Conditions: Stress Urinary Incontinence
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 19
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine whether GTx-024 is safe and effective in the treatment of stress urinary incontinence in postmenopausal women.

Detailed description:

Arms:
arm 1: GTx-024 softgel capsules will be administered once daily to a total dose of 3 mg for up to 12 weeks.

Interventions: intervention 1: GTx-024
Intervention descriptions: intervention 1: GTx-024 softgel capsules will be administered once-daily to a total dose of 3 mg

Protocol document:
Prot_SAP_000.pdf: 
 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 1 of 76 
 
GTx-024 as a Treatment for Stress Urinary Incontinence in 
Women: A Proof of Concept Study 
 
Protocol G201001 
Version 1.0  
Confidential 
 
Principal Investigator: Kenneth M. Peters, M.D. 
Professor and Chair of Urology 
Oakland University William Beaumont School of Medicine  
3535 West 13 Mile Road, Suite 438 
Royal Oak, MI 48073-6769 
(248) 551-0387 
E-mail: kmpeters@beaumont.edu 
 GTx Program Official: Michael DeSordi, BS, MBA 
Senior Director, Clinical Operations 
GTx, Inc. 
175 Toyota Plaza, 7th Floor 
Memphis, TN 38103 
Tel: (901) 261-3795 
Fax: (901) 271-8679 
E-mail: mdesordi@gtxinc.com  
 
Version Number: 1.0 07 August 2015  
Protocol Amendment Number: N/A 
This template is adapted from the ICH guidance document E6 (Good Clinical Practice), 
Section 6.


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 2 of 76 
CONFIDENTIALITY STATEMENT 
 
All information contained within this document are the joint property of GTx, Inc. and 
Oakland University William Beaumont School of Medicine (collectively, the Parties), and 
are considered confidential. Acceptance of this document constitutes the agreement by 
the Parties that no information contained herein may be divulged or disclosed by either 
Party to third parties without prior written approval of the other Party, except to the extent 
necessary to obtain informed consent from subjects who participate in this study or in 
connection with the reporting of serious adverse events as set forth in Section 9.2. 
Acceptance of this document by any recipient other than the Parties constitutes the 
agreement by such recipient that no information contained herein may be divulged or 
disclosed to third parties without prior written approval of GTx and Oakland University 
William Beaumont School of Medicine. Do not copy this protocol without the express 
written permission of GTx, Inc. and Oakland University William Beaumont School of 
Medicine.  


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 3 of 76 
STATEMENT OF COMPLIANCE 
The 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) ICH E6;  62 Federal Register 25691 (May 9, 1997)  
  




 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 5 of 76 
TABLE OF CONTENTS 
PROTOCOL SIGNATURE PAGE 
4 
TABLE OF CONTENTS 
5 
1 
PROTOCOL SUMMARY 
13 
1.1 
NAMES, AFFILIATIONS, AND ROLES OF CONTRIBUTING INDIVIDUALS 
18 
2. INTRODUCTION: BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE 
20 
2.1 
BACKGROUND/RATIONALE 
20 
2.2 
RISKS ANALYSIS AND RISK ASSESSMENT 
26 
 
2.2.1 POTENTIAL ANTICIPATED ADVERSE EVENTS 
26 
 
2.2.2 STUDY RISKS 
29 
3. OBJECTIVES 
30 
3.1 
PRIMARY OBJECTIVE 
30 
3.2 
SECONDARY OBJECTIVES 
30 
3.3 
STUDY ENDPOINTS 
32 
4. METHODOLOGY 
33 
4.1 
STUDY DESIGN 
33 
4.2 
MEDICAL MONITORING 
33 
5. STUDY ENROLLMENT AND WITHDRAWAL 
33 
5.1 
SUBJECT INCLUSION CRITERIA 
34 
5.2 
SUBJECT EXCLUSION CRITERIA 
34 
5.3 
STRATEGIES FOR RECRUITMENT, RETENTION, AND TO IMPROVE ADHERENCE TO 
INTERVENTION PROTOCOLS 
35 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 6 of 76 
5.4 
TREATMENT ASSESSMENT PROCEDURES 
35 
 
5.4.1 REASONS FOR WITHDRAWAL 
35 
 
5.4.2 EARLY TERMINATION OR SUSPENSION OF THE STUDY 
35 
6. STUDY INTERVENTION/INVESTIGATIONAL PRODUCT 
36 
6.1 
STUDY PRODUCT DESCRIPTION 
36 
6.2 
ACQUISITION 
36 
6.3 
FORMULATION, PACKAGING, AND LABELLING 
36 
6.4 
PRODUCT STORAGE AND STABILITY 
36 
6.5 
DOSAGE, PREPARATION, AND ADMINISTRATION OF STUDY 
INTERNEVTION/INVESTIGATIONAL PRODUCT 
36 
6.6 
ACCOUNTABILITY PROCEDURES FOR THE STUDY INVESTIGATIONAL PRODUCT(S) 36 
6.7 
ASSESSMENT OF SUBJECT COMPLIANCE WITH STUDY 
INTERVENTION/INVESTIGATIONAL PRODUCT 
37 
6.8 
CONCOMITANT MEDICATIONS/TREATMENTS 
38 
7. STUDY SCHEDULE 
38 
7.1 
STUDY VISITS 
38 
7.2 
EARLY TERMINATION 
40 
8. STUDY PROCEDURES/EVALUATIONS 
40 
9. ASSESSMENT OF SAFETY 
43 
9.1 
METHODS AND TIMING FOR ASSESSING, RECORDING, AND ANALYZING SAFETY 
PARAMETERS 
43 
 
9.1.1 ADVERSE EVENTS 
43 
 
9.1.2 INTENSITY OF EVENT 
44 
 
9.1.3 DRUG – ADVERSE EVENT RELATIONSHIP 
44 
 
9.1.4 SERIOUS ADVERSE EVENTS 
45 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 7 of 76 
9.2 
REPORTING PROCEDURES 
46 
 
9.2.1 SERIOUS ADVERSE EVENTS 
46 
 
9.2.2 REGULATORY REPORTING 
47 
9.3 
TYPE AND DURATION OF FOLLOW-UP OF SUBJECTS AFTER ADVERSE EVENTS 
48 
9.4 
HALTING RULES 
48 
10. STATISTICAL CONSIDERATIONS 
49 
10.1 
STATISTICAL METHODS 
49 
11. QUALITY CONTROL AND QUALITY ASSURANCE 
51 
12. ETHICS/PROTECTION OF HUMAN SUBJECTS 
52 
12.1 
ETHICAL CONSIDERATIONS 
52 
12.2 
INSTITUTIONAL REVIEW BOARD/ INDEPENDENT ETHICS COMMITTEE 
52 
12.3 
PRE-STUDY DOCUMENTATION 
53 
12.4 
INFORMED CONSENT PROCESS 
53 
12.5 
SUBJECT CONFIDENTIALITY 
54 
12.6 
PROTOCOL ADHERENCE 
54 
12.7 
PERMISSION TO REVIEW SUBJECTS’ SOURCE RECORDS 
54 
12.8 
PROTOCOL AMENDMENTS 
54 
12.9 
CHANGE IN INVESTIGATOR 
55 
12.10 STUDY DISCONTINUATION 
55 
12.11 INDEMNITY 
55 
13. DATA HANDLING AND RECORD KEEPING 
55 
13.1 
DATA CAPTURE METHODS 
56 
 
13.1.1 DATA COLLECTION 
56 
13.2 
STUDY SITE RESPONSIBILITIES 
56 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 8 of 76 
13.3 
CRF TIMING/REPORTS 
56 
13.4 
STUDY RECORDS RETENTION 
56 
13.5 
PROTOCOL DEVIATIONS 
57 
14. PUBLICATION POLICY 
58 
15. LITERATURE REFERENCES 
59 
1. APPENDIX A: MESA URINARY QUESTIONNAIRE 
64 
2. APPENDIX B: PATIENT GLOBAL IMPRESSION OF SEVERITY 
(PGI-S) SCALE AND PATIENT GLOBAL IMPRESSION OF 
IMPROVEMENT (PGI-I) SCALE 
67 
3. APPENDIX C: URINARY DISTRESS INVENTORY (UDI-6) AND 
INCONTINENCE IMPACT QUESTIONNAIRE (IIQ-7) 
68 
4. APPENDIX D: FEMALE SEXUAL FUNCTION INDEX (FSFI) 
70 
5. APPENDIX E: VOIDING DIARY 
76 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 9 of 76 
LIST OF ABBREVIATIONS 
 
 
AE 
Adverse Event 
AMDC 
Adult Muscle Derived Cells 
ALT 
Alanine Transaminase 
AR 
Androgen Receptor 
AR+/TNBC 
AR Positive, Triple Negative Breast Cancer 
AST 
Aspartate Aminotransferase 
BCRP 
Breast Cancer Resistance Protein 
BMI 
Body Mass Index 
°C 
Degrees Celsius 
CB 
Clinical Benefit 
CBC 
Complete Blood Count 
CD-ROM 
Compact Disk Read Only Memory 
CFR 
Code Of Federal Regulations 
CR 
Complete Response 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CTCAE 
Common Terminology Criteria For Adverse Events 
DHEA 
Dehydroepiandrosterone 
DHT 
Dihydrotestosterone 
DSMB 
Data And Safety Monitoring Board 
DXA 
Dual-Energy X-Ray Absorptiometry 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EOS 
End of Study 
CRF 
Case Report Form 
EMG 
Electromyography 
ER 
Estrogen Receptor 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 10 of 76 
ER+BC 
Estrogen Receptor Positive Breast Cancer 
ºF 
Degrees Fahrenheit 
FDA 
Food And Drug Administration 
FSFI 
Female Sexual Function Index 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practices 
GGT 
Gamma-Glutamyl Transferase  
GTx 
GTx, Inc. 
GTx-024 
Enobosarm 
HBsAg 
Hepatitis B Surface Antigen 
HDL 
High-Density Lipoprotein 
HIV 
Human Immunodeficiency Virus 
HRQOL 
Health Related Quality Of Life 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference On Harmonization 
IEC 
Independent Ethics Committee 
IIQ-7 
Incontinence Impact Questionnaire 
IMP 
Investigational Medicinal Product 
IN 
Investigator Notification 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISD 
Intrinsic Sphincter Deficiency 
LBM 
Lean Body Mass 
LDL 
Low-Density Lipoprotein 
LUTS 
Lower Urinary Tract Symptoms 
MESA 
Medical, Epidemiological And Social Aspects Of Aging 
Mg 
Milligram 
MMRM 
Mixed Model Repeat Measurement 
MRI 
Magnetic Resonance Imaging 
MUCP 
Maximum Urethral Closure Pressure 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 11 of 76 
NA 
Not Applicable 
NCI-CTCAE 
National Cancer Institute-Common Terminology Criteria For 
Adverse Events 
NOAEL 
No-Observable-Adverse-Effect-Levels 
NSCLC 
Non-Small Cell Lung Cancer 
PCOS 
Polycystic Ovarian Syndrome 
Pgi-I 
Patient Global Impression Of Improvement Scale 
Pgi-S 
Patient Global Impression Of Severity Scale 
PFM 
Pelvic Floor Muscle 
PFS 
Progression Free Survival 
PI 
Principal Investigator 
PO 
Per Os (Oral) 
PrR 
Progesterone Receptor 
PR 
Partial Response 
PSA 
Prostate Specific Antigen 
PT 
Physical Therapy 
PVR 
Post Void Residual 
QA 
Quality Assurance 
QOL 
Quality of Life 
RECIST 
Response Evaluation Criteria In Solid Tumors 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SARM 
Selective Androgen Receptor Modulator 
SCP 
Stair Climb Power 
SD 
Stable Disease 
SHBG 
Sex Hormone Binding Globulin 
SUI 
Stress Urinary Incontinence 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TEAE 
Treatment Emergent Adverse Events 
TNBC 
Triple Negative Breast Cancer 
 
 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 12 of 76 
UA 
Urinalysis 
UDI 
Urinary Distress Inventory 
UI 
Urinary Incontinence  
ULN 
Upper Limit of Normal 
UNK 
Unknown 
UPP 
Urethral Pressure Profile 
US 
Ultrasound 
UTI 
Urinary Tract Infection 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 13 of 76 
1 PROTOCOL SUMMARY 
Title:  
GTx-024 as a Treatment for Stress Urinary Incontinence in Women: A 
Proof of Concept Study 
Sponsor:  
GTx, Inc. 
Indication:  
Stress Urinary Incontinence (SUI) 
Study Design:  
This is a single site, single-arm, open-label proof of concept feasibility 
study.  
Objectives:  
Primary Objective  
Describe the effect of 12 weeks of treatment of GTx-024 on the number of 
stress incontinence episodes/day as assessed by the 3 day voiding diary. 
 
Secondary Objectives 
Describe the effect of 12 weeks of treatment of GTx-024 on the number of 
voids/day as assessed by the 3 day voiding diary. 
 
Describe the effect of 12 weeks of treatment of GTx-024 on urine volume 
per void as assessed by the 3 day voiding diary. 
 
Describe the effect of 12 weeks of treatment of GTx-024 on SUI as 
assessed by 24 hour pad weight test. 
 
Describe the effect of 12 weeks of treatment of GTx-024 on SUI as 
assessed by the Urethral Pressure Profile (UPP). 
 
Describe the effect of 12 weeks of treatment of GTx-024 on SUI as 
assessed by the Bladder Stress Test. 
 
Describe the effect of 12 weeks of treatment of GTx-024 on patient 
reported stress urinary incontinence symptoms as assessed by the MESA 
Urinary Questionnaire. 
 
Describe the effect of 12 weeks of treatment of GTx-024 on patient 
reported impression of stress urinary incontinence severity as assessed 
by the Patient Global Impression of Severity Scale (PGI-S) 
 
Describe the effect of 12 weeks of treatment of GTx-024 on patient 
reported impression of improvement as assessed by the Patient Global 
Impression of Improvement Scale (PGI-I). 
 
Describe the effect of 12 weeks of treatment of GTx-024 on patient 
reported urogenital distress as assessed by the Urinary Distress Inventory 
Questionnaire (UDI-6). 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 14 of 76 
 
Describe the effect of 12 weeks of treatment of GTx-024 on patient 
reported impact of urinary incontinence on daily life as assessed by the 
Incontinence Impact Questionnaire (IIQ-7). 
 
Describe the effect of 12 weeks of treatment of GTx-024 on patient 
reported sexual function as indicated on the completion of the Female 
Sexual Function Index Questionnaire (FSFI). 
 
Describe the effect of 12 weeks of treatment of GTx-024 on pelvic floor 
muscles as measured by MRI.  
 
Safety objective:  
To describe the safety profile of GTx-024 3 mg PO daily in subjects with 
SUI. 
Target Population:  
Adult postmenopausal women with SUI 
  
Subject Inclusion Criteria: Subjects eligible for inclusion in this study 
must meet all of the following criteria:  
 
1. Give voluntary, written and signed, informed consent 
2. Female 
3. Age 18 to 80 years old  
4. Clinically confirmed as postmenopausal. Subjects must have 
undergone the onset of spontaneous, medically induced or surgical 
menopause prior to the start of this study. Postmenopausal is defined 
as 12 months of spontaneous amenorrhea or 6 months of 
spontaneous amenorrhea with serum FSH levels > 40 mIU/ml or 6 
weeks postsurgical bilateral oophorectomy with or without 
hysterectomy. 
5. SUI symptoms for at least 6 months duration 
6. Predominant SUI (MESA questionnaire) 
7. 24 hour pad weight >3 gms at baseline 
8. At least 4, but no more than 15, SUI episodes on each day of the 3 
day baseline voiding diary 
9. Serum AST and ALT within normal limits  
10. Total bilirubin within normal limits 
11. Positive Bladder Stress Test 
12. Subject agrees to not start any new treatment (medication or 
otherwise) that is known to affect lower urinary tract function 
throughout the treatment and follow up periods. 
13. Subject agrees to maintain on a stable dose of any medication known 
to affect lower urinary tract function, including but not limited to 
anticholinergics, tricyclic antidepressants, or alpha-adrenergic 
blockers, throughout the treatment and follow-up period.  


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 15 of 76 
 
Subject Exclusion Criteria: Subjects eligible for this study must not meet 
any of the following criteria:  
 
1. Pelvic floor physical therapy within the last 6 months    
2. History of pelvic radiation treatment  
3. History of urethral diverticula 
4. History of urethral sling, anterior prolapse repair, ureteral bulking 
agents and/or other SUI procedure or surgery 
5. Known vesicoureteral reflux, vaginal prolapse beyond the introitus, or 
other significant pelvic floor abnormalities 
6. Patient has urinary incontinence of neurogenic etiology 
7. Patient is morbidly obese (defined as 100 pounds over their ideal body 
weight, or body mass index 40 or greater) 
8. Chronic hepatitis 
9. Hepatic cirrhosis 
10. HIV and/or hepatitis A, B, or C 
11. Subjects taking systemic hormone products (excludes intravaginal 
application of estradiol topical/tablet agents and hormones delivered 
via vaginal rings)   
12. Subjects with a history of breast or endometrial cancer.  
13. Subjects with cerebrovascular disease, thromboembolic disorders, 
myocardial infarction, or angina. 
14. Subject with an entry measurement of > 5 mm endometrial stripe 
thickness as measured by MRI. 
15. Clinically confirmed urinary tract infection 
16. Any other condition which per investigators’ judgement may increase 
subject risk 
 
Phase:  
2  
Number of Sites:  
1 
Study Duration:  
12 weeks 
Number of Subjects / 
Participation Duration:  
Up to 35 subjects. Each subject may complete up to 5 months of study 
participation.  
Estimated Time to 
Complete Enrollment:  
6 months 
Indication for Product 
Use:  
GTx-024 has been tested as a treatment for muscle wasting associated 
with cancer cachexia, but is not currently marketed.  
Instructions for 
Product Use:  
Subjects will be instructed to take one 3 mg softgel capsule per day by 
mouth, without regard to food intake. 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 16 of 76 
Statistical 
Considerations:  
This is a proof of concept feasibility study, so no power calculation is 
needed. Therefore, up to 35 subjects meeting inclusion/exclusion criteria 
will be recruited until 30 subjects have completed treatment. Descriptive 
statistics will be performed to explore changes in primary and secondary 
outcomes measures between baseline and end of treatment. The primary 
efficacy measure will be a reduction in the number of stress incontinence 
episodes/day. Secondary efficacy measures will include reduction in 
number of voids per day, volume of voids, 24 hour pad weight, responses 
to validated questionnaires, changes in UPP measures, changes in 
sexual function, and changes in pelvic floor muscles as measured by 
MRI.  
  
Safety will be determined by the number and type of adverse events 
reported during treatment. Various imputation methods may be explored.  
Study 
Intervention/Treatment:  
Participation in this study includes 5 in person study visits and two 
telephone and/or mailed questionnaire visits. Additional in person and/or 
telephone visits may be added as needed.  
 
Study subjects will receive 3 mg of GTx-024 orally daily.  


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 17 of 76 
Table 1. Schedule of Measures. 
 
Screening 
Visit 
Days -21-0 
 
 
Clinic Visit 
Additional 
Screening 
Days -21-0 
 
 
Clinic Visit 
Visit 1. 
Baseline3 
Week 0 
 
 
Clinic Visit 
Visit 2. 
 
Week 1± 3 
days 
 
Phone Call 
Visit 3. 
 
Week 4 ± 3 
days 
 
Clinic Visit 
Visit 4. 
 
Week 8 ± 3 
days 
 
Clinic Visit 
Visit 5. 
 
Week 12 ± 3 
days 
 
Clinic Visit 
Visit 6. 
 
Week 16 ± 
7 days 
 
Phone Call 
and Mail 
Consent 
x 
 
 
 
 
 
 
 
Inclusion/Exclusion 
x 
 
x 
 
 
 
 
 
History 
 
 
x 
 
 
 
 
 
Interview/Vital 
Signs 
x 
 
x 
 
x 
x 
x 
 
Height/Weight 
x 
 
 
 
x 
x 
x 
 
24 hour Pad Weight 
Instruct 
 
x 
 
x 
x 
x 
 
3 day Voiding Diary 
Instruct 
 
x 
 
x 
x 
x 
 
Serum AST, ALT, 
Total Bilirubin 
x 
 
 
 
x 
x 
x 
 
Serum FSH¹ ,  
x 
 
 
 
 
 
 
 
CBC 
 
 
x 
 
 
 
x 
 
UA Dipstick (with 
culture as needed) 
x 
 
x 
 
 
 
x 
 
Lipid Panel 
 
 
x 
 
 
 
x 
 
Testosterone 
Levels 
 
 
x 
 
 
 
x 
 
SHBG 
 
 
x 
 
 
 
x 
 
UPP  
 
 
x 
 
 
 
x 
 
Pelvic MRI 
 
x 
 
 
 
 
x 
 
Bladder Stress Test 
x 
 
 
 
 
 
x 
 
Mammogram² 
 
x 
 
 
 
 
 
 
Begin Daily4 
Treatment 
 
 
x 
 
 
 
 
 
End Treatment 
 
 
 
 
 
 
x 
 
Concomitant Meds 
x 
 
x 
x 
x 
x 
x 
x 
Adverse Events 
 
 
x 
x 
x 
x 
x 
x 
HIV, Hep A, B, C 
Testing 
x 
 
 
 
 
 
 
 
UDI-6;  IIQ 
 
 
x 
 
x 
x 
x 
x 
PGI-S 
 
 
x 
 
x 
x 
x 
x 
MESA 
Questionnaire 
x 
 
 
 
x 
x 
x 
x 
PGI-I 
 
 
 
 
x 
x 
x 
x 
FSFI Questionnaire  
 
 
x 
 
x 
x 
x 
x 
Bladder Scan PVR 
 
 
x 
 
x 
x 
x 
 
Ciprofloxacin 500 
mg po 
(or equivalent) 
 
 
x 
 
 
 
x 
 
Focused Physical 
Exam 
 
 
x 
 
 
 
x 
 
¹ Age 18 to 80 years old is clinically confirmed as postmenopausal. Subjects must have undergone the onset of spontaneous, medically induced or 
surgical menopause prior to the start of this study. Postmenopausal is defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous 
amenorrhea with serum FSH levels > 40 mIU/ml or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. 
² Mammogram within the last 6 months conducted outside the protocol may be utilized. Provided the data is available for assessment in this protocol, 
an additional mammogram will not be required. 
3Visit 1, Baseline, may not be completed until all results of screening tests have been evaluated. 
4 After confirmation of meeting all eligibility criteria. 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 18 of 76 
ROLES AND RESPONSIBILITIES  
1.1 
NAMES, AFFILIATIONS, AND ROLES OF CONTRIBUTING 
INDIVIDUALS 
Principal Investigator 
Kenneth M. Peters, M.D.  
Professor and Chair of Urology 
Oakland University William Beaumont School of Medicine 
William Beaumont Hospital, Royal Oak 
3535 W. 13 Mile Road Ste. 438 
Royal Oak, MI 48073-6769 
(248) 551-3637 
E-mail: kmpeters@beaumont.edu  
 
GTx, Inc. 
Diane C. Young, M.D. 
Vice President, Chief Medical Officer 
GTx, Inc. 
175 Toyota Plaza, 7th Floor 
Memphis, TN 38103 
Tel: (901) 507-6948 
Fax: (901) 271-8679 
E-mail: dyoung@gtxinc.com 
 
Michael DeSordi, BS, MBA 
Senior Director, Clinical Operations 
GTx, Inc. 
175 Toyota Plaza, 7th Floor 
Memphis, TN 38103 
Tel: (901) 261-3795 
Fax: (901) 271-8679 
E-mail: mdesordi@gtxinc.com 
 
Mayzie Johnston, PharmD 
Vice President, Medical Affairs and Clinical Operations 
GTx, Inc. 
175 Toyota Plaza, 7th Floor 
Memphis, TN 38103 
Tel: (901) 261-3858 
Fax: (901) 271-8677 
E-mail: mjohnston@gtxinc.com 
 
 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 19 of 76 
Jeff Hesselberg, MBA  
Vice President, Regulatory Affairs, Corporate Quality & Drug Safety 
GTx, Inc. 
175 Toyota Plaza, 7th Floor 
Memphis TN 38103 
Tel: (901) 523-9700 
Fax: (901) 271-8707 
E-mail: jhesselberg@gtxinc.com 
 
Michael L. Hancock, MS 
Director, Biostatistics 
GTx, Inc. 
175 Toyota Plaza, 7th Floor 
Memphis TN 38103 
Tel: (901) 271-8700 
Fax: (901) 271-8677 
E-mail: mhancock@gtxinc.com 
 
Beaumont Hospital Clinical Research 
Larry T. Sirls, M.D., FACS 
Professor of Urology 
Oakland University William Beaumont School of Medicine 
William Beaumont Hospital, Royal Oak 
3535 W. 13 Mile Road Ste. 438 
Royal Oak, MI 48073-6769 
E-mail: lsirls@beaumont.edu 
 
Kim Killinger, RN, MSN 
William Beaumont Hospital, Royal Oak  
3535 W. 13 Mile Road Ste. 438 
Royal Oak, MI 48073-6769 
E-mail: KKillinger@beaumont.edu  
 
Deborah Hasenau, RN, MS 
William Beaumont Hospital, Royal Oak  
3535 W. 13 Mile Road Ste. 438 
Royal Oak, MI 48073-6769 
E-mail: Deborah.Hasenau@beaumont.edu 
 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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2. 
INTRODUCTION: BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE 
2.1 
BACKGROUND/RATIONALE 
Stress urinary incontinence (SUI), the involuntary leakage of urine during activities that 
increase abdominal pressure (e.g. coughing, sneezing, physical exercise), affects up to 
35% of adult women (Luber, 2004). Urinary incontinence and pelvic floor disorders are 
major health problems for women especially as they age.  
There are a variety of treatments that may be used to treat SUI in women (Rovner, 
2004). Behavioral modification and pelvic floor physical therapy are common initial 
treatment approaches even though surgical procedures (e.g. sling; bladder neck 
suspension) are often ultimately the most effective. Biological and other materials for 
injection into the urethra have also been marketed for treating intrinsic sphincter 
deficiency (ISD), a cause of SUI symptoms. In a study of autologous fat injected into the 
urethral sphincter only 22% of patients improved compared to 21% after placebo 
injection (Lee, 2001). However, the injection of muscle derived stem cells (AMDC) is a 
promising new therapy for SUI currently being tested in clinical trials. In a dose 
escalation study of AMDC, injected into the urethral sphincter, all dose groups had 
significantly fewer diary stress leaks at 12 months, but only patients who received the 
highest dose of AMDC had statistically significant reduction in mean pad weight (Peters, 
2014). Pharmacologic therapies for SUI also have been tested with varying results. In a 
study of duloxetine (a selective serotonin reuptake inhibitor), the median incontinence 
episode frequency decreased 41% in the placebo group compared to 54% receiving 
duloxetine 20 mg/day, 59% for duloxetine 40 mg/day, and 64% for duloxetine 80 
mg/day (Norton, 2002). Dmochowski and colleagues also demonstrated a statistically 
significant reduction in incontinence episode frequency with duloxetine therapy 
compared with placebo (50% vs 27%, respectively) (Dmochowski, 2003).  
 
Pelvic floor muscle relaxation has been found to correlate with lower urinary tract 
symptoms (LUTS). 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 prolapse and urinary incontinence. As 
such, efforts have been made to improve pelvic floor muscle strength and function 
especially in post-reproductive and elderly women, to improve, if not cure, LUTS 
(specifically urinary incontinence, urinary frequency and nocturia). However, pelvic floor 
physical therapy (PT) is often less effective than more aggressive treatment such as 
surgery (Labrie, 2013). A prospective randomized trial of PT vs. surgery showed that 
49% of women in the PT group crossed over to surgical treatment. Others have shown 
that after 3 to 15 years, 25 to 50% of women initially treated with physiotherapy have 
proceeded to surgery (Cammu, 2004; Lamers, 2007; B. K, Kvarstein, 2005). Yet, 
surgery is much more invasive and is associated with risk and complications (Brubaker 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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et al, 2011). Treatments with better outcomes than pelvic floor PT or those that augment 
the response to pelvic floor PT, are clearly needed. Androgen supplementation may be 
a novel treatment to augment pelvic floor muscle response and improve objective and 
subjective outcomes for SUI. Basic science literature indicates that smooth muscle cells 
in various female urogenital tissues have expressed androgen receptors (Berman, 
2003) and that the levator ani and urethral sphincter, both containing large numbers of 
androgen receptors (Copas, 2001; Celayir, 2002), are sensitive to androgens (Nnodim, 
1999; Nnodim, 2001).  
 
In addition to the use of instruments to measure the efficacy of therapeutic approaches 
to SUI, MRI measurements of the pelvic floor have been utilized as tools to determine 
the impact on the supporting pelvic floor muscles (Tunn et al, 1999).  Measurements of 
the levator hiatus, including the area, as well as, the anteroposterior and transverse 
diameters, have been demonstrated to be reproducibly measured and correlative with 
pelvic floor damage (Lammers et al., 2013).  Similar measurements have been made to 
examine the recovery of levator ani muscle after vaginal delivery (Tunn et al, 1999).  
Therefore, MRI based measurements can provide for a non-invasive quantitative 
assessment of pelvic floor muscles and their potential response to therapeutic 
approaches with additional value to that provided by symptomatic assessments alone. 
MRI will also be used in this study to assess endometrial thickness at baseline. An 
endometrial stripe > 5 mm may exclude the subject from participating (Stanislavsky, 
Weerakkody, et al., 2015; Nakamura et al., 2014). 
 
Androgen receptors in the pelvic floor/urethra 
The para-urethral extracellular matrix is a target for sex steroid hormones, however the 
effects are not well known. Androgens stimulate collagen synthesis and inhibit 
degradation leading to increased collagen fibre compactness (Shin, 2005;  Berger, 
2005). Androgen receptors are densely expressed in both muscle and stromal cells of 
the levator ani muscle and fascia in women (Copas, 2001) and the levator ani muscle is 
considered to be one of the most androgen sensitive tissues in the body.  
 
Impact of anabolic steroids 
The effect of testoterone on urodynamic findings and histopathomorphology of the 
pelvic floor muscles has been studied in rat models of SUI. Testosterone was found to 
improve leak point pressures and significantly increase the size of myofibers in treated 
rats, suggesting that testosterone has both preventative and curative effects on rat 
models of SUI (Mammadov,2011). Since free testosterone levels were also higher in the 
treated group, there is potential for concerns regarding side effects of supplemental 
steroidal testosterone in women with SUI.  
 
The anabolic effects of androgens in men have been widely studied, but less is known 
about the role and use of androgens in women. Prior studies have found that urinary 
levels of androgens were significantly higher in postmenopausal patients with SUI than 
in postmenopausal patients without incontinence (Jung, 2001). Furthermore, 
concentrations of androgen metabolites in urine of these patients were related positively 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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to the bladder neck descensus when measured by perineal ultrasound (a_Bai, 2003 ). 
Aizawa K et al. and others have published data demonstrating that increases in muscle 
mass due to resistance training or exercise is due, at least in part, to increases in local 
androgen concentrations and expression of androgen-synthesizing enzymes (Aizawa K, 
2011). These findings support the notion that pelvic floor muscle strengthening exercise 
improves SUI symptoms by increasing androgen levels locally. These and other studies 
suggest that androgens may play a substantial role in SUI and that androgen 
metabolites might be involved in the relaxation of bladder muscle (b_Bai, 2003). This 
relaxation effect on the bladder may be related to the up regulation of nitric oxide 
synthase by androgens to produce more nitric oxide. The action of androgen on the 
lower urinary tract and pelvic floor is complex and may depend on anabolic effects, 
hormonal modulation, receptor expression, nitric oxide modulation, or combination of 
these factors (Ho MH, 2004). 
 
Intriguing data come from studies conducted in women with polycystic ovarian 
syndrome (PCOS). PCOS is a hyper-androgenic disorder (>70 ng/dL compared to 15-
50 ng/dL in normal pre-menopausal women) and clinical studies have demonstrated 
that PCOS can eliminate the increased risk for UI observed in obese women. 
Furthermore, obese women with PCOS have a similar prevalence of UI as those 
considered to have a normal body mass index (Montezuma T, 2011). In a separate 
study, none of the women with PCOS (18.6% with UI) suffered from UI compared to 
matched controls,even though pelvic floor muscle strength was not different (Antonio FI, 
2013). These studies support the hypothesis that women with higher androgen levels, 
or potentially women treated with a selective androgen receptor modulator  
(SARM) will show improvements in UI symptoms. 
  
Selective androgen receptor modulators  
Although anabolic steroids may increase muscle mass and strength, lack of oral 
bioavailability and known potential risks have limited their use. Selective androgen 
receptor modulators (SARMS) have great potential to achieve similar benefits of 
anabolic steroid therapy (improved muscle mass, cholesterol/triglyceride levels, glucose 
metabolism, and bone density) with fewer adverse effects, such as hirsuitism and acne, 
in women.  
 
SARMS may provide a new therapeutic option for pelvic floor and lower urinary tract 
disorders, as both testosterone and its more potent metabolite converted by 5-a 
reductase, dihydrotestosterone (DHT), have anabolic effects on muscle. The potential 
for SARMS as a treatment for SUI is strengthened by studies showing that urethral 
closure pressure is the factor most strongly associated with SUI (Delancey, 2007;  
Delancy, 2008). This finding is supported by both morphological and electromyographic 
(EMG) evidence. In imaging studies, the striated urethral sphincter has been found to 
be smaller in women with SUI compared to continent controls (Athanasiou, 1999;  
Morgan; 2009). In EMG studies, the striated urethral sphincters of women with SUI 
exhibit smaller EMG amplitudes and shorter motor-unit-potential durations, with more 
phases, than continent controls (Kenton, 2011; Takahashi, 2000), indicating primarily 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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myogenic changes. Furthermore, it is well accepted that pelvic floor muscle (PFM) 
rehabilitation is an effective treatment for SUI (Hay-Smith, 2009). PFM rehabilitation 
may be effective because it strengthens not only the pelvic floor but may also 
strengthen the striated urethral sphincter. This idea is supported by a recent publication 
that reported, based on ultrasound (US), a 12-week PFM exercise program produced a 
significant increase in the cross-sectional area of the urethra, at the level of the striated 
urethral sphincter, in middle-aged women (McLean, 2013). Because of limits in the 
resolution of US images, the authors were not able to determine which part of the 
urethra hypertrophied. The investigators suggested that PFM rehabilitation in older 
women with SUI could condition the striated urethral sphincter leading to measurable 
hypertrophy, observable on MRI. 
 
In a later study, Madill extended the findings of the McLean group (Madill, 2014). Using 
MRI, they were able to differentiate between smooth and striated sphincter muscle 
layers and determined that changes occurred primarily in the striated urethral sphincter 
of older women. These findings suggest that not only does the striated urethral 
sphincter contract synergistically with PFMs during voluntary and automatic contractions 
[Nnodim, 1999; Nnodim, 2001; Celayir, 2002], but also that PFM rehabilitation stresses 
the striated urethral sphincter sufficiently to produce a muscular hypertrophy training 
effect (Madill, 2014). 
 
Selective androgen receptor modulators (SARMS) are currently in development for 
patients with muscle wasting secondary to cancer diagnosis. This class of drugs has 
been shown to stimulate the growth of skeletal muscle, similar to traditional anabolic 
steroids, but without undesirable side effects. SARMS, such as GTx-024, are orally 
bioavailable and tissue-selective, whereas testosterone and other anabolic steroids also 
have limited oral bioavailability and are only available in transdermal and intramuscular 
formulations potentially leading to skin reactions and fluctuations in serum 
concentrations of testosterone. SARMS may exhibit the beneficial effects of anabolic 
agents without the known associated risks (Mohler, Bohl, 2009).  
 
Recently utilizing an ovariectomized rat model to miminc SUI by disrupting urethral 
continence,  investigators demonstrated that the use of a SARM (GSK2849466A) was 
able to increase urethral baseline pressure (UBP) and the amplitude of urethral 
responses during sneezing (AURS) by 64% and 74%, respectively, as compared with 
the vehicle control.  Further, all of the rats (8/8) in the vehicle treated group experience 
fluid leakage during sneezing whereas only one of the rats (1/8) in the SARM treated 
group experience 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 provides further support to the potential use of 
SARMs for the treatment of SUI.  (Kadekawa et al, AUA Annual Meeting 2015, New 
Orleans, LA.  PD27-11) 
 
 
 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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Summary of GTx-024 
 
Preliminary studies related to stress urinary incontinence 
 
Extensive clinical data related to the use of GTx-024 are described below;  however, 
there are both pre-clinical and clinical data supporting the specific investigation of GTx-
024 for the treatment of SUI. Among the preclinical findings are that GTx-024 has 
androgenic and anabolic activity in male and female rat models (Preclinical Reports 
n030105GTx024 and n112012.1). 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 (similar to what might be expected in females), GTx-024 has the 
ability to induce hypertophy of the levator ani muscle to approximately 120% of an intact 
male. These studies together provide an approximation of the expected effect of GTx-
024, since currently there are no data in female models regarding levator ani 
hypertrophy or stress urinary inconcentince (Preclinical Report n112012.1). In two 
phase 3 studies (G300504 and G300505), 3 mg daily GTx-024 results in a mild increase 
(approximately 1.7%) in lean body mass with no differential effect in males and females. 
Based upon these preclinical and clinical analyses, we anticipate significant 
growth/bulking of the levator ani in females with SUI, which may also result in 
improvements in associated symptoms, and are therefore the focus of the study 
outlined herein. 
 
Ongoing and Completed Clinical Trials with GTx-024 
 
The following Phase 1, 2, and 3 clinical trials have been completed or are ongoing with 
GTx-024.   
1. Protocol G100401, a Phase 1 single ascending dose study in 96 healthy, young, 
male volunteers;  
2. Protocol G100402, a Phase 1 multiple ascending dose study in 50 healthy, 
young, male volunteers, and 23 elderly male volunteers with truncal obesity;  
3. Protocol G100503, a Phase 1 single dose pharmacokinetic study to assess the 
effect of a dosage regimen that simulates a sustained release formulation to an 
immediate release formulation in 18 healthy, young male volunteers and 18 
postmenopausal women;  
4. Protocol G100506, a Phase 1 single dose pharmacokinetic study to assess the 
relative bioavailability of a 3 mg hard shell capsule formulation to be used during 
continued clinical development and to assess the effect of food on the 
pharmacokinetics of the 3 mg softgel formulation in 27 healthy, young, male 
volunteers;  
5. Protocol 006, a Phase 1 single dose and multiple dose pharmacokinetic study in 
24 postmenopausal, Japanese women;  
6. Protocol G200501, a Phase 2 study in 60 postmenopausal women and 60 elderly 
men to assess lean body mass and physical function;  
7. Protocol 003, a Phase 1b study in 44 postmenopausal women;  
8. Protocol G200502, a Phase 2b study in 159 men and postmenopausal women 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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with cancer to assess lean body mass and physical function;  
9. Protocol G100511, a Phase 1 study to assess the effect of severe renal 
impairment on the pharmacokinetics of GTx-024;  
10. Protocol G100508, a Phase 1 study to assess the effect of mild and moderate 
hepatic impairment on the pharmacokinetics of GTx-024;  
11. Protocol G100509, a Phase 1 mass balance study of GTx-024 in healthy 
volunteers;  
12. Protocol G100507, a Phase 1 study to assess the pharmacokinetics and 
absolute oral bioavailability of GTx-024 in Caucasian and African American men 
and women;   
13. Protocol G100510, a single-dose, randomized, double-blind, comparative, 
positive and placebo-controlled, four-period crossover Phase 1 study to define 
the electrocardiogram (ECG) effects of GTx-024, at therapeutic and 
supratherapeutic doses, in healthy male and female subjects: a thorough ECG 
trial;   
14. Protocol G100512, a Phase 1 study to assess the effect of ketoconazole 
(Cytochrome P450, Family 3,Subfamily A [CYP3A4] inhibitor) on the 
pharmacokinetics of GTx-024;  
15. Protocol G100513, a Phase 1 study to assess the effect of rifampin (CYP3A4 
inducer) on the pharmacokinetics of GTx-024;  
16. Protocol G100514, a Phase 1 study to assess the pharmacokinetic drug: drug 
interaction of GTx-024 and celecoxib (CYP2C9);  
17. Protocol G100515, a Phase 1 study to assess the pharmacokinetic drug: drug 
interaction of GTx-024 and probenecid (UGT2B7);  
18. Protocol G100516, a Phase 1 study to assess the pharmacokinetic drug: drug 
interaction of GTx-024 and rosuvastatin (breast cancer resistance protein 
[BCRP]);  
19. Protocol G300504, a Phase 3 randomized, double-blind, placebo-controlled 
study of the effect of GTx-024 on muscle wasting in 321 subjects with non-small 
cell lung cancer receiving first line platinum plus a taxane chemotherapy;  
20. Protocol G300505, a Phase 3 randomized, double-blind, placebo-controlled 
study of the effect of GTx-024 on muscle wasting in 320 subjects with non-small 
cell lung cancer receiving first line platinum plus a non-taxane chemotherapy;  
21. Protocol G200801, an ongoing, Phase 2, open label study to examine AR status 
and the activity of GTx-024 hormonal therapy in 22 women with ER positive 
metastatic breast cancer who have previously responded to hormone therapy. 
22. Protocol G200802, an ongoing, a Phase 2, open label, multi-center, 
multinational, randomized, parallel design study investigating the efficacy and 
safety of GTx-024 on metastatic or locally advanced ER+/AR+ Breast Cancer 
(BC) in Postmenopausal Women. 
23. Protocol G200901, an ongoing, Phase 2, open label, multi-center, multinational 
study investigating the efficacy and safety of GTx-024 on advanced, Androgen 
Receptor-Positive Triple Negative Breast Cancer (AR+ TNBC)  
 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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2.2 
RISKS ANALYSIS AND RISK ASSESSMENT  
 
2.2.1 POTENTIAL ANTICIPATED ADVERSE EVENTS 
 
An adverse event is any clinical event that impacts, or that has the potential to impact, 
the health or safety of a Clinical Study subject caused by or associated with the study 
device and/or testing. Assessment for potential adverse events will be ongoing 
throughout this trial.  
 
The benefits of treatment may include improvement in the frequency, or severity of urine 
loss, and improvement in quality of life. Decreases in serum triglycerides, cholesterol, 
and body fat, and improvements in insulin resistance, lean body mass and physical 
endurance are also possible benefits. 
 
Adverse event tables and serious adverse events discussed  below and are presented 
separately by adverse events reported among healthy volunteers on a single trial of 86 
days of GTx-024 3 mg versus placebo and those enrolled on cancer trials of at least 86 
days exposure to GTx-024 3 mg or placebo.  
 
Adverse events reported among > 5% of GTx-024 3mg  
treated healthy subjects 
Percentage of subjects reporting a given adverse event at least once 
 
Primary System Organ Class 
Preferred Term 
GTx-024 
N=24 
Placebo 
N=24 
Gastrointestinal disorders 
Diarrhea 
8.3 
12.5 
 
Dyspepsia 
8.3 
8.3 
 
Vomiting 
8.3 
0.0 
General disorders and administration 
site conditions 
Vessel puncture site bruise 
12.5 
4.2 
 
Fatigue 
8.3 
8.3 
 
Malaise 
8.3 
0.0 
Infections and infestations 
Herpes simplex 
8.3 
0.0 
Injury, poisoning and procedural 
complications 
Contusion 
8.3 
4.2 
Investigations 
Alanine aminotransferase 
increased 
20.8 
0.0 
Musculoskeletal and connective 
tissue disorders 
Back pain 
12.5 
16.7 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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Primary System Organ Class 
Preferred Term 
GTx-024 
N=24 
Placebo 
N=24 
Nervous system disorders 
Headache 
20.8 
20.8 
 
Dizziness 
12.5 
4.2 
Respiratory, thoracic and mediastinal 
disorders 
Pharyngolaryngeal pain 
12.5 
12.5 
 
No serious adverse events (SAEs) were reported on this trial. 
 
These side effects are based on information obtained from a clinical study (G200501) 
administering GTx- 024 3 mg for 86 days in healthy subjects– elderly males and 
postmenopausal females. Studies suggest that side effects associated with the study 
drug resolve after GTx-024 is stopped. 
 
Adverse events reported among > 5% of GTx-024 3 mg treated cancer subjects 
Percentage of subjects reporting a given adverse event at least once  
 
Primary System Organ Class 
Preferred Term 
GTx-024 
N=432 
Placebo 
N=378 
Blood and lymphatic system 
disorders 
Anemia 
34.7 
34.7 
 
Neutropenia 
18.3 
23.3 
 
Thrombocytopenia 
10.4 
10.8 
 
Leukopenia 
8.3 
9.0 
Gastrointestinal disorders 
Nausea 
34.7 
34.9 
 
Vomiting 
20.1 
21.2 
 
Constipation 
12.3 
10.1 
 
Diarrhea 
11.6 
12.7 
 
Abdominal pain 
5.1 
3.7 
General disorders and 
administration site conditions 
Fatigue 
15.7 
16.7 
 
Asthenia 
15.3 
13.5 
 
Disease progression 
11.8 
16.7 
 
Pyrexia 
10.2 
9.8 
Infections and infestations 
Pneumonia 
5.6 
7.1 
Investigations 
Blood creatinine increased 
8.1 
5.0 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
Page 28 of 76 
Primary System Organ Class 
Preferred Term 
GTx-024 
N=432 
Placebo 
N=378 
 
Weight decreased 
6.0 
4.8 
Metabolism and nutrition disorders Decreased appetite 
10.6 
14.8 
Musculoskeletal and connective 
tissue disorders 
Arthralgia 
8.1 
7.9 
 
Pain in extremity 
5.6 
4.2 
Nervous system disorders 
Headache 
7.4 
6.1 
 
Peripheral sensory 
neuropathy 
5.8 
3.4 
 
Dizziness 
5.6 
6.3 
Respiratory, thoracic and 
mediastinal disorders 
Dyspnoea 
12.3 
7.4 
 
Cough 
9.5 
9.3 
Skin and subcutaneous tissue 
disorders 
Alopecia 
17.8 
18.5 
 
Serious adverse events (SAEs) reported among > 2% of GTx-024 3 mg  
treated cancer subjects 
Percentage of subjects reporting a given serious adverse event at least once 
 
Primary System Organ Class 
Preferred Term 
GTx-024 
N=432 
Placebo 
N=378 
Blood and lymphatic system disorders Anemia 
4.2 
3.7 
 
Neutropenia 
3.2 
3.7 
 
Febrile neutropenia 
2.3 
1.6 
Blood and lymphatic system disorders Thrombocytopenia 
2.3 
1.6 
General disorders and administration 
site conditions 
Disease progression 
7.9 
11.9 
Infections and infestations 
Pneumonia 
3.5 
3.2 
Neoplasms benign, malignant and 
unspecified (incl cysts and 
Malignant neoplasm 
progression 
2.8 
2.1 
 
An AE that appears related to GTx-024 in clinical trials has been a dose-dependent, 
transient, asymptomatic increase in ALT. However, these increases were modest at 
doses up to 10 mg per day. Most of the subjects studied to date had ALT levels that 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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remained within normal limits. One subject was discontinued for an ALT > 3 times the 
ULN. 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. 
 
The effect of GTx-024 on a fetus has not been evaluated; therefore, the subjects in the 
current investigation will be post-menopausal. 
 
2.2.2 STUDY RISKS  
  
Study Procedures 
Urethral catheterization 
Less Frequent (occurring more than 1%, but less than 10% of the time) 
Discomfort 
 
Mild cramping 
Infection 
Rare (occurring less than 1% of the time) 
 
 
Bleeding 
 
 
Urinary tract infection 
 
 
Inability to pass urine 
Puncture of the bladder 
 
 
Burning with urination 
 
Antibiotic (a medicine to prevent infection) 
Less Frequent (occurring more than 1% but less than 10% of the time) 
Diarrhea 
Nausea and vomiting 
Cramping 
Rare (occurring less than 1% of the time) 
Headache 
Itching 
Rash 
Allergic reaction 
 
Blood Drawing  
Most Frequent (occurring more than 10% of the time):  
Pain 
Bleeding 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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Bruising at the needle puncture site 
Rare (occurring less than 1% of the time):  
Blood clot 
Infection 
Feeling lightheaded 
Fainting 
 
Mammogram 
Most Frequent (occurring more than 10% of the time):  
Discomfort 
 
Gynecological Exam 
Rare (occurring less than 1% of the time):  
Discomfort 
 
Pelvic MRI 
Rare (occurring less than 1% of the time):  
Discomfort 
 
2.2.3 METHODS TO MINIMIZE RISK 
 
Subjects will be monitored at each visit for changes since last visit and adverse effects 
of treatment. Since elevations in ALT are possible, serum liver function tests will be 
monitored during treatment. (Refer to Section 9.4 Halting Rules) 
 
Subjects will receive a prophylactic antibiotic at visits where catheterization/UPP occur 
to decrease risk of urinary tract infection (UTI). Any infection will be appropriately 
treated. 
 
3. 
OBJECTIVES 
 
3.1 
PRIMARY OBJECTIVE 
 
1. Describe the effect of 12 weeks of treatment of GTx-024 on the number of 
stress incontinence episodes/day as assessed by the 3 day voiding diary. 
 
 
3.2 
SECONDARY OBJECTIVES  
  
1. Describe the effect of 12 weeks of treatment of GTx-024 on the frequency of 
voids/day as assessed by the 3 day voiding diary. 
 
2. Describe the effect of 12 weeks of treatment of GTx-024 on urine volume per 
void as assessed by the 3 day voiding diary. 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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3. Describe the effect of 12 weeks of treatment of GTx-024 on SUI as assessed 
by 24 hour pad weight test. 
 
4. Describe the effect of 12 weeks of treatment of GTx-024 on SUI as assessed 
by the Urethral Pressure Profile (UPP). 
 
5. Describe the effect of 12 weeks of treatment of GTx-024 on SUI as assessed 
by the Bladder Stress Test. 
 
6. Describe the effect of 12 weeks of treatment of GTx-024 on patient reported 
stress urinary incontinence symptoms as assessed by the MESA Urinary 
Questionnaire.  
 
7. Describe the effect of 12 weeks of treatment of GTx-024 on patient reported 
impression of symptom severity as assessed by the Patient Global 
Impression of Severity Scale (PGI-S). 
 
8. Describe the effect of 12 weeks of treatment of GTx-024 on patient reported 
impression of improvement as assessed by the Patient Global Impression of 
Improvement Scale (PGI-I). 
 
9. Describe the effect of 12 weeks of treatment of GTx-024 on patient reported 
urogenital distress as assessed by the Urinary Distress Inventory 
Questionnaire (UDI-6). 
 
10. Describe the effect of 12 weeks of treatment of GTx-024 on patient reported 
impact of urinary incontinence on daily life as assessed by the Incontinence 
Impact Questionnaire (IIQ-7). 
 
11. Describe the effect of 12 weeks of treatment of GTx-024 on patient reported 
sexual function as assessed by the Female Sexual Function Index 
Questionnaire (FSFI). 
 
12. Describe the effect of 12 weeks of treatment of GTx-024 on pelvic floor 
muscles as measured by MRI. 
 
 
 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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3.3 
STUDY END POINTS 
 
Primary end point 
 
1. Change in frequency of daily stress urinary incontinence episodes from 
Baseline to Week 12. 
 
Secondary end points 
 
1. Change in frequency of daily voids from Baseline to Week 12. 
 
2. Change in urine volume per void from Baseline to Week 12. 
 
3. Change in 24 hour pad weight from Baseline to Week 12. 
 
4. Change in maximum urethral closure pressure measurements from Baseline 
to Week 12. 
 
5. Change in urine leakage (yes/no) on the Bladder Stress Test from Baseline to 
Week 12 as assessed while (a) coughing, and/or (b) performing a Valsalva 
maneuver. 
 
6. Change in total score on the stress incontinence section of the MESA Urinary 
Questionnaire from Baseline to Week 12. 
 
7. Change in Patient Global Impression of Severity (PGI-S) Scale from Baseline 
to Week 12. 
 
8. Patient Global Impression of Improvement (PGI-I) Scale at Week 12. 
 
9. Change in total score on the Urinary Distress Inventory (UDI-6) from Baseline 
to Week 12. 
 
10. Change in total score on the Incontinence Impact Questionnaire (IIQ-7) from 
Baseline to Week 12. 
 
11. Change in total score on the Female Sexual Function Index (FSFI) from 
Baseline to Week 12 as well as the change in subdomain scores: libido, 
arousal, lubrication, orgasm, satisfaction, and pain. 
 
12. Change in pelvic floor muscles from Baseline to Week 12 as measured by 
MRI.  Quantitative assessments may include the area of the levator hiatus, 
the anteroposterior and transverse diameters, and other relevant parameters.  
 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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4. 
METHODOLOGY 
 
4.1 
STUDY DESIGN 
 
This is a single site, proof of concept feasibility study to describe the effect of GTx-024  
3 mg in postmenopausal female subjects with SUI. Postmenopausal will be defined as 
clinically confirmed female subjects who have undergone the onset of spontaneous, 
medical or surgical menopause prior to the start of this study. Durability of treatment will 
also be explored by evaluating validated measures at 4 weeks after last dose. Up to 35 
subjects will be enrolled in this study. 
 
Institutional Review Board (IRB) approval from Beaumont’s Human Investigations 
Committee will be obtained prior to beginning any study activity. Once IRB approval is 
obtained, potential participants will be identified from existing medical records, or 
physician or other referrals.  
 
Potential subjects may be prescreened by telephone prior to the first in person study 
visit (initial screening visit). At the first in person study visit, subjects will be seen in the 
Urology Clinical Research space and informed consent will be obtained prior to any 
study activity. At Study Visit, 2, inclusion/exclusion criteria will be verified, study data will 
be collected, and consented participants may begin treatment.  
 
Enrolled subjects will agree to maintain on a stable dose of any medication known to 
affect lower urinary tract function, including but not limited to anticholinergics, tricyclic 
antidepressants, or alpha-adrenergic blockers, throughout the treatment and follow-up 
period. Subjects enrolled in the study will agree to not start any new treatment 
(medication or otherwise) that is known to affect lower urinary tract function throughout 
the treatment and follow up periods. Subjects will also agree to refrain from performing 
any Kegal exercises and maintain current dietary habits throughout the treatment and 
follow up periods.  
 
4.2 
MEDICAL MONITORING 
 
A Medical Monitor will be responsible for monitoring the safety and data of this trial. The 
data that will be monitored include adverse events related to the study drug and 
procedures. 
 
5. STUDY ENROLLMENT AND WITHDRAWAL 
 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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5.1 SUBJECT INCLUSION CRITERIA 
 
Subject Inclusion Criteria: Subjects eligible for inclusion in this study must meet all of 
the following criteria:  
1. Give voluntary, written and signed, informed consent 
2. Female 
3. Age 18 to 80 years old  
4. Clinically confirmed as postmenopausal. Subjects must have undergone the onset of 
spontaneous, medically induced or surgical menopause prior to the start of this 
study. Postmenopausal is defined as 12 months of spontaneous amenorrhea or 6 
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml or 6 weeks 
postsurgical bilateral oophorectomy with or without hysterectomy. 
5. SUI symptoms for at least 6 months duration 
6. Predominant SUI (MESA questionnaire) 
7. 24 hour pad weight >3 gms at baseline 
8. At least 4, but no more than 15, SUI episodes on each day of the 3 day baseline 
voiding diary. 
9. Serum AST and ALT within normal limits  
10. Total bilirubin within normal limits 
11. Positive Bladder Stress Test 
12. Subject agrees to not start any new treatment (medication or otherwise) that is 
known to affect lower urinary tract function throughout the treatment and follow up 
periods. 
13. Subject agrees to maintain on a stable dose of any medication known to affect lower 
urinary tract function, including but not limited to anticholinergics, tricyclic 
antidepressants, or alpha-adrenergic blockers, throughout the treatment and follow-
up period.  
 
5.2 SUBJECT EXCLUSION CRITERIA 
 
Subject Exclusion Criteria: Subjects eligible for this study must not meet any of the 
following criteria: 
1. Pelvic floor physical therapy within the last 6 months    
2. History of pelvic radiation treatment  
3. History of urethral diverticula 
4. History of urethral sling, anterior prolapse repair, ureteral bulking agents and/or 
other SUI procedure or surgery 
5. Known vesicoureteral reflux, vaginal prolapse beyond the introitus, or other 
significant pelvic floor abnormalities 
6. Patient has urinary incontinence of neurogenic etiology 
7. Patient is morbidly obese (defined as 100 pounds over their ideal body weight, or 
body mass index 40 or greater) 
8. Chronic hepatitis 
9. Hepatic cirrhosis 
10. HIV and/or hepatitis A, B, or C 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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11. Subjects taking systemic hormone products (excludes intravaginal application of 
estradiol topical/tablet agents and hormones delivered via vaginal rings) 
12. Subjects with a history of breast or endometrial cancer.  
13. Subjects with cerebrovascular disease, thromboembolic disorders, myocardial 
infarction, or angina. 
14. Subject with an entry measurement of > 5 mm endometrial stripe thickness as 
measured by MRI. 
15. Any other condition which per investigators’ judgement may increase subject risk 
16. Clinically confirmed urinary tract infection 
 
5.3 STRATEGIES FOR RECRUITMENT, RETENTION, AND TO 
IMPROVE ADHERENCE TO INTERVENTION PROTOCOLS 
 
Potential subjects will be identified from existing medical records, physician referrals, or 
recruited via advertisement or word of mouth. During initial telephone contact, patients’ 
history will be reviewed for inclusion/exclusion criteria. Those subjects who initially 
qualify will be invited to an in person study visit (study visit 1). 
 
5.4 TREATMENT ASSIGNMENT PROCEDURES 
 
All subjects enrolled in this study will receive a daily oral dose of GTx-024, 3 mg. 
 
5.4.1 REASONS FOR WITHDRAWAL 
 
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 reasons potentially including:  
• Unable to tolerate study treatment (AE requiring permanent discontinuation of 
study treatment) 
• AEs that require treatment with a prohibited medication or a procedure 
• Development of any condition that may pose an additional risk to the subject or 
PI decision that this is in the best interest of the subject 
• Study terminated by sponsor 
• Subject unable to follow Investigators’ instructions and comply with the study 
procedures 
• Major protocol violation 
 
The clinical study report will include reasons for all subject withdrawals from treatment 
and from the study as well as details relevant to violations of Study Prohibitions and 
Concomitant Therapy. 
 
5.4.2 EARLY TERMINATION OR SUSPENSION OF THE STUDY 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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Any decision to suspend enrollment or terminate the study will be made by the Sponsor, 
PI and, if appropriate, the local IRB. If a decision is made to terminate the study, 
subjects who have received treatment will be followed for up to 28 days. 
 
6. 
STUDY INTERVENTION/INVESTIGATIONAL PRODUCT 
 
 
6.1 
STUDY PRODUCT DESCRIPTION 
 
GTx-024 (enobosarm); United States Adopted Names Council official generic name) is 
an orally bioavailable nonsteroidal SARM with tissue-selective anabolic and androgenic 
pharmacologic activity (Dalton, 2011). 
 
6.2 
ACQUISITION 
 
GTx-024 3 mg Softgels (capsules) will be supplied by GTx, Inc. 
 
6.3 
FORMULATION, PACKAGING, AND LABELLING 
 
The drug product will be supplied as opaque, white to off-white, size 5, oval Softgel 
capsules containing 3 mg GTx-024. “GTx” will be imprinted in black ink on the outer 
shell of the capsule. The liquid Softgel fill is composed of GTx-024 dissolved in 
polyethylene glycol 400 (PEG400). 
 
GTx-024 3 mg Softgels will be packaged in high density polyethylene (HDPE) bottles 
with induction seal and child-resistant closure. Each bottle will contain sufficient study 
drug for 35 days of dosing according to the study protocol. Each bottle of study drug will 
be labeled with dosing and storage instructions. 
 
6.4 
PRODUCT STORAGE AND STABILITY 
 
Recommended storage will be at controlled room temperature 15°C–25°C (59°F–77oF), 
with excursions permitted to 30°C (86°F), protected from moisture. 
 
6.5 
DOSAGE, PREPARATION, AND ADMINISTRATION OF STUDY 
INTERVENTION/INVESTIGATIONAL PRODUCT 
 
One (1) GTx-024 3 mg Softgel capsule will be taken PO with water at approximately the 
same time each day, with or without food.  
 
6.6 
ACCOUNTABILITY PROCEDURES FOR THE STUDY 
INVESTIGATIONAL PRODUCT(S) 
 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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The Investigator is responsible for the correct storage of study medication according to 
GTx, Inc. recommendations. The study medication made available for this clinical trial 
must be used in accordance with the protocol and dispensed only under the supervision 
of the Investigator and documented sub-Investigators. The Investigator must maintain 
complete and accurate records, showing the receipt and disposition of all supplies of the 
study medication delivered by the GTx, Inc. authorized representative. These records 
must include a master record which lists the date of receipt of all study medication 
shipments, batch numbers, expiration date, and quantities received. In addition, a 
dispensing record which includes all quantities dispensed, identification of the subject to 
whom study medication was dispensed, the date of each dispensing, and the 
identification of the dispenser will also be maintained. The master dispensing records 
are separate from records kept for individual trial subjects. 
 
It is the Investigator’s responsibility to ensure that study medication used by trial 
subjects plus unused study medication equal the total amount received from the GTx, 
Inc. authorized representative. Damaged and/or contaminated packets must also be 
accounted for in the dispensing records. All discrepancies must be explained in writing. 
The study personnel responsible for study medication administration to the subject will 
record the date and time the initial treatment is given to the subject. In addition, the 
Drug Accountability case report form (CRF) will document any treatment interruptions or 
discontinuation. 
 
6.7 
ASSESSMENT OF SUBJECT COMPLIANCE WITH STUDY 
INTERVENTION/INVESTIGATIONAL PRODUCT  
 
Subjects should be instructed to return all unused study medication and containers at 
each clinic visit during the clinical trial period so that drug accountability can be 
performed. The dispensing pharmacy is required to count all returned study capsules 
and record this on the proper CRF.  
 
All study medication returned by subjects must be accounted for and verified by the 
study research nurse clinician and research pharmacist. After verification of all study 
medication, used packages and unused study medication will be returned to GTx, Inc., 
or authorized representative. 
 
Treatment Compliance 
 
Study subjects should be counseled on the need to meet 100% compliance with taking 
study drug. The investigator or designee should ensure that study subjects meet this 
goal throughout the study period. Compliance will be verified by the accounting of study 
drug at each in person visit after baseline. When study drug is administered at the 
research facility, it will be administered under the supervision of study personnel. 
Compliance with taking study drug will be monitored by the accounting of 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 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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counsel the subject and ensure steps are taken to improve compliance. Subjects who 
are less than 80% or more than 120% compliant with the dosage regimen for any two 
consecutive visit periods during the study may be withdrawn from the study. 
 
6.8 
CONCOMITANT MEDICATIONS/TREATMENTS  
 
Forbidden medications and treatments during the study duration include:  
• Systemic hormonal products including but not limited to estrogens, progestins, 
testosterone, methyltestosterone, oxandrolone (Oxandrin®), oxymetholone, 
danazol, fluoxymesterone (Halotestin®), other androgenic compounds, including 
herbals. Intravaginal application of estradiol topical/tablet agents and hormones 
delivered via vaginal ring are allowed. 
• Treatment with any investigational agent within 6 months before the first dose of 
study treatment;  
 
Previous and Concomitant Medication (Drugs and Therapies) 
The Investigator or designee must record the use of previous (all medication taken 
within 30 days prior to Screening (Visit 1) and current concomitant treatment, both drug 
and non-drug therapies, prescribed and over-the-counter and all alternative medicines, 
in the CRFs. This also includes drugs used on a chronic and as-needed basis. Subjects 
must be instructed not to start any new medication, both prescribed and over-the-
counter, without consulting the Investigator, unless the new medication is required for 
emergency use. Subjects must be instructed to notify the Investigator immediately if 
medications were required for emergency use. 
 
7. 
STUDY SCHEDULE 
 
7.1 
STUDY VISITS 
 
Each subject may complete up to 5 months of study participation. 
 
Screening Visit, Days -21-0 
The study will be explained in detail and adequate time will be allowed for answering 
potential subjects questions prior to signing the IRB approved informed consent 
document. Informed consent will be obtained from those volunteers meeting initial 
inclusion/exclusion criteria and expressing willingness to participate prior to conducting 
any further study tests or measures. 
  
Once informed consent is obtained, a detailed interview with vital signs will be 
conducted to further review for inclusion/exclusion criteria. A subject number will be 
assigned. Height and weight will be measured. Subjects will complete the MESA 
questionnaire to assess incontinence type (stress, urge, or mixed). If urinary 
incontinence type is stress predominant, then the subject will be instructed to complete 
a 24 hour pad weight and 3 day voiding diary prior to the next study visit. A bladder 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
Page 39 of 76 
stress test will be done to confirm SUI.  Lab tests will also be drawn at this visit as 
outlined in Table I. A baseline urinalysis will be obtained. Concomitant medications will 
also be assessed and recorded. 
 
Additional Screening, Days -21-0 
If the subject has qualified for the study during the Screening visit, the following 
procedures will be performed between Screening Visit and Visit 1. Mammogram, if not 
done within the last 6 months, will be performed. Pelvic MRI will be performed 
 
Study Visit 1: Week 0, Clinic Visit 
Subjects still meeting inclusion/exclusion criteria after all Screening study measures 
have been completed and reviewed will return for Visit 1 where the 24 hour pad weight 
and 3 day voiding diary will be collected and reviewed. An interview with vital signs will 
be conducted. A detailed medical history will be taken, including past gynecological and 
obstetric history (gravida, para, prior abortions and deliveries) and a focused physical 
exam, including standard gynecological pelvic exam and skin assessment, will be done. 
Urine dipstick will be done and PVR will be measured. If subject still meets 
inclusion/exclusion criteria, UPP will be performed. A dose of Ciprofloxacin or equivalent 
will be given prophylactically to prevent bladder infection. Serum lab tests consisting of 
a CBC, lipid panel and testosterone level will be drawn.Questionnaires (UDI-6, IIQ, 
FSFI, and PGI-S) will also be completed at this visit.  Concomitant medications and 
adverse events, will be assessed and recorded. A baseline MRI measurement will be 
scheduled and/or completed prior to receiving study drug. 
 
Subjects who meet all the inclusion and none of the exclusion criteria will receive study 
drug. Study drug will be packaged in bottles. Each study drug bottle will be preprinted 
with a Medication ID number. The Medication ID number assigned to the subject will be 
noted in the case report form (CRF) for study drug.  
 
The first dose of study drug will be taken during this visit if the subject meets all criteria 
for enrollment. A one month supply of study drug (35 count bottles) will be dispensed 
with administration instructions.  
 
Study Visit 2: Week 1, Phone Call 
Approximately 1 week after beginning treatment, subjects will be contacted by phone to 
assess for concomitant meds and adverse events. Subjects will also be instructed to 
complete a 24 hour pad weight and 3 day voiding diary within the week preceding their 
next study visit. 
 
Study Visit 3: Week 4, Clinic Visit 
Approximately 4 weeks after beginning treatment, subjects will return to the clinical 
research office for an in person visit. An interview with vital signs will be conducted. 
Height and weight and PVR will be measured. Pad weights will be measured, and the 3 
day voiding diary will be collected and reviewed. Blood will also be drawn to measure 
serum AST, ALT, and total bilirubin. Questionnaires will also be completed, and 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
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concomitant meds and adverse events, including any vaginal bleeding, discharge, 
infections and/or spotting, will be assessed and recorded. Subjects will also be 
instructed to complete a 24 hour pad weight and 3 day voiding diary in the week 
preceding their next study visit. A 30 day supply of study drug will be dispensed with 
administration instructions.  
 
Study Visit 4: Week 8, Clinic Visit 
Approximately 8 weeks after beginning treatment, subjects will return to the clinical 
research office for an in person visit. An interview and vital signs will be conducted. 
Height and weight and PVR will be measured. Pad weights will be measured, and the 3 
day voiding diary will be collected and reviewed.  Blood will also be drawn to measure 
serum AST, ALT, and total bilirubin. Questionnaires will also be completed and 
concomitant meds and adverse events including any vaginal bleeding, discharge, 
infections and/or spotting,will be assessed and recorded. Subjects will also be 
instructed to complete a 24 hour pad weight and 3 day voiding diary in the week 
preceding their next study visit. A 30 day supply of study drug will be dispensed with 
administration instructions.  
 
Study Visit 5: Week 12, Clinic Visit 
Approximately 12 weeks after beginning treatment, subjects will return to the clinical 
research office for an in person visit. An interview with vital signs will be conducted. A 
focused physical exam will be done. Gynecological pelvic exam will only be done at this 
visit if clinically indicated. Urine dipstick will be done and PVR will be measured Height 
and weight will be measured. 24 hour pad weights and 3 day voiding diaries will be 
collected/reviewed. Blood will also be drawn to measure laboratory values as outlined in 
Table 1. UPP,Bladder Stress Test, and MRI will be performed at end of treatment, 
questionnaires will be administered, and concomitant medications/adverse events will 
be assessed and recorded. All study medication will be collected and accounted for. 
 
Study Visit 6: Week 16, Telephone/mailed questionnaire visit 
Approximately 4 weeks after study drug treatment has ended, subjects will be contacted 
by phone to assess for concomitant meds and adverse events. Subjects will also be 
instructed to complete and return mailed questionnaires.  
 
7.2 
EARLY TERMINATION 
 
Subjects may withdraw from the study voluntarily. In addition, if the PI determines that 
continued participation might present a safety risk for the subject then the PI may 
withdraw the subject from the study. Those subjects who receive study drug will be 
followed for 28 days after stopping study participation. Every effort will be made to 
obtain all end of treatment measures as outlined in (Table 1.Visit 6) in the event that a 
subject withdraws, or is withdrawn, from the study before completing treatment. 
 
8. 
STUDY PROCEDURES/EVALUATIONS 


 
 
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Compound No.: GTx-024 
 
 
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Please see Table1 Schedule of Measures for an outline of the timing of the study 
procedures. Please see Appendix A, B, C, D, E for outcomes measures. 
 
Interview with Vital Signs 
All potential subjects will be interviewed/assessed to confirm inclusion/absence of 
exclusion criteria. A review of systems will be completed, concomitant medications will 
be assessed, and vital signs (temperature, blood pressure, pulse and respirations) will 
be assessed. Laboratory results will also be reviewed at specified time points as 
outlined in Table 1. 
 
History 
A detailed history will include review of gravida, prior abortions,, parity, deliveries, and 
history of gynecological conditions and/or cancer.  
 
Focused Physical Exam 
A standard brief physical exam will be done. This will include a gynecological pelvic 
exam and visual skin exam with specific attention to androgenic changes. 
 
Urinalysis 
A clean catch midstream voided urine specimen will be obtained, and evaluated by 
urine dipstick. If results or clinical symptoms indicate, the specimen will be sent for 
culture and the patient will receive appropriate treatment for UTI per standard of care. 
  
24 Hour Pad Weight Test 
The 24-hour pad test should be completed during 1 day of each scheduled 3-day 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 should be given one type of incontinence pad 
at the clinic. They may choose from a “light” pad or a “heavy” pad, but the pads 
dispensed MUST be used for the 24- hour test. Subjects should receive 8 incontinence 
pads for use during each 24-hour test period. 
 
Urethral Pressure Profile (UPP) and Bladder Stress Test 
To conduct the UPP and Bladder Stress Test, a urodynamic catheter will be placed and 
the bladder will be filled with 300 ml of fluid, such as saline. UPP will be performed. 
Subjects will be instructed to perform a provocative maneuver to increase abdominal 
pressure (cough, Valsalva, or similar event). Urine loss during this even indicates a 
positive stress test.  
 
Ultrasound Bladder Scan 
Subjects will be asked to void, and the volume of urine remaining in the bladder after 
voiding (post void residual) will be measured via bladder ultrasound scan. 
 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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Mammogram 
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 detection of breast cancer, typically through detection of characteristic masses 
and/or microcalcifications. 
 
Magnetic Resonance Imaging(MRI) 
MRI will be done at baseline and end of treatment to observe changes in pelvic floor 
muscles along with the thickness of the endometrium (mm). Quantiative assessments 
may include the area of the levator, the anteroposterior and transverse diameters, 
and/or other relevant parameters. Endometrial thickness can accurately be assessed by 
MRI (Stanislavsky, Weerakkody, et al., 2015; Nakamura et al., 2014); therefore, it is 
being used as a safety assessment in this study. 
 
Medical, Epidemiological and Social Aspects of Aging (MESA) Questionnaire 
The MESA questionnaire measures severity of specific types (stress, urgency, mixed) of 
urinary incontinence (UI). Two subscales, the urgency UI (6 items) and the stress UI (9 
items). Test-retest reliability on “any incontinence” is high (agreement coefficient = .89). 
Validity (agreement between self-report on the MESA and clinician’s assessment) = 
87% in women. The MESA questionnaire has demonstrated agreement on incontinence 
= 79% and 69% and 72% accuracy in predicting urodynamic diagnosis of stress UI and 
uninhibited detrusor contraction (Herzog, 1990a; Herzog, 1990b).  
 
3 Day Voiding Diary 
Subjects will record each episode of urinary leakage and record its severity. Subjects 
will also be asked to record urinary frequency, and urgency. Urine volume will also be 
recorded. 3 day bladder diaries are reliable measures of mean number of UI 
episodes/day, UI type, mean voids/24 hours, and mean voids during sleeping hours. 2-
week test-retest results correlate with diurnal micturition (r=.89, p<0.001) and UI 
episodes (r=.91, p<0.001). Compared to participant recall of the previous week, 
Spearman rank correlation = .57 for voiding frequency and .70 for UI episodes (Brown, 
2003: Locher, 2001; Wyman, 1988). For this study, any episode of vaginal discharge or 
spotting will also be recorded on the diary. 
 
Patient Global Impression of Improvement (PGI-I) 
PGI-I is a global rating of improvement using 7-point scale. Construct validity was 
established in two randomized controlled studies (n=1,133 subjects) of drug treatment 
for predominant stress incontinence (Wagner, 1996; Yalcin, 2003).  
 
Patient Global Impression of Severity (PGI-S) 
PGI-S is a global rating of symptoms severity using a 7 point scale (Yalcin, 2003).  
 
UDI-6 and IIQ-7 
The Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-
7) assess symptom distress and the impact of urinary incontinence on daily life. The 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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07 August 2015      CONFIDENTIAL 
Page 43 of 76 
urogenital distress inventory (UDI) and incontinence impact questionnaire (IIQ) were 
both developed to assess the impact of UI on HRQoL (Shumaker, 1994; Wyman, 1987). 
Short versions of the UDI and IIQ, UDI- 6, and IIQ-7, were developed to reduce the 
respondents’ burden. The UDI-6 and IIQ-7 are both ‘‘A grade’’ recommended by the 
Fourth International Consultation on Incontinence (Shumaker, 1994; Wyman, 1987;  
Uebersax, 1995; Staskin, 2008). 
 
Female Sexual Function Index (FSFI)  
The FSFI is a 19-question validated tool evaluating sexual function in several domains: 
libido, arousal, lubrication, orgasm, satisfaction and pain (Rosen et al, 2000). Each 
subdomain is scored separately and the total score is calculated. 
 
 
9. 
ASSESSMENT OF SAFETY 
 
9.1 
METHODS AND TIMING FOR ASSESSING, RECORDING, AND 
ANALYZING SAFETY PARAMETERS 
 
9.1.1 ADVERSE EVENTS 
 
ICH E6 defines an AE as any untoward medical occurrence in a subject or clinical 
investigation subject administered a pharmaceutical product regardless of its causal 
relationship to the study treatment. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or 
not considered related to the medicinal (investigational) product.  
 
The occurrence of an AE may come to the attention of study personnel during study 
visits and interviews of a study subject presenting for medical care, or upon review by a 
study monitor.  
 
The period of observation for which AEs are to be collected begins after the subject has 
signed the ICF, throughout the study intervention period, and for 28 days post 
treatment.  
 
All AEs, whether reported by the subject or noted by study personnel, will be recorded 
in the subject’s medical record and captured on the appropriate CRF. 
 
Information to be collected includes event description, time of onset, Investigator’s 
assessment of severity, Investigator’s assessment of relationship to study drug, and 
time of resolution/stabilization of the event. All AEs occurring while on study must be 
documented appropriately regardless of relationship to study drug. All AEs will be 
followed to adequate resolution as per Section 9.3 TYPE AND DURATION OF 
FOLLOW-UP OF SUBJECTS AFTER ADVERSE EVENTS. 


 
 
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Compound No.: GTx-024 
 
 
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Any medical condition that is present at the time that the subject is screened will be 
considered as baseline and not reported as an AE. However, if the condition 
deteriorates at any time during the study, it will be recorded as an AE. 
All AEs must be graded for intensity and relationship to study drug.  
 
9.1.2 INTENSITY OF EVENT  
 
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 from  
 
Table 1 should be used:  
 
Table 1: Description of Grades According to the CTCAE  
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 
5 
Death related to AE 
 
If the intensity changes within a day, the maximum intensity should be recorded. If the 
intensity changes over a longer period of time, the changes should be recorded as 
separate events (having separate onset and stop dates for each change in intensity). 
Changes in the intensity of an AE will be documented to allow an assessment of the 
duration of the event at each level of intensity to be performed. AEs characterized as 
intermittent require documentation of onset and duration of each episode. 
 
9.1.3 DRUG – ADVERSE EVENT RELATIONSHIP 
 
Classification of Relationship/Causality of Adverse Events (AE/SAE) to study drug:  The 
investigator will determine the relationship between the study drug administration and 
the occurrence of an AE/SAE as defined below: 
 
Not Related:  The temporal relationship of the adverse event is determined to be Not 
Related to study drug administration. 
 
Possibly Related:  The temporal relationship of the adverse event to study drug 
administration makes a causal relationship possible. Other medications, therapeutic 
interventions, or underlying conditions provide a probable explanation for the observed 
event. 
 


 
 
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Compound No.: GTx-024 
 
 
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Probably Related:  The temporal relationship of the adverse event to study drug 
administration makes a causal relationship. 
 
Probable:  Other medications, therapeutic interventions or underlying conditions provide 
a possible explanation for the observed event.  
 
Related:  The temporal relationship of the adverse event is determined to be Related to 
study drug administration.  
 
Unable to Determine: The temporal relationship of the adverse event to study drug 
administration makes a causal relationship unable to determine or unknown. 
 
 
9.1.4 SERIOUS ADVERSE EVENTS 
 
An SAE is defined as an AE that meets 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  
• Results in congenital anomaly or birth defect 
• Results in a persistent or significant disability/incapacity 
• Any other important medical event that may not result in death, be life 
threatening, or require hospitalization, may be considered a serious adverse 
experience when, based upon appropriate medical judgment, the event may 
jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed above. 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 
 
All SAEs will be:  
• Recorded on the appropriate CRF 
• Reported to the designated Safety department/pharmacovigilance contractor 
using a SAE Report Form within 24 hours of awareness 
• Followed through to resolution by a study Investigator 
• Reviewed and evaluated by a study Investigator 
 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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9.2 
REPORTING PROCEDURES 
 
9.2.1 SERIOUS ADVERSE EVENTS  
 
All SAEs, including death due to any cause, which occur after the subject signs the ICF 
and within 28 days following the last administration of study drug, whether or not related 
to the study drug, must be reported immediately to the designated Safety 
Department/pharmacovigilance contractor within 24 hours by e-fax, e-mail, or 
telephone (see contact information below). At the very least, the following information 
must be reported:  
• Date and time of report 
• Reporter’s name and phone number 
• Investigator’s name and site number 
• Subject number 
• SAE information: event term, onset date, causal relationship 
• Study drug: start date of study drug and whether or not study drug has been 
withheld or discontinued 
 
SAE Reporting Contact Information:  
US Safety Toll-Free E-Fax Line: 1 866 966 2970 
US Safety Toll-Free Unmanned Hotline: 1 866 966 8429 
Safety E-mail: sae@cmedresearch.com  
 
Information about all SAEs is collected and recorded on the SAE Report Form. The 
Investigator must assess the relationship of any SAE to study drug, complete the SAE 
Report Form, and send the completed, signed form by e-fax or e-mail within 24 hours to 
the assigned drug safety group. As a back-up, the site may report SAEs using the 
unmanned safety hotline, with a completed SAE Report Form forwarded to the assigned 
drug safety group within 24 hours following notification on the hotline. The original copy 
of the SAE Report Form and the e-fax confirmation sheet must be kept with the case 
report form documentation at the study site.  
 
Follow-up information must also be sent to the same assigned drug safety group by e-
fax or e-mail using either a new SAE Report Form stating that this is a follow-up to the 
previously reported SAE (giving the date of the original report), or by using a follow-up 
query form.  
 
If an SAE is not previously documented (new occurrence) in the Investigator’s Brochure 
(IB) and is thought to be related to the relevant Investigational Medicinal Product (IMP), 
the assigned drug safety group may urgently require further information from the 
Investigator for Regulatory Authority reporting. The drug safety group may need to issue 
an Investigator Notification (IN) to inform all Investigators involved in any study with the 
same drug that this SAE has been reported. Suspected Unexpected Serious Adverse 
Reactions (SUSARs) will be collected and reported to the regulatory/competent 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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authorities and relevant IRBs/IECs in accordance with Food and Drug Administration 
(FDA) regulations 21 CFR 312.32, International Conference on Harmonization (ICH) 
guidelines, and European Clinical Trials Directive 2001/20/EC, or as per national 
regulatory requirements in participating countries. Adequate documentation must be 
maintained showing that Regulatory Authorities and IRBs/IECs have been properly 
notified. 
 
SAEs must be reported within 24 hours, regardless of relationship, on a SAE Report 
Form to allow the Sponsor to take appropriate measures to address potential new risks 
in a clinical trial. The Investigator must report such events to the Sponsor immediately;  
under no circumstances should reporting take place more than 24 hours after the 
Investigator learns of the event. 
 
The term sudden death should be used only when the cause is of a cardiac origin as 
per standard definition. The terms death and sudden death are clearly distinct and must 
not be used interchangeably. The study will comply with all local regulatory 
requirements and adhere to the full requirements of the ICH Guideline for Clinical Safety 
Data Management, Definitions and Standards for Expedited Reporting, Topic E2. 
 
The SAE Report Form must be signed by the PI or assigned designee.  
 
Other supporting documentation of the event may be requested by the safety 
department/pharmacovigilance contractor and should be provided as soon as possible. 
 
All SAEs will be followed until satisfactory resolution as per Section 9.3 TYPE AND 
DURATION OF FOLLOW-UP OF SUBJECTS AFTER ADVERSE EVENTS. 
 
9.2.2 REGULATORY REPORTING  
 
Suspected (considered related to the study drug) and unexpected (not previously 
described in the reference safety document) serious adverse reactions (SUSARs) will 
be reported in an expedited manner by GTx, Inc. to applicable Regulatory Authorities, 
EudraVigilance, IECs and IRBs, and Investigators in compliance with FDA regulations 
21 CFR 312.32, ICH guidelines, the European Clinical Trials Directive 2001/20/EC, the 
European Commission’s “Detailed guidance on the collection, verification and 
presentation of adverse event/reaction reports arising from clinical trials on medicinal 
products for human use” (CT-3, June 2011), and other applicable local regulations and 
guidelines, as required. The timelines stipulated by applicable national regulations and 
guidelines shall be adhered to, typically death and life-threatening SUSARs shall be 
reported within 7 days and all other SUSARs shall be reported within 15 days. 
 
Additionally, events may occur during a clinical trial which do not fall within the definition 
of a SUSAR and thus are not subject to the reporting requirements for SUSARs, even 
though they may be relevant in terms of subject safety. Examples are new events 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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related to the conduct of a trial or the development of an IMP likely to affect the safety of 
subjects such as:  
• A SAE which could be associated with the trial procedures and which could 
modify the conduct of the trial  
• A significant hazard to the subject population such as lack of efficacy of an IMP 
used for the treatment of a life-threatening disease  
• A major safety finding from a newly completed animal study (such as 
carcinogenicity)  
 
These events/observations are not to be reported as SUSARs, but they might require 
other action, such as urgent safety measures and their notification, substantial 
amendments, or early termination of the trial, and shall be reported in accordance with 
applicable local regulations and guidelines. 
 
All serious events designated as expected and/or “not related” to study drug(s), will be 
reported to the applicable Regulatory Authorities and IECs/IRBs at least annually in a 
summary format”. 
 
9.3 
TYPE AND DURATION OF FOLLOW-UP OF SUBJECTS AFTER 
ADVERSE EVENTS 
 
AEs will be collected up until 28 days after the last dose of study treatment, and will 
continue to be followed up until one of the following occurs:  
 
Resolved or improved to baseline 
Death 
Investigator confirms that no further improvement can be expected 
 
9.4 
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 × ULN 
ALT or AST > 5 × ULN for more than 2 weeks 
ALT or AST > 3 × ULN and ((total bilirubin > 2 × ULN or 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 (> 5%) 
 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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All subjects discontinued from the study should be followed until abnormal values return 
to normal.  
 
ALL DISCONTINUATIONS SHOULD BE DISCUSSED WITH THE MEDICAL 
MONITOR PRIOR TO DISCONTINUATION. 
 
 
10. 
STATISTICAL CONSIDERATIONS 
 
Since this is a proof of concept feasibility study, no power calculation is needed. Based 
on Dalton, 2011, 10-20% of patients may withdraw from the study before completing 
treatment. Therefore, we will recruit up to 35 patients meeting inclusion/exclusion 
criteria until 30 subjects have completed treatment. Descriptive statistics will be used to 
explore changes in primary and secondary outcomes measures between baseline and 
end of treatment. Although the primary efficacy measure will be a change in frequency 
of daily stress leaks between Baseline and Week 14 weeks, response to treatment will 
also consider secondary efficacy measures (change in frequency of voids per day, urine 
volume per void , change in 24 hour pad weight , responses to validated questionnaires, 
changes in UPP measures, changes in sexual function), and change in pelvic floor 
muscles as measured by MRI. Safety will be reported by the number and type of 
adverse events reported during treatment. No imputations for missing data will be 
conducted. There will be no adjustment for multiple testing. 
 
10.1 STATISTICAL METHODS 
 
Primary end point 
 
• The average number of episodes per day of leaking (SUI) will be calculated by 
summing the number of episodes over the 3 day period and dividing by 3, the 
change from Baseline to Week 12 will be computed and this change will be 
summarized with descriptive statistics (min, max, median, mean, standard 
deviation) and analyzed for a significant change from Baseline using the Exact 
Wilcoxon sign rank test.  
 
Secondary end points 
• The average number of voids per day will be calculated by summing the number 
of voids over the 3 day period and dividing by 3, the change from Baseline to 
Week 12 will be computed and this change will be summarized with descriptive 
statistics (min, max, median, mean, standard deviation) and analyzed for a 
significant change from Baseline using the Exact Wilcoxon sign rank test.  
 
• The average volume per void  will be calculated by summing the total urine 
amount over the 3 day period and dividing by the total number of voids recorded 
over 3 days, the change from Baseline to Week 1[2 will be computed and this 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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change will be summarized with descriptive statistics (min, max, median, mean, 
standard deviation) and analyzed for a significant change from Baseline using 
the Exact Wilcoxon sign rank test.  
 
• 
Change in maximum urethral closure pressure measurements from Baseline to 
Week 12 will be computed and this change will be summarized with descriptive 
statistics (min, max, median, mean, standard deviation) and analyzed for a 
significant change from Baseline using the Exact Wilcoxon sign rank test. 
 
• Change in 24 hour pad weight from Baseline to Week 12 will be computed and 
this change will be summarized with descriptive statistics (min, max, median, 
mean, standard deviation) and analyzed for a significant change from Baseline 
using the Exact Wilcoxon sign rank test.  
 
• Change in total score on the stress incontinence section of the MESA Urinary 
Questionnaire from Baseline to Week 12 will be computed and this change will 
be summarized with descriptive statistics (min, max, median, mean, standard 
deviation) and analyzed for a significant change from Baseline using the Exact 
Wilcoxon sign rank test. 
 
• Change in Patient Global Impression of Severity (PGI-S) Scale from Baseline to 
Week 12 will be computed and this change will be summarized with descriptive 
statistics (min, max, median, mean, standard deviation) and analyzed for a 
significant change from Baseline using the Exact Wilcoxon sign rank test 
 
• Patient Global Impression of Improvement (PGI-I) Scale at Week 12. Descriptive 
statistics, (min, max, median, mean, standard deviation) will summarize these 
scores. 
 
• Change in total score on the Urinary Distress Inventory (UDI-6) from Baseline to 
Week 12 will be computed and this change will be summarized with descriptive 
statistics (min, max, median, mean, standard deviation) and analyzed for a 
significant change from Baseline using the Exact Wilcoxon sign rank test. 
 
• Change in total score on the Incontinence Impact Questionnaire (IIQ-7) from 
Baseline to Week 12 will be computed and this change will be summarized with 
descriptive statistics (min, max, median, mean, standard deviation) and analyzed 
for a significant change from Baseline using the Exact Wilcoxon sign rank test. 
 
• Change in total score on the Female Sexual Function Index (FSFI) as well as the 
change in subdomain scores: libido, arousal, lubrication, orgasm, satisfaction, 
and pain from Baseline to Week 12 will be computed and these changes will be 
summarized with descriptive statistics (min, max, median, mean, standard 
deviation) and analyzed for a significant change from Baseline using the Exact 
Wilcoxon sign rank test. 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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• Changes in pelvic floor muscles from Baseline to Week 12 will be summarized 
with descriptive statistics (min, max, median, mean, standard deviation) and 
analyzed for a significant change from Baseline using the Exact Wilcoxon sign 
rank test. 
 
• Qualitative changes in pelvic muscles will be described as decreased, increased 
or no change at Week 12 relative to Baseline. 
 
Exploratory Analyses 
 
Changes from baseline to each of the assessment times prior to Week 12 for the above 
endpoints will be explored, described and tested for significance using the same 
analytical methods noted for the primary and secondary objectives above. Durability   
treatment will be assessed by evaluating changes in study measures between week 12 
and 16 (end of study). There will be no adjustment for multiple testing, nor will any data 
be imputed. 
 
Repeated measures (mixed models) will be used to examine the change over time by 
incorporating all available assessment times to test for a significant non-zero slope over 
time and estimate that slope and its standard error. 
 
Various imputation methods may be explored if any of the above analyses indicate 
promise for the compound in the treatment of SUI. These imputation methods may allow 
for better estimation of effect size and consequently sample size estimation in future 
trials.  
 
11. 
QUALITY CONTROL AND 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, 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 study. 
 
An authorized Quality Assurance auditor will audit the study data and procedures at 
periodic intervals as indicated. Domestic or foreign regulatory authorities, the IRB/IEC, 
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. 


 
 
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Compound No.: GTx-024 
 
 
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Electronic data systems will be in accordance with applicable aspects of 21 CFR Part 
11, ICH Guidelines, GCP, local laws and legislation, and the Health Insurance 
Portability and Accountability Act.  
 
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. 
 
12. 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
 
12.1 ETHICAL CONSIDERATIONS 
 
This clinical study will be conducted in accordance with the ethical principles that have 
their origin in the Declaration of Helsinki and in accordance with global regulations 
including 21 CFR 312. 
 
The investigator is responsible for obtaining approval for this clinical study from the 
relevant IRB at the associated institution. The study will not begin until a favorable 
opinion of the IRB has been obtained. The investigator is responsible for complying with 
requirements imposed by the IRB and/or regulatory authority. Furthermore, the 
investigator will ensure that local regulations concerning data protection are followed. 
For ethical considerations, all patients will be required to sign a consent indicating their 
willingness to participate and that they have been fully informed of the risks and benefits 
of participation. 
 
12.2 INSTITUTIONAL REVIEW BOARD/ INDEPENDENT ETHICS 
COMMITTEE 
 
The protocol and the proposed ICF will be reviewed and approved by a properly 
constituted IRB/IEC before the study start. A signed and dated statement that the 
protocol and informed consent have been approved by the IRB/IEC will be given to 
GTx, Inc. or designee before study initiation. The signed IRB/IEC approval letter must 
identify the documents approved (i.e., list the Investigator’s name, the protocol number 
and title, the date of the protocol, and the date of approval of the protocol and the 
informed consent document). Any advertisements used to recruit subjects must also be 
reviewed by the IRB/IEC. Clinical supplies will not be shipped to a site until a signed 
approval letter from the IRB/IEC has been received and a contractual agreement has 
been signed by both parties. 
 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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Prior to study start, the Investigator will be required to sign a protocol signature page 
confirming his/her agreement to conduct the study in accordance with these documents 
and all of the instructions and procedures found in this protocol and to give access to all 
relevant data and records to GTx, Inc. monitors, auditors, GTx, Inc. Clinical Quality 
Assurance representatives, designated agents of GTx, Inc., IRBs/IECs/Research Ethics 
Boards (REBs), and regulatory authorities as required. 
 
 
12.3 PRE-STUDY DOCUMENTATION 
 
The Investigator must provide GTx or its designee with the following documents prior to 
the enrollment of any subjects:  
• Copy of the signed Investigator Agreement page 
• Copy of the IRB/IEC approval letter for protocol and informed consent  
• Completed, signed, and dated Form FDA 1572 
• Current curricula vitae, licenses, and financial disclosures for the Investigator(s) 
and sub Investigators listed on the 1572 
• Where applicable, list of IRB/IEC committee members and a statement of 
adherence to GCP 
• Copy of approved informed consent document 
• Executed clinical trial agreement  
• Name, location, certification number, and date of certification of the laboratory to 
be used for laboratory assays and those of other facilities conducting tests. GTx 
or its designee must be notified if the central laboratory is changed or if any 
additional laboratory is to be used 
• List of normal laboratory values (i.e., reference ranges and units of measure) for 
each central laboratory to be used during the study. GTx or its designee must be 
notified if normal values change 
 
12.4 INFORMED CONSENT PROCESS 
 
Eligible subjects will only be included in the study after providing written (witnessed, 
where required by law or regulation), IRB/IEC-approved informed consent. 
 
The informed consent documents must be reviewed and approved by GTx or its 
designee and the investigative site IRB/IEC prior to the initiation of the study. 
 
Each subject will receive an IRB/IEC approved informed consent document with study 
information. Subjects should be given ample time to read the information and the 
opportunity to ask questions. Informed consent must be obtained from each subject 
prior to performing any protocol-specific evaluations. The signed ICF will be retained 
with the study records and the subject will receive a copy of the signed informed 
consent for his/her records. The process of obtaining informed consent will be 
documented in the subject source documents. 


 
 
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Compound No.: GTx-024 
 
 
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The date when a subject’s informed consent was actually obtained will be captured in 
their CRFs. 
 
The Investigator (or designated staff) will explain the nature of the study as well as its 
risks and benefits to the subject (or the subject’s legal representative). 
 
  
12.5 SUBJECT CONFIDENTIALITY 
 
Subject confidentiality is strictly held in trust by the participating Investigators, their staff, 
and the Sponsor(s) and their agents. This confidentiality is extended to cover testing of 
biological samples and genetic tests (if applicable) in addition to the clinical information 
relating to participating subjects.  
 
The study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study or the data will be 
released to any unauthorized third party without prior written approval of the Sponsor. 
 
The study monitor or other authorized representatives of the Sponsor may inspect all 
documents and records required to be maintained by the Investigator, including but not 
limited to, medical records (office, clinic, or hospital) and pharmacy records for the 
subjects in this study. The clinical study site will permit access to such records. 
 
12.6 PROTOCOL ADHERENCE 
 
By signing the Form FDA 1572, the Investigator agrees to conduct the study according 
to the protocol and the FDA regulations set forth in 21 CFR Parts 50, 54, 56, and 312. 
 
12.7 PERMISSION TO REVIEW SUBJECTS’ SOURCE RECORDS 
 
The Investigator agrees to allow the FDA and other regulatory agencies, individuals 
delegated by the IRB/IEC and Competent Authorities, and the Sponsor or its designee 
to have access to all the original documentation of the study, including the ICFs signed 
by the subjects enrolled into the study and the relevant subject medical files. The 
individuals who are given access to the documentation must take every reasonable 
precaution to keep the identity of the subjects and the proprietary information of the 
Sponsor as confidential information in accordance with relevant applicable legislation. 
 
12.8 PROTOCOL AMENDMENTS 
 
All amendments to the study protocol must be submitted to the IRB/IEC for written 
approval. The approval letter, signed by the IRB/IEC Chairperson, must refer 
specifically to the Investigator, the protocol number and protocol title, the protocol 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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amendment number, and the date of the protocol amendment. A copy of the approval 
letter and revised informed consent document (if applicable) must be sent to GTx or its 
designee. A protocol amendment may be implemented only after it has been approved 
by the IRB/IEC and has been approved by the appropriate regulatory authority. In the 
case of a protocol change intended to eliminate an apparent immediate hazard to 
subjects, the change may be implemented immediately, but the change must then be 
documented in a protocol amendment and approved as described above. 
 
12.9 CHANGE IN INVESTIGATOR 
 
If any Investigator retires, relocates, or withdraws from an investigation during the 
conduct of the study the responsibility for conduct of the study may be transferred to 
another appropriately qualified Investigator at the investigative site. GTx or its designee 
must be notified. An updated Form FDA 1572 must be submitted to GTx or its designee. 
 
12.10 STUDY DISCONTINUATION 
 
GTx, Inc. reserves the right to discontinue this study under the conditions specified in 
the clinical study agreement.  
 
12.11 INDEMNITY 
 
The Sponsor certifies that it has taken out a liability insurance policy that is consistent 
with the requirements for which the study is being conducted. This insurance policy is in 
accordance with local laws and requirements. An insurance certificate will be provided 
to the PI requiring this document. The insurance of the Sponsor does not relieve the PI 
and the collaborators of any obligation to maintain their own liability insurance policy as 
required by applicable law. 
 
13. 
DATA HANDLING AND RECORD KEEPING 
 
The Investigator is responsible to ensure the accuracy, completeness, legibility, and 
timeliness of the source data. All source documents should be completed in a neat, 
legible manner to ensure accurate interpretation of data. Dark ink is required to ensure 
clarity of reproduced copies. When making changes or corrections, cross out the 
original entry with a single line, and initial and date the change. DO NOT ERASE, 
OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the CRF will be provided for use as source documents and maintained for 
recording data for each subject enrolled in the study. Data reported in the CRF derived 
from source documents should be consistent with the source documents or the 
discrepancies should be explained. 
 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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Study records will be maintained in locked offices with access limited to authorized 
individuals. Each participant will be given an identification number that will be used to 
enter the data into a password protected database and for the analysis.  
  
13.1 DATA CAPTURE METHODS 
 
13.1.1 DATA COLLECTION  
 
Study specific data will be collected on paper case report forms (CRFs). Completed 
questionnaires and voiding diaries will be used as source documents, and these 
documents will be kept in the study files. Blank data fields should be noted as unknown 
(UNK) or not applicable (NA) if source information is not available or data not collected. 
While completing the questionnaire, if a subject leaves a question blank, it will be 
deemed permanently missing. All CRFs will be maintained at the study site for the 
length of time as determined by the IRB and federal regulations and as provided in the 
site’s clinical study agreement. Data will be entered into a password protected electronic 
database that does not contain subject identifiers. Identifiers linked to unique Study ID 
will be kept separately from the study data. Data entry will be reviewed for accuracy.  
 
13.2 STUDY SITE RESPONSIBILITIES 
 
All data requested on the CRF must be recorded. Data will be transcribed by authorized 
personnel at the study site from the source documents into the CRF for enrolled 
subjects. All information on the CRF must be traceable to these source documents. All 
electronic entries (including any changes or updates) will be traceable through the 
system. Only the PI or authorized staff may enter or modify data in the database using 
their unique password. The Investigator must certify that the data entered in the CRFs 
are complete and accurate by electronically signing the CRF. 
 
13.3 CRF TIMING/REPORTS 
 
A final report for the study will be completed upon completion of the study and the 
analysis of data. Please see information concerning publication policy (Section 14). 
 
13.4 STUDY RECORDS RETENTION 
 
Study documents must be retained for a minimum of 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 until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These 
documents will be retained for a longer period, however, if required by local regulations. 
No records will be destroyed without the written consent of GTx, Inc., if applicable. It is 
the responsibility of GTx, Inc. to inform the PI when these documents no longer need to 
be retained. 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
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Compound No.: GTx-024 
 
 
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13.5 PROTOCOL DEVIATIONS 
 
A protocol deviation is any noncompliance with the clinical trial protocol that affects a 
subject’s safety and primary efficacy, GCP, or Manual of Procedures requirements. The 
noncompliance may be either on the part of the subject, the PI, or the study site staff. 
As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly.  
 
These practices are consistent with ICH E6:  
 
4.5 
Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
5.1 
Quality Assurance and Quality Control, section 5.1.1 
5.20 Noncompliance, sections 5.20.1 and 5.20.2 
 
It is the responsibility of the site to use continuous vigilance to identify and report 
deviations within 5 working days of identification of the protocol deviation.  
All deviations from the protocol must be addressed in study subject source documents. 
A completed copy of the Protocol Deviation Form will be maintained in the regulatory 
file, as well as in the subject’s source document. Protocol deviations will be sent to the 
local IRB/IEC per their guidelines. The PI/study staff is responsible for knowing and 
adhering to their IRB/IEC requirements. 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
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Compound No.: GTx-024 
 
 
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14. 
PUBLICATION POLICY 
Following completion of the study, it is expected some Investigators may wish to publish 
the results of this research in scientific journal(s). Publication rights are governed by the 
investigatory site’s clinical trial agreement with GTx, Inc. The Investigator may request 
to publish this study in a scientific journal, but must have written authorization of GTx, 
Inc.  
 
The data generated by this study are confidential information and the property of GTx, 
Inc. This confidential information may be published only in collaboration with 
participating personnel from GTx, Inc. or upon GTx’s written consent, or otherwise 
under terms of the investigatory site’s clinical trial agreement with GTx, Inc. All 
unpublished information shall not be disclosed to any third parties without the prior 
written consent of GTx, Inc. 
 
The International Committee of Medical Journal Editors member journals have adopted 
a trials-registration policy as a condition for publication. This policy requires that all 
clinical trials be registered in a public trials registry such as ClinicalTrials.gov, which is 
sponsored by the U.S. National Library of Medicine. It is GTx’s responsibility to register 
this trial in an acceptable registry.  
 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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15. 
LITERATURE REFERENCES 
Aizawa K, Iemitsu M, Maeda S, Mesaki N, Ushida T, Akimoto T. Endurance exercise 
training enhances local sex steroidogenesis in skeletal muscle. Medicine and science in 
sports and exercise 2011; 43(11): 2072-80. 
 
Antonio FI, Bo K, Ferriani RA, de Sa MF, de Sa Rosa e Silva AC, Ferreira CH. Pelvic 
floor muscle strength and urinary incontinence in hyperandrogenic women with 
polycystic ovary syndrome. International urogynecology journal 2013; 24(10): 1709-14. 
 
Athanasiou S, Khullar V, Boos K, Salvatore S, Cardozo L. Imaging the urethral 
sphincter with three-dimensional ultrasound. Obstet Gynecol 1999; 94(2): 295-301 
 
Bai SW, Jung BH, Chung BS, et al. Relationship between urinary profile of the 
endogenous steroids and postmenopausal women with stress urinary incontinence. 
Neurourol Urodynam 2003; 22: 198-205. 
 
Bai SW, Jung BH, Chung BC, et al. Relationship between urinary endogenous steroid 
metabolites and lower urinary tract function in postmenopausal women. Yonsei Med J 
2003; 44: 279-87. 
 
Berger L, El-Alfy M, Martel C, Labrie F. Effects of dehydroepiandrosterone, Premarin 
and Acolbifene on histomorphology and sex steroid receptors in the rat vagina. J 
Steroid Biochem Mol Biol. 2005; 96: 201-15.  
 
Berman JR, Almeida FG, Jolin J, et al. Correlation of androgen receptors, aromatase, 
and 5-alpha reductase in the human vagina with menopausal status. Fertil Steril 2003; 
79: 925–931. 
 
Brown JS, McNaughton KS, Wyman JF, Burgio KL, Harkaway R, Bergner D, Altman 
DS. Kaufman J, Kaufman K, and Girman CJ, Measurement characteristics of a voiding 
diary for use by men and women with overactive bladder. Urology, 2003. 61(4): 802-9.  
 
Brubaker L, Norton PA, Albo ME, Chai TC, Dandreo KJ. Adverse events over two years 
after retropubic or transobturator midurethral sling surgery: findings from the Trial of 
Midurethral Slings (TOMUS) study. Am J Obstet Gynecol 2011, 205: 498.e1–498.e6 
 
Cammu H, Van Nylen M, Blockeel C, Kaufman L, Amy J-J. Who will benefit from pelvic 
floor muscle training for stress urinary incontinence? Am J Obstet Gynecol 2004; 191: 
1152-7.  
 
Celayir S, Ilce Z, Dervisoglu S. The sex hormone receptors in the bladder in childhood-I: 
preliminary report in male subjects. Eur J Pediatr Surg 2002; 12: 312–317. 


 
 
Protocol: GTx-024  as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
 
 
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Copas P, Bukovsky A, Asbury B, et al. Estrogen, progesterone, and androgen receptor 
expression in levator ani muscle and fascia. J Women Health Gend Based Med 2001; 
10: 785–795. 
 
Dalton JT, Barnette KG, Bohl CE, et al. The selective androgen receptor modulator 
GTx-024 improves lean body mas and physical function in healthy elderly men and 
postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J 
Cachexia Sarcopenia Muscle 2011; 2: 153-61. 
 
DeLancey JO, Miller JM, Kearney R, Howard D, ReddyP, Umek W, Guire KE, Margulies 
RU, Ashton-Miller JA. Vaginal birth and de novo stress incontinence: relative 
contributions of uretliral dysfiinction and mobility. Obstet Gynecol 2007; (2Pt I); 
354~362.  
 
DeLancey JO, Trowbridge ER, Miller JM, Morgan DM, Guire K, Fenner DE, Weadock 
WJ, Ashton-Miller JA. Stress urinary incontinence: relative importance of urethral 
support and urethral closure pressure. J Urol. 2008; 179 (6);  2286-2290. 
 
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: 1259-1263.  
 
Hay-Smith J, Berghmans B, Burgio K, Dumoulin C, Hagen S, Moore K, Nygaard I, 
N'dow J (2009) Committee 12 adult conservative management. In: Abrams P, Cardozo 
L, Khoury S, Wein A (eds) Incontinence, 4th edn. Health Publications Ltd., Paris 
 
Herzog AR, Diokno AC, Brown MB, Normolle DP, and Brock BM, Two-year incidence, 
remission, and change patterns of urinary incontinence in noninstitutionalized older 
adults. J Gerontol 1990, 34: M67-74. 
 
Herzog AR, Fultz NH. Prevalence and incidence of urinary incontinence in community-
dwelling populations. J Am Geriatr Soc, 1990. 38(3): p. 273-81. PMID 2179368 adults. J 
Gerontol, 1990. 45(2): M67-74.  
 
Ho MH, Bhatia NN, Bhasin S. Anabolic effects of androgens on muscles of female 
pelvic floor and lower urinary tract. Current opinion in obstetrics & gynecology 2004;  
16(5): 405-9. 
 
Jung BH, Bai SW, Chung BC. Urinary profile of endogenous steroids in 
postmenopausal women with stress urinary incontinence. J Reprod Med 2001; 46: 969–
974. 
 
Kadekawa et al, AUA Annual Meeting 2015, New Orleans, LA.  PD27-11. 


 
 
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Compound No.: GTx-024 
 
 
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Kenton K, Mueller E, Bmbaker L. Continent women have better urethral neuromuscular 
function than those with stress incon¬tinence. Int Urogynecol J. 2011; 22(12): 1479-
1484.  
 
Kvarstein B.K., Nygaard I. Lower urinary tract symptoms and pelvic floor muscle 
exercise adherence after 15 years. Obstet Gynecol 2005; 105: 999-1005 
 
Labrie J, Berghmans BLCM, Fischer K, Milani A, van der Wijk I, et al. Surgery versus 
physiotherapy for stress urinary incontinence. NEJM 2013; 369: 1124-1133. 
 
Lamers BHC, van der Vaart CH. Medium- term efficacy of pelvic floor muscle training 
for female urinary incontinence in daily practice. Int Urogynecol J Pelvic Floor Dysfunct 
2007; 18: 301-7.  
 
Lee PE, Kumg RC, Drutz HP. Periurethral autologous fat injection as a treatment for 
female stress urinary incontinence-a randomized double-blind controlled trial. J Urol 
2001; 165;  153-158 
 
Locher JL, Goode PS, Roth DL, Worrell RL, and Burgio KL, Reliability assessment of 
the bladder diary for urinary incontinence in older women. J Gerontol A Biol Sci Med 
Sci, 2001. 56(1): M32-5.  
 
Luber KM: The definition, prevalence, and risk factors for stress urinary incontinence. 
Rev Urol, suppl., 2004; 6: S3. 
 
Madill SJ, Pontbriand-Drolet S, Tang A, Dumoulin C. Changes in urethral sphincter size 
following rehabilitation in older women with stress urinary incontinence. Int Urogynecol J 
2014, September, epub ahead of print. 
 
Mammadov R, Sinsir A, Tuglu I, Eyren V, Gurer E, Ozyurt C. The effect of testosterone 
treatment on urodynamic findings and histopathomorphology of pelvicjHoor muscles in 
female rats with experimentally induced stress urinary incontinence. Int Urol Nephrol 
2011; 43: 1003-1008 
 
McLean L, Varette K, Gentilcore-Saulnier B, Harvey MA, Baker K, Sauerbrei E (2013) 
Pelvic floor muscle training in women with stress urinary incontinence causes 
hypertrophy of the urethral sphincters and reduces bladder neck mobility during 
coughing. Neurourol Urodyn 32(8): 1096-n02. doi;  10.1002/nau.22343 
 
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. 
 


 
 
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Compound No.: GTx-024 
 
 
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Montezuma T, Antonio FI, Rosa e Silva AC, Sa MF, Ferriani RA, Ferreira CH. 
Assessment of symptoms of urinary incontinence in women with polycystic ovary 
syndrome. Clinics (Sao Paulo, Brazil) 2011; 66(11): 1911-5. 
 
Morgan DM, Umek W, Guire K, Morgan HK, Garabrant A, DeLancey JO. Urethral 
sphincter morphology and function with and without stress incontinence. J Urol. 2009; 
182(l);  203-209.  
 
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: 40-8 
 
Nnodim JO. Quantitative study of the effects of denervation and castration on the 
levator ani muscle of the rat. Anat Rec 1999; 255: 324–333. 
 
Nnodim JO. Testosterone mediates satellite cell activation in denervated rat levator ani 
muscle. Anat Rec 2001; 263: 19–24. 
 
Peters KM, Dmochowski RR, Carr LK, Magali R, Kaufman MR, Sirls LT, Herschorn S, 
Birch C, Kultgen PL, Chancellor MB.Autologous muscle derived cells for treatment of 
stress urinary incontinence in women. J Urol 2014; 192: 469-476. 
 
Rosen R, Brown C, Heiman J, Leiblum S, Meston CM, Shabisigh R, Ferguson D, 
D’Agostino R, Jr. The Female Sexual Function Index (FSFI): a multidimensional self-
report instrument for the assessment of female sexual function. J Sex Mar Ther 2000; 
26, 191-208. 
 
Rovner ES, Wein AJ. Treatment options for stress urinary incontinence. Reviews in 
Urology 2004; 6: s 29-s47 
 
Santen RJ, Vaginal administration of estradiol: effects of dose, preparation and timing 
on plasma estradiol levels Climacteric 2015; 18:121-134 
 
Shin MH, Rhie GE, Park CH, Kim KH, Cho KH, Eun HC, et al. Modulation of collagen 
metabolism by the topical application of dehydroepiandrosterone to human skin. J 
Invest Dermatol. 2005; 124: 315-23. 
 
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: 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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Compound No.: GTx-024 
 
 
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Takahashi S, Homnia Y, Fujishiro T, Hosaka Y, Kitamura T, Kawabe K. 
Electromyographic study of the striated urethral sphincter in type 3 stress incontinence: 
evidence of myogenic-dominant damages. Urology 2000, 56(6); 946-950 
 
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: 131–9. 
 
Wagner TH, Patrick DL, Bavendam TG, Martin ML, Buesching DP. Quality of life of 
persons with urinary incontinence: development of a new measure. Urology, 1996. 
47(1): 67-71; discussion 71-2.  
 
Wyman JF, Choi SC, Harkins SW, Wilson MS, and Fantl JA, The urinary diary in 
evaluation of incontinent women: a test-retest analysis. Obstet Gynecol, 1988. 71(6 Pt 
1): 812-7.  
 
Wyman JF, Harkins SW, Choi SC. et al. Psychosocial impact of urinary 
incontinence in women. Obstet Gynecol 1987; 70: 378–81. 
 
Yalcin I, Bump RC. Validation of two global impression questionnaires for incontinence. 
Am J Obstet Gynecol, 2003. 189(1): 98-101.  
 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
Author: _____________ 
 
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1. 
APPENDIX A: MESA URINARY QUESTIONNAIRE 
 
MESA Urinary Questionnaire 
NAME (printed): ______________________________________________ 
1. 
Over the past three months, have you had urine loss beyond your control?  Yes      No 
2.  
How long ago did your urine loss start?  Years      Months     Days 
 
Urge Incontinence 
1. 
Some people receive very little warning and suddenly find that they are losing, or about to lose, urine beyond their control. How often does this happen to you? 
 
 Often  
 Sometimes  
 Rarely  
 Never  
2. 
If you can’t find a toilet or find a toilet that is occupied and you have an urge to urinate, how often do you end up losing urine and wetting yourself? 
 
 Often 
 Sometimes  
 Rarely 
 Never 
3. 
Do you lose urine when you suddenly have the feeling that your bladder is full? 
 
 Often 
Sometimes 
 Rarely 
 Never 
4. 
Does washing your hands cause you to urinate? 
 
 Often 
 Sometimes 
 Rarely 
 Never 
5. 
Does cold weather cause you to lose urine? 
 
 Often 
 Sometimes 
 Rarely 
 Never 
6. 
Does drinking cold beverages cause you to lose urine? 
 
 Often 
 Sometimes 
 Rarely 
 Never 
 
Stress Incontinence 
1. 
Does coughing gently cause you to lose urine? 
 
 Often 
 Sometimes 
 Rarely 
 Never 
2. 
Does coughing hard cause you to lose urine? 
 
 Often 
 Sometimes 
 Rarely 
 Never 


 
 
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Compound No.: GTx-024 
Author: _____________ 
 
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3. 
Does sneezing cause you to lose urine? 
 
 Often 
 Sometimes 
 Rarely 
 Never 
4. 
Does lifting things cause you to lose urine? 
 
 Often  
 Sometimes  
Rarely  
 Never  
5. 
Does bending over cause you to lose urine? 
 
 Often 
 Sometimes  
 Rarely 
 Never 
6. 
Does laughing cause you to lose urine? 
 
 Often 
 Sometimes 
 Rarely 
 Never 
7. 
Does walking briskly cause you to lose urine?  
 
 Often 
 Sometimes 
 Rarely 
 Never 
8. 
Does straining, if you are constipated, cause you to lose urine? 
 
 Often 
 Sometimes 
 Rarely 
 Never 
9. 
Does getting up from a sitting to a standing position cause you to lose urine? 
 
 Often 
 Sometimes 
 Rarely 
 Never 
 


 
 
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Compound No.: GTx-024 
Author: _____________ 
 
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Total Calculator:  
URGE SYMTOM INDEX LOOK-UP TABLE 
1/18 = 6% 
5/18 = 28% 
9/18 = 50% 
13/18 = 72% 
17/18 = 94% 
2/18 = 11% 
6/18 = 33% 
10/18 = 56% 
14/18 = 78% 
18/18 = 100% 
3/18 = 17% 
7/18 = 39% 
11/18 = 61% 
15/18 = 83% 
 
4/18 = 22% 
8/18 = 44% 
12/18 = 67% 
16/18 = 89% 
 
 
Total Score _______/18 
STRESS SYMPTOM INDEX LOOK-UP TABLE 
1/27 = 4% 
5/27 = 19% 
9/27 = 33% 
13/27 = 48% 
17/27 = 63% 
21/27 = 78% 
25/27 = 93% 
2/27 = 7% 
6/27 = 22% 
10/27 = 37% 
14/27 = 52% 
18/27 = 67% 
22/27 = 81% 
26/27 = 96% 
3/27 = 11% 
7/27 = 26% 
11/27 = 41% 
15/27 = 56% 
19/27 = 70% 
23/27 = 85% 
27/27 = 100% 
4/27 = 15% 
8/27 = 30% 
12/27 = 44% 
16/27 = 59% 
20/27 = 74% 
24/27 = 89% 
 
 
Total Score ______/27 


 
 
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Compound No.: GTx-024 
Author: _____________ 
 
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2. 
APPENDIX B: PATIENT GLOBAL IMPRESSION OF SEVERITY 
(PGI-S) SCALE AND PATIENT GLOBAL IMPRESSION OF 
IMPROVEMENT (PGI-I) SCALE  
Patient Global Impression of Severity (PGI-S) Scale  
Check the one number that best describes how your urinary tract condition is now. 
1. Normal 
2. Mild 
3. Moderate 
4. Severe 
 
Patient Global Impression of Improvement (PGI-I) Scale 
Check the one number that best describes how your urinary tract condition is now, 
compared with how it was before you began taking medication in this study. 
1. Very much better 
2. Much better 
3. A little better 
4. No change 
5. A little worse 
6. Much worse 
7. Very much worse 


 
 
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Compound No.: GTx-024 
Author: _____________ 
 
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3. 
APPENDIX C: URINARY DISTRESS INVENTORY (UDI-6) AND 
INCONTINENCE IMPACT QUESTIONNAIRE (IIQ-7)  
 
Urinary Distress Inventory (UDI-6)  
1. Do you experience, and, if so, how much are you bothered by frequent urination? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
2. Do you experience, and, if so, how much are you bothered by urine leakage related 
to the feeling of urgency? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
 
3. Do you experience, and, if so, how much are you bothered by urine leakage related 
to physical activity, coughing, or sneezing? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
 
4. Do you experience, and, if so, how much are you bothered by small amounts of urine 
leakage 
(drops)? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
 
5. Do you experience, and, if so, how much are you bothered by difficulty emptying your 
bladder? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
6. Do you experience, and, if so, how much are you bothered by pain or discomfort in 
the lower 
abdominal or genital area? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 


 
 
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Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
Author: _____________ 
 
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Incontinence Impact Questionnaire (IIQ-7) 
 
7. Has urine leakage affected your ability to do household chores (cooking, cleaning, 
laundry, etc)? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
8. Has urine leakage affected your physical recreation such as walking, swimming, or 
other exercise? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
9. Has urine leakage affected your entertainment activities (movies, concerts, etc.)? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
10. Has urine leakage affected your ability to travel by car or bus more than 30 minutes 
from home? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
11. Has urine leakage affected your participation in social activities outside your house? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
12. Has urine leakage affected your emotional health (nervousness, depression, etc.)? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
13. Has urine leakage affected your feeling frustrated? 
Not at all 0  Slightly 1  
Moderately 3  
Greatly4 
 
14. Total Score for UDI-6=________________________ 
 
15. Total Score for IIQ-7=______________________________ 


 
 
Protocol: GTx-024 as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
Author: _____________ 
 
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4. 
APPENDIX D: FEMALE SEXUAL FUNCTION INDEX (FSFI) 
Female Sexual Function Index (FSFI) 
 
Name ________________________________       Date ________________ 
 
INSTRUCTIONS: These questions ask about your sexual feelings and responses during the 
past 4 weeks. Please answer the following questions as honestly and clearly as possible. Your 
responses will be kept completely confidential. In answering these questions the following 
definitions apply:  
• 
Sexual activity can include caressing, foreplay, masturbation and vaginal intercourse. 
• 
Sexual intercourse is defined as penile penetration (entry) of the vagina. 
• 
Sexual stimulation includes situations like foreplay with a partner, self-stimulation 
(masturbation), or sexual fantasy. 
 
CHECK ONLY ONE BOX PER QUESTION. 
Sexual desire or interest is a feeling that includes wanting to have a sexual experience, feeling 
receptive to a partner's sexual initiation, and thinking or fantasizing about having sex. 
 
1. Over the past 4 weeks, how often did you feel sexual desire or interest? 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
2. Over the past 4 weeks, how would you rate your level (degree) of sexual desire 
or interest? 
Very high 
High 
Moderate 
Low 


 
 
Protocol: GTx-024 as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
Author: _____________ 
 
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Very low or none at all 
Sexual arousal is a feeling that includes both physical and mental aspects of sexual excitement. 
It may include feelings of warmth or tingling in the genitals, lubrication (wetness), or muscle 
contractions. 
3. Over the past 4 weeks, how often did you feel sexually aroused ("turned on") 
during sexual activity or intercourse? 
No sexual activity 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
4. Over the past 4 weeks, how would you rate your level of sexual arousal ("turn 
on") during sexual activity or intercourse? 
No sexual activity 
Very high 
High 
Moderate 
Low 
Very low or none at all 
5. Over the past 4 weeks, how confident were you about becoming sexually 
aroused during sexual activity or intercourse? 
No sexual activity 
Very high confidence 
High confidence 
Moderate confidence 
Low confidence 
Very low or no confidence 
6. Over the past 4 weeks, how often have you been satisfied with your arousal 
(excitement) during sexual activity or intercourse? 
No sexual activity 
Almost always or always 


 
 
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Compound No.: GTx-024 
Author: _____________ 
 
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Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
7. Over the past 4 weeks, how often did you become lubricated ("wet") during 
sexual activity or intercourse? 
No sexual activity 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
8. Over the past 4 weeks, how difficult was it to become lubricated ("wet") during 
sexual activity or intercourse? 
No sexual activity 
Extremely difficult or impossible 
Very difficult 
Difficult 
Slightly difficult 
Not difficult 
9. Over the past 4 weeks, how often did you maintain your lubrication ("wetness") 
until completion of sexual activity or intercourse? 
No sexual activity 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
10. Over the past 4 weeks, how difficult was it to maintain your lubrication 
("wetness") until completion of sexual activity or intercourse? 
No sexual activity 
Extremely difficult or impossible 


 
 
Protocol: GTx-024 as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
Author: _____________ 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 73 of 76 
Very difficult 
Difficult 
Slightly difficult 
Not difficult 
11. Over the past 4 weeks, when you had sexual stimulation or intercourse, how 
often did you reach orgasm (climax)? 
No sexual activity 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
12. Over the past 4 weeks, when you had sexual stimulation or intercourse, how 
difficult was it for you to reach orgasm (climax)? 
No sexual activity 
Extremely difficult or impossible 
Very difficult 
Difficult 
Slightly difficult 
Not difficult 
 
13. Over the past 4 weeks, how satisfied were you with your ability to reach orgasm 
(climax) during sexual activity or intercourse? 
No sexual activity 
Very satisfied 
Moderately satisfied 
About equally satisfied and dissatisfied 
Moderately dissatisfied 
Very dissatisfied 
14. Over the past 4 weeks, how satisfied have you been with the amount of 
emotional closeness during sexual activity between you and your partner? 
No sexual activity 


 
 
Protocol: GTx-024 as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
Author: _____________ 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 74 of 76 
Very satisfied 
Moderately satisfied 
About equally satisfied and dissatisfied 
Moderately dissatisfied 
Very dissatisfied 
15. Over the past 4 weeks, how satisfied have you been with your sexual 
relationship with your partner? 
Very satisfied 
Moderately satisfied 
About equally satisfied and dissatisfied 
Moderately dissatisfied 
Very dissatisfied 
16. Over the past 4 weeks, how satisfied have you been with your overall sexual life? 
Very satisfied 
Moderately satisfied 
About equally satisfied and dissatisfied 
Moderately dissatisfied 
Very dissatisfied 
 
17. Over the past 4 weeks, how often did you experience discomfort or pain during 
vaginal penetration? 
Did not attempt intercourse 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
18. Over the past 4 weeks, how often did you experience discomfort or pain following 
vaginal penetration? 
Did not attempt intercourse 
Almost always or always 
Most times (more than half the time) 


 
 
Protocol: GTx-024 as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
Author: _____________ 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 75 of 76 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
19.Over the past 4 weeks, how would you rate your level (degree) of discomfort or 
pain during or following vaginal penetration? 
Did not attempt intercourse 
Very high 
High 
Moderate 
Low 
Very low or none at all 
 
Thank you for completing this questionnaire 


 
 
Protocol: GTx-024 as a Treatment for Stress Urinary 
Incontinence in Women: A Proof of Concept Study 
 
Compound No.: GTx-024 
Author: _____________ 
 
GTx, Inc. SUI Protocol; Version 1.0  
07 August 2015      CONFIDENTIAL 
Page 76 of 76 
5. APPENDIX E: VOIDING DIARY 
 
VOIDING DIARY 
 
 
 
 
 
 
Wake Time: ______________ 
 
 
 
 
Study ID: ____________ 
Bed Time: ______________ 
 
 
 
 
Date (m/d/y): _____________________ 
Time  
Fluid Intake 
(ounces) 
Urine Amount 
cc's/ml's or 
ounces (oz)     
Leaking (if you leak, 
first give the episode a 
"score" in the first 
column then circle if 
you think it is stress or 
urge incontinence, or 
both in the second 
column) 
Urgency 
Pad 
Replaced 
Bowel Movement Pelvic and/or 
Bladder/Urinar
y Related Pain 
Vaginal 
discharge 
color 
Vaginal 
discharge 
amount 
A: a.m.  
P: p.m. 
 
Amount Voided 
0: None      
1: Mild        
5: Mod.     
10: Severe 
S: Stress    
U: Urge 
0: None          
1: Mild            
5: Mod.        
10: Severe 
1: Tissue      
2: Pantiliner 
3: Thick Pad 
4: Diaper 
N: Normal               
C: Constipated       
D: Diarrhea             
L: Leaking stool 
0: None               
1: Mild 
5: Mod  
10: Severe 
.               
 
0: no 
discharge 
1: red 
2: brown 
3: white 
4: yellow 
1: Spotting 
2: dime size 
3: quarter size 
5: more than 
quarter size 
5:00 AM   
  
S  U 
  
  
  
  
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