LLC) under the supervision of Urovant Sciences, Inc. 
Statistical programming will start after data have been collected and are available in the 
database.  Blinded dry-runs using dummy treatment code will be performed prior to database 
lock to ensure programming displays and algorithms are developed as planned.   
The planned final analysis will be performed once the clinical database lock has taken place and 
treatment codes have been unblinded. 


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3. ANALYSIS POPULATION  
3.1. 
Analysis Sets 
All analysis sets defined below include subjects from both Part 1 and Part 2 except for the Safety 
Analysis Set for orthostatic blood pressure for subjects in Part 1, and the Urodynamics Evaluable 
Set and Per-Protocol Set for Urodynamics which include subjects who participate in the 
urodynamics sub-study in Part 2 only. 
3.1.1. 
Screened Set 
The Screened Set consists of all subjects who are screened for the study. This population is used 
primarily for subject accounting purposes and will generally not be used for summary or 
analysis. This set includes all subjects that signed the informed consent form and have screening 
data entered into the database, including screen failures (subjects who did not receive any run-in 
treatment), run-in failures (subjects who discontinued after receiving run-in treatment and prior 
to randomization), and randomized subjects. 
3.1.2. 
Placebo Run-in Set 
The Placebo Run-In Set consists of all subjects who receive placebo run-in treatment. Subjects 
will be considered run-in failures if they receive run-in treatment but are not randomized to 
receive double-blind medication. Subjects who inadvertently received vibegron during run-in are 
not included in the placebo run-in set. 
3.1.3. 
Randomized Set 
The Randomized Set consists of all subjects who are randomized to receive any double-blind 
study medication regardless of whether they took a dose or not.  
3.1.4. 
Safety Analysis Set  
The Safety Analysis Set will serve as the primary population for the analysis of safety data in 
this trial. Since Part 1 includes additional orthostatic blood pressure assessments while Part 2 
includes an additional sub-study with urodynamics measurements, it is necessary to have 
separate FAS definitions for these assessments. The following SAF populations are defined in 
the study: 
x Safety Analysis Set (SAF): consists of all randomized subjects who receive at least one 
dose of double-blind study medication. Subjects will be classified according to the 
treatment they actually received; subjects who receive any dose of vibegron will be 
classified as vibegron subjects, subjects who receive only doses of placebo will be 
classified as placebo subjects. 
x Safety Analysis Set for Orthostatic Blood Pressure (SAF – Orth): a subset of SAF      
      to include all subjects in Part 1 who received at least one dose of double-blinded study  
      medication and have at least one evaluable change from baseline orthostatic blood  
      pressure measurement.  
 


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3.1.5. 
Urodyamics Evaluable Set 
The Urodynamics Evaluable Set (UES) consists of all subjects in Part 2 who were randomized to 
the urodynamics sub-study, received at least one dose of double-blind study medication, had 
both Qmax and PdetQmax measurements at baseline and at least one Qmax or PdetQmax 
measurement at the post-baseline timepoint. 
3.1.6. 
Full Analysis Set  
The Full Analysis Set (FAS) population will serve as the primary population for the analysis of 
efficacy data in this trial. Since the endpoints related to incontinence only apply to subjects who 
meet the definition of incontinence at trial entry, it is necessary to have a separate FAS definition 
with an additional criterion to define the primary analysis population for incontinence endpoints.  
The following FAS populations are defined in the study: 
x Full Analysis Set (FAS):  consists of all randomized subjects who took at least one dose    
of double-blind study medication and have at least one evaluable change from baseline 
micturition measurement. Subjects will be analyzed according to their randomized 
treatment, irrespective of premature discontinuation, according to the Intent-to-Treat 
principle. 
x Full Analysis Set for Incontinence (FAS-I): consists of all randomized subjects with  
incontinence at baseline (as calculated from the baseline diary) who took at least one dose 
of double-blind study treatment and have at least one evaluable change from baseline 
urinary incontinence measurement. 
 
Note that “subjects with urinary incontinence at baseline” are defined as meeting the following 
criteria based on the 3-day bladder diary completed by the subject during the Run-in period: 
x An average of ≥ 8.0 micturitions per Diary Day. A “Diary Day” is defined as the time 
between when the subject gets up for the day each morning (i.e., the time the subject got 
up for the day yesterday to the time the subject got up for the day today; approximately a 
24-hour period). 
x  An average of ≥ 1.0 urinary incontinence episodes per Diary Day 
3.1.7. 
Per-Protocol Set  
The Per-Protocol Set (PPS) and Per-Protocol Set for Incontinence (PPS-I) exclude patients from 
the FAS and FAS-I due to important deviations from the protocol that may substantially affect 
the results of the efficacy endpoints (i.e., Major PDs associated with efficacy). The Per-Protocol 
set for Urodynamics (PPS-UES) exclude subjects from UES due to important deviations from 
the protocol that may substantially affect the results of the urodynamics endpoints. A supportive 
analysis using the PPS and PPS-I will be performed for the co-primary and secondary efficacy 
endpoints, and a supportive analysis using the PPS-UES will be performed for the primary 
urodynamics parameters (Qmax and PdetQmax). The final determination on protocol deviations, 
and thereby the composition of the Per-Protocol Sets, will be made prior to the unblinding of the 
database and will be documented per the Protocol Deviation Plan during the blinded data review 


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meeting. Subjects will be included in the treatment group to which they are randomized, 
regardless of which treatment was actually received, for the analyses of efficacy data using the 
PPS and PPS-I. 
3.2. 
Violations and Deviation  
Subjects who do not meet eligibility criteria but are still randomized will be analyzed 
according to the analysis sets described in Section 3.1. 
Major protocol deviations are considered to have major impact on subject safety, efficacy or the 
validity of the study data. 
 
Patients with major efficacy protocol deviations will be excluded from the PPS and PPS-I under 
the assumption that the deviation may have an impact on the efficacy analysis, and from PPS-
UES under the assumption that the deviation may have an impact on the urodynamics analysis. 
This may include, but is not limited to the following:  
 
x Subjects who do not meet the following inclusion criteria: 
o On a stable dose of alpha blocker 
o Average frequency of ≥ 8 and ≤20 micturitions per day in the baseline diary 
o Average frequency of ≥ 3 urgency episodes per day in the baseline diary 
o Average frequency of ≥ 2 nocturia episodes per night in the baseline diary 
x Subjects who meet any of the following exclusion criteria: 
o Total 24-hour urine volume output of >3000 mL based on any baseline diary day 
o History of prostate surgery 
o Subject started using diuretics within 28 days prior to screening 
o Nocturnal Polyuria (> 1/3 of total urine output per 24 hours occurring at 
nighttime) assessed on any day of the baseline diary 
o Has received an intravesical or intraprostatic treatment with any botulinum toxin, 
resiniferatoxin, or capsaicin within 6 months prior to screening 
o Use of any prohibited anticholinergics or beta-3 adrenergic agonists as detailed in 
protocol section 10.6 within 28 days prior to screening 
x Concomitant use of prohibited medications as detailed in protocol section 10.6 
x <70% Investigational Product [IP] compliance from Baseline through Week 12 
x Visit delay at or prior to Week 12 causing more than 14 days without IP 
x Failed to complete any diary day for an expected Week 12 diary within Study Day 68-
102 [PPS and PPS-I only] 
 
Exclusion from per-protocol analysis is noted for each protocol deviation in the Protocol 
Deviation specifications. 
 
The final list of major protocol deviations will be finalized and documented before database lock 
except for the deviation of wrong treatment which will be confirmed upon study unblinding. All 
major protocol deviations related to efficacy will be finalized prior to unblinding. Only major 
protocol deviations will be summarized and listed in the Clinical Study Report (CSR).  


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4. GENERAL STATISTICAL CONSIDERATIONS 
4.1. 
General Principles for Data Analysis  
4.1.1. 
Multicenter Study  
In this study the stratified permuted block randomization is not done within centers.  The 
analyses will be conducted by pooling data from all study centers and will not include study 
center as a covariate in the statistical modeling. 
4.1.2. 
Testing Strategy and Multiplicity Adjustments  
A hierarchical gate-keeping procedure will be used to control the overall family-wise Type-I 
error rate at 2-sided α=0.05 level over the co-primary and key secondary hypotheses stated in 
Section 1.2.3.  
If statistical significance for both co-primary efficacy endpoints is achieved (i.e., if two-sided p-
value for each endpoint is less than 0.05), then the secondary efficacy endpoints will be tested 
sequentially in the pre-defined order below.  
1. Average number of nocturia episodes per night 
2. Average number of daily urge urinary incontinence episodes for subjects with urinary  
      incontinence at baseline 
3. IPSS Storage score (1-week recall) 
4. Average volume voided per micturition 
Once a secondary efficacy endpoint is found to be insignificant (i.e., two-sided p-value ≥ 0.05), 
the testing procedure will stop. For all subsequent secondary efficacy endpoints, nominal p-
values will be provided but will not be considered a formal test of the hypotheses. Unless 
otherwise stated, all statistical tests will be conducted at the 2-sided α=0.05 level of significance. 
All other additional and exploratory efficacy endpoints will be considered supportive and no 
multiplicity adjustments will be performed for these other efficacy endpoints. Nominal p-values 
will be computed for other efficacy endpoints as a measure of the strength of the treatment effect 
rather than formal tests of hypotheses, if applicable.  
All confidence intervals will be 2-sided 95% confidence intervals, unless stated otherwise. 
4.1.3. 
Examination of Subgroups  
To determine whether the treatment effect is consistent across various subgroups, the co-primary 
endpoints will be summarized descriptively for each of the following subgroups: 
x 
Alpha blocker use with or without 5-ARI (with vs. without) 
x 
Baseline urinary incontinence (yes vs. no) 
x 
Region (US vs. Non-US) 


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x 
Age category 1 (<55, ≥55 to <65, ≥65 to < 75, ≥75 years) 
x 
Age category 2 (<65, ≥65 years) 
x 
Age category 3 (<65, ≥65 to <75, ≥75 to <85, ≥85 years) 
x 
Race (White, Black or African American, Asian and Other) 
x 
Prior anticholinergic use (yes vs. no) 
x 
Prior beta-3 agonist use (yes vs. no) 
If any single subgroup constitutes <5% of total subjects, categories may be combined. 
4.2. 
General Data Handling Conventions 
4.2.1. 
Study Treatment Description 
Randomized treatment groups will be displayed as shown in the following table: 
Data Displays for Reporting 
Description 
Order in TLF 
Placebo 
1 
Vibegron 75mg  
2 
Overall (Demographic and baseline data) 
3 
4.2.2. 
Reporting Conventions 
General rules 
In general, all collected safety data and any derived efficacy and patient reported outcome (PRO) 
data will be presented in subject data listings for all enrolled subjects. Listings will be ordered by 
treatment group, subject number, and assessment week or event date. The treatment group 
presented in listings will be based on the planned assignment, unless otherwise noted. 
Summary tables will be provided for all randomized subjects. Unless otherwise specified, all 
demographic and baseline data will be presented by treatment arm and overall. Efficacy, PRO 
and safety data will be presented by treatment arm. In general, continuous variables will be 
summarized to indicate the population sample size (N), number of subjects with available data 
(n), arithmetic mean, SD, median, minimum, Q1, Q3 and maximum values. Categorical variables 
will be summarized by the population size (N), number of subjects with available data (n), 
number of subjects in each category, and the percentage of subjects in each category. Unless 
otherwise noted, the denominator to determine the percentage of subjects in each category will 
be based on the number of subjects with available data (n) in the analysis set of interest. Select 
ordinal data may be summarized using both descriptive statistics and counts and percentages of 
subjects in each category, as appropriate. 


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For selected continuous safety endpoints, least squares means and 95% CIs will be derived from 
an analysis of covariance (ANCOVA) model with restricted maximum likelihood estimation. All 
models will include the baseline value of the parameter and any additional covariates will be 
noted; separate models will be fit for each timepoint. Example SAS code of a change from 
baseline at Week 12 is provided below: 
proc mixed data = datain method = reml; 
    class TRTA; 
    model CHG = TRTA BASE / solution;  
    where avisit = "Week 12"; 
    lsmeans TRTA / pdiff cl alpha=0.05; 
run; 
In the above code, CHG represents change from baseline, TRTA is the actual treatment received, 
and BASE is baseline value of the parameter.   
The data analyses will be conducted using the SAS® System (SAS Institute Inc., Cary, NC) 
version 9.4 or above. The eClinical Solutions standard operating procedures will be followed for 
the creation and validation of all SAS programs and outputs. 
Formats 
Numeric data will be reported at the precision collected on the eCRF.  The reported precision 
from non eCRF sources may be adjusted to a clinically interpretable number or decimal places. 
P-values will be reported to 4 decimal places, with p-values less than 0.0001 noted as <0.0001. 
Unscheduled Visits 
All visits, including unscheduled visits will be assigned to an analysis study visit using the all-
inclusive windows defined in Section 4.2.4.  However, data summaries will only report the visit 
nearest to the planned assessment time points for each parameter if multiple visits are within the 
analysis visit window, according to the Time and Events table. Assessments at unscheduled 
visits will be included for “any time On-treatment” timepoints and in data listings, as well as 
algorithms to determine the maximum or minimum. 
4.2.3. 
Premature Withdrawal and Missing Data  
All data collected in the study database after the subject’s cessation of study treatment should be 
included in summary and analysis. Data of subjects who withdraw after the screening 
examination or are not treated will only be listed. Assessments taken after the End of Study visit 
date for subjects continuing on to study URO-901-3006 will not be included in analysis or 
listings for study URO-901-3005; it will be included in datasets to support inclusion in analysis 
of study URO-901-3006. 
If any visits are missing diary data, no explicit missing data imputation will be performed for the 
primary analysis of change from baseline since a mixed model for repeated measures (MMRM) 
will be applied to change from baseline analysis. If time to bed or time to awaken the next 
morning is missing from a diary day, the average of non-missing days for that subject at that visit 


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will be used. If no visit average bedtime or time of awakening is calculable, no nocturia 
measurements will be calculated for that subject at that visit. 
 
Missing items from the subject reported outcomes (PROs) will be handled according to the 
respective measure instructions as described in Section 4.3.2. 
 
Missing return dates from the study drug log will be imputed as the day of the subsequent drug 
dispensation, end of treatment visit, or subject discontinuation in the study, whichever is first. 
Non-return of IP will be considered taken per protocol for calculation of treatment compliance 
but will be noted in the listing of study medication. 
 
If the first dose of double-blind study medication is not witnessed, the start of medication will be 
imputed as the day after the drug was dispensed. 
 
In general, missing safety data will not be imputed and only observed values will be analyzed.  
 
If the relationship of an AE record (“Relationship to investigational product” on AE CRF) is 
missing this AE will be considered “Probably Related” to the study treatment. If the AE intensity 
is missing every effort should be made to acquire the information from the investigator. “Severe” 
will be assigned to a missing intensity for reporting purposes. 
The general imputation rules of partial missing date and time for both AE and concomitant 
medication is detailed below: 
 
Dates missing the day of the year will adhere to the following conventions:  
x The missing day of onset date will be set to: 
 First day of the month that the event occurred, if the onset YYYY-MM is after the 
YYYY-MM of first double-blind treatment 
 The day of the first double-blind study treatment, if the onset YYYY-MM is the same as 
YYYY- MM of the first double-blind treatment 
 The day of the first run-in treatment, if the onset YYYY-MM is the same as YYYY-
MM of the first run-in treatment, but different from YYYY-MM of the first double-
blind treatment 
 
 The date of informed consent, if the onset YYYY-MM is before the YYYY-MM of the 
first run-in treatment. 
 
x The missing day of end date will be set to: 
 The death date, if the end date YYYY-MM is the same as the YYYY-MM of the death 
date  
 The end of study participation, if the end date YYYY-MM is the same as the YYYY-
MM of the end of study participation date 
 The last day of the month of the occurrence otherwise. 
 
Dates missing both the day and month of the year will adhere to the following conventions: 
x Missing onset date will be set to: 


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 January 1 of the year of the onset, if the onset YYYY is after the YYYY of the first 
double-blind treatment 
 The date of the first run-in treatment, if the onset YYYY is the same as YYYY of the 
first run-in treatment, but different from YYYY of the first double-blind treatment 
 The date of the first double-blind treatment, if the onset YYYY is the same as YYYY of 
the first double-blind treatment 
 The date of informed consent, if the onset YYYY is before YYYY of the first run-in 
treatment 
x The missing end date will be set to: 
 The death date, if the end date YYYY is the same as the YYYY of the death date 
 The end of study participation, if the end date YYYY is the same as the YYYY of the 
end of study participation date 
 December 31 of the year of occurrence otherwise. 
4.2.4. 
Assessment Windows 
4.2.4.1. 
Study Reporting Periods 
Based on study design and variables under consideration, study time periods are defined as 
below. 
Table 2:  
Definition of Study Reporting Periods 
Analysis 
description 
Analyzing 
Study Period 
Start Date  
End Date 
General 
Screening  
Date of informed 
consent 
Date of first run-in dose 
 
Run-in  
Date of first run-in 
single-blind dose 
Date of last run-in single-
blind dose 
 
Treatment (Day 
1 – Week 24) 
Date of first double-
blind dose 
Date of last double-blind 
dose + 5 days 
 
Follow-up (up to 
Week 27) 
>Date of last dose + 5 
days  
Date of EOS visit 
Adverse 
events (based 
on AE start 
date) 
Prior  
Date of informed 
consent 
Date of first run-in dose 
 
Run-in  
Date of first single-blind 
run-in dose 
Date of first double-blind 
dose 
 
TEAE  
Date of first double-
blind dose* 
Date of last dose + 5 days 
 
Post-Treatment  
Date of last dose + 5 
days 
N/A 
Concomitant 
Medication/ 
Procedure 
(any overlap 
with period) 
Prior medication/ 
procedure 
N/A 
Date of first double-blind 
dose 


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Analysis 
description 
Analyzing 
Study Period 
Start Date  
End Date 
 
Concomitant 
medication/ 
procedure 
Date of first double-
blind dose 
Date of last double-blind 
dose + 5 days 
 
Post medication/ 
procedure 
>Date of last double-
blind dose + 5 days 
N/A 
EOS: End of study is defined as the date when the subject has completed one of the 
following: completes Week 24 Visit for subjects who enroll into Study URO-901-3006 or 
Safety Follow-up for subjects who do not enroll into Study URO-901-3006, discontinued from 
the study, or is lost to follow-up. 
*AEs with a start date equal to the date of first double-blind dose will be considered treatment-
emergent unless the relatedness to study drug is marked ‘Not applicable’. 
Overlapping period: Medication start date<= period start date<medication end date, 
medication start date<period end date<=medication end date, or period start 
date<=medication start or end date<period end date, then the medication is considered 
overlapping with the period. 
4.2.4.2. 
Analysis Visit Windows  
 
Analysis visit windows for both diary and non-diary data are defined as shown in Table 3. All 
observations will be given an analysis visit, assigned based on relative study day, as defined in 
section 4.3.3. If fewer than three diary days are within the analysis window, only the data within 
the window will be used to calculate visit-level averages. Unless otherwise noted, all data will be 
listed. 
 
Table 3:  
Analysis Window Slotting 
Analysis window 
label 
Nominal 
visit 
Nominal 
day 
Non-Diary Visit 
Window 
Diary Visit 
Window 
Screening  
Visit 1 
-49 to - 21 
date of informed 
consent to date of 
first run-in dose 
 
Run-in  
Visit 2 
-14 
date of first run-in 
dose to day -1 
7 days prior to date 
of first run-in dose 
           Baseline         
Visit 3 
1 
[-1,1] 
date of first run-in 
dose to day -1 
Week 1 
Visit 4 
8 
[2, 11] 
 
Week 2 
Visit 5 
15 
[12, 22] 
[7, 18] 
Week 4 
Visit 6 
29 
[23, 42] 
[19, 39] 
Week 8  
Visit 7 
57 
[43, 70] 
[47, 67] 
Week 12  
Visit 8  
85 
[71, 98]* 
[68, 102] 
Week 16 
Visit 9 
113 
[99, 126] 
[103, 123] 
Week 20 
Visit 10 
141 
[127, 154] 
[131, 151] 


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Analysis window 
label 
Nominal 
visit 
Nominal 
day 
Non-Diary Visit 
Window 
Diary Visit 
Window 
Week 24 
Visit 11 
169 
[155, last dose date + 
5] 
[159, 179] 
Follow-Up for 
Early Withdrawals 
NA 
NA 
>Last dose date + 5 
 
Follow-Up for 
Completers 
NA 
NA 
 >Last dose date + 5 
 
*Urodynamics window for Week 12 is [57, 113] 
For subjects who withdraw early, assessments taken at the end of study visit will also be 
summarized with scheduled data if they fall within an on-study visit window and are 
within 21 days after the last treatment date. 
For parameters which were not scheduled to be collected at all visits, still use the all-
inclusive visit intervals defined for all visits (i.e., the window defined above) to slot 
records. However, if a value is slotted to a visit unscheduled for a parameter, it will not 
be summarized (and not be included in the efficacy datasets) but will be included in data 
listings.  
1. If after all records have been slotted, there are multiple valid records within a visit, use 
the record by the following the rules below: 
x If there are more than three bladder diary days within the window, the three days 
closest to the nominal visit day will be used to calculate analysis visit averages. If two 
days are equidistant to the nominal visit day, the earlier day will be selected first. 
x If there are multiple values for other efficacy endpoints in one window, the visit 
closest to the nominal day will be selected for assessing endpoints at a particular visit 
and for by-visit displays. If the visits are equidistant from the nominal day, then the 
earlier visit will be selected. All values will be stored in analysis datasets.  
x The same visit windows will be used for safety and laboratory assessments. If there 
are multiple safety or laboratory values in one time window on-treatment, the worst 
value (furthest from the center of the normal range if both high and low abnormalities 
exist) will be selected for the by-visit analyses.  
4.3. 
Data Definitions and Derivations of Endpoints 
4.3.1. 
Bladder Diary Endpoints 
The bladder diary recorded what time subjects woke up for the day, what time they went to bed, 
and asked the subjects to record every time they had a urination event or leakage. For each event, 
subjects recorded the time, if they had a need to urinate immediately, if they urinated in the 
toilet, if they had accidental urine leakage and if they had leakage the main reason for the 
leakage (urge or other) for 3 consecutive days, and volume voided per micturition (over one 24-
hour period) prior to each required timepoint.  The following efficacy parameters will be derived 
based on the Diary data for baseline, Weeks 2, 4, 8, 12, 16, 20 and 24. Parameters will be derived 


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for the visit only if there is at least one valid diary day within the analysis window. If a subject 
answered ‘no’ to all three questions for every record on a diary day, with no volume recorded on 
any record, that day will be treated as missing for analysis purposes but will be included in the 
listings. 
4.3.1.1. 
 Co-primary Efficacy Endpoint  
 
Although these endpoints are automatically derived in eCRF Day 3 Bladder Diary page, the final 
statistical analysis will use the value derived by the biometrics team based on the algorithm 
described below. 
CFB in average number of daily micturition episodes to Week 12 (co-primary endpoint) 
The number of micturition episodes will be defined as the number of times a subject has voided 
in the toilet as indicated on the Bladder Diary, either by marking the ‘urinated in toilet’ question 
as yes or recording a non-zero volume voided. This will be derived from individual log lines 
within each diary day; automatically derived daily totals on the eCRF Bladder Diary pages will 
not be used.  Average number of micturition episodes per day at each study visit will be 
calculated using records within the diary analysis visit windows described in Table 3 divided by 
non-missing diary days (diary days with at least one void reported).   
 
CFB in average number of daily urgency episodes to Week 12 (co-primary endpoint) 
 
The number of urgency episodes will be defined as the number of times a patient has checked 
that he had the need to urinate immediately as indicated on the Bladder Diary.  Average number 
of daily urgency episodes at each study visit will be calculated as the total number of urgency 
episodes within the diary analysis visit windows divided by non-missing diary days.  
 
4.3.1.2. 
Secondary Efficacy Endpoint (Bladder Diary) 
CFB in average number of daily nocturia episodes to Week 12 (secondary endpoint #1) 
Nocturia episodes will be calculated in the same manner as average number of daily micturition 
episodes but only include episodes occurring during sleep (after bedtime on the current diary day 
and prior to wake-up time on the subsequent day). Although the endpoint is automatically 
derived in eCRF Day 3 Bladder Diary page (and daily totals are automatically derived on the 
eCRF Bladder Diary pages), the final statistical analysis will use the value derived by the 
biometrics team based on the algorithm described above.  
CFB in average number of daily urge urinary incontinence (UUI) episodes to Week 12 for 
subjects with UI at baseline (secondary endpoint #2) 
The number of UUI episodes will be defined as the number of times a subject has checked 
that they had “urge” as the main reason for the leakage. Average UUI episodes per day at each 
study visit will be calculated in the same manner as described above for the micturition endpoint. 
The UUI endpoint will be analyzed for subjects with UI at baseline. 
CFB in average volume voided per micturition to Week 12 (secondary endpoint #4) 


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The total volume voided will be calculated using all urinary volumes collected regardless of 
whether patients checked “Urinated in Toilet or not”. Average volume voided per micturition at 
each study visit will be calculated as the total volume voided over diary days within the analysis 
visit window divided by the total number of micturition episodes with recorded volume.  
4.3.1.3. 
Other Exploratory Efficacy Endpoints  
Average number of daily urinary incontinence (UI) episodes for subjects with UI at baseline 
(exploratory) 
Average number of urinary incontinence episodes per day will be calculated as the total number 
of “Accidental Urine Leakage” regardless of the choice of “Main Reason for Leakage” over  
diary days within the analysis visit window divided by non-missing diary days.   
 
Urgency episodes 50% daily responder (exploratory) 
The achievement of at least a 50% reduction from baseline in average daily urgency episodes is a 
binary variable of 0 (endpoint is not attained) or 1 (endpoint is attained). Subjects will be 
considered as responders when the endpoint is attained.  
 
Urgency urinary incontinence (UUI) episodes daily 75% responder (exploratory) 
The achievement of at least a 75% reduction from baseline in average daily UUI episodes is a 
binary variable of 0 (endpoint is not attained) or 1 (endpoint is attained). Subjects will be 
considered as responders when the endpoint is attained. The endpoint will be analyzed for 
subjects with UI at baseline. 
4.3.2. 
Patient Reporting Questionnaire Scoring 
4.3.2.1. 
International Prostate Symptom Score 
The International Prostate Symptom Score (IPSS) is based on the responses to 7 questions 
concerning urinary symptoms and 1 question concerning quality of life. Each question concerning 
urinary symptoms allows the subject to choose 1 out of 6 answers indicating increasing severity of 
the particular symptom. The responses are assigned points from 0 to 5. The total score can therefore 
range from 0 to 35 (asymptomatic to very symptomatic).  
The questions refer to the following urinary symptoms: 
Questions  Symptom  
Subscale Category 
1  
Incomplete emptying  
Voiding 
2  
Frequency  
Storage 
3  
Intermittency  
Voiding 
4  
Urgency  
Storage 
5  
Weak Stream  
Voiding 
6  
Straining  
Voiding 
7  
Nocturia  
Storage 
Question 8 refers to the subject’s perceived quality of life (QoL). The answers to the single question 
to assess the quality of life this question range from “delighted” to “terrible” or 0 to 6. 




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Raw scores for each scale will be calculated as the sum of responses to all the questions within 
the scale, with missing values imputed as the average value over the scale if <50% of the scale 
items are missing. If ≥ 50% of the items are missing, no scale score will be calculated, and the 
subscale score will be considered missing. 
To transform the raw scores to a unified score ranging from 0 to 100, the following algorithms 
are used to derive the corresponding score at baseline, Week 12 and Week 24.  
x For the Symptom Bother Score, the transformed score is: 
ݏܿ݋ݎ݁= (ݏݑ݉ ݋݂ ܽܿݐݑ݈ܽ ݏܿ݋ݎ݁−݈݋ݓ݁ݏݐ ݌݋ݏݏܾ݈݅݁ ݏܿ݋ݎ݁)
ݎܽ݊݃݁
× 100 = ݏݑ݉ ݋݂ ܽܿݐݑ݈ܽ ݏܿ݋ݎ݁−8
40
× 100 
For Symptom Bother, higher scores correspond to the symptoms having a larger bother and 
lower scores represent a lower amount of bother due to symptoms. 
x For the Coping, Concern, Sleep, Social Interaction, and Total HRQL Scores, the 
transformed score is: 
ݏܿ݋ݎ݁= (ℎ݅݃ℎ݁ݏݐ ݌݋ݏݏܾ݈݅݁ ݏܿ݋ݎ݁− ݏݑ݉ ݋݂ ܽܿݐݑ݈ܽ ݏܿ݋ݎ݁)
ݎܽ݊݃݁
× 100 
In this case, higher scores correspond to a higher quality of life and lower scores represent a 
lower quality of life.  
4.3.2.3. 
 
covers 5 dimensions of quality of life: mobility, self-care, usual 
activities, pain/discomfort, anxiety/depression, with respondents selecting one of 5 responses for 
each dimension. Each dimension has 5 levels: no problems, slight problems, moderate problems, 
severe problems and extreme problems. The subject is asked to indicate his/her health state by 
ticking the box next to the most appropriate statement in each of the five dimensions. This 
decision results in a 1-digit number that expresses the level selected for that dimension. The 
digits for the five dimensions can be combined into a 5-digit number that describes the patient’s 
health state. The 5-digit number will be mapped to an index value using the crosswalk link 
function for the US value set based on the published 
 [4] 
at baseline, Week 12 and Week 24. At Week 12 and Week 24, the Pareto Classification of Health 
Change will also be assessed, which classifies health state relative to baseline: 
x Health state is better if it is better in at least one dimension and no worse in any other 
dimension 
x Health state is worse if it is worse in at least one dimension and no better in any other 
dimension 
x Health state is unchanged if it all dimensions remain the same 


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x Health state is mixed if it is better in at least one dimension and worse in at least one 
dimension. 
 also includes a visual analog scale (VAS) to capture a patient’s overall health 
rating.  
4.3.3. 
Study Day and Duration  
Study day is relative to the start date of the double-blind treatment. This is used to describe the 
relative time of an event or assessment that happened during the study. The first day of the study 
is defined as the day a patient first receives either vibegron or placebo in the double-blind 
treatment period. This is expected to be the same day as the randomization as Day 1.  There is no 
study Day 0 defined in the study.  
x For event or assessment occurring on or after the first dose of double-blind treatment 
date:   
       Study day = Date of event or examination – date of first double-blind treatment + 1 
x For event or assessment occurring prior to the first dose of double-blind treatment date:   
       Study day = Date of event or examination – date of first double-blind treatment 


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A duration between any two dates (such as AE duration) expressed in days will be calculated 
using the following convention: 
x Duration = Later date – earlier date + 1 
4.3.4. 
Baseline and Change from Baseline 
In general, the last recorded value on or prior to the date of randomization will serve as the 
baseline measurement for efficacy endpoints while the last recorded value prior to first double-
blind dose of study treatment will serve as the baseline measurement for safety endpoints. The 
mean of multiple values will be used as baseline for the following situations: 
x If multiple measurements are scheduled on the same baseline day (i.e., blood pressure) 
x If multiple measurements are collected on the same baseline day without the time or 
“repeat” status to differentiate the records 
For efficacy endpoints derived from the Bladder Diary, the baseline will be the average value 
over the diary days in the baseline analysis visit window.   
Change from baseline will be calculated as the post-baseline value minus the baseline value. 
Percentage change from baseline will be calculated as the change from baseline divided by the   
baseline value, multiplied by 100. If either the baseline or post-baseline value is missing, then 
change from baseline and percentage change from baseline will be set to missing. 
4.3.5. 
Pre-existing and Baseline Hypertension 
Pre-existing Hypertension will be assigned based on a search of a subject’s medical history for 
the presence (Yes) of any or absence (No) of all the following coded terms:  
x Accelerated hypertension 
x Diastolic hypertension 
x Essential hypertension 
x Hypertension 
x Hypertensive crisis 
x Hypertensive emergency 
x Hypertensive heart disease 
x Malignant hypertension 
x Malignant hypertensive heart disease 
x Secondary hypertension 
x Supine hypertension 
x Systolic hypertension 
Baseline Hypertension will be assigned based on a subject’s baseline vital signs: 
x Visit average SBP ≥ 140 
x Visit average DBP ≥ 90  


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5. STUDY SUBJECTS 
5.1. 
Subject Disposition and Withdrawals 
Subject disposition will be summarized by treatment arm for the screened, run-in and 
randomized subjects. The summary table will present the frequency and percentage of subjects in 
each of the analysis sets and those who discontinued the study prematurely along with the 
primary reasons for discontinuation.  
For the summary for the randomized subjects, the following additional categories will be 
presented as well; randomized, received treatment with study drug, did not receive treatment 
with study drug, completed treatment with study drug, discontinued treatment with study drug 
(and reason), discontinued treatment with study drug but completed study follow-up, completed 
study, and withdrawn from study (and reason). 
The frequency and percentage of subjects with at least one major Protocol Deviation (PD), major 
PD by classification and reasons/category for PD will be summarized by treatment arm for the 
FAS. Inclusion in each of the analysis sets (SAF, SAF-Orth, SAF-UDS, UES, FAS, FAS-I, PPS, 
PPS-I), and any reasons for exclusion will be summarized by treatment arm for the Randomized 
Set.  
Screen Failure, Run-in and Double-Blind Period disposition, with reasons for discontinuation of 
study will also be listed if applicable, including the date of discontinuation. 
Eligibility criteria, screening failures (including date and primary reason for failure), and 
informed consent (protocol version, informed consent version date and date signed) will be listed 
for all patients screened. 
A summary of randomized subjects by country and investigator will be provided. Randomization 
details will also be listed, including the date of randomization, randomization number and 
randomization strata. 
5.2. 
Demographic and Baseline Characteristics 
All demographic and baseline characteristic data will be summarized by treatment group using 
descriptive statistics for all subjects for each of the following analysis sets: SAF, SAF-Orth, 
UES, PPS-UES, FAS, FAS-I, PPS and PPS-I.  
The summary table will include Sex, Ethnicity and Race, Region (US and non-US), Prior 
Anticholinergic Use (Yes/No), Prior Beta-3 agonist Use (Yes/No), Diabetes Mellitus (Yes/No), 
Baseline Hypertension (Yes/No), Pre-existing Hypertension (Yes/No), Age category 1 (<55, ≥55 
to <65, ≥65 to <75, ≥75 years), Age category 2 (<65, ≥65 years), Age category 3 (<65, ≥65 to 
<75, ≥75 to <85, ≥85 years), treatment with alpha blocker, treatment with 5-ARI, baseline 
average micturition episodes per day (≤ 12 vs > 12),  Alpha blocker use with or without 5-ARI 
(with vs without), Urinary Incontinence (yes or no) and IPSS total score. Stratification factors 
will be summarized both as randomized and corrected if any misstratification was present. 


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Prior Anticholinergic Use and Prior Beta-3 agonist Use will be calculated from all prior 
medications documented on the Prior and Concomitant Medications electronic case report form 
(eCRF).  
Pre-existing and Baseline hypertension are defined in section 4.3.5. 
Age (years), height (cm), weight (kg), BMI (kg/m2) captured at Screening, and baseline IPSS 
total score will be summarized as continuous variables. 
Unless otherwise stated, percentages will be calculated out of the number of patients in the given 
analysis set. 
All demographic data will be listed. 
5.3. 
Other Baseline Characteristics 
The data from the 3-day bladder diary during run-in period (reviewed at Visit 3 Baseline visit) 
prior to first dose of double-blind medication will be used as baseline for each subject. This 
includes average number of daily micturition episodes, average number of daily urgency 
episodes, average number of nocturia per night, average number of daily urge urinary 
incontinence episodes, and average volume voided per micturition.  In addition, the baseline 
IPSS Storage score, prostate volume, Qmax (maximal urinary flow) at baseline as determined by 
uroflowmetry (see section 7.7 for details), and baseline post-void residual urine will be 
presented. These will be summarized by treatment group and overall using descriptive statistics 
for continuous data for all subjects in FAS, FAS-I, PPS and PPS-I analysis sets. 
5.4. 
Medical History and Concomitant Disease 
Descriptions of medical history findings will be coded using Medical Dictionary for Regulatory 
Activities (MedDRA) version 22.0 or higher. 
A disease or illness reported as medical history without a start date will be included in medical 
history without a date assigned. Medical history will be sorted by descending overall frequency, 
by system organ class (SOC) and preferred term (PT) in the summary table. Medical history data 
listings will be sorted by treatment, subject number, start date, SOC and PT. The SAF will be the 
analysis set for medical history data.  
5.5. 
Procedures 
Procedures will be coded using Medical Dictionary for Regulatory Activities (MedDRA) version 
22.0 or higher. 
Prior procedures are defined as procedures with a start date prior to the first dose of double-blind 
treatment. Concomitant procedures will be defined as procedures started on or after the first dose 
of double-blind medication but prior to the last dose of the double-blind medication + 5 days, or 
started prior to double-blind medication and were ongoing during the double-blind period. Post 
procedure is any procedure initiated after last dose of double-blind medication + 5 days (See 
Table 2). Partial procedure start dates will be imputed as detailed in 4.2.3. 


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All procedures will be listed for the SAF population, sorted by treatment, subject number, start 
date, SOC and PT, with indicators of prior and concomitant status. 
5.6. 
Prior and Concomitant Medication  
Prior and concomitant medications will be coded using the World Health Organization (WHO) 
Drug B3-Sept Format, 2018 version or higher. Except for Prior OAB medication, the number 
and percentage of subjects taking prior medications and concomitant medications will be 
summarized overall by ATC (Anatomical Therapeutical Chemical) Levels 2 and 4 for all 
subjects in the SAF. Prior OAB medications will be summarized by ATC Levels 2, 4 and 
Preferred Term in the SAF. Prior medications OAB medication and concomitant medications 
will be listed for all subjects in the SAF. 
5.6.1. 
Prior Medication 
Prior medications are defined as those medications taken prior to the first dose of double-blind 
treatment. The prior non-OAB and prior OAB medications will be summarized separately.  
The following criterion will be used for selecting prior OAB medication: 
Table 6:  
OAB Medication Selection 
Class 
Variable Selected 
Selection 
Anticholinergics  
Preferred Term 
darifenacin,  
fesoterodine,  
festoterodine fumarate hyoscyamine, 
oxybutynin, 
oxybutynin hydrochloride,  
propantheline, 
solifenacin,  
solifenacin succinate,  
tolterodine, 
tolterodine l-tartrate,  
trospium,  
trospium chloride 
Beta-3 adrenergic 
agonists 
Preferred Term 
mirabegron,  
vibegron, 
solabegron 
5.6.2. 
Concomitant Medication 
Concomitant medications will be defined as medications started on or after the first dose of 
double-blind medication but prior to the last dose of the double-blind medication + 5 days, or 
started prior to double-blind medication and ongoing during the double-blind period. Post 
medication is the medication taken after the last dose of double-blind medication + 5 days (See 
Table 2). Partial medication start dates will be imputed as detailed in 4.2.3.  


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Non-OAB and OAB concomitant medications will be summarized separately. 
5.7. 
ECG 
12-Lead ECG data will be collected at the screening visit only. All data collected will be listed. 
5.8. 
Prostate Volume Measurements 
Prostate volume is measured at Screening or historically within 12 months of screening via 
ultrasound. All prostate volume measurements will be listed. 
5.9. 
 Treatment Exposure 
The duration of exposure during the double-blind treatment period will be expressed as the time 
in days from the first dose as recorded on the Study Drug Administration CRF page through to 
last treatment day (inclusive) as recorded on the End of Treatment CRF page, excluding any days 
where it is recorded that an interruption has occurred on the AE CRF page or gaps in the study 
drug log. If no dose was witnessed at the baseline visit, the date of baseline study drug 
dispensation + 1 will be used. If no last treatment date is recorded, it will be imputed as the 
minimum of the date of the last visit on the study and the date when last dispensed study 
treatment was scheduled to be exhausted (last dispensation date + number of doses dispensed). 
Gaps in the study drug log will be determined by comparing the dispensation date of a record to 
the previous dispensation date (where multiple bottles may have been dispensed). If one bottle 
was dispensed, then the gap is measured from study day of previous dispensation + 32; if two 
bottles were dispensed then the gap is measured from study day of previous dispensation + total 
number of pills dispensed. 
Interruption in days = date interruption stated – date interruption stopped + 1  
The duration is calculated by the following formula: 
ܦݑݎܽݐ݅݋݊ (݀ܽݕݏ) = ݀ܽݐ݁ ݈ܽݏݐ ݀݋ݑܾ݈݁ ܾ݈݅݊݀ ݀݋ݏ݁ − ݀ܽݐ݁ ݂݅ݎݏݐ ݀݋ݑܾ݈݁ ܾ݈݅݊݀ ݀݋ݏ݁ –     
                                 interruption days + 1 
Duration of exposure will be summarized by treatment group and overall for the SAF using 
summary statistics for continuous variables. Total drug interruption days due to AE and gaps in 
the study drug log will also be summarized. A listing will present the treatment start and end date 
together with the date of interruption, and the overall duration of exposure. 
5.10. 
Treatment Compliance 
Study treatment compliance (%) will be calculated as the actual number of doses divided by the 
expected number of doses, multiplied by 100 and summarized by treatment group and double-
blind treatment period. 
These numbers will be determined by the number of tablets dispensed and returned unused by 
the subject. Where no treatment bottle is returned, and thus the actual number of doses is 


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unknown, it will be assumed that the subject took medication as directed until their supply was 
exhausted. Imputed values will be clearly noted in the listing. 
The expected number of doses is the same as the calculated duration of exposure detailed in 
section 7.1. 
Overall compliance will be calculated for run-in and the double-blind treatment period, 
respectively.  
ܱݒ݁ݎ݈݈ܽ ܥ݋݉݌݈݅ܽ݊ܿ݁ (%) = 
ܰݑܾ݉݁ݎ ݋݂ ݀݋ݏ݁ݏ ݐܽ݇݁݊
ܧݔ݌݁ܿݐ݁݀ ݊ݑܾ݉݁ݎ ݋݂ ݀݋ݏ݁ݏ × 100% 
The number of doses taken is summed from values recorded on the drug accountability CRF. If 
number of doses taken is missing for a log line within the drug accountability CRF, it will be 
imputed as the minimum of (number of doses dispensed, subsequent dispensation date – current 
dispensation date). 
Treatment Compliance will be summarized for the SAF and FAS population. Additionally, the 
number and percentage of subjects within each treatment with compliance in the following 
categories will be provided: <80%, 80 – 120%, and >120%. All data will be listed. 
6. EFFICACY ANALYSIS 
Subjects were asked to fill out a Bladder Diary for 3 consecutive days prior to the Run-in visit, 
Baseline visit, and at Weeks 2, 4, 8, 12, 16, 20, and 24.  
In general, the FAS will be used for all analyses of efficacy endpoints except for incontinence 
efficacy endpoints where the FAS-I will be used.  
All outputs that present a CFB will also present descriptive statistics on the baseline value of the 
parameter. 
6.1. 
Co-Primary Endpoint Analysis 
6.1.1. 
Primary Analysis  
The primary analysis will be based on the FAS. Descriptive summary for observed and CFB will 
be provided by visit and treatment for both co-primary endpoints. Refer to parameter derivations 
from Bladder Diary data on Section 4.3.1.  
Co-primary 1: CFB to Week 12 in average number of daily micturition episodes  
For the assessment of difference between the treatment groups in change from baseline to Week 
12 in average number of daily micturition episodes, a mixed model for repeated measures 
(MMRM) will be used incorporating on-treatment values at all time points (Weeks 2, 4, 8, 12, 
16, 20, and 24). The model takes account of any correlation within the same subject over time by 
using all available data on the subjects. With the assumption of missing at random (MAR), this 
approach will provide unbiased estimates of treatment effects derived from the model.   


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The MMRM model will include terms for treatment, visit, baseline value (average number of 
daily micturition episodes), alpha blocker use with or without 5-ARI (with vs. without), baseline 
urinary incontinence (yes vs. no), region (US vs. non-US), and interaction of visit by treatment. 
Stratification factors as randomized will be used in the model. The Kenward-Roger adjustment 
will be used with restricted (or residual) maximum likelihood (REML) to make statistical 
inference.  An unstructured covariance matrix will be used to model the correlation among 
repeated measurements. If the unstructured covariance model fails to converge with the default 
Newton-Raphson algorithm, the Fisher scoring algorithm will be used to provide initial values of 
the covariance parameters.  In the rare event that none of the above methods yield convergence, 
the following structures will be investigated:  heterogeneous Toeplitz, Toeplitz, heterogeneous 
First-Order Autoregressive [AR (1)], heterogeneous compound symmetry (HCS), and compound 
symmetry (CS).  The covariance structure converging to the best fit, as determined by Akaike’s 
information criterion (AIC), will be used. 
Primary inference will be drawn from the treatment difference between vibegron and placebo at 
Week 12. Results will be presented in terms of least square means (LSMEANS), treatment 
differences in LSMEANS, 95% confidence intervals for the treatment difference for all 
timepoints.  Although nominal p-values for the treatment differences will be presented for all 
visits, the primary inference is at Week 12.  The estimated LSMEANS (Standard Error (SE)) of 
CFB over time from the model will be plotted by treatment. 
An example of the SAS code for the base procedure is given below: 
    proc mixed data = datain method = reml; 
  class TRTP AVISITN USUBJID ALPHAB UI REGION; 
  model CHG = TRTP AVISITN ALPHAB UI REGION BASE TRTP*AVISITN 
        / ddfm=KR solution chisq; 
  repeated AVISITN / subject=USUBJID type=UN r rcorr; 
  lsmeans TRTP*AVISITN / pdiff=all cl alpha=0.05; 
    run; 
 
Where TRTP is the planned treatment, AVISITN is the visit number, USUBJID is the unique 
subject identifier, ALPHAB indicates if the subject used 5-ARI in addition to alpha blockers at 
baseline, UI indicates baseline urinary incontinence, REGION indicates if the subject is in the 
United States or in the non-US countries and BASE indicates baseline value. The default 
Newton-Raphson algorithm is employed for type = UN. If the default algorithm fails to 
converge, use Fisher scoring algorithm to include option scoring = 5 in the model.  
The normality assumptions for the primary analysis model will be assessed by inspection of the 
residuals from the model and normal probability plots. If assumptions of normality are not met, 
additional supportive analysis of the data will be performed in order to assess the robustness of 
the conclusions drawn from the primary analysis.   
Co-primary 2: CFB to Week 12 average number of daily urgency episodes 
The primary analysis will be identical to the analyses specified for the first co-primary described 
above with the addition of fitting in the categorical covariate of baseline average number of daily 
micturition episodes (≤ 12 vs. > 12, stratification factor as randomized).  


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Multiplicity of Co-Primary Endpoints 
No multiplicity adjustment is required for the co-primary endpoints since both endpoints need to 
be statistically significant at the 0.05 level in order to claim trial success.  
6.1.2. 
Sensitivity Analysis  
6.1.2.1. 
Per-Protocol Analysis 
To assess the robustness of the results from primary analysis, the same MMRM models will be 
conducted to both co-primary endpoints based on PPS.  
6.1.2.2. 
Analysis of Covariance with Multiple Imputed data  
 
An ANCOVA model will be used as a sensitivity analysis. For patients with missing Week 12 
assessment due to any reason, the Week 12 value will be imputed using multiple imputation (see 
Appendix 11.1 for further details). The model will include terms for treatment, baseline value of 
the parameter, region (US vs. non-US), and stratification factors as randomized: alpha blocker 
use (with vs. without 5-ARI), baseline urinary incontinence (yes vs. no), baseline number of 
average daily micturition episodes (≤ 12 vs. > 12, only included for the urgency parameter). The 
analysis will be performed on FAS and PP analysis sets. 
 
An example of the SAS code for the base procedure is given below: 
   proc mixed data = datain method = reml; 
  class TRTP ALPHAB UI REGION; 
  model CHG = TRTP AVISITN ALPHAB UI REGION BASE  
        / ddfm=KR solution chisq; 
  Where AVISIT = “Week 12”; 
  lsmeans TRTP/ pdiff cl alpha=0.05; 
   run; 
 
A tipping point analysis will accompany the multiply imputed ANCOVA results, and the 
estimated shift parameter will be presented to two decimal places. 
 
The normality assumptions for the ANCOVA analysis model will be assessed by inspection 
of the residuals from the model and normal probability plots. If assumptions of normality 
are not met, additional supportive analysis of the data will be performed in order to assess 
the robustness of the conclusions drawn from the primary analysis. 
 
This supportive analysis will use the multiple imputation (MI) data at Week 12 using a non-
parametric analysis of covariance within the framework of the extended Cochran-Mantel-
Haenszel test. Specifically, a Cochran-Mantel Haenszel mean score test will be used on the 
standardized mid-ranks of the residuals from an ordinary least squares regression with Week 12 
MI response as a linear function of the baseline score (as a continuous variable). P-value for the 
between treatment comparison for each primary endpoint will be derived for the model. 
 
This methodology will be carried out as follows: 


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1.  The observed value of the primary endpoint (i.e., the last on treatment average 
number of daily micturition episodes) will be fitted using an ordinary least squares 
regression as a 
function of the baseline value at each visit 
 
2.  Standardized mid-ranks of the residuals from the regression will be calculated. 
 
3.  The standardized mid-rank from the last observation will be carried forward for missing 
     values at week 12 
 
4.  Standardized mid-ranks will be recalculated 
 
5.  A CMH mean score statistic and p-value adjusting for the stratification groupings will be   
     calculated for between treatment comparisons 
 
An example of the SAS code for the base procedure is given below: 
proc glm Data=datain; 
   by Avisitn; 
   model aval = Base; 
   output out=glmout residual=Residual; 
   run;  
 
proc rank data=glmout out=Rank1 nplus1 ties=mean; 
by Avisitn; 
var Residual; 
ranks RANKOBS; 
    run; 
 
    proc sort data=rank1; 
   by subject avisitn; 
    run; 
 
 
   data rankmi; 
   set rank1; 
   by subject avisitn; 
   if last.subject; 
   run; 
 
   proc rank data=rankmi out=ADRANK nplus1 ties=mean; 
    by avisitn; 
    var RANKOBS; 
    ranks Rankana; 
   run; 
 
   proc freq data = ADRANK; 
   tables stratified vars*TRTP*Rankana / cmh2 scores = table; 
   run; 
 


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6.1.2.3. 
MMRM with Stratification Factors as Observed 
If more than 7% of subjects are misstratified, the co-primary MMRM efficacy analysis will be 
repeated using stratification factors as calculated from the baseline diary (baseline average 
number of daily micturition episodes, baseline incontinence) and prior medications (alpha 
blocker use with or without 5-ARI). 
6.1.3. 
Subgroup Analysis  
For following selected subgroups listed in Section 4.1.3, a separate MMRM model will be fit on 
co-primary endpoints, respectively, based on the FAS.  
x Alpha blocker use with or without 5-ARI (with vs. without, stratification factor as 
randomized) 
x Baseline urinary incontinence (yes vs. no, stratification factor as randomized) 
x Region (US vs. Non-US) 
x Age category 2 (<65, ≥65 years) 
x Race (White, African American, Asian and Other) 
The same model terms as used for the primary analysis specified in Section 6.1.1 will be applied 
with additional terms for subgroup main effect, treatment by subgroup interaction, and treatment 
by subgroup by visit interaction. Only the estimate and p-value for the interaction term from the 
MMRM will be provided. With the exception of Age category 2 and Race subgroups, if less than 
20% of randomized subjects are in a subgroup the corresponding subgroup analysis will not be 
performed. Descriptive summary statistics will be provided for all subgroups.  
A forest plot will be provided to present the results from subgroup analyses. Side-by-side 95% 
confidence intervals will be plotted for each comparison to control within each subgroup, where 
the 95% confidence intervals are taken from the analysis table described above. The confidence 
intervals are stacked vertically on the page, with a reference line at zero for mean. All the 
subgroups should be plotted on a single figure (using multiple pages, if necessary). 
The following subgroups will be used for descriptive statistics only: Age category 1, Age 
category 3, Prior anticholinergic, and Prior beta-3 agonist use. 
6.2. 
Secondary Efficacy Analyses  
Descriptive summary for observed and CFB will be provided by treatment and visit for each 
endpoint.  Refer to Bladder Diary related parameter derivations in Section 4.3.1 and average 
IPSS Storage score in Section 4.3.2.1.  
The following secondary efficacy endpoints will be analyzed based on the FAS:  
x CFB to Week 12 in the average number of nocturia episodes per day 
x CFB to Week 12 in the International Prostate Symptom Score (IPSS) Storage     
      score (1-week recall)  


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x CFB to Week 12 in the average volume voided per micturition  
The following secondary efficacy endpoint will be analyzed based on the FAS-I:  
x CFB to Week 12 in the average number of daily urge urinary incontinence episodes for 
subjects with urinary incontinence at baseline  
All four secondary endpoints will be analyzed and presented similarly as described in the 
primary analysis of co-primary efficacy endpoints in Section 6.1.1. The same MMRM model 
used for the CFB to Week 12 in average number of daily urgency episodes will be applied to all 
secondary endpoints except for CFB to Week 12 in the average number of daily urge urinary 
incontinence episodes. For this incontinence endpoint, the baseline urinary incontinence (yes vs. 
no) strata will not be fitted in the MMRM model.   
As described in Section 4.1.2, a hierarchical gate-keeping procedure will be used to claim 
statistical significance for the secondary efficacy endpoints sequentially if statistical significance 
is achieved at the 0.05 level for both co-primary endpoints.  
6.3. 
Other/Exploratory Endpoints 
Refer to diary related parameter derivations in Section 4.3.1 and quality of life related parameters 
in Section 4.3.2.  These analyses will be based on FAS, unless stated otherwise.   
6.3.1. 
Efficacy 
The CFB at Weeks 4, 8, 16 (where collected), 20, and 24 for all primary and secondary efficacy 
variables will be included into the MMRM models along with Week 12 data as described in 
Sections 6.1 and 6.2. The additional continuous exploratory endpoints will be summarized 
descriptively.  
x CFB to Weeks 4, 8, 12, 20, and 24 in the IPSS total score and IPSS Quality of Life, Storage, 
and Voiding scores (FAS) 
x CFB to Weeks 2, 4, 8, 12, 16, 20, and 24 in the average number of total daily incontinence 
episodes per day for subjects with urinary incontinence at baseline (FAS-I)  
The number and percentage of responders and non-responders for the following exploratory 
endpoints will be tabulated by treatment and visit.   
x Urgency episodes 50% responder (exploratory) at Weeks 4, 8, 12, 16, 20, and 24 
x Urgency urinary incontinence (UUI) episodes 75% responder (exploratory) at Weeks 4, 8, 
12, 16, 20, and 24  
The treatment comparison of responder will use a Cochran-Mantel-Haenszel (CMH) common  
risk difference estimate stratified by appropriate strata per randomization stratification [6] with 
weights proposed by Greenland and Robins [7], which is calculated as follows. For the urgency 
episode responder analysis, the strata groups include baseline average micturition episodes per 
day (≤ 12 vs > 12), alpha blocker use with or without 5-ARI (with or without) and urinary 


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Incontinence (yes or no). For the incontinence responder analysis, urinary Incontinence (yes or 
no) will not be included in.  
ߜመெு=
∑
௪೔∙ఋ෡೔
ೠ
೔సభ
∑
௪೔
ೠ
೔సభ
 , where  
ߜመ௜= ݔ௜
݊௜
 − ݕ௜
݉௜
  denotes the risk difference in stratum ݅, ݅= 1, ⋯, ݑ 
ݓ௜=
௡೔∙௠೔
௡೔ା௠೔  denotes the weight of stratum ݅, ݅= 1, ⋯, ݑ  
ݔ௜ denotes the number of subjects with event in treatmentଵin stratum i, ݅= 1, ⋯, ݑ 
ݕ௜ denotes the number of subjects with event in treatmentଶ in stratum i, ݅= 1, ⋯, ݑ 
݊௜ denotes the number of subjects on treatmentଵin stratum i, ݅= 1, ⋯, ݑ 
݉௜ denotes the number of subjects on  treatmentଶin stratum i, ݅= 1, ⋯, ݑ 
The estimated variance of ߜመெு is calculated as: 
ݒܽݎ
ෞ൫ߜመெு൯=
∑
ܮ௜
௨
௜ୀଵ
(∑
ݓ௜
௨
௜ୀଵ
)ଶ 
where ܮ௜= ݔ௜(݊௜−ݔ௜) ݉௜
ଷ+ ݕ௜(݉௜−ݕ௜) ݊௜
ଷ
݊௜∙݉௜∙(݊௜+ ݉௜)ଶ
 , ݅= 1, ⋯, ݑ 
Assuming a normal distribution of ߜመெு , an approximate 95% CI is given as follows, where 
ݖ଴.ଽ଻ହ is the 97.5% quantile of the standard normal distribution: 
ܥܫ= ቈߜመெு ± ݖ଴.ଽ଻ହ∙ටݒܽݎ
ෞ൫ߜመெு൯቉ 
Also, the approximate p-value can be calculated using the following: 
p −value =  2 ∙Pr
⎣
⎢
⎢
⎡
ܼ> ተተ
ߜመெு
ටݒܽݎ
ෞ൫ߜመெு൯
ተተ 
⎦
⎥
⎥
⎤
 , where ܼ ~ ܰ(0, 1) 
If there is a stratum for a treatment group that has 0 subjects in it, the 0 count will be replaced 
by 0.5 in order to prevent dividing by 0 in the above equations, as suggested in Greenland and 
Robins.   
The estimated common risk difference, and associated p-value and 2-sided 95% confidence 
interval will be tabulated.  


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6.3.2. 
Quality of Life 
The FAS will be the analysis population for the PRO data unless stated otherwise. 
6.3.2.1. 
CFB in 
 Scores 
The questionnaire is assessed at baseline, Week 12 and Week 24. The derivation of 
 
scores for Symptom Bother, Coping, Concern, Sleep, Social Interaction and total HRQL are 
detailed in Section 4.3.2.2. These derived scores and CFB will be descriptively summarized by 
treatment and visit.  
6.3.2.2. 
  
 questionnaire is assessed at baseline, Week 12 and Week 24. The 5 questions 
related to mobility, self-care, usual activities, pain/discomfort and anxiety/depression will be 
summarized descriptively as categorical variables by treatment and visit.  Each domain includes 
5 level answers: no problems, slight problems, moderate problems, severe problems and extreme 
problems. At Week 12 and Week 24 the Pareto Classification of Health Change will be presented 
relative to baseline (better, worse, same, or mixed). The mapped Crosswalk index value and 
change from baseline will be summarized as a continuous variable by treatment and visit. 
Observed VAS value, change from baseline and percent change from baseline will be 
summarized as a continuous variable by treatment and visit.  
 
6.3.2.3. 
Patient Global Impression Scores 
The questionnaire is assessed at baseline, Week 4, Week 12 and Week 24.  The Patient Global 
Impression (PGI) questions are designed to assess a subject’s overall impression of OAB in 5 
categories: 
  
Each of the responses to the PGI questions will be assigned a numerical value starting from 1. A 
higher score represents worse outcome in each category. 
Table 7:  
PGI Scoring 
PGI Category 
Score 
PGI-
 
1 = None 
2 = Mild 
3 = Moderate 
4 = Severe 
PGI-
 
1 = Complete control 
2 = A lot of control 
3 = Some control 
4 = Only a little control 
5 = No control 




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All reported AEs (whether treatment emergent or not) will be included in by-subject AE listings. 
Sorting will be by country, site, subject, date of event, SOC, PT and then verbatim description. 
An AE will be considered treatment emergent (TEAE) if it begins or worsens in severity after the 
first dose of the double-blind Study Treatment through 5 days after the last dose of Study 
Treatment or rollover to the extension study, whichever occurs first. Partial AE start dates will be 
imputed as detailed in Section 4.2.3. 
Summary tables will be based on TEAEs. The incidence of TEAEs will be presented using 
counts and percentages of subjects with TEAEs and tabulated by SOC and PT. SOC will be 
sorted in descending frequency and PT within SOC will be sorted by descending frequency 
based on the incidence across subjects overall. If a subject has multiple occurrences (start and 
stop) of an event associated with a specific SOC or PT within a SOC, a subject will only be 
counted once in the incidence count for the SOC or PT within SOC respectively. 
An overall summary table of AEs by treatment group will be presented detailing the number and 
percentage of subjects, and number of events for the following categories: 
x 
At least one TEAE; 
x 
At least one Treatment-Related TEAE; 
x 
At least one Grade ≥ 3 TEAE (Mild = Grade 1, Moderate = Grade 2, Severe or 
Medically Significant = Grade 3, Life-Threatening = Grade 4, Death = Grade 5) 
x 
At least one Grade ≥ 3 Treatment-Related TEAE; 
x 
At least one Serious TEAE; 
x 
At least one Serious Treatment-Related TEAE; 
x 
At least one TEAE leading to Discontinuation from Study Medication; 
x 
At least one TEAE of Special Interest; 
x 
At least one Treatment-Related TEAE of Special Interest 
 
Where not otherwise noted, all the following summaries are presented by PT in descending 
overall frequency:  
x 
All TEAEs (by SOC and PT in descending overall frequency); 
x 
All TEAEs (by PT in descending overall frequency) 
x 
Treatment-Related TEAEs (i.e., possibly or probably related); 
x 
All TEAEs by SOC, PT, and maximum severity (where the maximum intensity per 
patient will be counted at each level of summarization);  
x 
TEAES with Grade ≥ 3; 
x 
Treatment-Related TEAES with Grade ≥ 3; 


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x 
Serious TEAEs; 
x 
Treatment-Related Serious TEAEs; 
x 
Fatal TEAEs; 
x 
TEAEs leading to Discontinuation from Study Treatment; 
x 
TEAE of Special Interest; 
x 
Treatment-Related TEAE of Special Interest; 
x 
Non-fatal TEAEs; 
x 
Hypertension TEAEs by Pre-existing Hypertension (Yes vs No) and Baseline 
       Hypertension (Yes vs. No). Hypertension TEAEs will be selected as any TEAE with    
       preferred term of Hypertension.  
x 
Non-serious TEAEs occurring in 2% or more of any treatment group. 
In addition, a summary of all TEAEs by PT occurring in at least 2% of subjects in the vibegron 
arm and greater than the placebo arm will be created and sorted by descending frequency in the 
vibegron arm. 
Adverse events of special interest for this study include:  
x 
Adverse events consistent with urinary retention 
x 
Adverse events suggestive of cystitis or urinary tract infection (UTI)  
x 
Potential major cardiac and cerebrovascular events, including death (or any event with 
fatal outcome), myocardial infarction, cerebrovascular accident, hospitalization for 
unstable angina or chest pain, hospitalization for heart failure requiring hospitalization, 
and coronary revascularization/angioplasty/stent  
x 
Adverse events consistent with hypertension (see protocol section 8.4.6)  
x 
Elevated serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab 
value requiring that study drug be temporarily withheld or permanently discontinued  
x 
Neoplasms 
 
Treatment listings will include the treatment arm, start and stop dates of the AE, and days on 
study relative to the day of first dose of study treatment. A Treatment related AE is defined as 
an AE for which the investigator classifies the AE as being “Probably Related” or “Possibly 
Related” to study treatment on Adverse Event CRF. Missing relationship and severity 
(intensity) will be imputed per Section 4.2.3. 
 
The following additional listings will be provided: 
x 
Listing of deaths 
x 
Listing of Serious TEAEs 


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x 
Listing of treatment-emergent AESIs 
x 
Listing of TEAEs leading to withdrawal or Interruption of study treatment 
 
Listing of all AEs with a flag for TEAEs and onset (Prior = prior to first dose of single-blind 
medication, Run-in = on or after first dose of single-blind medication but prior to first dose of 
double-blind medication, or Treatment = on or after first dose of double-blind medication.) 
A listing of all medical history and pre-double-blind treatment adverse events with coded 
preferred terms belonging to the standard MedDRA query of hypertension will be created. 
7.2. 
Laboratory Evaluations 
All continuous laboratory parameters will be summarized descriptively by absolute value at each 
visit by treatment group, together with the corresponding changes from baseline. All parameters 
will be summarized in SI units. 
The number and percentage of subjects with laboratory measurements outside of the central 
laboratory normal range will also be summarized by treatment group and visit. Shift tables from 
baseline to maximum post-baseline value, to minimum post-baseline value, last post-baseline 
value, and at each post-baseline visit will be provided for hematology and chemistry parameters 
to display low, normal, high, and missing values by treatment group in a 3-by-3 contingency 
table. Denominators for percentages will be the number of subjects with non-missing data at the 
specific assessment and baseline. 
Maximum post-baseline total bilirubin will be presented (<2 and ≥2 x ULN) and plotted against 
maximum post-baseline ALT (<3, ≥3 - <5, ≥5-<10, and ≥10 x ULN), expressed as multiples of 
ULN. This will be repeated to show maximum post-baseline total bilirubin against maximum 
post-baseline AST. 
Data for subjects with ALT or AST ≥3 x ULN, and bilirubin ≥2 x ULN will be presented, which 
will include all visits for this subset of subjects. A line plot of liver biochemistry test results 
(including ALP, ALT, AST, total bilirubin, and GGT) over time will also be presented for this 
subset of patients. 
A sample for the urinalysis and urine culture will be sent to the central laboratory only if the 
urine dipstick performed at the site tests positive for the presence of leukocytes, nitrites, or blood 
cells. Dipstick results and central urinalysis data will be provided only in the listing. 
Any data outside the central laboratory normal reference ranges will be explicitly noted on the 
listings that are produced.  
7.3. 
Vital Sign Assessments 
7.3.1. 
Height, Weight, and Sitting Vital Signs  
Vital sign data including systolic and diastolic blood pressure, pulse rate, respiration rate, body 
temperature and weight will be collected at all study visits except for the safety follow-up visit. 
Height will be measured at Screening only. Blood pressure will be measured in triplicate at each 


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visit. The average of triplicates will be used for summary; if fewer than three measurements were 
collected the average of available measurements will be used. For subjects in Study Part 1 and 
visits with orthostatic blood pressure assessments, blood pressure (in triplicate) and pulse rate 
taken pre-dose in sitting position are equivalent to pre-dose regular vital sign values and will be 
used.  
Vital signs will be summarized using absolute value and change from baseline. A summary by-
visit according to the visit window rule in Section 4.2.4.2, the maximum, and last post-baseline 
observation for each subject will be summarized for each of the vital signs. For change from 
baseline in blood pressure and pulse rate, least squares mean estimates and 95% CIs as described 
in section 4.2.2 will be presented from an ANCOVA model including terms for treatment, age, 
baseline parameter value, and pre-existing hypertension (Yes vs. No).  
The line plot of mean (SE) of change from baseline in blood pressure and pulse rate over time 
will be prepared. A by-subject listing, sorted by subject identifier, will be presented including all 
vital sign results (scheduled or unscheduled). 
7.3.1.1. 
Vital Sign Subgroups 
The vital sign data for blood pressure and pulse rate will be summarized by subgroups that may 
be at a higher risk, in Table 8 
Table 8: 
At Risk Subgroup for Vital Sign Summaries 
Subgroup 
Definition of At Risk Subgroup 
Age 
≥ 75 years 
Pre-Existing 
Hypertension  
Pre-Existing Hypertension will be based on medical history 
and/or baseline hypertension, as defined in Section 4.3.5 
High BMI at baseline 
 BMI ≥ 35 kg/m2 
At Risk eGFR Group 
eGFR ≤ 60 mL/min/SA 
 
7.3.1.2. 
Categorical/Threshold Analysis 
Categorical analyses (e.g. percentage of patients with an absolute change from baseline of ≥ 5, 
10, or 15 mmHg for blood pressure and ≥ 5, 10, or 15 bpm for heart rate) of any post-baseline 
change and at 2 consecutive post-baseline visits timepoints. 
The categorical analysis will be produced for the safety population and for subgroups that might 
be at a higher risk (e.g., pre-existing hypertension, older patients [age ≥ 75 years], renal 
impairment [≤ 60 mL/min/SA], and high BMI ([≥ 35 kg/m2]), as well as their complements. 
7.3.2. 
Orthostatic Blood Pressure and Pulse Rate (Part 1 only) 
Blood pressure and pulse rate measurements are collected at Screening, Run-in, Baseline, Week 
2 and 4 to assess for potential orthostatic vital sign changes. Triplicate measurements are 


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obtained for both sitting and standing blood pressure assessments at Hour 0 (pre-dose) and Hours 
1, 2, 4, and 6 post-dose. A singular pulse rate is also obtained in sitting and standing positions at 
the same hourly timepoint. The average blood pressure of triplicates will be used for summary. 
Within each timepoint, orthostatic blood pressure and pulse rate will be derived by subtracting 
time-matched standing average values from sitting average values. Then time-matched change 
from Day 1 will be derived as follows:  
x Step 1: calculate change from pre-dose at each visit 
           CFPre at baseline visit: (Baseline 1 hr – Baseline pre); (Baseline 2hr – Baseline pre) ….         
                                                  (Baseline 6 hr – Baseline pre) 
           CFPre at Week 2 visit: (Week 2 1 hr – Week 2 pre); (Week 2 2hr – Week 2 pre) ….  
                                                  (Week 2 6 hr – Week 2 pre) 
           CFPre at Week 4 visit: (Week 4 1 hr – Week 4 pre); (Week 4 2hr – Week 4 pre) ….  
                                                 (Week4 6 hr – Week4 pre) 
x Step 2: calculate time-matched from Day 1 by subtracting time-matched CFPr of 
Baseline visit from CFPr of Week 2 and Week 4 
            [(Week 2 1 hr – Week 2 pre) - (Baseline 1 hr – Baseline pre)]  
            [(Week 2 2hr – Week 2 pre) - (Baseline 2 hr – Baseline pre)] 
               … 
            [(Week2 6hr – Week2 pre) - (Baseline 6hr – Baseline pre)] 
Observed SBP, DBP, and pulse rate will be summarized by treatment, visit and assessment time 
including corresponding change from baseline value. Baseline is the average of pre-dose 
measurement at Day 1. The following summary tables will be prepared for derived orthostatic 
SBP, DBP and pulse rate: 
x Time-matched orthostatic parameters by treatment, visit and assessment time  
x Time-matched change from Day 1 in orthostatic parameters by treatment, visit and 
assessment time 
x Maximum CFB over 6 hours in in orthostatic parameters by treatment and visit 
x Average CFB over 6 hours in orthostatic parameters by treatment and visit 
In addition, the following plots will be prepared for orthostatic vital sign parameters 


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x Line plot over time of time-matched change from Day 1 of orthostatic parameters 
x Empirical cumulative distribution function of maximum CFB over 6 Hours 
For SBP and DBP, the number and percentage of subjects with a decrease of ≥20 mmHg for SBP 
and ≥10 mmHg for DBP from sitting to standing position will also be presented by treatment, 
visit and assessment time. All orthostatic blood pressure and pulse rate measurements will be 
listed. 
7.4. 
Physical Examination 
Brief physical examination data will be collected at Screening, Baseline, Week 12 and 24. A 
listing of all physical exam results for subjects with at least one abnormal result will be 
produced.  
7.5. 
Post-Void Residual (PVR) Urine Volume 
PVR urine volume data will be summarized at Baseline and every visit, including change from 
baseline for post-baseline visits. Least squares mean estimates and 95% CIs as described in 
section 4.2.2 will be presented from an ANCOVA model including terms for treatment and 
baseline parameter value.  
Categorical summaries of PVR at the following categories: <100 mL, ≥ 100 and < 200 mL, ≥ 
200 and < 300 mL, ≥ 300 mL will be presented. Line plots of least squares means change from 
baseline and 95% CIs by visit and treatment will be presented. All PVR data will be listed. 
7.6. 
Urodynamics Assessments (Urodynamics Sub-study Only) 
Urodynamics assessments are collected at or within 6 months prior to Baseline and at Week 12 
for Part 2 subjects who consented to participate in the Urodynamics sub-study. Urodynamics 
parameter estimates will be assessed by a central reviewer. The following parameters will be 
measured: 
x Peak flow rate during voiding (Qmax) (mL/s) 
x Detrusor pressure at peak flow rate (Corrected PdetQmax) (cmH2O) 
x Instilled volume at first involuntary detrusor contraction (IDC) (Vol@1st IDC) (mL), if 
an IDC occurs 
x Maximum detrusor pressure during the first involuntary detrusor contraction (Corrected 
Pdet@1st IDC) (cmH2O), if an IDC occurs 
x Maximum cystometric capacity (Corrected MCC) (mL) 
x Maximum detrusor pressure during the storage phase (Corrected PdetQmax Storage) 
(cmH2O) 
x Voided volume (VV) (mL) 


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Additional parameters will be derived from the measured values: 
x Bladder Outlet Obstruction Index (BOOI)=PdetQmax-2∙Qmax 
x Bladder Contractility Index (BCI)=PdetQmax + 5∙Qmax 
x Bladder Voiding Efficiency (BVE)=(VV∙100)/MCC 
Descriptive statistics of observed values at Baseline, Week 12, any time post-baseline,and 
change from baseline to Week 12 and to any time post-baseline will be presented for each of the 
parameters for the UES set. Least squares mean estimates and 95% CIs as described in section 
4.2.2 will be presented from an ANCOVA model including terms for treatment and baseline 
parameter value. One-sided 95% CIs will be provided for Qmax and PdetQmax. 
Categorical summaries of BOOI [Unobstructed (<20), Equivocal (20-40), and Obstructed (>40)] 
and BCI [Strong (>150), Normal (100-150), Weak (<100)] will also be presented. 
If PP-UES differs from UES by more than 5 subjects, Qmax and PdetQmax will be summarized 
as above for the PP-UES population. 
All urodynamics assessments will be listed, including investigator derived parameters. If a 
urodynamics measurement was taken after the end of study date in URO-901-3005 (implying 
that the subject initiated URO-901-3006 before the evaluation), that measurement will not be 
included in any tabular summaries but will be listed. 
7.7. 
Uroflow Measures 
Uroflowmetry is conducted at Screening and Week 24 (or early withdrawal). Measured 
parameters include maximum flow rate (Qmax) (mL/s), average flow rate (Qave) (mL/s), and 
volume voided (VV) (mL).  
Uroflowmetry measures require a minimum void of 125 mL to be interpretable. Summary 
statistics will only be provided for uroflow tests where VV≥125 mL. The summary will comprise 
a continuous summary at baseline and post-baseline, including change from baseline. Least 
squares mean estimates and 95% CIs as described in section 4.2.2 will be presented from an 
ANCOVA model including terms for treatment and baseline parameter value.   
If a uroflow measurement was taken after the end of study date in URO-901-3005 (implying that 
the subject initiated URO-901-3006 before the evaluation), that measurement will not be 
included in any tabular summaries but will be listed. All Uroflow measurements will be listed. 
7.8. 
IPSS Total Score 
IPSS total score at Screening, Day 1, Weeks 4, 8, 12, and 24 (or early withdrawal) will be 
summarized by treatment and visit, including change from baseline.  


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8. COVID-19 CONSIDERATIONS 
This study was conducted during the COVID-19 global pandemic (starting around March 2020).  
During the time period of the pandemic, it is anticipated that changes in study visit schedules, 
missed visits, or patient discontinuations may lead to missing information (e.g., for protocol-
specified procedures). In accordance with the FDA Guidance titled Statistical Considerations for 
Clinical Trials During the COVID-19 Public Health Emergency (first issued in June 2020), it is 
important to capture specific information in the case report form that explains the basis of the 
missing data, including the relationship to COVID-19 for missing protocol-specified information 
(e.g., from missed study visits or study discontinuations due to COVID-19).  
The proportion of subjects with COVID-19 impact on visits will be summarized by treatment 
group overall and by visit.  The reasons (e.g. subject acquired COVID-19, subject unable to 
travel due to COVID-19, investigative site closure due to COVID-19, etc) will also be 
summarized. A listing of subjects who had COVID-19 information collected will be generated 
which will document the date of contact, visit, visit impact, reason for visit impact, and if any 
doses were missed due to IP availability. 


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9. CHANGE FROM ANALYSIS PLANNED IN PROTOCOL 
9.1. 
Exploratory endpoints 
In protocol Section 3, the changes from baseline at Week 12 for the following endpoints are 
specified as other/exploratory endpoints. In addition, the CFB at Week 24 will be included.  
x 
Symptom Bother Score as assessed by 
  
x 
HRQL total score as assessed by 
 
 
IPSS total score is included as an exploratory efficacy endpoint as well as a safety endpoint. 
 
9.2. 
Responder Analysis  
Protocol Section 9.4.4 mentions using CMH risk difference estimate for response efficacy 
endpoints. Missing Week 12 data will be analyzed using multiple imputation (MI). Considering 
the responder endpoints are exploratory in the study, the proposed MI analysis will not be carried 
out.  
9.3. 
COVID-19 Considerations 
The COVID-19 global pandemic developed during the conduct of the study. The recommended 
impact analysis was therefore added to the SAP, as the operational change of increased visit 
windows had been initially communicated via study memo with no protocol amendment. 
COVID-19 expanded visit windows are spelled out in Protocol Amendment 2; 6-week visit 
extensions due to COVID-19 were available starting in March 2020.  


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10. REFERENCES 
[1] Abrams P, Kaplan S, De Koning Gans HJ et al: Safety and tolerability of tolterodine for the 
treatment of overactive bladder in men with bladder outlet obstruction. J Urol 2006; 175: 999. 
 
[2] Nitti V, Mitcheson HD, Rosenberg S, et al. Urodynamics and safety of the B3-adrenoceptor 
agonist, Mirabegron, in males with lower urinary tract symptoms and bladder outlet obstruction. 
J Urol 2013; 190: 1320–7. 
 
[3]  Jiang YH, Lin VC, Liao CH, Kuo HC. International Prostatic Symptom Score-
voiding/storage subscore ratio in association with total prostatic volume and maximum flow rate 
is diagnostic of bladder outlet-related lower urinary tract dysfunction in men with lower urinary 
tract symptoms. PLoS One. 2013;8(3):e59176.  
[4] EQ-5D-5L crosswalk value set https://euroqol.org/eq-5d-instruments/eq-5d-5l-
about/valuation-standard-value-sets/crosswalk-index-value-calculator/ 
[5]  “Guideline on adjustment for baseline covariates in clinical trials.” EMA, 26-Feb-2015 
[6] Chunlei Ke, Jianming Wang, Charlie Zhang, Qi Jiang & Steven Snapinn (2017): On Errors in 
Stratified Randomization, Statistics in Biopharmaceutical Research, 
DOI:10.1080/19466315.2016.1270229  
[7] S. Greenland and J. M. Robins, “Estimation of a Common Effect Parameter from Sparse 
Follow-Up Data,” Biometrics, vol. 41, no. 1, p. 55, Mar. 1985.  
[8] Example 80.13 Sensitivity Analysis with the Tipping-Point Approach 
https://documentation.sas.com/doc/en/pgmsascdc/9.4_3.4/statug/statug_mianalyze_examples13.
htm 


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11. APPENDIX 
11.1. 
Appendix 1. Multiple Imputation for the Response Efficacy 
Endpoints 
 
This section summarizes the multiple imputation approach for the sensitivity analysis of primary 
efficacy endpoints to assess the robustness of the treatment effect under different underlying 
assumptions to account for missing data. The goal is to impute missing values as follows: 
x Average number of daily micturition episodes   
x Average number of daily urgency episodes  
 
First the average daily numbers will be derived for all post-baseline visits as described in 
Section 4.3.1 respectively, then the following two-stage imputation will be applied. The 
following steps will be followed to perform this analysis. 
 
Step 1: Create a horizontal dataset for the efficacy data where each patient has 1 row per 
parameter and a column for each visit from baseline through week 12, inclusive. 
 
Step 2: Impute missing average daily numbers at Weeks 2, 4, and 8 based on MCMC to obtain a 
monotone missing data pattern with 30 replicates. Example code is: 
 
 proc mi data = datain1 out = dataout1 seed = 123 nimpute=30 noprint; 
var baseline WEEK_02 WEEK_04 WEEK_08; 
mcmc chain = multiple impute=monotone; 
em maxiter = 1000; 
run; 
 
Step 3: For each of the 30 replicates from Stage 1, impute the missing data following a 
monotone missing data pattern so that there are 30 replicates of the complete dataset. 
Example code is: 
 
proc mi data = dataout1 out = dataout2 seed = 321 nimpute=1 noprint; 
class TRTP OABTYPE REGION ; 
monotone regression (WEEK_12 = baseline WEEK_02 WEEK_04 WEEK_08); 
var WEEK_12 baseline WEEK_02 WEEK_04 WEEK_08; 
run; 
 
Step 4: Transpose the dataset out2 to the usual ADaM-like dataset with 1 row per patient, 
per parameter, per analysis visit. 
 
Step 5: Fit the ANCOVA model from Section 6.1.1 for each of the replicate complete datasets. 
 
Step 6: Combine the results from Step 4 using PROC MIANALYZE. 
 
proc mianalyze data = MIdatain; 
modeleffects ESTIMATE; 


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stderr STDERR; 
ods output ParameterEstimates = MIout; 
run; 
 
The tipping point analysis will use the same approach and follow Example 80.13 from 
SAS/STAT User’s Guide [8]. 
 


 
 
 
11.2. 
Table of Contents for Data Display Specifications 
11.2.1. 
Output Tables 
Table 9:  
List of Output Tables 
Title 
Population 
 
Programming notes 
Study Population  
14.1.1.1 
Subject Disposition 
Screened 
Include three sections: screened, run-
in, randomized  
14.1.1.2 
Subject Randomization by Country and Investigator 
Randomize
d 
 
14.1.2.1 
Major Protocol Deviations 
FAS 
 
14.1.2.2 
Reasons for Exclusion from Analysis Sets 
Randomize
d 
 
14.1.3.1 
Subject Demographic and Baseline Characteristics 
SAF 
 
14.1.3.2 
Subject Demographic and Baseline Characteristics 
SAF-Orth 
 
14.1.3.3 
Subject Demographic and Baseline Characteristics 
FAS 
 
14.1.3.4 
Subject Demographic and Baseline Characteristics 
FAS-I 
 
14.1.3.5 
Subject Demographic and Baseline Characteristics 
PPS 
 


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Title 
Population 
 
Programming notes 
14.1.3.6 
Subject Demographic and Baseline Characteristics 
PPS-I 
 
14.1.3.7 
Subject Demographic and Baseline Characteristics 
SAF-UDS 
 
14.1.3.8 
Subject Demographic and Baseline Characteristics 
UES 
 
14.1.3.9 
Other Baseline Characteristics 
FAS 
 
14.1.3.10 
Other Baseline Characteristics 
FAS-I 
 
14.1.3.11 
Other Baseline Characteristics 
PPS 
 
14.1.3.12 
Other Baseline Characteristics 
PPS-I 
 
14.1.4 
Medical History 
SAF 
 
14.1.5.1 
Prior Non-Overactive-Bladder (OAB) Medication 
SAF 
 
14.1.5.2 
Prior Overactive Bladder (OAB) Medication 
SAF 
 
14.1.6.1 
Treatment Exposure  
SAF 
Double-blind period 
14.1.6.2 
Treatment Exposure  
FAS 
Double-blind period 
14.1.6.3 
Treatment Compliance Double-Blind Period 
SAF 
 
14.1.6.4 
Treatment Compliance Double-Blind Period 
FAS 
 
14.1.7.1 
COVID-19 Impact 
SAF 
 


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Title 
Population 
 
Programming notes 
Efficacy Endpoints 
Co-Primary Endpoints 
 
 
14.2.1.1 
Average Number of Daily Micturition Episodes  
FAS 
Descriptive statistics, include CFB 
14.2.1.2 
Change from Baseline in Average Number of Daily 
Micturition Episodes Primary Efficacy Analysis 
(MMRM) 
FAS 
Include all intervals but Week 12 in 
the front 
14.2.1.3 
Change from Baseline at Week 12 in Average 
Number of Daily Micturition Episodes Primary 
Efficacy Sensitivity Analysis (ANCOVA with MI) 
FAS 
 
14.2.1.4 
Change from Baseline in Average Number of Daily 
Micturition Episodes Primary Efficacy Analysis 
PPS 
Descriptive statistics, include CFB 
14.2.1.5 
Change from Baseline at Week 12 in Average 
Number of Daily Micturition Episodes Primary 
Efficacy Sensitivity Analysis (ANCOVA with MI) 
PPS 
Include all intervals but Week 12 in 
the front 
14.2.1.6 
Average Number of Daily Micturition Episodes by 
Subgroup 
FAS 
Descriptive statistics, include CFB 
14.2.1.7 
Change from Baseline in Average Number of Daily 
Micturition Episodes Primary Efficacy Analysis 
(MMRM) by Subgroup 
FAS 
Include all intervals but Week 12 in 
the front 
14.2.2.1 
Average Number of Daily Urgency Episodes  
FAS 
Descriptive statistics, include CFB 


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Title 
Population 
 
Programming notes 
14.2.2.2 
Change from Baseline in Average Number of Daily 
Urgency Episodes Primary Efficacy Analysis 
(MMRM) 
FAS 
Include all intervals but Week 12 in 
the front 
14.2.2.3 
Change from Baseline at Week 12 in Average 
Number of Daily Urgency Episodes Primary 
Efficacy Sensitivity Analysis (ANCOVA with MI) 
FAS 
 
14.2.2.4 
Change from Baseline in Average Number of Daily 
Urgency Episodes Primary Efficacy Analysis 
(MMRM) 
PPS 
Include all intervals but Week 12 in 
the front 
14.2.2.5 
Change from Baseline in Average Number of Daily 
Urgency Episodes Primary Efficacy Sensitivity 
Analysis (ANCOVA with MI) 
PPS 
Include all intervals but Week 12 in 
the front 
14.2.2.6 
Average Number of Daily Urgency Episodes by 
Subgroup 
FAS 
Descriptive statistics, include CFB 
14.2.2.7 
Change from Baseline in Average Number of Daily 
Urgency Episodes Primary Efficacy Analysis 
(MMRM) by Subgroup 
FAS 
Include all intervals but Week 12 in 
the front 
Secondary Efficacy Endpoints 
 
 
14.2.3.1 
Average Number of Nocturia Episodes per Day 
FAS 
Descriptive statistics, include CFB 
14.2.3.2 
Change from Baseline in Average Number of 
Nocturia Episodes per Day (MMRM) 
FAS 
Include all intervals but Week 12 in 
the front 


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Title 
Population 
 
Programming notes 
14.2.3.3 
Change from Baseline in Average Number of 
Nocturia Episodes per Day (MMRM) 
PPS 
Include all intervals but Week 12 in 
the front 
14.2.4.1 
Average Number of Daily Urge Urinary 
incontinence Episodes  
FAS-I 
Descriptive statistics, include CFB 
14.2.4.2 
Change from Baseline in Average Number of Daily 
Urge Urinary incontinence Episodes (MMRM) 
FAS-I 
Include all intervals but Week 12 in 
the front 
14.2.4.3 
Change from Baseline in Average Number of Daily 
Urge Urinary incontinence Episodes (MMRM) 
PPS-I 
Include all intervals but Week 12 in 
the front 
14.2.5.1 
International Prostate Symptom Score (IPSS) 
Storage Score 
FAS 
Descriptive statistics, include CFB 
14.2.5.2 
Change from Baseline in International Prostate 
Symptom Score (IPSS) Storage Score (MMRM) 
FAS 
Include all intervals but Week 12 in 
the front 
14.2.5.3 
Change from Baseline in International Prostate 
Symptom Score (IPSS) Storage Score (MMRM) 
PPS 
Include all intervals but Week 12 in 
the front 
14.2.6.1 
Average Volume Voided per Micturition 
FAS 
Descriptive statistics, include CFB 
14.2.6.2 
Change from Baseline in Average Volume Voided 
per Micturition (MMRM) 
FAS 
Include all intervals but Week 12 in 
the front 
14.2.6.3 
Change from Baseline in Average Volume Voided 
per Micturition (MMRM) 
PPS 
Include all intervals but Week 12 in 
the front 


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Title 
Population 
 
Programming notes 
Other Efficacy and PROs Endpoints 
 
 
14.2.7.1 
International Prostate Symptom Score (IPSS) 
Quality of Life Score 
FAS 
Descriptive statistics, include CFB 
14.2.7.2 
International Prostate Symptom Score (IPSS) 
Voiding Score 
FAS 
Descriptive statistics, include CFB 
14.2.8.1 
Urgency Episodes per Day 50% Responder Analysis 
(CMH) 
FAS 
Descriptive statistics 
14.2.9.1 
Change from Baseline in Average Number of Total 
Incontinence Episodes per Day  
FAS-I 
Descriptive statistics, include CFB 
14.2.9.2 
Urge Urinary Incontinence Episodes per Day 75% 
Responder Analysis (CMH) 
FAS-I 
Descriptive statistics 
14.2.10.1 
Symptom Bother Score as Assessed by 
 
(1-week recall) 
FAS 
Descriptive statistics, include CFB 
14.2.10.2 
Health-Related Quality of Life (HRQL) Subscale 
Coping Score as Assessed by 
(1-week 
recall) 
FAS 
Descriptive statistics, include CFB 
14.2.10.3 
Health-Related Quality of Life (HRQL) Subscale 
Concern Score as Assessed by 
(1-week 
recall) 
FAS 
Descriptive statistics, include CFB 


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Title 
Population 
 
Programming notes 
14.2.10.4 
Health-Related Quality of Life (HRQL) Subscale 
Sleep Score as Assessed by 
(1-week 
recall) 
FAS 
Descriptive statistics, include CFB 
14.2.10.5 
Health-Related Quality of Life (HRQL) Subscale 
Social Interaction Score as Assessed by 
 
(1-week recall) 
FAS 
Descriptive statistics, include CFB 
14.2.10.6 
Health-Related Quality of Life (HRQL) Total Score 
as Assessed by 
(1-week recall) 
FAS 
Descriptive statistics, include CFB 
14.2.11.1 
 Domains  
FAS 
Include 5 domain categorical 
summaries: mobility, self-care, usual 
activities, pain/discomfort and 
anxiety/depression 
14.2.11.2 
Crosswalk Index Value  
FAS 
Descriptive statistics, include CFB 
14.2.11.3 
VAS Value  
FAS 
Descriptive statistics, include CFB 
and percent CFB 
14.2.12.1 
Overall Symptom Severity Bladder Symptoms 
Based on Patient Global Impression of 
 
(PGI
 
FAS 
Let’s try to include both continuous 
variables (score and change from 
baseline) and categorical variable on 
the same table which will facilitate 
review 


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Title 
Population 
 
Programming notes 
14.2.12.2 
Overall Symptom Control over Bladder Symptoms 
Based on Patient Global Impression of 
 
(PGI
 
FAS 
Repeat 14.2.12.1 
14.2.12.3 
Overall Symptom Frequency Based on Patient 
Global Impression of 
 (PGI-
 
FAS 
Repeat 14.2.12.1 
14.2.12.4 
Overall Urgency-Related Leakage over Bladder 
Symptoms Based on Patient Global Impression of 
 (PGI-
 
FAS-I 
Repeat 14.2.12.1 
14.2.12.5 
Overall Change of Bladder Symptoms Based on 
Patient Global Impression of 
 (PGI
 
FAS 
Categorical summary 
14.2.12.1 
 
 Domain Scores and Overall Satisfaction Score 
FAS 
Include CFB 
 
 
 
 
Safety Endpoints 
Adverse Events 
 
 
14.3.1.1 
Overall Summary of Treatment Emergent Adverse 
Events 
SAF 
 
14.3.1.2 
Treatment Emergent Adverse Events by System 
Organ Class and Preferred Term 
SAF 
 


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Title 
Population 
 
Programming notes 
14.3.1.3 
Treatment-Related Treatment Emergent Adverse 
Events by Preferred Term 
SAF 
 
14.3.1.4 
Treatment-Emergent Adverse Events by Preferred 
Term and Maximum Intensity 
SAF 
 
14.3.1.5 
Treatment Emergent Adverse Events with Grade ≥ 3 
by Preferred Term 
SAF 
 
14.3.1.6 
Treatment-Related Emergent Adverse Events with 
Grade ≥ 3 by Preferred Term 
SAF 
 
14.3.1.7 
Treatment-Emergent Adverse Events occurring in ≥ 
2% subjects of Vibegron Arm and Greater Than the 
Placebo by Preferred Term 
SAF 
 
14.3.1.8 
Serious Treatment Emergent Adverse Events by 
Preferred Term 
SAF 
 
14.3.1.9 
Treatment-Related Serious Treatment Emergent 
Adverse Events by Preferred Term 
SAF 
 
14.3.1.10 
Treatment Emergent Adverse Events Leading to 
Discontinuation from Study Treatment by Preferred 
Term 
SAF 
 
14.3.1.11 
 Fatal TEAEs by Preferred Term 
SAF 
 


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Title 
Population 
 
Programming notes 
14.3.1.12 
Treatment Emergent Adverse Events of Special 
Interest by Preferred Term 
SAF 
 
14.3.1.13 
Treatment-Related Treatment Emergent Adverse 
Events of Special Interest by Preferred Term 
SAF 
 
14.3.1.14 
Non-Fatal Treatment-Emergent Adverse Events by 
Preferred Term 
SAF 
 
14.3.1.15 
Hypertension Treatment Emergent Adverse Events 
by Preferred Term, and Pre-Existing Hypertension 
SAF 
 
14.3.1.16 
Hypertension Treatment Emergent Adverse Events 
by Preferred Term, and Baseline Hypertension 
SAF 
 
14.3.1.17 
Listing of Deaths 
SAF 
 
14.3.1.18 
Listing of Treatment Emergent Serious Adverse 
Events 
SAF 
 
14.3.1.19 
Listing of Treatment Emergent Adverse Events 
Leading to Withdrawal or Interruption of Study 
Treatment 
SAF 
 
14.3.1.20 
Listing of TEAEs of Special Interest 
SAF 
 
Safety Labs 
 
 
14.3.2.1 
Hematology Laboratory Parameters 
SAF 
Include observed and CFB 


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Title 
Population 
 
Programming notes 
14.3.2.2 
Clinical Chemistry Laboratory Parameters 
SAF 
Include observed and CFB 
14.3.2.3 
Urinalysis Laboratory Parameters 
SAF 
Include observed and CFB 
14.3.2.4 
Summary of Other Laboratory Parameters 
SAF 
 
14.3.2.5 
Abnormal Classification of Hematology Laboratory 
Parameters 
SAF 
 
14.3.2.6 
Abnormal Classification of Clinical Chemistry 
Laboratory Parameters 
SAF 
 
14.3.2.7 
Abnormal Classification of Urinalysis Laboratory 
Parameters 
SAF 
 
14.3.2.8 
Abnormal Classification Summary of Other 
Laboratory Parameters 
SAF 
 
14.3.2.9 
Shift Table of L/N/H Classification for Hematology 
Laboratory Parameters 
SAF 
 
14.3.2.10 
Shift Table of L/N/H Classification for Chemistry 
Laboratory Parameters 
SAF 
 
14.3.2.11 
Maximum Post-baseline ALT and AST vs. 
Maximum Post-baseline Bilirubin 
SAF 
 
14.3.2.12 
Listing of Subjects who Potentially Met Hy’s Law 
SAF 
 


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Title 
Population 
 
Programming notes 
Concomitant Medication 
 
 
14.3.3.1 
Non-OAB Concomitant Medication  
SAF 
 
14.3.3.2 
OAB Concomitant Medication  
SAF 
 
Regular and Orthostatic Vital Signs 
 
 
14.3.4.1 
Vital Sign Parameters 
SAF 
Include all observed and CFB 
14.3.4.2 
Vital Sign Parameter Change from Baseline Shifts at 
3 Consecutive Visits 
SAF 
SBP, DBP and PR 
14.3.4.3 
Vital Sign Parameter Change from Baseline Shifts at 
Week 24 
SAF 
SBP, DBP and PR 
14.3.4.4 
Vital Sign Parameter Maximum Post-Baseline 
Change from Baseline  
SAF 
SBP, DBP and PR 
14.3.4.5 
Orthostatic Blood Pressure and Pulse Rate 
SAF-Orth  
 
14.3.5.1 
Time-Matched Change from Sitting to Standing 
Position in Orthostatic Blood Pressure and Pulse 
Rate 
SAF-Orth 
 
14.3.5.2 
Time-Matched Change from Day 1 in Orthostatic 
Blood Pressure and Pulse Rate 
SAF-Orth  
 


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Title 
Population 
 
Programming notes 
14.3.5.3 
Maximum CFB over 6 Hours in in Orthostatic Blood 
Pressure and Pulse Rate 
SAF-Orth 
 
14.3.5.4 
Average CFB over 6 Hours in Orthostatic Blood 
Pressure and Pulse Rate 
SAF-Orth  
 
14.3.5.5 
Categorical Shift from Sitting to Standing in Blood 
Pressure 
SAF-Orth 
 
Urodynamics 
 
 
14.3.6.1 
Urodynamics Assessments 
SAF-UDS 
 
Other 
 
 
14.3.7.1 
Prostate Volume Measurements 
SAF 
 
14.3.8.1 
Uroflow Measurements 
SAF 
 
14.3.9.1 
Total IPSS score 
SAF 
 
14.3.10.1 
Physical Examination Shift from Baseline 
SAF 
 
 


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11.2.2. 
Output Figures 
Table 10: 
List of Output Figures 
Title 
Population    Programming notes 
Efficacy Endpoints 
 
 
14.2.1.1 
Plot of LS Means (SE) of Change from Baseline in 
Average Number of Daily Micturition Episodes 
Primary Efficacy Analysis (MMRM) 
FAS 
Including all visits 
14.2.1.2 
Forest Plot of Vibegron Treatment Effect vs. Placebo 
on Average Number of Daily Micturition Episodes at 
Week 12 by Subgroup Primary Efficacy Analysis 
(MMRM) 
FAS 
 
14.2.2.1 
Plot of LS Means (SE) of Change from Baseline in 
Average Number of Daily Urgency Episodes Primary 
Efficacy Analysis (MMRM) 
FAS 
Including all visits 
14.2.2.2 
Forest Plot of Vibegron Treatment Effect vs. Placebo 
on Average Number of Daily Urgency Episodes at 
Week 12 by Subgroup Primary Efficacy Analysis 
(MMRM) 
FAS 
 
14.2.3.1 
Plot of LS Means (SE) of Change from Baseline in 
Average Number of Nocturia Episodes per Day 
(MMRM) 
FAS 
Including all visits 
14.2.4.1 
Plot of LS Means (SE) of Change from Baseline in 
Average Number of Daily Urge Urinary incontinence 
Episodes (MMRM) 
FAS-I 
Including all visits 


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Title 
Population    Programming notes 
14.2.5.1 
Plot of LS Means (SE) of Change from Baseline in 
International Prostate Symptom Score (IPSS) Storage 
Score (MMRM) 
FAS 
Including all visits 
14.2.6.1 
Plot of LS Means (SE) of Change from Baseline in 
Volume Voided per Micturition (MMRM) 
FAS 
Including all visits 
Safety Endpoints 
 
 
14.3.3.1 
Scatter Plot of Maximum ALT Post-Baseline versus 
Maximum Total Bilirubin Expressed as Multiples of 
ULN 
SAF 
 
14.3.3.2 
Scatter Plot of Maximum AST Post-Baseline versus 
Maximum Total Bilirubin Expressed as Multiples of 
ULN 
SAF 
 
14.3.3.3 
Line Plot of Liver Chemistry Test Results over Time 
for Subjects with Elevated ALT or AST, and Elevated 
Total Bilirubin at Any Time 
SAF 
Only produce for subjects who 
potentially met Hy’s law 
14.3.4.1 
Line Plot of Mean (SE) in CFB of Systolic Blood 
Pressure  
SAF 
X-axis starts from baseline visit  
14.3.4.2 
Line Plot of Mean (SE) in CFB of Diastolic Blood 
Pressure 
SAF 
X-axis starts from baseline visit  
14.3.4.3 
Line Plot of Mean (SE) in CFB of Pulse Rate 
SAF 
X-axis starts from baseline visit  
14.3.5.1 
Line Plot of Mean (SE) in Time-Matched Change 
from Day 1 of Orthostatic Systolic Blood Pressure 
SAF-Orth  
 


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Title 
Population    Programming notes 
14.3.5.2 
Line Plot of Mean (SE) in Time-Matched Change 
from Day 1 of Orthostatic Diastolic Blood Pressure 
SAF-Orth  
 
14.3.5.3 
Line Plot of Mean (SE) in Time-Matched Change 
from Day 1 of Orthostatic Pulse Rate 
SAF-Orth 
 
14.3.5.4 
Empirical Cumulative Distribution Function of 
Maximum Change from Baseline over 6 Hours to 
Week 2 and Week 4 Orthostatic Systolic Blood 
Pressure 
SAF-Orth 
Week 2 and Week 4 CDF plots side-
by-side on the same page 
14.3.5.5 
Empirical Cumulative Distribution Function of 
Maximum Change from Baseline over 6 Hours to 
Week 2 and Week 4 Orthostatic Diastolic Blood 
Pressure 
SAF-Orth 
Week 2 and Week 4 CDF plots side-
by-side on the same page 
14.3.5.6 
Empirical Cumulative Distribution Function of 
Maximum Change from Baseline over 6 Hours to 
Week 2 and Week 4 Orthostatic Pulse Rate 
SAF-Orth 
Week 2 and Week 4 CDF plots side-
by-side on the same page 
 
11.2.3. 
Output Listings 
Table 11: 
List of Output Listings 
Title 
Population Programming notes 
Disposition and Demographics 
 
 
16.2.1.1 
Subject Disposition – Screen Failures 
Screened 
 


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Title 
Population Programming notes 
16.2.1.2 
Eligibility Criteria-Inclusion/Exclusion Criteria – 
Screen Failures 
Screened 
 
16.2.1.3 
Run-in Treatment Administration 
Run-in 
 
16.2.1.4 
Subject Disposition 
Randomize
d 
 
16.2.1.5 
Subject Randomization Details 
Randomize
d 
 
16.2.1.6 
Protocol Deviation 
FAS 
 
16.2.1.7 
Exclusion from Analysis Sets 
Randomize
d 
 
16.2.1.8 
Demographic and Baseline Characteristics 
Randomize
d 
 
16.2.1.9 
Medical History  
SAF 
 
16.2.1.1
0 
Procedures 
SAF 
 
16.2.1.1
1 
Prior Non-OAB Medications 
SAF 
Separate from prior OAB medication 
listing. 
16.2.1.1
2 
Concomitant Medications 
SAF 
 
16.2.1.1
3 
Prior OAB Medication  
SAF 
 
16.2.1.1
4 
Randomization and Treatment Administration 
 
 
16.2.1.1
5 
Study Drug Accountability 
SAF 
 


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Title 
Population Programming notes 
16.2.1.1
6 
Study Drug Compliance 
SAF 
 
Efficacy  
 
 
16.2.2.1 
Derived Average Bladder Diary Parameters  
FAS 
 
16.2.2.2 
Derived Responder Parameters from Bladder Dairy 
FAS 
 
16.2.2.3 
Derived Parameters from International Prostate 
Symptom Score (IPSS) Data 
FAS 
 
16.2.2.4 
(1-week recall) Data 
FAS 
 
16.2.2.5 
 Data 
FAS 
 
16.2.2.6 
Global Impression Data 
FAS 
 
16.2.2.7 
 
FAS 
 
Safety  
 
 
16.2.3.1 
 All Adverse Events 
SAF 
 
16.2.3.2 
All Adverse Events During Screening Period 
Screened 
 
16.2.3.3 
All Adverse Events During Run-in Period 
Run-in 
 
16.2.3.4 
All Adverse Events During Double-Blind Period 
SAF 
 
16.2.3.5 
Hematology Laboratory Parameters 
SAF 
 
16.2.3.6 
Clinical Chemistry Laboratory Parameters 
SAF 
 
16.2.3.7 
Urinalysis Laboratory Parameters 
SAF 
 
16.2.3.8 
Other Laboratory Parameters 
SAF 
 
16.2.3.9 
Vital Signs 
SAF 
 


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Title 
Population Programming notes 
16.2.3.1
0 
Orthostatic Blood Pressure and Pulse Rate 
SAF-Orth 
 
16.2.3.1
1 
Electrocardiogram (ECG) parameters 
SAF 
 
16.2.3.1
2 
 Physical Examination 
SAF 
 
16.2.3.1
3 
Post-Void Residual (PVR) Volume  
SAF 
 
16.2.3.1
4 
Urodynamics Assessment 
SAF-UDS 
 
16.2.3.1
5 
Prostate Volume Measurement 
SAF