Clinical trial NCT03241342
Conditions: Stress Urinary Incontinence
Sponsor: GTx
Start date: 2017-08-21; Completion date: 2018-09-21
Enrollment: 491 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
GTx-024 is an orally bioavailable and tissue-selective nonsteroidal selective androgen receptor modulator (SARM) that has demonstrated androgenic and anabolic activity and is currently being evaluated as a potential treatment for stress urinary incontinence (SUI) in postmenopausal women. Urinary incontinence and pelvic floor disorders are major health problems for women, especially as they age. Pelvic floor muscle relaxation has been found to correlate with lower urinary tract symptoms including SUI. Muscles of the pelvic floor and lower urinary tract are crucial for supporting the pelvic organs and micturition; however, damage to the muscles or lack of hormonal stimulation are thought to contribute to pelvic organ prolapse and urinary incontinence. Although anabolic steroids may increase muscle mass and strength, lack of oral bioavailability and known potential risks have limited their use. Nonsteroidal SARMs have potential to achieve benefits of anabolic steroid therapy (improved muscle mass, cholesterol/triglyceride levels, glucose metabolism, and bone density) with fewer adverse effects, such as hirsutism and acne, in women. Both nonclinical and clinical data suggest that SARMs may provide a new therapeutic option for pelvic floor and lower urinary tract disorders, as both testosterone and its more potent metabolite, dihydrotestosterone, have anabolic effects on muscle.

Detailed description:

Arms: arm 1: Study drug will be provided as softgel capsules in blister packaging, labeled and designed to protect study blinding. All subjects will take 2 softgel capsules orally, once daily. arm 2: Study drug will be provided as softgel capsules in blister packaging, labeled and designed to protect study blinding. All subjects will take 2 softgel capsules orally, once daily. arm 3: Study drug will be provided as softgel capsules in blister packaging, labeled and designed to protect study blinding. All subjects will take 2 softgel capsules orally, once daily.
Interventions: intervention 1: GTx 024 intervention 2: Placebo
Intervention descriptions: intervention 1: Study drug is an opaque, white to off-white, size 5, oval Softgel capsule containing the active ingredient GTx-024. intervention 2: Placebo study drug is identical in appearance to the GTx-024 study drug and contains polyethylene glycol 400 but not GTx-024.

Protocol documents:
Prot_SAP_000.pdf: 
CLINICAL TRIAL PROTOCOL 
IND NUMBER: 126605 
Double-Blind, Placebo-Controlled, Parallel Design, Phase 2 Study to Assess 
Clinical Activity and Safety of Enobosarm (GTx-024) in Postmenopausal 
Women With Stress Urinary Incontinence 
Protocol Number: G201002 
Sponsor: 
GTx, Inc. 
175 Toyota Plaza, 7th Floor 
Memphis, TN 38103 
Sponsor Contact: 
Mayzie Johnston, PharmD 
Vice President, Clinical Development 
Telephone: 901-261-3858 
Project Manager: 
Wesley Young 
Associate Director, Global Project Management 
PPD 
Wesley.Young@ppdi.com 
Telephone: 919-624-1193 
Safety Hotline: 
1-866-966-8429 (US toll free) 
Version of Protocol:  
4.0 
Date of Protocol:  
10 April 2018 
 
CONFIDENTIAL  
All financial and nonfinancial support for this study will be provided by GTx. The concepts 
and information contained in this document or generated during the study are considered 
proprietary and may not be disclosed in whole or in part without the expressed, written 
consent of GTx. 
The study will be conducted according to the International Council for Harmonisation 
harmonised tripartite guideline E6(R2): Good Clinical Practice. 




GTx, Inc. 
Protocol G201002 Version 4.0 
Protocol Approval – Lead Statistician
GTx-024
10 April 2018
 
 
Study Title 
Double-Blind, Placebo-Controlled, Parallel Design, Phase 2 Study to 
Assess Clinical Activity and Safety of Enobosarm (GTx-024) in 
Postmenopausal Women With Stress Urinary Incontinence 
Protocol Number 
G201002 
Protocol Date 
10 April 2018 
 
 
 
Protocol accepted and approved by: 
 
Lead Statistician 
 
Elaine B. Hoffman, PhD 
Statistical Science Director 
Biostatistics 
PPD 
3900 N Paramount Parkway 
Morrisville, NC 27660 
 
 
 
 
 
 
Signature 
Date 




GTx, Inc. 
GTx-024 
Protocol G201002 Version 4.0 
10 April 2018 
 
Declaration of Investigator 
I have read and understood all sections of the protocol entitled “Double-Blind, 
Placebo-Controlled, Parallel Design, Phase 2 Study to Assess Clinical Activity and Safety of 
Enobosarm (GTx-024) in Postmenopausal Women With Stress Urinary Incontinence” and the 
accompanying investigator’s brochure, version 16, dated 01 Aug 2017. 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in 
accordance with the Final Protocol Version 4.0, dated 10 April 2018, the International 
Council for Harmonisation harmonised tripartite guideline E6(R2): Good Clinical Practice 
and all applicable government regulations. I will not make changes to the protocol before 
consulting with GTx, Inc. or implement protocol changes without independent ethics 
committee approval except to eliminate an immediate risk to subjects. I agree to administer 
study treatment only to subjects under my personal supervision or the supervision of a 
subinvestigator. 
I will not supply the investigational drug to any person not authorized to receive it. 
Confidentiality will be protected. Subject identity will not be disclosed to third parties or 
appear in any study reports or publications. 
I will not disclose information regarding this clinical investigation or publish results of the 
investigation without authorization from GTx, Inc.  
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
Printed Name of Principal Investigator 
 
 
 


GTx, Inc. 
GTx-024 
Protocol G201002 Version 4.0 
10 April 2018 
 
Statement of Compliance 
 
This study will be carried out in accordance with Good Clinical Practice (GCP) as required 
by the following: 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies 
(45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) 
• International Council for Harmonization (ICH) E6; 62 Federal Register 25691 (May 9, 
1997) 
 


GTx, Inc. 
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Protocol G201002 Version 4.0 
10 April 2018 
 
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Table of Contents 
Protocol Approval – Sponsor Signatory .................................................................................... 2 
Protocol Approval – Lead Statistician ....................................................................................... 3 
Protocol Approval – Principal Investigator ................................................................................ 4 
Declaration of Investigator ........................................................................................................ 5 
Statement of Compliance ........................................................................................................... 6 
Table of Contents ....................................................................................................................... 7 
List of Tables ............................................................................................................................ 10 
PROTOCOL Synopsis ............................................................................................................. 11 
List of Abbreviations................................................................................................................ 26 
1 
Introduction ...................................................................................................................... 28 
1.1 
Background and Rationale ...................................................................................... 28 
2 
Study Objectives............................................................................................................... 30 
2.1 
Primary Objective ................................................................................................... 30 
2.2 
Secondary Objectives.............................................................................................. 30 
2.3 
Exploratory Efficacy Objectives ............................................................................. 31 
2.4 
Safety Objectives .................................................................................................... 32 
3 
Investigational Plan .......................................................................................................... 33 
3.1 
Study Design ........................................................................................................... 33 
3.1.1 
Rationale of Study Design ....................................................................... 34 
3.1.1.1 
Risk Mitigation ........................................................................................ 35 
4 
Subject Selection and Withdrawal Criteria ...................................................................... 37 
4.1 
Selection of Study Population ................................................................................. 37 
4.1.1 
Inclusion Criteria ..................................................................................... 37 
4.1.2 
Exclusion Criteria .................................................................................... 38 
4.2 
Withdrawal of Subjects From the Study ................................................................. 41 
4.2.1 
Reasons for Withdrawal/Discontinuation ................................................ 41 
4.2.2 
Handling of Withdrawals ......................................................................... 41 
4.2.3 
Replacements ........................................................................................... 42 
5 
Study Treatments .............................................................................................................. 43 
5.1 
Method of Assigning Subjects to Treatment Groups .............................................. 43 
5.2 
Treatments Administered ........................................................................................ 43 
5.3 
Identity of Study Drug ............................................................................................ 43 
5.4 
Management of Clinical Supplies ........................................................................... 43 


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5.4.1 
Study Drug Packaging and Storage ......................................................... 44 
5.4.2 
Study Drug Accountability ...................................................................... 44 
5.4.3 
Other Supplies ......................................................................................... 44 
5.5 
Overdose Management ........................................................................................... 45 
5.5.1 
Medication Errors .................................................................................... 45 
5.5.2 
Treatment of Medication Errors ............................................................... 45 
5.6 
Blinding .................................................................................................................. 45 
5.6.1 
Breaking the Blind ................................................................................... 45 
5.7 
Treatment Compliance ............................................................................................ 46 
5.8 
Prior and Concomitant Medications ....................................................................... 46 
5.8.1 
Prohibited Concomitant Medications and Treatments ............................. 47 
6 
Study Assessments and Procedures .................................................................................. 48 
6.1 
Study Visits ............................................................................................................. 48 
6.1.1 
Screening ................................................................................................. 48 
6.1.1.1 
Screening Visit, Days ‒28 to 0 ................................................................. 48 
6.1.1.2 
Additional Screening Procedures ............................................................ 49 
6.1.2 
Study Visit 1: Week 0, Clinic Visit .......................................................... 49 
6.1.3 
Study Visit 2: Week 1, Phone Visit .......................................................... 49 
6.1.4 
Study Visit 3: Week 4, Clinic Visit .......................................................... 50 
6.1.5 
Study Visit 4: Week 8, Clinic Visit .......................................................... 50 
6.1.6 
Study Visit 5: Week 12 or Early Withdrawal, Clinic Visit ....................... 51 
6.1.7 
Study Visit 6: Week 16, Clinic Visit ........................................................ 51 
6.1.8 
Study Visit 7: Week 20, Clinic Visit ........................................................ 52 
6.1.9 
Study Visit 8: Week 28, Clinic Visit ........................................................ 52 
6.2 
Efficacy Assessments .............................................................................................. 52 
6.2.1 
Three-Day Voiding Diary ........................................................................ 52 
6.2.2 
Bladder Stress Test (BST) ........................................................................ 53 
6.2.3 
Patient Global Impression of Severity ..................................................... 53 
6.2.4 
Patient Global Impression of Improvement ............................................. 53 
6.2.5 
Urogenital Distress Inventory and Incontinence Impact Questionnaire 
Short Form ............................................................................................... 53 
6.2.6 
Incontinence Quality of Life .................................................................... 54 
6.2.7 
Female Sexual Function Index ................................................................ 54 
6.2.8 
Vaizey Incontinence Severity Score ........................................................ 54 
6.2.9 
Twenty-Four Hour Pad Weight Test ........................................................ 54 
6.2.10 
Medical, Epidemiological, and Social Aspects of Aging Questionnaire . 55 
6.3 
Safety Assessments ................................................................................................. 55 
6.3.1 
Adverse Events ........................................................................................ 55 
6.3.1.1 
Definitions of Adverse Events ................................................................. 55 
6.3.1.2 
Eliciting and Documenting Adverse Events ............................................ 56 


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6.3.1.3 
Reporting Adverse Events ....................................................................... 56 
6.3.1.4 
Assessment of Severity ............................................................................ 57 
6.3.1.5 
Assessment of Causality .......................................................................... 58 
6.3.1.6 
Follow-Up of Subjects Reporting Adverse Events .................................. 59 
6.3.2 
Halting Rules ........................................................................................... 59 
6.3.3 
Safety Assessments .................................................................................. 60 
6.3.3.1 
Vital Sign Measurements ......................................................................... 60 
6.3.3.2 
Height and Weight ................................................................................... 60 
6.3.3.3 
Prior and Concomitant Medications ........................................................ 60 
6.3.3.4 
Medical History ....................................................................................... 61 
6.3.3.5 
Physical Examination .............................................................................. 61 
6.3.3.6 
Transvaginal Ultrasound .......................................................................... 61 
6.4 
Other Assessments .................................................................................................. 61 
6.4.1 
Pelvic Examination .................................................................................. 61 
6.4.2 
Mammography ......................................................................................... 61 
6.4.3 
Electrocardiography ................................................................................. 62 
6.5 
Pregnancy ................................................................................................................ 62 
6.6 
Laboratory Analyses ............................................................................................... 63 
6.7 
Sample Collections ................................................................................................. 64 
7 
Statistical and Analytical Plan .......................................................................................... 65 
7.1 
Primary Efficacy Endpoint ..................................................................................... 65 
7.2 
Secondary Efficacy Endpoints ................................................................................ 65 
7.3 
Exploratory Efficacy Endpoints .............................................................................. 66 
7.4 
Sample Size Calculation ......................................................................................... 67 
7.5 
Analysis Sets ........................................................................................................... 67 
7.6 
Description of Subgroups to be Analyzed .............................................................. 68 
7.7 
Statistical Analysis Methodology ........................................................................... 68 
7.7.1 
Analysis of the Primary Efficacy Endpoint ............................................. 68 
7.7.2 
Analysis of Secondary Efficacy Endpoints ............................................. 69 
7.7.3 
Analysis of Exploratory Efficacy Endpoints ........................................... 69 
7.7.4 
Safety Analyses ........................................................................................ 70 
7.8 
Data Quality Assurance........................................................................................... 70 
7.8.1 
On-Site Audits ......................................................................................... 71 
7.8.2 
Data Management .................................................................................... 71 
8 
Ethics ................................................................................................................................ 72 
8.1 
Institutional Review Board ..................................................................................... 72 
8.2 
Ethical Conduct of the Study .................................................................................. 72 
8.3 
Subject Information and Consent ........................................................................... 72 


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Protocol G201002 Version 4.0 
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9 
Investigator’s Obligations ................................................................................................ 74 
9.1 
Confidentiality ........................................................................................................ 74 
9.2 
Financial Disclosure and Obligations ..................................................................... 74 
9.3 
Investigator Documentation .................................................................................... 75 
9.4 
Study Conduct ......................................................................................................... 75 
9.5 
Adherence to Protocol ............................................................................................ 75 
9.6 
Adverse Events and Study Report Requirements ................................................... 76 
9.7 
Investigator’s Final Report ..................................................................................... 76 
9.8 
Records Retention ................................................................................................... 76 
9.9 
Publications ............................................................................................................. 76 
10 Study Management ........................................................................................................... 77 
10.1 Monitoring .............................................................................................................. 77 
10.1.1 
Monitoring the Study ............................................................................... 77 
10.1.2 
Inspection of Records .............................................................................. 77 
10.2 Management of Protocol Amendments and Deviations.......................................... 77 
10.2.1 
Modification of the Protocol .................................................................... 77 
10.2.2 
Protocol Deviations ................................................................................. 78 
10.3 Study Termination ................................................................................................... 78 
10.4 Final Report ............................................................................................................ 78 
11 Reference List................................................................................................................... 80 
12 Appendices ....................................................................................................................... 82 
12.1 Appendix: Schedule of Events ................................................................................ 82 
12.2 Appendix: Medical, Epidemiological, and Social Aspects of Aging Questionnaire86 
12.3 Appendix: Patient Global Impression of Severity .................................................. 89 
12.4 Appendix: Patient Global Impression of Improvement .......................................... 91 
12.5 Appendix: Urogenital Distress Inventory ............................................................... 93 
12.6 Appendix: Incontinence Impact Questionnaire Short Form ................................... 95 
12.7 Appendix: Incontinence Quality of Life ................................................................. 97 
12.8 Appendix: Female Sexual Function Index ............................................................ 105 
12.9 Appendix: Vaizey Incontinence Score .................................................................. 110 
 
List of Tables 
Table 12–1 
Schedule of Events for Protocol G201002....................................................... 83 


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PROTOCOL SYNOPSIS 
Protocol Number: 
G201002 
Name of Investigational 
Product:  
Enobosarm (GTx-024) 
Title of Study: 
Double-Blind, Placebo-Controlled, Parallel Design, 
Phase 2 Study to Assess Clinical Activity and Safety of 
Enobosarm (GTx-024) in Postmenopausal Women with 
Stress Urinary Incontinence 
Sponsor: 
GTx, Inc. 
Phase of Development: 
Phase 2 
Trial Site(s): 
Approximately 70 (US) 
Indication: 
Stress Urinary Incontinence 
Rationale: 
GTx-024 is an orally bioavailable and tissue-selective 
nonsteroidal selective androgen receptor modulator 
(SARM) that has demonstrated androgenic and anabolic 
activity and is currently being evaluated as a potential 
treatment for stress urinary incontinence (SUI) in 
postmenopausal women. 
Urinary incontinence and pelvic floor disorders are major 
health problems for women, especially as they age. Pelvic 
floor muscle relaxation has been found to correlate with 
lower urinary tract symptoms including SUI. Muscles of 
the pelvic floor and lower urinary tract are crucial for 
supporting the pelvic organs and micturition; however, 
damage to the muscles or lack of hormonal stimulation are 
thought to contribute to pelvic organ prolapse and urinary 
incontinence. 
Although anabolic steroids may increase muscle mass and 
strength, lack of oral bioavailability and known potential 
risks have limited their use. Nonsteroidal SARMs have 
potential to achieve benefits of anabolic steroid therapy 
(improved muscle mass, cholesterol/triglyceride levels, 
glucose metabolism, and bone density) with fewer adverse 
effects, such as hirsutism and acne, in women.  
Both nonclinical and clinical data suggest that SARMs 
may provide a new therapeutic option for pelvic floor and 
lower urinary tract disorders, as both testosterone and its 
more potent metabolite, dihydrotestosterone, have anabolic 
effects on muscle. 
GTx-024 has demonstrated androgenic and anabolic 
activity in male and female rat models. GTx-024 has 
consistently been observed to increase body weight, 


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Protocol G201002 Version 4.0 
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specifically muscle, in female rats. In a male rat model 
with castrate levels of serum testosterone, GTx-024 has the 
ability to induce hypertrophy of the levator ani muscle to 
approximately 120% of a noncastrate male. 
Another SARM (GSK2849466A), studied in an 
ovariectomized rat model that mimics SUI by disrupting 
urethral continence, was shown to increase urethral 
baseline pressure and the amplitude of urethral responses 
during sneezing by 64% and 74%, respectively, compared 
to the vehicle control (Kadekawa et al, AUA Annual 
Meeting 2015, New Orleans, LA. PD27-11). Furthermore, 
all of the rats (8/8) in the vehicle-treated group experienced 
fluid leakage during sneezing whereas only 1 of the rats 
(1/8) in the SARM-treated group experienced such leakage 
upon similar challenge. Histologically, the SARM-treated 
animals had a reversal of the atrophy in urethral muscle 
observed in the control group. This preliminary in vivo 
study supports the clinical study of SARMs for the 
treatment of SUI.  
A proof-of-concept clinical study is currently ongoing to 
investigate the effect of GTx-024 on symptoms of SUI in 
postmenopausal women. Available data from the 18 
subjects dosed at 3 mg GTx-024/day for 12 weeks showed 
a mean reduction in stress incontinence episodes of 81%, 
with all 18 subjects seeing a clinically significant reduction 
(> 50% reduction in stress leaks) in the number of stress 
incontinence episodes by Week 12. 
Objectives: 
Primary Objective - Efficacy 
The primary efficacy objective of this study is to compare 
the efficacy of GTx-024 (1 mg and 3 mg administered once 
daily) to that of placebo by evaluating the mean number of 
subject-reported stress incontinence episodes per day.  
The primary efficacy endpoint is a responder analysis, 
where a responder is defined as having a ≥ 50% reduction 
at the end of treatment (Week 12) compared to baseline in 
the mean number of stress incontinence episodes per day 
as assessed by the 3-day voiding diary. Subjects who have 
missing diary data for the Week 12 visit will be counted as 
non-responders for this analysis. 
Secondary Objectives - Efficacy 
The secondary efficacy objectives in this study are to 
compare, at each visit during the treatment period, the 
efficacy compared to baseline of 2 doses of GTx-024 
(1 mg and 3 mg administered once daily) to that of placebo 
in relation to the following: 
• Responder rate, where a responder is defined as 


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having a ≥ 50% reduction compared to baseline in 
the mean number of stress incontinence episodes per 
day as assessed by the 3-day voiding diary  
• Change in the number of stress incontinence 
episodes per day as measured by the 3-day voiding 
diary  
• Change in the total number of voids per day as 
measured by the 3-day voiding diary 
• Change in 24-hour pad weight as measured by the 
24-hour pad weight test 
• Change in the Bladder Stress Test (BST) (at Week 12 
only) 
• Change in subject-reported impression of SUI 
severity as measured by the Patient Global 
Impression of Severity scale (PGI-S)  
• Change in subject-reported impression of SUI 
improvement as measured by the Patient Global 
Impression of Improvement scale (PGI-I) 
• Change in subject-reported urogenital distress as 
measured by the Urinary Distress Inventory 
questionnaire (UDI-6) 
• Change in subject-reported impact of urinary 
incontinence on daily life as measured by the 
Incontinence Impact Questionnaire (IIQ-7) Short 
Form 
• Change in subject-reported impact of urinary 
incontinence on daily life as measured by the 
Incontinence Quality of Life questionnaire (I-QOL) 
• Change in subject-reported sexual function as 
measured by the Female Sexual Function Index 
questionnaire (FSFI) 
• Change in subject-reported assessment of fecal 
incontinence as measured by the Vaizey 
Incontinence Severity Score 
• Change in subject-reported stress incontinence, urge 
incontinence, and mixed incontinence as measured 
by the Medical, Epidemiological, and Social Aspects 
of Aging (MESA) incontinence questionnaire 
(Week 12 only) 
Exploratory Objectives - Efficacy 
The exploratory efficacy objectives of this study are to 
assess the durability of the effect of treatment at Week 16, 
Week 20, and Week 28 in relation to the following:   


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• Responder rate, where a responder is defined as 
having a ≥ 50% reduction compared to baseline in 
the mean number of stress incontinence episodes per 
day as assessed by the 3-day voiding diary  
• Number of stress incontinence episodes per day as 
measured by the 3-day voiding diary 
• Total number of voids per day as measured by the 
3-day voiding diary 
• Change in 24-hour pad weight as measured by the 
24-hour pad weight test 
• Subject-reported impression of SUI severity as 
measured by the PGI-S  
• Subject-reported impression of SUI improvement as 
measured by the PGI-I  
• Subject-reported urogenital distress as measured by 
the UDI-6  
• Subject-reported impact of urinary incontinence on 
daily life as measured by the IIQ-7 Short Form  
• Subject-reported impact of urinary incontinence on 
daily life as measured by the I-QOL  
• Subject-reported sexual function as measured by the 
FSFI 
• Subject-reported assessment of fecal incontinence as 
measured by the Vaizey Incontinence Severity Score. 
Additional sensitivity analyses may be included in 
exploratory analyses. 
Secondary Objectives - Safety 
The safety objectives of this study are to determine the 
safety and tolerability of 2 doses of GTx-024 (1 mg and 
3 mg administered once daily) compared to that of placebo 
therapy. Safety and tolerability will be assessed in relation 
to the following: 
• Incidence of adverse events (AEs) 
• Change from baseline in clinical laboratory 
evaluations 
• Change from baseline in sex hormone binding 
globulin (SHBG) and testosterone 
• Change from baseline in vital sign measurements 
• Change from baseline in endometrial stripe thickness 
as assessed by transvaginal ultrasound (only in 
subjects with an intact uterus) 


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Subject Population: 
Inclusion Criteria 
Each subject must meet all of the following criteria to be 
enrolled in this study: 
1. Able to read, understand, and provide written, 
dated, informed consent prior to screening, and be 
likely to comply with the study protocol and 
communicate with study personnel about AEs and 
other clinically important information 
2. Female, 18 to 80 years of age, inclusive, at 
screening 
3. Subjects must have undergone spontaneous, 
medically induced, or surgical menopause prior to 
the start of this study. Postmenopausal subjects are 
defined as those subjects who meet one of the 
following criteria: 
a) greater than or equal to 12 months of 
spontaneous amenorrhea, or; 
b) at least 6 months of spontaneous amenorrhea 
with serum follicle stimulating hormone levels 
> 40 mIU/ml, or; 
c) at least 6 weeks postsurgical bilateral 
oophorectomy with or without hysterectomy, 
or; 
d) subjects 60 years of age or older with previous 
hysterectomy without an oophorectomy with 
serum follicle stimulating hormone levels 
> 30 mIU/ml, or; 
e) subjects less than 60 years of age with previous 
hysterectomy without an oophorectomy with 
serum follicle stimulating hormone levels 
> 40 mIU/ml. 
4. SUI symptoms of at least 6 months duration  
5. Predominant SUI as determined at the Screening 
Visit using the MESA incontinence questionnaire. 
6. 24-Hour pad weight > 3 g during the screening 
period  
7. A minimum of 1 and no more than 15 SUI episodes 
on any single day AND no fewer than 9 total SUI 
episodes over 3 days as reported in the 3-day 
voiding diary, determined during the screening 
period 
8. Serum alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) levels < 1.5 times the 


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upper limit of normal at the Screening Visit (Note: 
laboratory values falling outside of prespecified 
ranges may be retested once at the discretion of the 
investigator. Results of the retest must be within 
prespecified ranges and must be available prior to 
the baseline visit) 
9. Positive bladder stress test conducted during the 
Screening Visit 
10. Subject agrees not to start any new treatment 
(medication or otherwise) during the treatment and 
follow-up periods, including vaginal rejuvenation, 
that is known or suspected to affect lower urinary 
tract function.  
11. Subject agrees to discontinue use of bladder 
support devices, including but not limited to 
vaginal pessary, during the screening, treatment, 
and follow-up periods. 
12. Subject agrees to maintain a stable dose of any 
medication known to affect lower urinary tract 
function, including but not limited to 
anticholinergics, tricyclic antidepressants, beta-3 
adrenergic agonist, or α-adrenergic blockers, 
throughout the treatment and follow-up periods.  
13. During screening, subject must provide evidence of 
having received a mammogram examination within 
the 6 months prior to screening, or she must agree 
to receive a mammogram examination during 
screening.  
 
Exclusion Criteria 
A subject meeting any of the following criteria will be 
excluded from the study: 
1. Pelvic floor physical therapy, including muscle 
training and/or electrostimulation, in a clinical 
setting within 30 days prior to screening  
2. History of pelvic radiation treatment  
3. History of urethral diverticula  
4. History of surgery for incontinence, including 
urethral sling, anterior prolapse repair, 
intra-detrusor botulinum toxin injection, sacral 
nerve stimulation, and percutaneous tibial nerve 
stimulation  
5. Treatment with urethral bulking agents within the 
6 months prior to the Screening Visit  


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6. Known vesicoureteral reflux, vaginal prolapse 
beyond the introitus, or other significant pelvic 
floor abnormalities that, in the investigator’s 
opinion, may impact the subject’s response 
7. Vaginal rejuvenation treatment, including laser 
treatments and radiofrequency therapy, within the 
6 months prior to the Screening Visit 
8. Subject has urinary incontinence of neurogenic 
etiology  
9. Subject is morbidly obese (defined as body mass 
index 40 or greater)  
10. Chronic hepatitis (i.e., inflammation of the liver 
that has been ongoing for at least 6 months) 
11. Hepatic cirrhosis due to, for example, sustained 
excessive alcohol consumption, hepatitis B virus, 
hepatitis C virus, or fatty liver disease  
12. Evidence of active infection with hepatitis B or 
hepatitis C as determined by serology  
13. History of human immunodeficiency virus (HIV) 
infection 
14. Subject is currently taking systemic sex-hormone 
products (excludes intravaginal application of 
estradiol topical/tablet agents and hormones 
delivered via vaginal rings). The following washout 
periods are required if systemic hormonal products 
are discontinued prior to screening: 
a) minimum of 4 weeks for prior transdermal 
products or products with systemic absorption 
applied topically; 
b) minimum of 8 weeks for prior oral products; 
c) minimum of 8 weeks for prior intrauterine 
products, and;  
d) minimum of 3 months for prior hormonal 
implants or injectable drug therapy.  
15. Subject has current cancer diagnosis (with the 
exception of non-melanoma skin cancer) or any 
history of breast or endometrial cancer  
16. Known history or current episode of: 
• New York Heart Association ≥ Stage 2 
hypertension (systolic blood pressure [BP] 
> 160 mmHg or diastolic BP > 100 mmHg) 
at screening and/or baseline. Subjects with 
hypertension that has been treated and 


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controlled with medication for at least 
2 weeks prior to screening are eligible for 
participation 
• Recent myocardial infarction or arterial or 
venous thromboembolic event (within 
1 year) or a history of more than 
1 myocardial infarction or arterial or venous 
thromboembolic event 
• Cardiac-related syncopal event within the 
past year 
• Cardio or cerebral vascular disease 
requiring surgical intervention (e.g., bypass 
surgery, angioplasty). For subjects with 
previous stent placement, please contact the 
medical monitor 
• Congestive heart failure (CHF) New York 
Heart Association Criteria > Stage 2 
• Angina pectoris 
• QT Fridericia-corrected ≥ 450 msec at 
screening (If QTcF is above this range, a 
repeat ECG can be done at the discretion of 
the investigator, and if the value is in range, 
the patient may be enrolled in the study.)  
17. For subjects with an intact uterus, > 5 mm 
endometrial stripe thickness as measured at 
screening by transvaginal ultrasound  
18. Clinically confirmed urinary tract infection, 
requiring treatment as determined by the 
investigator, at the Screening Visit  
19. Current or past history of any physical condition 
that, in the investigator’s opinion, might put the 
subject at risk, impact the absorption of the study 
drug, or interfere with study results interpretation. 
Study Design 
This is a double-blind, placebo-controlled, parallel design, 
randomized, multicenter, Phase 2 study. The study consists 
of the following periods: screening period, treatment 
period, follow-up period, and durability period.  
Screening Period (4 Weeks) 
Potential subjects will be evaluated during a screening 
period lasting no more than 4 weeks. After written 
informed consent is obtained, Screening Visit procedures 
will be performed as specified in the schedule of events for 
the study.  


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Treatment Period (12 Weeks)  
At Baseline (Visit 1, Week 0), subjects who continue to 
meet all eligibility criteria will be randomly assigned to 
one of the three treatment arms in a 1:1:1 ratio for a 
12-week, double-blind treatment period. Subjects will be 
assigned to one of the following treatment groups: 1 mg 
GTx-024, 3 mg GTx-024, or matching placebo.  
Randomized subjects will take their first dose of study 
drug during the Baseline visit.  
Following the Baseline visit, subjects will attend the clinic 
at Weeks 4, 8, and 12 during the treatment period. At each 
clinic visit, study procedures will be performed as 
specified in the schedule of events for the study. All unused 
study drug will be collected at Week 12 (Visit 5), the end 
of the treatment period.  
Follow-up Period (4 Weeks) and Durability Period 
(16 Weeks)  
Upon completion of Week 12 (Visit 5), all subjects will 
enter either a 4-week Follow-up Period or a 16-week 
Durability Period. 
The first 225 randomized subjects only will enter the 
16-week Durability Period of the study. Visit 5, 12 weeks 
after the start of treatment, is the baseline for the 16-week 
durability period, during which time no study drug will be 
administered. During the durability period, there will be 
clinic visits at Week 16, Week 20, and Week 28. At each 
visit, study procedures will be performed as specified in 
the schedule of events for the study. Data from the 
follow-up period will be used to assess the durability of the 
effect of GTx-024. 
All other randomized subjects will complete a 4-week 
Follow-up Period following Week 12 (Visit 5) during 
which time no study drug will be administered. The 
Follow-up Period includes a clinic visit at Week 16 where 
study procedures will be performed as specified in the 
schedule of events for the study. 
Extension Studies 
Two extension studies are planned and will be conducted 
under separate protocols. 
Subjects who complete the 16-week Durability Period will 
be offered the opportunity to enter into a 20-week 
durability extension study under a separate protocol. Data 
from this extension study will be used to further assess the 
durability of effect of GTx-024. No study drug will be 
administered during this durability extension study. 


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Subjects who complete the required treatment period and 
durability or follow-up periods of this study may be 
offered the opportunity to enter into an open-label 
extension study under a separate protocol. Subjects will 
receive study drug during this open-label extension study.  
Estimated Study Duration: 
Subject completion is defined as completing all phases of 
the study: through follow-up (Week 28) for the first 
225 randomized subjects and through follow-up (Week 16) 
for all other randomized subjects. The maximum duration 
of each subject’s participation will be ≤ 32 weeks.  
Efficacy Assessments: 
The following assessments will be conducted to evaluate 
efficacy: 
• 3-Day Voiding Diary 
The 3-day voiding diary is a study tool for subjects 
to report each episode of urinary void. The subject 
will be asked to record each episode of urinary 
leakage, the type (stress or urge) of leakage, and the 
severity of leakage. Subjects will also be asked to 
record each episode of voluntary urinary void and 
fluid intake. 
• Bladder Stress Test 
The Bladder Stress Test (BST) is used to confirm 
stress incontinence by simulating the accidental 
release of urine when a patient coughs, sneezes, 
laughs, or exercises. 
• PGI-S 
The PGI-S is a global rating of subject-reported 
impression of severity using a 4-point scale. 
Validity of the PGI-S has been established for 
application in SUI. 
• PGI-I 
The PGI-I is a global rating of subject-reported 
impression of improvement using a 7-point scale. 
Validity of the PGI-I has been established for 
application in SUI.  
• UDI-6 and IIQ-7 
The UDI-6 and IIQ-7 are validated subject 
questionnaires used to assess symptom distress and 
the impact of urinary incontinence on daily life. 
• I-QOL 
The I-QOL is a validated subject questionnaire used 
to assess the impact of urinary incontinence and 
treatments. 
• FSFI 
The FSFI is a self-administered questionnaire to 


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assess overall sexual experience that consists of 
19 questions that are scored from 0 to 5. The scale 
contains 6 domains: desire, arousal, lubrication, 
orgasm, satisfaction, and pain. The FSFI total score 
is a weighted average of the 6 domains with each 
contributing a maximum of 6 points to the total 
(maximum score of 36). 
• Vaizey Incontinence Severity Score 
The Vaizey Incontinence Severity Score is a 
self-administered questionnaire to assess a subject’s 
bowel symptoms and the impact of these symptoms 
on daily life. 
• 24-hour Pad Weight Test 
The 24-hour pad weight test is a quantitative test 
intended to provide information on the severity of 
incontinence. The amount of urine leaked over the 
24 hours of testing is quantified by measuring the 
change in weight of perineal pads used during 
testing.  
• MESA 
The MESA incontinence questionnaire consists of 
15 items divided into stress incontinence (9 items) 
and urge incontinence (6 items) subscales. Based 
on their responses, subjects can be characterized as 
having predominant stress incontinence, urge 
incontinence, or mixed incontinence (Herzog and 
Fultz 1990).   
Safety Assessments: 
Safety assessments will include:  
• Adverse events 
• Clinical laboratory analyses 
• Levels of SHBG and testosterone 
• Endometrial stripe thickness as assessed by 
transvaginal ultrasound (only for subjects with an 
intact uterus) 
Other standard safety assessments will include vital sign, 
height, and weight measurements, concomitant 
medications, medical history, and physical examination 
findings.  
Study Drug: 
Study drug will be provided as softgel capsules in blister 
packaging, labeled and designed to protect study blinding. 
Subjects will be randomized to one of three dosing groups: 
1 mg GTx-024, 3 mg GTx-024, or matching placebo. All 
subjects will take 2 softgel capsules orally, once daily.  


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Sample Size Calculation: 
The sample size calculation was performed using PASS 
v12.0.1 for binary outcomes. The sample size calculation 
was performed for a binary response (i.e., a responder is 
defined as having a ≥ 50% reduction at the end of 
treatment compared to baseline in the mean number of 
stress incontinence episodes per day as assessed by the 
3-day voiding diary). The assumptions were a 60% active 
treatment response and 40% placebo response. The overall 
discontinuation rate was anticipated to be approximately 
25%. 
Given these assumptions, a randomized sample size of 
approximately 400 subjects (randomized in a 1:1:1 ratio 
for placebo, 1 mg GTx-024, 3 mg GTx-024, respectively) 
will have 80% power to detect a treatment difference of 
20%. A 2-sided hypothesis test with 5% significance is 
used for each pairwise comparison between GTx-024 and 
placebo (i.e., alternatively using a 1-sided significance 
level of 2.5%). 


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Analysis Sets: 
Data analysis will be performed on a full analysis set 
(FAS), a per protocol set (PPS), an intent-to-treat (ITT) set, 
a durability set (DS), and a safety analysis (SA) set.  
The FAS is used for the primary analysis. The FAS consists 
of all randomized subjects who receive at least 1 dose of 
study drug and have at least 1 post baseline primary 
efficacy assessment (3-day voiding diary). All analyses 
using the FAS will group participants according to 
randomized treatment. 
The PPS is used for a supportive analysis and will also be 
defined as all subjects included in the FAS who do not 
have any significant protocol deviations. All analyses using 
the PPS will group subjects according to treatment actually 
received. 
The ITT set consists of all randomized subjects who 
receive at least 1 dose of study drug. All analyses using the 
ITT set will group subjects according to randomized 
treatment. Subjects who do not have any postbaseline 
assessments will be treated as non-responders for ITT 
analyses.  
The DS is used for exploratory analyses to assess the 
durability of the effect of treatment and will be defined as 
the first 225 randomized subjects who complete a Week 12 
final visit and at least one assessment during the Durability 
period. 
The SA set contains all subjects randomized in the study 
who receive at least 1 dose of study drug. 
All efficacy analyses performed on the FAS will be 
repeated on the PPS and the ITT set.  
Methods of Analysis: 
Before unblinding, a separate statistical analysis plan 
(SAP) will be finalized, providing detailed methods for all 
endpoints. In general, summary statistics (n, mean, 
standard deviation, median, minimum and maximum 
values for continuous variables, and number [%] of 
subjects in each category for categorical variable) will be 
provided by treatment group and visit. Source data for 
summary tables and statistical analyses will be presented 
as subject data listings. 
All statistical analyses will be performed using SAS (v9.4 
or higher). Unless stated otherwise, all statistical tests will 
be 2-sided using a 5% significance level, leading to 95% 
(2-sided) confidence intervals. No adjustment will be made 
for multiplicity due to 2 dose levels of GTx-024 being 
compared with placebo. The trial is not powered to show a 
statistical difference between the 2 dose arms of GTx-024. 


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The primary efficacy period is defined as baseline (Day 0) 
through Week 12. Change from baseline and determination 
of responder rate status will be between baseline and visits 
through Week 12. The durability period is defined as Week 
12 to Week 16, Week 20, and/or Week 28. 
Analysis of the Primary Efficacy Endpoint 
The primary analysis will be conducted on the primary 
endpoint using the FAS.  
The primary efficacy endpoint (i.e., a binary response 
indicator where a responder is defined as having a ≥ 50% 
reduction at the end of treatment compared to baseline in 
the mean number of stress incontinence episodes per day 
as assessed by the 3-day voiding diary) will be evaluated 
using a logistic regression model. The logistic regression 
model will include treatment group as a covariate. The 
odds ratio of response between each dose level of GTx-024 
and placebo (together with the corresponding 95% 
confidence interval) will be reported. The null hypothesis 
is that there is no treatment effect for either dose level of 
GTx-024. This will be tested against the alternative 
hypothesis that there is a treatment effect for at least 1 of 
the dose levels of GTx-024.  
The corresponding P-value for the comparison between 
each dose level of GTx-024 and placebo will be derived 
using the standard normal distribution. Subjects who have 
missing values at these visits will be counted as 
non-responders for this analysis. Sensitivity analyses will 
be specified in the SAP.  
Analysis of Secondary Efficacy Endpoints 
For binary secondary endpoints (responders), the treatment 
effect will be estimated using a logistic regression model 
with treatment as a covariate. 
For continuous secondary endpoints, treatment effects will 
be estimated using a mixed model repeated measures 
analysis (MMRM). The MMRM model will specify an 
unstructured variance/covariance matrix and will include 
treatment group, visit, and baseline as covariates. 
For ordinal endpoints, treatment effects will be estimated 
using a proportional odds model.  
Further details on the analysis of secondary efficacy 
endpoints will be provided in the SAP. 
Analysis of Exploratory Efficacy Endpoints 
Durability of treatment effect will be examined in the DS 
for the exploratory efficacy endpoints. Additional 
sensitivity analyses of exploratory and secondary efficacy 


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endpoints may also be conducted as exploratory analyses, 
including sensitivity analyses with regard to missing data. 
Further details of the exploratory analyses will be provided 
in the SAP.  
Safety Analyses 
All safety parameters (including AEs, vital signs, 
laboratory evaluations, SHBG, testosterone, and 
endometrial stripe thickness) will be summarized using the 
SA set. No formal hypothesis testing will be performed. 
All AEs will be coded using the latest version of Medical 
Dictionary for Regulatory Activities (MedDRA). All 
treatment-emergent AEs (TEAEs) will be summarized and 
presented in the listings by the number of subjects 
reporting an event, the percentage of subjects with that 
event, the number of events, and the grade, duration, and 
relationship to treatment. Percentages will be based on the 
number of subjects who received each treatment during the 
study.  
Clinical laboratory safety tests will be performed, and 
normal ranges will be provided for each lab test. Values 
outside the normal range will be assessed for clinical 
significance by the investigator. Shift tables (change from 
baseline value to on-treatment values) will be presented for 
each laboratory measurement and assessment time. Each 
parameter outside the normal range will be designated as 
high (H) or low (L) in the individual data listings.  
 


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List of Abbreviations 
Abbreviation 
Definition 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BST 
bladder stress test 
CFR 
Code of Federal Regulations 
DS 
durability set 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
FAS 
full analysis set 
FDA 
US Food and Drug Administration 
FSFI 
Female Sexual Function Index questionnaire 
GCP 
Good Clinical Practice 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IIQ-7 
Incontinence Impact Questionnaire 
INR 
international normalized ratio 
I-QOL 
Incontinence Quality of Life questionnaire 
IRB 
institutional review board 
ITT 
intent to treat 
IWRS 
interactive web response system 
MedDRA 
Medical Dictionary for Regulatory Activities 
MESA 
Medical, Epidemiological, and Social Aspects of Aging 
OTC 
over-the-counter 
PGI-I 
Patient Global Impression of Improvement Scale 
PGI-S 
Patient Global Impression of Severity Scale 
PPS 
per protocol set 
SAE 
serious adverse event 
SARMS 
selective androgen receptor modulators 
SA 
safety analysis  
SHBG 
sex hormone binding globulin 


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Abbreviation 
Definition 
SUI 
stress urinary incontinence 
TEAE 
treatment-emergent adverse event 
UDI-6 
Urinary Distress Inventory Questionnaire 
ULN 
Upper Limit of Normal 
 


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1 Introduction 
1.1 Background and Rationale 
Enobosarm (GTx-024) is an orally bioavailable and tissue-selective nonsteroidal selective 
androgen receptor modulator (SARM) that has demonstrated androgenic and anabolic 
activity and is currently being evaluated as a potential treatment for stress urinary 
incontinence (SUI) in postmenopausal women. 
Urinary incontinence and pelvic floor disorders are major health problems for women, 
especially as they age (Luber 2004). Pelvic floor muscle relaxation has been found to 
correlate with lower urinary tract symptoms including SUI. Muscles of the pelvic floor and 
lower urinary tract are crucial for supporting the pelvic organs and micturition; however, 
damage to the muscles and/or lack of hormonal stimulation are thought to contribute to 
pelvic organ prolapse and urinary incontinence.  
Although anabolic steroids may increase muscle mass and strength, lack of oral 
bioavailability and known potential risks have limited their use (Mohler et al 2009). 
Nonsteroidal SARMs have potential to achieve benefits of anabolic steroid therapy 
(improved muscle mass, cholesterol/triglyceride levels, glucose metabolism, and bone 
density) with fewer adverse effects, such as hirsutism and acne, in women.  
Both nonclinical and clinical data suggest that SARMs may provide a new therapeutic option 
for pelvic floor and lower urinary tract disorders, as both testosterone and its more potent 
metabolite, dihydrotestosterone, have anabolic effects on muscle.  
GTx-024 has demonstrated androgenic and anabolic activity in male and female rat models. 
GTx-024 has consistently been observed to increase body weight, specifically muscle, in 
female rats. In a male rat model with castrate levels of serum testosterone, GTx-024 has the 
ability to induce hypertrophy of the levator ani muscle to approximately 120% of a 
noncastrate male. 
Another SARM (GSK2849466A), studied in an ovariectomized rat model that mimics SUI 
by disrupting urethral continence, was shown to increase urethral baseline pressure and the 
amplitude of urethral responses during sneezing by 64% and 74%, respectively, compared to 
the vehicle control (GTx, Inc. 2017; Kadekawa et al 2015). Furthermore, all of the rats (8/8) 
in the vehicle-treated group experienced fluid leakage during sneezing whereas only 1 of the 


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rats (1/8) in the SARM-treated group experienced such leakage upon similar challenge. 
Histologically, the SARM-treated animals had a reversal of the atrophy in urethral muscle 
observed in the control group. This preliminary in vivo study supports the clinical study of 
SARMs for the treatment of SUI.  
A proof-of-concept study is currently ongoing to investigate the effect of GTx-024 on 
symptoms of SUI in postmenopausal women. Available data from the 18 subjects dosed at 
3 mg GTx-024/day for 12 weeks showed a mean reduction in stress incontinence episodes of 
81%, with all 18 subjects seeing a clinically significant reduction (> 50% reduction in stress 
leaks) in the number of stress incontinence episodes by Week 12. 


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2 Study Objectives 
2.1 Primary Objective 
The primary efficacy objective of this study is to compare the efficacy of GTx-024 (1 mg and 
3 mg administered once daily) to that of placebo by evaluating the mean number of 
subject-reported stress incontinence episodes per day through a responder analysis, where a 
responder is defined as having a ≥ 50% reduction at the end of treatment (Week 12) 
compared to baseline in the mean number of stress incontinence episodes per day as assessed 
by the 3-day voiding diary. Subjects who have missing diary data for the Week 12 visit will 
be counted as non-responders for this analysis. 
2.2 Secondary Objectives 
The secondary efficacy objectives in this study are to compare, at each visit during the 
treatment period, the efficacy compared to baseline of two doses of GTx-024 (1 mg and 3 mg 
administered once daily) to that of placebo in relation to the following:  
• Responder rate, where a responder is defined as having a ≥ 50% reduction compared to 
baseline in the mean number of stress incontinence episodes per day as assessed by the 
3-day voiding diary  
• Change in the number of stress incontinence episodes per day as measured by the 3-day 
voiding diary  
• Change in the total number of voids per day as measured by the 3-day voiding diary  
• Change in 24-hour pad weight as measured by the 24-hour pad weight test 
• Change in the Bladder Stress Test (BST) (at Week 12 only) 
• Change in subject-reported impression of SUI severity as measured by the Patient Global 
Impression of Severity scale (PGI-S)  
• Change in subject-reported impression of SUI improvement as measured by the Patient 
Global Impression of Improvement scale (PGI-I) 
• Change in subject-reported urogenital distress as measured by the Urinary Distress 
Inventory questionnaire (UDI-6) 


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• Change in subject-reported impact of urinary incontinence on daily life as measured by 
the Incontinence Impact Questionnaire (IIQ-7) Short Form 
• Change in subject-reported impact of urinary incontinence on daily life as measured by 
the Incontinence Quality of Life questionnaire (I-QOL) 
• Change in subject-reported sexual function as measured by the Female Sexual Function 
Index questionnaire (FSFI) 
• Change in subject-reported assessment of fecal incontinence as measured by the Vaizey 
Incontinence Severity Score 
• Change in subject-reported stress incontinence, urge incontinence, and mixed 
incontinence as measured by the Medical, Epidemiological, and Social Aspects of Aging 
(MESA) incontinence questionnaire (Week 12 only) 
2.3 Exploratory Efficacy Objectives 
The exploratory efficacy objectives of this study are to assess the durability of the effect of 
treatment at Week 16, Week 20, and Week 28 in the first 225 randomized subjects in relation 
to the following:  
• Responder rate, where a responder is defined as having a ≥ 50% reduction compared to 
baseline in the mean number of stress incontinence episodes per day as assessed by the 
3-day voiding diary  
• Number of stress incontinence episodes per day as measured by the 3-day voiding diary 
• Total number of voids per day as measured by the 3-day voiding diary 
• Change in 24-hour pad weight as measured by the 24-hour pad weight test  
• Subject-reported impression of SUI severity as measured by the PGI-S  
• Subject-reported impression of SUI improvement as measured by the PGI-I  
• Subject-reported urogenital distress as measured by the UDI-6  
• Subject-reported impact of urinary incontinence on daily life as measured by the IIQ-7 
Short Form  


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• Subject-reported impact of urinary incontinence on daily life as measured by the I-QOL  
• Subject-reported sexual function as measured by the FSFI 
• Subject-reported assessment if fecal incontinence as measured by the Vaizey 
Incontinence Severity Score 
Additional sensitivity analyses may be included in exploratory analyses.  
2.4 Safety Objectives 
The safety objectives of this study are to determine the safety and tolerability of 2 doses of 
GTx-024 (1 mg and 3 mg administered once daily) compared to that of placebo therapy. 
Safety and tolerability will be assessed in relation to the following: 
• Incidence of adverse events (AEs) 
• Change from baseline in clinical laboratory evaluations 
• Change from baseline in sex hormone binding globulin (SHBG) and testosterone 
• Change from baseline in vital sign measurements 
• Change from baseline in endometrial stripe thickness as assessed by transvaginal 
ultrasound (in subjects with an intact uterus) 


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3 Investigational Plan 
3.1 Study Design 
This is a double-blind, placebo-controlled, parallel design, randomized, multicenter, Phase 2 
study to assess the clinical activity and safety of GTx-024 in postmenopausal women with 
SUI. The study consists of the following periods: screening period, treatment period, 
follow-up period, and durability period.  
Screening Period (4 Weeks) 
Potential subjects will be evaluated during a screening period lasting no more than 4 weeks. 
After written informed consent is obtained, Screening Visit procedures will be performed as 
specified in the schedule of events (Table 12–1).  
Treatment Period (12 Weeks)  
At Baseline (Visit 1, Week 0), subjects who continue to meet all eligibility criteria will be 
randomly assigned to one of the three treatment arms in a 1:1:1 ratio for a 12-week, 
double-blind treatment period. Subjects will be assigned to one of the following treatment 
groups: 1 mg GTx-024, 3 mg GTx-024, or matching placebo.  
Enrolled subjects will take their first dose of study drug during the Baseline visit.  
Following the Baseline visit, subjects will have a phone call follow up at Week 1 and attend 
the clinic at Weeks 4, 8, and 12 during the treatment period. At each clinic visit, study 
procedures will be performed as specified in the schedule of events (Table 12–1). All unused 
study drug will be collected at Week 12 (Visit 5), the end of the treatment period.  
Follow-up Period (4 Weeks) and Durability Period (16 Weeks) 
Upon completion of Week 12 (Visit 5), all subjects will enter either a 4-week Follow-up 
Period or a 16-week Durability Period. 
The first 225 randomized subjects only will enter the Durability Period of the study. Visit 5, 
12 weeks after the start of treatment, is the baseline for the 16-week durability period, during 
which time no study drug will be administered. During the Durability period, there will be 
clinic visits at Week 16, Week 20, and Week 28. At each visit, study procedures will be 


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performed as specified in the schedule of events (Table 12–1). Data from the follow-up 
period will be used to assess the durability of the effect of GTx-024. 
All other randomized subjects (those not included in the first 225) will complete a 4-week 
follow-up period following Week 12 (Visit 5) during which time no study drug will be 
administered. The follow-up period includes a clinic visit at Week 16 where study procedures 
will be performed as specified in the schedule of events (Table 12–1). 
Subject completion is defined as completing all phases of the study through durability 
(Week 28) for the first 225 randomized subjects and through follow-up (Week 16) for all 
other randomized subjects. The maximum duration of each subject’s participation will be 
≤ 32 weeks.  
Extension Studies 
Two extension studies are planned and will be conducted under separate protocols. 
Subjects who complete the 16-week Durability Period will be offered the opportunity to enter 
into a 20-week durability extension study under a separate protocol. Data from this extension 
study will be used to further asses the durability of effect of GTx-024. No study drug will be 
administered during this durability extension study. 
Subjects who complete the required treatment period and durability or follow-up periods of 
this study may be offered the opportunity to enter into an open-label extension study under a 
separate protocol. Subjects will receive study drug during this open-label extension study. 
3.1.1 Rationale of Study Design  
A double-blind, placebo-controlled, parallel design study with a 12-week duration of 
treatment has demonstrated the efficacy of duloxetine for the treatment of North American 
women with SUI, using data from a voiding diary as the primary outcome variable 
(Norton et al 2002, Dmochowski et al 2003).  
In prior clinical studies, GTx-024 has been generally well tolerated, including single doses up 
to 100 mg and multiple doses up to 30 mg once daily for up to 14 days. In longer studies, 
GTx-024 has also been generally well tolerated at 1, 3, and 9 mg daily doses for up to 
833 days (GTx, Inc. 2017). The selection of the 3 mg GTx-024 maximum daily dose in this 


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study was informed by early data from a proof-of-concept study of 3 mg GTx-024 per day 
for 12 weeks in subjects with SUI, wherein all 18 subjects a clinically meaningful (> 50% 
reduction in stress leaks) decrease in the frequency of SUI episodes by 12 weeks of 
treatment.  
A 16-week durability period for a subset of subjects is included in the study design to assess 
the durability of effect after cessation of treatment.  
3.1.1.1 Risk Mitigation 
This study has been designed to mitigate known risks associated with the use of GTx-024. 
Clinical study G200501 observed the effects of administering doses of 0.1, 0.3, 1, and 3 mg 
of GTx-024 (or placebo) for 86 days to healthy subjects: postmenopausal women and elderly 
men. A dose-dependent increase in serum alanine aminotransferase (ALT) and aspartate 
aminotransferase was observed. A higher incidence of transient, asymptomatic increases in 
ALT reported as adverse events occurred in the group receiving 3 mg GTx-024 (20.8%) 
compared to placebo (0%). One subject receiving 3 mg per day of GTx-024 was discontinued 
for an ALT level > 3 times the upper limit of normal. The ALT levels returned to normal with 
continued exposure to GTx-024 in most cases and, further, in instances when dosing was not 
continued, levels returned to normal. No significant increases in total bilirubin, gamma 
glutamyl transferase, alkaline phosphatase, or lactate dehydrogenase have been observed in 
subjects with elevated ALT levels. Consistent with the effects of other orally administered 
anabolic agents, GTx-024 causes a dose dependent reduction in high-density lipoprotein 
(HDL), the clinical significance of which is unknown at this time. The proposed mechanism 
for reduction in HDL is due to stimulation of reverse cholesterol transport and increased 
HDL catabolism by hepatic lipase. Reductions in HDL are temporary and typically return to 
baseline 12 months after treatment initiation.  
In an ongoing Phase 2 study of GTx-024 in ER+/AR+ breast cancer examining daily doses of 
GTx-024 at 9 mg and 18 mg, several cases of clinically significant hypercalcemia have been 
observed that were assessed by the investigators as possibly related to GTx-024. Patients 
with hypercalcemia had ER+ breast cancer with bone metastases. Hypercalcemia has not 
been observed in previous studies of healthy individuals or at doses less than 9 mg. 
Subjects will be monitored at each visit for health changes since the previous visit and 
adverse effects of treatment. Since elevations of ALT have been observed in prior studies, 


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serum ALT and other liver function analytes will be monitored at each visit during treatment 
(Table 12–1). Stopping rules have been included for severe elevations of LFTs or other signs 
of hepatotoxicity (Section 6.3.2). Patients will also be monitored for changes in lipid profile 
and serum calcium. 
The effect of GTx-024 on a fetus has not been evaluated; therefore, the subjects in the current 
investigation will be postmenopausal.  


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4 Subject Selection and Withdrawal Criteria 
4.1 Selection of Study Population 
Approximately 400 subjects will be enrolled at approximately 70 sites in the United States. 
Subjects will be assigned to study treatment only if they meet all of the inclusion criteria and 
none of the exclusion criteria. 
Deviations from the inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability, or subject 
safety. Therefore, adherence to the criteria as specified in the protocol is essential. 
4.1.1 Inclusion Criteria 
Each subject must meet all of the following criteria to be enrolled in this study: 
1. Able to read, understand, and provide written, dated, informed consent prior to 
screening, and be likely to comply with study protocol and communicate with study 
personnel about AEs and other clinically important information. 
2. Female, 18 to 80 years of age, inclusive, at screening 
3. Subjects must have undergone spontaneous, medically induced, or surgical menopause 
prior to the start of this study. Postmenopausal subjects are defined as those subjects 
who meet one of the following criteria: 
a) greater than or equal to 12 months of spontaneous amenorrhea, or; 
b) at least 6 months of spontaneous amenorrhea with serum follicle stimulating 
hormone levels > 40 mIU/ml, or; 
c) at least 6 weeks postsurgical bilateral oophorectomy with or without 
hysterectomy, or; 
d) subjects 60 years of age or older with previous hysterectomy without an 
oophorectomy with serum follicle stimulating hormone levels > 30 mIU/ml, 
or; 
e) subjects less than 60 years of age with previous hysterectomy without an 
oophorectomy with serum follicle stimulating hormone levels > 40 mIU/ml. 
4. SUI symptoms of at least 6 months duration 


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5. Predominant SUI as determined at the Screening Visit using the MESA incontinence 
questionnaire. 
6. 24-Hour pad weight > 3 g during the screening period 
7. A minimum of 1 and no more than 15 SUI episodes on any single day AND no fewer 
than 9 total SUI episodes over 3 days as reported in the 3-day voiding diary, 
determined during the screening period 
8. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels 
< 1.5 times the upper limit of normal at the Screening Visit (Note: laboratory values 
falling outside of prespecified ranges may be retested once at the discretion of the 
investigator. Results of the retest must be within prespecified ranges and must be 
available prior to the baseline visit) 
9. Positive bladder stress test (BST) conducted during the Screening Visit 
10. Subject agrees not to start any new treatment (medication or otherwise) during the 
treatment and follow-up periods, including vaginal rejuvenation, that is known or 
suspected to affect lower urinary tract function. 
11. Subject agrees to discontinue use of bladder support devices, including but not limited 
to vaginal pessary, during the screening, treatment, and follow-up periods. 
12. Subject agrees to maintain a stable dose of any medication known to affect lower 
urinary tract function, including but not limited to anticholinergics, tricyclic 
antidepressants, beta-3 adrenergic agonist, or α-adrenergic blockers, throughout the 
treatment and follow-up periods.  
13. During screening, subject must provide evidence of having received a mammogram 
examination within the 6 months prior to screening, or she must agree to receive a 
mammogram examination during screening.  
4.1.2 Exclusion Criteria 
A subject meeting any of the following criteria will be excluded from the study: 
1. Pelvic floor physical therapy, including muscle training and/or electrostimulation, in a 
clinical setting within 30 days prior to screening 
2. History of pelvic radiation treatment 


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3. History of urethral diverticula 
4. History of surgery for incontinence, including urethral sling, anterior prolapse repair, 
intra-detrusor botulinum toxin injection, sacral nerve stimulation, and percutaneous 
tibial nerve stimulation  
5. Treatment with urethral bulking agents within the 6 months prior to the Screening 
Visit 
6. Known vesicoureteral reflux, vaginal prolapse beyond the introitus, or other 
significant pelvic floor abnormalities that, in the investigator’s opinion, may impact 
the subject’s response 
7. Vaginal rejuvenation treatment, including laser treatments and radiofrequency therapy, 
within the 6 months prior to the Screening Visit 
8. Subject has urinary incontinence of neurogenic etiology 
9. Subject is morbidly obese (defined as body mass index 40 or greater) 
10. Chronic hepatitis (i.e., inflammation of the liver that has been ongoing for at least 
6 months) 
11. Hepatic cirrhosis due to, for example, sustained excessive alcohol consumption, 
hepatitis B virus, hepatitis C virus, or fatty liver disease 
12. Evidence of active infection with hepatitis B or hepatitis C as determined by serology 
13. History of human immunodeficiency virus (HIV) infection 
14. Subject is currently taking systemic sex-hormone products (excludes intravaginal 
application of estradiol topical/tablet agents and hormones delivered via vaginal 
rings). The following washout periods are required if systemic hormonal products are 
discontinued prior to screening: 
a) minimum of 4 weeks for prior transdermal products or products with systemic 
absorption applied topically; 
b) minimum of 8 weeks for prior oral products; 
c) minimum of 8 weeks for prior intrauterine products, and; 
d) minimum of 3 months for prior hormonal implants or injectable drug therapy. 


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15. Subject has current cancer diagnosis (with the exception of non-melanoma skin 
cancer) or any history of breast or endometrial cancer 
16. Known history or current episode of: 
• 
New York Heart Association ≥ Stage 2 hypertension (systolic blood pressure 
[BP] > 160 mmHg or diastolic BP > 100 mmHg) at screening and/or baseline. 
Subjects with hypertension that has been treated and controlled with medication 
for at least 2 weeks prior to screening are eligible for participation. 
• 
Recent myocardial infarction or arterial or venous thromboembolic event 
(within 1 year) or a history of greater than 1 myocardial infarction or arterial or 
venous thromboembolic event 
• 
Cardiac-related syncopal event within the past year  
• 
Cardio or cerebral vascular disease requiring surgical intervention (e.g., bypass 
surgery, angioplasty). For subjects with previous stent placement, please contact 
the medical monitor 
• 
Congestive heart failure (CHF) New York Heart Association (NYHA) Criteria 
> Stage 2 
• 
Angina pectoris 
• 
QT Fridericia-corrected ≥ 450 msec at screening (If QTcF is above this range, a 
repeat ECG can be done at the discretion of the investigator, and if the value is 
in range, the patient may be enrolled in the study.) 
17. For subjects with an intact uterus, > 5 mm endometrial stripe thickness as measured at 
screening by transvaginal ultrasound 
18. Clinically confirmed urinary tract infection, requiring treatment as determined by the 
investigator, at the Screening Visit 
19. Current or past history of any physical condition that, in the investigator’s opinion, 
might put the subject at risk, impact the absorption of the study drug, or interfere with 
study results interpretation. 


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4.2 Withdrawal of Subjects From the Study 
The duration of the study is defined for each subject as the date signed written informed 
consent is provided through the last follow-up visit (Visit 8 at Week 28). 
4.2.1 Reasons for Withdrawal/Discontinuation 
Subjects are free to withdraw from the study at any time for any reason.  
In addition, subjects may be withdrawn from the study by the Principal Investigator (PI) in 
consultation with GTx, Inc. for any of the following reasons: 
• AEs that require treatment with a prohibited medication or procedure 
• Development of any condition that may pose an additional risk to the subject or that the 
PI decides is in the best interest of the subject to withdraw from the study 
• Sponsor’s decision 
• Subject is unable to follow Investigators’ instructions and/or to comply with the study 
procedures 
• Protocol deviation 
• Disease progression 
The clinical study report will include reasons for all subject withdrawals from treatment as 
well as details relevant to violations of Study Prohibitions and Concomitant Therapy. 
4.2.2 Handling of Withdrawals  
Subjects are free to withdraw from the study or study treatment at any time upon request. 
Subject participation in the study may be stopped at any time at the discretion of the 
investigator or at the request of the Sponsor. 
Subjects who discontinue study treatment or active participation in the study will no longer 
receive GTx-024 or placebo (study drug) and will be considered to have withdrawn from the 
study. When a subject withdraws from the study, the reason(s) for withdrawal shall be 
recorded by the investigator on the relevant page of the electronic case report form (eCRF). 
Those subjects who receive study drug will be monitored for AEs for 30 days after stopping 
treatment with study drug. Every effort will be made to obtain all end-of-treatment measures 


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(Visit 5), as outlined in Table 12–1, in the event that a subject withdraws, or is withdrawn, 
from the study before completing treatment. Subjects who are not returning for final 
assessments will be contacted (2 documented telephone calls followed by 1 registered letter) 
by the site in an attempt to improve their compliance. 
It is vital to obtain follow-up data on any subject withdrawn because of an AE or serious AE 
(SAE). In every case, efforts must be made to undertake protocol-specified, safety follow-up 
procedures. All data collected from all subjects, including early withdrawals and early 
discontinuations of treatment, will be used in the reporting and analysis of the study. 
4.2.3 Replacements 
Subjects who have been randomly assigned to receive study drug and who subsequently 
discontinue prematurely from the study will not be replaced. Subjects who fail to satisfy 
inclusion and exclusion criteria at screening may be rescreened 1 additional time at the 
discretion of the Sponsor.  


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5 Study Treatments 
Refer to Section 3.1 for a full description of the study design and randomization scheme. 
Investigational product will be administered orally once daily and supplied as opaque, white 
to off-white, size 5, oval Softgel capsules.  
Subjects assigned to receive GTx-024 1 mg will be required to take two (2) 0.5 mg GTx-024 
capsules once daily. Subjects assigned to receive GTx-024 3 mg will be required to take 
one (1) 3 mg GTx-024 capsule and one (1) placebo capsule once daily. Subjects assigned to 
receive placebo will be required to take two (2) placebo capsules once daily. 
5.1 Method of Assigning Subjects to Treatment Groups 
Subjects meeting all eligibility criteria will be randomized to receive placebo, 1 mg 
GTx-024, or 3 mg GTx-024 in a 1:1:1 ratio.  
An interactive web response system (IWRS) will be used to administer the randomization 
schedule. Biostatistics will generate the randomization schedules using SAS software Version 
9.4 (SAS Institute Inc., Cary, North Carolina) or later. The IWRS will link sequential subject 
randomization numbers to treatment codes.  
5.2 Treatments Administered 
Study drug (Section 5) will be taken orally with water at approximately the same time each 
day, with or without food. Subjects will be instructed to take 2 capsules each day.  
5.3 Identity of Study Drug 
The GTx-024 study drug is an opaque, white to off-white, size 5, oval Softgel capsule 
containing the active ingredient GTx-024 (0.5 mg or 3 mg) dissolved in the inactive excipient 
polyethylene glycol 400. The placebo study drug is identical in appearance to the GTx-024 
study drug and contains polyethylene glycol 400 but not GTx-024. All study drug capsules 
will be imprinted with “GTx” in black ink on the outer shell of the capsule.  
5.4 Management of Clinical Supplies 
GTx, Inc. will provide adequate supplies of study drug through a central distribution center to 
clinical sites. 


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5.4.1 Study Drug Packaging and Storage 
Study drug will be packaged in blister packaging that is designed and labeled in a manner to 
protect study blinding. Each blister pack will contain assigned dosing for 1 subject and will 
contain a sufficient quantity for each 4-week dispensing period plus 1 week of overage. 
Each blister pack will be a carton containing 5 blister cards. Each blister card will be 
composed of 2 blister strips encased in a child-resistant heat-sealed card. The blister strips are 
composed of a PVC/ACLAR base and an aluminum foil/PVC/PVAC copolymer and 
polymethacrylate lidding. Perforations on the back of the heat-seal card overlay the foil 
lidding. To remove study drug, subjects will release the appropriate perforation by depressing 
a release button on the inside of the card. Once released, the perforation can be removed and 
the study drug pushed through the foil. 
A clinical label will be affixed to the outside of each blister card and carton. The label will 
specify storage and dosing information.  
At the study site, study drug must be stored in a secure area (e.g., a locked cabinet), protected 
from moisture, and kept at a controlled room temperature 15oC-25oC (59oF-77oF) with 
excursions permitted to 30oC (86oF). 
5.4.2 Study Drug Accountability 
The investigator will maintain accurate records of receipt of all study drug, including dates of 
receipt. In addition, accurate records will be kept regarding when and how much study drug 
is dispensed to and used by each subject in the study. Reasons for departure from the 
expected dispensing regimen must be recorded. At the completion of the study, to satisfy 
regulatory requirements regarding drug accountability, all study drug will be reconciled and 
retained or destroyed according to applicable regulations and Sponsor requirements. 
5.4.3 Other Supplies 
Test kits for the 24-hour pad weight test will be provided to sites by the Sponsor. Test kits 
will include sanitary pads and subject instructions. 


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5.5 Overdose Management 
Subjects in this study will be dispensed a maximum of 105 mg of GTx-024 at any visit; this 
is therefore the maximum amount available to any subject at any time. In Phase 1 studies, 
subjects have safely received single doses of up to 100 mg GTx-024. The likelihood of a 
need for other than symptomatic treatment of overdose is considered extremely low. In the 
event of an overdose reported to the study site, the medical monitor should be contacted 
immediately. 
5.5.1 Medication Errors 
Dispensing study drug to subjects for self-administration in an outpatient study increases the 
risk of medication errors. All errors in medication dispensing or administration must be 
carefully documented. These errors may include (but are not limited to) providing the wrong 
dose, medication loss, or administration at the wrong time of day. Adherence to medication 
protocol will be emphasized at every visit.  
5.5.2 Treatment of Medication Errors 
The treatment of medication errors should be discussed with the medical monitor on a case 
by case basis.  
5.6 Blinding 
The study will be performed in a double-blind manner. All study drug will be supplied in 
identical packaging and will be similar in color, smell, taste, and appearance to enable 
double-blind conditions.  
5.6.1 Breaking the Blind 
A subject’s treatment assignment will not be broken until the end of the study unless medical 
treatment of the subject depends on knowing the study treatment the subject received. In the 
event that the blind needs to be broken because of a medical emergency, the investigator may 
unblind an individual subject’s treatment allocation. As soon as possible, the investigator 
should first contact the medical monitor to discuss the medical emergency and the reason for 
revealing the actual treatment received by that subject. The treatment assignment will be 
unblinded through IWRS. Reasons for treatment unblinding must be clearly explained and 


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justified in the eCRF. The date on which the code was broken together with the identity of 
the person responsible must also be documented. 
5.7 Treatment Compliance 
Individual subject compliance in taking study drug will be monitored by counting unused 
medication returned by the subject at visits. Compliance will be documented. If compliance 
is less than 80% or more than 120%, the Investigator or designee is to counsel the subject and 
ensure that steps are taken to improve compliance. Subjects who are less than 80% or more 
than 120% compliant with the dosage regimen for any 2 consecutive visit periods during the 
study may be withdrawn from the study. 
5.8 Prior and Concomitant Medications 
The Investigator or designee must record the use of prior medications (all medication taken 
within 30 days prior to Visit 1) and current treatment (including both drug and nondrug 
therapies and all prescribed, over-the-counter [OTC], and alternative medicines) in the 
eCRFs. The minimum requirement is that the drug name and dates of administration are to be 
recorded. This also includes drugs used on a chronic or as-needed basis. Subjects must be 
instructed not to start any new medication, either prescribed or OTC, without consulting the 
Investigator, unless the new medication is required for emergency use. Subjects must be 
instructed to notify the Investigator immediately if medications are required for emergency 
use. 
Any changes in concomitant medications also will be recorded in the subject’s eCRF. 
Any concomitant medication deemed necessary for the welfare of the subject during the 
study may be given at the discretion of the investigator. However, it is the responsibility of 
the investigator to ensure that details regarding the medication are recorded in full in the 
eCRF. 


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5.8.1 Prohibited Concomitant Medications and Treatments 
Prohibited medications and treatments during the study duration include the following: 
• Systemic hormonal products including but not limited to estrogens, progestins, 
testosterone, methyltestosterone, oxandrolone (Oxandrin®), oxymetholone, danazol, 
fluoxymesterone (Halotestin®), other androgenic compounds, including herbals such as 
fenugreek, Korean ginseng, goat weed, forskolin, ashwagandha, and Testro-X®. 
Intravaginal application of estradiol topical/tablet agents and hormones delivered via 
vaginal ring are allowed. 
• Any new treatment (medication or otherwise), including vaginal rejuvenation, that is 
known or suspected to affect lower urinary tract function throughout the treatment and 
follow-up periods 
• Treatment with any investigational agent within the 30 days before the first dose of study 
treatment 
• New pelvic floor exercises (including Kegel) throughout the treatment and follow-up 
period  


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6 Study Assessments and Procedures 
Before performing any study procedures, all potential subjects will sign an informed consent 
form (ICF). Subjects will have the opportunity to have any questions answered before 
signing the ICF. The investigator must address all questions raised by the subject. The 
investigator will also sign the ICF.  
6.1 Study Visits  
The schedule of events for this study is presented in Table 12–1.  
6.1.1 Screening 
6.1.1.1 Screening Visit, Days ‒28 to 0 
The study will be explained in detail and adequate time will be allowed for answering 
questions from a potential subject before she signs the institutional review board 
(IRB)-approved informed consent document. Informed consent will be obtained from those 
potential subjects meeting initial inclusion/exclusion criteria and expressing willingness to 
participate before study site personnel conduct any study assessments of such subjects.  
Once informed consent is obtained, a subject number will be assigned and a detailed 
interview will be conducted with the subject about her medical history, including past 
gynecological and obstetric history (gravida, para, prior abortions and deliveries) and about 
her concomitant medications. The subject will complete the MESA incontinence 
questionnaire to determine if she has predominant stress incontinence. If the urinary 
continence type is stress predominant, a BST will be conducted to confirm SUI. Height and 
weight will be measured, and vital signs will be assessed. A gynecologic pelvic examination 
and a physical examination will be conducted. A dipstick urinalysis will be performed and 
blood will be drawn for laboratory tests as presented in Table 12–1. The subject’s eligibility 
criteria will be reviewed and, if the subject is considered to be provisionally qualified, she 
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6.1.1.2 Additional Screening Procedures 
If the subject has provisionally qualified for the study during the Screening Visit, the 
following procedures will be performed between the Screening Visit and Visit 1 (Baseline): 
• A mammography examination will be performed, unless the subject provides evidence of 
a mammography examination performed within the 6 months prior to the Screening Visit  
• A transvaginal ultrasound examination will be performed in subjects with an intact uterus 
• A 12-lead electrocardiography examination will be performed 
• The subject will complete a 24-hour pad weight test 
• The subject will complete a 3-day voiding diary 
6.1.2 Study Visit 1: Week 0, Clinic Visit 
Concomitant medications and AEs will be reviewed. The results of the 24-hour pad weight 
test and the 3-day voiding diary will be reviewed, and continued eligibility for enrollment 
will be evaluated, also considering the results of laboratory tests during screening. A subject 
meeting the inclusion and exclusion criteria after all screening study measures have been 
completed and reviewed will be randomly assigned to treatment (randomization).  
Vital signs will be obtained, a dipstick urinalysis will be performed, and the subject will 
complete the UDI-6, IIQ-7 Short Form, I-QOL, FSFI, PGI-S, and Vaizey Incontinence 
Severity questionnaires.  
Study drug will be dispensed with administration instructions, and each package will be 
preprinted with a medication identification number. The medication identification number 
assigned to the subject will be noted in the eCRF for study drug. The subject will take the 
first dose of study drug during this visit.  
6.1.3 Study Visit 2: Week 1, Phone Visit 
Approximately 1 week after beginning treatment, the subject will be contacted by phone to 
assess for concomitant medications and AEs (which will be recorded in the eCRF). The 
subject will be instructed to complete a 24-hour pad weight and 3-day voiding diary within 
the week preceding her next study visit. The subject will be reminded to bring all unused 
study drug (in its original packaging) to her next clinic visit. 


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6.1.4 Study Visit 3: Week 4, Clinic Visit 
Approximately 4 weeks after beginning treatment, the subject will return to the study site for 
a clinic visit. Unused study drug will be collected. Concomitant medications and AEs will be 
reviewed. Weight and vital signs will be measured, and a physical examination will be 
performed. A dipstick urinalysis will be performed, and blood will be drawn for a 
comprehensive metabolic panel (CMP). Completion of a 24-hour pad weight test and a 3-day 
voiding diary will be verified.  
The subject will complete the UDI-6, IIQ-7 Short Form, I-QOL, FSFI, PGI-S, PGI-I, and 
Vaizey Incontinence Severity questionnaires. 
Study drug will be dispensed with administration instructions, and each package will be 
preprinted with a medication identification number. The medication identification number 
assigned to the subject will be noted in the eCRF for study drug.  
The subject will be instructed to complete a 24-hour pad weight and 3-day voiding diary 
within the week preceding her next study visit. The subject will be reminded to bring all 
unused study drug (in its original packaging) to her next clinic visit.  
6.1.5 Study Visit 4: Week 8, Clinic Visit 
Approximately 8 weeks after beginning treatment, the subject will return to the study site for 
a clinic visit. Unused study drug will be collected. Concomitant medications and AEs will be 
reviewed. Weight and vital signs will be measured, and a physical examination will be 
performed. A dipstick urinalysis will be performed, and blood will be drawn for a CMP. 
Completion of a 24-hour pad weight test and a 3-day voiding diary will be verified.  
The subject will complete the UDI-6, IIQ-7 Short Form, I-QOL, FSFI, PGI-S, PGI-I, and 
Vaizey Incontinence Severity questionnaires. 
Study drug will be dispensed with administration instructions, and each package will be 
preprinted with a medication identification number. The medication identification number 
assigned to the subject will be noted in the eCRF for study drug.  


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The subject will be instructed to complete a 24-hour pad weight and 3-day voiding diary 
within the week preceding her next study visit. The subject will be reminded to bring all 
unused study drug (in its original packaging) to her next clinic visit.  
6.1.6 Study Visit 5: Week 12 or Early Withdrawal, Clinic Visit 
Approximately 12 weeks after beginning treatment, the subject will return to the study site 
for a clinic visit. Unused study drug will be collected and accounted for. Concomitant 
medications and AEs will be reviewed. Weight and vital signs will be measured, and both a 
gynecologic pelvic examination and a physical examination will be performed. A dipstick 
urinalysis will be performed and blood will be drawn for laboratory testing as presented in 
Table 12–1. Completion of a 24-hour pad weight test and a 3-day voiding diary will be 
verified. A BST and, in subjects with an intact uterus, a transvaginal ultrasound examination 
will be performed.  
The subject will complete the MESA, UDI-6, IIQ-7 Short Form, I-QOL, FSFI, PGI-S, PGI-I, 
and Vaizey Incontinence Severity questionnaires. 
The subject will be instructed to complete a 24-hour pad weight and 3-day voiding diary 
within the week preceding her next study visit.  
6.1.7 Study Visit 6: Week 16, Clinic Visit 
Approximately 16 weeks after beginning treatment and 4 weeks after the last dose of study 
drug, the subject will return to the study site for a clinic visit. Concomitant medications and 
AEs will be reviewed. Weight and vital signs will be measured, and a physical examination 
will be performed. Blood will be drawn for laboratory testing as presented in Table 12–1. 
Completion of a 24-hour pad weight test and a 3-day voiding diary will be verified.  
The subject will complete the UDI-6, IIQ-7 Short Form, I-QOL, FSFI, PGI-S, PGI-I, and 
Vaizey Incontinence Severity questionnaires. 
Subjects continuing to Week 20 will be instructed to complete a 24-hour pad weight and 
3-day voiding diary within the week preceding her next study visit.  


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6.1.8 Study Visit 7: Week 20, Clinic Visit 
Approximately 20 weeks after beginning treatment and 8 weeks after the last dose of study 
drug, the subject will return to the study site for a clinic visit. Concomitant medications and 
AEs will be reviewed. Blood will be drawn for laboratory testing as presented in Table 12–1. 
Completion of a 24-hour pad weight test and a 3-day voiding diary will be verified. 
The subject will complete the UDI-6, IIQ-7 Short Form, I-QOL, FSFI, PGI-S, PGI-I, and 
Vaizey Incontinence Severity questionnaires. 
The subject will be instructed to complete a 24-hour pad weight and 3-day voiding diary 
within the week preceding her next study visit.  
6.1.9 Study Visit 8: Week 28, Clinic Visit 
Approximately 28 weeks after beginning treatment and 16 weeks after the last dose of study 
drug, the subject will return to the study site for a clinic visit. Concomitant medications and 
AEs will be reviewed. Blood will be drawn for laboratory testing as presented in Table 12–1. 
Completion of a 24-hour pad weight test and a 3-day voiding diary will be verified.  
The subject will complete the UDI-6, IIQ-7 Short Form, I-QOL, FSFI, PGI-S, PGI-I, and 
Vaizey Incontinence Severity questionnaires.  
6.2 Efficacy Assessments 
Efficacy assessments will include a 3-day voiding diary, PGI-S, PGI-I, UDI-6, IIQ-7, I-QOL, 
FSFI, Vaizey Incontinence Severity Score, and 24-hour pad weight test. Changes in 
subject-reported impressions will be noted.  
6.2.1 Three-Day Voiding Diary 
Subjects will record all urinary voids, specifying each episode of urinary leakage including 
type. Fluid intake will also be recorded as well as any episode of vaginal discharge or 
spotting.  
In each 3-day voiding diary, subjects are to record voiding data for 3 consecutive days in a 
paper diary. To be considered valid, each 3-day voiding diary must be recorded within 7 days 
on either side of a planned visit, based on the date of randomization.  


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Three-day voiding diaries are reliable measures of the mean number of urinary incontinence 
episodes per day, incontinence type, mean voids per 24 hours, and mean voids during 
sleeping hours.  
6.2.2 Bladder Stress Test (BST) 
Before the BST, a bladder scan will be performed by ultrasound to verify that the subject’s 
bladder contains at least 150 ml of urine. The volume of urine present in the bladder should 
be captured. Once the urine volume has been determined, the subject will stand over an 
absorbent pad and be instructed to cough forcefully and/or perform a Valsalva maneuver to 
elicit a urinary stress leak. If there is no observable urine loss on the absorbent pad, a paper 
towel will be placed lightly against the perineum to detect any urine leakage that may not 
have dropped onto the pad. Any urine loss observed by the research staff is indicative of a 
positive BST.  
After completion of the BST, subjects will be asked to void and the volume of urine 
remaining in the bladder after voiding (post void residual) will be measured via ultrasound 
bladder scan. The volume of urine present in the bladder post voiding should be captured. 
A BST will be conducted for each subject at the Screening Visit and at Visit 5 (Table 12–1). 
6.2.3 Patient Global Impression of Severity 
The PGI-S is a global rating of subject-reported impression of SUI severity using a 4-point 
scale (Appendix 12.3). Validity of the PGI-S has been established for application in SUI. 
6.2.4 Patient Global Impression of Improvement  
The PGI-I is a global rating of subject-reported impression of SUI improvement using a 
7-point scale (Appendix 12.4). Validity of the PGI-I has been established for application in 
SUI. 
6.2.5 Urogenital Distress Inventory and Incontinence Impact 
Questionnaire Short Form  
The UDI-6 (Appendix 12.5) and IIQ-7 Short Form (Appendix 12.6) are validated subject 
questionnaires used to assess symptom distress and the impact of urinary incontinence on 
daily life (Shumaker et al 1994; Uebersax et al 1995). The UDI-6 and IIQ-7 are both ‘‘A 


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grade’’ recommended by the Fourth International Consultation on Incontinence (Shumaker et 
al 1994; Uebersax et al 1995; Staskin et al 2008, 2009). 
6.2.6 Incontinence Quality of Life  
The I-QOL (Appendix 12.7) is a validated subject questionnaire used to assess the impact of 
urinary incontinence and treatments. 
6.2.7 Female Sexual Function Index 
The FSFI (Appendix 0) is a self-administered questionnaire to assess overall sexual 
experience that consists of 19 questions scored from 0 to 5. The scale contains 6 domains: 
desire, arousal, lubrication, orgasm, satisfaction, and pain (Rosen et al 2000). The FSFI total 
score is a weighted average of the 6 domains with each contributing a maximum of 6 points 
to the total (maximum score of 36).  
6.2.8 Vaizey Incontinence Severity Score 
The Vaizey Incontinence Severity Score is obtained through a self-administered 
questionnaire to assess a subject’s bowel symptoms and the impact if these symptoms of 
daily life. 
6.2.9 Twenty-Four Hour Pad Weight Test 
The 24-hour pad weight test is a quantitative test intended to provide information on the 
severity of incontinence. The amount of urine leaked over the 24 hours of testing is 
quantified by measuring the change in weight of perineal pads used during testing. 
The 24-hour pad test should be completed during 1 day of each scheduled 3-day voiding 
diary. Subjects will be instructed to record pad weight on a day that is typical for them in 
terms of activity level and fluid intake. Subjects must use the incontinence pads provided in 
the 24-hour pad weight test kit for the 24-hour test; no other pads are to be used. Subjects 
should receive 8 incontinence pads for use during each 24-hour test period. Pads will be 
returned before or at the next scheduled study visit.  


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6.2.10 Medical, Epidemiological, and Social Aspects of Aging Questionnaire  
The MESA incontinence questionnaire (Appendix 12.2) consists of 15 items divided into 
stress incontinence (9 items) and urge incontinence (6 items) subscales. Based on their 
responses, subjects can be characterized as having predominant stress incontinence, urge 
incontinence, or mixed incontinence (Herzog and Fultz 1990).   
6.3 Safety Assessments 
6.3.1 Adverse Events 
6.3.1.1 Definitions of Adverse Events 
The investigator is responsible for reporting all AEs that are observed or reported during the 
study regardless of their possible relationship to study drug or their clinical significance. 
An AE is defined as any untoward medical occurrence in a subject enrolled into this study 
regardless of its causal relationship to study drug. Subjects will be instructed to contact the 
investigator at any time after randomization if any symptoms develop. 
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to 
study drug or any event already present that worsens in either intensity or frequency after 
exposure to study drug and within the 30 days following discontinuation of drug treatment 
An SAE is defined as any event that results in one of the following conditions: 
• Death 
• Life-threatening event (defined as a subject at immediate risk of death at the time of the 
event) 
• An event requiring inpatient hospitalization or prolongation of existing hospitalization  
• An event that results in persistent or significant disability/incapacity  
• An event that results in a congenital anomaly/birth defect  


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• Any other important medical event that may not result in death, be life threatening, or 
require hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, the event may jeopardize the subject or may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
6.3.1.2 Eliciting and Documenting Adverse Events 
Adverse events will be assessed beginning at enrollment (date of signed informed consent) 
through the completion of the durability or follow up period.  
Serious AEs that occur more than 30 days after the last dose of study drug need not be 
reported unless the investigator considers them to be related to study drug. 
At every study visit, subjects will be asked a standard nonleading question to elicit any 
medically related changes in their well-being. They will also be asked if they have been 
hospitalized, had any accidents, used any new medications, or changed concomitant 
medication regimens (both prescription and OTC medications). 
In addition to subject observations, AEs identified from any study data (e.g., laboratory 
values, physical examination findings, electrocardiogram [ECG] changes) or identified from 
review of other documents (e.g., subject diaries) that are relevant to subject safety will be 
documented on the AE page in the eCRF. 
6.3.1.3 Reporting Adverse Events 
All AEs reported or observed during the study will be recorded on the AE page in the eCRF. 
Information to be collected includes drug treatment, dose, event term, time of onset, 
investigator-specified assessment of severity and relationship to study drug, time of 
resolution of the event, seriousness, any required treatment or evaluations, and outcome. 
Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, 
reactions to concurrent medications, or progression of disease states must also be reported. 
All AEs will be followed to adequate resolution. The Medical Dictionary for Regulatory 
Activities (MedDRA) will be used to code all AEs.  


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Any medical condition that is present at the time that the subject is screened should not be 
reported as an AE. However, if a pre-existing condition changes in intensity or frequency at 
any time during the study, it should be recorded as an AE. 
Any AE that meets SAE criteria (Section 6.3.1.1) must be entered into the electronic data 
capture (EDC) system immediately (i.e., within 1 business day) after site personnel first learn 
of the event. Once the qualifying SAE data are entered, pharmacovigilance will be notified 
by an email alert, which will contain high level safety information. Additional safety 
information will be obtained from the EDC system via applicable eCRF pages. If the EDC 
system is not available, the site should send a completed paper SAE report form to 
pharmacovigilance by fax or email: 
• Safety Fax Line: 1-866-966-2970 (US toll-free) 
• Safety Email: sae@cmedresearch.com 
When the EDC system is again available, the site must enter all applicable information into 
the EDC system. All supporting source information concerning the SAE (e.g., hospital 
records) should be provided by fax or email.  
If there is a question concerning an SAE, the site needs guidance regarding reporting of an 
SAE, the site is returning a call from a safety specialist, or the site urgently needs to report an 
SAE or make pharmacovigilance aware of an SAE, the Safety Hotline should be used:  
• Safety Hotline: 1-866-966-8429 (US toll free) 
If a site makes an initial report of an SAE by the safety hotline, the site must subsequently 
enter all applicable information into the EDC system immediately thereafter.  
6.3.1.4 Assessment of Severity 
All AEs will be assessed by the Investigator according to NCI-CTCAE, Version 4.0. For any 
AE that is not specifically covered in NCI-CTCAE, Version 4.0, the criteria below should be 
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Grade 
Description 
0 
No AE or within normal limits 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated  
2 
Moderate; minimal, local, or non-invasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living  
3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care activities of daily living  
4 
Life-threatening consequences; urgent intervention indicated 
 
Changes in the severity of an AE should be documented to allow an assessment of the 
duration of the event at each level of intensity to be performed. Adverse events characterized 
as intermittent do not require documentation of onset and duration of each episode. 
6.3.1.5 Assessment of Causality 
The investigator’s assessment of an AE’s relationship to study drug is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the 
study. If there is any doubt as to whether a clinical observation is an AE, the event should be 
reported. 
The relationship or association of the test article in causing or contributing to the AE will be 
characterized using the following classification and criteria: 


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Unrelated: 
This relationship suggests that there is no association between the study drug 
and the reported event. 
 
Possible: 
This relationship suggests that treatment with the study drug caused or 
contributed to the AE, i.e., the event follows a reasonable temporal sequence 
from the time of drug administration or follows a known response pattern to 
the study drug but could also have been produced by other factors. 
 
Probable: 
This relationship suggests that a reasonable temporal sequence of the event 
with drug administration exists and, based upon the known pharmacological 
action of the drug, known or previously reported adverse reactions to the drug 
or class of drugs, or judgment based on the investigator’s clinical experience, 
the association of the event with the study drug seems likely. The event 
disappears or decreases on cessation or reduction of the dose of study drug. 
 
Definite: 
This relationship suggests that a definite causal relationship exists between 
drug administration and the AE, and other conditions (concurrent illness, 
progression/expression of disease state, or concurrent medication reaction) do 
not appear to explain the event. The event reappears or worsens if the study 
drug is re-administered.  
 
6.3.1.6 Follow-Up of Subjects Reporting Adverse Events 
All AEs must be reported in detail on the appropriate page in the eCRF and be monitored to 
satisfactory resolution, until the investigator deems the event to be chronic or not clinically 
significant, or until the subject is considered to be stable. 
6.3.2 Halting Rules 
If in the opinion of the Investigator, the participation in the study is or is becoming 
detrimental to the well-being of a particular subject, this issue should be discussed with the 
medical monitor for this study and the subject’s participation in the study may be 
discontinued. 
Discontinuation of treatment should be considered if:  
• ALT or AST > 8 × upper limit of normal (ULN) 


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• ALT or AST > 5 × ULN for more than 2 weeks 
• ALT or AST > 3 × ULN and total bilirubin > 2 × ULN or international normalized 
ratio (INR) > 1.5 
• ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (differential count > 5%) 
In the event that ALT or AST is > 3 × ULN, the subject will return for an unscheduled clinic 
visit and blood will be drawn for a coagulation panel to determine the INR. The INR will be 
determined at a local laboratory.  
All subjects discontinued from the study should be followed until abnormal values return to 
normal, and all discontinuations should be discussed with the medical monitor prior to 
discontinuation.  
6.3.3 Safety Assessments 
The safety assessments will include AEs (Section 6.3.1), vital sign measurements, height and 
weight, concomitant medications, medical history, physical examination findings, 
transvaginal ultrasound, and clinical laboratory analyses (Section 6.6). Refer to Table 12–1 
for a detailed schedule of the timing of study procedures. 
6.3.3.1 Vital Sign Measurements 
Vital sign measurements include oral temperature, seated BP, pulse rate, and respiration rate. 
Vital sign measurements will be collected as indicated in Table 12–1.  
6.3.3.2 Height and Weight 
Height will be measured at screening only and weight will be measured as indicated in 
Table 12–1. 
6.3.3.3 Prior and Concomitant Medications 
At the Screening Visit, the Investigator or designee must record the use of prescription and 
OTC medication taken within the prior 30 days. Concomitant medications (including 


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prescription and OTC medications) will be assessed and recorded throughout the study 
(Table 12–1).  
6.3.3.4 Medical History 
A detailed review of medical history, conducted at the Screening Visit, will include review of 
gravida, prior abortions, parity, deliveries, and history of gynecological conditions, surgeries, 
and cancer. 
6.3.3.5 Physical Examination  
The purpose of the physical examination is to identify any medical conditions that would 
impact eligibility of the subject at screening, and to identify any changes that occur as a 
result of treatment. Physical examination will include visual inspection, chest auscultation, 
organ and lymph node palpation, skin turgor, and brief neurologic exam (muscle strength, 
reflexes, sensation). The visual inspection should include a visual skin examination with 
specific attention to any androgenic changes (acne, hirsutism). Physical examinations will be 
performed as indicated in Table 12–1. 
6.3.3.6 Transvaginal Ultrasound 
Only for subjects with an intact uterus, transvaginal ultrasound will be performed at 
screening and at the end of treatment (Visit 5) to observe changes in the endometrial stripe 
thickness (mm). Transvaginal ultrasound examinations will be evaluated locally.  
6.4 Other Assessments 
6.4.1 Pelvic Examination 
Gynecologic pelvic examination of each subject will be conducted at the Screening Visit and 
at Visit 5 (Table 12–1). The purpose of the pelvic examination at screening is to identify any 
gynecologic findings that might impact the patient’s participation in the trial, and at the end 
of the treatment period to note whether any changes have occurred. The pelvic exam should 
include external inspection, speculum, and bimanual examinations. 
6.4.2 Mammography  
Mammography is the process of using low-energy x-rays to examine the human breast, 
which is used as a diagnostic and screening tool. The goal of mammography is the early 


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detection of breast cancer, typically through detection of characteristic masses and/or 
microcalcifications. Mammography examination of each subject will be conducted during the 
screening period unless the subject provides evidence of a mammography examination 
performed within the 6 months prior to screening (Table 12–1). Mammograms will be read 
locally. 
6.4.3 Electrocardiography 
A standard 12-lead ECG will be obtained at screening. Tracings must be dated and signed by 
the Investigator (or his/her designee) and filed with the subject’s source documentation. Each 
ECG tracing should be labeled with the study number, subject initials (where regulations 
permit), and subject number. Interpretation of the tracing must be made by a qualified 
physician. Results from 12-lead ECG examination should be captured in the ECG Evaluation 
eCRF. Clinically significant abnormalities present at screening should be reported on the 
Medical History eCRF page. Clinically significant findings should be discussed with the 
medical monitor prior to randomizing the subject in the study. The PI will make the final 
decision if any observed deviations in the ECG are sufficient to require that the subject be 
excluded from the study. The ECG may be repeated at the discretion of the Investigator at 
any time during the study as clinically indicated, and any clinically relevant findings should 
be added to the AE eCRF.  
6.5 Pregnancy 
This study will enroll only postmenopausal women who are not taking hormone products. In 
the unlikely event of a pregnancy, any pregnancy must be reported to pharmacovigilance 
within 2 weeks of learning of its occurrence, using the EDC system (Section 6.3.1.3). The 
pregnancy must be followed-up to determine the outcome (including spontaneous 
miscarriage, elective termination, normal birth, or congenital abnormality) and status of 
mother and child, even if the subject was discontinued from the study. Pregnancy 
complications and elective terminations for medical reasons must be reported as an AE or 
SAE. Spontaneous miscarriages must be reported as an SAE. 
Any SAE occurring in association with a pregnancy, brought to the investigator’s attention 
after the subject has completed the study and considered by the investigator as possibly 
related to the study treatment, must be promptly reported to pharmacovigilance.  


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6.6 Laboratory Analyses 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (e.g., ECGs, radiological scans, or vital sign measurements), including 
those that worsen from baseline, felt to be clinically significant in the medical and scientific 
judgment of the investigator are to be recorded as AEs or SAEs. 
However, any clinically significant 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, are not to be reported as AEs or SAEs. 
Laboratory analyses include the following: 
• Comprehensive metabolic panel (Chem 14): includes calcium, carbon dioxide, glucose, 
potassium, sodium, total protein, and kidney and liver function tests (serum ALT, AST, 
γ-glutamyl transpeptidase, and total and direct bilirubin) will be performed (the 
investigator may repeat these checks if clinically indicated). 
• Serum follicle stimulating hormone  
• Complete blood count with differential  
• Urinalysis dipstick testing for blood, protein, and leukocytes will be performed on a clean 
catch midstream voided urine specimen. If results or clinical symptoms indicate a 
possible urinary tract infection (UTI), the specimen will be sent for culture. If the culture 
is positive, the subject will receive appropriate treatment for UTI per standard of care. If 
the subject has a positive urine culture at the time of screening, she will be considered a 
screening failure and will not be enrolled until she has been treated for a UTI, the UTI 
symptoms disappear, and a dipstick urinalysis is consistent with the absence of a UTI. 
The subject will then be eligible for rescreening 1 additional time at the discretion of the 
Sponsor. After a subject has qualified for enrollment based on a negative urinalysis and 
the absence of clinical symptoms of a UTI, any subsequent UTI will be treated and the 
subject will continue in the study.  
• Fasting lipid panel: including total cholesterol, low-density lipoprotein (LDL), 
high density lipoprotein (HDL), triglycerides, and HDL particle composition 
• C-reactive protein (CRP) 


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• Serology for evidence of active infection with hepatitis B or hepatitis C  
• Hormone panel: includes testosterone, free testosterone, and estradiol. 
• SHBG 
6.7 Sample Collections 
Instructions for sample collection, handling, and shipping will be presented in a separate 
laboratory manual that will be provided to study sites as a separate document. Required 
blood samples should be 12-hour fasting samples.  


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7 Statistical and Analytical Plan  
7.1 Primary Efficacy Endpoint 
The primary efficacy endpoint is a responder analysis, where a responder is defined as having 
a ≥ 50% reduction at the end of treatment (Week 12) compared to baseline in the mean 
number of stress incontinence episodes per day as assessed by the 3-day voiding diary. 
Subjects who have missing diary data for the Week 12 visit will be counted as 
non-responders for this analysis. Rules for recording valid diary data are presented in 
Section 6.2.1.  
7.2 Secondary Efficacy Endpoints 
The secondary efficacy endpoints in this study are the following assessments compared to 
baseline at each visit during the treatment period:  
• Responder rate, where a responder is defined as having a ≥ 50% reduction compared to 
baseline in the mean number of stress incontinence episodes per day as assessed by the 
3-day voiding diary  
• Change in the number of stress incontinence episodes per day as measured by the 3-day 
voiding diary  
• Change in the total number of voids per day as measured by the 3-day voiding diary 
• Change in the mean number of stress incontinence episodes per day as measured by the 
3-day voiding diary  
• Change in 24-hour pad weight as measured by the 24-hour pad weight test 
• Change in the results of the Bladder Stress Test (BST) 
• Change in subject-reported impression of SUI severity as measured by the PGI-S  
• Change in subject-reported impression of SUI improvement as measured by the PGI-I 
• Change in subject-reported urogenital distress as measured by the UDI-6 
• Change in subject-reported impact of urinary incontinence on daily life as measured by 
the IIQ-7 Short Form 


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• Change in subject-reported impact of urinary incontinence on daily life as measured by 
the I-QOL 
• Change in subject-reported sexual function as measured by the FSFI 
• Change in subject-reported assessment of fecal incontinence as measured by the Vaizey 
Incontinence Severity Score. 
• Change in subject-reported stress incontinence, urge incontinence, and mixed 
incontinence as measured by the MESA incontinence questionnaire (Week 12 only) 
7.3 Exploratory Efficacy Endpoints 
The exploratory efficacy endpoints in this study are the following assessments compared to 
Week 12 for all treatments at Week 16, Week 20, and Week 28:  
• Responder rate, where a responder is defined as having a ≥ 50% reduction compared to 
baseline in the mean number of stress incontinence episodes per day as assessed by the 
3-day voiding diary  
• Number of stress incontinence episodes per day as measured by the 3-day voiding diary 
• Total number of voids per day as measured by the 3-day voiding diary 
• Change in 24-hour pad weight as measured by the 24-hour pad weight test 
• Subject-reported impression of SUI severity as measured by the PGI-S  
• Subject-reported impression of SUI improvement as measured by the PGI-I  
• Subject-reported urogenital distress as measured by the UDI-6  
• Subject-reported impact of urinary incontinence on daily life as measured by the IIQ-7 
Short Form  
• Subject-reported impact of urinary incontinence on daily life as measured by the I-QOL  
• Subject-reported sexual function as measured by the FSFI 
• Subject-reported assessment of fecal incontinence as measured by the Vaizey 
Incontinence Severity Score 


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Additional sensitivity analyses may be included in exploratory analyses. These analyses will 
be described in further detail in the SAP.  
7.4 Sample Size Calculation 
The sample size calculation was performed using PASS v12.0.1 for binary outcomes. The 
sample size calculation was performed for a binary response (i.e., a responder is defined as 
having a ≥ 50% reduction at the end of treatment compared to baseline in the mean number 
of stress incontinence episodes per day as assessed by the 3-day voiding diary). The 
assumptions were a 60% active treatment response and 40% placebo response. The overall 
discontinuation rate was anticipated to be approximately 25%. 
Given these assumptions, a randomized sample size of approximately 400 subjects 
(randomized in a 1:1:1 ratio for placebo, 1 mg GTx-024, and 3 mg GTx-024, respectively) 
will have 80% power to detect a treatment difference of 20%. A 2-sided hypothesis test with 
5% significance is assumed for each pairwise comparison between GTx-024 and placebo 
(i.e., alternatively using a 1-sided significance level of 2.5%). 
7.5 Analysis Sets 
Data analysis will be performed on a full analysis set (FAS), a per protocol set (PPS), an 
intent-to-treat (ITT) set, a durability set (DS), and a safety analysis (SA) set.  
The FAS is used for the primary analysis. The FAS consists of all randomized subjects who 
receive at least 1 dose of study drug and have at least 1 post baseline primary efficacy 
assessment (3-day voiding diary). All analyses using the FAS will group participants 
according to randomized treatment. 
The PPS is used for a supportive analysis and will be defined as all subjects included in the 
FAS who do not have any significant protocol deviations. All analyses using the PPS will 
group subjects according to treatment actually received. 
The ITT set consists of all randomized subjects who receive at least 1 dose of study drug. All 
analyses using the ITT set will group subjects according to randomized treatment. Subjects 
who do not have any postbaseline assessments will be treated as non-responders for ITT 
analyses.  


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The DS is used for exploratory analyses to assess the durability of the effect of treatment and 
will be defined as all subjects who complete a Week 12 final visit and a Week 16, Week 20, 
or Week 28 assessment. 
The SA set contains all subjects randomized in the study who receive at least 1 dose of study 
drug. All analyses using the SA set will group subjects according to treatment actually 
received.  
All efficacy analyses performed on the FAS will be repeated on the PPS and the ITT set. 
Further details will be provided in the SAP.  
7.6 Description of Subgroups to be Analyzed 
No subgroup analyses are planned. 
7.7 Statistical Analysis Methodology 
Before unblinding, a separate SAP will be finalized, providing detailed methods for all 
endpoints. In general, summary statistics (n, mean, standard deviation, median, minimum and 
maximum values for continuous variables, and number [%] of subjects in each category for 
categorical variable) will be provided by treatment group and visit. Source data for summary 
tables and statistical analyses will be presented as subject data listings. 
All statistical analyses will be performed using SAS (v9.4 or higher). Unless stated 
otherwise, all statistical tests will be 2-sided using a 5% significance level, leading to 95% 
(2-sided) confidence intervals. No adjustment will be made for multiplicity due to 2 dose 
levels of GTx-024 being compared with placebo. The trial is not powered to show a 
statistical difference between the 2 dose arms of GTx-024. 
The primary efficacy period is defined as baseline (Day 0) through Week 12. Change from 
baseline and determination of responder rate status will be between baseline and visits 
through Week 12. The durability period is defined as Week 12 to Week 16, Week 20, and/or 
Week 28.  
7.7.1 Analysis of the Primary Efficacy Endpoint 
The primary analysis will be conducted on the primary endpoint using the FAS.  


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The primary efficacy endpoint (i.e., a binary response indicator where a responder is defined 
as having a ≥ 50% reduction at the end of treatment compared to baseline in the mean 
number of stress incontinence episodes per day as assessed by the 3-day voiding diary) will 
be evaluated using a logistic regression model. The logistic regression model will include 
treatment group as a covariate. The odds ratio of response between each dose level of 
GTx-024 and placebo (together with the corresponding 95% confidence interval) will be 
reported. The null hypothesis is that there is no treatment effect for either dose level of 
GTx-024. This will be tested against the alternative hypothesis that there is a treatment effect 
for at least 1 of the dose levels of GTx-024.  
The corresponding P-value for the comparison between each dose level of GTx-024 and 
placebo will be derived using the standard normal distribution. Subjects who have missing 
diary data for the screening period or the Week 12 visit will be counted as non-responders for 
this analysis.  
Sensitivity analyses will be specified in the SAP.  
7.7.2 Analysis of Secondary Efficacy Endpoints 
For binary secondary endpoints (responders), the treatment effect will be estimated using a 
logistic regression model with treatment as a covariate.  
For continuous secondary endpoints, treatment effects will be estimated using a mixed model 
repeated measures analysis (MMRM). The MMRM model will specify an unstructured 
variance/covariance matrix and include treatment group, visit, and baseline as covariates.  
For ordinal endpoints, treatment effects will be estimated using a proportional odds model.  
Further details on the analysis of secondary efficacy endpoints will be provided in the SAP. 
7.7.3 Analysis of Exploratory Efficacy Endpoints 
Durability of treatment effect will be examined in the DS for the exploratory efficacy 
endpoints. Additional sensitivity analyses of exploratory and secondary efficacy endpoints 
may also be conducted as exploratory analyses, including sensitivity analyses with regard to 
missing data. Further details of the exploratory analyses will be provided in the SAP.  


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7.7.4 Safety Analyses 
All safety parameters (including AEs, vital signs, laboratory evaluations, SHBG, 
testosterone, and endometrial stripe thickness) will be summarized using the SA set. No 
formal hypothesis testing will be performed.  
All AEs will be coded using the latest version of MedDRA. All TEAEs will be summarized 
and presented in the listings by the number of subjects reporting an event, the percentage of 
subjects with that event, the number of events, and the grade, duration, and relationship to 
treatment. Percentages will be based on the number of subjects who received each treatment 
during the study. 
Clinical laboratory safety tests will be performed, and normal ranges will be provided for 
each laboratory test. Values outside the normal range will be assessed for clinical significance 
by the investigator. Shift tables (change from baseline value to on-treatment values) will be 
presented for each laboratory measurement and assessment time. Each parameter outside the 
normal range will be designated as high (H) or low (L) in the individual data listings.  
7.8 Data Quality Assurance 
Standard operating procedures are available for all activities relevant to the quality of this 
study. Designated personnel will be responsible for implementing and maintaining quality 
assurance and quality control systems to ensure that the study is conducted and that data are 
generated, documented, and reported in compliance with the study protocol, Good Clinical 
Practice (GCP), and Good Laboratory Practice requirements as well as applicable regulatory 
requirements and local laws, rules, and regulations relating to the conduct of the clinical trial. 
An authorized quality assurance auditor will audit the study data and procedures at periodic 
intervals as indicated. Domestic or foreign regulatory authorities, the IRB, and a Sponsor-
authorized auditor may request access to all study documentation for an on-site inspection or 
audit. The Investigator must notify GTx, Inc. of any regulatory authority inspections and 
forward copies of the inspection report to GTx, Inc. 
Electronic data systems will be in accordance with applicable aspects of 21 Code of Federal 
Regulations (CFR) Part 11, ICH Guidelines, GCP, local laws and legislation, and the Health 
Insurance Portability and Accountability Act. 


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7.8.1 On-Site Audits 
At any time, quality assurance representatives of the Sponsor and/or regulatory bodies may 
visit the unit to carry out an audit of the study in compliance with regulatory guidelines and 
company policy. Such audits will require access to study records, documentation, and 
regulatory files. At all times, subject privacy will be of utmost importance and respected. 
Typically, sufficient notice will be given to the Investigator to prepare for the visit. 
7.8.2 Data Management 
As part of the responsibilities assumed by participating in the study, the investigator agrees to 
maintain adequate case histories for the subjects treated as part of the research under this 
protocol. The investigator agrees to maintain accurate eCRFs and source documentation as 
part of the case histories. Source documents may include, but are not restricted to, such 
documents as laboratory reports, ECG strips, and 3-day voiding diaries.  
Investigative site personnel will enter subject data into InForm® (the eCRF program). The 
analysis data sets will be a combination of these data and data from other sources 
(e.g., laboratory data). 
Clinical data management will be performed in accordance with applicable GTx standards 
and data cleaning procedures to ensure the integrity of the data, e.g., removing errors and 
inconsistencies in the data. Adverse events and concomitant medication terms will be coded 
using the MedDRA, an internal validated medication dictionary. 
After database lock, each study site will receive a CDROM containing all of their 
site-specific eCRF data as entered into Oracle Clinical Remote Data Capture for the study, 
including full discrepancy and audit history. Additionally, a CDROM copy of all of the study 
site’s data from the study will be created and sent to the Sponsor for storage. PPD will 
maintain a duplicate CDROM copy for their records. In all cases, subject initials will not be 
collected or transmitted to the Sponsor. 


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8 Ethics 
8.1 Institutional Review Board 
Federal regulations and the ICH guidelines require that approval be obtained from an IRB 
before participation of human subjects in research studies. Before study onset, the protocol, 
informed consent, advertisements to be used for the recruitment of study subjects, and any 
other written information regarding this study to be provided to the subject must be approved 
by the IRB. Documentation of all IRB approvals and of the IRB compliance with ICH 
harmonised tripartite guideline E6(R2): GCP will be maintained by the site and will be 
available for review by the Sponsor or its designee. 
All IRB approvals should be signed by the IRB chairman or designee and must identify the 
IRB name and address, the clinical protocol by title or protocol number or both, and the date 
approval or a favorable opinion was granted. 
The investigator is responsible for providing written summaries of the progress and status of 
the study at intervals not exceeding 1 year or otherwise specified by the IRB. The 
investigator must promptly supply the Sponsor or its designee, the IRB, and, where 
applicable, the institution, with written reports on any changes significantly affecting the 
conduct of the study or increasing the risk to subjects. 
8.2 Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki, ICH GCP, and all applicable regulations. 
8.3 Subject Information and Consent 
A written informed consent in compliance with US Title 21 CFR Part 50 shall be obtained 
from each subject before entering the study or performing any unusual or nonroutine 
procedure that involves risk to the subject. An informed consent template may be provided 
by the Sponsor to investigative sites. If any institution-specific modifications to study-related 
procedures are proposed or made by the site, the consent should be reviewed by the Sponsor 
or its designee or both before IRB submission. Once reviewed, the consent will be submitted 
by the investigator to his or her IRB for review and approval before the start of the study. If 


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the ICF is revised during the course of the study, all active participating subjects must sign 
the revised form. 
Before recruitment and enrollment, each prospective subject will be given a full explanation 
of the study and be allowed to read the approved ICF. Once the investigator is assured that 
the subject understands the implications of participating in the study, the subject will be 
asked to give consent to participate in the study by signing the ICF. 
The investigator shall retain the signed original ICF(s) and give a copy of the signed original 
form to the subject.  


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9 Investigator’s Obligations 
The following administrative items are meant to guide the investigator in the conduct of the 
study but may be subject to change based on industry and government standard operating 
procedures, working practice documents, or guidelines. Changes will be reported to the IRB 
but will not result in protocol amendments. 
9.1 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain subject confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the written 
permission of the subject, except as necessary for monitoring and auditing by the Sponsor, its 
designee, the FDA, or the IRB. 
The investigator and all employees and coworkers involved with this study may not disclose 
or use for any purpose other than performance of the study any data, record, or other 
unpublished, confidential information disclosed to those individuals for the purpose of the 
study. Prior written agreement from the Sponsor or its designee must be obtained for the 
disclosure of any said confidential information to other parties. 
9.2 Financial Disclosure and Obligations 
Investigators are required to provide financial disclosure information to allow the Sponsor to 
submit the complete and accurate certification or disclosure statements required under 
21 CFR 54. In addition, the investigator must provide to the Sponsor a commitment to 
promptly update this information if any relevant changes occur during the course of the 
investigation and for 1 year following the completion of the study. 
Neither the Sponsor nor PPD is financially responsible for further testing or treatment of any 
medical condition that may be detected during the screening process. In addition, in the 
absence of specific arrangements, neither the Sponsor nor PPD is financially responsible for 
further treatment of the subject’s disease. 


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9.3 Investigator Documentation 
Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 8.2 
and Title 21 of the CFR by providing the following essential documents, including but not 
limited to: 
• IRB approval 
• Original investigator-signed investigator agreement page of the protocol 
• Form FDA 1572, fully executed, and all updates on a new fully executed Form FDA 1572 
• Curriculum vitae for the investigator and each subinvestigator listed on Form FDA 1572 
• Financial disclosure information to allow the Sponsor to submit complete and accurate 
certification or disclosure statements required under 21 CFR 54. In addition, the 
investigators must provide to the Sponsor a commitment to promptly update this 
information if any relevant changes occur during the course of the investigation and for 
1 year after the completion of the study. 
• IRB-approved informed consent, samples of site advertisements for recruitment for this 
study, and any other written information regarding this study that is to be provided to the 
subject 
• Laboratory certifications and normal ranges for any local laboratories used by the site, in 
accordance with 42 CFR 493 
9.4 Study Conduct 
The investigator agrees that the study will be conducted according to the principles of ICH 
E6(R2). The investigator will conduct all aspects of this study in accordance with all 
national, state, and local laws or regulations. Study information from this protocol will be 
posted on publicly available clinical trial registers before enrollment of subjects begins. 
9.5 Adherence to Protocol 
The investigator agrees to conduct the study as outlined in this protocol in accordance with 
ICH E6(R2) and all applicable guidelines and regulations. 


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9.6 Adverse Events and Study Report Requirements 
By participating in this study, the investigator agrees to submit reports of SAEs according to 
the timeline and method outlined in the protocol. In addition, the investigator agrees to 
submit annual reports to the study site IRB as appropriate. 
9.7 Investigator’s Final Report 
Upon completion of the study, the investigator, where applicable, should inform the 
institution; the investigator/institution should provide the IRB with a summary of the study’s 
outcome and the Sponsor and regulatory authority(ies) with any reports required. 
9.8 Records Retention 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. It is the responsibility 
of the Sponsor to inform the investigator/institution as to when these events stated in 21 CFR 
312.62(c) have occurred. These documents should be retained for a longer period, however, 
if required by the applicable regulatory requirements or by an agreement with the Sponsor. 
9.9 Publications 
After completion of the study, the data may be considered for reporting at a scientific 
meeting or for publication in a scientific journal. In these cases, the Sponsor will be 
responsible for these activities and will work with the investigators to determine how the 
manuscript is written and edited, the number and order of authors, the publication to which it 
will be submitted, and other related issues. The Sponsor has final approval authority over all 
such issues. 
Data are the property of the Sponsor and cannot be published without prior authorization 
from the Sponsor, but data and publication thereof will not be unduly withheld. 


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10 Study Management 
10.1 Monitoring 
10.1.1 Monitoring the Study 
The clinical monitor, as a representative of the Sponsor, has the obligation to follow the study 
closely. In doing so, the monitor will visit the investigator and study site at periodic intervals, 
in addition to maintaining necessary telephone and letter contact. The monitor will maintain 
current personal knowledge of the study through observation, review of study records and 
source documentation, and discussion of the conduct of the study with the investigator and 
personnel. 
All aspects of the study will be carefully monitored, by the Sponsor or its designee, for 
compliance with applicable government regulation with respect to current GCP and current 
standard operating procedures. 
10.1.2 Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, 
audits, IRB review, and regulatory inspections by providing direct access to all study records. 
In the event of an audit, the investigator agrees to allow the Sponsor, representatives of the 
Sponsor, FDA, or other regulatory agency access to all study records. 
The investigator should promptly notify the Sponsor and PPD of any audits scheduled by any 
regulatory authorities and promptly forward copies of any audit reports received to the 
Sponsor. 
10.2 Management of Protocol Amendments and Deviations 
10.2.1 Modification of the Protocol 
Any changes in this research activity, except those necessary to remove an apparent, 
immediate hazard to the subject, must be reviewed and approved by the Sponsor or its 
designee. Amendments to the protocol must be submitted in writing to the investigator’s IRB 
for approval before subjects can be enrolled into an amended protocol. 


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10.2.2 Protocol Deviations 
The investigator or designee must document and explain in the subject’s source 
documentation any deviation from the approved protocol. The investigator may implement a 
deviation from, or a change of, the protocol to eliminate an immediate hazard to study 
subjects without prior IRB approval. As soon as possible after such an occurrence, the 
implemented deviation or change, the reasons for it, and any proposed protocol amendments 
should be submitted to the IRB for review and approval, to the Sponsor for agreement, and to 
the regulatory authorities, if required. 
A deviation from the protocol is an unintended or unanticipated departure from the 
procedures or processes approved by the Sponsor and the IRB and agreed to by the 
investigator. A significant deviation occurs when there is nonadherence to the protocol by the 
subject or investigator that results in a significant, additional risk to the subject. Significant 
deviations can include nonadherence to inclusion or exclusion criteria, enrollment of the 
subject without prior Sponsor approval, or nonadherence to FDA regulations or ICH GCP 
guidelines, and will lead to the subject being withdrawn from the study (Section 4.2). 
Protocol deviations will be documented by the clinical monitor throughout the course of 
monitoring visits. Principal investigators will be notified in writing by the monitor of 
deviations. The IRB should be notified of all protocol deviations in a timely manner. 
10.3 Study Termination 
Although GTx has every intention of completing the study, GTx reserves the right to 
discontinue the study at any time for clinical or administrative reasons. 
The end of the study is defined as the date on which the last subject completes the last visit 
(includes follow-up visit). 
10.4 Final Report 
Whether the study is completed or prematurely terminated, the Sponsor will ensure that the 
clinical study reports are prepared and provided to the regulatory agency(ies) as required by 
the applicable regulatory requirement(s). The Sponsor will also ensure that the clinical study 
reports in marketing applications meet the standards of the ICH harmonised tripartite 
guideline E3: Structure and content of clinical study reports. 


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Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results. 
Upon completion of the clinical study report, the Sponsor will provide the investigator with 
the full summary of the study results. The investigator is encouraged to share the summary 
results with the study subjects, as appropriate. The study results will be posted on publicly 
available clinical study registers. 


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11  Reference List 
Dmochowski RR, Miklos JR, Norton PA, et al. for the Duloxetine Urinary Incontinence 
Study Group. Duloxetine versus placebo for the treatment of North American women with 
stress urinary incontinence. J Urol. 2003;170(4 Pt 1):1259-63. 
GTx, Inc. GTx-024. Investigator’s brochure, 16th ed. Memphis (TN); 2017. 103 p. 
Herzog AR, Fultz NH. Prevalence and incidence of urinary incontinence in 
community-dwelling populations. J Am Geriatr Soc. 1990;38(3):273-81. 
Kadekawa et al. AUA Annual Meeting 2015, New Orleans, LA. PD27-11. 
Luber KM. The definition, prevalence, and risk factors for stress urinary incontinence. Rev 
Urol. 2004;6 Suppl 3:S3-9. 
Mohler ML, Bohl CE, Jones A, et al. Nonsteroidal selective androgen receptor modulators 
(SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for 
therapeutic benefit. J Med Chem. 2009;52(12):3597-617. 
Norton PA, Zinner NR, Yalcin I, Bump RC; Duloxetine Urinary Incontinence Study Group. 
Duloxetine versus placebo in the treatment of stress urinary incontinence. Am J Obstet 
Gynecol. 2002;187(1):40-8. 
Rosen R, Brown C, Heiman J, et al. The Female Sexual Function Index (FSFI): a 
multidimensional self-report instrument for the assessment of female sexual function. J Sex 
Mar Ther. 2000;26(2):191-208. 
Shumaker SA, Wyman JF, Uebersax JS, et al. Health-related quality of life measures for 
women with urinary incontinence: the Incontinence Impact Questionnaire and the Urogenital 
Distress Inventory. Continence Program in Women (CPW) Research Group. Qual Life Res. 
1994;3(5):291-306. 
Staskin D, Kelleher C. Incontinence, Patient-Reported Outcome Assessment. 4th 
International Consultation on Incontinence; July 5–8, 2008, 2009; Paris Data Collection 
Tools/Case Report Forms. 


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Uebersax JS, Wyman JF, Shumaker SA, et al. Short forms to assess life quality and symptom 
distress for urinary incontinence in women: the Incontinence Impact Questionnaire and the 
Urogenital Distress Inventory. Continence Program for Women Research Group. Neurourol 
Urodyn. 1995;14(2):131-9. 
 


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12 Appendices 
12.1 Appendix: Schedule of Events  
 
 


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Table 12–1 
Schedule of Events for Protocol G201002 
Procedure 
Screening 
Visit 
Additional 
Screening 
Procedures 
Baseline 
V1 
V2a 
V3 
V4 
V5 
V6  
V7 and V8 
Day or Week 
Days –28 to 
0 
Days –28 to 
0 
Week 0 
Week 1 
Week 4 
Week 8 
Week 12 or 
Early 
Withdrawal 
Week 16 or 
30 days after 
last dose of 
study drug 
Weeks 20 
and 28 
Visit Window (days) 
– 
– 
– 
±3 
±3 
±3 
±3 
±3 
±3 
Informed consent 
X 
 
 
 
 
 
 
 
 
Eligibility criteria review 
X 
 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
 
X 
X 
X 
X 
X 
X 
X 
MESA incontinence 
questionnaire 
X 
 
 
 
 
 
X 
 
 
Bladder stress test 
X 
 
 
 
 
 
X 
 
 
Heightb and weight 
X 
 
 
 
X 
X 
X 
X 
 
Vital signs 
X 
 
X 
 
X 
X 
X 
X 
 
Pelvic examination 
X 
 
 
 
 
 
X 
 
 
Physical examination 
X 
 
 
 
X 
X 
X 
X 
 
UA dipstick (with culture as 
needed) 
X 
 
X 
 
X 
X 
X 
 
 
CMP (Chem 14 panel)c 
X 
 
 
 
X 
X 
X 
X 
 
Viral serologyd 
X 
 
 
 
 
 
 
 
 
Serum FSH 
X 
 
 
 
 
 
 
 
 
CBC 
X 
 
 
 
 
 
X 
X 
 
Lipid panel 
X 
 
 
 
 
 
X 
X 
X 
C-reactive protein (CRP) 
X 
 
 
 
 
 
X 
X 
 
Hormone panel 
X 
 
 
 
 
 
X 
X 
X 


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Procedure 
Screening 
Visit 
Additional 
Screening 
Procedures 
Baseline 
V1 
V2a 
V3 
V4 
V5 
V6  
V7 and V8 
Day or Week 
Days –28 to 
0 
Days –28 to 
0 
Week 0 
Week 1 
Week 4 
Week 8 
Week 12 or 
Early 
Withdrawal 
Week 16 or 
30 days after 
last dose of 
study drug 
Weeks 20 
and 28 
Visit Window (days) 
– 
– 
– 
±3 
±3 
±3 
±3 
±3 
±3 
SHBG 
X 
 
 
 
 
 
X 
X 
X 
Mammographye 
 
X 
 
 
 
 
 
 
 
Transvaginal ultrasoundf 
 
X 
 
 
 
 
X 
 
 
Electrocardiography 
 
X 
 
 
 
 
 
 
 
24-Hour pad weight test 
 
X 
 
 
X 
X 
X 
X 
X 
3-Day voiding diary 
 
X 
 
 
X 
X 
X 
X 
X 
Randomization 
 
 
X 
 
 
 
 
 
 
Adverse event reviews 
 
 
X 
X 
X 
X 
X 
X 
X 
UDI-6 
 
 
X 
 
X 
X 
X 
X 
X 
IIQ-7 Short Form 
 
 
X 
 
X 
X 
X 
X 
X 
I-QOL 
 
 
X 
 
X 
X 
X 
X 
X 
FSFI  
 
 
X 
 
X 
X 
X 
X 
X 
PGI-S 
 
 
X 
 
X 
X 
X 
X 
X 
PGI-I 
 
 
 
 
X 
X 
X 
X 
X 
Vaizey Incontinence 
Severity Score 
 
 
X 
 
X 
X 
X 
X 
X 
Dispense study drug 
 
 
X 
 
X 
X 
 
 
 
Collect unused study drug 
 
 
 
 
X 
X 
X 
 
 
Abbreviations: CBC, complete blood count; CMP, comprehensive metabolic panel; FSFI, Female Sexual Function Index; FSH, follicular-stimulating 
hormone; IIQ-7, Incontinence Impact Questionnaire; I-QOL, Incontinence Quality of Life questionnaire; MESA, Medical, Epidemiological, and 
Social Aspects of Aging; PGI-I, Patient Global Impression of Improvement; PGI-S, Patient Global Impression of Severity; SHBG, sex 
hormone-binding globulin; UA, urinalysis; UDI-6, Urogenital Distress Inventory; V, visit. 


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a 
This visit is a telephone call.  
b 
Height will be measured at screening only.  
c 
Comprehensive metabolic panel (Chem 14) including serum calcium and liver function tests (can be repeated once at the Investigator’s 
discretion); the results of all tests/re-tests must be available within the screening window and prior to randomization. 
d 
The viral serology panel includes testing for active hepatitis B and active hepatitis C. 
e 
Evidence of mammography conducted within the 6 months prior to screening is acceptable and will remove the need for a mammography during 
screening.  
f 
The transvaginal ultrasound should be administered at the end-of-treatment visit if earlier than Week 12.  
 
 


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12.2 Appendix: Medical, Epidemiological, and Social Aspects of Aging 
Questionnaire  
 
 


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12.3 Appendix: Patient Global Impression of Severity 
 
 


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12.4 Appendix: Patient Global Impression of Improvement  
 
 


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12.5 Appendix: Urogenital Distress Inventory  
 
 


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12.6 Appendix: Incontinence Impact Questionnaire Short Form  
 
 


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12.7 Appendix: Incontinence Quality of Life 


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12.8 Appendix: Female Sexual Function Index 


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12.9 Appendix: Vaizey Incontinence Score 
 
 


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